Machine learning (ML) techniques can help predict survival among cancer patients and might help with a timely integration in palliative care. We aim to explore the importance of subjective variables self-reported and collected via electronic patient reported outcome measure (ePROM) for survival prediction. A total of 256 advanced cancer patients met the eligible criteria. We analyzed objective variables collected from electronic health records, subjective variables collected via ePROM and all clinical variables combined. We used logistic regression (LR), decision trees, and random forests to predict 1-year mortality. Receiver operating characteristic (ROC) curve - area under the curve (AUC) and the ML models feature importance were analyzed. The performance of all variables for predictions (LR reaches 0.80 [ROC AUC] and 0.72 [F1 Score]) does not improve over the performance of only clinical non-patient reported outcome (non-PRO) variables (LR reaches 0.81 [ROC AUC] and 0.72 [F1 Score]). Our study indicates that patient-reported outcome (PRO) variables, which measure subjective burden, cannot be reliably used to predict survival. Further research in this area is needed to clarify the role of self-reported patient's burden and mortality prediction via ML.

Leeches are well-known annelids due to their obligate blood-feeding habits. Some leech species secrete various biologically active substances which have important medical and pharmaceutical value in antithrombotic treatments. In this study, we provide a high quality genome of the Asian buffalo leech (Hirudinaria manillensis), based on which we performed a systematic identification of potential antithrombotic genes and their corresponding proteins. Combining automatic and manual prediction, we identified 21 antithrombotic gene families including fourteen coagulation inhibitors, three platelet aggregation inhibitors, three fibrinolysis enhancers, and one tissue penetration enhancer. A total of 72 antithrombotic genes, including two pseudogenes, were identified and most of their corresponding proteins forming three or more disulfide bonds. Three protein families (LDTI, antistasin, and granulin) have internal tandem repeats containing 6, 10, and 12 conserved cysteines, respectively. We also measured the anticoagulant activities of the five identified hirudins (hirudin_Hman1 ~ hirudin_Hman5). The results showed that three (hirudin_Hman1, hirudin_Hman2, and hirudin_Hman5), but not the remaining two, exhibited anticoagulant activities. Our study provides the most comprehensive collection of antithrombotic biomacromolecules from a leech to date. These results will greatly facilitate the research and application of leech derivatives for medical and pharmaceutical purposes of thrombosis.

Introduction: Sarcopenia, muscle loss, often coexists with MASLD, a common liver disorder, which is more prevalent in those with sarcopenia. Sarcopenia also increases the risk of liver conditions like steatosis and fibrosis. Studies on sarcopenia in MASLD are common in developed countries, but fewer follow the EWGSOP2 guidelines in Brazil. Aim: to assess sarcopenia prevalence in MASLD patients. Methods: Cross-sectional study conducted at the Gastroen-terology/Hepatology Service of ISCMPA with patients diagnosed with MASLD. The EWGSOP2 criteria were used to evaluate sarcopenia. Categorical data presented as absolute and relative frequency; parametric continuous data ex-pressed as mean±standard deviation; non-parametric continuous data as me-dian and IQR. Gender differences in were analyzed using Fisher's Exact Test or Chi-squared tests, and for continuous variables, T Student tests (parametric) and Mann-Whitney U tests for independent samples (non-parametric). The significance level was set at 5% (p<0.05). Results: The study involved 103 MASLD patients with an average age of 60.39 years, comprising 48 (46.60%) adults and 55 (53.40%) older individuals. Concerning sarcopenia diagnosis, four individuals exhibited decreased muscle strength; two had reduced MME (sarcopenia); and one showed decreased walking speed (severe sarcopenia). Among the participants, 63 (60.6%) were physically active. 35 (62.5%) had mild to moderate steatosis, while 21 (37.5%) had severe steatosis. In terms of EHNA, 13 subjects (24.08%) had moderate to severe EHNA. Regarding fibrosis classi-fication, 68 (72.34%) individuals had undetermined or high probability based on the NAFLD score, with higher prevalence in males (n=23; 88.5%). Fibrosis assessment via liver biopsy revealed 27 (28.72%) in F1 and F2 and 15 (16.96%) in F3 and F4. Stratification of fibrosis into F3 and F4 was more com-mon among men (n=9; 47.4%). Conclusion: Most of the population was physi-cally active. The parameters indicating sarcopenia exceeded the thresholds recommended by EWGSOP2. The prevalence of sarcopenia was low in individuals with MASLD.

Visceral leishmaniasis (VL) is a severe parasitic disease transmitted by phlebotomine sandflies. VL is endemic in West Pokot County, Kenya, where effective strategies to interrupt transmission are impeded by the limited understanding of VL risk factors. Therefore, this case-control study aimed to explore environmental, behavioral and household determinants of VL in West Pokot. From November 2022 to January 2023, a structured questionnaire was administered to 36 symptomatic primary VL cases attending the Kacheliba Sub-County Hospital and to 50 controls from local villages. The VL status of all participants was confirmed using an rK39 rapid diagnostic test. In an age-corrected univariate logistic regression analysis, significant associations were found between VL and housing characteristics, such as window presence and floor type. Furthermore, outdoor activities, including traveling outside the residence for more than 2 weeks, activities near termite mounds, and forest activities during the rainy season increased the risk of VL. VL cases more frequently reported the presence of cattle, dogs and sheep in their house yards at night. VL was also associated with cutting down trees in the house yard and house proximity to several Acacia tree species. To conclude, this work reports a number of previously undescribed risk factors for VL in the understudied West Pokot focus. Our findings warrant further research into sandfly ecology and potential zoonotic parasite reservoirs in West Pokot.

Although first described in the final decade of the 19th century, the axis responsible for atrioventricular conduction has long been the source of multiple controversies. Some of these continue to reverberate. When first described by His, for example, many doubted the existence of the bundle we now name in his honour, while Kent suggested that multiple pathways crossed the atrioventricular junctions in the normal heart. It was Tawara who clarified the situation, although many of his key definitions have not universally been accepted. In key studies in the third decade of the 20th century, Mahaim then suggested the presence of ubiquitous connections that provided "paraspecific" pathways for atrioventricular conduction. In this review, we show the validity of these original investigations, based on our own experience with a large number of datasets from human hearts prepared by serial histological sectioning. Using our own reconstructions, we show how the atrioventricular conduction axis can be placed back within the heart. We emphasise that newly emerging techniques will be key in providing the resolution to map cellular detail to the gross evidence provided by the serial sections

Background: Acute viral gastroenteritis remains a leading cause of health care cost globally, prompting the need for basic diagnostic strategies. Objectives: This study aims to assess the impact of viral gastroenteritis on hemogram and C-reactive protein. Methods: By conducting a retrospective study, three groups of children diagnosed with gastroenteritis (rotavirus positive, adenovirus positive and rota/adenovirus negative group) were compared in terms of hemogram parameters and C- reactive protein. Results: Among 756 children with gastroenteritis, 7.9% of patients were rotavirus positive and 6.5% of them were adenovirus positive. Our findings disclosed a statistically significant association between low lymphocyte (2.2 ± 1.45) and MPV value (7.38 ± 0.4 fL) with rotavirus gastroenteritis. Also, the analysis revealed a high neutrophil/lymphocyte ratio (2.8± 2.1) in rotavirus group. However, our study did not reveal any prominent laboratory marker that serves as a distinctive feature of adenovirus unlike rotavirus. Conclusions: In conclusion our research highlights the potential of decreased mean platelet volume and lymphopenia as diagnostic markers for rotavirus gastroenteritis.

Mesenchymal stromal cells (MSCs) are a subset of heterogeneous non-hematopoietic fibro-blast-like cells which play important roles in tissue repair, inflammation, and immune modula-tion. MSCs residing in the bone marrow microenvironment (BMME) functionally interact with hematopoietic stem progenitor cells regulating hematopoiesis. However, MSCs have also emerged in the last years as key regulator of tumor microenvironment. Indeed, they are now con-sidered as active players in the pathophysiology of hematologic malignancies rather than passive by-standers in hematopoietic microenvironment. Once the malignant event occurs, the BMME acquires cellular, molecular, and epigenetic abnormalities affecting tumor growth and progres-sion. In this context, MSC behavior is affected by signals coming from cancer cells. Furthermore, it has been showed that stromal cells themselves play a major role in several hematological malig-nancies’ pathogenesis. This bidirectional crosstalk creates a functional tumor niche unit wherein tumor cells acquire a selective advantage over their normal counterpart and are protected from drug treatment. It is therefore of critical importance to unveil the underlying mechanisms which activate a protumor phenotype of MSCs for defining unmasked vulnerabilities of hematological cancer cells which could be pharmacologically exploited to disrupt the tumor/MSCs coupling. The present review will focus on the current knowledge about MSC dysfunction mechanisms in the BMME of hematological cancers, sustaining tumor growth, immune escape, and cancer pro-gression.

Emotional eating (EE) can be understood as a manifestation of difficulties with emotion regulation (ER) among individuals with eating disorders. Existing interventions do not always successfully treat EE. We developed a novel ER intervention based upon virtual reality to improve EE among adults with an eating disorder diagnosis. The design pivoted to non-immersive virtual delivery to increase access, particularly given heightened demand during COVID-19 for EE treatment. The study aimed to investigate the feasibility, acceptability, and preliminary signals of effectiveness of this novel ER protocol that utilized evidence-based strategies such as mindfulness and imagery rescripting as well as innovative techniques such as virtual reality. Twenty-one adults with a history of an eating disorder diagnosis and self-reported EE were recruited from the Adult Eating Disorders Program within Stanford University to receive seven weekly one-hour virtual experiences (VE) focusing on ER. Participants chose between the novel VE-Emotion Regulation (VE-ER) intervention or continuing with their current treatment as usual. Before and after the seven sessions, participants completed an assessment by filling out online questionnaires. Overall, VE-ER treatment was feasible (100% completion), and participant and therapist acceptability of VE-ER treatment was fairly high. In terms of preliminary effectiveness, the results showed a significant reduction in the frequencies of disordered eating behaviors in both groups, but a greater improvement in EE in the VE-ER group. The VE-ER group also had a significant reduction in emotion dysregulation after the treatment.

Flaviviruses are a group of positive sense single-stranded RNA viruses predominantly transmitted by arthropods (mainly mos-quitoes), that cause severe endemic infections and epidemics on a global scale. It represents a major cause of systemic morbidity and death that are expanding worldwide. Among this group, Dengue fever, West Nile virus, Yellow Fever, Japanese Encephalitis, and recently Zika virus have been linked to a spectrum of ocular manifestations. The latter encompass subconjunctival hemor-rhage and conjunctivitis, anterior and posterior uveitis (inclusive of vitritis, chorioretinitis, and retinal vasculitis), maculopathy, retinal hemorrhages, and optic neuritis. Clinical diagnosis of these infectious diseases is primarily based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. Diagnosis confirmation relies on laboratory testing, including RT-PCR and serological testing. Ocular involvement typically follows a self-limited course but can result in irreversible visual impairment. Effective treatment for flavivirus infections is currently unavailable. Prevention remains the mainstay for arthropod vector and zoonotic disease control. Effective vaccines are available only for Yellow Fever virus, Dengue virus and Japanese Encephalitis virus. This review comprehensively summarizes the current knowledge regarding the ophthalmic mani-festations of the foremost flavivirus-associated human diseases.

Nudibranchs are marine gastropod mollusks that have been extensively studied for their poten-tial to yield new bioactive compounds. This review aims to share data about the chemical and biological activity of extracts and isolated compounds from nudibranchs. The systematic review followed the PRISMA (a systematic review protocol) and covers the studies from the literature published from January 1950 to September 2023, and various scientific databases, including Elsevier, web of science, ACS publications, Taylor and Francis, Wiley Online Library, MDPI, Springer and the Marine Pharmacology website. The results presented are based on the complete set of studies that met our inclusion criteria. Among the selected studies, chemical characteriza-tion was the focus in 79.6% of cases, while biological activity assessment accounted for 20.4%. Ten different types of biological activity assays were performed, with the most frequently studied activities being cytotoxicity (43.6%), antimycobacterial (43.6%), and ichthyotoxic (9.8%) effects. Most positive results obtained from these assays were related to antimycobacterial, cytotoxicity, and ichthyotoxic activities. Eight different types of metabolites were identified, with terpenes be-ing the most prevalent (78.5% of articles), followed by alkaloids (8.1%) and aromatic polyketides (4.7%). Gathering the existing evidence can aid in identifying research gaps and planning future investigations. Our findings indicate that certain nudibranch families, such as Cadlinidae, have received limited attention in terms of studies conducted, yet show promising results in terms of biological activities.

Exudative-pleural-effusion (ePE) is a common presentation in pulmonology clinics. Pleural biopsy is indicated for identifying the aetiology in undiagnosed ePE especially the ones with low adenosine-deaminase levels. The access to rigid and semi-rigid medical thoracoscopy is scarce and heterogeneous in a resource limited country like India. In such circumstances, using flexible bronchoscope via intercostal-chest-tube for visualization of parietal pleura and pleural biopsy offers a way out. Here, in this retrospective study, we have presented our experience of such practice on 25 cases. Mean age was 52.4±1 years. Adhesions were present in 40% of the subjects. Most common finding was presence of nodules. On an average 6.8 passes were taken with maximum of 10. In 32% cases only tiny tissue was obtained, hence requiring multiple passes. Large tissue could be obtained in 44% of the subjects. Mean duration of the procedure was 35.6±9.0 minutes. Tissue diagnosis was established in 80% with most common being malignancy (48%) followed by tuberculosis (20%). In 3 cases, the final diagnosis was made by exclusion. No major complications were recorded. In conclusion, medical thoracoscopy using flexible video bronchoscope via intercostal-chest-tube was a feasible alternative for the diagnosis of ePE effusion in resource limited settings.

Radiotherapy for cancer has been known to affect the responses of immune cells, especially those of CD8+ T cells that play a pivotal role in anti-tumor immunity. Clinical success of immune checkpoint inhibitors led to an increasing interest into the ability of radiation to modulate CD8+ T cell responses. Recent studies that carefully analyzed the CD8+ T cell responses following radiotherapy suggest the beneficial roles of radiotherapy on anti-tumor immunity. In addition, numerous clinical trials that evaluate the efficacy of combining radiotherapy with immune checkpoint inhibitors are undergoing. In this review, we summarize the current status of knowledge regarding the changes of CD8+ T cells following radiotherapy from various preclinical and clinical studies. Furthermore, key biologic mechanisms that underlie such modulation, including both direct and indirect effects, are described. Lastly, we discuss the current evidence and essential considerations for harnessing radiotherapy as a combination partner for immune checkpoint inhibitors.

Oral vaccines are highly envisaged for veterinary applications due to their convenience and ability to induce protective mucosal immunity as the first line of defense. The present investigation harnessed live-attenuated Salmonella Typhimurium to orally deliver novel expression vector systems containing the Cap and Rep genes from porcine circovirus type 2 (PCV2), a significant swine pathogen. The antigen expression by the vaccine candidates JOL2885 and JOL2886, comprising eukaryotic pJHL204 and pro-eukaryotic expression pJHL270 plasmids respectively, was confirmed by western blot and IFA. We evaluated their immunogenicity and protective efficacy through oral vaccination in a mouse model. This approach elicited both mucosal and systemic immunity against PCV2d. Oral administration of the candidates induced PCV2-specific sIgA, serum IgG antibodies, and neutralizing antibodies, resulting in reduced viral loads in the livers and lungs of PCV2d-challenged mice. T-lymphocyte proliferation and flow-cytometry assays confirmed enhanced cellular immune responses after oral inoculation. The synchronized elicitation of both Th1 and Th2 responses was also confirmed by enhanced expression of TNF-α, IFN-γ, IL-4, MHC-I, and MHC-II. Our findings highlight the effectiveness and safety of the constructs with an engineered-attenuated S. Typhimurium, suggesting its potential application as an oral PCV2 vaccine candidate.

Background: Despite advances in diagnosis and treatment, the incidence and mortality of infective endocarditis (IE) have increased in recent decades despite advances in diagnosis and treatment. Studies on the risk factors for mortality in endocarditis in Latin America are scarce. Methods: This retrospective cohort study included 240 patients diagnosed with IE according to the modified Duke criteria who were admitted to two university hospitals in Rio de Janeiro, Brazil from January 2009 to June 2021. Poisson regression analysis was performed for trend tests. The multivariate Cox proportional hazards model was used to estimate the hazard ratio (HR) of predictors of in-hospital mortality. Findings: The median age was 55 years (IQR: 39-66 years), 57% were male, and 41% had a Charlson comorbidity index (CCI) score &gt; 3. Healthcare-associated infective endocarditis (54%), left-sided native valve IE (77.5%), and staphylococcal IE (26%) predominated. Overall in-hospital mortality was 45.8%, and mortality was significantly higher in the following patients: aged ≥ 60 years (53%), CCI score ≥ 3 (60%), healthcare-associated infective endocarditis (HAIE) (53%), left-sided IE (51%), and enterococcal IE (67%). Poisson regression analysis showed no trend in in-hospital mortality per year. The adjusted multivariate model determined that age ≥ 60 years was an independent risk factor for in-hospital mortality (HR = 1.9; 95% CI 1.2-3.1; p = 0.008). Interpretation: In this 12-year retrospective cohort, there was no evidence of an improvement in survival in patients with IE. Since older age is a risk factor for mortality, consensus is needed for the management of IE in this group of patients.

Aerococcus urinae is an aerobic Gram-positive coccus that grows as tiny alpha-hemolytic colonies. Actinotignum schaalii is a slow-growing facultative anaerobic Gram-positive rod. These bacteria are part of the urogenital microbiota of healthy patients, but can also be involved in urinary tract infections (UTIs), particularly in elderly men and young children [1–3]. Because A. urinae and A. schaalii are fastidious and are difficult to identify with phenotypic methods, they are underestimated causes of UTIs. Their growth is slow and requires a blood-enriched medium and an incubation time of 48 hours under anaerobic or 5% CO2 atmosphere. Furthermore, accurate identification is only possible using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) or molecular-based methods. In rare cases, these bacteria can be responsible for invasive infections. We describe here the second case of bacteremic UTI caused by both A. schaalii and A. urinae in an 89-year-old woman who presented dyspnea and asymptomatic bacteriuria. This challenging clinical and microbiological diagnosis was made by our laboratory by Gram staining urine with a leucocyte count &gt;50/μL and/or a bacterial count &gt;14/μL, urinary culture on blood agar plate, and direct bacterial identification on positive blood culture bottles (BCBs) by MALDI-TOF MS. After 10 days of antimicrobial treatment consisting of 2g amoxicillin PO t.i.d the patient was discharged with complete clinical and biological recovery. A. schaalii and A. urinae are probably still underestimated causes of UTIs. Microbiologists should assess the presence of these two bacteria in urine using the appropriate culture and identification methods where direct examination is positive for small Gram-positive cocci or rods, and a urinary dipstick is negative for nitrites and associated with leukocyturia.

Post-operative pain is the unpleasant sensory and emotional experience after surgery, its origin being both the inflammatory reaction induced by the surgical trauma on the abdominal wall, and the splanchnic pain, induced by the activation of nociceptors of the viscera, which are highly sensi-tive to distension, ischemia and inflammation. Nowadays, it is well recognized that there is a close relationship between the gut microbiome and pain perception, and that microbiome is highly af-fected by both anaesthesia and surgical manipulation. Thus, efforts to restore the disturbed micro-biome by supplementation with beneficial bacteria, namely probiotics, seems to be effective. In this article the knowledge gained mainly from experimental research on this topic is analyzed, the con-cluding message being that each probiotic strain works in its own way towards pain relief.

The progressive reappearance of the Zika virus (ZIKV) infection since October 2013 and its circulation in >70 countries and territories (from French Polynesia to Brazil and other countries in the Americas, with sporadic spread in Europe and the East) has long been reported as a global public health emergency. ZIKV is a virus transmitted by arthropods (arboviruses), mainly by Aedes mosquitoes. ZIKV can also be transmitted to humans through mechanisms other than vector infection such as sexual intercourse, blood transfusions, mother-to-child transmission. The latter mode of transmission can give rise to a severe clinical form called Congenital Zika Syndrome (CZS) which can result in spontaneous abortion or serious pathological alterations in the fetus such as microcephaly, neurological and orofacial anomalies. In this study, beside a succinct overview of the etiological, microbiological, epidemiological aspects and modes of transmission of Zika virus infection, we have focused our attention on the pathogenetic and histopathological aspects in pregnancy and the pathogenetic and molecular mechanisms that can determine microcephaly, and consequently the clinical alterations, typical of the fetus and newborns, in a subject affected by CZS.

Regional anesthesia in postoperative pain management have developed in recent years, especially with the advent of fascial plane blocks. This study aims to compare the ultrasound-guided bilateral erector spinae plane block (ESPB) versus bilateral transversus abdominis plane block (TAPB) on postoperative analgesia after laparoscopic or robotic urologic surgery. This was a retrospective observational study; 97 patients (ESPB-group) received bilateral ultrasound-guided ESPB with 20 mL of ropivacaine 0.375% plus 0.5 mcg/kg of dexmedetomidine in each side at the level of T7-T9, and 93 patients (TAPB-group) received bilateral ultrasound-guided TAPB with ropivacaine 0.375% or 0.25%. The primary outcome was post-operative numeric rating scale (NRS) pain score, which was significantly lower in the ESPB-group on postoperative days 0, 2, and 3 (p=0.012, p=0.016 and p=0.004). Concerning the secondary outcomes, consumption of ropivacaine was significantly lower in ESPB-group (p<0.001) and the total amount of analgesic rescue doses was significantly lower in the ESPB-group than TAPB-group in postoperative days from 2 to 4 (1 vs 3, p>0.001). Incidence of postoperative nausea and vomiting was higher in the TAPB-group and no block related complications were observed. We conclude that ESPB provide better postoperative pain control with less consumption of local anesthetic and less total rescue analgesic therapies.

Allylbenzenes (apiol, dillapiol, myristicin and allyltetramethoxybenzene) are individual components of plant essential oils that demonstrate antitumor activity, as well as enhancing effect on cytotoxic drugs such as paclitaxel, doxorubicin, cisplatin, etc. Triphenylphosphine (PPh3) derivatives of allylbenzenes are 2-3 orders of magnitude more potent than allylbenzenes in terms of IC50. Inhibition of efflux pumps has been reported for allylbenzenes, and PPh3 moiety is deemed to be responsible for preferential mitochondrial accumulation and depolarization of mitochondrial membranes. However, due to poor solubility the practical use of these substances has never been an option. Cyclodextrin-based (CD) molecular containers suggested here provided solubilization of allylbenzenes and its PPh3-derivatives. So, in this study we have observed an increase antitumor activity of paclitaxel in the presence of PPh3-derivatives adjuvants by an order of magnitude (in terms of IC50) against adenocarcinomic human alveolar basal epithelial cells A549. At the same time, they are quite powerful cytostatics themselves against A549 cells. On the other hand, the cytotoxic formulations developed show pronounced selectivity of the antiproliferation activity: high against tumor cells line (A549) and low toxicity of these composition was demonstrated on normal cells HEK293T, red blood cells, and sea urchin embryos (a model close to the human genome). On non-cancer HEK293T cells, it was shown that PPh3-derivatives of allylbenzenes at a concentration of 100 µM cause the death of about 20% of cells, while on A549 cancer cells, 85% of cells die. PPh3 derivatives of allylbenzenes, when solubilized in CD molecular containers, show remarkable potential as adjuvants to some of the widely used cytotoxic drugs.

Few clinical factors can help predict spontaneous culture conversion (SCC) in patients with Mycobacterium avium complex-pulmonary disease (MAC-PD). We retrospectively classified 373 MPD patients who had undergone watchful waiting without antibiotics according to the so-called ‘body mass index (BMI), age, cavity, erythrocyte sedimentation rate (ESR), and sex (BACES)’ severity. We evaluated whether lower severity is associated with a higher rate of SCC. Of 373 patients, 153 (41%) achieved SCC without antibiotics during a median follow-up of 48.1 months. There was a trend toward a higher SCC rate in patients with lower BACES severity: 48% (87/183), 37% (58/157), and 24% (8/33) in the mild, moderate, and severe BACES groups, respectively. In addition, a favorable outcome, defined as maintaining SCC or having two consecutive negative sputum cultures until the last follow-up date, was also more common in patients with lower BACES severity with 53% (97/183), 34% (54/157), and 18% (6/33) in the mild, moderate, and severe BACES groups, respectively. In multivariate analysis, moderate (hazard ratio [HR]=0.63; 95% confidence interval [CI] 0.44 – 0.91; p = 0.013) and severe BACES (HR 0.37; 95% CI 0.16 – 0.90; p = 0.028) had a significantly negative impact on favorable outcomes compared to mild BACES. Lower BACES severity may be associated with SCC in MAC-PD patients.

Due to the low content, few studies are focused on the volatile compounds of Phlomoides rotata (Benth. ex Hook. f.) Mathiesen (PR, syn. Lamiophlomis rotata (Benth.) Kudô). However, such volatile compounds may have important pharmacological activities such as antioxidant, anticancer. In order to identify the chemical markers (CMs) in the essential oils (Es) and explore the potential bioactivities, we first conduct a thoroughly investigation on the volatile compounds and evaluate their anti-oxidant activities (AOAs), to the best of our knowledge. Light yellow Es with a fresh and elegant smell are obtained by hydro-distillation with an average yield of 0.11% (mL/g). After separation through cryoprecipitation, the crystals (Cs) and EOs removed crystals (RCs) were gotten, respectively. A total of 81 components are qualified and quantified in the Es, Cs and RCs, in which 44 ones are first reported from PR. As for content, the main compounds are long-chain fatty acids (LCFAs) and their esters. Among them, palmitic acid (PA), myristic acid (MA), linoleic acid (LA), oleic acid (OA) and methyl palmitate are highlighted, Besides, hexahydrofarnesyl acetone and phytol are also prominent Four kinds of C13-norisoprenoids are first reported from PR, in which, trans-β-damascenone is potent in flavour. In sum, these eight representative compounds can be chosen as the CMs. The AOAs of Es, Cs, RCs and four CMs such as PA, MA, LA and OA are evaluated by in vitro assays. In general, PA and MA present pro-oxidant activities (POAs) or weak AOAs. LA and OA show POAs or weak AOAs in lower concentration group, whereas demonstrate medium or strong AOAs in higher concentration group. Usually, the RCs demonstrate stronger AOAs and the Cs present weaker AOAs compared with those of the corresponding Es, which should be related to their different content of PA. This study can give some hints on the utilization of such Es which are abundant in LCFAs.

Body mass index has been studied as one of the factors that negatively influences COVID-19. In this work we intend to analyze this influence. A representative sample of the population of Beira Interior was used (around 2%), to which immunity research and a socio-demographic survey were carried out. It was found that obesity influences the vaccination rate, and all other variables analyzed were not influenced by the body mass index.

(1) The incidence of ankyloglossia ranges from 0.02 to 10.7%. The literature describes the effect of ankyloglossia on selected dysfunctions of the stomatognathic system, however no studies could be found reporting the influence of ankyloglossia on the occurrence of several disorders in a group of subjects. The aim of the present study was to assess the effect of lingual frenulum on swallowing, speech, occlusion, and periodontal status; (2) Methods: The subjects were 172 patients, 86 with ankyloglossia (study group) and 86 with normal tongue frenulum (control group). In all subjects, the length of tongue frenulum, the type of swallowing, tongue mobility, occlusion, periodontal status and speech abnormalities were assessed; (3) Results: All subjects from the control group and all those with mild ankyloglossia showed normal tongue mobility. A limited tongue mobility was found in 29.4% subject with moderate and in 70.6% subjects with severe ankyloglossia. Rhotacism was observed in 21.3% subjects with normal frenulum, in 2.1% with mild, 38.3% with moderate, and 38.3% with severe ankyloglossia. Malocclusion or crowding was diagnosed in subjects with mild, moderate and severe ankyloglossia in 7.4%, 33.9% and 20.7% subjects (total 62%), respectively, whereas in the control group - in 21.6% subjects. No abnormalities in the periodontium in the area of the lingual surfaces of the crowns of the lower central incisors were found in any of the examined persons. Among patients with infantile type of swallowing 24.4% had a normal length of the tongue frenulum, 11.1% - mild, 28.9% - moderate, and 35.6 - severe ankyloglossia. Among patients presenting a mature type of swallowing 58.7% had a normal length of the frenulum; (4) Conclusions: 1.A shortened tongue frenulum correlates with “infantile swallowing pattern”. 2. Moderate or severe ankyloglossia significantly limits tongue mobility. 3. Short tongue frenulum is related to speech disorders.

Aronia berries contain antioxidants that may have health promoting properties e.g., demonstrated positive effects on hypertension and dyslipidemia. There is a close link between cardiovascular diseases and hypertension and dyslipidemia, and cardiovascular events are the leading cause of death among subjects with T2D. Thus, we investigated the effect of 8 weeks supplementation with fermented aronia extract (FAE), non-fermented aronia extract (AE) and placebo on cardiovascular risk factors. The extracts were incorporated into snack bars containing 34 g (37%) aronia extract, or 17 g (21%) wheat bran for placebo, as well as raisins and coconut oil. The study was randomized and blinded with a triple-cross-over design. We examined the effects of aronia extracts on blood pressure, adiponectin and high-sensitive C-reactive protein and found no effects. After supplementation with placebo, there were significantly higher total-cholesterol, LDL-cholesterol, and HDL-cholesterol, with the placebo group showing significantly higher increases in total-cholesterol and LDL-cholesterol than the FAE group. Furthermore, we observed an increase in HDL-cholesterol in the AE group and an increase in triglyceride in the FAE group. Thus, we assume that raisins may have increased the participants’ cholesterol levels, however, with both AE and FAE having the potential to prevent this increase.

As of the end of 2022, despite the disruptions caused by the COVID-19 pandemic, the global HIV epidemic persists, with 39 million individuals living with the virus and 1.3 million new infections reported in that year. Opportunistic infections associated with AIDS claimed the lives of over 630,000 people in 2022, contributing to a cumulative death toll exceeding 40.4 million since the disease's emergence in 1981. Although advances in HIV diagnosis and antiretroviral therapy have transformed the disease into a manageable chronic condition, issues like drug resistance, low compliance, and high treatment costs persist. Until a vaccine becomes available, a comprehensive approach involving prevention and therapy is essential, particularly for high-risk populations. Research shows that prevention strategies are more cost-effective than treatment. The development of antiretroviral drugs has also spurred the creation of antivirals for other infections. The emergence of COVID-19 vaccines has opened new avenues for HIV vaccine development, as lessons from vaccine platform technologies like mRNA, viral vectors, and protein subunits can be applied to HIV. This review explores the most promising prophylactic and therapeutic HIV vaccine trials, emphasizing the need for a multi-pronged approach combining vaccines with non-vaccine strategies. Though significant progress is anticipated, the road to a viable HIV vaccine remains long, especially for high-risk populations, such as medical workers, blood transfusion recipients, and drug users. The combinatorial approach, capitalizing on various aspects of immunity, may hold the key to defeating HIV in the future.

The new class of mRNA vaccines is studied extensively, leading to many novel prospects based on the pivotal success of vaccines against the SARS-Cov-2 virus. Many novel mechanisms of immune response discovered have led to the possibility of mutation-resistant vaccines by combining multiple conserved epitopes as antigens to manipulate the T-cell and B-cell responses; these antigens can also come from different organisms, providing protection against numerous diseases and of most tremendous significance is the utility of mRNA vaccines in preventing and treating more than 100 autoimmune disorders. This is a significant humanitarian breakthrough given the ease and faster and low cost of mRNA vaccines, being a chemical entity. This paper provides a prospective analysis of mRNA vaccines with much broader applications than anticipated when these vaccines entered treating SARS-Cov-2 infections.

Metabolic syndrome is a growing global health problem. Evidence suggests that diets rich in phytochemical-containing herbs and spices can contribute to reduced risk of chronic disease. This review assesses the scope of evidence supporting the use of herbs and spices in the diet for prevention or treatment of metabolic syndrome and associated health conditions. A search of PubMed and Scopus databases was carried out to assess the available clinical or cohort evidence for culinary doses of commonly used herbs and spices. Trials that were measuring health factors related to metabolic disorders or the health of individuals with metabolic syndrome or associated diseases were included. Out of a total of 1742 papers identified, there were 146 relevant studies on black pepper, chilli, cardamom, cinnamon, coriander, cumin, fennel, fenugreek, garlic, ginger, Nigella seed, rosemary, sage and turmeric. No relevant research was found for cloves, mint, oregano, parsley or thyme. Cinnamon, fenugreek and ginger were the herbs/spices with the most published trials on them and showed promise for glycaemic control. Cardamom appears to have potential to reduce inflammatory markers, and cinnamon, ginger and turmeric for blood lipids. Patients with type 2 diabetes were the population most likely to be included in studies, but the preventative benefits of herbs/spices in healthy populations were also investigated, particularly for chilli, ginger and cinnamon. There is evidence for the beneficial effect of culinary doses of many common herbs/spices in the prevention and treatment of metabolic syndrome and associated disorders.

This paper first introduces the main classification of brain diseases and the main causes of these diseases. It is followed by wavelet analysis, which is a mathematical function or wave-like pattern used to transform data, which can decompose the signal into different wavelet functions, each of which is related to a specific scale or frequency. Wavelet analysis has been applied in many fields such as image processing, data analysis and engineering. In addition, wavelet is also used in the analysis of biological signals. Wavelet analysis breaks down brain signals, such as EEG or fMRI data, into various frequency components at different scales. Wavelet analysis provides time-frequency localization. Pattern recognition can be enhanced by isolating salient features in the data. Wavelet denoising can effectively separate noise from underlying brain signals. Wavelet denoising usually adopts threshold method. Wavelet analysis can enhance pattern recognition by isolating salient features in the data. Researchers can train machine learning models based on these wavelet-derived features to recognize specific patterns associated with different neurological disorders. Wavelet analysis can track these changes by continuously evaluating the frequency content of the neuroimage data over time. Through continuous efforts, wavelet theory and technology have become valuable tools in the field of neuroscience and brain disease research.

Human papillomavirus testing is increasingly central to screening programs for cervical cancer. Although HPV testing has excellent clinical sensitivity it suffers from modest clinical specificity. Cytology has taken an important role as a triage test, while more recently HPV16/18 genotyping has provided modest incremental benefits. Despite such progress issues remain to be addressed, some of which are how to: 1) improve access to the best methods, 2) decrease costs so more women can be screened, 3) simplify management algorithms, 4) Recognize the evolving diagnostic landscape created by widespread HPV vaccination. Part of the solution lies in improving the positive predictive value of the initial screen and reflex triage. An aspirational goal should be that most women attending colposcopy have true precancer; DNA methylation testing has a role to play here. Cervical cancers and CIN2/3 generally have high levels of methylation in target human and HPV genes. In contrast normal and healthy women with no intraepithelial lesions or malignancy usually have low methylation. Furthermore, there is an interesting and useful secular gradient of increasing cervical DNA methylation as women progress toward precancer and cancer. Recent results from clinical studies using commercially available routine qPCR-based DNA methylation tests have been encouraging, demonstrating the potential for higher sensitivity and specificity than current triage methods.

A healthy cornea is a nonvascularized, transparent tissue. It is nourished by diffusion through the tear film, aqueous fluid and neurotrophins supplied by the corneal innervation. The cornea is devoid of both blood and lymphatic vessels, which makes it an immunologi-cally privileged tissue. Corneal neovascularization develops due to an imbalance between angiogenic and anti-angiogenic factors and can lead to a significant decrease in visual acui-ty. It may cause scarring, lipid keratopathy, and corneal edema. The resulting pathological vascularization of the cornea reduces its immune privilege and significantly worsens the prognosis after subsequent penetrating keratoplasty, increasing the risk of rejection of the transplanted flap. Neovascularization is favored by many disease processes, including auto-immune diseases, viral inflammations, mainly herpes and varicella-zoster, and blepharitis [1]. There are several options to treat corneal neovascularization, both pharmacological and surgical. Angiostatic treatment involves inhibiting the growth of new vessels by suppressing inflammatory responses. VEGF inhibitors, steroids, cyclosporine A, and amniotic membrane grafts secured to the cornea work this way. VEGF inhibitors are the agents with the direct and most potent angiostatic effect. Angioregressive treatment, on the other hand, results in the regression of already existing pathological vessels. This therapy is also based on VEGF inhibitors, which, however, have the most potent effect on newly formed and small vessels but are less effective in reducing large-caliber and mature vessels. A more effective method for such vessels is ablation, which involves surgical closure. The most commonly used an-gio-occlusive method is needle diathermy and argon or yellow laser therapy. In advanced corneal neovascularization, corneal transplant surgery may be necessary. It is best performed after pretreatment with anti-VEGF preparations, often continued after corneal transplanta-tion to reduce the risk of transplant rejection [2]. This paper discusses the pathogenesis of corneal neovascularization and the current and future trends in its treatment.

Pregnant women are especially vulnerable to respiratory diseases. We aimed to study seroconversion rate during pregnancy in a cohort of consecutive pregnancies tested in the first and third trimesters and to compare maternal and obstetric complications between women who seroconverted in the first versus the third trimester. This is an observational, cohort study carried out at Hospital Universitario de Torrejón, in Madrid, Spain, during the first peak of the COVID-19 pandemic. All consecutive singleton pregnancies with a viable fetus attending their 11-13 weeks scan between January 1st and May 15th, 2020, were included and monthly follow up until delivery. Antibodies against SARS-CoV-2 (IgA and IgG) were analyzed on stored serum samples obtained from the first and third trimester routine antenatal bloods in 470 pregnant women. Antibodies against SARS-CoV-2 were detected in 31 (6.6%) women in the first trimester and in 66 (14.0%) in the third trimester, including 48 (10.2%) that were negative in the first trimester (seroconversion during pregnancy). Although the rate of infection was significantly higher in the third versus the first trimester (p = 0.003), no significant differences in maternal or obstetric complications were observed in women testing positive in the first versus the third trimester.

Prostate cancer (PCa) used to be one of the most common nondermatologic cancers in men that can be treated only with surgery. However, a revolutionary breakthrough came in the 1980s with the introduction of long-acting luteinizing hormone-releasing hormone (LHRH) agonists for the cu-rative treatment of PCa. This paradigm shift contributed to the combined use of androgen depri-vation therapy (ADT), chemotherapy, and radiotherapy for the treatment. The latest data high-light the use of treatment intensification (TI), i.e., combined use of radiotherapy (RT) and hormo-nal or drug treatments, for localized or locally advanced PCa. Indeed, the results of combined modality treatments have shown a reduction in disease-specific mortality and improved overall survival. Although TI seems promising, more research studies are warranted to confirm its effi-cacy. This review summarizes the latest available outcome results of pivotal trials and clinical studies on the efficacy of TI.

Serum carbohydrate antigen 19-9 (CA19-9) levels can increase in nontuberculous mycobacteria pulmonary disease (NTM-PD) and the levels correlate with disease activity. We compared the clinical characteristics of NTM-PD patients with and without elevated CA19-9 levels and evaluated its association with the antibiotic response in a retrospective study of NTM-PD patients diagnosed between January 1994 and December 2020. We analyzed 1,112 patients who had serum CA19-9 measured: 322 with elevated CA19-9 and 790 with normal CA19-9. The erythrocyte sedimentation rate and C-reactive protein levels were significantly higher in the elevated CA19-9 group (p < 0.001 and p = 0.029, respectively). The 1-year culture conversion rate after antibiotics did not differ between the elevated (n = 206) and normal (n = 377) CA19-9 groups (80% vs. 72%, p = 0.055). Analysis of a subset of 434 patients revealed that current smoking, bronchiectasis, acid-fast bacilli smear positivity, and the M. abscessus strain significantly reduced microbiological cure rates. Serum CA 19-9 levels did not have a significant association with microbiological cure in a multivariate analysis. These findings suggest that the role of serum CA19-9 in predicting antibiotic treatment outcomes is limited, and that elevated CA19-9 does not necessarily indicate a poor outcome.

Xpert MTB/RIF is rapid molecular diagnostic tool capable of simultaneously detecting Mycobacterium tuberculosis and rifampicin resistance. This study aimed to access the diagnostic precision of Xpert MTB/RIF assay to detect pulmonary and extra-pulmonary tuberculosis and to evaluate the performance for the detection of rifampicin resistance. Of 37695 samples, 7156(18.98%) were tuberculosis positive, 509(7.11%) were rifampicin-resistant. The sensitivity, specificity, PPV, NPV, Diseases prevalence and accuracy of Xpert MTB/RIF assay for PTB were 99.87% (95%CI:99.75-99.94), 99.92%(95%CI:99.88-99.95), 99.71%(95%CI:99.54-99.82),99.97%(95%CI:99.93-99.98),21.38% (95%CI:20.92-21.86),and 99.91%(95%CI:99.87-99.94), respectively. For EPTB, the sensitivity, specificity, PPV, NPV, Diseases prevalence and accuracy of Xpert MTB/RIF assay accounted for 99.45% (95%CI:98.73-99.82),99.84%(95%CI:99.73-99.92),98.70%(95%CI:97.73-99.25),99.93% (95%CI:99.84-99.97),10.64%(95%CI:9.99-11.31),and 99.80%(95%CI:99.68-99.88), respectively. Despite its high sensitivity for detecting tuberculosis and rifampicin resistance, Xpert MTB/RIF had contradictory results for 20.5% of cases among patients with negative smear results and 54.9% of cases among patients with a high risk of Multidrug-resistant tuberculosis. Of 47 fluoroquinolone-resistant, 16.56% (26/157) of Multidrug-resistant tuberculosis isolates and 4.02% (20/498) isoniazid-resistant are fluoroquinolone-resistant, a characteristic distribution leading to about 17.2% of fluoroquinolone resistance events and relevant marker gyr-A mutations in MDR tuberculosis isolates. Further, our study indicated that increased fluoroquinolone resistance among Rifampicin-resistant and isoniazid-resistant tuberculosis endangers the success of newly endorsed MDR-TB regimens.

Valsartan (Val) is an important antihypertensive medication with side effects such as dizziness and angioedema. These constraints are due to the low oral bioavailability and relatively short half-life. The goal here is to incorporate Val into a mixed micelles system that can enhance transdermal delivery. Thin-film hydration and micro-phase separation were used to produce Val-loaded mixed micelle systems. A variety of factors, including surfactant type and drug-to-surfactant ratio, were optimized to produce micelles with low size and high Val entrapment efficiency (EE). The size, polydispersity index (PDI), zeta-potential, and drug entrapment efficiency of the prepared micelles were all measured. The drug release profiles in vitro were assessed using dialysis bags, and the permeation through abdominal rat skin was assessed using a Franz diffusion cell. All formulations had high EE levels exceeding 90% and low particle charges. The micellar sizes ranged from 107.6 to 191.7nm, with average PDI values of 0.3. The in vitro release demonstrated a uniform slow rate that lasted one week with varying extents. F7 demonstrated a significant (P < 0.01) transdermal efflux of 68.84 ± 3.96 µg/cm2/h through rat skin when compared to the control. As a result, the enhancement factor was 16.57. Val-loaded mixed micelles were successfully prepared using two simple methods with high reproducibility, and extensive transdermal delivery was demonstrated in the absence of any aggressive skin modifying enhancers.

Acute-on-Chronic Liver Failure (ACLF) refers to the deterioration of liver function in individuals who already have chronic liver disease. In the setting of ACLF, liver damage leads to the failure of other organs and is associated with increased short-term mortality. Optimal medical management of patients with ACLF requires implementing complex treatment strategies, often in an intensive care unit (ICU). Failure of organs other than the liver distinguishes ACLF from other critical illnesses. Although there is growing evidence supporting the current approach of ACLF management, mortality associated with this condition remains unacceptably high. In this review, we discuss considerations for ICU care of patients with ACLF and highlight areas for further research.

Proprioceptive deficits accompanied with motor paresis after stroke, namely sensory ataxic motor paresis has a poorer prognosis of recovery than pure motor deficit. We aimed to investigate the effects of repetitive peripheral magnetic stimulation (rPMS) on sensory ataxic upper extremity (UE) paresis at acute stroke. Eighteen stroke participants with sensory ataxic UE paresis were randomized. rPMS group received five sessions of intervention per week, where 20 minutes of rPMS prior to 20 minutes of physical therapy (PT) every other day, alternating with 40 minutes of PT. The control group received five sessions of 40 minutes of PT/week. Outcome measures were Wolf motor function test (WMFT), UE motor section of Fugl-Meyer Motor Assessment Scale (FMA-UE), and Thumb localizing test (TLT). All assessments were compared before and after intervention. rPMS group received mean 6.5 sessions and the control group received 12.8 sessions, showing significantly imbalanced intervention due to different timing of hospital discharge. The imbalance was corrected by calculating gains of motor scores divided by sessions as Progress Rate (PR). Corrected gains (PR) of rPMS group was more significantly enhanced in WMFT and FMA-UE than control groups. rPMS group tended to improve TLT more than control one. rPMS might improve sensory ataxic UE paresis after stroke and proprioceptive deficit.

In a pre-post-treatment design, this feasibility study examines the effects of twelve weekly online Feldenkrais Awareness Through Movement (ATM) lessons on somatosensory tinnitus (ST), which is often associated with physical issues like neck pain. Two professional Feldenkrais teachers led online ATM lessons in two groups for a total of seventeen participants. Before and after treatment, we assessed tinnitus distress (using the Tinnitus Questionnaire, TQ), interoceptive awareness, and the short WHO quality-of-life questionnaire. We collected weekly changes in tinnitus severity (using the Tinnitus Functional Index, TFI) and neck pain (using the Neck Bournemouth Questionnaire), and assessed state anxiety and perceived tinnitus intensity directly before and after each ATM. Importantly, we found a significant reduction in tinnitus distress along with significant individual differences. Linear mixed-model analyses further suggest an overall decrease in tinnitus severity and neck pain over time. Notably, individual reductions in TFI correlated with reduced neck pain, and reductions in TQ correlated with increased interoceptive awareness. Although this study is limited in patient number, it provides valuable information about the characteristics of patients with ST and suggests a new method to reduce neck pain and perceived tinnitus in the comfort of patients’ homes. However, further studies are necessary to verify these results and to compare the effectiveness with conventional therapy approaches.

Abatacept (CTLA4-Ig) – a monoclonal antibody which restricts T cell activation – is an effective treatment for rheumatoid arthritis (RA). Herein, we aimed to investigate for biomarkers of response to abatacept. We performed a detailed immunological profiling of CTLA4-treated RA patients’ peripheral blood (PB) cells and sera using flow cytometry and proteomics analysis, respectively. At 6 months of treatment, 34.5% of patients attained clinical response. Notably, baseline levels of Th1 and myeloid cell populations were significantly elevated in PB of responders compared to non-responders (P-value<0.05). Additionally, proteomics analysis revealed 10 amongst 303 molecules which were associated with clinical responses. Should the present data be confirmed in a larger cohort could be of clinical value.

Chronic rhinosinusitis (CRS) can have a significant impact on quality of life. With persistent symptoms and the failure of initial medical treatments, surgical management is indicated. Despite the excellent results of endoscopic sinus surgery for persistent CRS, it is quite a challenging procedure for frontal sinusitis given the complex anatomy and location of the frontal sinus. Frontal sinus cells significantly contribute to the complexity of the frontal sinus, and numerous studies have sought to establish their association with sinusitis. This review offers a comprehensive understanding of the frontal sinus cells, their different classifications, their prevalence among different populations, and their relationship to sinusitis. After an extensive review of the current literature, the International Frontal Sinus Anatomy Classification (IFAC) is the most recent classification method and a preferred practical preoperative assessment tool. Although the Agger Nasi Cell is the most prevalent cell among all reported populations, ethnic variations are still influencing the other cells' distribution. Studies are inconsistent in reporting a relationship between frontal sinus cells and sinusitis, and that is mainly because of the difference in the classification method used. More research using a standardized classification method is needed to understand the association between frontal sinus cells and sinusitis.

Dentinal Hypersensitivity (DH), a prevalent oral health issue affecting approximately one-third of adults. In this six-months retrospective study, a comparison was made to assess the effectiveness of two diode lasers with different wavelengths (980 nm and 1064 nm) in the treatment of tooth affected by DH. In total, 160 patients were divided into two treatment groups: one receiving treatment with a 980 nm diode laser (n=80) and the other with a 1064 nm diode laser (n=80). Pain was assessed using the Visual Analogue Scale (VAS) at baseline, immediately post-treatment, and at 3- and 6-months follow-up. Both groups followed the same treatment protocol, involving the application of a graphite paste to the exposed dentin before laser irradiation. Both lasers operated at an output power of 0.5 W in continuous and non-contact mode, with a 320 µm spot size. A significant reduction in mean VAS scores at all follow-up intervals compared to baseline was noted. 980 nm group had mean VAS scores of 7.9, 2.36, 2.31, and 2.38, while the 1064 nm group had scores of 8.01, 1.01, 1.16, and 1.13 at baseline, immediately post-treatment, and at 3 and 6 months, respectively. At all times of follow-up, the 1064 nm wavelengths showed a statistically significant reduction in mean values of VAS compared to the 980 nm. The findings may inform future research on optimizing laser-based treatments for DH.

We investigated the biomechanical behaviour of different fixations of the tibial posterior malleolus (TPM), simulating distinct situations of involvement of the tibiotalar articular surface (TTAS) through a finite element model (FEM). A 3D computer-aided design model of the left ankle was obtained. The materials used were divided according to their characteristics into ductile and non-ductile, and all materials were assumed to be linear elastic, isotropic, and homogenous. Three different fracture lines of the TPM were defined, with sagittal angles of 10º, 25º, and 45º. For biomechanical comparison, different constructions using a trans-syndesmotic screw (TSS) only (Group T), a one-third tubular plate only with (Group PT) and without (Group PS) a TSS, and a locked compression plate with (Group LCPT) and without (Group LCPS) a TSS were tested. FEM was used to simulate the boundary conditions of vertical loading. Load application regions were selected in the direction of the 700N Z axis, 90% on the tibia and 10% on the fibula. Data on the displacement and stress in the FEM were collected, including the total principal maximum (MaxT) and total principal minimum (MinT) for non-ductile materials, total displacement (desT), localized displacement at the fragment (desL), localized displacement at syndesmosis (desS), and Von Mises equivalent stress for ductile materials. The data were analyzed using ANOVA and multiple comparison LSD tests were used. For TPM fractures with a sagittal angles 10º and 25º, desL in the PT and LCP groups was significantly lower, as well as Von Mises stress in Group LCPT in 10º, and PT and LCPT groups in 25º. TPM fractures with a sagittal angle of 45º, desL in the LCP group and Von Mises stress in Group LCPS and LCPT was significantly lower. We found that any TPM fracture may indicate instability of the distal tibiofibular syndesmosis, even when the fragment is small. Our study showed that in fragments involving 10% of the TTAS, the use of a TSS is sufficient, but when the involvement is greater than 25% of the TTAS, either non-locked or locked plate must be used to buttress the TPM. In posterior fragments affecting 45% or more of the TTAS, the use of a locking plate is recommended.

With more than half of U.S. adults reporting alcohol consumption the last 30 days and nearly 6% reporting heavy drinking, alcohol imposes a significant socioeconomic burden. While there are a host of current medications approved to treat alcoholism, they have limited effectiveness and lack support from both providers and patients. Semaglutide, a medication originally developed for obese type 2 diabetics, may offer a distinctly new approach. A survey to assess the impact of semaglutide on alcohol consumption and desire was designed and distributed in semaglutide-user Facebook and Reddit groups. Of those who had reported drinking before starting semaglutide, 21% of respondents (N= 121) ceased drinking altogether, and 88·4% of respondents (N=538) reported a reduction in their desire to consume alcohol after commencing their medication. Respondents also shared further personal accounts of decreased occurrences of compulsive or "addictive" behaviors beyond a reduction in the desire to consume alcohol. Considering the growing number of reports detailing experiences such as these, combined with our survey results indicating a reduction in both frequency and quantity of alcohol consumption, we strongly recommend conducting scientifically rigorous investigations and clinical trials to explore the potential of semaglutide for addressing conditions associated with alcohol use.

Multiphoton microscopy (MPM) is a cutting-edge nonlinear microscopy technique known for its exceptional capabilities in imaging dense tissues, making it an ideal tool for exploring human kidney tissue. This study delves into the application of MPM in evaluating renal cell tumors and characterizing tumor capsules. MPM encompasses two core methods: two-photon excitation fluorescence (TPEF) and second harmonic generation (SHG). It leverages femtosecond lasers to provide deep tissue imaging while minimizing phototoxicity, making it well-suited for live tissue analysis. The study analyzed 100 formalin-fixed paraffin-embedded (FFPE) kidney tissue samples, ensuring compliance with ethical standards. Using a Ti:Sapphire laser for femtosecond pulses and a variety of optical components and filters, the researchers captured TPEF and SHG signals, facilitating image analysis. Normal kidney tissue exhibited distinctive structures like glomeruli and tubules under MPM. Renal cell carcinoma (ccRCC) displayed unique TPEF patterns with eccentrically located nuclei and indistinct cytoplasmic membranes. Papillary RCC (pRCC) exhibited a papillary pattern with dark nuclei, while chromophobe RCC (chRCC) showcased distinct features like thick cell membranes, strong TPEF signal in nuclei, and granular cytoplasm. Renal oncocytoma (RO) presented strong TPEF signals in cuboidal cells with microcyst-like arrangements. Overall, MPM proved invaluable in assessing human kidney tissue, offering distinct TPEF patterns for different renal cell tumor types. This non-invasive technique has the potential to enhance pathological examinations and advance our understanding of complex biological processes, ultimately contributing to improved diagnostics and treatment strategies for renal diseases.

Background: The effect of rice bran arabinoxylan compound (RBAC), a plant-based immunomodulator, on the quality of life (QoL) in cancer patients and underlying physiological pathways remains unclear. Trial design: The RBAC-QoL study is a double-blind, randomised, controlled pilot feasibility study. The aim is to determine RBAC’s effects on QoL and the associated action mechanisms. Primary outcomes are the EORTC QLQ-C30 functional, symptom, and global QoL scores with inflammatory, nutritional, and cytokine parameters as secondary and exploratory outcomes. Methods: Recruitment targets adults diagnosed with solid organ tumours (≥ stage II) undergoing active treatment in several outpatient centres in New South Wales, Australia. Interventions are RBAC or matched placebo at 3g/day for 24 weeks allocated through stratified randomisation with participants, oncologists, and data collectors blinded. Data is collected from five study visits six weeks apart. The trial is ongoing. An interim intention-to-treat analysis was performed using repeated measure ANOVA with pairwise comparisons where statistical significance is observed and adjusted with covariates. Results: Global QoL scores from currently available data (n = 16; RBAC = 7, placebo = 9) were statistically different between groups (F[1,8] = 8.6, p = 0.019, eta2[g] = 0.267). Pairwise comparisons found significant differences at week 6 (p = 0.032, Cohen’s d = 1.454) and marginally at week 12 (p = 0.069, d = 1.427). Age-adjusted analysis showed a continuous upward trend in QoL improvement over time with RBAC, while the placebo group did not deviate from baseline QoL. Significant elevations of serum white blood cell count (week 18) and total protein (weeks 12 and 18) were detected in the RBAC group compared to placebo. The total protein levels correlated highly with white blood cell count (Pearson’s r = 0.539, p < 0.001) and moderately with the global QoL scores (r = 0.338, p = 0.01). No intervention-related adverse events were reported in both groups. Conclusions: RBAC improves QoL beyond placebo during active cancer treatment, possibly through the immuno-nutritional pathway. These findings are preliminary but valuable for future research. Funding and registration: Daiwa Pharmaceutical Co., Ltd, Japan; BioMedica Nutraceuticals Pty Ltd., Australia. ANZCTR Reg No: ACTRN12619000562178p.

Apraxia of speech is a persistent speech motor disorder that affects speech intelligibility. Studies on speech motor disorders with transcranial Direct Current Stimulation (tDCS) have been mostly directed to post-stroke aphasia. Only a few tDCS studies have focused on apraxia of speech or childhood apraxia of speech (CAS), and no study has investigated individuals with CAS and people with trisomy 21 (T21, Down Syndrome). This study examined the effects of tDCS combined with a motor learning task in developmental apraxia of speech co-existing with T21 (ReBEC RBR-5435x9). The accuracy of speech sound production of nonsense words (NSWs) during Rapid Syllable Transition Training (ReST) under 10 sessions of anodal tDCS (1.5 mA, 25 cm) over the Broca’s area with cathode over the contralateral region was compared to 10 sessions of sham-tDCS and 4 control sessions in a 20-year-old male individual with T21 presenting moderate-severe childhood apraxia of speech (CAS). The accuracy for NSWs production progressively improved (gain 40%) under tDCS only (sham-tDCS and control sessions showed <20% gain). A decrease in speech severity from moderate-severe to mild-moderate indicated transfer effects in speech production. The speech accuracy under tDCS was correlated with Wernicke’s area activation (P3 current source density), which in turn, was correlated with the activation of the left supramarginal gyrus and the Sylvian Parietal Temporal Junction. Repetitive bihemispheric tDCS paired with ReST may have facilitated the speech sound acquisition in a young adult with T21 and CAS, possibly by recruiting brain regions required for the phonological working memory.

Patients hospitalized with COVID-19 are at a higher risk of thrombotic events following discharge, however the role of extended thromboprophylaxis remains controversial. The purpose of this study is to evaluate current extended post-discharge thromboprophylaxis practice and its outcomes.This study was a single-center, retrospective chart review of patients within Hennepin Healthcare hospitalized with COVID-19 from April 1^st 2020 to December 31^st 2021 with increased risk of thrombotic event based on D-dimer. The primary outcome was to describe current prescribing practices based on the number of patients who were eligible and received anticoagulants on discharge. Secondary outcomes included comparing the patient’s risk for thromboembolism based on a modified International Medical Prevention Registry on Venous Thromboembolism (IMPROVE-VTE) score to the current internal prescribing practice guideline, evaluating efficacy outcomes based on new thromboembolic events, and assessing safety of extended-thromboprophylaxis using the International Society of Thrombosis and Hemostasis criteria for major bleeding within 30 days of hospitalization discharge.Of 1984 patients who were hospitalized with COVID-19 infection, 961 patients were eligible to receive thromboprophylaxis at discharge, with a total of 191 patients who received anticoagulation according to the Hennepin Healthcare practice guideline. However, using the IMPROVE-VTE score, only 206 patients qualified for post-discharge thromboprophylaxis, and 63 total patients received anticoagulation. A new thromboembolic event occurred in 20 patients (5.8%) and 14 patients (4.1%) experienced major bleeding.The Hennepin Healthcare guideline for extended thromboprophylaxis at discharge encompassed more patients compared to the IMPROVE-VTE score. The incidence of a new thromboembolic event and major bleeding were low in both groups, although venous thrombotic events occurred more in thromboprophylaxis group than in patients who did not receive anticoagulation at discharge, more clinical data are needed for a conclusion.

We have developed a simple, rapid, high-throughput RBD-based ELISA to assess the humoral immunity against emerging SARS-CoV-2 virus variants. The cDNAs of the his-tagged RBD proteins of the virus variants were stably engineered into HEK cells secreting the protein into the supernatant, and RBD purification was performed by Ni-chromatography and buffer exchange by membrane filtration. The simplified assay uses single dilutions of sera from finger-pricked native blood samples, purified RBD in 96-well plates, and a chromogenic dye for development. The results of this RBD-ELISA were confirmed to correlate with those of a commercial immunoassay measuring antibodies against the Wuhan strain, as well as direct virus neutralization assays assessing the cellular effects of the Wuhan and the Omicron (BA.5) variants. Here we document the applicability of this ELISA to assess the variant-specific humoral immunity in vaccinated and convalescent patients, as well as to follow the time course of selective vaccination response. This simple and rapid assay, easily modified to detect humoral immunity against emerging SARS-CoV-2 virus variants, may help to assess the level of antiviral protection after vaccination or infection.

: For a long time, atherosclerosis has been regarded as a mere lipid deposit in the blood vessels. However, in the recent years a growing body of experimental and clinical evidence have highlighted the role of inflammation and immunity as a central mechanism of disease. Moreover, in the last decade the coming of next-generation sequencing and its application to large human population has broken the barrier between inflammation and cancer. Indeed, acquired mutation in key genes related to the control of hematopoiesis and myeloproliferation have paved the way to establish the new concept of clonal hematopoiesis of indeterminate potential. This phenomenon is being considered not such “indeterminate”, but as an emerging cardiovascular risk factor. Thus, this may explain the mechanisms of myeloproliferation and inflammation in atherosclerosis. And in a bidirectional journey, it has helped to explain the extremely high cardiovascular risk in cancer survivors, in particular in myeloprolfierative neoplasm patients. A deeper understanding of these mechanisms may pave the way for the future early diagnosis and potential preemptive treatments of the leading worldwide cause of death.

Abstract Objectives To investigate histopathological changes and serous carcinoma precursors such as secretory cell outgrowths (SCOUTs) and p53 signature in bilateral tubal ligation (BTL) materials performed during cesarean section (S/C). Materials and Methods 138 patients who underwent S/C and tubal sterilization (TS) between October 2020 and May 2021 at Konya City Hospital. Patients’ data were obtained from the haospital’s system. All data andd findings were investigated and statistically evaluated. Results The mean age was 34.62 years (22 - 44), the mean gravity was 4.89 (2-15) and the mean parity was 3.46 (1-10). 5.79% SCOUT, 7.24% atypia and 9.42% p53 signatures were observed. Significant correlations were shown between epithelial cell lineage and age and between KI-67, SCOUT, and gravity, between KI-67 results and gravity and parity, and between P53 score and age. Conclusion TS is a common, safe, and effective method worldwide. Today, BTL is increasing along with increasing S/C ratios. In addition to the reduced risk of ovarian cancers with ligation alone, precursor lesions such as hyperplasia, SCOUT, p53 signature, and STIL/ Serous tubal intraepithelial carcinoma (STIC) are encountered in the ampulla materials obtained. Considering the low rates of re-anastomosis, tubal excision may be recommended instead of ligation in women of relatively higher gravity and age.

Lung cancer, globally recognized as the leading cause of cancer-related mortality, presents a pressing need for innovative treatment strategies. Increasing evidence points towards the potential of monoamine oxidase (MAO) inhibitors in modulating cancer progression, primarily due to their role in regulating cellular metabolism and apoptotic pathways. This extraordinary study delves into the multifaceted therapeutic implications of MAO inhibitors in lung cancer management, elucidating their ability to pave the way for clinical advancement via novel targets and pathways. Capitalizing on recent advances in molecular biology, this research explores the molecular mechanisms underlying the anticancer actions of MAO inhibitors. By examining their impact on cell proliferation, migration, invasion, and apoptosis in lung cancer cell lines, we provide insight into the intricate signaling pathways and biochemical processes modulated by these compounds. The study also investigates the synergistic effects of MAO inhibitors in combination with established chemotherapeutic agents, elucidating their potential to enhance treatment efficacy and reduce cytotoxicity. Furthermore, we delve into the implications of MAO inhibitors on the tumor microenvironment, evaluating their influence on angiogenesis, immune regulation, and the epithelial-mesenchymal transition. This comprehensive analysis enables the identification of novel molecular targets, which hold promise for the development of advanced therapeutics tailored for specific lung cancer subtypes. To substantiate our findings, in this review, we thoroughly analyze the existing literature using state-of-the-art bioinformatics tools." in vivo orthotopic lung cancer models, and clinical patient cohorts. This robust and multidisciplinary approach permits the generation of clinical evidence supporting the integration of MAO inhibitors in lung cancer management. Conclusion: This ground-breaking study establishes the therapeutic potential of monoamine oxidase inhibitors in lung cancer management by unearthing novel pathways and targets for clinical advancement. The outcomes open doors for the development of innovative treatment strategies and inspire continued research efforts to combat the global burden of lung cancer.

There is no well-defined threshold for intra-operative blood transfusion (BT) in advanced epithelial ovarian cancer (EOC) surgery. We developed a Machine Learning (ML)-driven prediction algorithm to trigger and explain a communication alert for BT based on anticipated peri-operative events irrespective of BT policies. We analysed prospectively collected data from 403 EOC patients who underwent cytoreductive surgery between 2014 and 2019. We calculated the estimated blood volume (EBV) using the formula EBV = weight x 80 and set off 10%EBV as threshold for individual intervention. Based on the known estimated blood loss (EBL) we identified two groups. We employed Receiver operating characteristic (ROC) curves for performance metrics. The model performance for the above threshold prediction was satisfactory (AUC 0.823, 95% CI 0.76-0.88). The top feature commonly shared between interrogators was operative time (OT). Intra-operative blood loss of at least 10%EBV was associated with OT&gt;250 minutes, primary surgery, serous histology, performance status 0, R2 resection and surgical complexity score &gt;4. Large bowel resection, stoma formation, ileocecal resection/right hemicolectomy, mesenteric resection, bladder and upper abdominal peritonectomy were amongst sub-procedures clearly associated with increased intervention risk. Precise prediction of blood requirements is not possible unless a rough estimate of OT is known in advance.

Background: Cervical cancer prevention in regions with limited access to screening and HPV vaccination necessitates innovative approaches. This study explored the potential of a test-and-treat strategy using mRNA HPV tests to impact cervical cancer prevention in a high-prevalence HIV population. Methods: A cervical screening study was conducted at three South African hospitals involving 710 under-screened, non-pregnant women (25 to 65 years) without known cervical diseases. Cytology, HPV testing, colposcopy, and biopsies were performed concurrently. Histopathologists determined final histological diagnoses based on biopsy and LLETZ histology. mRNA-HPV-genotyping for 3 (16, 18, 45) to 8 (16, 18, 31, 33, 35, 45, 52, 58) high-risk types was performed on leftover liquid-based cytology material. The preventive potential of the test-and-treat approach was estimated based on published data, reporting the causative HPV types in cervical cancer tissue from South African women. Treatment was provided as needed. Results: HPV positivity rate more than doubled from 3-type (15.2%; 95% CI: 12.6-17.8) to 8-type mRNA (31.5%; 95% CI: 28.8-34.9) combinations, significantly higher among HIV-positive women. CIN3+ prevalence among HIV-positive women (26.4%) was double that of HIV-negative women (12.9%) (p&lt;0.01). The 6-type combination showed the best balance of sensitivity, specificity and treatment group size, and effectiveness to prevent cervical cancer. A 4-type combination (16, 18, 35, 45) could potentially prevent 77.6% (95% CI: 71.2-84.0) of cervical cancer burden by treating 20% and detecting 41.1% of CIN3 cases in the study group. Similarly, a 6-type combination (16, 18, 31, 33, 35, 45), treating 25% and including 62% of CIN3 cases, might prevent 85% of cervical cancer cases (95% CI: 79.6-90.6) among HIV-positive and negative women. Conclusion: Employing mRNA HPV tests within a test-and-treat approach holds huge promise for targeted cervical cancer prevention in under-screened populations. Testing for mRNA of the 6 highest-risk HPV types in this population and treating them all is projected to effectively prevent progression from CIN3 to invasive cervical cancer while reducing overtreatment in resource-constrained settings.

As the COVID-19 pandemic has caused enormous damage to society, economy and public health security, it is crucial to combat the epidemic and allocate social and health resources effectively. Global optimization algorithms are extensively used in many domains to find optimal solutions to complex problems. Thus, a survey of three typical global optimizations applied on the COVID-19 pandemic is timely. This article is structured into three typical global optimization algorithms - Genetic Algorithm, Particle Swarm Optimization, and Cat Swarm Optimization - and summarizes the framework models and practical applications, as well as other optimization methods that may be applied to COVID-19. Finally, current unresolved challenges and future research opportunities to be explored are summarized.

: Background: Cartilage harvest and transplantation is a common surgery using costal, auricular, and septal cartilage for craniofacial reconstruction. However, absorption and warping of the cartilage grafts can occur due to inflammatory factors associated with wound healing. Transcriptional factor nuclear factor κB (NFκB) is activated by cytokines, such as interleukin-1 (IL-1), and plays a central role in the transactivation of this inflammatory cytokine gene. Inhibition of NFκB may have anti-inflammatory effects. The aim of this study was to explore the potential of an NFκB decoy oligodeoxynucleotide (Decoy) as a chondroprotective agent. Materials and Methods: Evaluation of safe and efficacious concentrations of Decoy were assessed using rabbit nasal septal chondrocytes (rNSCh) and assays for cytotoxicity, proteoglycan (PG) synthesis, and PG turnover. The efficacious concentration of Decoy determined from the rNSCh was then applied to human nasal septal cartilage (hNSC) in vitro and analyzed for PG turnover, the level of inflammatory markers, and catabolic enzymes in explant-conditioned culture medium. Results: Over the range of Decoy conditions and concentrations, no inhibition of PG synthesis or cytotoxicity was observed. Decoy at 10 μM effectively inhibited PG degradation in the hNSC explant, prolonging PG half-life 63% and decreasing matrix metalloprotease 3 (MMP3) by 70.7% (P = 0.027). Conclusions: Decoy may be a novel chondroprotective therapeutic agent in cartilage transplantation due to its ability to inhibit cartilage degradation due to inflammation cytokines.

This study investigates the therapeutic potential of new compound, potassium 2-[2-(2-oxo-4-phenylpyrrolidin-1-yl) acetamido]ethanesulfonate (Compound I), in depression. Willner's chronic unpredictable mild stress model of depression in 48 male Wistar rats was used a depression model. The rats were randomized into four groups, including an intact group, a Compound I group, a Fluoxetine group, and a control group receiving saline. Behavioral tests, such as the Porsolt forced swim test, hole-board test, elevated plus maze test, and light-dark box, were used to assess the animals' conditions. Our results demonstrated that Compound I effectively reduced the immobilization time of rats in the forced swim test, increased orientation and exploratory behavior, and decreased the latency period of going into the dark compartment compared to the control group. Hippocampal and striatal serotonin concentrations were increased in the Compound I group, and the compound also reduced the level of corticosterone in the blood plasma of rats compared to intact animals. These results suggest that Compound I has a reliable antidepressant activity, comparable to that of the reference antidepressant Fluoxetine.

This review summarizes the currently known biochemical neuroadaptive mechanisms of remote ischemic conditioning. In particular, it focuses on the significance of the pro-adaptive effects of remote ischemic conditioning, which allow prevention of neurological and cognitive impairments associated with hippocampal dysregulation after brain damage. The neuro-immuno-humoral pathway of transmitting a conditioning stimulus, as well as the molecular basis of the early and delayed phases of neuroprotection, including anti-apoptotic, antioxidant and anti-inflammatory components, are also outlined. Based on the close interplay between the effects of ischemia, especially mediated by interaction of HIF factors and steroid hormones, the involvement of the hypothalamic-pituitary-adrenocortical system in remote ischemic conditioning is also discussed.

Chronic lymphocytic leukemia (CLL) is a hematologic malignancy characterized by progressive accumulation of a rare population of CD5+ B lymphocytes in peripheral blood, bone marrow and lymphoid tissues. CLL exhibits remarkable clinical heterogeneity, with some patients presenting with indolent disease and others progressing rapidly to aggressive CLL. The significant heterogeneity of CLL underscores the importance of identifying novel prognostic markers. Recently, the RAS-related gene RRAS2 has emerged as both a driver oncogene and a potential marker for CLL progression, with higher RRAS2 expression associated with poorer disease prognosis. Although missense somatic mutations in the coding sequence of RRAS2 have not been described in CLL, this study reports the frequent detection of three somatic mutations in the 3' untranslated region (3'UTR) affecting positions +26, +53, and +180 downstream of the stop codon in the mRNA. An inverse relationship was observed between these three somatic mutations and RRAS2 mRNA expression, which correlated with lower blood lymphocytosis and better prognosis. These findings highlight the importance of RRAS2 overexpression in CLL development and prognosis and point to somatic mutations in its 3'UTR as novel mechanistic clues. Our results may contribute to the development of targeted therapeutic strategies and improved risk stratification for CLL patients.

Intracranial compliance (ICC) plays a pivotal role in understanding the underlying mechanisms of various brain disorders and is of great clinical importance. Therefore, addressing the challenges in practical application of ICC is crucial for neurosurgeons. This study explored the significance of ICC assessment considering the time-dependency of specific brain disorders through two distinct approaches: short and large time elapsed (TE) in measuring volume or intracranial pressure (ICP) changes in the ICC equation (∆Volume/∆ICP). Variations in ICC values were observed across various ICC assessment methods and different TE values. Notably, the compensatory response of the brain exhibited non-monotonic and variable changes in a large TE for certain brain disorders, diverging from patterns observed in short TE assessments. Furthermore, the recovery behavior of the brain changed under different brain disorders when exposed to short and long TE conditions. These findings emphasized the dynamic nature of ICC and provided valuable insights into the correct practical assessment of ICC by selecting the appropriate TE, as well as considering the differences in strain rates and loading durations on the brain in different brain disorders. These insights also shed light on the reasons why, despite its clinical significance, ICC monitoring has not yet become a standard component of clinical care, unlike ICP monitoring.

Arthroscopic capsular release (ACR) is used for persistent shoulder stiffness after an index surgery. No cases of post-ACR humeral head osteonecrosis have been reported to date. A 56-year-old male patient underwent open reduction and internal fixation using a hook plate for acromioclavicular joint dislocation. Despite hardware removal, the patient presented with unresolved shoulder pain and range-of-motion (ROM) limitation. He had a history of hypertension, chronic hepatitis B infection, and alcohol consumption. Preoperative ROM was forward flexion 90°and internal rotation sacral level. Preoperative functional status was visual analog scale (VAS) score 4, American Shoulder and Elbow Surgeons (ASES) score 51, and Constant–Murley (CMS) score 48, and normal radiography and magnetic resonance imaging. Standard ACR was performed with 360° release of the joint capsule via electrocautery ablation. Six-months post-ACR, ROM (forward flexion: 135°, abduction: 135°, external rotation: 70°, internal rotation: T10 vertebra) and functional outcomes (VAS 2; ASES79; CMS 75) were significantly improved, without interval change in radiographic assessment. However, 21 months later, he had recurrent shoulder pain and decreased ROM. Radiography revealed humeral head osteonecrosis. Patients with intrinsic or extrinsic risk factors related to humeral head circulation disturbance should be monitored for humeral head osteonecrosis post-ACR.

Utilization of medicine derived from plants has been documented in various traditional systems of medicines throughout the world for different diseases. Therefore, the current research work was carried out to evaluate the phytochemical and biological potential of Ficus carica L ethanolic leaf extract. For this purpose, physicochemical and phytochemical analysis, total phenolic and flavonoids contents was performed. Antioxidant potential was determined by FRAP, DPPH and H2O2 assay. Proteinase inhibition, heat induced hemolysis and BSA denaturation assay was carried out for inflammation. Antiglycation potential was assessed by fructosamine assay, Congo-red assay and estimation of free carbonyl groups. In-vivo antidiabetic, anti-obesity, effect on liver and kidney were investigated by high fat high sugar diet model. FTIR, HPLC and LCMS/MS analysis was performed to find out the compounds. Tablet based formulation was developed using wet granulation method and tested for physicochemical parameters. Results shows that total phenolic and flavonoids content was (333 mg GAE/g) and (123 mg RE/g) respectively, H2O2 assay shows 35.6% free radical inhibition potential, DPPH assay shows (IC50) inhibitory concentration at 0.58 mg/mL, and 88.769 µg/g Fe2SO4 solution FRAP values. Proteinase inhibition assay, Heat induced hemolysis and BSA-denaturation assay shows percentage inhibition of 28 ± 0.01, 55 ± 0.03 and 51.2 ± 0.05 respectively. In Antiglycation activity β-amyloid formation assay shows absorption of 0.017, Fructosamine assay shows inhibition of 19.4±0.06 and free carbonyl group estimation shows inhibition of 17.0±0.03. In in-vivo study FLE at (500 mg/kg) significantly decreased total bilirubin (p ≤ 0.001), decreased (p ≤ 0.05) alanine transferase, aspartate aminotransferase, alkaline phosphatase, decreased blood glucose, triglycerides and total cholesterol (p ≤ 0.01) while HDL (p ≤ 0.01) was significantly increased in comparison to obesity and diabetic-obesity groups. Different functional groups presence was confirmed by FTIR spectrum. HPLC analysis revealed the existence of ferulic acid, rutin, chlorogenic acid, coumarin and thymoquinone and these results are corelated by LC-MS/MS. Pre-compression characterization showed angle of repose (33.04°), bulk density (0.54 g/cm3), tapped density (0.73 g/cm3), compressibility index (35.179 %) and Hausner’s ratio (1.35), while the post-compression characterization showed weight variation 826±4.17 mg, thickness 10.50±0.25 kg/cm2, friability 0.57 %, and disintegration time 8.19 min. From the above results it is concluded that F. carica L. leaves extract has strong antioxidant, antidiabetic and hypolipidemic potential and can be used for an obesity and diabetes treatment.

Age estimation is an important tool when dealing with human remains or undocumented minors. Although the skull, the skeleton or the hand-wrist are used on age estimation as maturity indicators, they often present lack of good conditions for a correct identification or estimation. Few systematic reviews (SRs) have been recently published; therefore, this umbrella review critically assesses their level of evidence and provides a general comprehensive view. An electronic database search was conducted in four databases (PubMed, Cochrane, WoS, LILACS) up to December 2022, focusing on SRs of age estimation through forensic dentistry procedures. The methodological quality was analyzed using the measurement tool to assess SRs criteria (AMSTAR2). Eighteen SRs were included, five of critically low quality, six of low quality, three of moderate quality and four of high quality. The SRs posited that Willems’ method is more accurate and less prone to overestimation; most methods seem to be geographically sensitive; and 3D-Imaging and artificial intelligence tools demonstrate high potential. The quality of evidence on age estimation using dental approaches was rated as low to moderate. Well-designed clinical trials and high standard systematic reviews are essential to corroborate the accuracy of the different procedures of age estimation in forensic dentistry.

This study focused on the precise detection and concordant analysis of circulating tumor cells (CTCs) to verify the usefulness of CTCs as promising clinical markers. CTCs are traditionally achieved using immune-fluorescence and morphological techniques. By combining two prostate cancer-specific genes (PSA and PSMA) and two epithelial-specific genes (EpCAM and KRT19), the CTC detection efficiency can be enhanced. The detection rates of localized prostate cancer (LPC), locally advanced prostate cancer (LAPC), metastatic hormone-sensitive prostate cancer (mHSPC), and metastatic castration-resistive prostate cancer (mCRPC) were 63.04 % (29/46), 70.59% (34/51), 94.34% (50/53), and 90% (126/140), respectively. Subsequent correlation analysis between the four genes, baseline PSA, and CTC count revealed that only the CTC count correlated with baseline PSA in the localized stages of prostate cancer, whereas all four genes were correlated with baseline PSA and CTC count in the metastatic stages of prostate cancer. The precise detection of CTCs using both numerical and transcriptomic analyses can improve the accuracy of biomarker investigations. This study provides valuable insights into the limitations of serum PSA testing and offers a promising alternative to diagnose and manage prostate cancer via the CTC number and specific genes for prostate cancer.

Dacomitinib is an irreversible epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor indicated for the treatment of patients with advanced non-small cell lung cancer (NSCLC) and EGFR-activating mutations. Proton pump inhibitors decreased dacomitinib exposure. This anal-ysis summarizes the effect of H2RA on dacomitinib exposure. A within-patient comparison of steady-state trough concentrations (Ctrough,ss) of dacomitinib and its active metabolite and active moiety with and without concomitant use of H2RA was conducted using a linear mixed effects model with pooled data from 11 clinical studies in patients with NSCLC. An oral absorption PBPK model was constructed and verified using clinical PK data after a single dose of dacomitinib in healthy volunteers to estimate the effect of gastric pH altered by an H2RA on dacomitinib PK. The adjusted geometric mean of dacomitinib Ctrough,ss of dacomitinib parent, metabolite and active moiety following co-administration with H2RA was approximately 86%, 104% and 100% relative to that following dacomitinib 45 mg administration without H2RA (P>0.05). The PBPK modeling showed negligible change in dacomitinib Cmax and AUC over 0-24 hours after H2RA administra-tion, when compared with those administered dacomitinib alone. Co-administration of an H2RA with dacomitinib is not expected to have any clinically relevant effect on dacomitinib exposure.

Renal cell carcinoma (RCC), alternative term for kidney cancer, is becoming more common worldwide each year, and there are many different contributing factors. Among all cancers, RCC is the 14th most prevalent; and it ranks as the 14th and 9th most prevalent cancer overall for women and men respectively. RCC cases increased by more than 430,000 in 2020. While disease burdens are highest in Eastern Europe (Belarus and Russia) and North America (Canada and the United States), Africa, Asia, and Latin America are predicted to report increase in prevalence as these regions embrace change in lifestyle. The majority of RCC cases are accidentally found on imaging, and survival is greatly impacted by the disease stage at diagnosis, with a metastatic cancer having a 5-year survival rate of 12%. As a consequence of early discovery and more improved treatments, RCC mortality has declined. The key epidemiologic variables of RCC include vast regional and geographical heterogeneity in prevalence rates, and the cause is largely unclear. Recognized risk factors include smoking, being overweight, having previous episodes of hypertension, and suffering chronic renal illness. Unexpectedly swift, RCC diagnosis and therapy have advanced. RCC prevalence continues to rise although survival rates have sharply improved. Cancer survival and treatment have improved, and more gains are projected as a result of clinical and translational research. In this review, kidney cancer statistics and recent literatures are examined on a global scale. It covered aspects of kidney cancer, including its epidemiology, causes, risk factors, current immunotherapy, chances for prevention, and future planning.

This study aimed to elucidate the antibacterial efficacy and unique chemical compositions generated from plasma-activated water (PAW) when utilized a novel vaginal cleansing device. We conducted an analysis of antibacterial activity against probiotics and several chemical compositions including ions under various operational parameters of PAW, including electrical power (12 and 24 V), treatment duration (1, 10, and 20 min), and stay duration (immediate, 30 and 60 min). Our findings revealed that as treatment duration increased, hypochlorous acid (HOCl), Ca2+, and Mg2+ concentrations increased and Cl−concentrations decreased. Higher electrical power and longer treatment duration resulted in increased HOCl levels, which acts to prevent the growth of general microorganisms. Notably, PAW exhibited no antibacterial effects against a type of probiotic, Lactobacillus reuteri that produces lactic acid for vaginal health. This result demonstrated the ability of the vaginal cleaning device to generate ions, primarily HOCl and some cations (Ca2+ and Mg2+), thereby providing vaginal mucosa protecting and cleansing effects with the vaginal environment.

Two new compounds, named aspergilins A (1) and B (2), were isolated from the mangrove endophytic fungus Aspergillus sp. A1E3 associated with the fruit of Rhizophora mucronata, together with averufanin (3). The planar structures and absolute configurations of these compounds were unambiguously established by extensive NMR investigations, quantum-chemical electronic circular dichroism (ECD) calculations, and single-crystal X-ray diffraction analysis. Most notably, the absolute configuration of aspergillin A (1) was determined by single-crystal X-ray diffraction analysis of its tri-pivaloyl derivative 4, conducted with Cu Kα radiation, whereas that of averufanin (3) was first clarified by quantum-chemical ECD calculations. Aspergilin A is the first orsellinic acid–ribose–​pyridazinone-Noxide hybrid containing a unique β-oxo-2,3-dihydropyridazine 1-oxide moiety, whereas aspergilin B and averufanin are the sterigmatocystin and anthraquinone derivative, respectively. From the perspective of biosynthesis, aspergilin A could be originated from the combined assembly of three building blocks, viz., orsellinic acid, β-D-ribofuranose, and L-glutamine. It is an unprecedented alkaloid-Noxide involving biosynthetic pathways of polyketide, pentose, and amino acid. Aspergilin B (2) exhibited potent antiproliferative activity against four cancer cell lines. In addition, Aspergilin B (2) dose-dependently induced G2/M phase arrest in HepG2 cells.

Background and Objectives: Chemokines have various biological functions and potential roles in the development or progression of neuroinflammatory diseases. However, the specific pathogenic roles of chemokines in age-related macular degeneration (AMD), the leading cause of blindness in older individuals, remain elusive. Chemokines interact with their receptors expressed in the endothelium and on leukocytes. The sulfation of tyrosine residues in chemokine receptors increases the strength of ligand–receptor interaction and modulates signaling. Therefore, in the present study, we aimed to construct a human recombinant sulfated CXCR3 peptide trap (hCXCR3-S2) and mouse recombinant sulfated CXCR3 peptide trap (mCXCR3-S2) to demonstrate in vivo effects in preventing choroidal neovascularization and chemotaxis. Materials and Methods: First, the effect of hCXCR3-S was validated in vitro. Interestingly, hCXCR3-S2 inhibited the migration and invasion of two human cancer cell lines. Subsequently, the in vivo efficacy of mCXCR3-S2 was investigated using a mouse model of neovascular AMD. Results: Intravitreal injection of mCXCR3-S2 attenuated choroidal neovascularization and macrophage recruitment in neovascular lesions. These in vitro and in vivo effects were significantly stronger with CXCR3-S2 than with wild-type CXCR3 peptides. Conclusion: These findings demonstrate that the sulfated form of the CXCR3 peptide trap is a valuable tool that could be supplemented with antivascular endothelial growth factors in AMD treatment.

Following ischemic stroke, the degradation of myelin and other cellular membranes surpasses the lipid-processing capabilities of resident microglia and infiltrating macrophages. This imbalance leads to foam cell formation in the infarct and areas of secondary neurodegeneration, instigating sustained inflammation and furthering neurological damage. Given that mitochondria are the primary sites of fatty acid metabolism, augmenting mitochondrial biogenesis (MB) may enhance lipid processing, curtailing foam cell formation and post-stroke chronic inflammation. Previous studies have shown that the pharmacological activation of the β2-adrenergic receptor (β2-AR) stimulates MB. Consequently, our study sought to discern the effects of intensified β2-AR signal-ing on MB, the processing of brain lipid debris, and neurological outcome using a mouse stroke model. To achieve this goal, aged mice were treated with formoterol, a long-acting β2-AR ago-nist, daily for two and eight weeks following stroke. Formoterol increased MB in the infarct re-gion, modified fatty acid metabolism, and reduced foam cell formation. However, it did not re-duce markers of post-stroke neurodegeneration or improve recovery. Our findings suggest that boosting MB in myeloid cells is one component of a therapeutic avenue for improving brain lipid debris processing after stroke.

Spinal metastatic tumors are common and often cause debilitating symptoms. Image-guided percutaneous thermal ablation (IPTA) has gained significant recognition in managing spinal column tumors due to its exceptional precision and effectiveness. Conventional guidance modalities, including computed tomography, fluoroscopy, and ultrasound, have been important in targeting spinal column tumors while minimizing harm to adjacent critical structures. This study presents a novel approach utilizing a fusion of Cone Beam Computed Tomography with Magnetic Resonance Imaging to guide percutaneous thermal ablation for four patients with secondary spinal column tumors. The visual analog scale (VAS) evaluated procedure effectiveness during an 18-month follow-up. Percutaneous vertebroplasty was performed in two cases, and a thermostat was used during all procedures. Imaging was performed using the Stealth Station navigation system Spine 8 (SSS8) and a 1.5T MRI machine. The fusion of CBCT with MRI allowed precise tumor localization and guidance for thermal ablation. Initial results indicate successful tumor ablation and symptom reduction, emphasizing the potential of CBCT-MRI fusion in spinal column tumor management. This innovative approach is promising in optimizing therapy for secondary spinal column tumors. Further studies are necessary to validate its efficacy and applicability.

This narrative review aims to clarify the role of tertiary lymphoid structures in breast cancer. We examine their development, composition, prognostic value and current ways of recognising them. A comprehensive literature review was performed using PubMed/Medline, Scopus and EMBASE databases. A significant area of interest in breast cancer research involves targeting immune checkpoint molecules, particularly in the triple-negative subtype, where treatment options remain limited. However, existing biomarkers have limitations in accurately predicting treatment response.  In this context, tertiary lymphoid structures (TLS) emerge as a prognostic biomarker and also as a promising predictive marker for response. TLS are ectopic lymphoid formations or neo-organogenesis that can develop after prolonged exposure to inflammatory signals mediated by chemokines and cytokines. Their presence is inversely correlated with estrogen receptor (ER) and/or progesterone receptor (PR) expression, but positively associated with a higher pathologic complete response rate and improved overall  survival. In certain scenarios, TLS-positive tumors were associated with improved outcomes regardless of the presence of PDL-1 (programmed cell death ligand 1) expression or and TILs (tumor-infiltrating lymphocytes).

Ketamine as an old - new drug has variety of clinical implications. In the last 30 years, ketamine has become popular for acute use in humans. Ketamine at standard doses is principally utilized for the induction and maintenance in surgical procedures. Beside its use in anesthesia and analgesia, recently studies had shown that ketamine find the place in the treatment of asthma, epilepsy, depression, bipolar affective disorders, alcohol and heroin addiction. Its mechanism of action is complex, but it mostly acts as a noncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor. Ketamine is generally considered relatively secure and does not result in serious adverse effects when used at low doses and for short periods- Also, ketamine is known as a powerful psychostimulant. During the past decade, ketamine has been one of the commonly abused drug.

The success rate of extracorporeal shock wave lithotripsy (ESWL) is influenced by various factors, including stone density, which is determined through computed tomography scans in Hounsfield Units (HU). Materials and method: This retrospective single-center study was conducted in King Fahad hospital. Sixty-seven adult patients with renal and ureteric stones were selected randomly and enrolled in the study. Their age ranged from 20 to 69 years. The patients were examined with non-contrast enhancement (NCCT) to assess the HU of stones, consequently, treated with ESWL. Results: of the 67 patients, 37.3% of the stones were completely fragmented, while 62.7% were partially fragmented. HU, location of the stone, a multiplicity of the stone, and patient age were significant factors contributing to stone fragility (p-values&lt; 0.05). The HU has a positive significant linear correlation with serum calcium (r= .28, p-value=.036), while serum acid has a negative correlation (r=-.55, p-value= &lt; .001). Thus, the probability of calcium-containing stones formation increased with increased HU. In contrast, uric acid stone formation is likely to develop with decreasing HU with serum uric acid. Renal stones in patients with diabetes mellitus and hypertension were not completely fragmented compared to those without clinical history. Conclusion: Mean HU, location of the stone, laterality, status of stone, and the number of ESWL sessions were the most significant factors affecting stone fragility. CT attenuation values can predict the composition of stones from serum calcium and uric acid examinations. Hypertension and Diabetes mellitus are risk factors for renal stone fragmentation.

Pure silver as well as silver compounds have been used as antiseptics for centuries. Nowadays, the most frequently applied form of silver is a nanoparticle form. Several studies demonstrate the ability of silver nanoparticles and silver salts to accumulate in the brain of laboratory ani-mals as well as the ability of silver nanoparticles to influence behavioral and cognitive functions of laboratory mammals. For the first time, the influence of a silver salt, in particular, silver citrate on the change dynamics of behavioral and cognitive functions of laboratory mice at the daily oral exposure during 30, 60, 120 and 180 days is investigated in the present research. We observed the anxiety increase after 30 days of the exposure as well as the ability of mice to adapt to the prolonged oral exposure of silver citrate manifested in the anxiety decrease, increase of locomotor activity and the tendency of long-term contextual memory improvement. Increase of locomotor activity and memory improvement might be associated with the sensitivity increase and regarded as compensatory mechanism to anxiety increase. The observed phenomenon is classified as a hormetic effect. A comparison with the analogous study implemented polyvi-nylpyrrolidone coated silver nanoparticles is carried out. It was concluded that the nanoform is more neurotoxic.

Ovarian cancer affects thousands of women every year and represents the female cancer with the highest mortality rate. Surgery is currently the cornerstone of the treatment of this disease and several methods have been analyzed and developed to predict the possibility of obtaining a residual tumor of 0 (RT=0). The aim of this review is to analyze the data available in the literature about minimally invasive surgical methods to predict the optimal cytoreduction of patients with advanced epithelial ovarian cancer undergoing primary debulking surgery (PDS). A review of the literature has been performed on the available data about the criteria of cytoreducibility during PDS for the surgical treatment of advanced epithelial ovarian cancer. The assessment of the extent of intra and extrabdominal pathology is essential to guide the surgeon in the most appropriate therapeutic choice for patients with ovarian cancer, so radiological methods (MRI, PET-scan and CT), surgical (mini-laparotomy, laparoscopy) and serological (CA-125, HE4) can provide a huge help for tailoring the therapeutic approach of these patients.

Traumatic brain injury (TBI) is among the leading causes of mortality and long-term impairment globally. TBI has a dynamic pathology encompassing a variety of metabolic and molecular events that occur in two phases, primary and secondary. An external forceful blow to the brain initiates the primary phase, which is followed by a secondary phase that involves the release of calcium ions (Ca2+) and the initiation of a cascade of inflammatory processes, including mitochondrial dysfunction, rise in oxidative stress, activation of glial cells, and damage to the blood-brain barrier (BBB), resulting in paracellular leakage. There is currently no FDA-approved drug for TBI, but existing approaches rely on delivering small and macromolecular treatments, which are severely constrained by the BBB, poor retention, off-target toxicity, and complex pathology of TBI. Therefore, there is a demand for innovative and alternative therapeutics with effective delivery tactics for diagnosis and treatment of TBI. Tissue engineering and use of biomaterials is one such alternative approach. With this approach, neuronal stem cell therapy is combined with synthetically generated tissue materials such as hydrogels, self-assembling peptides, and electrospun nanofibers, which may induce neurite outgrowth, differentiation of human neural stem cells, and nerve gap bridging in TBI. This review examines tissue engineering and the use of biomaterials as potential treatments for TBI, including their synthesis, mechanisms of action, and limitations. The review also discusses challenges facing tissue engineering and biomaterial technology including survival rate of transplanted stem cells and the development of biodegradable, biocompatible, and mechanically flexible biomaterials. A better understanding of the mechanisms and drawbacks of these novel therapeutic approaches will help guide the design of future TBI therapies.

(1) Background: Although multiple studies have reported on the therapeutic effects of Atezo+Bev for the treatment of NASH-related liver cancer, few studies have focused on its effect on liver reserve. Here, we aimed to compare the changes in hepatic reserve during the Atezo+Bev treatment of NAFLD/NASH-related HCC and of non-NAFLD/non-NASH-related HCC. (2) Methods: We retrospectively compared the changes in ALBI score in 109 patients with NAFLD/NASH or non-NAFLD/non-NASH during 12 weeks of treatment with Atezo+Bev for advanced HCC between September 2019 and January 2022. PSM was performed, and the OS, PFS, and PPS of the two groups were compared. (3)Results: The ALBI after 12 weeks of Atezo+Bev treatment was significantly worse in the NAFLD/NASH group than in the non-NAFLD/non-NASH group. Analysis of the 24 propensity score-matched pairs of cases with NAFLD/NASH or non-NAFLD non-NASH yielded similar results. The prognoses of the two groups were similar with respect to OS and PFS, but the NAFLD/NASH group had a significantly shorter PPS. The 24 matched pairs had similar OS and PFS, but the PPS of the NAFLD/NASH group was shorter. (4)Conclusion: Atezo+Bev treatment may worsen hepatic reserve, and there-fore life expectancy, in patients with NAFLD/NASH-related liver cancer.

Nephrolithiasis affects around 10% of the population and is frequently associated with impaired dietary factors. The first one is insufficient fluid intake inducing reduced urine volume, urine supersaturation, and subsequently urinary lithiasis. Kidneys regulate 24-hour urine volume, which, under physiological conditions, approximately reflect daily fluid intake. Increasing fluid intake has a preventive effect on the risk of developing a first kidney stone (primary prevention) but also decreases the risk of stone recurrence (secondary prevention). Current guidelines recommend increasing fluid intake at least at 2.5L /day to prevent stone formation, and even at 3.5-4L in some severe forms of nephrolithiasis (primary or enteric hyperoxaluria or cystinuria). Fluid intake must also be balanced between day and night, to avoid urinary supersaturation during the night. Patients should be informed and supported in this difficult process of increasing urine dilution, with practical ways and daily routines to increase their fluid intake. The liquid of choice is water, which should be chosen depending on its composition (such as calcium, bicarbonate or magnesium content). Finally, some additional advices have to be given to avoid some beverages such as those containing fructose or phosphoric acid, which are susceptible to increase the risk of nephrolithiasis.

Background: Menarche as an important parameter in assessment of scoliosis progression in girls is proven to be dependent on geographical latitude. The aim of the study was to determine whether the age of menarche differs in scoliotic and non-scoliotic Balkan girls and the relation between menarche and laterality of scoliotic curves. Participants and methods: Retrospective study with three groups: scoliotic, non-scoliotic and control group. Patients data collection and analysis was approved by the Ethical committee of the Institute. Statistical analysis: Program SPSS 24 was used and included One-way ANOVA, Fisher’s and Chi-squared test to compare different groups. Statistical significance was defined as p&lt;0,05. Results: No statistically significant difference was found in age of menarche between the three groups (p=0,168). In scoliotic postmenarchal group, primary right curve was dominant in 54,80%, while in scoliotic premenarchal group primary left curve was dominant in 60,09% (p&lt;0,01). Conclusion: In Bosnia &amp; Herzegovina and Serbia Balkan girls, there was no significant difference in age of menarche between scoliotic and non-scoliotic girls. A significant difference was found in laterality of primary curve in premenarchal and postmenarchal scoliotic girls.

Background and aim We investigated the clinical outcomes of patients with hepatocellular carcinoma (HCC) who underwent next-generation microwave thermosphere ablation (MTA). Methods A total of 429 patients with 607 HCCs (maximum tumor diameter ≤40 mm) were included. Results The primary etiologies of HCC were hepatitis-related: 259 (60.4%) cases of HCV, 31 (7.3%) cases of HBV, and two instances of both. Median maximum tumor diameter was 15.0 (interquartile range, 10.0–21.0) mm. There were 86 tumors in areas of the liver where MTA is difficult. The most common area was near the primary and secondary branches of the intrahepatic portal vein (26 nodules). The cumulative local tumor recurrence rates at 1, 2, and 3 years were 4.4%, 8.0%, and 8.5%, respectively. The cumulative local tumor recurrence rate differed significantly by tumor size group: ≤20 mm group (n=483), 20–30 mm group (n=107), and ≥30 mm group (n=17) (p<0.001). The cumulative local tumor recurrence rate was similar by difficult-to-treat status (p=0.169). In the multivariable analysis, tumor size (per 1 mm) (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.03–1.11; p<0.001) and ablative margin (per 1 mm) (HR, 0.81; 95% CI, 0.70–0.92; p=0.002) were significantly associated with local tumor recurrence. Only tumor size (per 1 mm) (odds ratio, 1.08; 95% CI, 1.02–1.15; p=0.015) was significantly associated with complications. Conclusions MTA is a safe and effective local ablation therapy for HCC, even for tumors located in areas of the liver where local ablation therapy is difficult.

The chromatographic conditions were optimized using headspace gas chromatography, and a simple and rapid method was established for the simultaneous determination of five residual solvents in ursodeoxycholic acid raw materials. The corresponding quality standards were revised. The results showed that the concentration of methanol ranged from 0.06mg/ml to 0.3mg/ml, and the concentrations of acetone, tert butanol, ethyl acetate, and triethylamine showed a good linear relationship with the peak area within the range of 0.1mg/ml to 0.5mg/ml (r=0.999); The quantitation limits for methanol, acetone, tert-butanol, ethyl acetate, and triethylamine were 4.2, 0.9, 1.5, 1, and 0.1 μg/ml, respectively, with detection limits of 1.2, 0.25, 0.025, 0.3, and 0.025 μg/ml, respectively. The recovery rates of each solvent ranged from 92.9% to 106.0%, with RSD% (n=9) less than 3.8%; The method exhibited good repeatability, with RSD% (n=6) less than 2.5%. Furthermore, the durability is good. The established method is simple, accurate, specific, and highly sensitive, and can be used for the simultaneous and rapid determination of five residual solvents in ursodeoxycholic acid raw materials.

Next-generation cancer and oncology research needs to take full advantage of the multi-modal structured, or graph, information, with the graph datatypes ranging from molecular structures to spatially resolved imaging and digital pathology to biological networks to knowledge graphs. Graph Neural Networks (GNNs) efficiently combine the graph structure representations with the high predictive performance of deep learning, especially on the large multi-modal datasets. In this review article, we survey the landscape of recent (2020-present) GNN applications in the context of cancer and oncology research, and delineate six currently predominant research areas. Subsequently, we identify the most promising directions for future research. We compare GNNs with graphical models and "non-structured" deep learning, and devise the guidelines for cancer and oncology researchers or physician-scientists asking the question of whether they should adopt the GNN methodology in their research pipelines.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly termed nonalcoholic fatty liver disease (NAFLD), is a widespread global health concern that affects around 25% of the global population. Its influence is expanding, and it is anticipated to overtake alcohol as the leading cause of liver failure and liver-related death worldwide. Unfortunately, there are no approved therapies for MASLD; as such, national and international regulatory health agencies undertook strategies and action plans designed to expedite the development of drugs for treatment of MASLD. A sedentary lifestyle and an unhealthy diet intake are important risk factors. Western countries have a greater estimated prevalence of MASLD partly due to lifestyle habits. Mitochondrial dysfunction is strongly linked to the development of MASLD. Further, it has been speculated that mitophagy, a type of mitochondrial quality control, may be impaired in MASLD. Thyroid hormone (TH) coordinates signals from the nuclear and mitochondrial genomes to control mitochondrial biogenesis and function in hepatocytes. Mitochondria are known TH targets and preclinical and clinical studies suggest that TH, thyroid receptor β (TR-β) analogs, and synthetic analogs specific to liver could be of therapeutic benefit in treating MASLD. In this review, we highlight how mitochondrial dysfunction contributes to development of MASLD, and how understanding the role of TH in improving mitochondrial function paved the way for innovative drug development programs of TH-based therapies targeting MASLD.

Keywords: Post-Stroke; Hyperbaric oxygen therapy; Sequelae; Feasibility; Out-patient.

Sustained-release drug delivery systems have evolved significantly over the years, playing a pivotal role in pharmaceutical research and enhancing patient care [1]. This abstract synthesizes key insights from various references to highlight the noteworthy advancements in this field. Recent research has emphasized the importance of understanding drug properties and their impact on sustained-release system design [2] [9]. These advancements enable tailoring drug delivery to optimize therapeutic outcomes [2] [9]. Incorporating innovative technologies such as nanotechnology [1], biodegradable polymers [3], and matrix systems [4] has led to the development of more efficient and patient-friendly sustained-release systems [1] [3] [4] Moreover, the concept of personalized medicine is gaining prominence [5], opening doors to individualized drug delivery strategies [5]. These strategies promise to enhance treatment efficacy while minimizing adverse effects [5]. Theoretical analyses, as exemplified by Higuchi’s work [6], continue to shape the understanding of sustained-release mechanisms [6]. Furthermore, studies on enteric-coated timed-release tablets [10]. highlight advancements in specific drug formulations to meet patient needs [10]. In conclusion, advancements in sustained-release drug delivery systems reflect a dynamic landscape where drug properties, innovative technologies, and personalized approaches converge to improve patient outcomes and drug therapy [7] [8] [10].

Photon-counting Computed Tomography (PCCT) is a promising cardiovascular-imaging technique. Using detectors that count the number and energy of photons in multiple bins, PCCT offers several advantages over conventional CT, including a higher image quality, reduced contrast agent volume, radiation doses, and artifacts. Although PCCT is well established for cardiac imaging in assessing coronary artery disease, its application in vascular imaging remains limited. This review summarizes the available literature and provides an overview of the current use of PCCT for the diagnosis of vascular conditions. Of the 13 records selected in the initial search, 7 articles were included in the present review: 6 cohort studies and 1 case report. This review synthesized the available literature on PCCT in vascular imaging, focusing mainly on endoleaks detection and characterization after endovascular aneurysm repair (EVAR), contrast dose volume, and radiation exposure reduction, particularly in patients with chronic kidney disease and in those requiring follow-up CT.

Recently, nanobodies have taken center stage in research on drug discovery and development. Several therapeutic possibilities using nanobodies are presently undergoing clinical trials and waiting for FDA approval. The goal of this study was to emphasize the potential of nanobodies as therapeutic agents by concentrating on the most recent published studies that examined their properties, manufacturing, and possible applications. This article demonstrates that the unique properties of nanobodies in comparison to conventional antibodies, which are based on their small size and offer a number of benefits, make them seem to have a promising future. These advantages include the ability to access complex or hidden target sites that may be elusive to their larger antibody counterparts, and increased resilience against extreme conditions like tempera-ture changes and pH variations. As a result, nanobodies seem to have a bright future as adaptable tools for imaging in cancer and non-malignant diseases, as well as for in vitro and in vivo diagnostic and therapeutic potential for a variety of conditions, including oncology, infectious, metabolic, neurological, and other conditions like ophthalmologic, immune-mediated, and genetic disorders. More research is required to determine their effectiveness and safety in clinical applications. The current analysis offers a thorough overview of the therapeutic uses for nanobody products that are either on the market or undergoing clinical trials.

Background: Hematopoietic cell transplantation (HCT) is an established therapy for hematologic malignancies and serious non-malignant blood disorders. Despite its curative potential, HCT is associated with substantial toxicity and health resource utilization. Effective delivery of HCT requires complex hospital-based care, which limits the number of HCT centers in Canada. In Canada, the quantity, indications, temporal trends, and outcomes of patients receiving HCT are not known. Methods: A retrospective cohort study of first transplants reported to the Cell Therapy Transplant Canada (CTTC) registry between 2000 and 2019. We determined overall survival (OS) and non-relapse mortality (NRM), categorizing the cohort into early (2000-2009) and later (2010-2019) eras to investigate temporal changes. Results: Of 18,046 transplants, 10,475 were allogeneic and 7,571 were autologous. Comparing the two eras, allogeneic transplants increased in number by 22.3%, with greater use of matched unrelated donors in the later era. Autologous transplants increased by 10.9%. Temporal improvements in NRM were observed in children and adults. OS improved in pediatric patients and in adults receiving autologous HCT. In adults receiving allogeneic HCT, OS was stable despite the substantially older age of patients in the later era. Interpretation: HCT is an increasingly frequent procedure in Canada which has expanded to serve older adults. Noted improvements in NRM and OS reflect progress in patient and donor selection, preparation for transplant, and post- transplant supportive care. In allogeneic HCT, unrelated donors have become the most frequent donor source, highlighting the importance of continued growth of volunteer donor registries. These results serve as a baseline measure for quality improvement and health services planning in Canada.

Inflammation involves the activation of innate immune cells and is believed to play an important role in the development and progression of both infectious and non-infectious diseases such as neurodegeneration, rheumatoid arthritis or cancer. Inflammation in the brain is marked by the upregulation of the translocator protein (TSPO) in microglia. Moreover, high TSPO levels are found, for example in macrophages during rheumatoid arthritis and in malignant tumor cells compared to its relatively low physiological expression. The same applies for cycloxygenase-2 (COX-2), which is constitutively expressed in the kidney, brain, thymus and gastrointestinal tract, but induced in microglia, macrophages and synoviocytes during inflammation. This puts TSPO and COX-2 in the spotlight as important targets for the diagnosis of inflammation. Imaging modalities, such as positron emission tomography and single-photon emission tomography, can be used to localize inflammatory processes and to track their progression over time. They could also enable to monitor the efficacy of therapy and predict its outcome. This review focuses on the current development of PET and SPECT tracers not only for the detection of neuroinflammation, but also for emerging diagnostic measures in infectious and other non-infectious diseases like rheumatic arthritis, cancer, cardiac inflammation and in lung diseases.

Preconception or prenatal carrier screening for hereditary deafness is an effective early intervention strategy to reduce the incidence of newborn deafness, but current research is limited. This study aimed to investigate the carrier frequencies of common deafness genes in the Chinese population and to follow up on pregnancy outcomes in high-risk couples. Carrier screening for common deafness genes in the Chinese population, including the GJB2 and SLC26A4 genes, was performed using next-generation sequencing technology. Of the 9,993 subjects screened, the carrier rate was 2.86% for the GJB2 gene and 2.63% for the SLC26A4 gene. Of the six high-risk couples, four made alternative reproductive decisions (three with prenatal diagnosis and one with preimplantation genetic testing), with consequent successful termination of the birth of two affected fetuses. The frequencies of preconception or prenatal carrier screening for the deafness genes GJB2 and SLC26A4 in 9,993 subjects from China in this study were 2.86% and 2.63%, respectively. In addition, four out of six high-risk couples made alternative reproductive decisions, followed by the successful prevention of the birth of two affected fetuses. These findings confirmed the clinical utility of preconception or prenatal carrier screening for hereditary deafness.

Background: Autoimmune inner ear disease (AIED) is a rare autoimmune condition characterized by progressive sensorineural hearing loss with hearing fluctuations over weeks to months, presenting significant challenges in both diagnosis and treatment. Due to its rarity, treatment responses and prognosis in AIED remain poorly understood. Methods: This study reviewed medical records from Taipei Medical University Hospital documented between August 2016 and August 2021. Among 67 patients experiencing fluctuating hearing loss, 11 met the diagnostic criteria for AIED and underwent regular follow-up assessments within a 5-year timeframe. ROC curve was used to discriminate the power of these prognostic parameters. Results: In this study, several factors including younger age, milder initial hearing loss, meeting criteria for bilateral Meniere's disease (MD), having an ascending audiogram pattern, longer time interval between hearing impairment attacks in contralateral ears and responding well to steroids were associated with better prognosis. ROC curve demonstrated the diagnostic value of specific parameters such as the presence of bilateral MD (AUC 0.825, 95% CI 0.640–1.000), pretreatment HI ≤ 45 dB HL (AUC 0.808, 95% CI 0.610–1.000), response to steroids (AUC 0.800, 95% CI 0.595–1.000), and ascending audiogram (AUC 0.858, 95% CI 0.683–0.858). Conclusions: This study identified key prognostic factors for AIED, providing valuable insights for predicting AIED prognosis and facilitating personalized patient management.

Gastric perforations and leaks are significant complications that can arise from various gastrointestinal disorders and surgical interventions. Over the past decade, endoscopic techniques have emerged as effective method for managing these conditions. Furthermore, as endoscopic resection techniques have grown in popularity, the risk of acute and delayed perforations has also grown. This review aims to provide an in-depth analysis of the endoscopic management strategies employed in the management of gastric perforations and leaks. We will discuss the etiology, diagnostic modalities, and various endoscopic techniques utilized, and emerging trends in endoscopic management. Our attempt in writing this review paper is to educate and guide clinicians in making informed decisions when faced with gastric perforations and leaks.

Background and Objectives: The severity of acute pancreatitis (AP) is graded as mild (MAP), moderately severe (MSAP), and severe (SAP) according to the revised Atlanta Classification. Determining the severity of AP is the main goal in the early time of AP. The aim of this study was to compare laboratory parameters or indices including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-creatinine index (NCI) at admission for predicting severity of AP. Materials and Methods: In this retrospective study, the data from patients who admitted with diagnosis of AP between January 2018 and December 2021 were collected. Laboratory parameters and indices including NLR, PLR and NCI were compared in the discrimination of AP severity groups. Results: A total of 421 patients [MAP group (n=213), MSAP group (n=158) and SAP group (n=50)] were included. WBC count, neutrophil count, hematocrit, CRP, BUN, creatinine, NLR and NCI were significant parameters to discriminate AP subgroups. The AUROC analysis for discriminating MSAP from MAP showed that WBC (AUC: 0.723, 95% CI: 0.674-0.768, p&lt;0.001), hematocrit (AUC: 0.566, 95% CI: 0.514-0.607, p=0.032), NLR (AUC: 0.649, 95% CI: 0.598-0.698, p&lt; 0.001) and NCI (AUC: 0.749, 95% CI: 0.701-0.792, p&lt;0.001) were statistically significant parameters. Similarly, AUCs to discriminate SAP from MSAP were (AUC: 0.649, 95% CI: 0.579-0.713, p &lt; 0.001) for WBC, (AUC: 0.703, 95% CI: 0.621-0.785, p&lt; 0.001) for BUN, (AUC: 0.602, 95% CI: 0.532-0.669, p=0.029) for CRP and (AUC: 0.742, 95% CI: 0.676-0.800, p&lt;0.001) for NCI. Logistic regression analyses indicated that NCI was the only parameter to discriminate MSAP form MAP (OR: 1.119, 95% CI: 1.015-1.235, p=0.023) and SAP from MSAP (OR: 1.113, 95% CI: 1.042-1.888, p = 0.001). Conclusions: The present study enabled the identification of neutrophil-creatinine index as a new prognostic tool for the assessment AP severity at hospital admission.

Post operative recurrence (POR) is the rule in patients with Crohn’s disease (CD), mitigated with prophylactic therapy. The evidence for therapeutic choice and timing of intervention is lacking. We aimed to compare rates of POR in patients treated early with prophylactic 6-mercaptopurine (6-MP) or adalimumab. We conducted a prospective single center randomized open label clinical study, in which patients in surgical remission following their first ileocecectomy were randomized to receive early treatment with 6-MP or adalimumab. Patients were followed up clinically every 3 months and underwent endoscopy at weeks 32 and 58 post-operatively. The primary endpoint was endoscopic recurrence (ePOR) at 1 year (week 58), defined as a Rutgeerts score≥i2. We enrolled 35 patients (25 males, mean age 35±1.4 years, median disease duration 5±6.1 years) following ileocecectomy. Of these, 7(20%) were current smokers and 9(26%) biologics experienced. Patients allocated to adalimumab had significantly less ePOR than patients treated with 6MP at week 32 (21% vs 69%, p=0.004) and 58 (47% vs 75%), (p=0.03, HR=0.39, 95% CI=0.16-0.93). POR was associated with increased diameter of the resected small bowel surgical specimen, lower baseline body mass index (BMI), increased week 18 fecal calprotectin and serum alanine aminotransferase and decreased week 18 hemoglobin level. Adalimumab is more effective than 6-MP in preventing ePOR. Increased operative small bowel diameter and lower post-operative BMI were associated with ePOR. Eighteen weeks serum hemoglobin and ALT, and fecal calprotectin levels were predictive of endoscopic disease recurrence. (ClinicalTrials.gov ID NCT01629628).

In this study, we report the antibacterial mechanisms of action of uniform silver nanoparticles (AgNPs) and decorated activated carbon nanocomposite (CAC-AgNPs) obtained using a green synthesis approach. The nanomaterials were characterized by ultraviolet-visible (UV-vis) absorption spectra and Fourier transform infrared (FTIR) spectra. The antibacterial activity of the as-prepared nanomaterials was evaluated against an array of bacterial strains by microdilution method, whereas their cytotoxicity profile was evaluated on Vero cells (human mammalian cells). The antibacterial mechanistic studies of active nanomaterials were carried out through bacterial growth kinetics, nucleic acid leakage test, and catalase inhibition assay. A silver nanocomposite was successfully fabricated from Croton macrostachyus-based activated carbon. The as-prepared nanomaterials exhibited antibacterial activity against an array of bacterial strains (minimum inhibitory concentration (MIC) range: 62.5 to 500 µg/mL), the most susceptible being Escherichia coli and Staphylococcus aureus. Cytotoxicity studies of the nanomaterials on Vero cells revealed that the nanocomposite (median cytotoxic concentration (CC50): 213.6 µg/mL) was less toxic than the nanoparticles (CC50 value: 164.75 µg/mL) counterpart. Antibacterial mechanistic studies unveiled that the nanomaterials induced (i) bacteriostatic activity vis-à-vis E. coli and S. aureus and (ii) inhibition of catalase in these bacteria. This novel contribution on the antibacterial mechanisms of action of silver nanocomposite from C. macrostachyus-based activated carbon might contribute to the understanding of antibacterial action of these biomaterials. Nevertheless, more chemistry and in vivo experiments, as well as in depth antibacterial mechanistic studies are warranted for the successful utilization of these antibacterial biomaterials.

Chronic traumatic encephalopathy (CTE) is a unique neurodegenerative disease that is associated with repetitive head impacts (RHI) in both civilian and military settings. In 2014, the research criteria for the clinical manifestation of CTE, traumatic encephalopathy syndrome (TES) were proposed to improve the clinical identification and understanding of the complex neuropathological phenomena underlying CTE. This review provides a comprehensive overview of the current understanding of the neuropathological and clinical features of CTE, proposed biomarkers of traumatic brain injury (TBI) in both research and clinical settings, and a range of treatments based on previous preclinical and clinical research studies. Due to the heterogeneity of TBI, there is no universally agreed-upon serum, CSF, or neuroimaging marker for its diagnosis. However, as our understanding of this complex disease continues to evolve, it is likely that there will be more robust, early diagnostic methods and effective clinical treatments. This is especially important given the increasing evidence of a correlation between TBI and neurodegenerative conditions, such as Alzheimer's disease and CTE¹. As public awareness of these conditions grows, it is imperative to prioritize both basic and clinical research, as well as the implementation of necessary safe and preventative measures.

Background: Two types of medicinal systems are available in Korea: Western and oriental. These exist as separate services that independently provide medical care to patients. We determined the utility and benefits of compressive and integrated medical services (CIMS) comprising 12 sessions of acupuncture and healing programs over 6 weeks. Methods: In this two-group parallel single-center randomized controlled assessor-blinded trial, 24 participants were assigned to either the experimental (conventional medical treatment plus CIMS, n = 12) or control (conventional medical treatment, n = 13) group. Spinal nerve root block was performed on the compressed spinal nerve root (identified using magnetic resonance imaging) when no improvement was observed after the initial treatment. The experimental group received 12 cycles of acupuncture and manual therapy for 6 weeks; the control group received conventional medical treatment alone. Results: The average age of participants in the experimental and control groups was 70.73 ± 5.95 and 67.33 ± 8.89 years, respectively. There were no significant differences between the groups in terms of age, body mass index, Leeds Assessment of Neuropathic Symptoms and Signs, sex, and current medical history. We found high compliance for both programs (acupuncture and healing). On exclusion of between-group effects, the visual analog scale (VAS) score improved significantly over time (p = 0.045). Further, comparison of the groups after excluding the effects of visits revealed significantly lower VAS scores in the experimental group than in the control group (p = 0.000). Conclusions: Patients with degenerative lumbar spinal stenosis who mainly complain of radiating pain in the lower leg may benefit from CIMS after spinal nerve root block for ≤3 months after treatment. Our study findings suggest that this treatment improves spinal function and Oswestry Disability Index score. However, CIMS did not improve QoL.

Staphylococcus aureus is a causative agent of nosocomial infections and its antibiotic-resistant strains are concerning. Solutions are being explored to improve the treatment of these infections, including repositioning drugs such as statins and using nanoparticles with antimicrobial properties. This study aimed to evaluate the antimicrobial effects of simvastatin (SIM) and biologically synthesized silver nanoparticles (bio-AgNPs) in isolate form and in combination by assays of minimum inhibitory concentration (MIC), an in vitro biofilm model, and the association of antimicrobials against clinical strains of S. aureus. Bio-AgNPs showed a 53.8 ± 1.23-nm mean diameter and standard deviation, a 0.23 polydispersity index, and a −25.66 ± 2.19-mV mean potential and standard deviation. Transmission electron microscopy confirmed the formation of nanoparticles and the presence of Ag0 and AgCl. S. aureus strains were sensitive to bio-AgNPs and SIM, showing 31.88-187.5 and 74.66-149.32 μM concentrations, respectively. Our association assay showed 2.0 fractional inhibitory concentration indices (i.e., indifferent for clinical strains) and 0.32 values for the standard ATCC 29213 strain (synergy). Our biofilm inhibition assays with isolated SIM and bio-AgNPs showed decreased biofilm formation from 4× to ⅛ MICs, showing no synergism in association. These findings evince that simvastatin and bio-AgNPs at subinhibitory concentrations can serve as antimicrobial agents against S. aureus biofilm.

The α-synucleinopathies are a group of neurodegenerative diseases characterized by the deposition of α-synuclein aggregates (α-syn) in the brain. Currently, there is no suitable tracer to enable a definitive early diagnosis of these diseases. We reported candidates based on 4,4'-disarylbisthiazole (DABTA) scaffold with a high affinity towards α-syn and excellent selectivity over Aβ and tau fibrils. Based on prior in silico studies a focused library of 23 halide-containing and O-methylated DABTAs was prepared. The DABTAs were synthesized via a modified two-step Hantzsch thiazole synthesis, characterized, and used in competitive binding assays against [3H]PiB, and [3H]DCVJ. The DABTAs gave an overall chemical yield of 15 – 71%, with a calculated lipophilicity of 2.5 – 5.7. The ligands demonstrated an excellent affinity to α-syn with both [3H]PiB and [3H]DCVJ: Ki 0.1 – 4.9 nM and up to 20 – 3900-fold selectivity over Aβ and tau fibrils. It could be concluded that in-silico simulation is useful for the rational design of a new generation of DABTAs. Further investigation of the leads in the next step is encouraged: radiolabeling of the ligands with radioisotopes such as fluorine-18 or carbon-11 for in vivo, ex vivo and translational research and for further in vitro experiments on human-derived protein aggregates.

Few reports exist on the pathologies of the northern bottlenose whale (Hyperoodon ampullatus) and other Ziphiidae. We here describe a large exostosis in the right pterygoid bone of adult female H. ampullatus ANSP-3004 that stranded on the US Atlantic coast in 1867. Images of the skull and 14 cranial measurements were examined and compared with two ‘normal’ adult female H. ampullatus specimens. Surface scans of ANSP-3004 were made with a Faro Design Arm 1.0 scanner at 75µm resolution. The form, structure and width (15.9 cm) of the right pterygoid were found to be abnormal. Its distal extremity was curved in labial direction while its proximal extremity was deformed by a large, bulbous exostosis of 14.3 x 12.5 cm that partially obstructed the right nasal passage. Lytic lesions in the posterior end of the exostosis exposed deep resorption lacunae. The left pterygoid was thin (3.4 cm) and laterally displaced. No diagnosis was possible for lack of histological examination but the osteopathy was consistent with osteoma, a benign bone tumor commonly seen on the jaws and nasal sinuses of bovines, phylogenetical relatives of Cetacea. The partial nasal passage obstruction may have affected respiration to some degree, but since the female was lactating, general fitness appeared stable.