Background: Chronic pelvic pain is a debilitating condition affecting quality of life. Endometriosis is one of the leading causes of CPP, but recent studies highlighted the role of interstitial cystitis/bladder pain syndrome (IC/PBS) in causing CPP. Only some studies addressed the coexistence between these two conditions, which seems more frequent than what is supposed, leading to diagnostic delays and unnecessary surgeries. This systematic review aimed to evaluate the estimate of the coexistence of endometriosis and IC/PBS. Methods: We performed a systematic review of the literature indexed on PubMed, Scopus, ISI Web of Science, and Cochrane using a combination of keywords and text words represented by “painful bladder syndrome”, “endometriosis”, “interstitial cystitis”, “bladder pain syndrome”. We performed a meta-analysis of the results. Results: Meta-analysis shows that the coexistence of endometriosis and IC/PBS in women with CPP ranges between 15,5-78,3%, which is higher than the prevalence of IC/PBS in the general population. Conclusions: Women with CPP need a multidisciplinary approach and a referral to centers with specific expertise. In cases of endometriosis unresponsive to treatment, other reasons for CPP need to be ruled out, above all in women not responsive to treatment.

Background: Quality of life (QoL) in IC/BPS patients is an evidence gap in guidelines, because studies are limited and outdated. Therefore, guidelines might not reflect the current situation accurately, and no possible improvements in QoL of these patients. Secondly, guidelines suggest multimodal approach in therapy, however unknown is how the efficacy of these therapies are perceived by the patient themselves. The aim of this study is to investigate the perception of IC/BPS patients on their QoL and to determine which treatments they received and how they evaluate the efficacy of these various (alternative) therapies.Methods: Quantitative retrospective database study in IC/BPS patients, compiled of existing patient survey data (n=217) from July 2021. Results: The QoL of patients is affected significantly by IC/BPS. This is evident from the substantial self-reported impact by patients, the various affected domains on EQ-5D 5L. The QoL was not negatively affected by delayed diagnosis, but there were differences between female and males. Secondly, there was the wide array of (alternative) treatments utilized, although some have doubtful results and high dropout rates. Conclusion: QoL is considerably impaired in IC/BPS patients. Coagulation therapy and intravesical GAG therapy were most appreciated treatments. The diverse responses and adherence to various treatments warrant a personalized approach (phenotype-oriented therapy). To achieve improvement in the QoL, it is important to incorporate the patient’s perspective in treatment guidelines.

Research studies related to neuroplastic changes that occur secondary to a bout of cystitis at a critical neonatal period of development in female rats (P14-16) are reviewed. They reveal that neonatal bladder inflammation (NBI) leads to an adult phenotype with many of the features of the human disorder, interstitial cystitis. Neurochemical, behavioral and neurophysiological differences between rats which experienced NBI and control animals are discussed and new data presented.

Background: The laryngeal mask airway Vision Mask (LMA VM) is a supraglottic airway device (SAD) with vision guidance system. The ideal head and neck position for direct laryngoscopy is known, but the ideal position for placing a LMA is not. The objective of this study is to evaluate and compare the optimal position for placement of a video laryngeal mask airway. Methods: This was a prospective observational, transversal and analytical study of 72 consecutive patients. In the same patient, laryngeal vision was first assessed with the head and neck in the sniffing position and then with the head in the neutral position. Procedures were filmed and performed by the same investigator. Assessment of the laryngeal view was performed using two classifications: modified Cormack-Lehane classification and Brimacombe classification. Device placement was considered adequate when the Cormack-Lehane rating was scored from 1 to 2 and the Brimacombe rating was from 2 to 4. Results: 72 patients were included in this study. In the assessment of the glottis using the Cormack Lehane classification for fiberoptic view, laryngeal visibility was adequate in 64 (88.89%) patients in the neutral position and in 65 (90,28%) patients in the sniffing position (p>0,05). In the fiberoptic view of the glottis, assessed using the Brimacombe classification, laryngeal visibility was adequate in 68 (93%) patients in the neutral position and in 69 (95%) patients in the sniffing position, (p>0,05). There was no statistically significant difference in the rate of success between the sniffing position (70 patients, 97.22% success rate) and the neutral position (67 patients, 93.06% success rate) during the first insertion attempt. Two patients required a second attempt in the sniffing position, while five patients required a second attempt in the neutral position. Conclusion: An adequate sniffing position did not result in a better glottic view than neutral position, and the number and type of additional maneuvers were equal in both positions.

Iron is an essential nutrient for humans and microbes, such as bacteria. Iron deficiency occurs commonly in critically ill patients, but iron replacement therapy is not considered during the acute phase of critical illness, since it increases iron availability for invading microbes and oxidative stress. However, persistent iron deficiency in the recovery phase is harmful with potential adverse outcomes such as cognitive dysfunction, fatigue and cardiopulmonary dysfunction. Therefore, it is important to treat iron deficiency timely and efficiently. This article reviews current knowledge about iron-related biomarkers in critically ill patients and provides possible criteria to guide decision-making for iron supplementation in the recovery phase of critical illness.

In this non-exhaustive review, we discuss the importance of invariant vectors in atomic physics, such as the Laplace-Runge-Lenz vector, the Redmond vector in the presence of an electric field, the Landau-Avron-Sivardière vector when the system is subject to a magnetic field, and the supergeneralized Runge-Lenz vector for the two-center problem. Application to Stark and Zeeman effects are outlined. The existence of constants of motion in the charge-dyon system is also briefly mentioned.

Bladder cancer (BC) diagnosis is reliant on cystoscopy, an invasive procedure associated with urinary tract infections. This has sparked interest in identifying non-invasive biomarkers in body fluids such as blood and urine. A source of biomarkers in these biofluids are extracellular vesicles (EVs), nanosized vesicles that contain a wide array of molecular cargo, including small non-coding RNA such as microRNA and transfer RNA-derived fragments (tRF). Here we performed small-RNA next-generation sequencing for urine EVs, serum EVs and serum supernatant from 41 patients with non-muscle invasive BC (27 stage Ta, 14 stage T1) and 15 non-cancer patients (NCP) with benign cystoscopy findings. Serum and urine samples were collected before transurethral resection of bladder tumors (TUR-b) and at routine postsurgery check-ups. Expression levels of tRFs in presurgery samples were compared to those at postsurgery check-ups and to NCPs. To strengthen the reliability of our results, samples from 10 patients with stage T1 disease were resequenced. When comparing tRF expression in urine EVs between BC patients with stage T1 disease and NCPs, 14 differentially expressed tRFs (DEtRFs) were identified. In serum supernatant, six DEtRFs were identified among stage T1 patients when comparing presurgery to postsurgery samples, and four DEtRFs were found when comparing presurgery samples to NCPs. By performing a blast search, we found that sequences of DEtRFs aligned with genomic sequences pertaining to processes relevant to cancer development, such as enhancers, regulatory elements and CpG islands. Our findings display a number of tRFs that may hold potential as biomarkers for the diagnosis and recurrence-free survival of BC.

A ganglion cyst is a benign fluid-filled sac that typically appears on the dorsal aspect of the wrist, arising idiopathically near the joint capsule or tendon sheath. Diagnosis is primarily clinical, with MRI and ultrasound serving as confirmation tools. Treatment options range from immobilization, aspiration, hydrossection, steroid or hyaluronidase injection, to surgical intervention. Although relatively uncommon, Dorsal Ganglion Cysts (DGC) can lead to Dorsal Wrist Impingement (DWI) syndrome. This syndrome results from the thickening of the wrist capsule due to overuse, injury, or repetitive activities. This thickening can lead to the compression of the extensor carpi radialis brevis (ECRB) tendon during wrist extension and produce tenderness around the lunate. In some refractory cases, MRI findings may show recurrent ganglion cysts, while in others, they may appear "normal." Consequently, the diagnosis remains clinical, and imaging is primarily employed to rule out secondary causes. Management strategies encompass rest, immobilization, occupational therapy, non-steroidal anti-inflammatory drugs (NSAIDs), cortisone injections, and, in certain instances, surgical intervention. Despite the clinical significance of these conditions, limited studies have explored their interrelationship. In this context, we present a rare case involving a 23-year-old female with recurrent DGC accompanied by DWI syndrome. Initially, the patient reported idiopathic left dorsal wrist pain localized around the tendon sheath. Her initial X-ray did not reveal any abnormalities, but MRI identified two ganglion cysts. A series of treatments were initiated, including left tendon sheath hydrossection, corticosteroid injections into the left wrist, and the excision of ganglion cysts from the left wrist. Furthermore, occupational therapy, oral Meloxicam, and Voltaren gel treatments were integrated into the management plan. Subsequent imaging confirmed the resolution of the cysts and an overall enhancement in the range of motion and wrist strength. However, the patient experienced only minimal pain relief, and pain was still elicited during end-range wrist extension and upon dorsal wrist palpation. An electromyography (EMG) test ordered to rule out neuropathic causes did not yield any conclusive results. Nonetheless, a repeat X-ray revealed mild soft tissue swelling on the dorsal side of the wrist, and a follow-up MRI detected ganglion cysts on the dorsal aspect of the lunate and the ECRB tendons. These findings indicated a re-accumulation of dorsal ganglion cysts with a concurrent dorsal impingement syndrome component. Consequently, the patient was referred to an orthopedic surgeon for evaluation and potential revision surgery. This unique case underscores the possibility of developing DWI Syndrome after the removal of a DGC. The diagnosis of this syndrome can be elusive, particularly when X-rays, MRIs, and EMGs yield negative results. Trauma, such as repeated hand surgery or recurrent ganglion cysts, may exacerbate wrist pain despite improvements in range of motion and strength. Special consideration should be given to patients who undergo surgical cyst excisions, as this procedure heightens the risk of recurrence and can irritate the tendon sheath. Collaborative efforts between Physical Medicine and Rehabilitation (PM&R), Occupational Therapy (OT), and surgical teams may play a pivotal role in managing pain associated with these conditions. We propose that future research endeavors should focus on establishing guidelines for the management of this unique condition.

Myofascial pain is the most common cause of chronic pain in the masticatory region and can be assessed through clinical analysis and muscle palpation. Generally, it appears with headache and orofacial pain associated with sensitive points (trigger points) due to the excessive contraction of the masticatory muscle fibres. The study aims to evaluate how a correct treatment of myofascial pain can improve the life quality of the affected patients. In this case series, 300 patients with myofascial pain were divided into two groups: 150 with intra- and extra-articular disorder and 150 with the only extra-articular disorder. Each group included 75 males and 75 females. All the patients were treated with gnathological therapy through passive aligners and biofeedback exercises for 4 months. They underwent pain assessment (through a visual analogue scale and muscular palpation test) before, during and after the treatment, and nuclear magnetic resonance of the temporomandibular joint before and after the gnathological treatment. The treatment considerably reduced the pain in all patients, without drugs, in 4 months, according to the visual analogue scales and the palpation test. The temporomandibular magnetic resonance in each patient was similar before and after the gnathological treatment. The improvement in pain did not depend on a change in the relationship between the articular condyle and the disc.

The microbiota–gut–brain axis has garnered increasing attention in recent years for its role in various health conditions, including neuroinflammatory disorders like complex regional pain syndrome (CRPS). CRPS is a debilitating condition characterized by chronic neuropathic pain, and its etiology and pathophysiology remain elusive. Emerging research suggests that alterations in the gut microbiota composition and function could play a significant role in CRPS development and progression. Our paper explores the implications of microbiota in CRPS and the potential therapeutic role of boron (B). Studies have demonstrated that individuals with CRPS often exhibit dysbiosis, with imbalances in beneficial and pathogenic gut bacteria. Dysbiosis can lead to increased gut permeability and systemic inflammation, contributing to the chronic pain experienced in CRPS. B, an essential trace element, has shown promise in modulating the gut microbiome positively and exerting anti-inflammatory effects. Recent preclinical and clinical studies suggest that B supplementation may alleviate neuropathic pain and improve CRPS symptoms by restoring microbiota balance and reducing inflammation. Our review highlights the complex interplay between microbiota, inflammation, and neuropathic pain in CRPS and underscores the potential of B as a novel therapeutic approach to target the microbiota–gut–brain axis, offering hope for improved management of this challenging condition.

The development of anti-pain technologies in the complex treatment of pain syndromes is one of the most urgent tasks of modern medicine. We have undertaken a placebo-controlled experimental study of the therapeutic potential of low-intensity laser radiation when applied to acupuncture points, which are directly related to the autonomic nervous system. The adaptation effect of puncture photobiomodulation on the induction of stress-mediated autonomic reactions, oxidative metabolism and microcirculation in animals during the acute phase of pain stress was revealed. The data obtained are of interest for use in the complex rehabilitation of patients with pain syndrome.

Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheu-matoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and eth-nicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast–myofibroblast transition, epithelial–mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the his-topathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.

Twelve clinically healthy and sexually mature New Zealand White rabbits were studied. The non-contrast imaging included T1-weighted and T2-weighted spin echo and gradient echo sequences in transverse, sagittal and dorsal planes. Transverse MRI (Т2-weighted image) through L1 demonstrated only the right kidney. The transverse T2-weighted image through L2 showed both kidneys. The cranial part of the urinary bladder on T1-weighted transverse scans through L4 was flexed to the left. The T2-weighted sagittal image 30 mm to the right of the median plane showed the right kidney, the right ureter and the urinary bladder. The T2-weighted sagittal image 30 mm to the left of the median plane showed part of the left kidney, the left ureter and the urinary bladder. The T2-weighted sagittal image 45 mm to the left of the median plane presented the lateral part of the left kidney. The dorsal MRI image (Т2-weighted sequence) through the horizontal plane 30 mm ventral to the spine demonstrated the whole organs. The data will be useful in imaging anatomy and diagnostic studies of various pathologies of the excretory system in rabbits and other mammalian species.

To identify factors associated with interstitial lung disease (ILD) in patients with systemic sclerosis (SSc) and build an algorithm to better define this association, for a personalized application in clinical practice. Methods. 78 SSc patients underwent HRCT to assess ILD. Demographic, clinical and laboratory variables were collected, focusing on those associated either directly or indirectly with lung involvement. The discriminant value of each variable was determined using the operating characteristic curves (ROC) and included in a model to estimate the strength of ILD association in SSc. Results. Thirty-three (42.31%) patients showed ILD on HRCT. DLco, M-Borg, GERD-Q, and capillary density were significantly associated with the presence of ILD-SSc. A model including these variables had a coefficient of determination (R2) of 0.697. DLco had an AUC of 0.861 (p<0.001) with a cut-off ≤72.3% (sensitivity 78.8%, specificity 91.1%, +LR 8.86). The m-Borg scale showed an AUC of 0.883 (p<0.001) with a cut-off >2 (sensitivity 84.8%, specificity 82.2%, +LR 4.77), GERD-Q had an AUC of 0.815 (p<0.001) with a cut-off >7 (sensitivity 72.7%, specificity 86.7%, +LR 5.45). The capillary density showed an AUC of 0.815 (p<0.001) with a cut-off ≤4.78 (sensitivity 87.9%, specificity 68.9%, +LR 2.82). Based on the pre-test probability values, these four variables were applied to Fagan's nomogram to calculate the post-test probability of this association. Conclusions. Our study identified four associated clinical factors of ILD in SSc patients. Moreover, their inclusion in an algorithm for the post-test probability, tailored to the specific patients’ characteristics, significantly increases the ability to find out the presence of SSc-ILD.

Urethral pain syndrome (UPS) is still a pathology in which the diagnosis is formulated as a "diagnosis of exclusion". The exact pathogenetic mechanisms are not yet fully understood and clear recommendations for the prevention and treatment of UPS are absent. The goal of the study was to assess the condition of the tissues in the female urethra in UPS, by using transvaginal ultrasound (TVUS) and cross-polarization optical tomography (CP OCT). TVUS showed an expansion in the diameter of the internal lumen of the urethra, especially in the proximal region compared with the norm. Compression elastography revealed areas with increased stiffness (presence of fibrosis) in urethral and surrounding tissues. When studied with CP OCT it was shown that with UPS, the structure of the tissues in most cases was changed: trophic alterations in the epithelium (hypertrophy or atrophy) and fibrosis of underlying connective tissue were observed. The proximal fragment of the urethra with UPS underwent changes identical to those of the bladder neck. This paper showed that the introduction of new technology — CP OCT — in conjunction with TVUS will allow verification of structural changes in tissues of the lower urinary tract at the level of their architectonics and will help doctors understand better the basics of the UPS pathogenesis.

Background: To assess the prevalence of Hypertension (HTN) in Burning Mouth Syndrome (BMS) patients and to investigate its relationship with sociodemographic factors, pain and the psychological profile. Methods: A case-control study was conducted by enrolling 242 BMS patients and 242 controls matched for age and gender. Sociodemographic and clinical characteristics were recorded, and all the participants completed the numeric rating scale (NRS), the short-form of the McGill pain questionnaire (SF-MPQ), the Hamilton rating scale for anxiety and depression (HAM-A, HAM-D), the Pittsburgh sleep quality index (PSQI) and the Epworth sleepiness scale (ESS). Results: The BMS patients presented a statistically significant higher prevalence of HTN compared to the controls (55% versus 33.5%; p-value: <.001**) and higher median scores of the NRS, SF-MPQ, HAM-A, HAM-D, PSQI and ESS (p < .001**). Multivariate regression analysis in the BMS patients indicated positive correlations between HTN and age, systemic diseases, drug consumption and anxiety (p-value: <.001**) and these predictors were responsible for 11.3% of the HTN variance in the BMS patients, when considered together. Conclusions: The prevalence of HTN was significantly higher in the BMS patients, since ageing, the presence of comorbidities, drug consumption and anxiety were potential predictors. Further studies are needed to better investigate the relationship between BMS and HTN.

Background: Chronic post-surgical pain is a condition persisting at least three months after surgery. It is estimated that 25-60% of patients who underwent breast cancer removal surgery suffer from post-mastectomy pain syndrome and occurred anxiety, depression, sleep disturbance and catastrophizing. Physical activity can reduce the risk of chronic diseases and has a good impact on mood and cognitive function. Aim of this study was to evaluate the effects of physical activity on the intensity of pain, depression and anxiety in women underwent mastectomy for breast cancer removal. Methods: A prospective observational unicentric cohort study was performed. Patients were female underwent unilateral or bilateral mastectomy. Numerical Rating Scale (NRS), was used to assess pain intensity, Beck’s Depression Inventory (BDI) for depression and Generalized Anxiety Disorders-7 (GAD-7), for anxiety evaluation. Physical activity was assessed by International Physical activity questionnaire (IPAQ). Interleukin (IL)-17, IL-1β, cortisol, adrenocorticotropic hormone (ACTH) and brain-derived neurotrophic factor (BDNF) were also evaluated in the blood of patients. All the evaluation was assessed 3 and 6 months after the surgery. Results: Adequate physical activity reduced intensity of pain, depression and anxiety symptoms in women affected by post-mastectomy pain syndrome. Moreover, adequate active women, showed a reduction of biomarkers of inflammation, cortisol, ACTH and an increase of BDNF. Conclusions: Our results suggest that physical activity can improve quality of life, reducing intensity of pain, inflammatory markers and it can be useful in the reduction of associated anxiety and depression.

Depression, anxiety, and pain are part of a common phenomenon that requires to be studied together when evaluating patients with chronic pain. The aim of the study was to examine the correlations between depression, anxiety and pain intensity in patients with chronic pain and how they change when a depressive episode was added. A sample of 120 patients with chronic pain (age: 51.90±11.94; 81.7% female; 18.3% male) was studied in two stages with a three-month period between them. Patients with a depressive episode (n=61) were treated with antidepressants and analgesics, while a patient without depression (n=59) was treated only with analgesics. The scales used to achieve the objectives were: HAM-D-17, Spielberger‘s STAI and VAS. Insignificant correlations were found between depression, state and trait anxiety, and pain intensity (p<0,05) in the group without depression, except for a significant one between depression and state anxiety (p<0,01) in the second stage. Significant correlations were identified between all indicators (p<0,01) in the group with depression at the two stages. Those in the second stage were stronger. The interrelations between sensory and affective aspects of pain were stronger when a depressive episode occurs, the severity of which determines their dynamics.

(1) Background: Intravesical Chemotherapy is standard of care in intermediate risk non-muscle-invasive bladder cancer (NMIBC). Different agents are used across the world based on availability, cost and practice patterns. Epirubicin (EPI), one of these agents is used by many centers over many decades. However, its true differential efficacy compared to other agents and its tolerability is still poorly reported. We aimed to assess the differential efficacy and safety of intravesical EPI in NMIBC patients. (2) Methods: A systematic search of PUBMED, Webofscience, clinicaltrials.gov, and Google Scholar databases was performed on December 31, 2023. We reviewed 28 studies that included patients treated EPI after TURBT (transurethral resection of bladder tumors) for NMIBC and who compared oncological outcomes such as recurrence and progression to other adjuvant treatment such as Mitomycin C (MMC), Gemcitabine (GEM) and BCG. Further, we looked at the safety profile of EPI at room temperature under hyperthermia intravesically and at the oncological outcomes when administrated with hyperthermia; (3) Results: When compared to other chemotherapeutics (MMC/GEM), EPI seemed to be equally effective; however, EPI seems less effective in preventing disease management recurrence compared to BCG intravesical. The most common adverse events of EPI include cystitis, dysuria, and pollakiuria. (4) Conclusions: EPI exhibits similar oncological performances to Gemcitabine and Mitomycin C currently used for adjuvant therapy in NMIBC. Novel delivery mechanisms such as hyperthermia are promising newcomers.

Abstract: Laryngoscopy for tracheal intubation has been developed for many decades. Among various conventional laryngoscopes, videolaryngoscopes (VL) have been applied in different patient populations, including difficult airways. The safety and effectiveness of VL have been repeatedly studied in both normal and difficult airways. The superiority of VL then has been observed and is advocated as the standard of care. In contrast to laryngoscopy, the development of video-assisted intubating stylet (VS, also named as styletubation) has been noticed two dec-ades ago. Since then, sporadic clinical experiences of use have appeared in literature. In this re-view article, we presented our vast use experiences of the styletubation (more than 55,000 pa-tients since 2016). We found this technique is swift (the time to intubate: from 3 s to 10 s), smooth (first-attempt success rate: 100%), safe (no airway complications), and easy (high subjective satis-faction and fast learning curve for the novice trainees) in both normal and difficult airway sce-narios. We therefore propose styletubation technique can be feasibly applied as universal rou-tine use for tracheal intubation.

This study aimed to investigate the efficacy of manual therapy and exercise versus synchronized telerehabilitation with self-manual therapy and exercise in treating Subacromial Pain Syndrome (SAPS). Sixty individuals diagnosed with SPS, aged 18-50 years, were randomly assigned to home exercise (HE), manual therapy (MT), and telerehabilitation (TR) groups. Treatment protocols were administered over 8 weeks and included specific exercises and therapy interventions. Out-come measures included Visual Pain Scale (VAS), shoulder range of motion (ROM) via gonio-metric measurements, Quick Disability Arm-Shoulder-Hand Problems Survey (Q-DASH), and patient satisfaction. Results revealed that both MT and TR groups exhibited reduced pain, in-creased ROM, lower Q-DASH scores, and higher patient satisfaction compared to the HE group. However, no significant differences were found between MT and TR groups in pain levels, ROM, Q-DASH scores, or patient satisfaction. The study concludes that both telerehabilitation and manual therapy effectively alleviate pain and are well-received by patients with SPS. Addition-ally, manual therapy demonstrates superiority in enhancing functional levels compared to exer-cise-based interventions. (Registration: NCT05200130)

Urinary tract diseases are common in cats, and often require surgical reconstruction. Here, to explore the possibility of urinary tract reconstruction in cats using in-vivo tissue architecture (iBTA), biosheets fabricated using iBTA technology were implanted into the feline bladder and the regeneration process was histologically evaluated. The biosheets were prepared by embedding molds into the dorsal subcutaneous pouches of six cats for 2 months. A section of the bladder wall was removed, and the biosheets were sutured to the excision site. After 1 and 3 months of implantation, the biosheets were harvested and evaluated histologically. Implantable biosheets were formed with a success rate of 67%. There were no major complications following implantation, including tissue rejection, severe inflammation, or infection. Urinary incontinence was also not observed. Histological evaluation revealed the bladder lumen was almost entirely covered by urothelium after 1 month, with myofibroblast infiltration into the biosheets. After 3 months, the urothelium became multilayered, and mature myocytes and nerve fibers were observed at the implantation site. In conclusion, this study showed that tissue reconstruction using iBTA can be applied to cats, and that biosheets have the potential to be useful in both the structural and functional regeneration of the feline urinary tract.

As various services have been generating large scale graphs to represent multiple relationships between objects, studies have been conducted to obtain subgraphs with particular patterns. In this paper, we propose a distributed query processing method to efficiently search a subgraph for a large graph on Spark. To reduce unnecessary processing costs, the search order is determined by filtering scores using the probability distribution. The partitioned queries are searched in parallel in the distributed graph of each slave node according to the search order, and the local search results obtained from each slave node are combined and returned. The query is partitioned in triplets based on the determined search order. The performance of the proposed method is compared with the performance of existing methods to demonstrate its superiority.

Ehlers–Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders (HCTDs) characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Among the different types, the hypermobile EDS (hEDS) is the most frequent, and includes generalized joint hypermobility as the major diagnostic criterion. Joint hypermobility in hEDS is often associated with pain that not always allow the use of effective pain-reducing treatments. Patients with hEDS always talk about pain using a lot of descriptions. Eighty-nine patients with diagnosis of hEDS were recruited and evaluated. They were asked to write down what grief was to them. The texts were analyzed through LIWC. Correlational analyses were conducted between pain perception and language. A comparison of high/low pain perception and quality of metaphors was carried out. The results showed, depending on the level of pain perception, different language quality is evidenced. The greater the pain the lesser the positive effects and the greater the negative effects and dehumanizing metaphors. Moreover, greater pain seems to be related to a verbal experience of greater isolation and less self-care. In conclusion, the use of metaphors is a useful tool for exploring illness experience and may help clinicians in the rehabilitation program.

Detection and measurement of pain are crucial in designing effective pain management interventions to alleviate suffering and prevent functional decline in the medical domain. Traditional methods of pain identification rely on verbal patient reports or observable signs, which can be imprecise or subjective due to variability in patient self-assessments. Hence, there is a pressing need for automated methods to standardize pain measurement procedures. This paper proposes a novel facial expression-based automated pain assessment system as a behavioral indicator for pain evaluation. Our system integrates a fusion structure comprising Convolutional Neural Networks (CNNs) and Tensor-based extended Quantitative Expression Descriptors Analysis (TXQEDA). This innovative approach allows for joint learning of robust pain-related facial expression features from raw facial images, combining RGB appearance with shape-based latent representation. We extensively evaluated our proposed model using the UNBC-McMaster dataset for pain classification and intensity estimation. Our results demonstrate the efficacy of the proposed technique, achieving an impressive accuracy of 99.10% for pain level classification. Furthermore, our system excels in pain intensity estimation, showcasing its potential to provide precise and reliable assessments of pain severity. Overall, our research underscores the importance of automated pain assessment systems in improving patient care and clinical outcomes. By leveraging advanced deep learning techniques and fusion strategies, our proposed model offers a promising approach for standardizing pain measurement procedures and enhancing the quality of pain management interventions.

Objective:Over the last two decades one of the main surgical treatment for stress urinary incontinence (SUI) and pelvic organ prolapse (POP) surgery was the insertion of non-absorbable mesh to restore continence and prolapse respectively. Over time complications arose including mesh-associated pain syndrome (MAPS), mesh exposure, mesh-erosion, chronic bladder/vaginal infections, and dyspareunia. Consequently, women chose surgical mesh removal to counter these problems. However, little is known about the demographics, medical co-morbidities, mesh types involved and the timing from mesh insertion to mesh removal. This retrospective study will look at which of these factors may be closely associated with mesh removal surgery.Design:Retrospective studySetting:Female Pelvic Medicine and Reconstructive Surgery (FPMRS) Clinic at University College London Hospitals NHS Foundation Trust.Population:All patients presenting to the FPMRS Clinic between June 2011 to December 2019, requesting mesh removal surgery with a history of MAPS and other mesh complications were included in this study. Methods:Patient demographics including age, ethnicity, obstetric history, and medical co-morbidities; type of mesh/anatomical route used; onset of symptoms; and time from insertion to removal were recorded. Main Outcome Measures:Determination of correlation coefficients between patient demographics, patient reported symptoms and mesh removal surgery. Results:Three hundred and forty-five women with a history of MAPS were included in the study. Women in the 40-60 year old cohort accounted for 54.4% of mesh removal surgery; 54.8% had a BMI under 30 and almost 90% were Caucasian. 96.5% had had children, with over 77% having had a vaginal delivery. 91.9% of patients reported other health conditions including 18.8% with a concomitant history of mental health problems and 15.4% with a history of heart disease. Over 80% of women undergoing mesh removal surgery had a continence mesh (49% retropubic and 32% obturator continence mesh) removed, whereas 20% had an abdominal prolapse and/or vaginal prolapse mesh removed. The average time from mesh insertion to mesh removal was seven years, with the prevalence of mesh removal surgery averaging 85% (range 50 - 100%) depending on the comorbidity determined. Conclusions:All women presented to the clinic with a history of MAPS and other comorbidities which may have influenced their decision to pursue mesh removal surgery. There were no specific predictors, other than chronic pain associated with mesh, determining which women underwent surgery, though those with continence mesh were more likely to do so.

Iron plays a critical role in lung infections due to its function in the inflammatory immune response but also as an important factor for bacterial growth. Iron chelation represents a potential therapeutic approach to inhibit bacterial growth and pathologically increased pro-inflammatory mediator production. The present study was designed to investigate the impact of the iron chelator, DIBI, in murine lung infection induced by intratracheal Pseudomonas aeruginosa (strain PA14) administration. DIBI (80mg/kg) was given by intraperitoneal injection either as a single dose immediately after PA14 administration or a double dose (second dose 4 h after PA14 administration). The results showed that lung NF-κBp65 levels, as well as levels of various inflammatory cytokines (TNFα, IL-1β, IL-6) both in lung tissue and bronchoalveolar lavage fluid (BALF), were significantly increased 24h after PA14 administration. Single-dose DIBI did not affect the bacterial load or inflammatory response in the lungs or BALF. However, two doses of DIBI significantly decreased bacterial load, attenuated NF-κBp65 upregulation, reduced inflammatory cytokines production, and relieved lung tissue damage. Our findings support the conclusion that the iron chelator, DIBI, can reduce lung injury induced by P. aeruginosa, via its anti-bacterial and anti-inflammatory effects.

Lung cancer remains one of the leading causes of cancer-related mortality worldwide. There is evidence of a complex interplay between lung cancer and interstitial lung disease (ILD), affecting disease progression, management strategies, and patient outcomes. Both conditions develop as the result of common risk factors such as smoking, environmental exposures, and genetic predispositions. The presence of ILD poses diagnostic and therapeutic challenges in lung cancer management, including difficulties in interpreting radiological findings, increased susceptibility to treatment-related toxicities, such as acute exacerbation of ILD after surgery and pneumonitis after radiation therapy and immunotherapy. Moreover, due to the lack of large, phase III randomized controlled trials in patients with lung cancer and ILDs, the evidence-based therapeutic options remain limited. The role of antifibrotic treatment in the prevention of lung-cancer-related treatment toxicities remains to be elucidated. Emerging diagnostic modalities and biomarkers, and optimizing personalized treatment strategies are essential to improve outcomes in this patient population.

While the majority of previous studies assessing pain-related variables in psychopaths used electric shocks, little is known about the effectiveness of alternative pain-inducing methods to increase emotional responses such as fear and anxiety. A small sample of healthy undergraduate men (N = 15) was recruited to assess the effectiveness of a heat stimulus to induce pain in an immediate versus delayed punishment paradigm. Although pain catastrophizing, anxiety, and threat of pain did not increase throughout the experiment, participants experienced a significant increase of fear of pain and pain intensity, indicating that the heat stimulus was effective in inducing pain. Furthermore, subjects were slower in initiating the pain stimulus during the first five trials, but no time difference was found during the 15 remaining trials. No correlation was found between psychopathic traits and pain-related variables, with the exception of inconsistent results within the Fearless Dominance factor. Findings are discussed in terms of improvement for a larger scale study involving psychopathic individuals.

With the increasing occurrence of rotator cuff injuries every year, there is a great need for a reliable treatment option. Wharton’s Jelly contains several components that can positively impact the replacement and repair of musculoskeletal defects. The overall objective of this study is to evaluate the improvement of patient-reported pain scales after applying Wharton’s Jelly (WJ) in rotator cuff defects. Eighty-seven patients with rotator cuff defects who failed at least eight weeks of conservative treatment were selected from the retrospective repository. 2cc of WJ flowable allograft was applied to the specific affected anatomy, the most common being supraspinatus tendon, biceps tendon insertion, labral tear, and subscapularis tear. No adverse reactions were reported. Statistically significant improvements were found from the initial to Day 90 in all scales. Patient satisfaction was calculated using minimal clinically important differences. No statistically significant differences were found in mean changes between gender, BMI, and age. Scanning Electron Microscopy images reveal the similarities between the collagen matrix in WJ and the rotator cuff. The significant improvement in patient outcomes coincides with current literature analyzing WJ applications with other structural defects around the body. WJ is a promising alternative for musculoskeletal defects when the standard of care fails.

Knee osteoarthritis (KO) is an important health condition, affecting one third of the people aged 65 years or more. Pain is the main cause of disability. Pain management in KO includes pharmacological and non-pharmacological modalities. Patient education, lifestyle changes, physical exercise and physical agents are prescribed as a first approach for pain control. Laser therapy is part of many therapeutical protocols, with two forms, low-level laser therapy (LLLT) and high-intensity laser therapy (HILT). The paper aimed at stressing the advantages of HILT, based on a greater wavelength, higher energy delivery and deeper tissue penetration. Research on 23 published trials revealed that analgesic effect is rapid, cumulative and long lasting. Compared to sham, to LLLT or to other associations of therapeutical modalities, HILT provided significantly better results on pain reduction and functional improvement. Ultrasound examination showed reduction of intraarticular inflammation.

Background: The clinical spectrum of fibrotic interstitial lung diseases (ILD) is highly heterogeneous. We aimed to evaluate the prognostic value of widely available baseline biomarkers for improvement of lung function in patients with fibrotic ILD. Methods: This registry-based study included 142 patients with fibrotic ILD as defined by presence of reticulation, traction bronchiectasis or honeycombing on initial high-resolution computed tomography (HRCT). Functional improvement at 1 year was defined as relative increase of 5% in forced vital capacity (FVC) or of 10% in diffusion capacity for carbon monoxide (DLCO). The prognostic value of baseline biomarkers was evaluated for all patients and the subgroup with anti-inflammatory treatment. Results: At one year, 44 patients showed improvement while 73 progressed. Multivariate analyses found prognostic significance for age <60 years (OR 5.4; 95%CI 1.9-15.4; p=0.002), lactate dehydrogenase (LDH) >250U/L (OR 2.5; 95%CI 1.1-5.8; p=0.043) and blood monocyte count <0.8G/L (OR 3.5; 95%CI 1.1-11.3; p=0.034). In 84 patients undergoing anti-inflammatory treatment, multivariate analysis revealed age <60 years (OR 8.5 (95%CI 2.1-33.4; p=0.002) as the only significant variable. Conclusion: Younger age, higher LDH and lower blood monocyte count predicted functional improvement in fibrotic ILD patients, while in those treated with anti-inflammatory drugs, only age had significant implications.

Out of a worldwide annual incidence of ~150 million cases for urinary tract infection (UTI), >25% of outpatient prescriptions of oral antimicrobial treatment (OAT) are for cystitis not complicated by sepsis. OAT aids the immune cells infiltrating urothelium to eliminate uropathogens attaching and invading urothelium amidst hyperosmotic urine. This adaptability of uropathogens and the short interval between Penicillin sale and the first antimicrobial resistance (AMR) report suggests that AMR is a 3.8 billion years old evolutionary conserved heritable trait of surviving environmental threats through exponential proliferation of mutant strains selected by Darwinian principle. Therefore, OAT success with minimal AMR can be ensured by antimicrobial stewardship (AMS) following the principle of 5Ds -drug, dose, duration, drug-route, and de-escalation. While convenient to administer, the onset of minimum inhibitory concentration (MIC) for OAT in urine is a window of opportunity for uropathogens to survive the first contact with OAT and the descendant colonies armed with AMR are likely to survive subsequent higher urine OAT levels. Meanwhile, intravesical antimicrobial treatment (IAT) delivers the first strike well above MIC. The root cause analysis of AMR dovetails with the strengths, weaknesses, opportunity, and threat (SWOT) analysis of OAT in this interdisciplinary review.

Keywords: olfactory rehabilitation; chronic pain; fMRI;

Spinal cord stimulation (SCS) is a therapeutic modality for the treatment of various chronic pain conditions that has rapidly evolved over the past 50 years. Unfortunately, over time, patients implanted with SCS undergo a habituation phenomenon leading to decreased pain relief. Consequently, discovery of new stimulation waveforms and SCS applications have shown to prolong efficacy and reduce explantation rates. This article explores various SCS waveforms, their applications and proposes a graded approach to habituation mitigation. We suspect the neural habituation phenomenon parallels that seen in pharmacology. Consequently we urge further exploration of early introduction of these stimulation strategies to abate spinal cord stimulation habituation.

The overwhelming majority of bladder cancers are transitional cell carcinomas. Albeit mostly monotonous, carcinomas in the bladder may occasionally display a broad spectrum of histological features that should be recognized by pathologists because some of them represent a diagnostic problem and/or lead prognostic implications. Sometimes these features are focal in the context of conventional transitional cell carcinomas, but some others are generalized across the tumor making its recognition a challenge. For practical purposes, the review distributes the morphologic spectrum of changes in architectural and cytological. So, nested and large nested, micropapillary, myxoid stroma, small tubules and adenoma nephrogenic-like, microcystic, verrucous, and diffuse lymphoepithelioma-like, on one hand, and plasmacytoid, signet ring, basaloid-squamous, yolk-sac, trophoblastic, rhabdoid, lipid/lipoblastic, giant, clear, eosinophilic (oncocytoid), and sarcomatoid, on the other, are revisited. Key histological and immunohistochemical features useful in the differential diagnosis are mentioned. In selected cases, molecular data associated with the diagnosis, prognosis, and/or treatment are also included.

Although chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) have distinct clinical features, both diseases may coexist in a patient because they share similar risk factors such as smoking, male sex, and old age. Patients with both emphysema in upper lung fields and diffuse ILD are diagnosed with combined pulmonary fibrosis and emphysema (CPFE), which causes substantial clinical deterioration. Patients with CPFE have higher mortality compared with patients who have COPD alone, but results have been inconclusive compared with patients who have idiopathic pulmonary fibrosis (IPF). Poor prognostic factors for CPFE include exacerbation, lung cancer, and pulmonary hypertension. The presence of interstitial lung abnormalities, which may be an early or mild form of ILD, is notable among patients with COPD, and is associated with poor prognosis. Various theories have been proposed regarding the pathophysiology of CPFE. Biomarker analyses have implied that this pathophysiology may be more closely associated with IPF development, rather than COPD or emphysema. Patients with CPFE should be advised to quit smoking and undergo routine lung function tests, and pulmonary rehabilitation may be helpful. Various pharmacologic agents may be beneficial in patients with CPFE, but further studies are needed.

Ulcerative colitis (UC) is a chronic autoimmune disorder affecting the colonic mucosa. UC is a subtype of inflammatory bowel disease along with Crohn’s disease and presents with varying extraintestinal manifestations. No single etiology for UC has been found, but a combination of genetic and environmental factors is suspected. Research has focused on the role of intestinal dysbiosis in the pathogenesis of UC, including the effects of dysbiosis on the integrity of the colonic mucosal barrier, priming and regulation of the host immune system, chronic inflammation, and progression to tumorigenesis. Characterization of key microbial taxa and their implications in the pathogenesis of UC and colitis-associated cancer (CAC) may present opportunities for modulating intestinal inflammation through microbial-targeted therapies. In this review, we will discuss the microbiota-immune crosstalk in UC and CAC, as well as the evolution of microbiota-based therapies.

Objective: The Acute Cystitis Symptom Score (ACSS) was developed and validated as a self-reporting questionnaire for diagnosing and monitoring acute, uncomplicated cystitis (AC) in female patients. The study aims at the translation of the ACSS into Greek from original Russian as a source and American English as a new master version and at its linguistic validation. Material and Methods: Three independent professional native Greek translators, two of them experts in Russian and one in English, translated the ACSS from Russian and American English into Greek. The second group of three translators translated each of the three versions back into the original language to detect or correct any important discrepancies. These three Greek versions were then used for linguistic validation. Results: The English to Greek translation reflected more the spoken language, the two Russian to Greek translations more the written, formal language. A total of 60 randomly selected females and 30 healthcare professionals was asked about their preferences and to comment on each of the three translations. Considering all comments the scientific committee (SC) developed the Greek consensus version. For cognitive assessment additional 30 healthcare professionals and 30 females were asked to comment on the intelligibility of all items. Considering their comments the linguistically validated Greek study version was established by the SC. Conclusion: The linguistically validated Greek version of the ACSS can now be used for the clinical validation study.

Background To develop and validate the American-English version of the self-reporting Acute Cystitis Symptom Score (ACSS), a suitable tool for diagnosis and patient-reported outcome in female patients with acute uncomplicated cystitis (UC). Methods After certified translation into American-English and cognitive assessment, the clinical validation of the ACSS was performed as an embedded study in a US phase II trial (ClinicalTrials.gov Identifier: NCT03129295). Results A total of 167 female patients with typical symptoms of UC were included in the study following FDA guidance. At Day 1 (diagnosis) the mean(SD) sum score of the six ACSS typical symptoms reached 10.60(2.51). Of 100 patients followed-up last time on Day 5 or 6 (End-of-treatment, EoT), 91 patients showed clinical success according to the favoured ACSS criteria (sum score of typical symptoms 0.98(1.94)). There was no correlation between the severity of symptoms on Day 1 or between clinical success rate at EoT and level of bacteriuria on Day 1. Conclusion The American-English ACSS showed high predictive ability and responsiveness, and excellent levels of reliability and validity. It can now be recommended as the new master version in clinical and epidemiological studies, in clinical practice or for self-diagnosis of women with symptoms of UC.

Chemoradiation-based bladder preservation therapy (BPT) is currently a curative option for non-metastatic muscle-invasive bladder cancer (MIBC) patients at favorable risk or an alternative to radical cystectomy (RC) for those who are unfit for RC. In BPT, only patients who achieve complete response (CR) after chemoradiation have favorable prognosis and quality of life with preserved functional bladder. Thus, predicting CR and favorable prognosis is important for optimal patient selection for BPT. We reviewed biomarkers for predicting clinical outcomes of chemoradiation-based BPT. Biomarkers studied were categorized into those related to apoptosis, cell proliferation, receptor tyrosine kinases, DNA damage response genes, hypoxia, molecular subtype, and others. Among these biomarkers, Ki-67 labeling index (Ki-67 LI) and meiotic recombination 11 may be used for selecting BPT or RC. Ki-67 LI and erythroblastic leukemia viral oncogene homolog 2 (erbB2) may be used for predicting both chemoradiation response and prognosis of patients on BPT. Concurrent use of trastuzumab and a combination of carbogen and nicotinamide can overcome chemoradiation resistance conferred by erbB2 overexpression and tumor hypoxia. Further studies are needed to confirm the practical utility of these biomarkers for progress on biomarker-directed personalized management of MIBC patients.

Bacillus Calmette-Guérin (BCG) immunotherapy has been a cornerstone treatment for non-muscle invasive bladder cancer for decades and still faces challenges, such as severe immune adverse reactions, which reduce its use as a first-line treatment. This review examines BCG therapy’s history, mechanisms, and current status, highlighting how nanotechnology and bioengineering are revitalizing its application. We discuss novel nanocarrier systems aimed at enhancing BCG's efficacy while mitigating specific side effects. These approaches promise improved tumor targeting, better drug loading, and enhanced stimulation of anti-tumor immune responses. Key strategies involve using functional BCG cell wall components and co-delivering BCG with chemotherapeutics to achieve synergistic effects. While most studies remain experimental, this research direction offers hope for overcoming BCG's limitations and advancing bladder cancer immunotherapy. Further elucidation of BCG's mechanisms and rigorous safety evaluations of new delivery systems will be crucial for translating these innovations into clinical practice.

While Spinal Cord Stimulation (SCS) provides satisfaction to almost 2/3 of Persistent Spinal Pain Syndrome-Type 2 (PSPS-T2) patients implanted for refractory chronic back and/or leg pain when not adequately addressed the back pain component, leaves patients in a therapeutic cul-de-sac. Peripheral Nerve field Stimulation (PNfS) has shown interesting results addressing back pain in the same population. Far from placing these two techniques in opposition, we suggest that these approaches could be combined to better treat PSPS-T2 patients. We designed a RCT (CUMPNS), with a 12-month follow-up, to assess the potential added value of PNfS, as a salvage therapy, in PSPS-T2 patients experiencing a “Failed SCS Syndrome” in the back pain component. Fourteen patients were included in this study and randomized into 2 groups (“SCS + PNfS” group/n=6 vs “SCS only” group/n=8). The primary objective of the study was to compare the percentage of back pain surface decrease after 3 months, using a computerized interface to obtain quantitative pain mappings, combined with multi-dimensional SCS outcomes. Back pain surface decreased significantly greater for the ”SCS+PNfS” group (80.2% ± 21.3%) compared to the “SCS only” group (13.2% ± 94.8%) (p=0.012), highlighting the clinical interest of SCS+PNfS, in cases where SCS fails to address back pain.

Bubble (point defect) – a precursor of fuzz or under dense nanostructure formation is crystal lattice defect. Suitable selection of crystal lattice which inhibit Frenkel pair generation and intrinsically promotes self- interstitial solid solution strengthening contributes effectively towards making plasma facing material. For this, interstitial sites, their size, amount / fraction, positions, tendency of occupation and diffusion parameters (e.g. activation energies (Q), activation volumes) are determined. Fcc iron carbon alloys (austenitic stainless steels AISI / SAE 321, fcc structure, Pearson code cF4, space group Fm3̅m) are proposed as suitable candidates. Along with their room temperature fcc structure having 12 interstitial positions (4 octahedral, 6 coordination sites and 8 tetrahedral, 4 coordination sites / unit cell) to allow insertion of self (iron) atoms, they have excellent corrosion resistance, thermal conductivity, and non- magnetic properties. After their melting, casting, and machining to required dimensions and geometry, stabilizing heat treatment is applied to precipitate all carbon as TiC and prevent formation of Cr23C6 (sensitization). This resist heat and surface degradation and yield excellent architecture which not onlyinhibit Frankel pair generation but will also allow bulk assimilation or surface annihilation (loop punching) of this lattice point defect. A superior thermal, fluid, and structural design augment above. A second choice is presented as Co base superalloys owing to same fcc crystal structure and excellent properties (such as strength, dimensional stability, oxidation resistance) at high temperature.

Persistent Spinal Pain Syndrome Type 2 (PSPS-T2), (Failed Back Surgery Syndrome), dramatically impacts on patient quality of life, as evidenced by Health-Related Quality of Life (HRQoL) assessment tools. However, the importance of functioning, pain perception and psychological status in HRQoL can substantially vary between subjects. Our goal was to extract patient profiles based on HRQoL dimensions in a sample of PSPS-T2 patients and to identify factors associated with these profiles. Two classes were clearly identified using a mixture of mixed effect models from a clinical data set of 200 patients enrolled in “PREDIBACK”, a multicenter observational prospective study including PSPS-T2 patients with 1-year follow-up. We observed that HRQoL was more impacted by functional disability for first class patients (n=136) and by pain perception for second class patients (n=62). Males that perceive their work as physical were more impacted by disability than pain intensity. Lower education level, lack of adaptive coping strategies and higher pain intensity were significantly associated with HRQoL being more impacted by pain perception. The identification of such classes allows for a better understanding of HRQoL dimensions and opens the gate towards optimized health-related quality of life evaluation and personalized pain management.

Background. Recent studies revealed that differentiation of valvular interstitial cell into myofibroblasts played an important role in pathological valve remodeling in rheumatic valvular disease. Objective. To investigate effects of atorvastatin, olmesartan, and resveratrol on Transforming Growth Factor β1-induced fibrosis. Methods. Valvular interstitial cell was isolated from 12-weeks male New Zealand rabbit (Oryctolagus cuniculus). Culture cells was divided into 4 groups, control group, group I (0.5 mg/mL Atorvastatin), group II (100 nmol/L Olmesartan), group III (50 μM/L Resveratrol) and group IV (combinations). All group were exposed to 100 nM Transforming Growth Factor β1 for 24 hours. Results. Immunochemical staining demonstrated that cells were completely differentiated into myofibroblasts with mean expression of α-smooth muscle actin 24522.64±4566.994. Atorvastatin, olmesartan, resveratrol, and its combination significantly reduced α-smooth muscle actin expression (6823±1735.3, 6942.7±2455.9, 14176.2±3343.3, 5051.8±1612.2 respectively (p<0.001). Conclusion. Our data showed atorvastatin, olmesartan, resveratrol, and its combination significantly reduce Transforming Growth Factor β1-induced valvular fibrosis.

Drug-induced liver disease represents one of the main problems in the therapeutic field. As with most pathologies, also in this case various risk factors can be recognised, such as age, sex, but also the gut microbiota. Therefore all drugs on the market can, in fact, cause hepatotoxicity of varying degrees. Drugs used in the treatment of IBD can also cause these adverse effects and even lead to DILI. In this review, the various classes of drugs used in the treatment of IBD were taken into consideration and the various adverse effects on the liver were illustrated. In particular, a major role has emerged regarding hepatotoxicity of immunosuppressants. Biological drugs, however, seem to be responsible for these complications to a much lesser extent.

Introduction: Birth Asphyxia is a severe condition that includes many potential pathways of occurrence both in utero and during childbirth. We aimed to identify and describe specific macroscopic and microscopic placental injuries in birth asphyxia to serve as a quick tool to stratify a newborn’s potential further evolution, as hypoxic-ischemic encephalopathy can be responsible for neonatal death or severe neurologic sequelae further compromising the affected persons’ quality of life. Materials and methods: We conducted an observational prospective study over 3 years. 62 patients diagnosed with birth asphyxia which had placental histopathological examination performed were enrolled. The control group consisted of 69 term newborns that required neonatal intensive care for at least three days, in the same period, for any other reason and that also had available placental exams. In our study, placental histopathological lesions identified in birth asphyxia have been classified according to Amsterdam Criteria. Results: We analysed data gathered from both groups by applying specific statistical tests for each type of variable and hypothesis. Thus, umbilical cord abnormalities were associated with hypoxic-ischemic encephalopathy in a statistically significant manner when comparing the birth asphyxia group of newborns with the control group. Also, we identified a high statistical level of significance for maternal and fetal vascular malperfusion and the occurrence of hypoxic-ischemic syndrome when comparing the two groups (p = .00). Conclusion: The macroscopic and microscopic placental examination can provide important information on the evolution of the disease in selected newborns according to the identified lesions.

Introduction. Recent studies revealed that differentiation of valvular interstitial cell into myofibroblasts played an important role in pathological valve remodeling in rheumatic valvular disease. Objective. To investigate effects of atorvastatin, olmesartan, and resveratrol on Transforming Growth Factor β1-induced fibrosis. Methods. Valvular interstitial cell was isolated from 12-weeks male New Zealand rabbit (Oryctolagus cuniculus). Culture cells was divided into 4 groups, control group, group I (0.5 mg/mL Atorvastatin), group II (100 nmol/L Olmesartan), group III (50 μM/L Resveratrol) and group IV (combinations). All group were exposed to 100 nM Transforming Growth Factor β1 for 24 hours. Results. Immunochemical staining demonstrated that cells were completely differentiated into myofibroblasts with mean expression of α-smooth muscle actin 24522.64±4566.994. Atorvastatin, olmesartan, resveratrol, and its combination significantly reduced α-smooth muscle actin expression (6823±1735.3, 6942.7±2455.9, 14176.2±3343.3, 5051.8±1612.2 respectively (p<0.001). Conclusion. Our data showed atorvastatin, olmesartan, resveratrol, and its combination significantly reduce Transforming Growth Factor β1-induced valvular fibrosis.

Bladder cancer (BC) possesses distinct molecular profiles that influence progression depending on its biological nature and delivered treatment intensity. Muscle-invasive BC (MIBC) and non-MIBC (NMIBC) demonstrate great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. Transurethral resection of bladder tumor (TURBT) is the standard of care in treating NMIBC and serves both diagnostic and therapeutic purposes, despite the prevalent recurrence and progression among many patients. In particular, flat urothelial car-cinoma in situ and urothelial carcinoma with lamina propria invasion are the major precursors of MIBC. A new‐generation photosensitizer, 5‐Aminolevulinic acid (5-ALA), demonstrates high tumor specificity by illuminating the tumor lesion with a specific wavelength of light to produce fluorescence, and has been studied for photodynamic diagnosis to detect precise tumor areas by TURBT. Additionally, it has been applied for treatment by producing its cytotoxic reactive oxygen species, as well as screening for urological carcinomas by excreting porphyrin in the blood and urine. Moreover, 5-ALA may contribute to screening before and after TURBT in NMIBC. Here, we summarize the updated evidence and ongoing research on photodynamic technology for NMIBC, providing insight into the potential for improving patient outcomes.

Human urinary bladder cancer has similar development that invasive urothelial cancer that happens spontaneously in dogs. Then, research of these malignant tumors associated with the advances of new treatment drive to the specific fight of the urothelial tumor cell, is highly valuably related to efficiency and reduction of side effects of treatments, even extrapolating to humans. Thus, a review of the most important aspects on new advances on canine bladder cancer was achieved. Many forms of therapies are being reported; one of them, of highly promising feature is the treatment with immunomodulators. The resemblance between spontaneous urothelial cancer in canines and urinary bladder cancer in humans makes this canine tumor relevant animal model to research and advances of treatment that may be more efficient in management of tumor with less unfavorable effects. Immunomodulators exhibit important outcomes when used in the therapy of bladder cancer in dogs. Nanomaterials that are possible carriers of some kinds of drugs to the target tumor significantly raise the efficiently of the therapy. Therefore, the advancement of immunomodulator combined with nanoparticles can disrupt the therapy of bladder cancer in dogs and thereafter in humans.

There is an anecdotal impression that teenage patients report exaggerated postoperative pain scores that do not correlate with their actual level of pain. Nurse and parental perception of teenagers' pain can be complemented by knowledge of patient pain behavior, pain catastrophizing thoughts, anxiety, and mood level. Two hundred two patients completed the study: 56.4% female, 89.6% White, 5.4% Black, and 5% other race. Patient ages ranged from 11 to 17 years (mean = 13.8, SD = 1.9). The patient, the parent, and the nurse completed multiple questionnaires on day one after laparoscopic surgery to assess patient pain. Teenagers and parents (r=0.56) have a high level of agreement, and teenagers and nurses (r=0.47) have a moderate level of agreement on pain scores (p &lt;0.05). The correlation between patient APBQ (Adolescent Pain Behavior Questionnaire) and teenager VAS (Visual Analog Scale ) and between nurse APBQ and teenager VAS, while statistically significant (p &lt; 0.05), is weaker (r range = 0.14-0.17). There is a moderate correlation between teenagers' pain scores and their psychological assessments of anxiety, catastrophic thoughts, and mood (r range= 0.26 – 0.39; p &lt;0.05). A multi-modal evaluation of postoperative pain can be more informative than only assessing self-reported pain scores.

Metabolic syndrome (MetS) refers to the group of several interconnected risk factors that collectively double the risk of cardiovascular disease. Epilepsy is linked to MetS across all age groups, though its prevalence differs across various studies. This can be understood from the perspective of seizure-related metabolic abnormalities, long-term antiepileptic drugs (AEDs) use, and a more sedentary lifestyle due to epilepsy. The factors that are considered in developing MetS for patients with epilepsy (PWE) are age, residence, level of physical activity, food intake status, epilepsy subtype, epilepsy duration, current (AEDs) use, drug responsiveness status, body-mass index (BMI), total cholesterol and LDL-cholesterol levels. A deeper understanding of the epilepsy-AED-MetS connection and the exploration of lifestyle interventions hold the promise of significantly improving the overall health and well-being of PWE. Clinicians managing PWE should closely monitor various risk factors for developing MetS and consider them when selecting AED treatment.

Background: People with Down syndrome (DS) have a trisomy of chromosome 21 and marked deficits in verbal memory but relatively preserved visuospatial perception. Verbal memories are related to semantic knowledge. Little is known about the organization of semantic knowledge in people with DS, which was the aim of this study. Aims: The extent of false memory in people with DS was examined. Possible differences in the number of false memories induced by nominal and verbal themes were examined. Methods and Procedures: In the study phase, ten word lists with semantically related associates were presented. In the recognition phase, participants made judgments on whether each word had been represented previously as semantically related lures, old words, and semantically unrelated new words. Outcomes and Results: Differences in the processing of nominal and verbal theme-related lures were observed among people with DS. When processing nominal theme-related lures, people with DS showed delayed false positives. When processing verbal theme-related lures, people with DS showed no differences compared to controls. Similar patterns have been observed in people with DS when processing nominal theme-related associates and verbal theme-related associates. People with DS have delayed recognition of associates. When processing unrelated words, they showed significantly higher false positives than controls for both nominal and verbal eliciting themes. Further analyses of the themes revealed differences in false positives across syntactic categories among groups. Conclusions and Implications: People with DS showed a delayed recognition of associates and deviance in recognizing unrelated words in the nominal and verbal theme categories. People with DS were delayed in terms of nouns, but deviated with verbs in associated and unrelated words. Additionally, people with DS showed distinct patterns in processing five nominal lures and three verbal lures, suggesting that they formed false memories differently based on distinct syntactic categories. Thus, it was concluded that people with DS develop a deviant semantic structure. Category-based interventions for people with DS should be implemented in order to improve their semantic knowledge through lexical connections.

The multidimensionality of chronic pain forces us to look beyond isolated pain assessment such as pain intensity, which does not consider multiple key parameters, particularly in patients suffering from post-operative Persistent Spinal Pain Syndrome (PSPS-T2). Our ambition was to provide a novel Multi-dimensional Clinical Response Index (MCRI), including not only pain intensity but also functional capacity, anxiety-depression, quality of life and objective quantitative pain mapping assessments, the objective being to capture patient condition instantaneously, using machine learning techniques. Two hundred PSPS-T2 patients were enrolled in a real-life observational prospective PREDIBACK study with 12-month follow-up and received various treatments. From a multitude of questionnaires/scores, specific items were combined using exploratory factor analyses to create an optimally accurate MCRI; as a single composite index, using pairwise correlations between measurements, it appeared to better represent all pain dimensions than any other classical score. It appeared to be the best compromise among all existing indexes, showing the highest sensitivity/specificity related to Patient Global Impression of Change (PGIC). Novel composite indexes could help to refine pain assessment by changing the physician’s perception of patient condition on the basis of objective and holistic metrics, and by providing new insights to therapy efficacy/patient outcome assessments, before ultimately being adapted to other pathologies.

The prolonged static sitting at the workplace is considered as one of the main risks for development of musculoskeletal disorders (MSDs) and adverse health effects. Factors such as poor posture and extended sitting are perceived to be a reason for conditions such as lumbar hyperlordosis and lower back pain (LBP), even though the scientific explanation of this relationship is still unclear and raises disputes in the scientific community. This publication proposes the low back pain assessment (LBPA) dataset collected through experiment with 100 participants and consisting of photogrammetric images with intentionally placed body markers, calculated postural angles and tags correct and incorrect posture assessed by habilitated rehabilitator, as well as questionnaire-based self-reports regarding the occurrence of LBP and similar symptoms among the participants. Machine learning models trained with this data are employed for recognizing incorrect body postures. Two scenarios have been elaborated for modeling purposes: scenario 1, based on natural body posture tagged as correct and incorrect, and scenario 2, based on incorrect body postures, corrected additionally by the rehabilitator. The achieved accuracies of respectively 75.3% and 85% for both scenarios reveal the potential for future research in enhancing awareness and actively managing posture-related issues that elevate the likelihood of developing lower back pain symptoms.

1) Background. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe mucocutaneous reactions, characterized by extensive necrosis and detachment of the epidermis. 2) Case presentation. We present a case of a 46-year-old patient with late-stage high-grade serous ovarian cancer who was primarily treated with neoadjuvant chemotherapy and interval debulking which was followed by adjuvant chemotherapy. At first recurrence, she was again treated with chemotherapy and due to severe abdominal pain, an elastomeric pump containing analgesics, anti-inflammatories and ondansetron was administered. In the same month, she was admitted to the hospital due to severe dysphagia and in the following days, she developed haemorrhagic vesiculobullous lesions on facial skin and trunk. Stevens-Johnson syndrome was confirmed and ondansetron as a leading cause was discontinued. Despite multimodal treatment, her condition deteriorated, and she died. 3) Discussion and conclusion. Although gynaecologists rarely encounter Stevens-Johnson syndrome, high mortality of the disease should ensure a low threshold for diagnosing and treating this disease.

Background: Interstitial lung disease (ILD) is a frequent complication in systemic sclerosis (SSc). So, an increased awareness of this complication is a real need in the clinical setting, because it may affect the prognosis of patients. In particular, an accurate strategy is desirable in order to detect ILD in its stages. So, we investigate the validity of ultrasound (US) in detecting subclinical ILD in SSc, and to determine its potential in disease progression. Methods: 133 patients without respiratory symptoms and 133 healthy controls were included. Borg scale, Rodnan skin score (RSS), pulmonary auscultation, chest radiographs and respiratory function tests (RFT) were performed. An expert rheumatologist performed the lung US. High-resolution CT (HRCT) was also performed. After the baseline assessment, the patients were followed every 3 months for 12 months. Results: A total of 79 of 133 patients (59.4%) showed US signs of ILD in contrast to healthy controls (4.8%) (p=0.0001). The clinical and laboratory variables associated with ILD were anti-centromere antibodies (p=0.005) and RSS (p=0.004). A positive correlation was demonstrated between the US and HRCT findings (p=0.001). Sensitivity and specificity of US in detecting ILD was 91.2% and 88.6% respectively. A good inter-observer reliability was observed (k = 0.72). In the follow-up, a total of 30 patients out of 79 (37.9%) who demonstrated US signs of ILD at baseline, showed changes in the ILD score by US. Conclusions: US showed a high prevalence of subclinical ILD in SSc patients. It demonstrated to be a valid, reliable and feasible tool to detect ILD in SSc and to monitoring the disease progression.

We present the case of a 35-year-old patient without pathological history who developed hemopneumothorax due to altitude barotrauma during a commercial airline flight. The computed tomography of the chest identified the presence of emphysema "blebs" and bubbles, and the histopathological examination of the lung fragment obtained during the diagnostic and therapeutic thoracoscopy identified elements suggestive for the diagnosis of respiratory bronchiolitis associated with desquamative interstitial pneumonia (DIP).

The Acute Cystitis Symptom Score (ACSS) is a patient self-reporting questionnaire for the clinical diagnosis and patient-reported outcome (PRO) in women with acute uncomplicated cystitis (AC). The aim of the current study (part II) was the clinical validation of the Greek ACSS questionnaire. After linguistic validation according to internationally accepted guidelines and cognitive assessment (part I), the clinical validation was performed after ethical approval by using the Greek ACSS study version in 92 evaluable female participants including 53 patients with symptoms suspicious of AC and 39 controls. The clinical outcome using the ACSS questionnaire at different time points after the start of treatment was demonstrated as well. The age (mean±SD) of the 53 patients (44.7±17.0) and 39 controls (49.3±15.9) and their additional conditions at baseline visits, such as menstruation, premenstrual syndrome, pregnancy, menopause, diabetes mellitus, were comparable. There was, however, a significant difference (p&lt;0.001) between patients and controls at baseline visit regarding sum score of the ACSS domains, such as typical symptoms and quality of life. The clinical outcome of up to 7 days showed a fast reduction of the symptom scores and improvement of quality of life. The optimal thresholds for the patient-reported outcome of successful therapy could be established. The linguistically and clinically validated Greek ACSS questionnaire can now be used for clinical or epidemiological studies and also for patient’s self-diagnosis of AC and as a PRO measure tool.

Endometriosis is known to be a chronic, debilitating disease. The pathophysiological mechanisms of endometriosis development include local chronic inflammation and a certain degree of local immune deficit. We investigated the relationship between the endometriosis severity, IL-8, IL-10, BDNF, VEGF-A serum and tissue levels, patient-related pain, and physical activity in a cohort of 46 patients diagnosed with endometriosis who underwent surgery. The same panel of biomarkers was investigated in a control group of 44 reproductive-aged patients with non-endometriotic gynecological pathology who underwent surgical intervention. Our data show a high statistical significance between tissue expression of IL-8, IL-10, patient-related pain and the severity of endometriosis. No relationship was identified between serum or tissue levels of VEGF-A and BDNF and the severity of endometriosis. These results validate the presence of local chronic inflammation and immune deficit, thereby creating, alongside other studies in the field, an opportunity for the development of innovative and personalized treatment approaches in endometriosis.

Lynch syndrome (LS) is an inherited cancer predisposition disorder associated with an elevated risk of various epithelial cancers. Despite sharing the same pathogenic variant (PV), Lynch syn-drome variant heterozygotes (LSVH) exhibit considerable phenotypic variability in cancer risk. The role of Human Leukocyte Antigen (HLA) in modifying cancer risk prompted our investiga-tion into whether HLA variations act as genetic modifiers influencing age at cancer diagnosis in a unique cohort of LSVH carrying a PV in the hMLH1 gene in South Africa. Within our extensive LS cohort, 426 individuals carried the same hMLH1 PV (MLH1:c.1528C>T). We selected 100 indi-viduals with the greatest diversity in age at cancer diagnosis and the oldest unaffected individu-als for high-throughput HLA genotyping of 12 HLA class I and II loci using next-generation se-quencing. Statistical analyses employed Kaplan-Meier survival analyses with Logrank tests and Cox proportional hazards. Following the robust application of statistical correction methods, six HLA alleles (3.2%) were significantly associated with a young age at cancer diagnosis. Notably, HLA-B*15:17 and HLA-DPB1*55:01 correlated significantly with very young colorectal cancer (CRC) diagnosis (Mean age: 21y [17-25]; HR = 71.59; q

Polycystic Ovary Syndrome (PCOS) is the most common endocrine disorder that affects women of reproductive age representing the primary cause of anovulatory infertility. The nonapeptide oxytocin (OT) plays an important role in cognitive, emotional, and reproductive functions in human beings. Oxytocin receptors are expressed in several body parts including the ovaries. Despite this, the possible role played by oxytocin in symptoms of PCOS is not clear. The present systematic review aimed at understanding, the presence of possible oxytocin level alterations in PCOS, the connection between alterations of OT levels and the symptoms of PCOS, and the effect of oxytocin administration in PCOS. After a systematic search in the principal databases, seven studies, five human and two animal, were included. Most of the studies highlighted the role played by oxytocin in fertility issues related to PCOS. Studies that analyzed oxytocin basal levels in PCOS women agreed that PCOS is associated with a reduction in the serum level of oxytocin. Two studies found that in PCOS the serum levels of oxytocin were lower than healthy controls. One human and one animal study agreed about lower levels of PCOS, confirming a possible implication of a dysfunction of OT, in the pathogenesis of PCOS.

Superior mesenteric artery (SMA) syndrome or Wilkie’s syndrome is a vascular compression disorder that causes abnormal compression of the third portion of the duodenum by the SMA. It has a low incidence rate, higher in young women, and is rarely associated with the Nutcracker phenomenon: a condition of compression of the left renal vein between the SMA and the aorta, which manifests as pain in the left flank and pelvis. Here we report the case of a 54-year-old woman with a history of repeated episodes of abdominal pain caused by the Nutcracker syndrome and Wilkie's syndrome.

Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease characterized by progressive parenchymal fibrosis and respiratory failure. In a model of bleomycin-induced pulmonary fibrosis, the antifibrotic and anti-inflammatory activity of Longidaza (bovhyaluronidase azoxymer), which contains a conjugate of the hyaluronidase enzyme with a high molecular weight synthetic carrier azoxymer bromide, was investigated. Experiments were conducted in male C57BL/6 mice. Longidaza was administered at different doses by intranasal and intramuscular routes. Histology, hematology and enzyme-linked immunosorbent assay were used in the study. The use of Longidaza reduced pulmonary fibrosis as evidenced by an improvement in histopathologic damage to the lungs, a decrease in the area of connective tissue and the levels of profibrotic factors (TGF-β1, hydroxyproline, collagen I) in lung tissue. In addition, Longidaza inhibited the inflammatory response in pulmonary fibrosis, decreased the levels of IL-6, TNF-α, hyaluronic acid in lung tissue and the recruitment of inflammatory cells into lung tissue. The highest therapeutic efficacy was observed with the use of Longidaza at doses of 120 and 1200 U/kg intramuscularly, which was superior to that of the reference drug pirfenidone axunio. The data presented in this study suggest that Longidaza is a new and promising drug for the treatment of IPF that warrants further investigation in patients with fibrotic interstitial lung disease.

Background and Objectives: The aim of this study was to determine the job-related and individual features that influence BS and depression levels among dentists working in faculties, oral and dental health centres (ODHC) and private clinics. Materials and Methods: This prospective, cross sectional study was carried out on dentists working in different regions of Turkey. Data were collected using an on-line questionnaire created using Google Forms. The questionnaire consisted of demographic data, Maslach BS Inventory (MBI) and Beck Depression Inventory (BDI) sections. Demographics were age, height, weight, marital status, blood type, gender, monthly income, income satisfaction and having enough free time. The dentists were divided into 3 groups as faculty, private clinic and ODHC according to the institutions in which they worked. Results: Of the total 290 dentists enrolled in the study, there were 172 males and 118 females with a mean age of 36.98±5.6 years. 128 of the dentists worked in faculties, 72 in private clinics and 90 in ODHCs. It was observed that women's EE scores were higher than men's (P&lt;0.05). No statistically significant difference was found between the groups when comparing BS and depression scores according to marital status and blood group (P&gt;0.05). There was no significant relationship between emotional exhaustion (EE), depersonalisation (DP), personal accomplishment (PA) and depression scores according to age, BMI and work experience, age, work experience and BMI (P&lt;0.05). It was found that the EE scores of the dentists working in the faculty and private clinic were lower than those of the dentists working in the ODHC (P&lt;0.05). Monthly income was associated with depression (r = -0.35). Conclusions: This study showed that dentists working in ODHCs had more EE. These findings suggest that there is a need for improvement in the working conditions of dentists, particularly in ODHCs.

Introduction: Carcinoid heart disease is a rare cause of right-sided valvular dysfunction, an important complication in patients with carcinoid syndrome. Objectives: We aim to present our own experience regarding early myocardial dysfunction in patients with carcinoid syndrome. Methods: 64 patients (35-90 year old, 62,5% female, 37,5% male patients) with carcinoid syndrome were evaluated be-tween October 2017 and June 2021. All patients underwent two-dimensional echocardiography with additional tissue Doppler and speckle-tracking techniques. For all patients there were measured urinary level of 5- hydroxyindolacetic acid, serotonin and NT-proBNP values. Results: The following echocardiographic features: global longitudinal strain of both ventricles, mean systolic velocity of the left ventricle, systolic velocity of the free wall of right ventricle, correlated with high values of specific biomarkers: serotonin, and urinary 5-hydroxyindolacetic acid, and also with the presence of hepatic metastases and poorly differentiated tumors. Discussion: In this study we identified several patients with early myocardial dysfunction due to carcinoid syndrome, representing a predictive model of poor prognosis, requiring further investigations. Conclusion: Echocardiographic assessment based on the measurement of systolic velocities, as well as the global longitudinal strain of both ventricles, together with specific biomarkers may contribute to better recognition of carcinoid heart disease in clinical practice, but this needs validation through further studies enrolling larger number of patients.

Evans' Syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Thrombotic complications in ES patients are uncommon, particularly involving Buerger's Disease (BD). We report a case of a 49-year-old male with ES and a history of diabetes and heavy smoking, presenting with a necrotic wound on his right great toe. Diagnostic evaluations revealed severe stenosis and thrombosis in the lower limb arteries, diagnosed as BD. The patient underwent successful popliteal-tibioperoneal artery bypass surgery and subsequent disarticulation and revision of the distal phalanx, followed by the application of an acellular dermal matrix (ADM) to promote healing. Post-surgery, the patient showed significant improvement in blood flow and complete epithelialization without complications. This case highlights the importance of a multidisciplinary approach in managing complex wounds in ES patients, suggesting potential treatment pathways for future cases involving BD

Interstitial lung diseases (ILDs) constitute a group of more than 200 disorders, being idiopathic pulmonary fibrosis (IPF) one of the most frequent. Telomere length (TL) shortening causes loss of function of the lung parenchyma. However, little is known about its role as prognostic factor in ILD patients. With the aim of investigating the role of TL and telomerase activity in the prognosis of patients affected by ILDs, we analysed lung tissue samples from 61 patients. We measured relative TL and telomerase activity by conventional procedures. Both clinical and molecular parameters were associated with overall survival by the Kaplan-Meier method. Patients with IPF had poorer prognosis than patients with other ILDs (p = 0.034). When patients were classified according to TL, those with shortened telomeres reported lower overall survival (p = 0.085); differences reached statistical significance after excluding ILD patients who developed cancer (p = 0.021). In a Cox regression analysis, TL behaved as a risk-modifying variable for death associated with rheumatological disorders (RD) co-occurrence (p = 0.029). Also, in patients without cancer, ferritin was significantly increased in cases with RD and IPF co-occurrence (p = 0.032). In relation to telomerase activity, no significant differences were detected. In conclusion, TL in lung tissue emerges as a prognostic factor in ILD patients, Specifically, in cases with RD and IPF co-occurrence, TL can be considered as a risk-modifying variable for death.

Systemic sclerosis (also known as scleroderma) is a chronic fibrosing autoimmune disease with both skin and multisystem organ involvement. Scleroderma has the highest mortality among all rheumatic diseases. The pathophysiology mechanism of systemic sclerosis is a progressive self-amplifying process, which implicates the widespread microvascular damage, followed by a dysregulation of innate and adaptive immunity and inflammation, and diffuse fibrosis of the skin and visceral organs. Fibrosis of internal organs is a hint for systemic sclerosis, moreover associated with interstitial lung disease (SSc-ILD) is a complex process. We report a case of a 56 years old female, diagnosed with Systemic Sclerosis 16 years ago. The systemic and clinical manifestations, respiratory functional tests, radiological aspects and specific therapy were discussed.

Current epidemiological data about interstitial lung disease (ILD) are still poor. The principal cause of the discordant data is associated with a heterogeneous group of respiratory diseases that includes a large number, about 200 families, with low frequency, distinct and sometimes unknown etiology, and different progression. Furthermore, epidemiological data are limited. Scope of the narrative review is to report ILD incidence and prevalence in Registries from different Countries in the second millennium. We identified 16 ILD Registries (14 prospective and 2 retrospective) from major Countries in Europe (n = 10), Asia (n = 7), North America (n =2) and Oceania (n = 1). Significant discrepancies in ILD and ILD subtypes prevalence and incidence among countries are reported in Registries. These discrepancies could be determined by different ethnicities and socio-economic conditions as well as by updates in disease diagnosis and classification. ILD epidemiological Registries are progressively ameliorating through a better adherence to updated Guidelines and Classification codes. An accurate and definite compilation of ILD epidemiological Registries will be useful for a more precise monitoring of disease progression and treatment.

Objectives: This study was undertaken to reveal therapeutic effects and the preliminary mechanism of Chinese medicine formula Qianlie Tongli decoction (QTD) in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Methods: A total of 50 male C57BL/6 mice were randomly divided into five groups. All groups except the control group were injected subcutaneously T2 peptide emulsion, which induced the CP/CPPS model. After the induction of CP/CPPS, the model group was given 0.9% NaCl by oral gavage while low-dose, medium-dose, and high-dose groups were treated with Chinese medicine formula. Micturition habits and pain behavior of mice were analyzed for each group. Hematoxylin and eosin staining were used to investigate prostate inflammation. The serum level of tumor necrosis factor-α (TNF-α) was measured by enzyme-linked immunosorbent assay (ELISA) kit. Key findings: Chinese medicine formula significantly reduced the number of urine spots and improved pain response frequency in the medium-dose and high-dose group. The high-dose group showed reduced considerably inflammatory lesion and inflammatory cell infiltration than the low-dose and medium-dose groups. Serum levels of TNF-α in the high-dose group were significantly reduced compared with the model group. Conclusions: The results demonstrated the therapeutic effects of Qianlie Tongli decoction in CP/CPPS mice by analyzing clinically relevant symptoms (urinary tract system, pelvic pain, and prostate inflammation), and preliminary explored the inflammatory-related treatment mechanisms by measuring TNF-α.

The increasing prevalence of Metabolic Syndrome (MetS), a serious condition associated with elevated risks of cardiovascular diseases, stroke, and type 2 diabetes, underscores the urgent need for effective diagnostic tools. This research carefully examines the effectiveness of 16 diverse machine learning (ML) models in predicting MetS, a multifaceted health condition linked to increased risks of heart disease and other serious health complications. Utilizing a comprehensive, unpublished dataset of imbalanced blood test results, spanning from 2017 to 2022, from the Laboratory Information System of the General Hospital of Amfissa, Greece, our study embarks on a novel approach to enhance MetS diagnosis. By harnessing the power of advanced ML techniques, we aim to predict MetS with greater accuracy using non-invasive blood test data, thereby reducing the reliance on more invasive diagnostic methods. Central to our methodology is the application of the Borda count method, an innovative technique employed to refine the dataset. This process prioritizes the most relevant variables, as determined by the performance of the leading ML models, ensuring a more focused and effective analysis. Our selection of models, encompassing a wide array of ML techniques, allows for a comprehensive comparison of their individual predictive capabilities in identifying MetS. This study not only illuminates the unique strengths of each ML model in predicting MetS but also reveals the expansive potential of these methods in the broader landscape of health diagnostics. The insights gleaned from our analysis are pivotal in shaping more efficient strategies for the management and prevention of Metabolic Syndrome, thereby addressing a significant concern in public health.

Passive plasma spectroscopy is a well-established non-intrusive diagnostic technique. Depending on the emitter and its environment which determine the dominant interactions and effects governing emission line shapes, passive spectroscopy allows the determination of electron densities, emitter and perturber temperatures as well as other quantities like abundances. However, using spectroscopy needs appropriate line shape codes retaining all the physical effects governing the emission line profiles. This requires for line shape code developers to continuously correct or improve them to increase their accuracy when applied for diagnostics. This is exactly the aim expected from code-code and code-data comparisons. In this context, the He I 492 nm emitted in a helium corona discharge at room temperature represents an ideal case since its profile results from several broadening mechanisms: Stark, Doppler, resonance and van der Waals. The importance of each broadening mechanism depends on the plasma parameters. Here the profiles of the He I 492 nm in a helium plasma computed by various codes are compared for a selected set of plasma parameters. In addition, preliminary results related to plasma parameter determination using experimental spectra from a helium corona discharge at low pressure 1- 2 bars, are presented.

Vascular anomalies are a diverse group of abnormal blood vessel developments that can occur at birth or shortly afterward. Embolization and sclerotherapy have been utilized as a treatment option for these malformations but may cause moderate to severe pain. This study aims to evaluate the utilization of peripheral nerve blocks in opioid consumption, pain scores, and length of stay. A retrospective chart review was conducted at the UPMC Children's Hospital of Pittsburgh for all patients who underwent embolization and sclerotherapy between 2011 and 2020. Patient data was collected to compare opioid consumption, pain scores, and length of stay. Eight hundred fifty-four procedures were performed on 347 patients. The morphine milligram equivalent per kilogram mean ratio between groups was 0.9 (0.86, 0.95) with a p-value of &lt;0.001. The pain score mean ratio was –1.17 (–2.2, -0.1) and a p-value of 0.027. Length of stay had a mean ratio of 0.94 (0.4, 2) and a p-value of 0.875. By decreasing opioid consumption and postoperative pain scores, peripheral nerve blocks may have utility in patients undergoing embolization and sclerotherapy while not clinically increasing the length of stay for patients. Their use should be individualized and carefully discussed with the interventional radiologist.

Background: Glioblastoma is the deadliest, yet most common, brain tumor in adults, with poor survival and response to aggressive therapy. Therapeutic failure results from a number of causes inherent to these tumors. Imaging, computational, and drug delivery approaches can aid in the quest to access and kill each tumor cell in patients. One factor, interstitial fluid flow, is a driving force therapeutic delivery. However, convective and diffusive transport mechanisms are un-der-studied. In this study, we examine the application of a novel image analysis method to meas-ure fluid flow and diffusion in glioblastoma patients with MRI and compare to patient outcomes. Methods: Building on a prior imaging methodology tested and validated in vitro, in silico and in preclinical models of disease, here we apply our analysis method to archival patient data from the Ivy GAP dataset. Results: We characterize interstitial fluid flow and diffusion patterns in patients. We find strong correlations between flow rates measured within tumors and in the surrounding parenchymal space, where we hypothesized that velocities would be higher. Looking at overall magnitudes, there is significant correlation with both age and survival in this patient cohort. Additionally, we find that tumor size nor resection significantly alter the velocity magnitude. Last, we map the flow pathways in patient tumors and find variability in degree of directionality that we hypothesize in future studies may lead to information concerning treatment, invasive spread, and progression. Conclusions: Analysis of standard DCE-MRI in patients with glioblastoma offers more infor-mation regarding transport within and around tumor, can be measured post-resection and mag-nitudes correlate with patient prognosis.

Diffuse interstitial lung diseases (DILD) are a heterogeneous group of over 200 entities, some with dramatical evolution and poor prognostic. Because of their overlapping clinical, physiopathological and imagistic nature, successful management requires early detection and proper progression evaluation. This paper tests a complex networks (CN) algorithm for imagistic aided diagnosis fitness for the possibility of achieving relevant and novel DILD management data. 65 DILD and 31 normal high resolution computer tomography (HRCT) scans were selected and analyzed with the CN model. The algorithm is showcased in two case reports and then statistical analysis on the entire lot shows that a CN algorithm quantifies progression evaluation with a very fine accuracy, surpassing functional parameters’ variations. The CN algorithm can also be successfully used for early detection, mainly on the ground glass opacity Hounsfield Units band of the scan.

Interventional management of neuropathic pain (NP) is available to the many patients who do not attain satisfactory outcomes with pharmacotherapy, but evidence supporting this is sparse and fragmented. We attempted to summarize and critically appraise the existing data to identify strategies that yield maximum benefit, orient clinicians, and identify areas that merit further investigation. A two-round Delphi survey that involved pain clinic specialists with experience in the research and management of NP was done over an ad hoc 26-item questionnaire prepared by the authors. Consensus on each statement was defined as either at least 80% endorsement or rejection after the second round. Thirty-five and 29 panelists participated in the first and second round, respectively. Consensus was reached in 20 out of 26 statements. There is sufficient basis to treat postherpetic neuralgias and complex regional pain syndromes with progressive levels of invasiveness and failed back surgery syndrome with neuromodulation. Radiculopathies and localized NP could be treated with peripheral blocks and neuromodulation, or pulsed radiofrequency. Non-ablative radiofrequency and non-paresthetic neuromodulation are efficacious and better tolerated than ablative and suprathreshold procedures. A graded approach, from least to most invasive interventions has the potential to improve outcomes in many patients with common refractory NP conditions. Preliminary promising data warrant further research on new indications, and technical advances might enhance the safety and efficacy of current and future therapies.

Turner syndrome (TS) is caused by a complete or partial absence of an X or Y chromosome, including chromosomal mosaicism, affecting 1 in 2,500 female live births. Sister chromatid exchange (SCE) is used as a sensitive indicator of spontaneous chromosome instability. Cells from mosaic patients constitute useful material for SCE evaluations as they grow under the influence of the same genetic background and endogenous and exogenous factors. We evaluated proliferation dynamics and SCE frequencies of 45,X and 46,XN cells of 17 mosaic TS patients. In two participants, 45,X cells exhibited a proliferative disadvantage in relation to 46,XN cells after 72h of cultivation. The analysis of mean PI showed significant differences between 45,X and 46,XN lineages; however there were no intraindividual differences. On the other hand, mean SCE frequencies showed no differences between the two lineages, but there were intraindividual differences in 5 patients. The absence of mean SCE frequency differences between 45,X and 46,XN lineages may indicate that both were equally unstable, as more than 70% of the 46,XN lineages had an anomalous karyotype. However, 46,XN had a higher mean PI, suggesting that the amount of cells with a karyotype distinct from 45,X may increase with time in mosaic TS women.

The human gastrointestinal gut contains about 100 trillion of microorganisms including up to 5000 different types of bacteria called the "gut microbiome". Alterations in the composition of gut microorganisms (dysbiosis) can cause threatening for life diseases. This present seeks to evaluate if finally diet and more specifically functional foods affect the intestinal microbiome, and if obesity and the metabolic syndrome (Mets) are associated with the intestinal microbiome. This systematic review was accomplished according to PRISMA guidelines mostly using the key words functional foods, microbiome, obesity, Mets, Mediterranean diet. The search was carried out of recent scien-tific articles from the databases Pubmed, Scopus, and Google Scholar. The most studies discussed in this review showed a potential therapeutic effect of the Mediterranean diet rich in beneficial nutrients, on body weight, fat deposition, in correlation with modulation of the synthesis of gut microbiome. This literature review demonstrates a possible relationship between the metabolites of the microflora, the endotoxemia, obesity and Mets. The role of probiotics, prebiotics, and polyphe-nols in the prevention of obesity and Mets is of high importance in promoting healthy aging. The future challenge is to understand how different dietary patterns can regulate the composition of the gut microflora and whether these changes could be long-term.

The problems of modeling the human bladder and its stress-strain state under external static influence were considered. A method for identification of the anisotropic biomechanical characteristics of bladder tissue was proposed. A FEM model was created, which accepts into regard that the bladder is surrounded by fiber and affected by surrounding organs, and partially protected by pelvic bones. The model considered the presence of constant hydrostatic pressure on the walls of the bladder when it is full. It has been shown that isotropic mechanical characteristics of biological tissue can be used for studying the deformed state of a filled bladder if the filled bladder 300 ml is considered as initial non-deformed stage. This was shown by modeling and verification the effect of the external static force on the bladder. Numerical experiments were conducted based on the constructed model. To validate the results obtained, a series of natural experiments on the effect of external pressure on the bladder under ultrasound control was conducted. In the future, it is planned to use the constructed model to study rupture deformations of the bladder under the influence of static and dynamic loads.

Sarcopenia, the degenerative and systemic loss of skeletal muscle mass, indicates patient frailty and impaired physical function. Sarcopenia can be caused by multiple factors, including advanced age, lack of exercise, poor nutritional status, inflammatory diseases, endocrine diseases, and malignancies. Recently, growing evidence has indicated the importance of sarcopenia in the management of patients with various cancers. Sarcopenia is associated with not only higher rates of treatment-related complications but also worse prognosis in cancer-bearing patients. In this article, we conducted a systematic literature review regarding the significance of sarcopenia as a prognostic biomarker of bladder cancer. We also reviewed recent studies focusing on the prognostic role of changes in skeletal muscle mass during the course of treatment in bladder cancer patients.

Abstract: Delayed initiation of effective antifibrotic therapy in patients with interstitial lung diseases (ILD) may influence the progression and outcome of the disease. This study analyzes the differences in the journey of patients with ILD in the Brazilian and Mexican health systems. An evaluative study was conducted in reference centers for interstitial lung diseases in Brazil and Mexico with a panel of four specialists. The patient's journey in both countries begins when the patient seeks medical care after observing a chronic respiratory symptom. In both countries, due to diagnostic complexity, these patients arrive at ILD referral centers at an advanced stage of the disease. Once diagnosis is established, the treatment onset differs between Mexico and Brazil. Antifibrotic drugs are not yet available by SUS in Brazil, and the purchase is unfeasible for most of the population, which forces specialists to only offer support to patients until the treatment can get the drug. In Mexico, antifibrotics have been available in health sectors since 2018. Brazil and Mexico have several similarities regarding the initial journey of the patient due to diagnosis difficulties, but the outcome tends to be different due to a difference in access to treatment with antifibrotics. For this reason, advancing health policies that ensure proper treatment for patients with ILD is crucial for the sustainability and reliability of the health system.

The High-Resolution Computed Tomography (HRCT) detection and diagnosis of diffuse lung disease is primarily based on the recognition of a limited number of specific abnormal findings, pattern combinations or their distributions, as well as anamnesis and clinical information. Since texture recognition has a very high accuracy percentage if a complex network approach is used, this paper aims to implement such a technique customized for diffuse interstitial lung diseases (DILD). The proposed procedure translates HRCT lung imaging into complex networks by taking samples containing a secondary lobule, converting them into complex networks and analyzing them in 3 dimensions: emphysema, ground glass opacity and consolidation. This method was evaluated on a 60 patient lot and the results show a clear quantifiable difference between healthy and affected lungs. By deconstructing the image on three pathological axes, the method offers an objective way to quantify DILD details which, so far, have only been analyzed subjectively.

In this paper, we propose a novel approach to utilize silicon nanowires as high-sensitivity pH sensors. Our approach works based on fixing the current bias of silicon nanowires Ion Sensitive Field Effect Transistors (ISFETs) and monitor the resulting drain voltage as the sensing signal. By fine tuning the injected current levels, we can optimize the sensing conditions according to different sensor requirements. This method proves to be highly suitable for real-time and continuous measurements of biomarkers in human biofluids. To validate our approach, we conducted experiments, with real human sera samples to simulate the composition of human interstitial fluid (ISF), using both the conventional top-gate approach and the optimized constant current method . We successfully demonstrated pH sensing within the physiopathological range of 6.5 to 8, achieving an exceptional level of accuracy in this complex matrix. Specifically, we obtained a maximum error as low as 0.92\% (equivalent to 0.07 pH unit) using the constant-current method at the optimal current levels (1.71\% for top-gate). Moreover, by utilizing different pools of human sera with varying total protein content, we demonstrated that the protein content among patients does not impact the sensors' performance in pH sensing. Furthermore, we tested real-human ISF samples collected from volunteers. The obtained accuracy in this scenario was also outstanding, with an error as low as 0.015 pH unit using the constant-current method and 0.178 pH unit in traditional top-gate configuration.

Global public health systems have continuously faced challenges from the advent of novel infectious illnesses, necessitating quick and efficient actions to stop their spread.First discovered in Saudi Arabia in 2012, Middle East respiratory syndrome (MERS) is a viral respiratory disorder caused by the Middle East respiratory syndrome coronavirus (MERS-CoV). Since then, the nation has reported most cases and fatalities related to this sickness, with occasional outbreaks happening in other nations and regions. Severe sickness and high mortality are caused by MERS-CoV, especially in older persons and those with underlying chronic conditions. Through intimate contact, the virus can spread from people to dromedary camels and vice versa. It has sparked multiple epidemics both domestically and abroad in the Middle East, raising the possibility of fatalities and widespread transmission, especially in susceptible groups. The Riyadh region was the main target of the most current MERS-CoV outbreak in Saudi Arabia, which began in 2023 and ended on September 1, 2023, with 312 confirmed cases and ninety-seven fatalities. With the use of published studies and their contributions to the field, we hope to present a thorough overview of the MERS-CoV outbreak in Saudi Arabia in this review of the literature, including its epidemiological investigation, public health response, impact, and lessons learned. In addition to highlighting the importance and continued relevance of this problem, our work suggests ways to lower the risk of MERS-CoV transmission and avert further outbreaks.

Background and Objectives: The complications seen after lower impacted third molar surgery affect the quality of life of the patients. The aim of the study was to investigate the efficacy of a single preoperative dose of deflazacort on pain, swelling and trismus following impacted lower third molar surgery. Materials and Methods: This randomised, prospective, double-blind, split-mouth clinical study included 30 healthy individuals with bilaterally impacted lower third molars that was removed for orthodontic purposes between September 2017 and September 2018. Group 1 was given a placebo (single dose vitamin C tablet) and group 2 was given a single 30 mg dose of deflazacort 1 hour prior to the surgery. Pain was evaluated using the visual analog scale for 1 week postoperatively. Edema (in mm) and trismus (in mm) were evaluated preoperatively and on postoperative days 2 and 7. The Mann-Whitney U test was applied for group analysis. p values < 0.05 were considered statistically significant. Results: When postoperative pain scores were evaluated, a significant difference was found between the groups only at the 6th and 12th hours (p0.05). Even high trismus values were recorded on the 2nd day, it was observed that the trismus resolved on the 7th day. There were no significant differences in trismus between the groups at any time point (p>0.05). Evaluation of swelling showed that there was no statistically significant difference between the study and control groups at any time point (p>0.05). No side effect was detected in both the study and the control groups. Conclusions: This was the first split-mouth study evaluating the anti-inflammatory effect of deflazacort after lower impacted third molar surgery. A single dose of 30 mg deflazacort was shown to be effective in reducing pain at 6 and 12 hours postoperatively.

Dermal interstitial fluid (ISF) is a novel source of biomarkers that can be considered as an alternative to blood sampling for disease diagnosis and treatment. Nevertheless, in vivo extraction and analysis of ISF are challenging. On the other hand, microneedle (MN) technology can address most of the challenges associated with dermal ISF extraction and is well-suited for long-term, continuous ISF monitoring as well as in situ detection. In this review, we first briefly summarise the different dermal ISF collection methods and compare them with MN methods. Next, we elaborate on the design considerations and biocompatibility of MNs. Subsequently, the fabrication technologies of various MNs used for dermal ISF extraction, including solid MNs, hollow MNs, porous MNs and hydrogel MNs, are thoroughly explained. In addition, different sensing mechanisms of ISF detection will be discussed in detail. Subsequently, we identify the challenges and propose the possible solutions associated with ISF extraction. A detailed investigation is provided for the transport and sampling mechanism of ISF in vivo. Also, the current in vitro skin model integrated with the MN arrays will be discussed. Finally, future directions to develop a point-of-care (POC) device to sample ISF are proposed.

Lynch syndrome (LS) is one of the most common hereditary cancer syndrome in human populations, associated with germline variants in MLH1, MSH2/EPCAM, MSH6 and PMS2 genes. The advent of next generation sequencing has proven a significant impact in germline variant detection in the causative genes; however, a large proportion of patients with clinical criteria still receive uncertain or negative results. PMS2 is the least frequent reported gene, associated with up to 15% of LS cases with late-onset disease and low penetrance phenotype; however, the proportion of PMS2-LS cases is considered to be highly underestimated. In this context, we consulted public available databases (ClinVar, LOVD) for missense and intronic PMS2 variants and performed an in silico analysis of the genomic sequence. Splicing bioinformatics tools proven effective in other genes were used to assess both the wild-type DNA sequence and reported genetic variants. Splicing alterations were predicted in silico and using GTEx short-read RNA expression data. Out of the 2384 missense variants discovered, 90% were classified with uncertain significance (VUS). 4.9% of missense variants were shown to have a potential splicing consequence (DS &gt; 0.2) using SpliceAI. As described in the original publication, SpliceAI-visual was proven effective in annotation of short intronic variants (&lt; 50 bp). Four short intronic variants were identified using SpliceAI-visual as potentially splicing disturbing, in spite of using a lower threshold (DS &gt; 0.1). Moreover, we observed that Splicing Regulatory Elements (SREs) may play a fundamental role in alternative splicing in PMS2 gene, ESE motifs being overrepresented in highly expressed exons 5, 11 and 14. Computational analysis performed in our study serves as a valuable filtering step for guiding further RNA sequencing experiments. Additional functional data is necessary to evaluate the significance of our findings.

Rubella infection is typically mild or asymptomatic except when infection occurs during pregnancy. Infection in early pregnancy can cause miscarriage, stillbirth, or congenital rubella syndrome. Only individuals that are still susceptible to rubella infection during child-bearing age are vulnerable to this burden. Rubella containing vaccine (RCV) is safe and effective, providing life-long immunity. However, average age-at-infection increases with increasing vaccination coverage, which could potentially lead to increased disease burden as well, if the absolute risk of infection during child-bearing age increases. Dynamics of rubella transmission were explored using EMOD, a software tool for building stochastic, agent-based infection models. Simulations of pre-vaccine, endemic transmission of rubella virus introduced RCV at varying levels of coverage to determine the expected future trajectories of disease burden. Introducing RCV reduces both rubella virus transmission and disease burden for a period of around 15 years. Increased disease burden is only possible more than a decade post-introduction, and only for contexts with low current burden and high transmission intensity. Low or declining rubella virus transmission intensity is concurrently associated with both greater disease burden and greater vaccine effectiveness. The risk of increasing burden through vaccination only exists for locations with persistently high infectivity, high connectivity, and high fertility. A trade-off between the risk of a small, future burden increase and a large, immediate burden decrease strongly favors RCV introduction.

This study introduces a compact Raman spectrometer with a 1064 nm excitation laser coupled with a fiber probe and an inexpensive motorized stage, offering a promising alternative to widely used Raman imaging instruments with 785 nm excitation lasers. The benefits of 1064 nm excitation for biomedical applications include further suppression of fluorescence background and deeper tissue penetration. The performance of the 1064 nm instrument in detecting cancer in human bladder resectates is demonstrated. Raman images with 1064 nm excitation were collected ex vivo from 10 human tumor and non-tumor bladder specimens and the results are compared to previously published Raman images with 785 nm excitation. K-Means cluster (KMC) analysis is used after pre-processing to identify Raman signatures of control, tumor, necrosis, and lipid-rich tissues. Hierarchical cluster analysis (HCA) groups the KMC centroids of all specimens as input. The tools for data processing and hyperspectral analysis were compiled in an open source Python library called SpectraMap (SpMap). In conclusion, the 1064 nm Raman system can differentiate between tumor and non-tumor bladder tissues in a similar way to 785 nm Raman spectroscopy. These findings hold promise for future clinical hyperspectral imaging.

Peritoneal fluid is an ovarian exudate from the growing follicle or corpus luteum. Therefore, the free concentrations of estrogens and progesterone are always much higher than in plasma, especially after ovulation. The peritoneum is not vascularised, and peritoneal implants and the superficial portion of deep endometriosis are likely influenced mainly by peritoneal fluid. Follicular phase progesterone concentrations are as high as during the luteal phase in plasma. This explains that most peritoneal implants are rarely proliferative and out of phase with the endometrium. From some 5 mm of depth onwards, endometriosis is rather influenced by plasma hormone concentra-tions, and the deeper parts can be proliferative as the endometrium. Because of these progesterone concentrations, progesterone resistance has to be postulated, permitting endometriosis lesions to initiate and develop. This opens the discussion of whether endometriosis is similar to the basal endometrium. These peritoneal fluid concentrations are important to understand the natural history and medical therapy of endometriosis. Most medical therapies decrease ovarian function and affect peritoneal fluid steroid hormone concentrations. It is suggested that the efficacy of medical therapy for endometriosis-associated pain is a consequence of the decreased estrogen concentrations in the peritoneal cavity and that the local effect of progestins may not be determinant for pain relief. If this is true, a history of endometriosis should not be considered a contraindication for hormone re-placement therapy.

This review article discusses the involvement of the Brain-Derived Neurotrophic Factor (BDNF) in the control of pain. BDNF, a neurotrophin known for its essential role in neuronal survival and plasticity, has garnered significant attention for its potential implications as a modulator of nociception and pain. This comprehensive review aims to provide insights into the multifaceted interactions between BDNF and pain pathways, encompassing both physiological and pathological pain conditions. I delve into the molecular mechanisms underlying BDNF's involvement in pain processing and discuss potential therapeutic applications of BDNF and its mimetics in managing pain. Furthermore, I highlight recent advancements and challenges in translating BDNF-related research into clinical practice.

In this paper, the authors seek to discuss some of the complexities involved in cross-cultural working in relation to the communication and management of pain in older people. Specifically, the paper addresses the culture construction of ageing and how pain is often constructed as a natural part of ageing. The authors also suggests that with the rise of the ideology of active-ageing many older people who are disabled or living in chronic pain, may feel a moral imperative to hide pain and ill-health. The discussion extends into looking at the impact of culture and the communication of pain, including specific idioms of distress, somaticize and the lay-management of pain through stoicism.

Migraine and neuropathic pain (NP) are evocative of painful, disabling, chronic conditions which exhibit resembling symptoms and thus considered to share a common etiology. Calcitonin gene-related peptide (CGRP) has gained credit as a target for migraine management; nevertheless, the efficacy and the applicability of CGRP modifiers warrant search for more effective therapeutic targets for pain management. This scoping review overviews human studies of common pathogenic factors in migraine and NP to explore potential novel therapeutic targets. CGRP causes inflammation in the meninges; monoclonal antibodies and inhibitors target CGRP. Gluta-mate-induced hyperexcitability and subsequent sensitization are closely linked to an alteration of the tryptophan (Trp)-kynurenine (KYN) metabolic system; the Trp-KYN system may serve as a potential target. Microglial overaction is observed in migraine and NP; modifying the microglial activity may be a possible approach. Cytokine-induced inflammation is a leading hypothesis of the pathogenesis of the conditions; alleviating neuroinflammation may complement a pain-relieving armamentarium. Transient receptor potential (TRP) ion channels evoke the release of several substances; TRP ion channels may potentially emerge as new targets. The endocannabinoid system plays a major role in the pain trafficking pathway; modification of the system may open a new path toward discovery of new analgesics. Here we highlight the mechanism of those common pathogenic factors to explore therapeutic targets for innovative pain management in migraine and NP.

Rheumatoid arthritis (RA) is an autoimmune disease mainly characterized by joint inflammation. It presents extra-articular manifestations, with the lungs one of the affected areas. Among these, damage to the pulmonary interstitium (Interstitial Lung Disease -ILD) has been linked to proteins involved in the inflammatory process and related to extracellular matrix deposition and lung fibrosis establishment. Peptidyl arginine deiminase enzymes (PAD), which carry out protein citrullination, play a role in this context. A genetic association analysis was conducted on genes encoding two PAD isoforms, PAD2 and PAD4. This analysis also included ancestry informative markers and protein level determination in samples from patients with rheumatoid arthritis, RA-associated ILD, and clinically healthy controls. Significant single nucleotide variations (SNV) and a haplotype were identified as susceptibility factors for ILD-RA development. Elevated levels of PAD4 were found in ILD-RA cases, while PADI2 showed an association with RA susceptibility. This document presents the data obtained from the conducted research, which has been published.

The Interdisciplinary Canadian Collaborative ME Research Network (ICanCME), established in 2019, aims to foster research in Canada and contribute to finding the causes and possible treatments for myalgic encephalomyelitis /chronic fatigue syndrome (ME/CFS), thereby reducing the impact of ME/CFS on the health of Canadians. The main objectives of this paper are to suggest standards for ME/CFS research for the collection of data from participants (Recommended Data Elements) and to consider other factors, such as design, language, cultural issues, equity, and diversity. Consensus of the relevant contents of this research guideline was reached during the ICanCME working group meetings and were based on existing guidelines. Members of the working group contributed to guideline development based on their respective expertise. The proposed research guidelines could improve research quality and advance knowledge in the field of ME/CFS, and ultimately benefit ME/CFS patients.

Weight loss solutions are on the rise, and there is growing interest in natural alternatives to the pharmaceuticals in the market, which are not devoid of relevant side effects. To this end, the objective of the current study is to assess the effects of a botanical-based blend comprised of lemon verbena and hibiscus extracts in weight management, body fat, appetite, lipid, and glucose profiles, in an overweight population, for 90 days. As a result, the volunteers presented significant weight loss in absence of diet, which coincided with decreased body fat. Body fat was assessed by anthropometry, electrical bioimpedance and DEXA scan. Cholesterol levels were also significantly decreased. Satiety assessment revealed that the product contributed to increased feeling of fullness and satisfaction after a meal, compared to the placebo group, which could contribute to the weight loss observed. Blood glucose and blood pressure levels remained unchanged, which was expected as the volunteers were normoglycemic and their blood pressure was in the healthy range. In conclusion, daily supplementation of a botanical-based blend contributes to weight loss in overweight individuals, in absence of diet, while not affecting other parameters that are in the healthy range. This product could be a candidate alternative or add-on to other weight loss products, as part of a healthy lifestyle.

Palmitoylethanolamide (PEA) has been prescribed for neuropathic pain for several years. This study is mainly addressed to summarize what has been published on the topic in the last decades, and how appropriate the numerous prescriptions are. Among others, it examines the innovative EquiPEA^® patent, which aims to address obstacles encountered with conventional PEA formulations. EquiPEA^® seems to partially ameliorate the bioavailability and the targeted distribution. It seems to introduce novel advancements that have the potential to enhance the therapeutic effectiveness of PEA in terms of its anti-inflammatory, antioxidant, and analgesic properties. The deep literature analysis aims to examine the potential advantages of this innovative formulation, in the context of several pathological conditions that may benefit from this molecule. In particular, it investigates the potential enhanced bioavailability and targeted delivery system of EquiPEA^®. Also, it tries to understand if it can modernize the field of therapy based on PEA, thus offering a better treatment option for individuals with long-term inflammation, oxidative stress, and neuropathic or mixed pain with a neuropathic component. The study examines the possible impact of EquiPEA^® on personalized medicine strategies and its potential for translation into clinical practice. It analyses the possibilities that EquiPEA^® has in enhancing patient outcomes in a range of central nervous system and inflammatory conditions. This narrative review makes a valuable contribution to the ongoing comprehension of PEA therapy. It establishes a foundation for further exploration in research and potential uses in clinical settings.

Rett syndrome (RTT) is an X-linked neurodevelopment disorder associated with the single monogenic mutation in methyl-CpG binding protein 2 (MeCP2) in up to 95% of cases. The growing number of genome-wide association studies and incomplete concordance for autoimmune diseases in monozygotic twins concur to support the involvement of environmental factors, like infectious agents or chemicals, in the breakdown of tolerance leading to autoimmunity. In fact, the coexistence of a perturbation of the immune system in RTT patients has been previously hypothesized. We herein explored the hypothesis that an autoimmune component derived from environmental bacterial infection of non typeable Haemophilus influenzae may coexist in RTT. At this purpose we screened sera from RTT syndrome patients, non-RTT pervasive developmental disorders patients and healthy controls with the hyperglucosylated adhesin protein HMW1ct(Glc) used as a precise antigen in ELISA in order to identify specific antibodies to N-glucosylation sites. Results showed that HMW1ct(Glc) is able to significantly discriminate antibodies among RTT sera and controls. Competitive ELISA confirmed the specific interaction between antibodies characteristic of RTT syndrome and the N-glucosylation motifs of the bacterial adhesin protein HMW1ct(Glc).