This paper presents a dynamic homotopy technique that can be used to calculate a preliminary result for a power flow problem (PFP). This result can then be used as an initial estimate to efficiently solve the PFP using either the classical Newton-Raphson (NR) method or its fast decoupled version (FDXB) while still maintaining high accuracy. The preliminary stage for the dynamic homotopy problem is formulated and solved by employing integration techniques, where implicit and explicit schemes are studied. The dynamic problem assumes an initial condition that coincides with the initial estimate for a traditional iterative method such as NR. In this sense, the initial guess for the FPF is adequately set as a flat start, which is a starting for the case when this initialization is of difficult assignment for convergence. The static homotopy method requires a complete solution of a PFP per homotopy pathway point, while the dynamic homotopy is based on numerical integration methods. This approach can require only one LU factorization at each point of the pathway. Allocating these points properly helps avoid several PFP resolutions to build the pathway. The hybrid technique was evaluated for large-scale systems with poor conditioning, such as a 109272-bus model and other test systems under stressed conditions. A scheme based on the implicit backward Euler scheme demonstrated the best performance among other numerical solvers studied. It provided reliable partial results for the dynamic homotopy problem, which proved to be suitable for achieving fast and highly accurate solutions using both the NR and FDXB solvers.

In this paper, the experimental study of heating in 2 h lunch mode of air-conditioned bed system is carried out. The results show that the power consumption of heat conduction heating is only 0.34 kW·h, and the average heat dissipation is 81.3 W, while the power consumption of convection heating is 1.43 kW·h, with an average heat dissipation of 748.7 W. Regardless of power consumption or heat dissipation, convection heating is significantly higher than heat conduction heating, resulting in the room air temperature of the former increased from 12.3 °C to 17.3 °C, while the latter only increased from 14.4 °C to 15.2 °C. The study found that the water temperature of heat conduction heating can meet the thermal comfort needs of the human body in the range of 38~40 °C, while convection heating requires a higher temperature range, In contrast, the grade of hot water required for heat conduction heating is lower. Through the experiment, it is also found that the temperature of convection heating rises fast, but it is easy to appear dry feeling after a long time, while heat conductive heating has a slow temperature rise. there is a cool feeling within 20 min after the heating starts, and then the thermal comfort is better. The air conditioning system in this paper is used for the heating experiment in the winter lunch break mode, compared with convection heating, the overall thermal comfort of heat conduction heating is better and more energy efficient. it is suggested to adopt heat conduction heating mode in the winter heating of this system.

Non-union is one of the severe complications of traumatic fracture and still no standard therapeutic recommendations currently. A total of eleven patients were treated on the lesions for non-union, after the failure of open reduction internal fixation (ORIF) or total hip replacement, by autologous conditioned serum (ACS) for one to three times monthly and followed up. Seven patients received ACS three times, three patients received it two times, and the only one who underwent total hip replacement received it once. Ten patients achieved union at the last follow-up visit, indicating the effectiveness of ACS on patients who suffered from non-union after ORIF. ACS has the potential as an alternative or adjective treatment for non-union and is worthy to be investigated further for the benefits of patients.

Pediatric psychology action in the pediatric clinical-surgical high complexity unit has become increasingly necessary. It allows for the possibility of integrating complex pediatric clinical-surgical operations by reducing painful effects on the emotional world of children and adolescents. The pediatric psychologist in a pediatric unit continuously oversees children and adolescents (C/A) throughout the entire therapeutic process, extending activity to parents and healthcare personnel. In ill children and adolescents, physical pain and psychological suffering follow, with minimal temporary variations, the same clinical path with continuous changes which put a strain on the ability of children, adolescents, parents and healthcare staff to cope with stress.

Critically ill patients treated in the intensive care unit (ICU) can present many abdominal conditions that need a prompt diagnosis and timely treatment because of their general frailty. Clinical evaluation and diagnostic tools like ultrasound or CT scan are not reliable or feasible in these patients. Bedside laparoscopy (BSL) is a minimally invasive procedure that allows surgeons to assess the abdominal cavity directly in the ICU, thus avoiding unnecessary exploratory laparotomy or incidence related to intra-hospital transfer. We conducted a review of the literature to summarize the state-of-the-art of BSL. Medline, The Cochrane Central Register of Controlled Trials (CENTRAL), and Scopus databases were utilized to identify all relevant publications. Indications, contraindications, technical aspects, and outcomes are discussed. The procedure is safe, feasible, and effective. When other diagnostic tools fail to diagnose or exclude an intra-abdominal condition in ICU patients, BSL should be preferred over exploratory laparotomy.

Family Integrated Care (FICare) is associated with improved developmental outcomes and decreased parental mental health risks in stable preterm infants. However, less is known about its application in critically ill infants who are at greater risk for adverse outcomes. The objective of this study was to assess the safety and feasibility of implementation of FICare in critically ill infants in the first few weeks of life. In this prospective cohort study, 41 critically ill infants were enrolled: 17 in observational group receiving standard care (SC)and 24 in the FICare Plus group. Resources were developed for staff and parents to support earlier engagement in infant care. Outcomes were assessed using standardized questionnaires. The t-test or Wilcoxon Rank-Sum test were used to compare continuous variables, while Chi-square or Fisher exact test were used for categorical variables, respectively. Baseline maternal and infant characteristics were similar in both groups. The tools and procedures developed for FICare Plus successfully supported greater engagement in the care of their infant with no increase in adverse events and no increase in parent stress. Preliminary measures of infant efficacy were similar in both groups. Total anxiety scores were high among all parents at enrolment {83.1 (67-94) vs 77.3 (66-86); p-value 0.4}. However, the scores prior to discharge were lower in FICare Plus group {78 (71-90) vs 63 (52-74.5); p-value 0.02}. This pilot study showed that it is feasible and safe to implement family integrated care in critically ill infants.

The human gut microbiota consists of bacteria, archaea, fungi, and viruses. It is a dynamic ecosystem shaped by several factors, which play an essential role in both healthy and diseased states of humans. A disturbance of the gut microbiota, also termed “dysbiosis,” is associated with increased host susceptibility to a range of diseases. Because of splanchnic ischaemia, exposure to antibiotics, and/or underlying the disease critically ill patients loose 90% of the commensal organisms in their gut within hours after the insult. This is followed by a rapid overgrowth of potentially pathogenic and pro-inflammatory bacteria altering metabolic, immune, and even neurocognitive functions and turning the gut into the driver of systemic inflammation and multiorgan failure. Indeed, restoring healthy microbiota by means of faecal microbiota transplantation (FMT) in the critically ill is an attractive and plausible concept in intensive care. Yet, available data from controlled studies are limited to probiotics and FMT for severe C. difficile infection or severe inflammatory bowel disease. Case series and observational trials generate hypothesis that FMT might be feasible and safe in immunocompromised patients, refractory sepsis, or severe antibiotic-associated diarrhea in ICU. There is a burning need to test these hypotheses in randomized controlled trials powered for determination of patient-centered outcomes.

3,4-methylenedioxypyrovalerone (MDPV) is a new psychoactive substance (NPS) and the most widespread and life-threatening synthetic cathinone of the “bath salts”. Preclinical research has proven the cocaine-like psychostimulant effects of MDPV and its potential for abuse. Cannabidiol (CBD) is a non-psychotropic phytocannabinoid that has emerged as a new potential treatment for drug addiction. Here, we tested the effects of CBD (20 mg/kg) on MDPV (2 mg/kg)-induced conditioned place preference and MDPV (0.05 and 0.075 mg/kg/infusion) self-administration paradigm. We also assessed the effects of the combination of CBD, and MDPV (3 and 4 mg/kg) on anxiety-like behaviour using the elevated plus maze (EPM). CBD mitigated the MDPV-induced conditioned place preference. On the contrary, CBD administration throughout the MDPV (0.075 mg/kg/infusion) self-administration increased drug-seeking and taking behaviours, but only in the high-responders group of mice. Additionally, CBD exerted anxiolytic-like effects, but only in MDPV-treated mice. Taken together, our results indicate that CBD modulation of MDPV-induced motivational responses in mice vary depending on the requirements of the learning task, resulting in a complex response. More research attempting to decipher the behavioural and molecular interactions between CBD and MDPV is needed.

Background: Gram-negative bacteremia, especially from Klebsiella spp., Escherichia coli, and Pseudomonas aeruginosa, poses a significant public health threat due to multidrug resistance and high mortality rates. Cost-effective treatments are essential in low-middle income countries as Colombia. Methods: This descriptive, phase IV study was conducted in a tertiary care hospital in Colombia. Adult patients with Gram-negative bacteremia treated with generic piperacillin/tazobactam (Penibactam®) were evaluated. Clinical and microbiological responses were assessed over 12 months. Results: The study included 30 critically ill patients with an average APACHE II score of 22.12. The clinical response at day 7 was 66% (n = 20), and the microbiological response was 56.7% (n = 17). By the end of follow-up, clinical improvement was observed in 63.3% (n = 19), with a mortality rate of 23% (n = 7). The cardiovascular system was the most common infection site. Conclusions: Generic piperacillin/tazobactam demonstrated effectiveness and safety comparable to existing literature in treating Gram-negative bacteremia, offering a viable, cost-effective alternative for critically ill patients in real-world settings.

Introduction and Aims: COVID-19-associated invasive pulmonary aspergillosis (CAPA) is common and is associated with poor outcomes in critically ill patients. This prospective observational study aimed to explore the association between CAPA development and the incidence and prognosis of cytomegalovirus (CMV) reactivation in critically ill COVID-19 patients. Materials and Methods: We included all consecutive critically ill adult patients with confirmed COVID-19 infection who were admitted to three COVID-19 intensive care units (ICUs) in an Italian hospital from February 25, 2020, to May 8, 2022. A standardized procedure was employed for early detection of CAPA. Risk factors associated with CAPA and CMV reactivation and the association between CMV recurrence and mortality were estimated using adjusted Cox proportional hazard regression models. Results: CAPA occurred in 96 patients (16,6%) of the 579 patients analyzed. Among the CAPA population 40 (41,7%) patients developed CMV blood reactivation with a median time of 18 days (IQR 7-27). The CAPA+CMV group did not exhibit a significantly higher 90-day mortality rate (62.5% vs. 48.2%) than the CAPA alone group (p=0.166). The CAPA+CMV group had a longer ICU stay, fewer ventilation-free days, and a higher rate of secondary bacterial infections than the control group of CAPA alone. In the CAPA population, prior immunosuppression was the only independent risk factor for CMV reactivation (HR 2.33, 95% C.I. 1.21-4.48, p=0.011). Conclusions: In critically ill COVID-19 patients, CMV reactivation is common in those with a previous CAPA diagnosis. Basal immunosuppression before COVID-19 appeared to be the primary independent variable affecting CMV reactivation in patients with CAPA. Furthermore, the association of CAPA+CMV versus CAPA alone appears to impact ICU length of stay and secondary bacterial infections but not mortality.

Background Although aminoglycosides are often used as treatment for Gram-Negative infections, optimal dosing regimens remains unclear, especially in ICU patients. This is due to a large between- and within-subject variability in the aminoglycosides’ pharmacokinetics in this population. Objective The review provides comprehensive data on the pharmacokinetics of aminoglycosides in patients hospitalized in ICU by summarizing all published PopPK models in ICU patients for amikacin, gentamicin, and tobramycin. The objective was to determine the presence of a consensus on the structural model used, significant covariates included, and therapeutic targets considered during dosing regimen simulations. Methods A literature search was conducted from the Medline/PubMed database, using the terms: ‘amikacin’, ’gentamicin’, ’tobramycin’, ‘pharmacokinetic(s)’, nonlinear mixed effect’, population’, ‘intensive care’ and ‘critically ill’. Results Nineteen articles were retained where amikacin, gentamicin and tobramycin pharmacokinetics were described in six, eleven and five models, respectively. Two-compartment model best described amikacin and tobramycin pharmacokinetics, whereas one-compartment model majorly described gentamicin pharmacokinetics. The most recurrent significant covariates were renal clearance and bodyweight. Across all aminoglycosides, mean interindividual variability in clearance and volume of distribution were 41.6% and 22.0%, respectively. A common consensus for an optimal dosing regimen for each aminoglycoside was not reached. Conclusion This review showed models developed for amikacin, from 2015 until now and for gentamicin and tobramycin from the past decades. Despite growing challenges of external evaluation, the latter should be more considered during model development. Further research including new covariates, additional simulated dosing regimens and external validation should be considered to better understand aminoglycosides pharmacokinetics in ICU patients.

In this retrospective report we present five cases of critically ill pregnant or newly delivered women positive for Covid-19 admitted to our obstetrical departments at Karolinska University Hospital. They compose 6% of eighty-three pregnant women that tested positive for SARS-CoV-2 during the period March 25 to May 4, 2020. Three patients were at the time of admission in gestational week between 21+4 to 22+5 and treated during their antenatal period, meanwhile the other two were admitted within 1 week postpartum. All of them were in a need of intensive care, one was treated with high flow oxygen therapy, the other four with invasive mechanical ventilation (three with endotracheal intubation and one with extra corporeal membrane oxygenation). Age above thirty, overweight and gestational diabetes are notable factors in the cases presented. At the time of admission, they all presented with symptoms as fever, cough and dyspnea. Chest imaging with computer tomography scan was performed in each case and demonstrated multifocal pneumonic infiltrates in all of them but no pulmonary embolism was confirmed in any. Neither did the echocardiogram indicates any cardiomyopathy. Four of the patients have been discharged from the hospital, with an average of 20 hospital days. One antenatal pregnant woman needed prolonged ECMO therapy, in gestational week 27+3 she went into cardiac arrest, resulting in an urgent c-section on maternal indication. At the time of writing she is still hospitalized. In coherence with other published reports our cases indicate that critically ill pregnant women infected by SARS-Cov-2 may develop severe respiratory distress syndrome requiring prolonged intensive care. The material is limited for conclusions to be taken, more detailed information on symptoms, treatment, and outcomes for pregnant and postpartum women managed in intensive care is therefore needed.

Background: Ventilator-associated pneumonia (VAP) is among the most common healthcare-associated infections in Pediatric Intensive Care Units (PICUs). Because of the lack of a gold-standard diagnostic test, early diagnosis of VAP is challenging. We investigated whether bronchial biomarkers interleukin-4 (IL-4), plasminogen activator inhibitor-1 (PAI-1) and soluble receptor for advanced glycation end products (RAGE) could contribute in early VAP diagnosis through their fluctuation in time in critically ill pediatric patients. Methods: Bronchial secretions were collected from PICU patients with VAP on days 1 and 6. PAI-1, RAGE and IL-4 levels were measured by ELISA. Protein concentrations between high and low VAP suspicion patients were compared using unpaired Student’s t or Mann–Whitney U tests. Results: Twenty PICU patients, with median age 7.75yrs (range 0.5-15.3), mechanically ventilated for ≥48hrs with increased oxygenation requirements and VAP clinical/laboratory signs were enrolled. They were divided in VAP high-suspicion (n=12) or low-suspicion (n=8) groups based on Clinical Pulmonary Infection Score (cutoff:6). ΡΑΙ-1 και RAGE levels did not differ between high- or low-VAP suspicion groups the 1st or 6th days (p-value>0.05). IL-4 was not detected in bronchial secretions. Conclusion: Bronchial concentrations of IL-4, PAI-1 and RAGE in critically ill children are not correlated with high- or low-VAP suspicion.

Intratumour heterogeneity is often associated with poor response to treatment and bad prognosis. In addition to constitutive genetic/epigenetic sources, phenotypic and functional heterogeneity can reflect cell plasticity due to changes in gene expression patterns induced by signals from the tumour microenvironment or other cells. Positive interactions between cancer clones can increase their fitness and contribute to tumour growth, resistance to drugs and metastasis. Consequently, understanding the pathways involved in such behaviours is of great significance for cancer treatment. To explore if and how genetically distant clones can synergistically enhance each other's metastatic potential, this study used three (two breast and one lung) cancer cell lines with different aggressiveness levels. We found that (i) the conditioned media from the breast and lung aggressive lines induce mesenchymal features and increase the migration and invasion potential of the poorly metastatic breast line, and (ii) in both cases, this interclonal communication is based on the same soluble factor – namely, the tumour growth factor TGF-β1. Furthermore, when the two breast lines are mixed and co-cultured, the invasive potential of both lines is enhanced, and this outcome is dependent on the recruitment of the less aggressive clone into expressing a malignant phenotype. Based on our findings, we propose a two-tier model whereby highly metastatic clones can recruit weakly metastatic clones into acquiring an invasive phenotype, which in turn augments the invasion ability of the former (i.e., a “help me help you” strategy) through shared proteases and/or ECM remodelling. We suggest that such synergistic cooperation can easily emerge via cross-talk involving metastatic clones able to constitutively secrete signalling molecules that induce and maintain their own malignant state (i.e., autocrine/cell-autonomous signalling) and clones that have the ability to respond to those signals (i.e., paracrine/non-cell-autonomous signalling) and express a metastatic phenotype. Taking into account the lack of therapies to directly affect the metastatic process, interfering with such cooperative behaviours that tumour cells engage in during the early steps in the metastatic cascade could provide an additional strategy to increase patient survival.

Patients in intensive care unit often lose a considerable fraction of their gut microbiome due to exposure of broad-spectrum antibiotics and other reasons. Dysbiosis often results in prolonged diarrhea and increase occurrence of multi-drug resistant pathogens in the colon with clinical consequences not yet well understood. Restoring the microbioma by faecal microbial transplantation (FMT) is a plausible therapeutic possibility, so far only documented in case reports and case series using very heterogeneous methodologies. Before FMT in critically ill can be tested in randomised controlled trials, there is a burning need to describe a standardized operating procedure (SOP) of the whole process, respecting the specifics of critically ill population, such as the risk of disrubted intestinal barrier and time critical nature of the procedure. We describe the SOP that has been developed for experimental use in critically ill patients by a multidisciplinary team of intensivists, gastroenterologist and microbiologist based on feedback from regulatory authority (State Institue of Drug Control of the Czech Republic). The hallmarks of these SOPs are multi-donor freshly frozen transplantate quaranteeded for 3 months consisting of 7 aliqutes from 7 unrelated healthy donors, and administered by rectal tube. In this paper we discuss the rationale for this SOP and the process of its development in details and release the full proposed SOP is in the form of online appendix.

Historically, admission of hematological patients in the ICU shortly after the start of a critical illness is associated with better survival rates. Early intensive interventions administered by MET could have a role in the management of hematological critically ill patients, eventually reducing ICU admission rate. In this retrospective and monocentric study, we evaluate the safety and effectiveness of intensive treatments administered by the MET in a medical ward frame. The administered interventions were mainly helmet CPAP and pharmacological cardiovascular support. Frequent reassessment by the MET at least every 8 to 12 hours was guaranteed. We analyze data from 133 hematological patients that required MET intervention. In hospital mortality was 38%; mortality doesn’t increase in patients not immediately transferred to the ICU. Only 3 patients died without a former admission in ICU; in these cases, mortality was not related to the acute illness. Moreover, 37% of patients overcame the critical episode in the hematological ward. Higher SOFA and MEWS scores were associated with a worst survival rate, while neutropenia and pharmacological immunosuppression were not. The MET approach seems to be safe and effective. SOFA and MEWS confirmed to be effective tools for prognostication.

Among others, road traffic, industrial emissions, commercial activities, smoking and cooking are considered as major contributing factors for the increasing levels of pollutants in atmosphere. High levels of potentially toxic metals and microbes in atmosphere, especially in indoor air, may pose serious threat to human health. Therefore, concentration and associated health risks of potentially toxic trace metals (Cd, Cr, Cu, Fe, Mn, Pb, and Zn) and their risk to human health, and microbial load in indoor air was assessed using air condition (AC) filter dust samples collected from 5 locations representing residential, agricultural and industrial settings of Eastern Province, Kingdom of Saudi Arabia. The levels of trace metals varied considerably among sampling areas, with the highest levels of Cr and Cd recorded in the Industrial-area sites followed by the Agricultural and Urban-Residential sites. The highest levels of Pb and Fe were found in the Agricultural area sites followed by the Industrial and Urban-Residential area sites. The metals in dust sample, especially Cd, Cr and Pb, showed a considerable health risk through dermal pathway. Among the sites, the highest hazard quotient for these metals was found for Al-Qatif-Industrial areas sites and among the metals it was the highest for Cd. The cancer risk from the metals contained in AC filter dust was negligible. Samples collected from Agricultural and Industrial area sites were substantially contaminated with bacteria and fungi, respectively. Bacterial contaminants were mostly Gram Negative, with considerable antibiotic resistance and haemolytic activity. Thus, indoor air quality as assessed by AC filter dust depicted that a considerable health risk could be posed by the trace heavy metals and microorganisms for a long-term exposure. Furthermore, this study demonstrated that AC filters dust could be a unique and reliable test sample for the assessment of indoor environment.

Aims: Medical Nutritional Treatment (MNT) can be complex and associated to potential meta-bolic complications, which has been recently described as Nutritrauma. There is no data on the effect of applying this strategy in clinical practice. The aim of our work is to describe if applica-tion of Nutritrauma concept in real live is useful to detect metabolic complications associated to the prescription of MNT in critically ill patients. Methods: In this descriptive prospective study at a single center, we enrolled 30 consecutive crit-ical ill patients of a 14 beds medical – surgical Intensive Care Unit. The Nutritrauma strategy implementation was based in four M steps: Metabolic screening, MNT prescription, Biochemical Monitoring and Nutritional Management. The primary endpoint was to describe the metabolic complications of the MNT detected with Nutritrauma strategy. Secondary endpoint was to de-scribe the most frequent causes of inappropriate prescription. Results: We analysed 28 patients (mean age 69,7 ± 11,3 years; APACHE II 18,1 ± 8,1, SOFA 7,5 ± 3,7; Nutric Score modified 4,3 ± 2,01 and mean BMI 27,2 ± 3,8). The most frequent disease on admission was sepsis (46,4%). Length of ICU stay was 20,6 ± 15,1 days and 39,3% died during the ICU stay. Enteral nutrition (82,1%) was more frequent than parenteral nutrition (17,9%). During nutritional monitoring 54 specific analytical determinations were made. Hyperglycemia was the most frequent metabolic alteration (83,3% of the determinations). Electrolyte disturbance were hypocalcemia (50%), hypophosphatemia (29,6%) and hypokalemia (27,8%). The most frequent lipid profile abnormality were hypocholesterolemia (64,8%) and hypertriglyceridemia (27,8%). Furthermore, nutritional prescription was modified in the 53,6% of patients: increase protein dosage (25%), increase caloric dosage (21,4%) and change to an organ-specific diet (17,8%). Conclusions: The application of Nutritrauma strategy facilitate the detection of metabolic com-plications and the evaluation of the appropiate prescription of the MNT.

There is clinical concern about the combined use of alcohol and opiates. Several lines of evidence support an interaction between alcohol and the endogenous opioid system. Thus, we hypothesized that ethanol by causing the release of opioid peptides may sensitize the system to the action of exogenous opioids such as morphine. In this study, using the place conditioning paradigm as an animal model of reward, we determined whether a morphine challenge would alter the pre-established preference induced by ethanol conditioning in mice, and whether this response was mediated by the mu opioid receptor (MOP). Given that ethanol exposure stimulates the release of opioid peptides, we also assessed the role of beta-endorphin (β-END) and enkephalins (ENKs) in this response. Mice lacking MOP, β-END and/ or ENKs as well as their respective wild-type controls were tested for baseline place preference on day 1, conditioned with ethanol (2 g/kg) versus saline on days 2 to 4 and then tested under a drug-free state for postconditioning place preference on day 5. On day 8, mice received a single injection of morphine (5 mg/kg) and were tested for place preference. On each test day, mice were placed in the central neutral chamber and allowed to freely explore the conditioning chambers. The amount of time that mice spent in each chamber was recorded. We found that a challenge dose of morphine given on day 8 enhanced the CPP response in mice previously conditioned with ethanol. This response was abolished in MOP null mice, confirming the role of MOP in this response. Although this enhanced response was not altered in mice lacking either β-end or ENKs compared to their wild-type littermates/controls, it was completely blunted in mice lacking both β-end and enkephalins. Together, these results suggest that these opioid peptides jointly mediate the crosstalk between the rewarding actions of morphine and ethanol.

The present study compared the contralateral suppression and the amplitude of distortion product otoacoutsic emissions (DPOAEs) between smokers and non-smokers to determine the influence of smoking. Thirty smokers and thirty non-smokers within the age range of 18-40 years with a normal hearing sensitivity were considered for the study. For both the groups, DPOAEs were measured and the efferent auditory system functioning was measured by presenting the white noise of 50 dB HL to the contralateral side, while recording the DPOAEs. There was no significant effect of age on the amplitude of DPOAEs in both the groups. However, there were significant differences in the amplitude of DPOAEs between smokers and non-smokers. The amount of suppression and DPOAE amplitude were reduced in smokers when compared to non-smokers. The study found no significant correlation between the amount of smoking and amount of suppression between smokers and non-smokers. However, there were significant correlations between the amount of smoking and DPOAE at low and mid frequencies between smokers and non-smokers. Therefore, the present study highlights the increased damage to the efferent auditory system risk and the smoking ill-effects on the efferent auditory system.

This paper presents three types of tensor Conjugate-Gradient methods for solving large-scale linear discrete ill-posed problems based on the t-product between third-order tensors. An automatical determination strategy of a suitable regularization parameter is proposed for the tensor conjugate gradient (tCG) method. A truncated version and a preprocessed verion of the tCG method are further presented. The discrepancy principle is employed to determine a suitable regularization parameter. Several numerical examples are given to show the effectiveness of the proposed tCG methods in image and video restoration.

Background: Malnutrition in critically ill paitents is closely linked with clinical outcomes. During acute inflammatory states, nutrition cannot reverse the loss of body cell mass completely. Studies on nutritional screening and strategy considering metabolic changes not yet been conducted. We aimed to identify nutrition strategies using the modified Nutrition Risk in the Critically ill (mNUTIRC) score. Methods: Nutrition support data, laboratory nutrition indicators, and prognosis indices were prospectively collected on the 2nd and 7th day after admission. It is to identify the effect of changes on the metabolic status and critical target of nutrition intervention. To discriminate the high-risk group of malnutrition, receiver operating characteristic curves were plotted. Risk factors associated with 28 day-mortality were evaluated using multivariable Cox proportional hazards regression. Results: A total of 490 and 266 patients were analyzed on the 2nd and 7th day, respectively. Only the mNUTRIC score showed significant differences in nutritional risk stratification. The use of vasopressors, hypo-protein supply (< 1.0 g/kg/day), high mNUTRIC score and hypoalbuminemia (<2.5 mg/dl) in the recovery phase was strongly associated with 28-day mortality. Conclusions: The implementation of the mNUTRIC score and protein supply in the post-acute phase is critical to improve 28-day mortality in critically ill patients.

Excessive high fat diet (HFD) consumption can induce food addiction which is believed to involve the communication between the hypothalamus and mesolimbic dopaminergic neurons, originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc). These brain regions are densely populated with opioid receptors, raising the possibility that these receptors, and particularly mu opioid receptors (MORs), are involved in mediating reward induced by palatable foods. This study sought to investigate the involvement of MORs in high fat diet (HFD)-induced reward and if there is any difference between male and female subjects in this response. We also assessed if exposure to HFD would potentiate the rewarding action of oxycodone, a relatively selective MOR agonist. The place conditioning paradigm was used to determine if conditioning for a short time (STC, 2 h) or long time (LTC, 16 h) with HFD induces reward or alters the rewarding action of oxycodone. Male and female C57BL/6J mice as well as MOR knockout and wildtype mice of both sexes were tested for basal place preference on day 1 and then conditioned with HFD in one chamber and regular chow diet (RCD) in another chamber and tested for place preference again after three sets of STC and again after a set of LTC. Each set consisted of two conditioning with RCD and two conditioning with HFD. Controls were conditioned with RCD in both conditioning chambers. Following the last place preference test, mice were treated with oxycodone and conditioned in the HFD-paired chamber and saline in the RCD-paired chamber for one hour once a day to explore the possibility if the HFD could alter oxycodone reward. The result showed that HFD induced conditioned place preference (CPP) in both male and female subjects following the LTC. This response was further potentiated after oxycodone conditioning. The latter response was mediated via MORs, as it was blunted in MOR knockout mice. However, HFD-induced CPP was observed following LTC in only female MOR knockout mice, suggesting for sexual dimorphism in this response.

Abstract: This is a retrospective study of patients admitted to Jackson Hospital, Montgomery, Alabama with a diagnosis of COVID-19 from January 1, 2021, to February 15, 2022. The independent variable used in the models were patient sex, age, race, BMI category, daily D-dimer categories, categories of anticoagulation doses (Enoxaparin 40 mg VS. Enoxaparin 80 mg VS Enoxaparin 1mg/kg or equivalent), bleeding episodes, and vaccination status. The three different categories of anticoagulation doses were considered for the purpose of the study. Results: The study reviewed a total of one hundred (100) hospitalized patients. Intermediate-dose anticoagulation was found to be the optimal dose as only fourteen percent (14%) patients died compared to a thirty-six percent (36%) and fifty percent (57%) death rate among those treated with low-dose and high-dose anticoagulation, respectively. The multivariate linear regression model predicting patient oxygen requirements revealed D-Dimer and bleeding status to be statistically significant predictors with a p value of <0.01. For the patients who had a D-dimer value ≥ 2 µg/mL, the oxygenation requirement was predicted to be 31 L higher than those with a D-dimer <2 µg/mL (99% CI; p<0.01). When mean D-dimer and corresponding oxygen requirements were calculated per hospitalization days category, the D-dimer levels and oxygen requirements were noted to follow the same trends indicating both values tended to increase and decrease simultaneously. Conclusion: The study concludes daily D-dimer trends can predict COVID-19 patient survival or daily oxygen requirements indicating D-dimer can be the miracle molecule for COVID-19 prognosis.

No research to date has explored the possibility of context-specific, within-relationship fluctuation in attachment security. In this present article, two cross-sectional studies were designed (1) to develop and validate context-specific attachment scales in Traditional-Chinese, and (2) to explore fluctuations in within-parent attachment security between the contexts of sport and academics, in relation to global attachment patterns and indicators of psychological wellbeing. Results indicated that youth can and do perceive within-parent attachment patterns differently depending upon context but that the relationship of such differences to context-specific outcomes is complex. Of particular interest was that the degree of within-parent attachment variability between contexts was clearly and negatively related to indices of psychological wellbeing. This suggests that contextual variation may be a meaningful and useful way to explore within-parent attachment fluctuation.

Excess consumption of a high-fat diet has been identified as one of the contributing factors for obesity. Women are at higher risk for adult obesity than men, predisposing them to a different set of detrimental disease conditions. Furthermore, aging studies show that physiological decline also has a serious impact on changes in the endocrine properties of white adipose tissue. Howev-er, there is still relatively little known about the factors associated with obesity and aging and their compounding impact on women’s health. To investigate adipocytokine secretion profile changes, female C3H/HeJ mice were induced to obesity through long-term consumption of a high-fat diet. Weight gain measurements and Echo MRI analysis of fat composition showed in-creases were a due solely to the high fat content in the diet. Adipocytokine secretions were ana-lyzed in media conditioned from harvested visceral fat tissue that was organ cultured ex-vivo. Adipocytokine analysis across diets and age showed significant increases in Adiponectin and Leptin secretion in high-fat diets, accelerated increases in Resistin secretion with high-fat diets. Aging induced increased secretion of Lipcalin-2, Pentraxin-3 and Serpin E1, MCP-1 and ICAM-1, regardless of diet. Furthermore, comparisons of organoid cultured protein secretions and flash-frozen tissue samples differed greatly, suggesting the WAT organoid cultures may yield information more reflective of in situ conditions. Taken together, our results show that diet and aging significantly impact secretions from adipose tissue, that may contribute to women’s health issues.

All humans will experience the process of birth, old age, illness, and death. However, when faced with life-sustaining decisions, the families of patients are often faced with medical decisions as surrogates. In recent years, the families of patients have started to value the importance of the right to palliative care, although this often requires lengthy discussions. Therefore, this study explored the predictability of factors that affect the feeling experienced by patients’ families when signing Do-Not-Resuscitate Consent. This study used a cross-sectional study and interviewed 90 family members using a structural questionnaire. The study hypotheses were tested using a t-test, one-way analysis of variance, product–moment correlation, and hierarchical regression analysis. Attribute variables of family members, such as gender and whether they live with the patient, are predictors that affect the family member’s feeling experience when signing Do-Not-Resuscitate Consent. The emotional support from medical professionals to family members helps the family member to express their negative feelings on signing Do-Not-Resuscitate Consent; more informational support information provided to family members by medical professionals can alleviate negative feelings felt by family members when signing Do-Not-Resuscitate Consent. This study identified that family members’ knowledge about Do-Not-Resuscitate acquired from medical professionals is relatively low. It is suggested that critical care units regularly conduct training on hospice palliative care, implement standard care procedures of hospice palliative care at critical care units, and provide detailed medical information about advanced decisions to family members so as to reduce their emotional stress. This will ensure that intensive care units can also achieve the goal of critically ill hospice palliative care.

Tissue regeneration is an essential requirement for wound healing and recovery of organs’ dysfunction. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-β, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium. In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity in a concentration-dependent manner. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated by topical application of ERCM solution (4 x 109 exosome particles/100 μL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. The results indicate that ERCM from AMSCs containing a large amount of GFs and NFs improve wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production.

Tissue regeneration is an essential requirement for wound healing and recovery of organs’ function. It has been demonstrated that wound healing can be facilitated by activating paracrine signaling mediated by exosomes secreted from stem cells, since exosomes deliver many functional molecules including growth factors (GFs) and neurotrophic factors (NFs) effective for tissue regeneration. In this study, an exosome-rich conditioned medium (ERCM) was collected from human amniotic membrane stem cells (AMSCs) by cultivating the cells under a low oxygen tension (2% O2 and 5% CO2). The contents of GFs and NFs including keratinocyte growth factor, epidermal growth factor, fibroblast growth factor 1, transforming growth factor-β, and vascular endothelial growth factor responsible for skin regeneration were much higher (10-30 folds) in the ERCM than in normal conditioned medium (NCM). In was found that CM-DiI-labeled exosomes readily entered keratinocytes and fibroblasts, and that ERCM not only facilitated the proliferation of keratinocytes in normal condition, but also protected against H2O2 cytotoxicity. In cell-migration assay, the scratch wound in keratinocyte culture dish was rapidly closed by treatment with ERCM. Such wound-healing effects of ERCM were confirmed in a rat whole skin-excision model: i.e., the wound closure was significantly accelerated, remaining minimal crusts, by topical application of ERCM solution (4 x 109 exosome particles/100 μL) at 4-day intervals. In the wounded skin, the deposition of collagens was enhanced by treatment with ERCM, which was supported by the increased production of collagen-1 and collagen-3. In addition, enhanced angiogenesis in ERCM-treated wounds was confirmed by increased von Willebrand factor (vWF)-positive endothelial cells. The results indicate that ERCM from AMSCs with high concentrations of GFs and NFs improves wound healing through tissue regeneration not only by facilitating keratinocyte proliferation for skin repair, but also activating fibroblasts for extracellular matrix production, in addition to the regulation of angiogenesis and scar tissue formation.

Traditionally, palliative care (PC) systems focused on the needs of advanced cancer patients. But, most patients needing PC have end-stage organ diseases. Similarly, PC models focused on the needs of patients in hospice or at home; however, in most cases PC is provided in acute hospitals. Indeed, the symptom burden that these patients experience in the last year of life frequently forces them to seek care in Emergency Department. The majority of them are admitted to the hospital and many die. This issue poses important concerns. Despite the efforts of attending healthcare professionals, inhospital patients do not receive optimal care near the end-of-life. Also, evidence is emerging that delay in identifying patients needing PC have a detrimental impact on their quality of life (QoL). Therefore, there is an urgent need to early and properly identify these patients among those hospitalized. Several trials reported the efficacy of PC in improving the QoL in these patients. Each hospital should ensure that a multidisciplinary PC team is available to support attending physicians to achieve the best QoL for both PC patients and their families. This review discusses the role and the impact of inhospital PC in patients with end-stage disease or advanced cancer.

Rats, including those of the Sprague Dawley strain, may kill mice. Because of this muridical behavior, it is standard practice in many research animal housing facilities to separate mice from rats (i.e., the predators) to minimize stress for the mice. We therefore tested the effect of cohousing on the stress levels of mice from either the C57BL/6J (BL6) or the CD1 strain and Sprague Dawley (SD rat) by determining their fecal corticosterone or cortisol metabolites (FCM) concentration and investigated how cohousing impacts a behavioral assay, i.e., conditioned place preference for intragenus (i.e., mouse-mouse or rat-rat) dyadic social interaction (DSI CPP) that had been shown be sensitive to social factors, especially to handling by humans. We found that the two delivery batches of BL6 mice or SD rats, respectively, had different stress levels at delivery that were statistically significant for the BL6 mice. Even so, the BL6 mice cohoused with rats had significantly increased FCM concentrations, indicative of higher stress levels, as compared to (1) BL6 mice housed alone or (2) BL6 mice at delivery. In contrast to their elevated stress levels, the attractiveness for contextual cues associated with mouse-mouse social interaction (DSI CPP) even increased in rat-cohoused BL6 mice, albeit nonsignificantly. Thus, cohousing BL6 mice and rats did not impair a behavioral assay in BL6 mice that had proved to be sensitive to handling stress by humans in our laboratory. SD rats cohoused with BL6- or CD1 mice and CD1 mice cohoused with SD rats showed DSI CPP that was not different from our previously published data on SD rats and BL6 mice of the Jackson- or NIH substrain obtained in the absence of cohousing. Our findings suggest that the effect of cohousing rats and mice under the conditions described above on their stress levels as opposed to their behavior might be less clearcut than generally assumed and might be overriden by conditions that cannot be controlled, i.e., different deliveries. Our findings can help to use research animal housing resources, which usually are limited, more efficiently.

Horses are high performance athletes prone to sportive injuries such as tendonitis and desmitis. The formation of fibrous tissue in tendon repair becomes a therapeutic challenge to overcome. This impels regenerative medicine to develop innovative therapies that enhance tissue regenera-tion retrieving original tissue properties. Multipotent Mesenchymal Stem/ Stromal Cells (MSCs) have been successfully used to develop therapeutic products, as they secrete a variety of bioac-tive molecules that play a pivotal role in tissue regeneration. These factors are released in cul-ture media producing conditioned media (CM). The aforementioned assumptions led to the formulation of equine synovial membrane MSCs (eSM-MSCs) – the cellular pool that naturally regenerates joint tissue, combined with medium enriched in immunomodulatory factors (among other bioactive factors) produced by umbilical cord stroma-derived MSCs (eUC-MSCs), that nat-urally contribute to suppress the immune rejection in the maternal-fetal barrier. A clinical case of an equine acute desmitis, treated with this formulation is presented. Ultrasonographic ligament regeneration occurred in a reduced time frame, reducing stoppage time and allowing return to unrestricted competition after completion of a physical rehabilitation program. This study fo-cused on the determination of the formulation therapeutic potential and the evaluation of its synergistic effect in an equine desmitis treatment, utilizing the cells themselves and its secretome.

Horses are high performance athletes prone to sportive injuries such as tendonitis and desmitis. Fibrous tissue formation with loss of mechanical properties occurs in tendon repair, becoming a therapeutic challenge to overcome. This impels regenerative medicine to develop innovative therapies that enhance tissue regeneration retrieving original tissue properties. Mesenchymal stem cells (MSCs) have been successfully used to develop therapeutic products. They secrete a variety of bioactive molecules that play a pivotal role in tissue regeneration. These factors are released in culture media producing conditioned media (CM). The aforementioned assumptions impelled us to formulate equine synovial membrane stem cells (eSM-MSCs) – the cellular pool that naturally regenerates joint tissue, combined with medium enriched in immunomodulatory factors produced by umbilical cord stroma-derived MSCs (eUC-MSCs), that naturally contribute to suppress the immune rejection in the maternal-fetal frontier. A clinical case of an equine acute desmitis, treated with the abovementioned formulation is presented. Ligament regeneration occurred in a reduced time frame, reducing stoppage time, allowing return to unrestricted competition after completion of a physical rehabilitation program. This study focus was determination of the formulation therapeutic potential and the evaluation of its synergistic effect in an equine desmitis treatment, utilizing the cells themselves and its secretome.

This work implements a stable algorithm in Field-Programmable Gate Arrays (FPGAs) for which two architectures (unrolling the loop) were developed and analyzed. The algorithm recovers sources located at the boundary separating two homogeneous media that make up a two-dimensional non-homogeneous region from measurements on the boundary of such region. The problem of recovering these sources is an ill-posed inverse problem as small errors in the measurement can produce important changes in the source location. Inverse source problems have many applications in different areas, such as engineering and medicine, making the proposed implementation important. The first architecture (mode one) allows considering different operating speeds, which is an advantage depending on whether we work with fast or slow signals. The second one (mode two) reduces resource consumption by exploiting the characteristics of the source identification algorithm, which is an advantage for multichannel problems such as inverse electrocardiography or electroencephalography. The architectures were tested on four FPGAs of the 7 Series of Xilinx: Spartan-7 xc7s100fgga484, Virtex-7 xc7v585tffg1157, Kintex-7 xc7k70tfbg484, and Artix-7 xc7a35tcpg236. The two FPGA implementations of the algorithm were validated using synthetic examples implemented in MATLAB. The results presented here can be extended to concentric spheres and complex geometries.

Irrational belief is a product of complex personality traits and Machiavellianism Intelligence. The present study is conducted to trace the significance of predictive nature of personality characteristics and Machiavellianism Intelligence (Mach Intelligence) on irrational beliefs among chronically ill older people. The research method is cross-sectional with correlational design, purposive sampling with a total of 200 chronically ill older people aged between 40–60 years with disease type such as Systemic lupus erythematosus, Complicated Diabetes, Glomerulonephritis and Chronic Heart Failure. The analysis revealed that personality characteristics and irrational belief subscales such as worrying, rigidity, problem avoidance and Mach Intelligence are significantly positively correlated; however, Emotional irresponsibility has significant negative correlation with personality characteristics and Mach Intelligence. Gender differences revealed that males are high on all the subscales of personality characteristics, irrational beliefs (except emotional irresponsibility) and Mach Intelligence as com-pared to female chronically ill older people. Predictive analysis also revealed that overall personality characteristics explained a total of 67% variance in irrational beliefs. Moreover, Mach Intelligence predicts irrational beliefs. Future health related recommendations should be planned accordingly.

Articular cartilage healing and repair is one of the biggest clinical challenges in trauma and orthopaedic medicine, leading to high economic loss due to athletic impairment in sport horses. Multipotent Mesenchymal stem/stromal cells are part of novel therapeutic arsenal aimed at tissue regeneration and restoring organ function. These cells release biomolecules and factors in the culture media, producing the so called conditioned medium, which have a pro-regenerative effect through paracrine mechanisms. Considering this, a therapeutic product combining equine synovial membrane derived Mesenchymal stem/stromal cells and equine umbilical cord stroma-derived Mesenchymal stem/stromal cells conditioned medium was employed. In this work the treatment of two articular defects, in the first phalanx and third metacarpus of the left front limb of a five-year-old horse, is described. Following surgical debridement of the lesions, the treatment comprised two intra-articular administrations of the above-mentioned therapeutic combination, 15 days apart. This was followed by a thorough rehabilitation program. A second-round treatment was performed 6 months later. Diagnostic imaging demonstrated significant improvement of the articular defects. The clinical outcome allowed a full return to the athletic performance demonstrating the safety and potential advantages of this approach when compared with other therapeutic options.

Cell secretome has been explored as a cell-free technique with high scientific and medical interest for Regenerative Medicine. In this work, the secretome produced and collected from Olfactory Mucosa Mesenchymal Stem Cells and Olfactory Ensheating Cells was analyzed and therapeutically applied to promote peripheral nerve regeneration. The analysis of the conditioned medium revealed the production and secretion of several factors with immunomodulatory functions, capable of intervening beneficially in the phases of nerve regeneration. Subsequently, the conditioned medium was applied to sciatic nerves of rats after neurotmesis, using Reaxon^® as tube-guides. Over 20 weeks, the animals were subjected to periodic functional assessments, and after this period, the sciatic nerves and cranial tibial muscles were evaluated stereologically and histomorphometrically, respectively. The results obtained allowed to confirm the beneficial effects resulting from the application of this therapeutic combination. The administration of conditioned medium from Olfactory Mucosal Mesenchymal Stem Cells led to the best results in motor performance, sensory recovery, and gait patterns. Stereological and histomorphometric evaluation also revealed the ability of this therapeutic combination to promote nervous and muscular histologic reorganization during the regenerative process. The therapeutic combination discussed in this work shows promising results and should be further explored to clarify irregularities found in the outcomes and to allow establishing the use of cell secretome as a new therapeutic field applied in the treatment of peripheral nerves after injury.

Antimicrobial peptides provide a powerful toolkit for combating multidrug resistance. Combatting eukaryotic pathogens is complicated by the fact, the intracellular drug targets in the eukaryotic pathogen are frequently homologs of cellular structures of vital importance in the host organism. The entomopathogenic bacteria, (symbionts of entomopathogenic nematode species), release a series of non-ribosomal templated antimicrobial peptides, some may be potential drug candidates. The ability of an entomopathogenic nematode /entomopathogenic bacterium symbiotic complex to survive in a given polyxenic milieu is a coevolutionary product, explaining that those gene complexes which are responsible for the biosynthesis of different non-ribosomal templated antimicrobial protective peptides (including those which are potently capable to inactivate the protist mammalian -pathogen Leishmania and the gallinaceous bird pathogen Histomonas) are co-regulated. Our approach is based on comparative antimicrobial bioassays of the culture media of the wild-type and regulatory mutant strains. We concluded that Xenorhabdus budapestensis and X. szentirmaii are excellent sources of non-ribosomal templated antimicrobial peptides, that are efficient antagonists of the mentioned pathogens. Data on selective cytotoxicity of different cell-free culture media encourages us to forecast that the recently discovered “easy-PACId” research strategy is suitable for constructing EPB strains producing and releasing single, harmless, non-ribosomal templated antimicrobial peptides with considerable drug, (probiotic) -candidate potential.

Whether the different NR-AMPs could ever be utilized as drugs not only against prokaryotic (bacteria) pathogens but eukaryotic (fungal pathogens, and parasitic protists) depends on the side effects. To get experimental experience about the option of applying EPB-produced antimicrobials to pathogens, and parasites of veterinary significance, we present here the results of an in vitro, and an accompanying in vivo study on chicken. In the in vitro study, we tested the cytotoxic potential of the cell-free conditioned culture media (CFCM) of three entomopathogenic bacterium species, - X. budapestensis, DSM16342 (EMA); X. szentirmaii DSM16338 (EMC); Photorhabdus luminescens ssp. akhurstii TT01 - on chicken tissue culture cells, namely, on the Leghorn Male Hepatoma (LMH), [92] cells, (a permanent confluent hepato-carcinoma cell line). Each CFCM proved rather cytotoxic in this test. In the in vivo study, we fed freshly hatched male broiler chickens for 42 days with XENOFOOD [39] which contained autoclaved cultures of EMA, and EMC). These bacteria were grown on standard chicken (starter and grower) [HM3] [u4] feed, and the whole culture was used as a “food supplement”. [HM5]. It had been known that these EPB species cannot grow that is, not viable) atbody temperature (above 33 C).