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Background: BK virus (BKV) is a member of the polyomavirus family. The determination of anti-BKV immunoglobulin G (IgG) antibody levels in kidney donors and recipients has been reported as a possible predictor of the risk of BK nephropathy. Allograft dysfunction is a significant risk factor. The main objective of this study was to address the high prevalence of renal failure due to BKV nephropathy in kidney transplant recipients. This investigation aims to determine whether donors and recipients of renal transplants had BKV IgG antibodies before transplantation. Methods: Blood samples were collected from 46 kidney transplant recipients and their corresponding 46 donors. An enzyme-linked immunosorbent assay was used to qualitatively analyze human BKV IgG. Results: Ninety-two participants, 46 kidney transplant donors, and 46 kidney transplant recipients, were analyzed. Pretransplantation anti-BKV antibody levels were higher in kidney transplant donors (73%) than in recipients (63%). Donors and recipients included in the study were grouped into seropositive and seronegative recipients, with the highest proportion of seropositive recipient-donor groups (48%) and the lowest percentages in the seronegative donor and seronegative recipient groups. Fifty-one percent of the participants were male and 49% were female. The age distribution of most subjects was >50 years old. Conclusion: BKV can cause kidney transplant rejection. Routine screening of transplant recipients and donors for BKV IgG seropositivity is recommended before renal transplantation. This can improve transplant outcomes and prevent rejection.

Background: The COVID-19 pandemic has exacerbated the global overdose crisis, increased opioid-related deaths and highlighted the need for innovative treatment strategies. This study critically evaluates the efficacy of take-home methadone for patients with opioid use disorders (OUDs) during public health emergencies. Methods: Adhering to PRISMA reporting guidelines, this systematic review scrutinized RCTs and quasi-experimental studies on opioid agonist treatments (OATs), notably methadone, from Medline, Web of Science (core collection), Embase, Cochrane Library, and Scopus, spanning January 2020 to May 2024. It targeted global patients of any age, contrasting take-home methadone with in-clinic dosing, omitting non-English studies or those solely analyzing program delivery modifications without take-home dose discussions. Key outcomes included emergency room (ER) visits, treatment retention, overdose rates, alongside secondary outcomes like patient health, quality of life (QoL), and satisfaction. Registered with PROSPERO (CRD42023474723), the review prioritized treatment impacts and language inclusivity. Findings: The final search yielded 1,222 records, with two studies included (four records). Despite included only two studies (four records) due to a focused selection criterion, findings indicate overall participant satisfaction with take-home methadone, suggesting its potential as a viable treatment modality during public health emergencies. However, the limited study number and focus on indirect outcome measures underscore the need for further comprehensive research. Interpretation: This review champions flexible dosing, technology integration, and stigma reduction in OUD treatment, urging longitudinal research on take-home methadone's continued impacts. Despite constraints, it enriches OUD management for enhanced public health outcomes, highlighting future research avenues.

Heat transfer occurs as a result of density differences caused by temperature changes. It has several industrial applications. To improve performance, one must investigate the heat transfer behaviour of the working fluid. Hence, the purpose of this work is to report a heat transfer analysis of a partially heated trapezoid cavity filled with a hybrid nanofluid. The temperature conditions of the cavity are such that the bottom boundary is partially heated, inclined side boundaries are kept at a lower temperature, and the upper boundary is kept adiabatic. A trapezoidal shape heated obstacle is considered in the cavity’s centre. The heat transfer and flow take place inside the cavity due to density variation. The mechanism is regulated by mass, momentum, and energy conservation, as well as related boundary constraints. The solutions are determined by the use of a numerical technique known as the Finite Element Method after the governing equations are transformed into non-dimensional form, which brings up physical parameters affecting the heat transfer and flow. The initial study is performed for three types of nanofluids with silver 𝐴𝑔 and magnesium oxide 𝑀𝑔𝑜 nanoparticles inside water 𝐻2𝑂, kerosene 𝐾𝑒, and engine oil 𝐸𝑂. The study revealed that the engine oil-based hybrid nanofluid produced an increased heat transfer rate. Simulation is performed using engine-based hybrid nanofluid with the range of physical parameters, such as Rayleigh number 𝑅𝑎 (105≤𝑅𝑎≤107), Hartmann number 𝐻𝑎 (0≤𝐻𝑎≤100) and nanoparticles volume fraction 𝜙 (0≤𝜙≤0.2). It is found that the heat transfer rate is enhanced by increasing the fraction of nanoparticles in the base fluid. Moreover, imposition of magnetic field has reverse impact on the fluid movement.

The aim of the current study is to investigate the heat transfer performance of 𝐴𝑙2𝑂3 and 𝐶𝑢 nanoparticles suspended based in 𝐻2𝑂 nanofluids inside a partially heated C-shaped enclosure. The governing equations for heat and flow transfer are solved using the Finite Element Method. Heat transmission is affected by the type and form of nanoparticles. To study the improved heat transfer performance, four different shapes of nanoparticles-spherical, cylindrical, column, and lamina-have been used. The investigation showed that among the considered shapes of nanoparticles, the lamina shape of nanoparticles performed best. Considering lamina nanoparticles, in comparison to the simple nanofluids 𝐴𝑙2𝑂3−𝐻2𝑂 and 𝐶𝑢−𝐻2𝑂 the hybrid nanofluid 𝐴𝑙2𝑂3−𝐶𝑢−𝐻2𝑂 provides the enhanced heat transfer rate. The heat transfer is governed by convection at a higher Rayleigh number. On the other hand, the heat transfer rate is decreasing by increasing the impact of the magnetic field. For the increased heat transfer rate, the best choice is lamina nanoparticles and hybrid nanofluid 𝐴𝑙2𝑂3−𝐶𝑢−𝐻2𝑂.

Abstract Background Clinical utility of Ki-67 immunohistochemistry (IHC) in breast cancer (BC) is mainly limited to decide for the use of chemotherapy and estimate prognosis in patients with either Ki-67 index 30%; however, lacunae still exists pertaining to its analytical validity. Neutrophilia is common in cancer with accompanying lymphocytopenia. Neutrophil to lymphocyte ratio (NLR) captures the intricate balance between pro-tumor neutrophilia and anti-tumor lymphocyte immunity. This study aimed to correlate cellular proliferation in breast cancer with NLR. Methods An observational study was carried out including 73 cases of BC; pre-treatment NLR and Ki-67 grading were performed. NLR 0.05) and molecular subtype (p > 0.05); however, NLR was found to be significantly correlated with TNM stage (p

Treatment of carbapenem-resistant Acinetobacter baumannii (CRAb) infections has become a significant challenge for physicians due to its resistance to common antibiotics. Colistin, previously banned, has been reintroduced despite debates about its effectiveness and safety. We aimed to synthesize evidence on the effectiveness of Colistin in the CRAb infection management, based on current literature. We conducted a comprehensive search to identify relevant studies on the effectiveness of Colistin in treating CRAb infection in major databases such as Medline through PubMed, Embase, Web of Science, The Cochrane Library, and Scopus. We did not limit the search by age of participants, sex, region, or year of publication, but we only included randomized controlled trials (RCTs), quasi-experimental studies, cohort studies, case-control studies, and cross-sectional studies published in English, which had at least one comparison control group. Two independent authors screened articles, extracted data, and assessed the risk of bias in selected articles using the RoBANS tool. Our search retrieved 7907 articles, of which five were included after the sequential screening. All five studies were retrospective case-control studies from five different countries, with a total of 776 participants. Two studies showed a lower mortality rate in the intervention (Colistin) group as the primary outcome, whereas two studies showed the opposite mortality trend. One study reported a higher rate of infection remission in the intervention group, but the result was not statistically significant. Our systematic review could not find any robust evidence to support the effectiveness of Colistin over commonly used antibiotics. Due to the large discrepancy among the primary outcomes of the included studies, we recommend further randomized controlled trials with a larger number of participants to determine the suitability of Colistin for treating CRAb infections.

Ferroptosis is a recently discovered iron dependent form of programmed cell death, characterized by accumulation of lipid reactive oxygen species (ROS). It shows a strikingly different set of morphological characteristics from other forms of cell death, like reduced mitochondrial volume, increased bi-layer membrane density, and reduction of mitochondrial cristae with absence of any nuclear changes. Ferroptosis is mainly regulated by two core biochemical processes, namely iron accumulation and lipid peroxidation. Lipid peroxides exert their toxic effects by disturbing the integrity, structure and composition of bi-lipid cell membranes. However, being highly reactive compounds, they further propagate the generation of ROS, leading to cross-linking of DNA and proteins. Key regulators of ferroptosis include various genes involved in the above pathways, inhibition of the antioxidant system and upregulation of the oxidant system. Recent studies have shown the ferroptotic pathway to be involved in the patho-physiology of many diseases, including cancer. Understanding the biochemical mechanisms and key substances upregulating/inhibiting this pathway, may have an implication towards development of targeted therapies for various cancers, and, hence, has become a hotspot for biomedical research. This review article summarizes the core biochemical processes involved in ferroptosis, with a brief summary of its role in various diseases and possible therapeutic targets.

Purpose: The purpose of the current study is to determine whether patients diagnosed with glioblastoma multiforme (GBM) who underwent radiotherapy (RT) using intensity-modulated RT (IMRT) technique were benefitting from this highly conformal treatment in terms of doses received by planning target volume (PTV) and organs at risk (OARs) in comparison to three-dimensional conventional RT (3DCRT). Materials and Methods: Twelve patients treated with IMRT for GBM were selected for dosimetric comparison with 3DCRT. The prescribed dose was 60 Gy in 30 fractions and seven non-coplanner beams were used in IMRT to cover 95% of target volume. The irradiated patients of GBM were retrieved and replanned with 3DCRT techniques. Dosimetric comparison was done by performing two plans for the same patient; prescription dose and normal tissue constraints were identical for both plans. The dose–volume histograms of target volumes and OAR, dose conformity, and dose homogeneity with 3DCRT and IMRT planning were compared. Statistical analysis was performed to determine the differences. Results: The mean conformity index was 0.99 ± 0.001 for IMRT and 0.97 ± 0.002 for 3DCRT, P = 0.001. The mean homogeneity index was 1.03 ± 0.02 for IMRT and 1.06 ± 0.009 for 3DCRT, P = 0.003, which is statistically significant. The IMRT technique enables dose reduction of normal tissues including brainstem (Dmean by 33.78 ± 5.34 and Dmax 51.84 ± 4.43), optic chiasm (Dmean by 36.92 ± 1.99 and Dmax 44.61 ± 3.72), left optic nerve (Dmean by 28.97 ± 6.51 and Dmax 46.08 ± 10.58), right optic nerve (Dmean by 31.93 ± 11.68 and Dmax 44.63 ± 13.54), left eye (Dmean by 18.66 ± 8.92 and Dmax 37.43 ± 13.47), right eye (Dmean by 14.40 ± 4.87 and Dmax 40.37 ± 11.37), left lens (by Dmax 5.45 ± 1.85), and right lens (Dmax 5.07 ± 0.63). Conclusion: The IMRT provides a real dosimetric advantage, especially for normal brain tissue, and in terms of target coverage. It allows treatment of tumors while respecting OARs' dose constraints. The IMRT technique shows significant advantage in PTV coverage, dose homogeneity, and conformity. In IMRT, the coverage is better where PTV was overlapping with critical OARs.

Background: The demographic profile and fatality varied across different waves with the appearance of new variants. Further the trends varied from country to country and within the country. We have analyzed the trends from a selected geographic area. Aims and Objectives: To assess the trends in COVID-19 cases and deaths and to compare the characteristics of three different COVID-19 waves in Kashmir Division. Materials and Methods: It is a cross sectional study based on secondary data. Results: The mean age of deaths increased from 64.53 years in first wave to 65.02 years in the second wave and further to 69.23 years in the third wave (p-value = 0.006). An overall CFR of 0.85% was observed in our population with a maximum case fatality of 1.67% in first wave followed by 0.79% in second wave and only 0.13% in third wave (p < 0.0001). Lowest CFR of 0.04% was observed in the age group of

Abstract The chemical senses of olfaction and taste are well developed in fish and play a vital role in its various activities such as navigation, mate recognition, and food detection. The small teleost fish Astyanax mexicanus consists of interfertile river‐dwelling and cave‐dwelling populations, referred to as “surface fish” and “cavefish” respectively. An important anatomical feature of cavefish is the lack of eyes leading them to be referred to as blind fish and suggesting an enhanced functional role for other senses such as taste. In this study, we characterize the expression of bitter taste receptors (T2Rs or Tas2Rs) in A. mexicanus and investigate their functionality in a heterologous expression system. The genome database of A. mexicanus (ensemble and NCBI) showed 7 Tas2Rs, among these Tas2R1, Tas2R3, Tas2R4, and Tas2R114 are well characterized in humans and mice but not in A. mexicanus. Therefore, the 4 Tas2Rs were selected for further analysis and their expression in A. mexicanus was confirmed by in situ hybridization and RT‐PCR in early developmental stages. These Tas2Rs are expressed in various oral and extraoral organs (liver, fins, jaws, and gills) in A. mexicanus, and Tas2R1 has maximum expression and is localized throughout the fish body. Using the heterologous expression of A. mexicanus T2Rs in HEK293T cells coupled with cell‐based calcium mobilization assays, we show that A. mexicanus T2Rs are activated by commonly used fish food and known bitter agonists, including quinine. This study provides novel insights into the extraoral expression of T2Rs in A. mexicanus and suggests their importance in extraoral food detection.

Background and Aims: Acute appendicitis is one of the most common surgical emergencies encountered by general surgeon. Early diagnosis and management is critical in order to prevent drastic complication. This study was done to analyze the applicability and accuracy of RIPASA scoring in diagnosing acute appendicitis. Methods: This prospective observational study included all the patients above the age of 12 years with clinical feature of acute appendicitis admitted in surgery department. Patients with palpable appendicular lump, appendicular abscess, previous history of urolithiasis and pelvic inflammatory disease were excluded from the study. All the patients were evaluated with complete history taking and clinical examination and subjected to baseline investigation. The patients were subjected to routine baseline investigations including abdominal ultrasonography. We used RIPASA scoring system for all our subject to reach the definitive diagnosis of acute appendicitis. The score has 14 parameters and each parameter is given a numerical value. We classified the patients into four groups according to the score; a) Score 12.0= Definite acute appendicitis. The patients were properly resuscitated before any surgical intervention. Informed written consent was taken and procedure details were explained to the patient and legal attendant. Results: Total of 100 patients was studied. Out of total 100 patients 93 patients (93%) were documented as having appendicitis by histopathology where as 7% of patients had no evidence of appendicitis on histopathology. The sensitivity and specificity of RIPASA scoring system in our study came out to be 92.47% and 86.92% respectively. The positive predictive value and negative predictive values were 86% and 93% respectively. The diagnostic accuracy rate and negative appendectomy rate were 85.56% and 7% respectively. Conclusion: The RIPASA scoring system is easy and simple to apply as majority of the parameters can be obtained from history, clinical examination and few laboratory tests and looked promising when applied to our setting with better sensitivity, specificity, and diagnostic accuracy.

In this paper, a Photonic Crystal Fiber (PCF) based Surface Plasmon Resonance (SPR) biosensor for the detection of four bacteria such as Vibrio Cholera, Escherichia Coli (E. coli), Bacillus Anthracis, and Enterococcus Faecalis is proposed and evaluated numerically using finite element method (FEM)-based simulation tool. The proposed sensor exhibits excellent performance characteristics and has the configuration of identifying analyte samples externally. The sensor is designed with a basic square lattice of PCF, covered with a thin chemically stable gold layer. The proposed sensor can detect these four bacteria from pure water and has the highest wavelength sensitivity of 5161 nm/RIU for Enterococcus Faecalis. Other critical parameters such as Signal to Noise Ratio, Detection Limit, Sensor Length, Quality Factor, and Detection Accuracy are also calculated and presented for the proposed PCF biosensor.

Fauziah Rabbani,1,2 Hyder Ali Khan,2 Suneel Piryani,2 Nousheen Akber Pradhan,2 Natasha Shaukat,2 Anam Shahil Feroz,2 Shagufta Perveen2 1Office of Research and Graduate Studies, The Aga Khan University, Karachi, Sindh, Pakistan; 2Department of Community Health Sciences, The Aga Khan University, Karachi, Sindh, PakistanCorrespondence: Fauziah RabbaniOffice of Research and Graduate Studies, The Aga Khan University, Stadium Road, P.O Box 3500, Karachi, 74800, Sindh, PakistanEmail fauziah.rabbani@aku.eduPurpose: Diarrhea and pneumonia greatly contribute to high childhood mortality in Pakistan. Frontline community health workers or the Lady Health Workers (LHWs) provide care at the doorstep of over 60% of Pakistan’s rural residents. Difficult terrain, lack of supplies, and inadequate supervision put these LHWs at an added disadvantage in the timely diagnosis and delivery of known treatment options to community caregivers (CCGs). This study aims to assess whether a supportive supervision intervention through Lady Health Supervisors (LHSs) using enhanced mentorship and written feedback cards have the potential to improve case management of childhood diarrhea and pneumonia.Study Setting and Design: This perception-based qualitative inquiry nested within the Nigraan Plus trial included LHSs, LHWs, and CCGs as the participants. Twenty-two in-depth interviews (IDIs) and 16 focus group discussions (FGDs) were conducted before a supportive supervision intervention in 2017, and 10 FGDs were conducted in 2019 once the intervention concluded. Data were analyzed using manual content analysis.Results: The perceived ability of LHWs and LHSs to describe the danger signs of diarrhea and pneumonia, classify dehydration and relate respiratory rate to the severity of pneumonia improved over time. Appropriate prescription of zinc in diarrhea and antibiotics in pneumonia was noted. Furthermore, CCGs’ trust in LHWs increased following the intervention, and they reported a growing inclination to contact LHWs as their first point of care. LHWs in the intervention arm were more satisfied with their job due to frequent supervisory visits and continuous feedback by LHSs.Conclusion: Despite geographic, social, and economic inequities, supportive supervision has the potential to improve knowledge, practice, and skills of frontline health workers related to CCM of childhood diarrhea and pneumonia in disadvantaged rural communities. Additionally, the trust of CCGs in the health workers’ ability to manage such cases is also enhanced.Keywords: community health workers, community caregivers, community case management, childhood diarrhea and pneumonia, supportive supervision, Pakistan

In many countries where funding for education has been directed at improving access, the redirection towards funding of quality education has been slow. In Fiji, studies have found that symptoms of the lack of funding for quality education include: large class sizes in urban areas; multi-grade classes in rural areas; low levels of qualifications in the teaching force; teachers’ general frustration with curriculum development; and the pressures of external examination systems as asystemmatic. In this context, the pressures on individual teachers are high, while support for them and for the schools they serve is low. An aspect that was discussed of the result of this ongoing pressure is the impact on pre-service teachers who become part of these school communities for their field experience (or practicum). This paper reports on the frustrations and disappointments expressed by one group of pre-service teachers as they reflect on their practicum experiences in schools in Fiji qualitative research design and data gathered were content analyzed. The findings shed light on the difficulties faced by all teachers in Fiji. Recommendations include not only supporting pre-service teachers during their practicum, but also supporting the teachers in the field whose responsibility for preparing the new generation of teachers is sometimes taken for granted.

Introduction: Austere environments include the wilderness and many lower- and middle-income countries, with many of these countries facing unrest and war. The access to advanced diagnostic equipment is often unaffordable, even if available, and the equipment is often liable to break down. Methods: A short review paper examining the options available to medical professionals to undertake clinical and point-of-care diagnostic testing in resource-constrained environments that also illustrates the development of mobile advanced diagnostic equipment. The aim is to provide an overview of the spectrum and functionality of these devices beyond clinical acumen. Results: Details and examples of products covering all aspects of diagnostic testing are provided. Where relevant, reliability and cost implications are discussed. Conclusions: The review highlights the need for more cost-effective accessible and utilitarian products and devices that will bring cost-effective health care to many in lower- and middle-income or austere environments.

The objective of present study was to investigate the effect of incorporation of varying concentrations (2% to 14%) of Tragacanth gum (TG) to alginate/aloe vera composite films to enhance their functional properties. The resulting films were investigated for their mechanical, barrier, optical properties and biodegradability. The WVP, swelling capacity and thickness of films increased significantly by the addition of TG while film solubility was dropped at higher concentration of TG. It was observed that TG acted as an efficient reinforcing agent for enhancing the strength and flexibility of the films. The tensile strength (TS) of films increased more than threefold as compared to control, reaching a maximum value 67.64 N/mm2at 12% concentration of TG. Colour properties were affected by the addition of TG as the higher the concentration, the darker the films.

ABSTRACT β-Lactam antibiotics exploit the essentiality of the bacterial cell envelope by perturbing the peptidoglycan layer, typically resulting in rapid lysis and death. Many Gram-negative bacteria do not lyse but instead exhibit “tolerance,” the ability to sustain viability in the presence of bactericidal antibiotics for extended periods. Antibiotic tolerance has been implicated in treatment failure and is a stepping-stone in the acquisition of true resistance, and the molecular factors that promote intrinsic tolerance are not well understood. Acinetobacter baumannii is a critical-threat nosocomial pathogen notorious for its ability to rapidly develop multidrug resistance. Carbapenem β-lactam antibiotics (i.e., meropenem) are first-line prescriptions to treat A. baumannii infections, but treatment failure is increasingly prevalent. Meropenem tolerance in Gram-negative pathogens is characterized by morphologically distinct populations of spheroplasts, but the impact of spheroplast formation is not fully understood. Here, we show that susceptible A. baumannii clinical isolates demonstrate tolerance to high-level meropenem treatment, form spheroplasts upon exposure to the antibiotic, and revert to normal growth after antibiotic removal. Using transcriptomics and genetic screens, we show that several genes associated with outer membrane integrity maintenance and efflux promote tolerance, likely by limiting entry into the periplasm. Genes associated with peptidoglycan homeostasis in the periplasm and cytoplasm also answered our screen, and their disruption compromised cell envelope barrier function. Finally, we defined the enzymatic activity of the tolerance determinants penicillin-binding protein 7 (PBP7) and ElsL (a cytoplasmic ld-carboxypeptidase). These data show that outer membrane integrity and peptidoglycan recycling are tightly linked in their contribution to A. baumannii meropenem tolerance. IMPORTANCE Carbapenem treatment failure associated with “superbug” infections has rapidly increased in prevalence, highlighting the urgent need to develop new therapeutic strategies. Antibiotic tolerance can directly lead to treatment failure but has also been shown to promote the acquisition of true resistance within a population. While some studies have addressed mechanisms that promote tolerance, factors that underlie Gram-negative bacterial survival during carbapenem treatment are not well understood. Here, we characterized the role of peptidoglycan recycling in outer membrane integrity maintenance and meropenem tolerance in A. baumannii. These studies suggest that the pathogen limits antibiotic concentrations in the periplasm and highlight physiological processes that could be targeted to improve antimicrobial treatment.

Video-recorded robotic-assisted surgeries allow the use of automated computer vision and artificial intelligence/deep learning methods for quality assessment and workflow analysis in surgical phase recognition. We considered a dataset of 209 videos of robotic-assisted laparoscopic inguinal hernia repair (RALIHR) collected from 8 surgeons, defined rigorous ground-truth annotation rules, then pre-processed and annotated the videos. We deployed seven deep learning models to establish the baseline accuracy for surgical phase recognition and explored four advanced architectures. For rapid execution of the studies, we initially engaged three dozen MS-level engineering students in a competitive classroom setting, followed by focused research. We unified the data processing pipeline in a confirmatory study, and explored a number of scenarios which differ in how the DL networks were trained and evaluated. For the scenario with 21 validation videos of all surgeons, the Video Swin Transformer model achieved ~0.85 validation accuracy, and the Perceiver IO model achieved ~0.84. Our studies affirm the necessity of close collaborative research between medical experts and engineers for developing automated surgical phase recognition models deployable in clinical settings.

In this paper, an extremely sensitive Photonic Crystal Fiber (PCF) based Surface Plasmon Resonance (SPR) sensor having D-shaped structure has been proposed. Gold has been used as the plasmonic material, and it has been coated outside of the fiber on its glassy surface to detect the change in the refractive index of the surrounding medium. Gold has been chosen as it is chemically stable and has no impact on the surrounding aqueous medium. Maximum Wavelength Sensitivity (WS) of 216,000 nm/RIU and Amplitude Sensitivity (AS) of 1680 RIU-1 have been achieved for the analyte refractive index range 1.23 to 1.42 by the proposed sensor. After conducting a detailed literature review in the relevant field, it has been revealed that the proposed sensor possesses the highest wavelength sensitivity among recently reported PCF-SPR sensors to this date. The proposed sensor also exhibits a resolution of 4.63 × 10-7 RIU and FOM of 1200. Consequently, the proposed sensor can become an ideal candidate in the field of biomedical sensing, chemical sensing, and other lower RI analytes sensing.

Remarkable advances in histocompatibility testing have immensely improved the safety of transplantation and have decreased the incidence of rejections. Human leukocyte antigen (HLA) typing and crossmatches by complement-dependent cytotoxicity or flow cytometer-based methods are the vital tests involved in pretransplant histocompatibility testing. Continuous development in these testing technologies since the 1960s has refined these methodologies that can be used to predict graft rejection. Advancements from polymerase chain reaction-based methods to sequence based in HLA typing, and from cell-based cross-matches to virtual cross-matches using advanced solid-phase platforms, have enhanced our understanding about the donor-specific antibodies (DSAs) and have challenged the concept that the presence of DSA is an absolute contraindication to transplantation. Despite various developments, it is very difficult to perform a plethora of tests for pretransplant workup due to cost constraints in a developing country like India. In this review, we would discuss the advantages, limitations, and cost involved in the pretransplant immunologic workup along with an algorithmic approach for physicians that may help in decision-making amidst multiple information from different platforms.

Abstract High concentrations of carotenoids are protective against cardiometabolic risk traits (CMTs) in adults and children. We recently showed in non-diabetic Mexican American (MA) children that serum α-carotene and β-carotene are inversely correlated with obesity measures and triglycerides and positively with HDL cholesterol and that they were under strong genetic influences. Additionally, we previously described a Pediatric Metabolic Index (PMI) that helps in the identification of children who are at risk for cardiometabolic diseases. Here, we quantified serum lycopene and β-cryptoxanthin concentrations in approximately 580 children from MA families using an ultraperformance liquid chromatography-photodiode array and determined their heritabilities and correlations with CMTs. Using response surface methodology (RSM), we determined two-way interactions of carotenoids and PMI on Matsuda insulin sensitivity index (ISI). The concentrations of lycopene and β-cryptoxanthin were highly heritable [h2 = 0.98, P = 7 × 10–18 and h2 = 0.58, P = 1 × 10–7]. We found significant (P ≤ 0.05) negative phenotypic correlations between β-cryptoxanthin and five CMTs: body mass index (− 0.22), waist circumference (− 0.25), triglycerides (− 0.18), fat mass (− 0.23), fasting glucose (− 0.09), and positive correlations with HDL cholesterol (0.29). In contrast, lycopene only showed a significant negative correlation with fasting glucose (− 0.08) and a positive correlation with HDL cholesterol (0.18). Importantly, we found that common genetic influences significantly contributed to the observed phenotypic correlations. RSM showed that increased serum concentrations of α- and β-carotenoids rather than that of β-cryptoxanthin or lycopene had maximal effects on ISI. In summary, our findings suggest that the serum carotenoids are under strong additive genetic influences and may have differential effects on susceptibility to CMTs in children.

Summary: Background: There is an enormous knowledge gap on management strategies, clinical outcomes, and follow-up after kidney transplantation (KT) in recipients that have recovered from coronavirus disease (COVID-19). Methods: We conducted a multi-center, retrospective analysis in 23 Indian transplant centres between June 26, 2020 to December 1, 2021 on KT recipients who recovered after COVID-19 infections. We analyzed clinical and biopsy-confirmed acute rejection (AR) incidence and used cox-proportional modeling to estimate multivariate-adjusted hazard ratios (HR) for predictors of AR. We also performed competing risk analysis. Additional outcome measures included graft loss, all-cause mortality, waiting time from a positive real-time polymerase test (RT-PCR) to KT, laboratory parameters, and quality of life in follow-up. Findings: Among 372 KT which included 38(10·21%) ABO-incompatible, 12(3·22%) sensitized, 64(17·20%) coexisting donors with COVID-19 history and 20 (5·37%) recipients with residual radiographic abnormalities, the incidence of AR was 34 (9·1%) with 1(0·26%) death censored graft loss, and 4(1·07%) all-cause mortality over a median (interquartile range) follow-up of 241 (106–350) days. In our cox hazard proportional analysis, absence of oxygen requirement during COVID-19 compared to oxygen need [HR = 0·14(0·03–0·59); p-value = 0·0071], and use of thymoglobulin use compared to other induction strategies [HR = 0·17(0·03–0.95); p-value = 0·044] had a lower risk for AR. Degree of Human leukocyte antigen (HLA) DR mismatch had the highest risk of AR [HR = 10.2(1·74–65·83); p-value = 0·011]. With competing risk analysis, with death as a competing event, HLA DR mismatch, and oxygen requirement continued to be associated with AR. Age, gender, obesity, inflammatory markers, dialysis vintage, steroid use, sensitization and ABO-incompatibility have not been associated with a higher risk of AR. The median duration between COVID-19 real time polymerase test negativity to transplant was 88(40–145) days (overall), and ranged from 88(40–137), 65(42–120), 110(49–190), and 127(64–161) days in World Health Organization ordinal scale ≤ 3, 4, 5, and 6–7, respectively. There was no difference in quality of life, tacrolimus levels, blood counts, and mean serum creatinine assessed in patients with a past COVID-19 infection independent of severity. Interpretation: Our findings support that the outcomes of KT after COVID-19 recovery are excellent with absence of COVID-19 sequelae during follow-up. Additionally, there does not seem to be a need for changes in the induction/immunosuppression regimen based on the severity of COVID-19. Funding: Sanofi

High voltage alternating current and high voltage direct current has inspired different authors to concentrate on insulation system, that withstand the rising high voltage level; various researchers have carried out experimental work to prove strength and abilities of transformer oil. This is done by adding different nanoparticles in the oil (Nano fluid) for different transformer applications. In short, this study presents a collection of research studies, which involves preparation of various types of nanomaterial's and their synthetisation. The performance of Nano fluids like electrical breakdown voltage, impulse test and dielectric and thermal behaviour has also been discussed in detail.

Data are scarce regarding the prevalence of frailty in elderly patients undergoing maintenance hemodialysis (HD) in India. We conducted a cross-sectional observational study aimed to study the prevalence of frailty and cognitive dysfunction in patients aged 75 years or more undergoing maintenance HD in three tertiary care hospitals and associated stand-alone dialysis centers in North Kerala. Frailty was ascertained by two methods. In method 1 (physical performance measurement based), dichotomous scoring (0 or 1) of five domains, namely weight loss, exhaustion, low physical activity, weak grip, and slow walking, was done, and a score of 3/5 was used to define frailty. In method 2 (self-report measure based), scores on the Medical Outcomes Study Short-Form 36-item Questionnaire (SF-36) physical function domain were used instead of hand grip strength and walking speed, and a score of 3 years in 33.3% of patients. Frailty was documented in 22 (56.4%) patients by method 1 and in 25 (64.1%) by method 2. There was a statistically significant difference between the two methods in documenting frailty (P < 0.001, Chi-square test). Cognitive impairment was present in 89.7% of patients and significantly associated with frailty (P < 0.001, Fisher’s exact test). Frailty and cognitive dysfunction are highly prevalent in elderly people undergoing maintenance HD in North Kerala. Physical performance and self-report measure-based methods correlate well in frailty documentation.

Transplantation across the ABO blood group (ABOI-Tx) has facilitated to increase in donor pool for living donor kidney transplantation. Increased risk of rejection despite augmented immunosuppression has been the concern for many transplant programs in initiating an ABOI-TX program. The benefits of induction immunosuppression on long-term graft survival in immunologically low-risk individuals are still not clear. Increased immunosuppression of ABOI-Tx recipients before transplantation could provide an opportunity to transplant without induction with IL2-R blockers or Lymphocyte depleting agents. The aim of our study is to analyze the outcome of our series of 25 consecutive ABOI-Tx patients who underwent transplantation without routine thymoglobulin or IL2R-blocker induction. Our study is a prospective observational study for the first 25 consecutive patients who had undergone ABOI-Tx from two tertiary care centers in Kerala, India, having the same IS protocol. Anti-A and anti-B titers ≤1:512 by Gel-method (Biorad) were accepted for desensitization. Patients underwent CDC-crossmatch, Flow-crossmatch, and Luminex-anti-HLA-antibody-screen. Desensitization regimen included- Rituximab 200 mg on Day-21, Triple IS Prednisolone 10 mg, mycophenolate mofetil 1000 mg, and Tacrolimus 0.06 mg/bodywt from Day-14 and Plasma-exchange (PLEX) 3-4 sessions from day -7 to attain titer of 1:8 before transplantation. Transplantation was done without induction IS. Twenty-five patients underwent ABOI-Tx from both centers. Twenty recipients were male. The average age was 34.5 ± 8 years with follow-up of 503 ± 120 days. Eight donors were spouse, 13 were parents and three siblings. The average age of the donor was 46.3 ± 10.5 years. Twenty-two patients have normal functioning transplant with creatinine 1.23 ± 0.2 mg/dL. Kaplan–Meier analysis showed patient survival of 91.2% and death censored graft survival of 95.6% at 36 months. Two patients were lost; one on the postoperative day (POD)-3 due to ACS and second on POD-22 due to sepsis. One graft loss occurred due to posttransplant HUS. Of the functioning 22 allograft-recipients, one had cellular rejection, which resolved with pulse steroids; one developed HUS due to CNI, which recovered with PLEX and switch to non-CNI based IS. One patient developed AMR on POD-4, which was completely reversed with PLEX, intravenous immunoglobulin (IVIG), and augmentation of IS. Three patients had CMV viremia and another three patients had BKV viremia, all resolved with treatment and tailoring of IS. Achieving acceptable anti-A/B titers prior to transplantation is the most critical step in ABOI-Tx. Avoidance of induction IS can reduce cost and infectious complications. Our data showed that there is no increased incidence of rejections in the first post-transplant year for immunologically low-risk individuals from histocompatibility standpoint undergoing ABOI-Tx without induction immunosuppression.

Abstract Background Doctors, despite being the public health leaders, are predisposed to the early development of chronic noncommunicable diseases (NCDs). This study was done to determine the prevalence of risk factors of NCDs among doctors. Methods A cross‐sectional study was conducted among the doctors of a course under the Distance Learning Program at BIRDEM General Hospital, Dhaka. It was done from March 2015 to February 2016. Data were collected using a self‐administered questionnaire, and physical and biochemical measurements. However, the measured variables were collected by the investigators. WHO STEPS questionnaire V 3.1, with adaptation to the local context, was used. Results A total of 404 (223 men and 181 women) of 451 registered doctors participated (89.6%) in the study. The prevalence of smoking was 18.8% among men, and there was no woman smoker. Among the respondents, 17% of men and 0.6% of women drank alcohol at least once in their lifetime. Low physical activity (

Background We have shown previously that low‐density lipoprotein (LDL) can be oxidized in the lysosomes of macrophages, that this oxidation can be inhibited by cysteamine, an antioxidant that accumulates in lysosomes, and that this drug decreases atherosclerosis in LDL receptor–deficient mice fed a high‐fat diet. We have now performed a regression study with cysteamine, which is of more relevance to the treatment of human disease. Methods and Results LDL receptor–deficient mice were fed a high‐fat diet to induce atherosclerotic lesions. They were then reared on chow diet and drinking water containing cysteamine or plain drinking water. Aortic atherosclerosis was assessed, and samples of liver and skeletal muscle were analyzed. There was no regression of atherosclerosis in the control mice, but cysteamine caused regression of between 32% and 56% compared with the control group, depending on the site of the lesions. Cysteamine substantially increased markers of lesion stability, decreased ceroid, and greatly decreased oxidized phospholipids in the lesions. The liver lipid levels and expression of cluster of differentiation 68, acetyl–coenzyme A acetyltransferase 2, cytochromes P450 (CYP)27, and proinflammatory cytokines and chemokines were decreased by cysteamine. Skeletal muscle function and oxidative fibers were increased by cysteamine. There were no changes in the plasma total cholesterol, LDL cholesterol, high‐density lipoprotein cholesterol, or triacylglycerol concentrations attributable to cysteamine. Conclusions Inhibiting the lysosomal oxidation of LDL in atherosclerotic lesions by antioxidants targeted at lysosomes causes the regression of atherosclerosis and improves liver and muscle characteristics in mice and might be a promising novel therapy for atherosclerosis in patients.

The internal fluidic parameters of microfluidic channels must be analyzed to solve fundamental microfluidic problems, including microscale transport problems involving thermal analysis, chemical reactivity, velocity, pressure drop, etc., for developing good-quality chemical and biological products. Therefore, the characterization and optimization of the interaction of chemical and biological solutions through microfluidic channels are vital for fluid flow design and engineering for quality assurance in microfluidic platforms. As the internal structures and kinetics of microfluidic channels are becoming increasingly complex, experiments involving optimal fluidic and transport designs are challenging to perform with high accuracy. However, highly integrated simulation tools can guide researchers without specialized computational fluid backgrounds to design numerical prototypes of highly integrated devices. In this study, a microfluidic chip with two inlet wells and one outlet well was fabricated from polydimethylsiloxane following which simulations were performed using an ANSYS Fluent tool influenced by computational fluid dynamics at a nearly identical scale. The pressure drop and velocity profiles of the interaction of two pH buffer solutions (pH 4 and 10) through the designed microfluidic chip were qualitatively estimated from experimental data analysis and validated with the simulation results obtained from the CFD-influenced ANSYS Fluent tool.

A highly sensitive surface plasmon resonance (SPR) sensor on a dual-core photonic crystal fiber (PCF) for low refractive index (RI) detection is presented in this paper. Plasmonic material silver (Ag) is deposited outside of the fiber structure to detect changes of the surrounding medium's refractive index. To prevent oxidation a thin layer of titanium dioxide (TiO2) is employed on top of the silver. The sensor shows maximum wavelength sensitivity and amplitude sensitivity of 116,000 nm/RIU and 2452 RIU-1 with corresponding resolutions (R) of 8.62 × 10-7 and 5.55 × 10-6 RIU, respectively. A thorough study of the relevant literature yielded that these attained sensitivities in both interrogation methods are the highest among reported PCF-SPR sensors to date. In addition, the sensor possesses a very high figure of merit of 2320 in the sensing range of 1.29 to 1.39. Therefore, it would be a suitable candidate for pharmaceutical inspection, organic chemical sensing, and biosensing and other analytes detection.

We have shown that aggregated LDL is internalized by macrophages and oxidized in lysosomes by redox-active iron. We have now investigated to determine whether the lysosomal oxidation of LDL impairs lysosomal function and whether a lysosomotropic antioxidant can prevent these alterations. LDL aggregated by SMase (SMase-LDL) caused increased lysosomal lipid peroxidation in human monocyte-derived macrophages or THP-1 macrophage-like cells, as shown by a fluorescent probe, Foam-LPO. The pH of the lysosomes was increased considerably by lysosomal LDL oxidation as shown by LysoSensor Yellow/Blue and LysoTracker Red. SMase-LDL induced senescence-like properties in the cells as shown by β-galactosidase staining and levels of p53 and p21. Inflammation plays a key role in atherosclerosis. SMase-LDL treatment increased the lipopolysaccharide-induced secretion of TNF-α, IL-6, and MCP-1. The lysosomotropic antioxidant, cysteamine, inhibited all of the above changes. Targeting lysosomes with antioxidants, such as cysteamine, to prevent the intralysosomal oxidation of LDL might be a novel therapy for atherosclerosis.

The fabrication of microflow channels with high accuracy in terms of the optimization of the proposed designs, minimization of surface roughness, and flow control of microfluidic parameters is challenging when evaluating the performance of microfluidic systems. The use of conventional input devices, such as peristaltic pumps and digital pressure pumps, to evaluate the flow control of such parameters cannot confirm a wide range of data analysis with higher accuracy because of their operational drawbacks. In this study, we optimized the circular and rectangular-shaped microflow channels of a 100 μm microfluidic chip using a three-dimensional simulation tool, and analyzed concentration profiles of different regions of the microflow channels. Then, we applied a deep learning (DL) algorithm for the dense layers of the rectified linear unit (ReLU), Leaky ReLU, and Swish activation functions to train and test 1600 experimental and interpolation of data samples which obtained from the microfluidic chip. Moreover, using the same DL algorithm, we configured three models for each of these three functions by changing the internal middle layers of these models. As a result, we obtained a total of 9 average accuracy values of ReLU, Leaky ReLU, and Swish functions for a defined threshold value of 6×10−5 using the trial-and-error method. We applied single-to-five-fold cross-validation technique of deep neural network to avoid overfitting and reduce noises from data-set to evaluate better average accuracy of data of microfluidic parameters.

Background: Helicobacter pylori eradication rates has been suboptimal despite multiple-drug regimens owing to increasing drug resistance. Purpose: To assess the efficacy of a novel sequential therapy based on moxifloxacin and nitazoxanide for eradication of Helicobacter pylori infection and ulcer healing. Material and Methods: From January 2018 to December 2019, 160 patients of duodenal ulcer related to H. pylori infection received this novel sequential therapy for 14 days. H. pylori infection was diagnosed on histologic evidence of H. pylori by modified Giemsa staining or a positive rapid urease test by gastric mucosal biopsy. Upper gastrointestinal endoscopy was repeated to assess for healing of ulcers. Successful eradication of H. pylori infection was defined as a negative 13C-urea breath test four weeks after the completion of treatment. H. pylori eradication rates, ulcer healing, treatment compliance and adverse events were end-points of the study. Results: The H. pylori eradication rate was 91.5%. The duodenal ulcer healing was complete in 96% and partial in 4% patients. The adverse events reported in 42 (27.2%) patients were mostly mild-to-moderate in severity. Conclusion: This novel sequential therapy based on moxifloxacin and nitazoxanide of Helicobacter pylori infection eradication was found to be highly effective. The duodenal ulcer healing rate was also very high. Moreover, it showed very good tolerability and safety profile.

Introduction: The aim of the study was to report the perioperative and functional results of Robotic assisted kidney transplantation (RAKT) in Grafts with multiple vessels (GMVs) and compare it to the results of Open kidney transplantation (OKT) with GMVs.Materials and Methods: Patients undergoing RAKT from living donors using GMVs were reviewed from prospectively collected RAKT database at our institution between March 2013 and March 2018. Patient undergoing Open kidney transplantation (OKT) using GMVs served as controls. Ex-vivo bench surgical reconstruction of GMVs was done according to specific anatomy. Propensity score matching was used to balance the sample size in the two groups.Results: Of 153 RAKT and OKT procedures, 86 cases were eligible for propensity score matching for the statistically significant variables (standardized difference >0.10) and 43 procedures were assigned to each group. Median anastomoses, total and cold ischemia and rewarming times did not differ significantly between the RAKT and OKT groups. In comparison with OKT in GMVs we found that RAKT with GMVs had less pain score on post op 2nd day (p = 0.03). There was also a significant difference in mean analgesic requirement (p = 0.02), hospital stay (p = 0.05) and incision length (p = 0.04). Most of the major, minor surgical, and medical postoperative complications were comparable between the two groups except for wound related events (p = 0.002).Conclusion: Multiplicity of renal vessels in RAKT does not adversely affect patient or graft survival compared with the OKT. Satisfactory functional outcome can be achieved by RAKT similar to OKT in GMVs. RAKT seems to have advantage over OKT in that it is less invasive and has the potential to cause fewer low grade complications. Small sample size and short follow-up are the main limitations of the study.

The objective of present research work is to analyze the homogeneous-heterogeneous reactions on the MHD two-dimensional stagnation-point flow of non-Newtonian Prandtl fluid flow and heat transfer towards horizontal linear stretching sheet. The governing boundary layer equations using similarity transformation are reduced to ordinary differential equations suitable to be solved using Finite Difference Method. The quantities of interests are thoroughly analyzed under the effects of various emerging parameters. Comparison of the results obtained from limiting case of present model with already existing literature is in good agreement which shows the validity of the present numerical solution. The study concludes that homogeneous and heterogeneous reaction strength decreases the heat transfer rate. On the other hand, Prandtl fluid parameter and elastic parameter increases heat transfer rate. Keywords: Homogenous-heterogeneous reactions, Nanoparticles, Prandtl fluid, Stretching sheet, Numerical solution

Both tungsten (W) and platinum (Pt) are materials of interest in modern science and technology. Here, in this paper, we report the growth of multi-walled carbon nanotubes (MWCNTs) by thermal chemical vapour deposition (CVD) on Pt–W catalyst with MgO as a support material. The XRD studies were used to determine the structural characteristic of the as-prepared catalyst. Raman spectroscopy studies confirm the growth of MWCNTs with less structural defects and non-crystalline carbonaceous products. The images of field scanning electron microscope (FESEM) show that the grown network of carbon nanotubes (CNTs) contains less impurities, whereas the high-resolution transmission electron microscope (HRTEM) images indicate that the grown MWCNTs have good crystallinity with no lateral carbon deposit. TGA of the unpurified CNT product shows the addition of catalyst particles with the sample. This study will pave way for the new research area in the synthesis of CNTs and their applications in the electronic industry. Moreover, the results were compared with the previously reported results in the literature.

Background: We sought to develop an objective implant selection guideline based on the ratio of patient body mass index (BMI) to age in order to select implants preoperatively and reduce cost while maintaining quality. The BMI-to-age ratio can be used to distinguish patient demand and select those patients who may benefit from newer technology and higher cost implants and those who would do well with standard-demand implants. Methods: A retrospective analysis investigated the types of implants received by patients undergoing total knee arthroplasty from January 2012 to August 2014. Patients with a BMI-to-age ratio >0.60 were categorized as high demand and were eligible for either a high-demand implant or a standard-demand implant. Patients with a BMI-to-age ratio ≤0.60 were recognized as standard demand and would be eligible for only standard-demand implants. The actual implant received was identified and compared with the implant as predicted by the BMI-to-age ratio and potential cost savings were identified. Results: A total of 1507 operative knees were identified. The high-demand implant carries a 31% greater cost than that of a standard-demand implant. Thirty-eight of 1084 high-demand implants were placed in standard-demand knees. An additional 1.1% cost was realized with 38 standard-demand knees receiving high-demand implants and 28.6% if high-demand knees had been used in all standard-demand patients. Conclusions: Limiting the use of high-demand implants to high-functional-demand patients based on the BMI-to-age ratio may guide the surgeon's choice in optimizing implant selection while providing value-based purchasing criteria to the selection of total knee arthroplasty implants. Keywords: TKA, Implant, BMI, Demand, Matching, Knee

In this study, heat generation/absorption effects are studied in the presence of nonlinear thermal radiation along a moving slip surface. Uniform magnetic field and convective condition along the stretching surface are adjusted to deal the slip mechanisms in term of Brownian motion and thermophoresis for nanofluid. The mathematical model is constructed in the form of coupled partial differential equations. By introducing the suitable similarity transformation, system of coupled nonlinear ordinary differential equations are obtained. Finite difference approach is implemented to obtain the unknown functions of velocity, temperature, nanoparticle concentration. To deduct the effects at the surface, physical quantities of interest are computed under the effects of controlled physical parameters. Present numerical solutions are validated via numerical comparison with existing published work for limiting cases. Present study indicates that due to increase in both Brownian motion and thermophoresis, the Nusselt number decreases while Sherwood number shows the gradual increase. Keywords: Heat generation/absorption, Nonlinear thermal radiation, Nanofluid, Stagnation point, Convective boundary, Numerical solution

Renal replacement therapy in India is predominantly a private health-care-driven initiative making it an expensive treatment option due to high out-of-pocket expenditures. Moreover, with the rapid increase in the number of chronic kidney disease patients requiring dialysis, hemodialysis units (HDUs) are getting saturated. Community “stand-alone” dialysis centers could be an important alternative to HDUs in meeting the growing demand in an affordable model. The aim of this study was to find hemodialysis (HD) delivery in “stand-alone” dialysis units (SAUs) with respect to expanding coverage, patient costs, and patient safety safeguards. The total number of HD sessions was collected at three points. The information regarding patient safety safeguards at SAUs and impact of SAUs on patient costs were collected by interviews and from hospital records. There was 11.5 times increase in HD sessions from 2008 to 2017, out of which 75.3% was provided at SAUs. Following objective clinical and safety measures, high-quality dialysis was delivered at SAUs and it significantly reduced the mean patient cost of treatment per session.

Background: Preoperative total hip arthroplasty templating can be performed with radiographs using acetate prints, digital viewing software, or with computed tomography (CT) images. Our hypothesis is that 3D templating is more precise and accurate with cup size prediction as compared to 2D templating with acetate prints and digital templating software. Methods: Data collected from 45 patients undergoing robotic-assisted total hip arthroplasty compared cup sizes templated on acetate prints and OrthoView software to MAKOplasty software that uses CT scan. Kappa analysis determined strength of agreement between each templating modality and the final size used. t tests compared mean cup-size variance from the final size for each templating technique. Interclass correlation coefficient (ICC) determined reliability of digital and acetate planning by comparing predictions of the operating surgeon and a blinded adult reconstructive fellow. Results: The Kappa values for CT-guided, digital, and acetate templating with the final size was 0.974, 0.233, and 0.262, respectively. Both digital and acetate templating significantly overpredicted cup size, compared to CT-guided methods (P < .001). There was no significant difference between digital and acetate templating (PÂ = .117). Interclass correlation coefficient value for digital and acetate templating was 0.928 and 0.931, respectively. Conclusions: CT-guided planning more accurately predicts hip implant cup size when compared to the significant overpredictions of digital and acetate templating. CT-guided templating may also lead to better outcomes due to bone stock preservation from a smaller and more accurate cup size predicted than that of digital and acetate predictions. Keywords: robotic, templating, hip, arthroplasty, CT-guided, implant

Abstract Background Maternal exposure to environmental stressors poses a risk to fetal development. Oxidative stress (OS), microglia activation, and inflammation are three tightly linked mechanisms that emerge as a causal factor of neurodevelopmental anomalies associated with prenatal ethanol exposure. Antioxidants such as glutathione (GSH) and CuZnSOD are perturbed, and their manipulation provides evidence for neuroprotection. However, the cellular and molecular effects of GSH alteration in utero on fetal microglia activation and inflammation remain elusive. Methods Ethanol (EtOH) (2.5 g/kg) was administered to pregnant mice at gestational days 16–17. One hour prior to ethanol treatment, N-acetylcysteine (NAC) and L-buthionine sulfoximine (BSO) were administered to modulate glutathione (GSH) content in fetal and maternal brain. Twenty-four hours following ethanol exposure, GSH content and OS in brain tissues were analyzed. Cytokines and chemokines were selected based on their association with distinctive microglia phenotype M1-like (IL-1β, IFN γ, IL-6, CCL3, CCL4, CCL-7, CCL9,) or M2-like (TGF-β, IL-4, IL-10, CCL2, CCL22, CXCL10, Arg1, Chi1, CCR2 and CXCR2) and measured in the brain by qRT-PCR and ELISA. In addition, Western blot and confocal microscopy techniques in conjunction with EOC13.31 cells exposed to similar ethanol-induced oxidative stress and redox conditions were used to determine the underlying mechanism of microglia activation associated with the observed phenotypic changes. Results We show that a single episode of mild to moderate OS in the last trimester of gestation causes GSH depletion, increased protein and lipid peroxidation and inflammatory responses inclined towards a M1-like microglial phenotype (IL-1β, IFN-γ) in fetal brain tissue observed at 6–24 h post exposure. Maternal brain is resistant to many of these marked changes. Using EOC 13.31 cells, we show that GSH homeostasis in microglia is crucial to restore its anti-inflammatory state and modulate inflammation. Microglia under oxidative stress maintain a predominantly M1 activation state. Additionally, GSH depletion prevents the appearance of the M2-like phenotype, while enhancing morphological changes associated with a M1-like phenotype. This observation is also validated by an increased expression of inflammatory signatures (IL-1β, IFN-γ, IL-6, CCL9, CXCR2). In contrast, conserving intracellular GSH concentrations eliminates OS which precludes the nuclear translocation and more importantly the phosphorylation of the NFkB p105 subunit. These cells show significantly more pronounced elongations, ramifications, and the enhanced expression of M2-like microglial phenotype markers (IL-10, IL-4, TGF-β, CXCL10, CCL22, Chi, Arg, and CCR2). Conclusions Taken together, our data show that maintaining GSH homeostasis is not only important for quenching OS in the developing fetal brain, but equally critical to enhance M2 like microglia phenotype, thus suppressing inflammatory responses elicited by environmental stressors.