Low triiodothyronine (T3) levels predict worse outcomes in autoimmune encephalitis-A meta-analysis of current literature.

INTRODUCTION: An unusual association between thyroid dysfunction and autoimmune encephalitis (AE) was noticed when patients presented with low free triiodothyronine (fT3) levels and antithyroid antibodies. We conducted a meta-analysis to investigate whether thyroid dysfunction, that is, lower fT3 levels are associated with worsening clinical manifestations and prognosis in patients with AE. METHODS: Literature search of five electronic databases was performed till April 5, 2023. Inclusion criteria were as follows: Observational studies reporting patients with all subtypes of AE and assessing thyroid dysfunction categorized as low fT3 and non-low fT3. Primary endpoints included modified Rankin scale (mRS) at admission, abnormal magnetic resonance imaging, length of stay, seizures, and consciousness declination. RESULTS: Comprehensive literature search resulted in 5127 studies. After duplicate removal and full-text screening, six observational studies were included in this analysis. Patients with low fT3 were 2.95 times more likely to experience consciousness declination (p = .0003), had higher mRS at admission (p < .00001), had 3.14 times increased chances of having a tumor (p = .003), were 3.88 times more likely to experience central hypoventilation, and were 2.36 times more likely to have positivity for antithyroid antibodies (p = .009) as compared to patients with non-low fT3. CONCLUSION: The findings of our study suggest that low fT3 levels might be related to a more severe disease state, implying the significance of thyroid hormones in AE pathogenesis. This finding is crucial in not only improving the early diagnosis of severe AE but also in the efficient management of the disease.

Valve-in-Valve Transcatheter Aortic Valve Replacement Versus Redo-Surgical Aortic Valve Replacement in Patients With Aortic Stenosis: A Systematic Review and Meta-analysis.

Aortic stenosis is a common and significant valve condition requiring bioprosthetic heart valves with transcatheter aortic valve replacement (TAVR) being strongly recommended for high-risk patients or patients over 75 years. This meta-analysis aimed to pool existing data on postprocedural clinical as well as echocardiographic outcomes comparing valve-in-valve (ViV)-TAVR to redo-surgical aortic valve replacement to assess the short-term and medium-term outcomes for both treatment methods. A systematic literature search on Cochrane Central, Scopus, and Medline (PubMed interface) electronic databases from inception to August 2023. We used odds ratios (OR) for dichotomous outcomes and mean differences (MD) for continuous outcomes. Twenty-four studies (25,216 patients) were pooled with a mean follow-up of 16.4 months. The analysis revealed that ViV-TAVR group showed a significant reduction in 30-day mortality (OR 0.50, 95% confidence interval [CI] 0.43 to 0.58, p <0.00001), new-onset atrial fibrillation (OR 0.34, 95% CI 0.17 to 0.67, p = 0.002), major bleeding event (OR 0.28, 95% CI 0.17 to 0.45, p <0.00001) and lower rate of device success (OR 0.25, 95% CI 0.12 to 0.53, p = 0.0003). There were no significant differences between either group when assessing 1-year mortality, stroke, myocardial infarction, postoperative left ventricular ejection fraction, and effective orifice area. ViV-TAVR cohort showed a significantly increased incidence of paravalvular leaks, aortic regurgitation, and increased mean aortic valve gradient. ViV-TAVR is a viable short-term option for older patients with high co-morbidities and operative risks, reducing perioperative complications and improving 30-day mortality with no significant cardiovascular adverse events. However, both treatment methods present similar results on short-term to medium-term complications assessment.

Role of adjunctive cariprazine for treatment-resistant depression in patients with major depressive disorder: A systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: Cariprazine is an orally active dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, being considered as a treatment for refractory MDD. Therefore, we aim to perform the first meta-analysis of current literature, to collate changes in depression from baseline and assess tolerability of adjunctive cariprazine in MDD populace. METHODS: PubMed, Embase, Google Scholar, ClinicalTrials.Gov, and Cochrane Library were searched from inception till 1st September 2023. RCTs of adult patients with refractory MDD under adjunctive cariprazine vs. placebo were included. Primary outcomes included improvement in MADRS, CGI-S, and HAM-D 17 scores. Secondary outcomes included treatment-emergent adverse events. The statistical analysis was performed using generic inverse variance with random-effects model. The overall risk ratios (RR) were calculated for dichotomous outcomes. RESULTS: A total of five RCTs were analysed, enrolling 2013 participants (cariprazine: 959 participants, Placebo: 1054). Supplementation of ADT with cariprazine demonstrated a significant improvement in MADRAS, CGI-S and HAMD-17 scores from baseline (LSMD: -1.88, 95% CI [-2.94, -0.83], p=0.0005), (LSMD: -0.18, 95% CI [-0.29, -0.07], p=0.002), and (LSMD: -0.96, 95% CI [-1.70, -0.21], p=0.01) respectively. Treatment with adjunctive cariprazine therapy demonstrated significantly increased incidence of akathisia, nausea, dizziness, fatigue, restlessness, somnolence, and tremors when compared with placebo. CONCLUSION: Our meta-analysis provides evidence supporting the efficacy of adjunctive cariprazine in patients with refractory MDD. However, it is essential to consider the safety profile of cariprazine, particularly the increased risk of adverse events. The vigilant monitoring and management of these side effects should be integrated into clinical practice to minimize discontinuation rates and optimize patient outcomes.

Genome-wide identification and characterization of wall-associated kinases, molecular docking and polysaccharide elicitation of monoterpenoid indole alkaloids in micro-propagated Catharanthus roseus.

Wall-associated kinases (WAKs) are a unique family of proteins that are predominantly localized on the plasma membrane and simultaneously bound to the cell wall. WAKs play a pivotal role in signal transduction to regulate growth, defense, and response to environmental stimuli in plants. These kinases have been identified and characterized in various plant species, however, similar information for Catharanthus roseus is scarce. C. roseus is an evergreen ornamental plant that produces a repertoire of biologically active compounds. The plant is best characterized for the production of antineoplastic monoterpenoid indole alkaloids (MIAs) namely vinblastine and vincristine. Owing to the diverse composition of phytochemicals, C. roseus is known as a "model non-model" plant for secondary metabolite research. Genome analyses showed 37 putative CrWAK genes present in C. roseus, largely localized on the plasma membrane. Phylogenetic analysis revealed six clusters of CrWAKs. Diverse cis-acting elements, including those involved in defense responses, were identified on the promotor regions of CrWAK genes. The highest binding affinity (- 12.6 kcal/mol) was noted for CrWAK-22 against tri-galacturonic acid. Tri-galacturonic acid stimulated 2.5-fold higher production of vinblastine, sixfold upregulation of the expression of ORCA3 transcription factor, and 6.14-fold upregulation of CrWAK-22 expression. Based on these results it was concluded that the expression of CrWAK genes induced by biotic elicitors may have an important role in the production of MIAs. The current findings may serve as a basis for functional characterization and mechanistic explanation of the role of CrWAK genes in the biosynthesis of MIAs upon elicitation.

Transcatheter Edge-to-Edge Repair for Tricuspid Regurgitation-A Systematic Review and Meta-Analysis.

Transcatheter edge-to-edge repair (TEER) has emerged as a widely accepted procedure for tricuspid regurgitation (TR) as gauged by echocardiographic parameters and clinical outcomes. Our study aims to assess TR severity and other echocardiographic outcomes in patients undergoing TEER with TriClip, MitraClip, and PASCAL devices. A literature search of 5 databases was performed until 1st June 2023. Randomized controlled trials (RCTs) or observational studies with moderate to severe (grade III-V) TR patients undergoing isolated TEER were considered eligible. Echocardiographic, and quality of life determining outcomes such as improvement in TR severity grade ≥3, New York Heart Association (NYHA) class ≥3, procedural success, 6-minute walking distance (6MWD), and adverse outcomes were analyzed. Grade assessment was performed and studies were assessed for risk of bias and publication bias. We included 15 studies (14 observational and 1 RCT) in our paper. Analysis revealed a substantial reduction in TR volume (P < 0.00001), TR grading (P < 0.00001), tricuspid annular diameter (P < 0.00001), proximal isovelocity surface area radius (P < 0.00001), effective regurgitant orifice area (P < 0.00001), and improvement in NYHA class (P < 0.00001) at 30 days from baseline, postprocedurally. A significant increase in 6MWD at 1 year (P = 0.001) was also recorded. No significant differences in left ventricular ejection fraction (P = 0.87), fractional area change (P = 0.37), or tricuspid annular plane systolic excursion (P = 0.76) were observed. TEER procedural success was 97%. TEER produced a significant reduction in TR grade and volume, NYHA class, 6MWD, and showed prominent procedural success. Large scale RCTs comparing the TEER devices are needed to strengthen the present findings.

The effectiveness of kangaroo mother care in lowering postpartum depression in mothers of preterm and low birth weight babies: a systematic review and meta-analysis.

Background: Kangaroo mother care (KMC) intervention involves skin-to-skin contact between mother and infant. Some studies have shown a decrease in postpartum depression (PPD) in mothers of preterm and low birth weight (LBW) infants. However, the literature is scattered and of variable quality. Aims: To conduct a systematic review of available literature and provide a comprehensive picture of the effect of KMC on PPD among mothers of preterm and LBW infants. Methods: The study was reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Guidelines. After PROSPERO registration, a systematic search was conducted using PubMed, Cochrane Central Library, and Google Scholar from the inception of the databases till 14 June 2021. Of the 2944 studies assessed for titles and abstracts, nine studies with 2042 participants were included in the review. Included articles targeted mothers with LBW (<2500 g) or preterm infants (<37 weeks), used an authentic PPD tool, and had standard care or an incubator as the control group. Studies not published in English and in which mothers had a previous psychiatric illness were excluded. The risk of bias was assessed using the Cochrane Risk of Bias Tool for randomized control trials and the Newcastle-Ottawa Scale for observational studies. All the results were converted to standard mean deviation and pooled together using a random-effects model with a 95% CI. A P-value of less than 0.05 is considered significant. Results: KMC Intervention was significantly associated with a lower depression score than control groups. The reduction in depression in the intervention (KMC) group was moderate: SMD=-0.38 (-0.68 to -0.08; 95% CI; I 2=86%; P=0.013). No significant difference was found between the PPD scores of both groups using the Edinburgh Postpartum Depression Scale score. Conclusions: The authors conclude that the negative effects of LBW and preterm birth experience on maternal mental health can be avoided to a moderate degree by KMC. Due to a lack of methodological uniformity, different scales for outcome measurement, and discrepancies in intervention features, significantly high heterogeneity was detected. The authors need further larger-scale studies with a uniform study design to better predict the efficacy of KMC better.

Effectiveness of thermal radiations and homogeneous-heterogeneous reactions in Maxwell flow field across a rotating cylinder.

This paper investigates the impact of cubic autocatalysis on energy transport in Maxwell fluid flow induced into a rotating cylinder inspired by a solar radiative surface. The homogeneous-reaction is assumed to be furnished by the kinetics of isothermal cubic autocatalytic and the heterogeneous reaction by kinetics of first order. To prevent induced axial secondary flow, the cylinder's rotation is maintained at a constant rate. The characteristics of thermal radiation are also investigated to regulate the pace of heat transmission. A magnetic beam is projected in the upward radial direction to control the fluid momentum. A suitable flow ansatz is used to convert the entire physical problem of thermal energy transmission and fluid flow from partial differential equations (PDEs) to nonlinear ordinary differential equations (ODEs). Results obtained numerically with the bvp4c approach are presented graphically and explained physically. It is observed that by flourishing the Reynolds parameter, the penetration depth decreases. Further, when the thermal relaxation period increases, the temperature field degrades. Moreover, when the homogeneous-heterogeneous reaction's strength is increased, a reduction in fluid concentration is shown.

Shrinkage Compensation and Effect of Building Orientation on Mechanical Properties of Ceramic Stereolithography Parts.

Stereolithography additive manufacturing (SLA-AM) can be used to produce ceramic structures by selectively curing a photosensitive resin that has ceramic powder in it. The photosensitive resin acts as a ceramic powder binder, which is burned, and the remaining ceramic part is sintered during post-processing using a temperature-time-controlled furnace. Due to this process, the ceramic part shrinks and becomes porous. Moreover, additive manufacturing leads to the orthotropic behavior of the manufactured parts. This article studies the effect of the manufacturing orientation of ceramic parts produced via SLA-AM on dimensional accuracy. Scaled CAD models were created by including the calculated shrinkage factor. The dimensions of the final sintered specimens were very close to the desired dimensions. As sintering induces porosity and reduces the mechanical strength, in this study, the effect of orientation on strength was investigated, and it was concluded that the on-edge specimen possessed by far the highest strength in terms of both compression and tension.

Significance of thermal relaxation on energy transport of Maxwell fluid rotating over a cylindrical surface with homogeneous-heterogeneous reactions.

Many industrial applications, including coating processes, roller bearing uses, and cooling gas turbine rotors, involve non-Newtonian fluid flow across rotating cylinders. The current study aims at evaluating the energy transport of the Maxwell fluid rotating over a horizontal cylindrical surface using the Cattaneo-Christov heat flux conduction model. This model predicts the properties of thermal relaxation by revising conventional Fourier's law. Isothermal cubic autocatalytic kinetics provides a homogeneous reaction, while first-order kinetics yields a heterogeneous reaction. With the help of transformations, the system of ODEs relating the equations for energy, momentum, and concentration is produced. For a numerical solution, the bvp4c scheme, which is based on the finite difference technique in Matlab 9.7 R2019b, is used. The importance of dominant parameters is displayed with the graphical depictions for axial, radial, and azimuthal flows, as well as temperature and concentration distributions. The noteworthy results illustrate that the Maxwell parameter has a declining influence on all velocity components. Further, thermal relaxation time causes a decline in the temperature field as well. Moreover, as the homogeneous-heterogeneous reaction parameters are increased, a reduction in fluid concentration is shown.

Magneto-bioconvection flow of Casson nanofluid configured by a rotating disk in the presence of gyrotatic microorganisms and Joule heating.

In this article, we investigate the bioconvection flow of Casson nanofluid by a rotating disk under the impacts of Joule heating, convective conditions, heat source/sink and gyrotactic microorganisms. When Brownian diffusion and thermophoretic effects exist, the Casson fluid is examined. The existing physical problem of Casson nanofluid flow with energy transports is demonstrated under the above considerations in the form of partial differential equations (PDEs). Using the appropriate transformations, the PDEs are converted into non-linear ordinary differential equations (ODEs). The mathematical results are calculated through MATLAB by using the function bvp4c. The problem's results are rigorously examined graphically and described with physical justifications. Velocity fields decrease as the bioconvection Rayleigh parameter rises. The thermal profile and soluteal field of species also magnify with an upsurge in thermophoresis number estimations. The microorganism's fields are decayed by larger microbes Biot number.

Giant Cell Tumor of the Distal Fibula Managed by an Autologous Proximal Fibula Graft.

A giant cell tumor of the bone is among the most common bone tumors encountered by orthopedic surgeons. These benign and aggressive tumors are most commonly present around the knee joint; however, rare cases may involve the distal fibula. An 18-year-old man presented with a painless swelling of the lateral aspect of the left ankle. Clinical examination, radiologic evaluation, and biopsy confirmed the diagnosis of a giant cell tumor of the distal fibula. The patient was treated with resection of the distal fibula followed by reconstruction using an ipsilateral proximal fibula graft. The post-operative recovery was uneventful, and the patient was doing well on the last visit, one month after the intervention.

Effectiveness of locally produced ready to use supplementary food on hemoglobin, anthropometrics, and plasma micronutrients concentrations of 6 to 23 months age children: a non-randomized community-based trial from Pakistan.

Background: Micronutrient deficiencies including vitamin A, vitamin D, and zinc are highly prevalent in children below 5 years of age in low and -middle-income countries. We aimed to evaluate the effectiveness of ready-to-use Lipid-based Nutrient Supplement-Medium Quantity (LNS-MQ) local name "Wawa-mum" on plasma micronutrient status, hemoglobin concentration and anthropometric measurements. Methods: A community-based non-randomized trial was conducted in the Kurram district of Khyber Pakhtunkhwa from January 2018 to June 2019. A total of 110 children aged 6 to 23 months old were recruited and allocated to the intervention and control arm of the study. A total of 57 children in the intervention arm received a daily ration of 50 g of Wawa-mum, for one year. To assess the impact of the intervention on primary outcome measures, i.e., serum vitamin A, D concentration, plasma zinc, and hemoglobin concentration. Blood samples were collected at baseline and after one year following the intervention. The vitamins concentration in serum were assessed using Enzyme-Linked Immunosorbent Assay (ELISA) and plasma zinc by atomic absorption spectrometry. The hemoglobin concentration was measured by an automated hematology analyzer. A 24-h dietary recall interview was used to assess the nutrient intake adequacy. Multivariate Linear regression models were used to analyze the outcomes while controlling for potential confounders. Results: In the intervention arm, children had on average 6.2 µg/dL (95% CI 3.0-9.3, value of p<0.001) increase in the serum vitamin A concentration, 8.1 ng/mL (95% CI 1.3-14.9, value of p 0.02) increase in serum vitamin D concentration and 49.0 µg/dL (95% CI 33.5-64.5, value of p<0.001) increase in the plasma zinc concentration, and 2.7 g/dL (95% CI 2.0-3.3, value of p<0.001) increase in hemoglobin concentration while adjusted for covariates. An addition, length-for-age z-score (LAZ), weight-for-length z-score (WLZ), weight-for-age z-score (WAZ), and prevalence of undernutrition including stunting, wasting, and underweight were calculated as a secondary outcome to investigate the impact of micronutrients on growth parameters, that has been improved significantly after receiving the Wawa-mum. Conclusion: Wawa-mum (LNS-MQ) is an effective intervention to improve the micronutrient status, hemoglobin concentration, and growth parameters in 6 to 23 months children, which can be scaled up in the existing health system to address the alarming rates of under nutrition in Pakistan and other developing countries. Clinical trial registration: https://doi.org/10.1186/ISRCTN94319790, ISRCTN94319790.

Novel mutations in genes of the IL-12/IFN-γ axis cause susceptibility to tuberculosis.

BACKGROUND: The IL-12/23/ISG15-IFN-γ pathway is the main immunological pathway for controlling intra-macrophagic microorganisms such as Mycobacteria, Salmonella, and Leishmania spp. Consequently, upon mutations in genes of the IL-12/23/ISG15-IFN-γ pathway cause increased susceptibility to intra-macrophagic pathogens, particularly to Mycobacteria. Therefore, the purpose of this study was to characterize the mutations in genes of the IL-12/23/ISG15-IFN-γ pathway in severe tuberculosis (TB) patients. METHODS: Clinically suspected TB was initially confirmed in four patients (P) (P1, P2, P3, and P4) using the GeneXpert MTB/RIF and culturing techniques. The patients' Peripheral blood mononuclear cells (PBMCs) were then subjected to ELISA to measure Interleukin 12 (IL-12) and interferon gamma (IFN-γ). Flow cytometry was used to detect the surface expressions of IFN-γR1 and IFN-γR2 as well as IL-12Rß1and IL-12Rß2 on monocytes and T lymphocytes, respectively.The phosphorylation of signal transducer and activator of transcription 1(STAT1) on monocytes and STAT4 on T lymphocytes were also detected by flow cytometry. Sanger sequencing was used to identify mutations in the IL-12Rß1, STAT1, NEMO, and CYBB genes. RESULTS: P1's PBMCs exhibited reduced IFN-γ production, while P2's and P3's PBMCs exhibited impaired IL-12 induction. Low IL-12Rß1 surface expression and reduced STAT4 phosphorylation were demonstrated by P1's T lymphocytes, while impaired STAT1 phosphorylation was detected in P2's monocytes. The impaired IκB-α degradation and abolished H2O2 production in monocytes and neutrophils of P3 and P4 were observed, respectively. Sanger sequencing revealed novel nonsense homozygous mutation: c.191 G>A/p.W64 * in exon 3 of the IL-12Rß1 gene in P1, novel missense homozygous mutation: c.107 A>T/p.Q36L in exon 3 of the STAT1 gene in P2, missense hemizygous mutation:: c.950 A>C/p.Q317P in exon 8 of the NEMO gene in P3, and nonsense hemizygous mutation: c.868 C>T/p.R290X in exon 8 of CYBB gene in P4. CONCLUSION: Our findings broaden the clinical and genetic spectra associated with IL-12/23/ISG15-IFN-γ axis anomalies. Additionally, our data suggest that TB patients in Pakistan should be investigated for potential genetic defects due to high prevalence of parental consanguinity and increased incidence of TB in the country.

Therapeutic and safety outcomes of intracoronary nicardipine in coronary artery disease patients: a systematic review.

Aim: This systematic review aimed to shed light on the efficacy of intracoronary (IC) nicardipine in treating no reflow with CAD undergoing revascularization. Methods: Literature search was performed on databases with following eligibility criteria: adult patients with CAD; clinical trials or observational studies; IC nicardipine as intervention; therapeutic and safety outcome reported. Results: A total of 1249 papers were yielded during the literature search. Of these, 11 studies were finalized for this systematic review. Complete restoration of TIMI 3 flow was observed in 98.6% of the patients receiving IC nicardipine. A significant increase in the CBF after infusion of IC nicardipine (p < 0.05) was also observed. Conclusion: IC nicardipine significantly increases CBF and decreases coronary vascular resistance.

Coronary artery disease (CAD) is a condition that results in the narrowing or blockage of heart arteries. Arteries are blood vessels that bring oxygen-rich blood from your heart to the rest of your body's cells. We aimed to evaluate the effects of intracoronary (IC) nicardipine, a drug that blocks calcium from entering the muscle cells and blood vessels of the heart, which causes the vessels to relax and widen, allowing for blood to flow more easily, on a phenomenon known as coronary slow flow (CSF). CSF is defined as a delayed widening of the blood vessels of the heart. CSF or the no reflow phenomenon is a major negative complication associated with surgical procedures such as percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG), both of which are used to open up blocked arteries. The systematic search identified studies that evaluated the effect of IC nicardipine in patient during CAD treatment, undergoing PCI, CABG, or having confirmed or suspected narrowing of the aortic valve or one of the four valves of the heart, which results in restricted blood flow from the heart to the body. From the results of studies discussed in the review, it can be concluded that IC nicardipine significantly increases blood flow to the heart and can help prevent the no reflow phenomenon in patients undergoing PCI. Nicardipine proved to be a safe and effective option in the management of complications such as no reflow in patients receiving therapies to restore blood flow following CAD.

Coronary Artery Stenosis Severity in Patients With Different Coronary Artery Calcium Scores on Coronary Computed Tomography Angiography.

Background In this study, we aimed to determine coronary artery stenosis severity in patients with different coronary artery calcium (CAC) scores. Methodology A total of 145 patients were included in the study. All patients were given beta-blockers 12 hours and two hours before the test to keep their heart rate between 55 and 65 beats per minute. Computed tomography angiography was done from the pulmonary hilum up to the base of the heart and the patients were asked to hold their breath. The CAC score and stenosis were assessed. Results The mean age of the patients was 41.35 ± 4.95 years. In total, 112 (77.24%) patients were male and 33 (22.76%) were female. Regarding the frequency of the CAC score, a score of 0-9 was observed in 43 (29.66%) patients, 10-99 was observed in 55 (37.93%) patients, and 100-400 was observed in 47 (32.41%) patients. The CAC score was 0-9 in 86.4% of patients having normal coronary arteries. Two (5.2%) patients with a CAC score of 100-400 had mild coronary artery stenosis, 11 (32.3%) patients had moderate coronary artery disease, and 33 (66.0%) patients had severe coronary artery disease (p < 0.00001). Conclusions There is a strong association between CAC scores and the severity of coronary artery stenosis. A CAC score of zero is associated with a very low risk of having coronary artery stenosis.

Genomic study of TEX15 variants: prevalence and allelic heterogeneity in men with spermatogenic failure.

Introduction: Human spermatogenesis is a highly intricate process that requires the input of thousands of testis-specific genes. Defects in any of them at any stage of the process can have detrimental effects on sperm production and/or viability. In particular, the function of many meiotic proteins encoded by germ cell specific genes is critical for maturation of haploid spermatids and viable spermatozoa, necessary for fertilization, and is also extremely sensitive to even the slightest change in coding DNA. Methods: Here, using whole exome and genome approaches, we identified and reported novel, clinically significant variants in testis-expressed gene 15 (TEX15), in unrelated men with spermatogenic failure (SPGF). Results: TEX15 mediates double strand break repair during meiosis. Recessive loss-of-function (LOF) TEX15 mutations are associated with SPGF in humans and knockout male mice are infertile. We expand earlier reports documenting heterogeneous allelic pathogenic TEX15 variants that cause a range of SPGF phenotypes from oligozoospermia (low sperm) to nonobstructive azoospermia (no sperm) with meiotic arrest and report the prevalence of 0.6% of TEX15 variants in our patient cohort. Among identified possible LOF variants, one homozygous missense substitution c.6835G>A (p.Ala2279Thr) co-segregated with cryptozoospermia in a family with SPGF. Additionally, we observed numerous cases of inferred in trans compound heterozygous variants in TEX15 among unrelated individuals with varying degrees of SPGF. Variants included splice site, insertions/deletions (indels), and missense substitutions, many of which resulted in LOF effects (i.e., frameshift, premature stop, alternative splicing, or potentially altered posttranslational modification sites). Conclusion: In conclusion, we performed an extensive genomic study of familial and sporadic SPGF and identified potentially damaging TEX15 variants in 7 of 1097 individuals of our combined cohorts. We hypothesize that SPGF phenotype severity is dictated by individual TEX15 variant's impact on structure and function. Resultant LOFs likely have deleterious effects on crossover/recombination in meiosis. Our findings support the notion of increased gene variant frequency in SPGF and its genetic and allelic heterogeneity as it relates to complex disease such as male infertility.

Long-Term Impact of Multiple Micronutrient Supplementation on Micronutrient Status, Hemoglobin Level, and Growth in Children 24 to 59 Months of Age: A Non-Randomized Community-Based Trial from Pakistan.

Cost-effective interventions are needed to address undernutrition, particularly micronutrient deficiencies, which are common in children under the age of five in low- and middle-income countries. A community-based, non-randomized clinical trial was undertaken in the Kurram district of Khyber Pakhtunkhwa from January 2018 to June 2019, to evaluate the effect of locally produced micronutrient powder (local name: Vita-Mixe) on plasma micronutrient status, hemoglobin level, and anthropometric outcomes. Children aged 24-48 months old were recruited and allocated to the intervention and control arm of the study. The enrolled children in the intervention arm received one micronutrient powder (MNP) sachet for consumption on alternate days for 12 months. To assess the impact of the intervention on plasma levels of zinc, vitamin D, vitamin A, and hemoglobin level, blood samples were taken at baseline and after one year following the intervention. The analysis was conducted using Enzyme-Linked Immunosorbent Assay (ELISA), atomic absorption spectrometry, and an automated hematology analyzer. For the impact on growth parameters, the anthropometric assessment was performed using WHO standard guidelines. A 24 h dietary recall interview was used to assess the nutrient intake adequacy. Results showed that in the intervention arm, children had on average a 7.52 ng/mL (95% CI 5.11-9.92, p-value < 0.001) increase in the plasma level of vitamin A, 4.80 ng/mL (95% CI 1.63-7.95, p-value < 0.002) increase in vitamin D levels and 33.85 µg/dL (95% CI 24.40-43.30, p-value < 0.001) increase in the plasma zinc level, as well as a 2.0g/dL (95% CI 1.64-2.40, p-value < 0.001) increase in hemoglobin level. Statistically significant improvement was observed in the weight-for-height z-score (WHZ) (from -1.0 ± 0.88 to -0.40 ± 1.01, p < 0.001) and weight-for-age z-score (WAZ) (from -1.40 ± 0.50 to -1.05 ± 0.49, p < 0.001) in the intervention group compared to the control group. No statistically significant change was observed in the height-for-age z-score (HAZ) in the intervention group (p = 0.93). In conclusion, micronutrient powder supplementation is a cost-effective intervention to improve the micronutrient status, hemoglobin level, and growth parameters in under-five children, which can be scaled up in the existing health system to address the alarming rates of undernutrition in Pakistan and other developing countries.

COMPARISON OF INTRAMUSCULAR VERSUS INTRAVENOUS KETAMINE FOR SEDATION IN CHILDREN UNDERGOING MAGNETIC RESONANCE IMAGING EXAMINATION.

OBJECTIVE: The aim: To compare efficacy of intramuscular (IM) versus intravenous (IV) ketamine for sedation in children undergoing brain MRI scanning in children. PATIENTS AND METHODS: Materials and methods: Children who required elective brain MRI were selected for this study. They were randomly divided into two groups; group I received 1.5 mg/kg IV Ketamine and group II received 4 mg/kg IM ketamine. In each group supplementary 0.1 mg/kg midazolam intravenously before positioning on MRI table was given. Patients were monitored for pulse rate, SPO2, and respiratory wave. RESULTS: Results: Children who received IM ketamine had significantly shorter scan time and a greater success rate of sedation with first dose than the IV group. The proportions of scan interruption and scan repeat were significantly higher among the IV group than in the IM group. The scan time was longer among the IV group than in the IM group with significantly more scan interruption and repeat. Satisfaction with sedation as expressed by the technicians was significantly more in the IM group than in IV group (98.1% vs. 80.8%, P= 0.004). CONCLUSION: Conclusions: Intramuscular ketamine injection was predicted to have a better sedative success rate and takes less time to complete than intravenous admin¬istration. This makes IM ketamine more appealing in certain conditions.