Perfluorooctane Sulfonate Exposure Induces Cardiovascular Dysfunction in Female Rats: Role of Ovaries.

Per- and polyfluoroalkyl substances (PFAS) are pervasive environmental pollutants frequently detected in drinking water worldwide. Reports linking PFAS exposure to cardiovascular disease have increased significantly in recent years. Furthermore, women appear to be more susceptible to the adverse effects of PFAS. However, the potential role of ovaries in the increased vulnerability of females to PFAS-related health effects remains unknown. In this study, we investigated the impact of perfluorooctane sulfonate (PFOS), a prominent PFAS, on the cardiovascular function in female rats with intact ovaries and ovariectomized (OVX) females. Bilateral OVX or sham surgeries were performed in 8-week-old female SD rats. Following recovery from surgeries, the rats were given drinking water containing 50 µg/mL of PFOS for 3 weeks. Control groups received PFOS-free water. PFOS exposure significantly reduced body weight but increased blood pressure similarly in both intact and OVX rats. Echocardiography analysis revealed that PFOS exposure decreased cardiac output, end-systolic volume, and end-diastolic volume in intact but not OVX rats. Vascular function studies demonstrated that PFOS equally reduced endothelium-dependent and -independent relaxation responses in intact and OVX rats. The endothelium-independent contractile responses were more pronounced in both intact and OVX rats. eNOS protein levels were similarly decreased in both intact and OVX rats. In conclusion, PFOS affects cardiac function through hormone-dependent mechanisms, while vascular function is impaired independent of ovarian status, indicating an intricate interplay between PFOS exposure, ovarian status, and cardiovascular function.

Gestational Intermittent Hypoxia Impairs AT2R-Mediated Vascular Protection in Female Offspring on a High-Fat, High-Sucrose Diet.

Background: Gestational intermittent hypoxia (GIH), a hallmark of maternal obstructive sleep apnea, sex-differentially causes hypertension and endothelial dysfunction in adult male offspring but not in females. This study investigated whether the GIH-exposed female offspring, a "protected" group against the hypertensive effects of maternal GIH exposure, exhibit increased susceptibility to hypertension and cardiovascular dysfunction when fed a high-fat high-sucrose (HFHS) diet and whether this effect could be reversed by pharmacological intervention activating the angiotensin II type 2 receptor (AT2R). Methods: Female offspring of control and GIH-exposed (10.5% O2, 8 h/d, E10-21) dams were assigned either an HFHS diet or a standard diet from 12 weeks of age. Blood pressure was monitored. At 28 weeks, a systemic CGP42112 (AT2R agonist) or saline infusion was administered through the osmotic pump. At 30 weeks, the heart was weighed and collected for H&E staining, mesenteric arteries for vascular reactivity assessment and protein analysis, and plasma for ELISA. Results: The HFHS diet induced similar increases in body weight gain and blood pressure in control and GIH female offspring. HFHS feeding did not affect heart structure, but impaired endothelial-dependent vascular relaxation with associated decreased AT2R and eNOS expression and reduced plasma bradykinin levels in both control and GIH offspring. CGP42112 administration effectively mitigated HFHS-induced hypertension and endothelial dysfunction only in control offspring, accompanied by restored AT2R, eNOS, and bradykinin levels, but not in the GIH counterparts. Conclusion: These findings suggest that GIH induces endothelial dysfunction and AT2R insensitivity in female offspring exposed to an HFHS diet.

H2S Donor GYY4137 Mitigates sFlt-1-Induced Hypertension and Vascular Dysfunction in Pregnant Rats.

BACKGROUND: Gestational hypertension, often associated with elevated soluble Fms-related receptor tyrosine kinase 1 (sFlt-1), poses significant risks to both maternal and fetal health. Hydrogen sulfide (H2S), a gasotransmitter, has demonstrated blood pressure-lowering effects in hypertensive animals and humans. However, its role in pregnancy-induced hypertension remains unclear. OBJECTIVE: This study aimed to investigate the impact of GYY4137, a slow-release H2S donor, on sFlt-1-induced hypertension in pregnant rats and examine the underlying mechanisms. METHODS: Pregnant rats were administered sFlt-1 (6 µg/kg/day, intravenously) or vehicle from gestation day (GD) 12 to 20. A subset of these groups received GYY4137 (an H2S donor, 50 mg/kg/day, subcutaneously) from GD 16 to 20. Serum H2S levels, mean arterial blood pressure (CODA tail-cuff), uterine artery blood flow (ultrasonography), vascular reactivity to vasopressors and endothelial-dependent relaxation (myography), endothelial nitric oxide synthase (eNOS) protein expression in uterine arteries (Western blotting) were assessed. In addition, maternal weight gain, as well as fetal and placental weights, were measured. RESULTS: Elevated sFlt-1 reduced both maternal weight gain and serum H2S levels. GYY4137 treatment restored both weight gain and H2S levels in sFlt-1 dams. sFlt-1 increased mean arterial pressure and decreased uterine artery blood flow in pregnant rats. However, treatment with GYY4137 normalized blood pressure and restored uterine blood flow in sFlt-1 dams. sFlt-1 dams exhibited heightened vasoconstriction to phenylephrine and GYY4137 significantly mitigated the exaggerated vascular contraction. Notably, sFlt-1 impaired endothelium-dependent relaxation, while GYY4137 attenuated this impairment by upregulating eNOS protein levels and enhancing vasorelaxation in uterine arteries. GYY4137 mitigated sFlt-1-induced fetal growth restriction. CONCLUSION: sFlt-1 mediated hypertension is associated with decreased H2S levels. Replenishing H2S with the donor GYY4137 mitigates hypertension and improves vascular function and fetal growth outcomes. This suggests modulation of H2S could offer a novel therapeutic strategy for managing gestational hypertension and adverse fetal effects.

A comprehensive review on starch-based sustainable edible films loaded with bioactive components for food packaging.

Biopolymers like starch, a renewable and widely available resource, are increasingly being used to fabricate the films for eco-friendly packaging solutions. Starch-based edible films offer significant advantages for food packaging, including biodegradability and the ability to extend shelf life. However, they also present challenges such as moisture sensitivity and limited barrier properties compared to synthetic materials. These limitations can be mitigated by incorporating bioactive components, such as antimicrobial agents or antioxidants, which enhance the film's resistance to moisture and improve its barrier properties, making it a more viable option for food packaging. This review explores the emerging field of starch-based sustainable edible films enhanced with bioactive components for food packaging applications. It delves into fabrication techniques, structural properties, and functional attributes, highlighting the potential of these innovative films to reduce environmental impact and preserve food quality. Key topics discussed include sustainability issues, processing methods, performance characteristics, and potential applications in the food industry. The review provides a comprehensive overview of current research and developments in starch-based edible films, presenting them as promising alternatives to conventional food packaging that can help reduce plastic waste and environmental impact.

Male infertility and Perfluoroalkyl and poly-fluoroalkyl substances: Evidence for alterations in phosphorylation of proteins and fertility-related functional attributes in bull spermatozoa.

BACKGROUND: Perfluoroalkyl and poly-fluoroalkyl substances (PFAS) are pervasive environmental pollutants and emerging risk factors for reproductive health. Although epidemiological evidence supports the link between these substances and male infertility, their specific effects on male fertility remain poorly understood. OBJECTIVES: Investigate the effect of perfluorooctane sulfonic acid (PFOS), the most prevalent and prominent PFAS, on bull sperm protein phosphorylation, a post-translational modification process governing sperm functionality and fertility. METHODS: We exposed bull sperm to PFOS at 10 µM (average population level) and 100 µM (high-exposure level), and analyzed global proteome and phosphoproteome profile by TMT labeling and NanoLC-MS/MS. We also measured sperm fertility functions by flow cytometry. RESULTS: PFOS at 10 µM altered sperm proteins linked to spermatogenesis and chromatin condensation, while at 100 µM, PFOS affected proteins associated with motility and fertility. We detected 299 phosphopeptides from 116 proteins, with 45 exhibiting differential expression between control and PFOS groups. PFOS dysregulated phosphorylation of key proteins (ACRBP, PRKAR2A, RAB2B, SPAG8, TUBB4B, ZPBP, and C2CD6) involved in sperm capacitation, acrosome reaction, sperm-egg interaction, and fertilization. PFOS also affected phosphorylation of other proteins (AQP7, HSBP9, IL4I1, PRKAR1A, and CCT8L2) related to sperm stress resistance and cryotolerance. Notably, 4 proteins (PRM1, ACRBP, TSSK1B, and CFAP45) exhibited differential regulation at both the proteomic and phosphoproteomic levels. Flow cytometric analysis confirmed that PFOS increased protein phosphorylation in sperm as well as reduced sperm motility, viability, calcium, and membrane potential and increased mitochondrial ROS in a dose-dependent manner. CONCLUSIONS: This study shows that PFOS exposure adversely impacts phosphorylation of proteins critical for bull sperm function and fertilization. Moreover, the concentration of PFOS influences the severity of these effects. The comprehensive bull sperm phosphoproteomics data from this study can help us understand the molecular mechanisms of environmental exposure-related male infertility.

Gain-of-function human UNC93B1 variants cause systemic lupus erythematosus and chilblain lupus.

UNC93B1 is a transmembrane domain protein mediating the signaling of endosomal Toll-like receptors (TLRs). We report five families harboring rare missense substitutions (I317M, G325C, L330R, R466S, and R525P) in UNC93B1 causing systemic lupus erythematosus (SLE) or chilblain lupus (CBL) as either autosomal dominant or autosomal recessive traits. As for a D34A mutation causing murine lupus, we recorded a gain of TLR7 and, to a lesser extent, TLR8 activity with the I317M (in vitro) and G325C (in vitro and ex vivo) variants in the context of SLE. Contrastingly, in three families segregating CBL, the L330R, R466S, and R525P variants were isomorphic with respect to TLR7 activity in vitro and, for R525P, ex vivo. Rather, these variants demonstrated a gain of TLR8 activity. We observed enhanced interaction of the G325C, L330R, and R466S variants with TLR8, but not the R525P substitution, indicating different disease mechanisms. Overall, these observations suggest that UNC93B1 mutations cause monogenic SLE or CBL due to differentially enhanced TLR7 and TLR8 signaling.

Internal Mammary Artery-saphenous Vein Y Anastomosis in Coronary Artery Bypass Grafting - Is there a Possibility of Coronary Steal?

Recent advances in coronary revascularization include total arterial grafting, however, in a few cases, harvesting the right internal thoracic artery (RITA) is not possible due to various reasons. In such cases, where the aorta is also calcified, few surgeons perform Y anastomosis configuration with the left internal thoracic artery(LITA) and saphenous vein which can have disastrous complications. Our patient is a 65-year-old man who was diagnosed with multivessel coronary disease and presented with a coronary steal during coronary artery bypass grafting surgery. The RITA was not harvested due to osteoporosis sternum. LITA-saphenous vein Y anastomosis configuration was done as the aorta was calcified. The anastomosis was done between the LITA to the left anterior descending (LAD) artery and the Y arm saphenous vein was anastomosed to an obtuse marginal (OM)branch. He developed coronary steal following anastomosis of the Y graft to the OM branch. The patient had ischemic changes inside the operation theatre in LAD territory, hence grafts were revised following which the patient became stable. There is a high possibility of a coronary steal when the caliber of the Y arm does not match with the LITA. LITA-saphenous vein Y anastomosis can cause more complications as the saphenous vein is much bigger in caliber compared to the LITA.

Idiopathic intracranial hypertension as the initial presenting manifestation of systemic lupus erythematosus in a child.

Idiopathic intracranial hypertension (IIH) is a diagnosis of exclusion characterized by features of raised intracranial pressure (ICP) in the absence of brain parenchymal lesion, vascular malformations, hydrocephalus, or central nervous system (CNS) infection. Commonly used other terms for this entity include benign intracranial hypertension (BIH) or pseudotumor cerebri. Few case reports of systemic lupus erythematosus (SLE) presenting as IIH are available in the literature. We report a 12-year-old girl presented with chronic holocranial headache and occasional episodes of projectile vomiting for the last 6 months and then developed blurring of vision for the last month. She fulfilled the criteria for IIH. Subsequent evaluation revealed a diagnosis of SLE. The occurrence of IIH in SLE is not coincidental and is reported in 1%-5.4% of patients with SLE. Though corticosteroids have not been widely used in IIH, underlying SLE warranted administering corticosteroids with subsequent complete resolution of IIH. Pediatricians, neurologists, intensivists, and ophthalmologists should consider SLE as a differential diagnosis in children presenting with IIH.

Enhancing underwater target localization through proximity-driven recurrent neural networks.

Environmental monitoring, ocean research, and underwater exploration are just a few of the marine applications that require precise underwater target localization. This study goes into the field of underwater target localization using Recurrent Neural Networks (RNNs) enhanced with proximity-based approaches, with a focus on mean estimation error as a performance metric. In complex and dynamic underwater environments, conventional localization systems frequently face challenges such as signal degradation, noise interference, and unstable hydrodynamic conditions. This paper presents a novel approach to employing RNNs to increase the accuracy of underwater target localization by exploiting the temporal dynamics of proximity-informed data. This method uses an RNN architecture to track changes in audio emissions from underwater targets sensed by a microphone network. Using the temporal correlations represented in the data, the RNN learns patterns indicative of target localization quickly and correctly. Furthermore, the addition of proximity-based features increases the model's ability to understand the relative distances between hydrophone nodes and the target, resulting in more accurate localization estimates. To evaluate the suggested methodology, thorough simulations and practical experiments were carried out in a variety of underwater environments. The results show that the RNN-based strategy beats conventional methods and works effectively even in difficult settings. The utility of the proximity-aware RNN model is demonstrated, in particular, by considerable reductions in the mean estimate error (MEE), an important performance measure.

Acute Encephalitis Syndrome in Children and Adolescents: A Five-Year Descriptive Study From South India.

OBJECTIVE: Acute encephalitis syndrome (AES) in children results in significant neurocognitive deficits or mortality. It is pertinent to study the AES patterns periodically to identify the changes in the etiological trends and outcomes. Our objective was to find the etiological agents of AES, mode of diagnosis, treatment given, and outcomes. METHODS: We reviewed the electronic records of children aged 1 month to 15 years who were admitted with AES in our centre from January 2015 to December 2019. We analyzed the the clinical, laboratory, and radiological profile of these children and adolescents in relation to their outcome. Poor outcome was defined as death, discharge against medical advice with neurological deficits, or Glasgow Outcome Score Extended (GOS-E) d≤ 5 at the time of discharge. RESULTS: Among 250 patients admitted with AES during the study period, a definitive etiological diagnosis was established in 56.4% of children (30.4% viral, 22% bacterial). Scrub typhus (11.2%) and dengue (9%) were the two most common underlying illnesses. Serology helped in clinching the diagnosis in 30% of children. A surge in AES cases in the post-monsoon season was observed in our cohort. Third-generation cephalosporin drugs (85.7%) and acyclovir (77.7%) were the most commonly used empiric antimicrobial drugs. About one-third of children (n = 80) had a poor outcome. GCS ≤ 8 at presentation and requirement for invasive ventilation were found to be significant predictors of poor outcome. CONCLUSION: A definitive diagnosis was obtained in about half of the children with AES. Viral (30.4%) and rickettsial infections (22%) were the common etiologies identified. Poor outcome was observed in 32% of patients.

Antiviral Effect of Antimicrobial Peptoid TM9 and Murine Model of Respiratory Coronavirus Infection.

New antiviral agents are essential to improving treatment and control of SARS-CoV-2 infections that can lead to the disease COVID-19. Antimicrobial peptoids are sequence-specific oligo-N-substituted glycine peptidomimetics that emulate the structure and function of natural antimicrobial peptides but are resistant to proteases. We demonstrate antiviral activity of a new peptoid (TM9) against the coronavirus, murine hepatitis virus (MHV), as a closely related model for the structure and antiviral susceptibility profile of SARS-CoV-2. This peptoid mimics the human cathelicidin LL-37, which has also been shown to have antimicrobial and antiviral activity. In this study, TM9 was effective against three murine coronavirus strains, demonstrating that the therapeutic window is large enough to allow the use of TM9 for treatment. All three isolates of MHV generated infection in mice after 15 min of exposure by aerosol using the Madison aerosol chamber, and all three viral strains could be isolated from the lungs throughout the 5-day observation period post-infection, with the peak titers on day 2. MHV-A59 and MHV-A59-GFP were also isolated from the liver, heart, spleen, olfactory bulbs, and brain. These data demonstrate that MHV serves as a valuable natural murine model of coronavirus pathogenesis in multiple organs, including the brain.

Discovery of First-in-Class PROTAC Degraders of SARS-CoV-2 Main Protease.

We have witnessed three coronavirus (CoV) outbreaks in the past two decades, including the COVID-19 pandemic caused by SARS-CoV-2. Main protease (MPro), a highly conserved protease among various CoVs, is essential for viral replication and pathogenesis, making it a prime target for antiviral drug development. Here, we leverage proteolysis targeting chimera (PROTAC) technology to develop a new class of small-molecule antivirals that induce the degradation of SARS-CoV-2 MPro. Among them, MPD2 was demonstrated to effectively reduce MPro protein levels in 293T cells, relying on a time-dependent, CRBN-mediated, and proteasome-driven mechanism. Furthermore, MPD2 exhibited remarkable efficacy in diminishing MPro protein levels in SARS-CoV-2-infected A549-ACE2 cells. MPD2 also displayed potent antiviral activity against various SARS-CoV-2 strains and exhibited enhanced potency against nirmatrelvir-resistant viruses. Overall, this proof-of-concept study highlights the potential of targeted protein degradation of MPro as an innovative approach for developing antivirals that could fight against drug-resistant viral variants.

AcumenTM hypotension prediction index guidance for prevention and treatment of hypotension in noncardiac surgery: a prospective, single-arm, multicenter trial.

BACKGROUND: Intraoperative hypotension is common during noncardiac surgery and is associated with postoperative myocardial infarction, acute kidney injury, stroke, and severe infection. The Hypotension Prediction Index software is an algorithm based on arterial waveform analysis that alerts clinicians of the patient's likelihood of experiencing a future hypotensive event, defined as mean arterial pressure < 65 mmHg for at least 1 min. METHODS: Two analyses included (1) a prospective, single-arm trial, with continuous blood pressure measurements from study monitors, compared to a historical comparison cohort. (2) A post hoc analysis of a subset of trial participants versus a propensity score-weighted contemporaneous comparison group, using external data from the Multicenter Perioperative Outcomes Group (MPOG). The trial included 485 subjects in 11 sites; 406 were in the final effectiveness analysis. The post hoc analysis included 457 trial participants and 15,796 comparison patients. Patients were eligible if aged 18 years or older, American Society of Anesthesiologists (ASA) physical status 3 or 4, and scheduled for moderate- to high-risk noncardiac surgery expected to last at least 3 h. MEASUREMENTS: minutes of mean arterial pressure (MAP) below 65 mmHg and area under MAP < 65 mmHg. RESULTS: Analysis 1: Trial subjects (n = 406) experienced a mean of 9 ± 13 min of MAP below 65 mmHg, compared with the MPOG historical control mean of 25 ± 41 min, a 65% reduction (p < 0.001). Subjects with at least one episode of hypotension (n = 293) had a mean of 12 ± 14 min of MAP below 65 mmHg compared with the MPOG historical control mean of 28 ± 43 min, a 58% reduction (p< 0.001). Analysis 2: In the post hoc inverse probability treatment weighting model, patients in the trial demonstrated a 35% reduction in minutes of hypotension compared to a contemporaneous comparison group [exponentiated coefficient: - 0.35 (95%CI - 0.43, - 0.27); p < 0.001]. CONCLUSIONS: The use of prediction software for blood pressure management was associated with a clinically meaningful reduction in the duration of intraoperative hypotension. Further studies must investigate whether predictive algorithms to prevent hypotension can reduce adverse outcomes. TRIAL REGISTRATION: Clinical trial number: NCT03805217. Registry URL: https://clinicaltrials.gov/ct2/show/NCT03805217 . Principal investigator: Xiaodong Bao, MD, PhD. Date of registration: January 15, 2019.

Extent of Smartphone Addiction and its Association with Physical Activity Level, Anthropometric Indices, and Quality of Sleep in Young Adults: A Cross-Sectional Study.

Background: Smartphone addiction among young adults is a growing concern that is often underestimated despite its significant health hazards. The objective of this study was to assess the extent of smartphone addiction and its association with physical activity level, anthropometric indices, and quality of sleep in young adults. Material and Methods: This cross-sectional study was conducted among 138 allied health sciences undergraduates of a tertiary care medical school in Puducherry, South India. The participants' extent of smartphone addiction, physical activity, and sleep quality were assessed using the Smartphone Addiction Scale (SAS), International Physical Activity Questionnaire, and Pittsburgh Sleep Quality Index (PSQI), respectively. Anthropometric indices (body mass index [BMI], waist-to-hip [W: H] ratio, waist-to-height [W: Ht] ratio, Conicity Index, and A Body Shape Index [ABSI]) were also measured following standardized procedures. Correlations between smartphone addiction, physical activity, anthropometric indices, and sleep quality were evaluated using Pearson's/Spearman's rank correlation coefficient. P <0.05 was considered statistically significant. Result: Over 50% of participants showed smartphone addiction and poor sleep quality. Although a significant negative correlation was observed between SAS scores and physical activity levels, significant positive correlations were noted between SAS scores and BMI and SAS and PSQI scores. Conclusion: Smartphone addiction is associated with decreased physical activity, increased BMI, and poor sleep quality in young adults.

Multifunctional embelin- poly (3-hydroxybutyric acid) and sodium alginate-based core-shell electrospun nanofibrous mat for wound healing applications.

In this study, coaxial electrospinning is employed to make core-shell fibers, which represents a major advance in biomaterial innovation. Fibers that combine a protective shell and a therapeutic agent-loaded core, herald a revolutionary era in tissue engineering and wound care. Besides supporting cell growth, these fibers also preserve sterility, which makes them ideal for advanced wound dressings. We used embelin as the basis for this study because of its natural antibacterial properties. Its effectiveness in inhibiting the growth of bacteria made it the ideal candidate for our research. We have synthesized core-shell nanofibers that contain Sodium Alginate (SAL) in a Poly (ethylene oxide) (PEO) shell and Embelin in a Poly (3-hydroxybutyric acid) (PHB) core, which exhibit the homogeneity and flawless structure required for biomedical applications. When using SAL-PEO and EMB-PHB solutions dissolved in 1,1,1,3,3,3 hexafluoro-2-propanol (HFIP), high consistency in results can be achieved. A biocompatibility study was conducted using NIH-3T3 fibroblasts, which demonstrated remarkable adhesion and proliferation, with over 95 % growth supporting both PHB + SAL-PEO and EMB-PHB + SAL-PEO fibers. In addition, the scaffold loaded with Embelin shows strong antibacterial activity and cytocompatibility. The combined activity demonstrates the potential of EMB-PHB + SAL-PEO fibers in wound healing, where tissue regeneration and preservation of sterility are crucial. The optimized concentration of Embelin within these scaffolds demonstrates robust antibacterial efficacy while exhibiting minimal toxicity, thus positioning them as highly promising candidates for a wide range of biological applications, including wound healing.

Obstructive Sleep Apnea-Associated Intermittent Hypoxia-Induced Immune Responses in Males, Pregnancies, and Offspring.

Obstructive sleep apnea (OSA), a respiratory sleep disorder associated with cardiovascular diseases, is more prevalent in men. However, OSA occurrence in pregnant women rises to a level comparable to men during late gestation, creating persistent effects on both maternal and offspring health. The exact mechanisms behind OSA-induced cardiovascular diseases remain unclear, but inflammation and oxidative stress play a key role. Animal models using intermittent hypoxia (IH), a hallmark of OSA, reveal several pro-inflammatory signaling pathways at play in males, such as TLR4/MyD88/NF-κB/MAPK, miRNA/NLRP3, and COX signaling, along with shifts in immune cell populations and function. Limited evidence suggests similarities in pregnancies and offspring. In addition, suppressing these inflammatory molecules ameliorates IH-induced inflammation and tissue injury, providing new potential targets to treat OSA-associated cardiovascular diseases. This review will focus on the inflammatory mechanisms linking IH to cardiovascular dysfunction in males, pregnancies, and their offspring. The goal is to inspire further investigations into the understudied populations of pregnant females and their offspring, which ultimately uncover underlying mechanisms and therapeutic interventions for OSA-associated diseases.

Does bilateral hearing aid fitting improve spatial hearing ability: a systematic review and meta-analysis.

Objectives: The ability to localize sound sources is crucial for everyday listening, as it contributes to spatial awareness and the detection of warning signs. Individuals with hearing impairment have poorer localization abilities, which further deteriorate when they are fitted with a hearing aid. Although numerous studies have addressed this phenomenon, there is a lack of systematic evidence. The aim of the current systematic review is to address the following research question, "Do behavioural measures of spatial hearing ability improve with bilateral hearing aid fitting compared to the unaided hearing condition?"Design: A comprehensive search was conducted by two independent authors utilizing electronic databases, using various electronic databases, covering the period of 1965 to 2022. The inclusion and exclusion criteria were formulated using the Population, Intervention, Compression, Outcome, and Study design (PICOS) format, and the certainty of evidence was determined using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines.Results: The comprehensive search resulted in 2199 studies, 17 studies for qualitative synthesis and 15 studies for quantitative synthesis. The collected data was divided into two groups, namely vertical and horizontal localization. The results of the quantitative analysis indicate that the localization performance was significantly better in the unaided condition for both vertical and horizontal planes. The certainty of our evidence was judged to be moderate, meaning that "we are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different".Conclusion: The review findings demonstrate that the bilateral fitting of the hearing aid did not effectively preserve spatial cues, which resulted in poorer localization performance irrespective of the plane of assessment.Review Registration: Prospective Register of Systematic Reviews (PROSPERO); CRD42022358164.

Hearing aids are a widely used rehabilitative method to compensate for the loss of audibility in individuals with hearing impairment. The current review highlights that, even though hearing aids can enhance audibility, they often fail to preserve spatial cues.This review paper provides a comprehensive summary of the existing literature, focusing on the preservation of spatial cues by hearing aids and the technologies that can enhance localization performance to a certain degree.The findings of the current study encourage both researchers and hearing aid manufacturers to advance their research methods pertaining to the preservation of spatial cues. This advancement has the potential to improve spatial awareness and possibly improve speech perception in the presence of noise in hearing aid users.

Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in children. The International League of Associations for Rheumatology (ILAR) has defined JIA as "arthritis of unknown etiology persisting for ≥6 wk with an onset at <16 y of age, after excluding other causes of joint inflammation". Synovial inflammation is the result of a complex interplay of aberrant immune systems (both adaptive and innate) in a genetically susceptible individual, with possible external stimuli/triggers. Diagnosis of JIA essentially remains clinical, and laboratory investigations usually help to assess the severity of disease activity. Few investigations like antinuclear antibodies (ANA), human leukocyte antigen (HLA)-B27, and rheumatoid factor (RF) help to categorize or prognosticate a child with JIA. Timely use of effective therapeutic interventions including biological has shown good long-term outcomes of JIA.

Homozygous CARD14 variant presenting as infantile erythroderma.

A wide range of inherited and acquired conditions can manifest as infantile erythroderma, among which CARD14-associated papulosquamous eruption (CAPE) is a rare cause. An infant boy presented with a psoriasiform rash that progressed to erythroderma and was unresponsive to topical steroids and cyclosporine. The early onset of the disease, its severity and resistance to conventional treatment were suggestive of a genetic cause. Genetic evaluation revealed a homozygous CARD14 variant of uncertain significance establishing the diagnosis of CAPE, and his parents were heterozygous carriers. There was only minimal improvement in the condition with supportive management and treatment with acitretin. Unfortunately, the child succumbed to sepsis and metabolic complications following a sudden worsening of skin disease. This case highlights the significance of genetic studies in diagnosing treatment-refractory cases of infantile erythroderma and emphasises the importance of early recognition of this rare condition.