Genome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations.

Epiretinal membrane (ERM) is a common retinal condition characterized by the presence of fibrocellular tissue on the retinal surface, often with visual distortion and loss of visual acuity. We studied European American (EUR), African American (AFR), and Latino (admixed American, AMR) ERM participants in the Million Veteran Program (MVP) for genome-wide association analysis-a total of 38,232 case individuals and 557,988 control individuals. We completed a genome-wide association study (GWAS) in each population separately, and then results were meta-analyzed. Genome-wide significant (GWS) associations were observed in all three populations studied: 31 risk loci in EUR subjects, 3 in AFR, and 2 in AMR, with 48 in trans-ancestry meta-analysis. Many results replicated in the FinnGen sample. Several GWS variants associate to alterations in gene expression in the macula. ERM showed significant genetic correlation to multiple traits. Pathway enrichment analyses implicated collagen and collagen-adjacent mechanisms, among others. This well-powered ERM GWAS identified novel genetic associations that point to biological mechanisms for ERM.

Cardiac markers in left-sided breast cancer patients receiving adjuvant radiotherapy: a prospective study.

OBJECTIVES: To investigate the association between radiotherapy (RT) and cardiac biomarkers in women with left-sided breast cancer. METHODS: This prospective observational study recruited patients with stage I-III left-sided breast cancer without coronary heart disease who required adjuvant RT. High-sensitivity troponin I(hsTnI), N-terminal pro-brain natriuretic peptide(NT-proBNP), and high-sensitivity C-reactive protein(hsCRP) levels were measured pre-RT, immediately after RT, and 3 months post-RT. Cardiac-sparing RT techniques were utilized (Field-in-Field IMRT/VMAT ± voluntary deep inspiration breath-hold). Statistical analyses were performed using non-parametric tests and multivariable quantile regression (QR). RESULTS: One hundred five patients completed the study, with 63 evaluable at three months post-RT. Pre- and post-RT biomarkers showed no significant differences. Median pre-RT and post-RT values were: hsTnI (0.012ng/mL; 0.012ng/mL), hsCRP (3.1 mg/L; 2.8 mg/L), and NT-proBNP (59pg/mL; 45pg/mL). Three months post-RT, hsTnI, hsCRP and NT-proBNP levels also showed no significant differences. Multivariable QR revealed no association between heart Dmean [median(IQR): 2.87 Gy (2.05-3.94)] and post-RT biomarkers. Age and BMI were associated with hsCRP and NT-proBNP, respectively. CONCLUSIONS: hsTnI, NT-proBNP, and hsCRP are not correlated with contemporary low cardiac exposure in left-sided breast cancer patients treated with contemporary RT techniques.

School-Based Mobile Clinics to Improve Vaccine Access: A Cross-sectional Study of COVID-19 Vaccination.

School-based COVID-19 vaccine clinics were more likely to vaccinate children who identified as a racial minority, who lacked a regular source of primary care, and who lacked private insurance compared to those vaccinated in non-school-based community locations.

Novel Chitosan-Coated Liposomes Coloaded with Exemestane and Genistein for an Effective Breast Cancer Therapy.

For achieving high effectiveness in the management of breast cancer, coadministration of drugs has attracted a lot of interest as a mode of therapy when compared to a single chemotherapeutic agent that often results in reduced therapeutic end results. Owing to their proven effectiveness, good patient compliance, and lower costs, oral anticancer drugs have received much attention. In the present work, we formulated the chitosan-coated nanoliposomes loaded with two lipophilic agents, namely, exemestane (EXE) and genistein (GEN). The formulation was prepared using the ethanol injection method, which is considered a simple method for getting the nanoliposomes. The formulation was optimized using Box-Behnken design (BBD) and was extensively characterized for particle size, ζ-potential, Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), and X-ray diffraction (XRD) analysis. The sizes of conventional and coated liposomes were found to be 104.6 ± 3.8 and 120.3 ± 6.4 nm with a low polydispersity index of 0.399 and 0.381, respectively. The ζ-potential of the liposomes was observed to be -16.56 mV, which changed to a positive value of +22.4 mV, clearly indicating the complete coating of the nanoliposomes by the chitosan. The average encapsulation efficiency was found to be between 70 and 80% for all prepared formulations. The compatibility of the drug with excipients and complete dispersion of the drug inside the system were verified by FTIR, XRD, and DSC studies. Furthermore, the in vitro release studies concluded the sustained release pattern following the Korsmeyer-Peppas model as the best-fitting model with Fickian diffusion. Ex vivo studies showed better permeation of the chitosan-coated liposomes, which was further confirmed by confocal studies. The prepared chitosan-coated liposomes showed superior antioxidant activity (94.56%) and enhanced % cytotoxicity (IC50 7.253 ± 0.34 µM) compared to the uncoated liposomes. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay displayed better cytotoxicity of the chitosan-coated nanoliposomes compared to the plain drug, showing the better penetration and enhanced bioavailability of drugs inside the cells. The formulation was found to be safe for administration, which was confirmed using the toxicity studies performed on an animal model. The above data suggested that poorly soluble lipophilic drugs could be successfully delivered via chitosan-coated liposomes for their effective delivery in breast cancer.

Formulation of Functional Liquid Diets Under IDDSI Levels 0 to 2 for Dysphagia Patients: Physico-Chemical, Sensory, Antioxidant and Electromyographic Oral Processing Analyses.

Dysphagia is a significant health concern especially amongst the old age population. It is an ailment brought on by the weakening of the swallowing muscles. To reduce the risk of choking in dysphagia patients, the food is usually diluted to suit their swallowing ability. But dilution results in reducing the nutritional density of the foods thus causing undernutrition and malnutrition in patients. In this study, functional liquid diets were formulated under International Dysphagia Diet Standardization Initiative (IDDSI) levels 0-2. The developed diets were analysed for their proximate composition, colour, antioxidant and sensory properties. Antioxidant activities were determined using 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+), 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP) and total phenolic content (TPC) methods. The highest ABTS+ value was observed in pumpkin puree (level-2) i.e. 98.59%. Black carrot juice (level-1) showed the highest DPPH free radical scavenging activity and FRAP value viz. 88.43% and 689.33 µM TE/g, respectively. Electromyography (EMG) is an upcoming technique of food texture evaluation which provides real-time information about food oral processing. In this study, an EMG was conducted to measure the myoelectrical activity of human suprahyoid and masseter muscles by placing electrodes on the skin's surface during the oral processing of liquid. The EMG parameters correlated significantly with viscosity, ease of swallowing and IDDSI levels of the formulated diets. Hence EMG can be used as a tool for design and development of textured-modified diets for dysphagia patients. The sensory scores of formulated diets in this study were high indicating that these liquid diets may be incorporated into the diet plans of dysphagia patients.

Coding and non-coding variants in the ciliopathy gene CFAP410 cause early-onset non-syndromic retinal degeneration.

Inherited retinal degenerations are blinding genetic disorders characterized by high genetic and phenotypic heterogeneity. The implementation of next-generation sequencing in routine diagnostics, together with advanced clinical phenotyping including multimodal retinal imaging, have contributed to the increase of reports describing novel genotype-phenotype associations and phenotypic expansions. In this study, we describe sixteen families with early-onset non-syndromic retinal degenerations in which affected probands carried rare bi-allelic variants in CFAP410, a ciliary gene previously associated with syndromic recessive Jeune syndrome. The most common retinal phenotypes were cone-rod and rod-cone dystrophies, but the clinical presentations were unified by their early onset as well as the severe impact on central visual function. Twelve variants were detected (three pathogenic, seven likely pathogenic, two of uncertain significance), eight of which were novel. One deep intronic change, c.373+91A>G, led to the creation of a cryptic splice acceptor site in intron four, followed by the inclusion of a 200- base pair pseudoexon and subsequent premature stop codon formation. To our knowledge this is the first likely pathogenic deep-intronic variant identified in this gene. Meta-analysis of all published and novel CFAP410 variants revealed no clear correlation between the severity of the CFAP410-associated phenotypes and the identified causal variants. This is supported by the fact that the frequently encountered missense variant p.(Arg73Pro), often found in syndromic cases, was also associated with non-syndromic retinal degeneration. This study expands the current knowledge of CFAP410-associated ciliopathy by enriching its mutational landscape and supports its association with non-syndromic retinal degeneration.

A genome-wide investigation into the underlying genetic architecture of personality traits and overlap with psychopathology.

Personality is influenced by both genetic and environmental factors and is associated with other psychiatric traits such as anxiety and depression. The "Big Five" personality traits, which include neuroticism, extraversion, agreeableness, conscientiousness, and openness, are a widely accepted and influential framework for understanding and describing human personality. Of the big five personality traits, neuroticism has most often been the focus of genetic studies and is linked to various mental illnesses including depression, anxiety, and schizophrenia. Our knowledge of the genetic architecture of the other four personality traits is more limited. Utilizing the Million Veteran Program (MVP) cohort we conducted a genome-wide association study (GWAS) in individuals of European and African ancestry. Adding other published data, we performed GWAS meta-analysis for each of the five personality traits with sample sizes ranging from 237,390 to 682,688. We identified 158, 14, 3, 2, and 7 independent genome-wide significant (GWS) loci associated with neuroticism, extraversion, agreeableness, conscientiousness, and openness, respectively. These findings represent 55 novel loci for neuroticism, as well as the first GWS loci discovered for extraversion and agreeableness. Gene-based association testing revealed 254 genes showing significant association with at least one of the five personality traits. Transcriptome-wide and proteome-wide analysis identified altered expression of genes and proteins such as CRHR1, SLC12A5, MAPT, and STX4. Pathway enrichment and drug perturbation analyses identified complex biology underlying human personality traits. We also studied the inter-relationship of personality traits with 1,437 other traits in a phenome-wide genetic correlation analysis, identifying new associations. Mendelian randomization showed positive bidirectional effects between neuroticism and depression and anxiety while a negative bidirectional effect was observed for agreeableness and these psychiatric traits. This study improves our comprehensive understanding of the genetic architecture underlying personality traits and their relationship to other complex human traits.

First ever reported case of right-sided rupture of eventration of the diaphragm: Thoraco-laparoscopic approach.

ABSTRACT: Diaphragmatic eventration (DE) is an abnormal condition where a portion or the entire hemidiaphragm elevates due to insufficient muscle or nerve function while maintaining its anatomical attachments. On the other hand, congenital diaphragmatic hernias occur due to the abnormal development of muscular entities of the diaphragm, resulting in the displacement of abdominal contents into the thorax. The difference between diaphragmatic hernia and eventration is important as there is no true defect in DE. Ruptured eventration of the diaphragm is a rare entity, with only three cases reported in adults in literature till date, all on the left side. We report the first case of ruptured eventration of the diaphragm on the right side, which was repaired by a combination of laparoscopy and thoracoscopy and with double-mesh placement.

Polystyrene microplastics induced disturbances in neuronal arborization and dendritic spine density in mice prefrontal cortex.

An increasing use of plastics in daily life leads to the accumulation of microplastics (MPs) in the environment, posing a serious threat to the ecosystem, including humans. It has been reported that MPs cause neurotoxicity, but the deleterious effect of polystyrene (PS) MPs on neuronal cytoarchitectural morphology in the prefrontal cortex (PFC) region of mice brain remains to be established. In the present study, Swiss albino male mice were orally exposed to 0.1, 1, and 10 ppm PS-MPs for 28 days. After exposure, we found a significant accumulation of PS-MPs with a decreased number of Nissl bodies in the PFC region of the entire treated group compared to the control. Morphometric analysis in the PFC neurons using Golgi-Cox staining accompanied by Sholl analysis showed a significant reduction in basal dendritic length, dendritic intersections, nodes, and number of intersections at seventh branch order in PFC neurons of 1 ppm treated PS-MPs. In neurons of 0.1 ppm treated mice, we found only decrease in the number of intersections at the seventh branch order. While 10 ppm treated neurons decreased in basal dendritic length, dendritic intersections, followed by the number of intersections at the third and seventh branch order were observed. As well, spine density on the apical secondary branches along with mRNA level of BDNF was significantly reduced in all the PS-MPs treated PFC neurons, mainly at 1 ppm versus control. These results suggest that PS-MPs exposure affects overall basal neuronal arborization, with the highest levels at 1 and 10 ppm, followed by 0.1 ppm treated neurons, which may be related to the down-regulation of BDNF expression in PFC.

RTN4IP1-associated non-syndromic optic neuropathy and rod-cone dystrophy.

BACKGROUND: Biallelic variants in RTN4IP1 are a well-established cause of syndromic and nonsyndromic early-onset autosomal recessive optic neuropathy. They have more recently been reported to cause a concomitant but later-onset rod-cone dystrophy with or without syndromic features. METHODS: A comprehensive evaluation was performed that included assessment of visual and retinal function, clinical examination, and retinal imaging. Childhood ophthalmic records as well as the results of genetic testing were evaluated. RESULTS: A 24-year-old female described longstanding reduced visual acuity with more recent subjective impairment of dark adaptation. Visual acuity was subnormal in both eyes. Goldmann kinetic perimetry demonstrated scotomas in a pattern consistent with the presence of both optic neuropathy and rod-cone dystrophy with fundus exam as well as retinal imaging showing corroborating findings. Full-field electroretinography further confirmed the presence of a rod-cone dystrophy. Genetic testing demonstrated biallelic variants in RTN4IP1, one of which was novel, in association with the ocular findings. CONCLUSIONS: RTN4IP1-associated early-onset bilateral optic neuropathy with rod-cone dystrophy is a recently described clinical entity with limited reports available to-date. The present case provides additional support for this dual phenotype and identifies a novel causative variant.

The Use of Optical Coherence Tomography for Early Glaucoma Screening in a Population of Patients with Diabetes.

PURPOSE: The utility of screening for early diagnosis of glaucoma remains a widely debated topic in the care of ophthalmic patients. There are currently no population-based guidelines regarding screening for glaucoma. The purpose of this study is to determine the utility of optical coherence tomography (OCT) for early glaucoma screening in a population of diabetic patients. The results of this study may inform future screening practices. METHODS: The current study is a post hoc analysis of OCT data collected from diabetic patients screened for eye disease over 6 months. Glaucoma suspects (GS) were identified based on abnormal retinal nerve fiber layer (RNFL) thickness on OCT. Fundus photographs of GS were graded by two independent raters for vertical cup-to-disc ratio (CDR) and other signs of glaucomatous changes. RESULTS: Of the 807 subjects screened, 50 patients (6.2%) were identified as GS. The mean RNFL thickness for GS was significantly lower than the mean RNFL in the total screening population (p < .001). Median CDR for GS was 0.44. Twenty-eight eyes of 17 GS were marked as having optic disc notching or rim thinning by at least one grader. Cohen's kappa statistic for inter-rater reliability was 0.85. Racial differences showed that mean CDR was significantly higher in non-whites (p < .001). Older age was associated with thinner RNFL (r = -0.29, p = .004). CONCLUSIONS: Results of this study suggest that in a sample of diabetic patients, a small but clinically significant minority may be flagged as GS based on OCT. Nearly one-third of GS eyes were found to have glaucomatous changes on fundus photography by at least one grader. These results suggest screening with OCT may be useful in detecting early glaucomatous changes in high-risk populations, particularly older, non-white patients with diabetes.

Hepatic Vitamin A Concentrations and Association with Infectious Causes of Child Death.

OBJECTIVES: To assess postmortem vitamin A (VA) concentrations in children under 5 years of age and evaluate the association between VA deficiency (VAD) and infectious causes of death (CoD). STUDY DESIGN: In this cross-sectional study from the Child Health and Mortality Prevention Surveillance (CHAMPS) Network, liver biopsies collected within 72 hours of death were analyzed from 405 stillbirths and children under 5 years in Kenya and South Africa. Total liver VA (TLVA) concentrations were quantified using ultra-performance liquid chromatography, and cutoffs of ≤0.1 µmol/g, >0.1 to <0.7 µmol/g, ≥0.7 to <1.0 µmol/g, and ≥1.0 µmol/g were used to define VAD, adequate VA status, high VA, and hypervitaminosis A, respectively. CoD were determined by expert panel review. RESULTS: Among 366 liver samples with viable extraction, pooled prevalences of VAD, adequacy, high VA, and hypervitaminosis were 34.2%, 51.1%, 6.0%, and 8.7%, respectively. VAD was more common among neonates compared with stillbirths, infants, or children, and among those with low birthweight (LBW), underweight, or stunting (P < .05). When adjusting for site, age, and sex, there was no significant association of VAD with increased infectious CoD (OR 1.9, 95% confidence interval [CI] 0.9, 3.8, P = .073). In stratified analyses, VA deficient boys, but not girls, had an increased risk of infectious CoD (OR 3.4, 95% CI 1.3, 10.3, P = .013). CONCLUSIONS: Definitive postmortem assessment of VA status identified both VAD and VA excess among children under 5 years of age in Kenya and South Africa. VAD in boys was associated with increased risk of infectious mortality. Our findings may inform a transition from universal VA supplementation (VAS) to targeted strategies in certain countries.

The von Hippel-Lindau protein forms fibrillar amyloid assemblies that are mitigated by the anti-amyloid molecule Purpurin.

The von Hippel-Lindau protein (pVHL) is a tumor suppressor involved in oxygen regulation via dynamic nucleocytoplasmic shuttling. It plays a crucial role in cell survival by degrading hypoxia-inducible factors (HIFs). Mutations in the VHL gene cause angiogenic tumors, characterized as VHL syndrome. However, aggressive tumors involving wild-type pVHL have also been described but the underlying mechanism remains to be revealed. We have previously shown that pVHL possesses several short amyloid-forming motifs, making it aggregation-prone. In this study, using a series of biophysical assays, we demonstrated that a pVHL-derived fragment (pVHL104-140) that harbors the nuclear export motif and HIF binding site, forms amyloid-like fibrillar structures in vitro by following secondary-nucleation-based kinetics. The peptide also formed amyloids at acidic pH that mimics the tumor microenvironment. We, subsequently, validated the amyloid formation by pVHL in vitro. Using the Curli-dependent amyloid generator (C-DAG) expression system, we confirmed the amyloidogenesis of pVHL in bacterial cells. The pVHL amyloids are an attractive target for therapeutics of the VHL syndrome. Accordingly, we demonstrated in vitro that Purpurin is a potent inhibitor of pVHL fibrillation. The amyloidogenic behavior of wild-type pVHL and its inhibition provide novel insights into the molecular underpinning of the VHL syndrome and its possible treatment.

Current Scenario and Future Prospects of Adverse Drug Reactions (ADRs) Monitoring and Reporting Mechanisms in the Rural Areas of India.

BACKGROUND: Pharmacovigilance (PV) deals with the detection, collection, assessment, understanding, and prevention of adverse effects associated with drugs. The objective of PV is to ensure the safety of the medicines and patients by monitoring and reporting all adverse drug reactions (ADRs) associated with prescribed medicine usage. Findings have indicated that about 0.2- 24% of hospitalization cases are due to ADRs, of which 3.7% of patients have lethal ADRs. The reasons include the number of prescribed drugs, an increased number of new medicines in the market, an inadequate PV system for ADR monitoring, and a need for more awareness and knowledge about ADR reporting. Severe ADRs lead to enhanced hospital stays, increased treatment costs, risk of death, and many medical and economic consequences. Therefore, ADR reporting at its first instance is essential to avoid further harmful effects of the prescribed drugs. In India, the rate of ADR reporting is less than 1%, whereas worldwide, it is 5% due to a need for more awareness about PV and ADR monitoring among healthcare providers and patients. The main objective of this review is to highlight the current scenario and possible futuristic ways of ADR reporting methods in rural areas of India. We have searched the literature using PubMed, Google scholar, Indian citation index to retrieve the resources related to ADR monitoring and reporting in India's urban and rural areas. Spontaneous reporting is the most commonly used PV method to report ADRs in India's urban and rural areas. Evidence revealed that no effective ADR reporting mechanisms developed in rural areas causing underreporting of ADR, thus increasing the threat to the rural population. Hence, PV and ADR reporting awareness among healthcare professionals and patients, telecommunication, telemedicine, use of social media and electronic medical records, and artificial intelligence are the potential approaches for prevention, monitoring, and reporting of ADRs in rural areas.

Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications.

As recreational use of cannabis is being decriminalized in many places and medical use widely sanctioned, there are growing concerns about increases in cannabis use disorder (CanUD), which is associated with numerous medical comorbidities. Here we performed a genome-wide association study of CanUD in the Million Veteran Program (MVP), followed by meta-analysis in 1,054,365 individuals (ncases = 64,314) from four broad ancestries designated by the reference panel used for assignment (European n = 886,025, African n = 123,208, admixed American n = 38,289 and East Asian n = 6,843). Population-specific methods were applied to calculate single nucleotide polymorphism-based heritability within each ancestry. Statistically significant single nucleotide polymorphism-based heritability for CanUD was observed in all but the smallest population (East Asian). We discovered genome-wide significant loci unique to each ancestry: 22 in European, 2 each in African and East Asian, and 1 in admixed American ancestries. A genetically informed causal relationship analysis indicated a possible effect of genetic liability for CanUD on lung cancer risk, suggesting potential unanticipated future medical and psychiatric public health consequences that require further study to disentangle from other known risk factors such as cigarette smoking.

When the Going Gets Tough: A Case Report and Review of Calcinosis Cutis in an Infant with Pseudo-Hypoaldosteronism.

Calcium gluconate solutions are an essential part of the intensive care medication armamentarium. Calcium-related extravasations are not an infrequent occurrence. However, occult extravasation presenting solely as an isolated mass lesion with no preceding cutaneous manifestation is rare. Calcinosis cutis is an extraosseous collection of calcium deposits in the skin and subcutaneous tissues. Multiple etiopathogenetic factors play a role in its manifestations. We illustrate a case of a seven-week-old infant diagnosed with pseudo-hypoaldosteronism with a mysterious swelling on the left leg during the third week of hospitalization, which was attributed to occult iatrogenic calcinosis cutis.

PFOS-induced dyslipidemia and impaired cholinergic neurotransmission in developing zebrafish: Insight into its mechanisms.

Perfluorooctane sulfonate (PFOS) is a persistent organic pollutant that has been widely detected in the environment and is known to accumulate in organisms, including humans. The study investigated dose-dependent mortality, hatching rates, malformations, lipid accumulation, lipid metabolism alterations, and impacts on cholinergic neurotransmission. Increasing PFOS concentration led to higher mortality, hindered hatching, and caused concentration-dependent malformations, indicating severe abnormalities in developing zebrafish. The results also demonstrated that PFOS exposure led to a significant increase in total lipids, triglycerides, total cholesterol, and LDL in a concentration-dependent manner, while HDL cholesterol levels were significantly decreased. Additionally, PFOS exposure led to a significant decrease in glucose levels. The study identified TGs, TCHO, and glucose as the most sensitive biomarkers in assessing lipid metabolism alterations. The study also revealed altered expression of genes involved in lipid metabolism, including upregulation of fasn, acaca, and hmgcr and downregulation of ldlr, pparα, and abca1, as well as decreased lipoprotein lipase (LPL) and increased fatty acid synthase (FAS) activity,suggesting an impact on fatty acid synthesis, cholesterol uptake, and lipid transport. Additionally, PFOS exposure led to impaired cholinergic neurotransmission, evidenced by a concentration-dependent inhibition of acetylcholinesterase activity, altered gene expressions related to neural development and function, and reduced Na+/K+-ATPase activity. STRING network analysis highlighted two distinct gene clusters related to lipid metabolism and cholinergic neurotransmission, with potential interactions through the pparα-creb1 pathway. Overall, this study provide important insights into the potential health risks associated with PFOS exposure, including dyslipidemia, cardiovascular disease, impaired glucose metabolism, and neurotoxicity. Further research is needed to fully elucidate the underlying mechanisms and potential long-term effects of PFOS exposure.

Calponin 2 regulates ketogenesis to mitigate acute kidney injury.

Calponin 2 (CNN2) is a prominent actin stabilizer. It regulates fatty acid oxidation (FAO) by interacting with estrogen receptor 2 (ESR2) to determine kidney fibrosis. However, whether CNN2 is actively involved in acute kidney injury (AKI) remains unclear. Here, we report that CNN2 was induced in human and animal kidneys after AKI. Knockdown of CNN2 preserved kidney function, mitigated tubular cell death and inflammation, and promoted cell proliferation. Distinct from kidney fibrosis, proteomics showed that the key elements in the FAO pathway had few changes during AKI, but we identified that 3-hydroxymethylglutaryl-CoA synthase 2 (Hmgcs2), a rate-limiting enzyme of endogenous ketogenesis that promotes cell self-renewal, was markedly increased in CNN2-knockdown kidneys. The production of ketone body ß-hydroxybutyrate and ATP was increased in CNN2-knockdown mice. Mechanistically, CNN2 interacted with ESR2 to negatively regulate the activities of mitochondrial sirtuin 5. Activated sirtuin 5 subsequently desuccinylated Hmgcs2 to produce energy for mitigating AKI. Understanding CNN2-mediated discrete fine-tuning of protein posttranslational modification is critical to optimize organ performance after AKI.

Impact of anthropometry training and feasibility of 3D imaging on anthropometry data quality among children under five years in a postmortem setting.

BACKGROUND: The Child Health and Mortality Prevention Surveillance Network (CHAMPS) identifies causes of under-5 mortality in high mortality countries. OBJECTIVE: To address challenges in postmortem nutritional assessment, we evaluated the impact of anthropometry training and the feasibility of 3D imaging on data quality within the CHAMPS Kenya site. DESIGN: Staff were trained using World Health Organization (WHO)-recommended manual anthropometry equipment and novel 3D imaging methods to collect postmortem measurements. Following training, 76 deceased children were measured in duplicate and were compared to measurements of 75 pre-training deceased children. Outcomes included measures of data quality (standard deviations of anthropometric indices and digit preference scores (DPS)), precision (absolute and relative technical errors of measurement, TEMs or rTEMs), and accuracy (Bland-Altman plots). WHO growth standards were used to produce anthropometric indices. Post-training surveys and in-depth interviews collected qualitative feedback on measurer experience with performing manual anthropometry and ease of using 3D imaging software. RESULTS: Manual anthropometry data quality improved after training, as indicated by DPS. Standard deviations of anthropometric indices exceeded limits for high data quality when using the WHO growth standards. Reliability of measurements post-training was high as indicated by rTEMs below 1.5%. 3D imaging was highly correlated with manual measurements; however, on average 3D scans overestimated length and head circumference by 1.61 cm and 2.27 cm, respectively. Site staff preferred manual anthropometry to 3D imaging, as the imaging technology required adequate lighting and additional considerations when performing the measurements. CONCLUSIONS: Manual anthropometry was feasible and reliable postmortem in the presence of rigor mortis. 3D imaging may be an accurate alternative to manual anthropometry, but technology adjustments are needed to ensure accuracy and usability.

VISUAL AND ANATOMICAL CHANGES AFTER DRUG CESSATION IN PENTOSAN POLYSULFATE SODIUM-ASSOCIATED MACULOPATHY.

PURPOSE: The purpose of this study was to describe a case of development of pentosan polysulfate sodium (PPS)-related maculopathy that exhibited potential improvement in imaging findings after drug cessation. METHODS: This study is a case report. RESULTS: A 66-year-old woman presented with progressive pigmentary maculopathy associated with long-term PPS usage, including development of a choroidal neovascular membrane in her right eye. After discontinuation of PPS, her clinical course was notable for partial subjective and objective improvement in visual acuity, as well as partial improvement in outer retinal architecture on ocular coherence tomography, but persistence of retinal pigment epithelium atrophy and autofluorescence changes. CONCLUSION: The course of retinopathy after discontinuation of PPS has yet to be fully determined and has so far been suggested to be progressive. Anatomical improvements seen in our case suggest that further investigations are warranted to determine whether there is potential for partial reversal of some changes in PPS maculopathy.