The role of enhanced expression of Cx43 in patients with ulcerative colitis.

The pathogenesis of ulcerative colitis (UC) involves chronic inflammation of the submucosal layer and disruption of epithelial barrier function within the gastrointestinal tract. Connexin 43 (Cx43) has been implicated in the pathogenesis of intestinal inflammation and its associated carcinogenic effects. However, a comprehensive analysis of Cx43's role in mucosal and peripheral immunity in patients with UC is lacking. In this study, the colon tissues of patients with UC exhibited severe damage to the intestinal mucosal barrier, resulting in a significant impairment of junctional communication as observed by transmission electron microscopy. The mRNA expression of Cx43 was found to be significantly elevated in the UC group compared to the control group, as determined using the Affymetrix expression profile chip and subsequently validated using qRT-PCR. The immunofluorescence analysis revealed a significantly higher mean fluorescence intensity of Cx43 in the UC group compared to the control group. Additionally, Cx43 was observed in both the cell membrane and nucleus, providing clear evidence of nuclear translocation. The proportion of Cx43 in the UC group for CD4+ and CD8+ T lymphocytes was increased in the control group, but only the proportion of Cx43 for CD8+ T lymphocytes showed significant difference by flow cytometry. The involvement of Cx43 in the pathogenesis of UC and its potential role in mucosal immunity warrants further investigation, as it holds promise as a prospective biomarker and therapeutic target for this condition. The proportion of Cx43 in the UC group for CD4+ and CD8+ T lymphocytes was increased in the control group, but only the proportion of Cx43 for CD8+ T lymphocytes showed a significant difference.

The influence of candidates' race on examiners' ratings in standardised assessments of clinical practice.

PURPOSE: Delivering fair and reliable summative assessments in medical education assumes examiner decision making is devoid of bias. We investigated whether candidate racial appearances influenced examiner ratings in undergraduate clinical exams. METHODS: We used an internet-based design. Examiners watched a randomised set of six videos of three different white candidates and three different non-white (Asian, black and Chinese) candidates taking a clinical history at either fail, borderline or pass grades. We compared the median and interquartile range (IQR) of the paired difference between scores for the white and non-white candidates at each performance grade and tested for statistical significance. RESULTS: 160 Examiners participated. At the fail grade, the black and Chinese candidates scored lower than the white candidate, with median paired differences of -2.5 and -1 respectively (both p < 0.001). At the borderline grade, the black and Chinese candidates scored higher than the white candidate, with median paired differences of +2 and +3, respectively (both p < 0.001). At the passing grade, the Asian candidate scored lower than the white candidate (median paired difference -1, p < 0.001). CONCLUSION: The racial appearance of candidates appeared to influence the scores awarded by examiners, but not in a uniform manner.

Deconstructing the sex gap in child undernutrition in India: Are Indian boys at elevated risk of anthropometric failure than the girls?

BACKGROUNDS & OBJECTIVES: The privileging of boys in immunization coverage, breastfeeding, and other child care practices in Indian patriarchal society raises questions about whether there are sex differences in the prevalence of undernutrition among children. This study evaluates the sex gap in the prevalence of Composite Index of Anthropometric Failure (CIAF) among Indian children from 2015-16 to 2019-21. Additionally, it seeks to identify the sex-specific determinants and persistent sex gap at national and subnational levels (social, economic, religious, and geopolitical regions) in anthropometric failure among the children from 2015-16 to 2019-21. MATERIALS AND METHODS: The study utilizes the 4th (2015-16) and 5th (2019-21) rounds of the National Family Health Survey data. Logistic regression models and the Fairlie decomposition technique were employed to explore the persistent and significant sex gap in the prevalence of CIAF, as well as the sex-specific determinants of CIAF among children in 2015-16 and 2019-21. RESULTS: The study reveals a significant sex gap (approximately 4%-points), with boy's disadvantage in the prevalence of CIAF from 2015-16 to 2019-21 at both the national and subnational levels (social, religious, socioeconomic groups, and geopolitical regions). The gap is more pronounced in the first year of life and decreases in later stages. A comparatively faster CIAF decline among girls from 2016 to 2021 has widened the sex gap in final year than the previous. Child, mother, household, community, and geographic backgrounds explains about 5%-6% of the sex gap in the prevalence of CIAF from 2015-16 to 2019-21. The remaining 94%-95% of the unexplained sex gap may be attributed to biological factors or other factors. Currently, a heightened boy's disadvantage in CIAF risk is observed in ST community, wealthiest families, and the northern India. CONCLUSION: The findings suggest a special attention for boys under 3 years to offset biological disadvantages like greater disease sensitivity and fragility compared to girls early on.

Levator-urethra gap: is there a need for individualization of cut-offs?

OBJECTIVE: To determine whether age, height, weight and BMI are associated with the levator urethra gap measurement, and whether these factors confound the relationship between LUG and symptoms and signs of POP. METHODS: Retrospective study of women seen at a tertiary urogynecology unit between January 2020 and December 2021. Postprocessing of saved ultrasound volume data was utilised to measure the levator- urethra gap, blinded against all other data. This measurement was tested for its association with organ descent and hiatal area, and height, weight and body mass index were investigated for any potential confounding effect. RESULTS: The 624 women seen during the inclusion period presented mostly with stress urinary incontinence (448, 72%), urgency urinary incontinence (469, 75%) and/ or prolapse (338, 54%). Mean age at assessment was 58 (range, 20-94) years, mean height was 163 (range, 142-182) cm, mean weight 80 (41- 153) kg, mean BMI was 30 (17-65) kg/m2. LUG measurements could be obtained in 613 women, resulting in 12*613= 7356 measurements. The average LUG in individual women was 2.35 cm on the right and 2.32 cm on the left (n.s.), for an average of 2.34 cm (SD 0.63) overall. Mean LUG was associated with symptoms and signs of prolapse, both on POPQ and on imaging, but not with height (P= 0.36), weight (P= 0.2) or BMI (P= 0.09). CONCLUSION: Levator- urethra gap measurements do not seem to be associated with height, weight or BMI in our population, obviating the need for individualisation of LUG. However, this does not exclude interethnic variability of this biometric measure. This article is protected by copyright. All rights reserved.

Ethylene Glycol Poisoning: A Case Study of a 71-Year-Old Male with a History of Alcohol Abuse and Suicide Attempts.

A 71-year-old male with a history of alcohol abuse and multiple suicide attempts was brought to the emergency department in an unconscious state. Initial assessment revealed profound obtundation and malnutrition. Laboratory findings demonstrated a significant anion gap metabolic acidosis with a high osmolar gap, suggestive of possible toxic alcohol ingestion. Despite negative serum alcohol levels, ethylene glycol poisoning was confirmed with a level of 226. Treatment included fluid resuscitation, bicarbonate therapy, and fomepizole administration. However, due to progressive multi-organ failure, continuous veno-venous hemodialysis was initiated. Despite interventions, the patient deteriorated rapidly, leading to a decision for hospice care, ultimately resulting in death. Ethylene glycol poisoning presents significant challenges in management, with potential complications including renal failure and multi-organ dysfunction. Fomepizole remains the cornerstone of treatment, but additional therapies such as ethanol administration were considered but ultimately deemed unnecessary due to associated risks. This case highlights the complexity and severity of ethylene glycol poisoning, emphasizing the need for early recognition and aggressive management strategies.

Research on the impact of climate change on the income gap between urban and rural areas-empirical analysis based on provincial panel data in China.

Narrowing the income gap between urban and rural areas is the key to achieving common prosperity in China. On the basis of analyzing the mechanism of climate change's impact on urban-rural income gap, this article empirically analyzes the impact of climate change on urban-rural income gap using provincial-level panel data of 30 provinces in China from 2011 to 2020. Research indicates that climate change significantly impacts the urban-rural income gap at the 1% significance level, implying that climate change exacerbates the urban-rural income gap. This widening effect varies significantly across different regions, particularly in the western regions and areas with lower fiscal support for agriculture. Further analysis reveals that there is a mediating role between the total agricultural output value and resource mismatch in the impact of climate change on urban-rural income inequality; the digital rural construction plays a regulatory role in the impact of climate change on the urban-rural income gap. On this basis, policy recommendations are proposed to promote the development of climate-resilient agriculture, improve the meteorological forecast and early warning system, increase financial support, and optimize the allocation of agricultural resources.

Astroglial gap junctions strengthen hippocampal network activity by sustaining afterhyperpolarization via KCNQ channels.

Throughout the brain, astrocytes form networks mediated by gap junction channels that promote the activity of neuronal ensembles. Although their inputs on neuronal information processing are well established, how molecular gap junction channels shape neuronal network patterns remains unclear. Here, using astroglial connexin-deficient mice, in which astrocytes are disconnected and neuronal bursting patterns are abnormal, we show that astrocyte networks strengthen bursting activity via dynamic regulation of extracellular potassium levels, independently of glutamate homeostasis or metabolic support. Using a facilitation-depression model, we identify neuronal afterhyperpolarization as the key parameter underlying bursting pattern regulation by extracellular potassium in mice with disconnected astrocytes. We confirm this prediction experimentally and reveal that astroglial network control of extracellular potassium sustains neuronal afterhyperpolarization via KCNQ voltage-gated K+ channels. Altogether, these data delineate how astroglial gap junctions mechanistically strengthen neuronal population bursts and point to approaches for controlling aberrant activity in neurological diseases.

The gap year for college students interested in medicine: Can they contribute to your mission?

Gap years taken between undergraduate completion and entrance into medical school have become increasingly popular. We examine the role of gap years among college graduates interested in medicine and how they might contribute to academic research productivity within clinical environments. Recently, academic faculty have struggled to balance increasing clinical responsibilities with their scholarly endeavors. Academic medical departments may have incentives to hire pre-medical students to help ease the research burden on faculty. Properly motivated pre-medical students may view research positions in academic medical departments as ideal opportunities to learn in areas that will broaden their scientific knowledge and help prepare them for medical school, while greatly enhancing their medical school applications through distinguishing themselves as co-authors published in medical journals. Our experience, with two co-authors working as research associates while preparing for their medical school applications and careers, suggests that pre-medical students can strengthen their medical school applications during their gap year(s) while proving instrumental in enhancing research output thus alleviating the workload of clinical faculty.

Global trends of dioxin and dioxin-like PCBs in animal-origin foods: a systematic review and gap areas.

Dioxins and dioxin-like polychlorinated biphenyls are a group of lipophilic compounds classified under persistent environmental pollutants (POPs). Significant sources of dioxin emissions include industrial effluents, open burning practices, and biomedical and municipal waste incinerators. These emissions will enter the food chain and accumulate in animal-origin foods (AOFs). A systematic review was conducted to analyze the global levels of dioxins and dioxin-like PCBs in AOFs using PRISMA guidelines 2020. The data on the dioxin contamination in AOFs were extracted from 53 publications based on their presence in eggs, meat and meat products, milk and dairy products, marine fish and fish products, and freshwater fish and crabs. A gap analysis was conducted based on the systematic review to understand the grey areas to be focused on the  future. No trend of dioxin contamination in AOFs was observed. A significant gap area was found in the need for nationwide data generation in countries without periodic monitoring of AOFs for dioxin contamination. Source apportionment studies need to be explored for the dioxin contamination of AOFs. Large-scale screening tests of AOFs using DR-CALUX based on market surveys are required for data generation. The outcomes of the study will be helpful for stakeholders and policyholders in framing new policies and guidelines for food safety in AOFs.

Green Synthesis of Highly Fluorescent NCQDs: A Comprehensive Study on Synthesis, Characterization, Photophysical Properties, pH Sensing, Heavy Metal Detection, and Solvatochromic Behavior through Hydrothermal Method.

Solvatochromic studies in conjunction with NCQDs and analysis of material at different pH levels provide valuable insights about the process of metal ion sensing. Metal ion sensing holds significant importance in various fields like environment monitoring, biomedical diagnostics and various industrial purpose. The detection of metal ions by mixing the nitrogen-doped quantum dots (NCQDs) in the solvent at different pH levels for the analysis of the photoluminescence spectra is the unique property to achieve selective metal ion detection. In present study, the synthesis of NCQDs was performed by the use of flowers of Tecoma stans. The synthesis of NCQDs to best of our knowledge using flowers of Tecoma stans as natural carbon source via hydrothermal process has been done for the first time. The NCQDs exhibit absorption bands ranging from 190 to 450 nm, with the energy band gap varying from 3.55 to 5.42 eV when mixed with different solvent such as, 1-4 dioxane, acetone, acetonitrile, ethyl- acetate, ethanol, methanol and toluene. The fluorescence spectra exhibited highly intense range from approximately 390 to 680 nm across various solvents. XRD analysis further confirmed the crystalline nature of the particles with an average size of 6.96 nm. Different peak positions of the FTIR spectra support functional groups having C-H stretching, C = O (carbonyl) stretching, and C = C stretching vibrations. In the study a notable solvatochromic shift was observed, indicating sensitivity to change in solvent polarity. Additionally, the investigation of the ratio of ground to excited state dipole moment based on solvatochromic shift yielded a value of 3.30. This provide valuable information about optical and electronic properties of NCQDs. Overall, our study sheds light on the unique properties of NCQDs synthesized from Tecoma stans flowers and their potential applications in metal ion sensing, pH probing, and solvent polarity studies.

Intraspecific divergence in a coastal plant, Euphorbia jolkinii, at a major biogeographic boundary in East Asia.

PREMISE: Quaternary climatic fluctuations and long-distance seed dispersal across the sea are critical factors affecting the distribution of coastal plants, but the spatiotemporal nature of population expansion and distribution change of East Asian coastal plants during this period are rarely examined. To explore this process, we investigated the genome-wide phylogenetic patterns of Euphorbia jolkinii Boiss. (Euphorbiaceae), which grows widely on littoral areas of Japan, Korea, and Taiwan. METHODS: We used plastome sequences and genome-wide single nucleotide polymorphisms in samples across the species range to reveal phylogeographic patterns and spatiotemporal distributional changes. We conducted ecological niche modeling for the present and the last glacial maximum (LGM). RESULTS: Genetic differentiation was observed between the northern and southern populations of E. jolkinii, separated by the major biogeographic boundary, the Tokara Gap. These two groups of populations differentiated during the glacial period and subsequently intermingled in the intermorainic areas of the central Ryukyu Islands after the LGM. Ecological niche models suggested that the potential range of E. jolkinii was restricted to southern Kyushu; however, it was widespread in the southern Ryukyu Islands and Taiwan during the LGM. CONCLUSIONS: This study provides evidence of genetic differentiation among coastal plant populations separated by the prominent biogeographical boundary. Although coastal plants are typically expected to maintain population connectivity through sea-drifted seed dispersal, our findings suggest that genetic differences may arise because of a combination of limited gene flow and changes in climate during the glacial period.

Shades of Blue: A Case Series of Acquired Methemoglobinemia.

Acquired methemoglobinemia (MetHb) is a rare but potentially life-threatening condition that has varied etiology, usually toxin- or drug-induced. We had five cases of acquired methemoglobinemia during six months. Their presentation varied from an asymptomatic state to respiratory distress. The presence of cyanosis and low oxygen saturation (SpO2), despite normal partial pressure of oxygen (PaO2) and chocolate brown-colored blood, were diagnostic clues present in all cases. A high level of methemoglobinemia was detected on arterial blood gas (ABG), confirming the diagnosis. Methylene blue was used as an antidote along with supportive care in symptomatic cases. All these cases of methemoglobinemia recovered completely. A high index of suspicion for methemoglobinemia should be maintained in cases presenting with persistent hypoxia or cyanosis despite normal PaO2.

The efficacy and real-world effectiveness of a diet low in fermentable oligo-, di-, monosaccharides and polyols in irritable bowel syndrome: A systematic review and meta-analysis.

BACKGROUND & AIMS: A diet low in fermentable oligo-, di-, monosaccharides, and polyols (LFD) has been shown to effectively reduce irritable bowel syndrome (IBS) symptoms. Effects resulting from real-world studies may differ from those seen in efficacy studies because of the diversity of patients in real-world settings. This systematic review and meta-analysis aimed to compare the effect of the LFD on reducing IBS symptoms and improving the quality of life (QoL) in efficacy trials and real-world studies. METHODS: Major databases, trial registries, dissertations, and journals were systematically searched for studies on the LFD in adults with IBS. Meta-analysis was conducted using a random effects model with standardized mean differences (SMD) and 95% confidence intervals (CI). Outcomes of interest were all patient-reported: stool consistency, stool frequency, abdominal pain, overall symptoms, adequate symptom relief, IBS-specific QoL and adherence to the LFD. RESULTS: Eleven efficacy and 19 real-world studies were reviewed. The meta-analysis results for abdominal pain (SMD 0.35, 95% CI 0.16 to 0.54) and QoL (SMD 0.23, 95% CI -0.05 to 0.50) showed the LFD was beneficial in efficacy studies with no statistically significant results for stool frequency (SMD 0.71, 95% CI 0.34 to 1.07). Real-world studies found improvements in abdominal pain and QoL. Due to heterogeneity, no meta-analysis was done for stool consistency and overall symptoms. In these outcomes, results were mostly supportive of the LFD, but they were not always statistically significant. CONCLUSIONS: The results of this systematic review and meta-analysis suggest the LFD improves outcomes compared to a control diet (efficacy studies) or baseline data (real-world studies). Because of diverse study designs and heterogeneity of results, a clear superiority of the LFD over control diets could not be concluded. There are no indications of an efficacy-effectiveness gap for the LFD in adults with IBS.

Theoretical Study of the Magnetic and Optical Properties of Ion-Doped LiMPO4 (M = Fe, Ni, Co, Mn).

Using a microscopic model and Green's function theory, we calculated the magnetization and band-gap energy in ion-doped LiMPO4 (LMPO), where M = Fe, Ni, Co, Mn. Ion doping, such as with Nb, Ti, or Al ions at the Li site, induces weak ferromagnetism in LiFePO4. Substituting Li with ions of a smaller radius, such as Nb, Ti, or Al, creates compressive strain, resulting in increased exchange interaction constants and a decreased band-gap energy, Eg, in the doped material. Notably, Nb ion doping at the Fe site leads to a more pronounced decrease in Eg compared to doping at the Li site, potentially enhancing conductivity. Similar trends in Eg reduction are observed across other LMPO4 compounds. Conversely, substituting ions with a larger ionic radius than Fe, such as Zn and Cd, causes an increase in Eg.

Refractory hypoxia and saturation gap in a COVID-19 patient.

Acquired methemoglobinemia, predominantly due to oxidizing medications occurs when heme iron in hemoglobin is oxidized from ferrous to ferric ion and binds oxygen irreversibly leading to functional anemia, cyanosis, and tissue hypoxia. We report a case of a 60-year-old man with multiple comorbidities who was diagnosed with coronavirus disease 2019 (COVID-19) and developed methemoglobinemia after consumption of prescribed supplements. He presented with dyspnea and cyanosis. An oxygen saturation gap with characteristic chocolate-brown arterial blood indicated methemoglobinemia. Outsourced methemoglobin (MetHb) was increased at 9.0%. Despite aggressive intervention, he succumbed to his illness. In this case, we discuss the pathophysiology of why some individuals, especially the elderly with COVID-19 are more susceptible to develop methemoglobinemia after possibly being exposed to oxidizing agents. Laboratory methods for assessing oxygen saturation, including pulse oximetry, arterial blood gas and co-oximetry are examined in relation to this case. The importance of considering a diagnosis of methemoglobinemia based on clinical and biochemical findings although MetHb assay or co-oximetry are not readily available is also emphasized.

Good agricultural practices (GAP) adoption intensity and production constraints in apple orchards of western Nepal.

The declaration of 'Fruits Decade 2016/17-2026/27' and the enaction of the 'NepalGAP Scheme' by the Government of Nepal has redirected increased public investments to promote apple production and marketability in the western high hills of Nepal. This study explores major good agricultural practices (GAP) related to orchard management, factors influencing their adoption intensity, and key underlying constraints to production using cross-sectional survey data from apple growers in Dolpa district, Nepal. The results showed that farmers mostly adopted GAP such as frequent weeding, intercropping, and nutrient management in apple orchards. Based on the negative binomial regression estimates, household characteristics such as gender of the orchard owner, experience, and number of literate household members were found influential in determining the GAP adoption intensity. The analysis of the problem severity index implied that apple production is mostly constrained by limited access to production inputs and transportation. The findings provide useful insights to the farmers and policymakers regarding the current scenario of GAP adoption along with the diversity of barriers that severely limits the realization of apple production potential in western Nepal.

Corrigendum: Electrical synapses for a pooling layer of the convolutional neural network in retinas.

[This corrects the article DOI: 10.3389/fncel.2023.1281786.].

Spontaneous Repolarization Alternans Causes VT/VF Rearrest That Is Suppressed by Preserving Gap Junctions.

BACKGROUND: Ventricular tachycardia (VT)/ventricular fibrillation (VF) rearrest after successful resuscitation is common, and survival is poor. A mechanism of VT/VF, as demonstrated in ex vivo studies, is when repolarization alternans becomes spatially discordant (DIS ALT), which can be enhanced by impaired gap junctions (GJs). However, in vivo spontaneous DIS ALT-induced VT/VF has never been demonstrated, and the effects of GJ on DIS ALT and VT/VF rearrest are unknown. OBJECTIVES: This study aimed to determine whether spontaneous VT/VF rearrest induced by DIS ALT occurs in vivo, and if it can be suppressed by preserving Cx43-mediated GJ coupling and/or connectivity. METHODS: We used an in vivo porcine model of resuscitation from ischemia-induced cardiac arrest combined with ex vivo optical mapping in porcine left ventricular wedge preparations. RESULTS: In vivo, DIS ALT frequently preceded VT/VF and paralleled its incidence at normal (37°C, n = 9) and mild hypothermia (33°C, n = 8) temperatures. Maintaining GJs in vivo with rotigaptide (n = 10) reduced DIS ALT and VT/VF incidence, especially during mild hypothermia, by 90% and 60%, respectively (P < 0.001; P < 0.013). Ex vivo, both rotigaptide (n = 5) and αCT11 (n = 7), a Cx43 mimetic peptide that promotes GJ connectivity, significantly reduced DIS ALT by 60% and 100%, respectively (P < 0.05; P < 0.005), and this reduction was associated with reduced intrinsic heterogeneities of action potential duration rather than changes in conduction velocity restitution. CONCLUSIONS: These results provide the strongest in vivo evidence to date suggesting a causal relationship between spontaneous DIS ALT and VT/VF in a clinically realistic scenario. Furthermore, our results suggest that preserving GJs during resuscitation can suppress VT/VF rearrest.

Genetically engineered human embryonic kidney cells as a novel vehicle for dual patch clamp study of human gap junction channels.

Mutations in more than half of human connexin genes encoding gap junction subunits have been linked to inherited human diseases. Functional studies of human gap junction (GJ) channels are essential for revealing mechanistic insights on the etiology of disease-linked connexin mutants. However, the commonly used Xenopus oocytes, N2A, HeLa, and other model cells for recombinant expression of human connexins have different and significant limitations. Here we developed a human cell line (HEK293) with each of the endogenous connexins (Cx43 and Cx45) knocked out using the CRISPR-Cas9 system. Double knockout HEK293 cells showed no background GJ coupling, were easily transfected with several human connexin genes (such as those encoding Cx46, Cx50, Cx37, Cx45, Cx26, and Cx36) which successfully formed functional GJs and were readily accessible for dual patch clamp analysis. Single knockout Cx43 or Cx45 HEK cell lines could also be used to characterize human GJ channels formed by Cx45 or Cx43, respectively, with an expression level suitable for studying macroscopic and single channel GJ channel properties. A cardiac arrhythmia linked Cx45 mutant R184G failed to form functional GJs in DKO HEK293 cells with impaired localizations. These genetically engineered HEK293 cells are well suited for patch clamp study of human GJ channels.