Long-term spatiotemporal variations of ammonia in the Yangtze River Delta region of China and its driving factors.

This study focuses on the spatiotemporal distribution, urban-rural variations, and driving factors of ammonia Vertical Column Densities (VCDs) in China's Yangtze River Delta region (YRD) from 2008 to 2020. Utilizing data from the Infrared Atmospheric Sounding Interferometer (IASI), Generalized Additive Models (GAM), and the GEOS-Chem chemical transport model, we observed a significant increase of NH3 VCDs in the YRD between 2014 and 2020. The spatial distribution analysis revealed higher NH3 concentrations in the northern part of the YRD region, primarily due to lower precipitation, alkaline soil, and intensive agricultural activities. NH3 VCDs in the YRD region increased significantly (65.18%) from 2008 to 2020. The highest growth rate occurs in the summer, with an annual average growth rate of 7.2% during the period from 2014 to 2020. Agricultural emissions dominated NH3 VCDs during spring and summer, with high concentrations primarily located in the agricultural areas adjacent to densely populated urban zones. Regions within several large urban areas have been discovered to exhibit relatively stable variations in NH3 VCDs. The rise in NH3 VCDs within the YRD region was primarily driven by the reduction of acidic gases like SO2, as emphasized by GAM modeling and sensitivity tests using the GEOS-Chem model. The concentration changes of acidic gases contribute to over 80% of the interannual variations in NH3 VCDs. This emphasizes the crucial role of environmental policies targeting the reduction of these acidic gases. Effective emission control is urgent to mitigate environmental hazards and secondary particulate matter, especially in the northern YRD.

Quantitative impacts of meteorology and emissions on the long-term trend of O3 in the Yangtze River Delta (YRD), China from 2015 to 2022.

Extensive spatiotemporal analyses of long-trend surface ozone in the Yangtze River Delta (YRD) region and its meteorology-related and emission-related have not been systematically analyzed. In this study, by using 8-year-long (2015-2022) surface ozone observation data, we attempted to reveal the variation of multiple timescale components using the Kolmogorov-Zurbenko filter, and the effects of meteorology and emissions were quantitatively isolated using multiple linear regression with meteorological variables. The results showed that the short-term, seasonal, and long-term components accounted for daily maximum 8-hr average O3 (O3-8 hr) concentration, 46.4%, 45.9%, and 1.0%, respectively. The meteorological impacts account for an average of 71.8% of O3-8 hr, and the YRD's eastern and northern sections are meteorology-sensitive areas. Based on statistical analysis technology with empirical orthogonal function, the contribution of meteorology, local emission, and transport in the long-term component of O3-8 hr were 0.21%, 0.12%, and 0.6%, respectively. The spatiotemporal analysis indicated that a distinct decreasing spatial pattern could be observed from coastal cities towards the northwest, influenced by the monsoon and synoptic conditions. The central urban agglomeration north and south of the YRD was particularly susceptible to local pollution. Among the cities studied, Shanghai, Anqing, and Xuancheng, located at similar latitudes, were significantly impacted by atmospheric transmission-the contribution of Shanghai, the maximum accounting for 3.6%.

Development of an equation to predict delta bilirubin levels using machine learning.

OBJECTIVE: Delta bilirubin (albumin-covalently bound bilirubin) may provide important clinical utility in identifying impaired hepatic excretion of conjugated bilirubin, but it cannot be measured in real-time for diagnostic purposes in clinical laboratories. METHODS: A total of 210 samples were collected, and their delta bilirubin levels were measured four times using high-performance liquid chromatography. Data collected included age, sex, diagnosis code, delta bilirubin, total bilirubin, direct bilirubin, total protein, albumin, globulin, aspartate aminotransferase, alanine transaminase, alkaline phosphatase, gamma-glutamyl transferase, lactate dehydrogenase, hemoglobin, serum hemolysis value, hemolysis index, icterus value (Iv), icterus index (Ii), lipemia value (Lv), and lipemia index. To conduct feature selection and identify the optimal combination of variables, linear regression machine learning was performed 1,000 times. RESULTS: The selected variables were total bilirubin, direct bilirubin, total protein, albumin, hemoglobin, Iv, Ii, and Lv. The best predictive performance for high delta bilirubin concentrations was achieved with the combination of albumin-direct bilirubin-hemoglobin-Iv-Lv. The final equation composed of these variables was as follows: delta bilirubin = 0.35 × Iv + 0.05 × Lv - 0.23 × direct bilirubin - 0.05 × hemoglobin - 0.04 × albumin + 0.10. CONCLUSION: The equation established in this study is practical and can be easily applied in real-time in clinical laboratories.

Seroprevalence and assessment the associated risk factors for Fasciola hepatica infection in water buffaloes in Egypt.

Fasciolosis is a zoonotic neglected parasitic disease that affects a variety of hosts, resulting in substantial economic losses. The epidemiological information about fasciolosis in water buffaloes in Egypt is very scarce. Hence, the present study aimed to determine the seroprevalence of F. hepatica in water buffaloes using commercial ELISA kits in three governorates at north of Egypt and to estimate the associated risk factors for F. hepatica infection. The total seroprevalence of F. hepatica in buffaloes was 15.4% (63/410), with a higher seroprevalence in Kafr Elsheikh governorates 17.9% (25/140) than in other areas. Fasciolosis was more likely in older buffaloes (OR = 3.4, 95%CI:1.5-7.8), throughout the winter season (OR = 5.3, 95%CI:1.9-14.7). Moreover, the absence of prophylactic treatment (OR = 2.3, 95%CI:1.2-4.2) increased the risk of F. hepatica infection in buffaloes, particularly in animals suffered from diarrhea (OR = 3.8, 95%CI:1.4-10.6). The present study confirmed the prevalence of F. hepatica in water buffaloes in north of Egypt. Consequently, the implementation of preventive and control for the parasite and its intermediate host are very necessary to decrease the economic losses and public health hazard.

Impact of COVID-19 in pregnancy on maternal and perinatal outcomes during the Delta variant period: a comparison of the Delta and pre-delta time periods, 2020-2021.

BACKGROUND: To describe the impact on maternal and perinatal outcomes of the Delta variant of COVID-19 compared to the pre-Delta period in pregnant women with COVID-19 infections in one large public, non-profit hospital system. METHODS: We conducted a retrospective chart review of identified COVID-19 diagnosed pregnant women with the outcome of pregnancy (livebirth or stillbirths). We assessed maternal and perinatal outcomes between the pre-delta and Delta variant time periods. RESULTS: A study cohort of 173 mother-baby dyads was identified from January 2020 to November 2021. Maternal outcomes showed a higher rate of cesarean section (33.8%,49%; p = 0.047), with a higher frequency for worsening maternal condition due to COVID-19 (2.8%, 13.7%; p = 0.016) and association with non-reassuring fetal heart tones as indications for cesarean Sect. (53.8%, 95%; p = 0.008) during the Delta time period. There were more preterm births (16.9%, 32.4%; p = 0.023) even when excluding stillbirths (16.9%,30%; p = 0.05). Cesarean section due to "worsening maternal condition" was an independent risk factors for early delivery (ß = 2.66, 93.32-62.02, p < 0.001). The neonates had a longer mean (7.1 days, 9.9 days; p < 0.001) and median (2 days, 3 days; p < 0.001) length of stay during the Delta period. There was no difference in Apgar scores, NICU admissions or need for respiratory support between time periods. CONCLUSION: In a public, non-profit health system, from January 2020 to November of 2021, mothers with a diagnosis of COVID-19 during pregnancy, there were more preterm deliveries during the Delta time period, as well as longer length of stay for liveborn babies.

Yield-limiting nutrient response of lowbush blueberry grown in recent and ancient alluvial soils of the Mekong Delta.

Background: Blueberries are ornamental plants grown in pots in many yards in the Mekong Delta (MD) region. In this region, the recent alluvial (RA) soil is fertile and ancient alluvial (AA) soil is considered degraded because it only has around a quarter of the nutrient content of the RA soil. Both soils have a high clay content, so organic matter is needed to improve their physical condition. This study aimed to identify the nutrients that limit the yield of blueberries in RA and AA soils of the MD. Methods: The pot experiment was performed using a factorial randomized block design (RBD) with two factors: (a) two soil types (RA and AA) and (b) four omission or treatment conditions (NPK, PK, NK, and NP). The same fertilizer formula was used for all treatments, including 45N-20P2O5-20K2O and mixing CHC (10 tha-1) into the potting soil. Results: The blueberry yield in AA soil was only 81% of that in RA soil. In both RA and AA soils, N omission caused foliar N content deficiency (10.42 g kg-1), resulting in the content of foliar P (0.84 g kg-1) and K (3.78 g kg-1) to fall below the Trevett threshold. In both RA and AA, N omission resulted in reduced fruit yield (47% and 39%, respectively) as well as reduced weight of the stem (70% and 42%, respectively) and leaf (59% and 46%, respectively). Increased crop yields in soils were mainly related to nitrogen fertilizer. The indigenous nutrient supply (INS) of RA, which is fertile, was high but its apparent nutrient recovery efficiency (ARE) index was low, whereas the INS of AA, or the level of degraded soil, was low but its ARE index was high. In alluvial soils, the higher the INS level, the less positive the impact on the ARE index. In AA soil, the indigenous N and K supplies can be improved through fertilizer investment; however, a balance must be achieved considering economic efficiency.

Relationship Between High Frequency Component of Heart Rate Variability and Delta EEG Power During Sleep in Women With Irritable Bowel Syndrome Compared to Healthy Women.

OBJECTIVE: To explore the relationship between the high frequency (HF) heart rate variability (HRV) and electroencephalogram (EEG) delta band power in women with irritable bowel syndrome (IBS) versus healthy control women. MATERIALS AND METHODS: Twenty women with IBS and twenty healthy controls were studied over three consecutive nights using polysomnography in a sleep laboratory. To avoid the first night effect, only second-night data were analyzed. Power spectral analysis was applied to HRV and EEG recordings. The linear system coherence/phase analysis assessed the relationship between normalized HF power of HRV and normalized delta band power of EEG during the first four NREM-REM sleep cycles. RESULTS: Women with IBS exhibited a significantly higher percentage of NREM sleep, higher normalized HF, lower normalized low frequency (LF) and decreased LF/HF ratio of HRV in the first four NREM-REM sleep cycles compared to controls. Additionally, their normalized delta band power was significantly lower in these sleep cycles and over the whole night. The phase shift between HF and delta band power was significantly longer in the IBS group. While the coherence between normalized HF and normalized delta band power was lower in the IBS group, the difference was not statistically significant. CONCLUSIONS: The coherence/phase analysis showed a dysregulated interaction between autonomic and central nervous systems in women with IBS, manifested by increased lag time between cardiac and EEG delta band power compared to healthy controls. Whether this dysregulation contributes to the pathophysiology of IBS remains to be determined.

Associations between clinical data, vaccination status, antibody responses, and post-COVID-19 symptoms in Thais infected with SARS-CoV-2 Delta and Omicron variants: a 1-year follow-up study.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), led to a global pandemic from 2020. In Thailand, five waves of outbreaks were recorded, with the fourth and fifth waves driven by the Delta and Omicron variants, resulting in over 20,000 new confirmed cases daily at their peaks. METHODS: This cross-sectional study investigated the associations between clinical symptoms, vaccination status, antibody responses, and post-COVID-19 sequelae in COVID-19 patients. Plasma samples and clinical data were collected from participants admitted to hospitals in Thailand between July 2021 and August 2022, with follow-ups conducted for one year. The study included 110 participants infected with either the Delta (n = 46) or Omicron (n = 64) variants. Virus genotypes were confirmed by RT-PCR of nasal swab RNA and partial nucleotide sequencing of the S gene. IgG and IgA antibody levels against the receptor-binding domain (RBD) of SARS-CoV-2 Delta and Omicron variants were measured in plasma samples using ELISA. RESULTS: Pneumonia was found to be associated with Delta variant infections, while sore throat, congestion or runny nose, and headache were linked to Omicron infections. Vaccination with fewer than two doses and diabetes mellitus were significantly associated with higher disease severity. Specific IgG and IgA antibodies against the RBD of the Delta variant generally rose by day 14 and were maintained for up to two months, whereas the pattern of antibody response to the Omicron variant was less clear. Antibody risings were found to be positively associated with pneumonia, certain underlying conditions (obesity, hypertension, dyslipidemia, and diabetes mellitus), and age ≥ 60 years. Delta variant infections were associated with forgetfulness, hair loss, and headache during the 1-year post-infection period. Females were more likely to experience hair loss, forgetfulness, and joint pain, while older age was associated with joint pain. CONCLUSIONS: This study enhances our understanding of SARS-CoV-2 infections in Thais, particularly concerning the Delta and Omicron variants. The findings can inform public health planning and response strategies for future outbreaks of SARS-CoV-2 or other emerging viral diseases.

Delta neutrophil index (DNI) as a potential biomarker for fetal growth restriction: insights from maternal hematological changes and neonatal outcomes.

BACKGROUND: This study investigates the role of Delta Neutrophil Index (DNI), an inflammation marker, in late-onset fetal growth restriction (LO-FGR) and its prediction of composite adverse neonatal outcomes. METHODS: A retrospective study was conducted on 684 pregnant women (456 with normal fetal development and 228 with LO-FGR) who delivered at Health Sciences University Etlik Zubeyde Hanim Women's Health Training and Research Hospital between January 1, 2015, and June 30, 2018. Composite adverse neonatal outcomes were defined as at least one of the following: 5th minute APGAR score < 7, respiratory distress syndrome (RDS), or neonatal intensive care unit (NICU) admission. RESULTS: The FGR group had significantly higher levels of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), monocyte to lymphocyte ratio (MLR), and DNI compared to controls (p < 0.05, for all). For FGR diagnosis, the DNI demonstrated the highest area under the curve (AUC = 0.677, 95% CI: 0.642-0.711) with a cut-off value of > -2.9, yielding a sensitivity of 78.41%, a specificity of 52.97%, a positive likelihood ratio (+ LR) of 1.68, and a negative likelihood ratio (-LR) of 0.37 (p < 0.001). For predicting composite adverse neonatal outcomes in the FGR group, DNI again demonstrated superior performance with an AUC of 0.635 (95% CI: 0.598-0.670), a cut-off value of > -2.2, a sensitivity of 69.90%, a specificity of 55.36%, a + LR of 1.56, and a -LR of 0.51 (p < 0.001). NLR, PLR, and MLR had AUCs below 0.55, indicating poor discriminative ability, with none reaching statistical significance. CONCLUSION: This study highlights the potential role of DNI as a promising biomarker for detecting inflammatory processes associated with LO-FGR and its complications.

Protein Kinase C and Matrix Metalloproteinases Expression Using Phorbol Myristate Acetate in Degenerative Intervertebral Disc Cells.

Background: Degeneration of nucleus pulposus (NP) cells involves multiple factors. The relationship between the canonical Wnt/ß-catenin signaling pathway and matrix metalloproteinases (MMPs) is important in cellular senescence. Protein kinase C (PKC), an intermediate of the non-canonical Wnt pathway stimulated by phorbol myristate acetate (PMA), possibly prevents NP cell senescence, although not yet demonstrated in human-based studies. This study aimed to investigate the effect of PMA stimulation on the non-canonical and canonical Wnt pathways and MMP expression in human NP cells to ascertain its inhibitory effects on the senescence of NP cells. Methods: Human disc tissues of Pfirrmann grades 1 and 2 were collected from patients during spinal surgery and subsequently cultured. Protein and ribonucleic acid (RNA) were isolated from NP cells treated with PMA (400 nM) for 24 hours. Expression of MMP1, MMP13, tissue inhibitor of matrix metalloproteinase 1 (TIMP1), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), transient receptor potential vanilloid 4 (TRPV4), interleukin-6 (IL-6), and ß-catenin were detected using western blot analysis. Messenger RNA (mRNA) expression of type II collagen and glycosaminoglycan (GAG) were analyzed using reverse transcription polymerase chain reaction. IL-6 and prostaglandin E2 (PGE2) levels were measured using enzyme-linked immunosorbent assay. Results: Expression of PKC-δ (intermediate of the non-canonical Wnt pathway) and ß-catenin (intermediate of the canonical Wnt pathway) was increased by PMA treatment. The mRNA levels of type II collagen and GAG increased; however, their protein levels were not altered. PMA treatment increased the expression of MMP1, TIMP1, ADAMTS5, IL-6, PGE2, and TRPV4; however, the expression of MMP13 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) was unaltered. Conclusions: PMA activated PKC-δ, affecting the non-canonical Wnt pathway; however, its effect on ß-catenin in the canonical Wnt pathway was limited. ß-catenin activation through the TRPV4 channel led to increased expression of MMP1 and ADAMTS5 and that of IL-6 and PGE2 owing to NF-κB expression. Consequently, the degeneration of NP cells was not prevented.

Long-term follow-up of givosiran treatment in patients with acute intermittent porphyria from a phase 1/2, 48-month open-label extension study.

BACKGROUND: Acute hepatic porphyria is a group of multisystem disorders of which acute intermittent porphyria is the most common subtype. Givosiran, a subcutaneously administered RNA interference therapeutic targeting liver ALAS mRNA, is approved for treating these disorders. This Phase 1/2 open-label extension study (NCT02949830) evaluated the long-term safety and efficacy of givosiran in adults with acute intermittent porphyria, with follow-up of up to 48 months, which is the longest follow-up of givosiran treatment to date. Participants were adults aged 18-65 years who completed part C of the Phase 1 givosiran study (NCT2452372). METHODS: Enrollees received givosiran for up to 48 months. Primary and secondary endpoints included the incidence of adverse events, changes in urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels, annualized rate of porphyria attacks, and annualized hemin use. Quality of life was assessed using the EQ-5D-5L instrument as an exploratory endpoint. RESULTS: Sixteen patients (median age: 39.5 years) participated. Common adverse events included abdominal pain, nasopharyngitis, and nausea (50% each), with injection-site erythema (38%) and injection-site pruritus (25%) noted as frequent treatment-related reactions. Givosiran therapy reduced annualized rates of porphyria attacks and hemin use by 97% and 96%, respectively. From months > 33 to 48, all patients were free from attacks requiring significant medical intervention and did not use hemin. There were substantial reductions in median urinary ALA and PBG of 95% and 98%, respectively. Additionally, a clinically meaningful improvement in quality of life was observed. CONCLUSIONS: In the longest follow-up of givosiran-treated patients reported to date, the therapy maintained an acceptable safety profile and demonstrated sustained improvements in clinical outcomes over 4 years in patients with acute intermittent porphyria.

A Deficiency in Glutamine-Fructose-6-Phosphate Transaminase 1 (Gfpt1) in Skeletal Muscle Results in Reduced Glycosylation of the Delta Subunit of the Nicotinic Acetylcholine Receptor (AChRδ).

The neuromuscular junction (NMJ) is the site where the motor neuron innervates skeletal muscle, enabling muscular contraction. Congenital myasthenic syndromes (CMS) arise when mutations in any of the approximately 35 known causative genes cause impaired neuromuscular transmission at the NMJ, resulting in fatigable muscle weakness. A subset of five of these CMS-causative genes are associated with protein glycosylation. Glutamine-fructose-6-phosphate transaminase 1 (Gfpt1) is the rate-limiting enzyme within the hexosamine biosynthetic pathway (HBP), a metabolic pathway that produces the precursors for glycosylation. We hypothesized that deficiency in Gfpt1 expression results in aberrant or reduced glycosylation, impairing the proper assembly and stability of key NMJ-associated proteins. Using both in vitro and in vivo Gfpt1-deficient models, we determined that the acetylcholine receptor delta subunit (AChRδ) has reduced expression and is hypo-glycosylated. Using laser capture microdissection, NMJs were harvested from Gfpt1 knockout mouse muscle. A lower-molecular-weight species of AChRδ was identified at the NMJ that was not detected in controls. Furthermore, Gfpt1-deficient muscle lysates showed impairment in protein O-GlcNAcylation and sialylation, suggesting that multiple glycan chains are impacted. Other key NMJ-associated proteins, in addition to AChRδ, may also be differentially glycosylated in Gfpt1-deficient muscle.

Reduced protein kinase C delta in a high molecular weight complex in mitochondria and elevated creatine uptake into Barth syndrome B lymphoblasts.

Aim: Barth syndrome (BTHS) is a rare X-linked genetic disease in which mitochondrial oxidative phosphorylation is impaired due to a mutation in the TAFAZZIN gene. The protein kinase C delta (PKCδ) signalosome exists as a high molecular weight complex in mitochondria and controls mitochondrial oxidative phosphorylation. Method: Here, we examined PKCδ levels in mitochondria of aged-matched control and BTHS patient B lymphoblasts and its association with a higher molecular weight complex in mitochondria. Result: Immunoblot analysis of blue-native polyacrylamide gel electrophoresis mitochondrial fractions revealed an increase in total PKCδ protein expression in BTHS lymphoblasts compared to controls. In contrast, PKCδ associated with a higher molecular weight complex was markedly reduced in BTHS patient B lymphoblasts compared to controls. Given the decrease in PKCδ associated with a higher molecular weight complex in mitochondria, we examined the uptake of creatine, a compound whose utilization is enhanced upon high energy demand. Creatine uptake was markedly elevated in BTHS lymphoblasts compared to controls. Conclusion: We hypothesize that reduced PKCδ within this higher molecular weight complex in mitochondria may contribute to the bioenergetic defects observed in BTHS lymphoblasts and that enhanced creatine uptake may serve as one of several compensatory mechanisms for the defective mitochondrial oxidative phosphorylation observed in these cells.

Pichia pastoris secreted peptides crossing the blood-brain barrier and DSIP fusion peptide efficacy in PCPA-induced insomnia mouse models.

Background: Pichia pastoris-secreted delta sleep inducing peptide and crossing the blood-brain barrier peptides (DSIP-CBBBP) fusion peptides holds significant promise for its potential sleep-enhancing and neurotransmitter balancing effects. This study investigates these properties using a p-chlorophenylalanine (PCPA) -induced insomnia model in mice, an approach akin to traditional methods evaluating sleep-promoting activities in fusion peptides. Aim of the study: The research aims to elucidate the sleep-promoting mechanism of DSIP-CBBBP, exploring its impact on neurotransmitter levels and sleep regulation, and to analyze its composition and structure. Materials and methods: Using a PCPA-induced insomnia mouse model, the study evaluates the sleep-promoting effects of DSIP-CBBBP. The peptide's influence on neurotransmitters such as 5-HT, glutamate, dopamine, and melatonin is assessed. The functions of DSIP-CBBBP are characterized using biochemical and animal insomnia-induced behavior tests and compared without CBBBP. Results: DSIP-CBBBP demonstrates a capacity to modulate neurotransmitter levels, indicated by changes in 5-HT, glutamate, DA, and melatonin. DSIP-CBBBP shows a better restorative effect than DSIP on neurotransmitter imbalance and the potential to enhance sleep. Conclusion: The study underscores DSIP-CBBBP potential in correcting neurotransmitter dysregulation and promoting sleep, hinting at its utility in sleep-related therapies.

Interruption of glucagon signaling augments islet non-alpha cell proliferation in SLC7A2- and mTOR-dependent manners.

OBJECTIVE: Dysregulated glucagon secretion and inadequate functional beta cell mass are hallmark features of diabetes. While glucagon receptor (GCGR) antagonism ameliorates hyperglycemia and elicits beta cell regeneration in pre-clinical models of diabetes, it also promotes alpha and delta cell hyperplasia. We sought to investigate the mechanism by which loss of glucagon action impacts pancreatic islet non-alpha cells, and the relevance of these observations in a human islet context. METHODS: We used zebrafish, rodents, and transplanted human islets comprising six different models of interrupted glucagon signaling to examine their impact on delta and beta cell proliferation and mass. We also used models with global deficiency of the cationic amino acid transporter, SLC7A2, and mTORC1 inhibition via rapamycin, to determine whether amino acid-dependent nutrient sensing was required for islet non-alpha cell growth. RESULTS: Inhibition of glucagon signaling stimulated delta cell proliferation in mouse and transplanted human islets, and in mouse islets. This was rapamycin-sensitive and required SLC7A2. Likewise, gcgr deficiency augmented beta cell proliferation via SLC7A2- and mTORC1-dependent mechanisms in zebrafish and promoted cell cycle engagement in rodent beta cells but was insufficient to drive a significant increase in beta cell mass in mice. CONCLUSIONS: Our findings demonstrate that interruption of glucagon signaling augments islet non-alpha cell proliferation in zebrafish, rodents, and transplanted human islets in a manner requiring SLC7A2 and mTORC1 activation. An increase in delta cell mass may be leveraged for future beta cell regeneration therapies relying upon delta cell reprogramming.

A Strategic Framework of SARS-CoV-2 Genomic Surveillance in Bangladesh.

BACKGROUND: The global pandemic caused by SARS-CoV-2 has underlined the significance of strict genomic surveillance to track virus evolution and the possible emergence of new variants, particularly in densely populated countries like Bangladesh. This study outlines a strategic framework of genomic surveillance to track the evolution of the virus in Bangladesh between June 2021 and December 2022 through the National SARS-CoV-2 Variant Surveillance (NSVS) program involving collaboration across 4 major institutes and 13 hospitals nationwide. METHODS: We aimed to capture the variants of SARS-CoV-2 throughout the country utilizing standardized procedures, modern sequencing technology, and stringent quality control, promoting data accuracy and the timely detection of new variants of concern. We sequenced over 2200 genomes, documenting the prevalence of the Delta variant initially, followed by the emergence of Omicron variants BA.1, BA.2, BA.5, and XBB, each affecting transmission rates and vaccine efficacy differently. RESULTS: The clinical manifestations of the variants differed, with some symptoms occurring more frequently in Delta cases and vice versa. Vaccinated individuals were more affected by Omicron cases compared to Delta cases. These variants were responsible for two major COVID-19 waves in the country, each with significant clinical effects. Phylogenetic analyses placed the local SARS-CoV-2 variants within a global context, indicating the Delta variant likely entered from India and Omicron from Europe. CONCLUSION: This research highlights the significance of collaborative surveillance strategies for guiding public health choices and the critical role of genomic analysis in monitoring virus evolution, shaping targeted pandemic responses. Bangladesh's contributions significantly enhance global insight into COVID-19's genomic evolution.

Repetitive subconcussion results in disrupted neural activity independent of concussion history.

Concussion is a public health crisis that results in a complex cascade of neurochemical changes that can have life-changing consequences. Subconcussions are generally considered less serious, but we now realize repetitive subconcussions can lead to serious neurological deficits. Subconcussions are common in contact sports and the military where certain personnel are exposed to repetitive occupational blast overpressure. Post-mortem studies show subconcussion is a better predictor than concussion for chronic traumatic encephalopathy-a progressive and fatal neurodegenerative tauopathy, only diagnosable post-mortem-thus, an in vivo biomarker would be transformative. Magnetoencephalography captures the dynamics of neuronal electrochemical action, and functional MRI shows that functional connectivity is associated with tauopathy patterns. Therefore, both imaging modalities could provide surrogate markers of tauopathy. In this cross-sectional study, we examined the effects of repetitive subconcussion on neuronal activity and functional connectivity using magnetoencephalography and functional MRI, and on neurological symptoms and mental health in a military sample. For magnetoencephalography and outcome analyses, 81 participants were split into 'high' and 'low' blast exposure groups using the generalized blast exposure value: n = 41 high blast (26.4-65.7 years; 4 females) and n = 40 low blast (28.0-63.3 years; 8 females). For functional MRI, two high blast male participants without data were excluded: n = 39 (29.6-65.7 years). Magnetoencephalography revealed disrupted neuronal activity in participants with a greater history of repetitive subconcussions, including neural slowing (higher delta activity) in right fronto-temporal lobes and subcortical regions (hippocampus, amygdala, caudate, pallidum and thalamus), and functional dysconnectivity in the posterior default mode network (lower connectivity at low and high gamma). These abnormalities were independent of concussion or traumatic stress history, and magnetoencephalography showed functional dysconnectivity not detected in functional MRI. Besides magnetoencephalography changes, those with higher blast exposure had poorer somatic and cognitive outcomes, with no blast-related differences in mental health or associations between neurological symptoms and neuronal activity. This study suggests that repetitive subconcussions have deleterious effects on brain function and that magnetoencephalography provides an avenue for both treatment targets by identifying affected brain regions and in prevention by identifying those at risk of cumulative subconcussive neurotrauma.

Optogenetic targeting of cortical astrocytes selectively improves NREM sleep in an Alzheimer's disease mouse model.

Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by memory impairments and distinct histopathological features such as amyloid-beta (Aß) accumulations. Alzheimer's patients experience sleep disturbances at early stages of the disease. APPswe/PS1dE9 (APP) mice exhibit sleep disruptions, including reductions in non-rapid eye movement (NREM) sleep, that contribute to their disease progression. In addition, astrocytic calcium transients associated with a sleep-dependent brain rhythm, slow oscillations prevalent during NREM sleep, are disrupted in APP mice. However, at present it is unclear whether restoration of circuit function by targeting astrocytic activity could improve sleep in APP mice. To that end, APP mice expressing channelrhodopsin-2 (ChR2) targeted to astrocytes underwent optogenetic stimulation at the slow oscillation frequency. Optogenetic stimulation of astrocytes significantly increased NREM sleep duration but not duration of rapid eye movement (REM) sleep. Optogenetic treatment increased delta power and reduced sleep fragmentation in APP mice. Thus, optogenetic activation of astrocytes increased sleep quantity and improved sleep quality in an AD mouse model. Astrocytic activity provides a novel therapeutic avenue to pursue for enhancing sleep and slowing AD progression.

Hepatitis B virus entry, assembly, and egress.

SUMMARYHepatitis B virus (HBV) is an important human pathogen that chronically infects approximately 250 million people in the world, resulting in ~1 million deaths annually. This virus is a hepatotropic virus and can cause severe liver diseases including cirrhosis and hepatocellular carcinoma. The entry of HBV into hepatocytes is initiated by the interaction of its envelope proteins with its receptors. This is followed by the delivery of the viral nucleocapsid to the nucleus for the release of its genomic DNA and the transcription of viral RNAs. The assembly of the viral capsid particles may then take place in the nucleus or the cytoplasm and may involve cellular membranes. This is followed by the egress of the virus from infected cells. In recent years, significant research progresses had been made toward understanding the entry, the assembly, and the egress of HBV particles. In this review, we discuss the molecular pathways of these processes and compare them with those used by hepatitis delta virus and hepatitis C virus , two other hepatotropic viruses that are also enveloped. The understanding of these processes will help us to understand how HBV replicates and causes diseases, which will help to improve the treatments for HBV patients.

The Incidence and Characteristics of Oral Candidiasis in Patients Hospitalized for SARS-CoV-2 Infection During the Circulation of Alpha, Beta, and Delta Variants.

BACKGROUND: Oral candidiasis has been documented in patients with SARS-CoV-2 infection, with varying prevalence rates across geographic regions and patient demographics. This study aimed to ascertain the incidence, characteristics, and risk factors associated with the development of oral candidiasis in patients hospitalized for SARS-CoV-2 infection in a tertiary infectious diseases hospital in Romania. METHODS: A retrospective analysis was conducted on adult patients hospitalized between March 2020 and December 2022 with moderate or severe forms of SARS-CoV-2 infection, for whom a culture of lingual scrapings for Candida spp. was performed. RESULTS: A total of 294 patients were deemed eligible for inclusion in the analysis, with an incidence rate of oral candidiasis of 17.0%. The incidence of oral candidiasis was 4.2 times higher in patients with severe forms of SARS-CoV-2 infection compared to those with moderate forms. Patients with a diagnosis of COVID-19 and oral candidiasis were more likely to receive antibiotics (98.0% vs. 86.1%, p = 0.017) and corticosteroids (100% vs. 83.6%, p = 0.003) than those without oral candidiasis. These findings were associated with a 19% higher relative risk of developing oral candidiasis for patients who received corticosteroid therapy compared to those who did not, and a 13% higher relative risk for those who were administered antibiotics compared to those who were not. The presence of respiratory insufficiency increased the odds of oral candidiasis association 4.7-fold (88.0% vs. 61.1%, p < 0.001). CONCLUSIONS: Although the data have been analyzed retrospectively, we have shown that individuals with severe forms of COVID-19 exhibited an elevated risk of developing oral candidiasis. The administration of antibiotics and corticosteroids was identified as a positive predictor for the development of oral candidiasis. The data presented here suggest that a key aspect of the therapeutic management of patients with SARS-CoV-2 infection should include the implementation of preventive measures to minimize the risk of secondary fungal infections.