Multicenter Cohort Study to Evaluate the Relationship between Radiological Findings and Disability in Moderate and Severe Head Injury Patients.

This was a multicenter cohort study to evaluate the relationship between radiological findings and disability in moderate and severe head injury patients. The study places were the Neurosurgery department of Sylhet M A G Osmani Medical College Hospital, Sylhet Women's Medical College Hospital (SWMCH) and King Faisal Hospital (KFH), Taif, KSA. Sample size was 104 and the study period was 36 months (July 2021 to December 2022). On the basis of radiological findings the participants were divided into three arms. The different arms were diffused traumatic brain injury (arm-1), focal traumatic brain injury (arm-2) and both (diffused and traumatic) types traumatic brain injury (arm-3). Outcome was assessed by modified Rankin Score (mRS). Mean age was significantly higher in female. Overall mean age was 40.28 year. Highest number was in the below 20-year age group followed by the 41-50-year age group. Lowest number of participants was in the above 60-year group. Improved group was significantly higher than 'not improved' and the 'died' group (p<0.00001). Improved participants were significantly higher in the arm-1 and arm-2. Mortality was significantly higher (p<0.00001) in the arm-3 group.

Gut microbiome and metabolome profiling in Framingham heart study reveals cholesterol-metabolizing bacteria.

Accumulating evidence suggests that cardiovascular disease (CVD) is associated with an altered gut microbiome. Our understanding of the underlying mechanisms has been hindered by lack of matched multi-omic data with diagnostic biomarkers. To comprehensively profile gut microbiome contributions to CVD, we generated stool metagenomics and metabolomics from 1,429 Framingham Heart Study participants. We identified blood lipids and cardiovascular health measurements associated with microbiome and metabolome composition. Integrated analysis revealed microbial pathways implicated in CVD, including flavonoid, γ-butyrobetaine, and cholesterol metabolism. Species from the Oscillibacter genus were associated with decreased fecal and plasma cholesterol levels. Using functional prediction and in vitro characterization of multiple representative human gut Oscillibacter isolates, we uncovered conserved cholesterol-metabolizing capabilities, including glycosylation and dehydrogenation. These findings suggest that cholesterol metabolism is a broad property of phylogenetically diverse Oscillibacter spp., with potential benefits for lipid homeostasis and cardiovascular health.

Modular Phoneme Processing in Human Superior Temporal Gyrus.

Modular organization is fundamental to cortical processing, but its presence is human association cortex is unknown. We characterized phoneme processing with 128-1024 channel micro-arrays at 50-200µm pitch on superior temporal gyrus of 7 patients. High gamma responses were highly correlated within ~1.7mm diameter modules, sharply delineated from adjacent modules with distinct time-courses and phoneme-selectivity. We suggest that receptive language cortex may be organized in discrete processing modules.

Protein Language Models Uncover Carbohydrate-Active Enzyme Function in Metagenomics.

In metagenomics, the pool of uncharacterized microbial enzymes presents a challenge for functional annotation. Among these, carbohydrate-active enzymes (CAZymes) stand out due to their pivotal roles in various biological processes related to host health and nutrition. Here, we present CAZyLingua, the first tool that harnesses protein language model embeddings to build a deep learning framework that facilitates the annotation of CAZymes in metagenomic datasets. Our benchmarking results showed on average a higher F1 score (reflecting an average of precision and recall) on the annotated genomes of Bacteroides thetaiotaomicron, Eggerthella lenta and Ruminococcus gnavus compared to the traditional sequence homology-based method in dbCAN2. We applied our tool to a paired mother/infant longitudinal dataset and revealed unannotated CAZymes linked to microbial development during infancy. When applied to metagenomic datasets derived from patients affected by fibrosis-prone diseases such as Crohn's disease and IgG4-related disease, CAZyLingua uncovered CAZymes associated with disease and healthy states. In each of these metagenomic catalogs, CAZyLingua discovered new annotations that were previously overlooked by traditional sequence homology tools. Overall, the deep learning model CAZyLingua can be applied in combination with existing tools to unravel intricate CAZyme evolutionary profiles and patterns, contributing to a more comprehensive understanding of microbial metabolic dynamics.

Genetic Screens Identify Additional Genes Implicated in Envelope Remodeling during the Engulfment Stage of Bacillus subtilis Sporulation.

During bacterial endospore formation, the developing spore is internalized into the mother cell through a phagocytic-like process called engulfment, which involves synthesis and hydrolysis of peptidoglycan. Engulfment peptidoglycan hydrolysis requires the widely conserved and well-characterized DMP complex, composed of SpoIID, SpoIIM, and SpoIIP. In contrast, although peptidoglycan synthesis has been implicated in engulfment, the protein players involved are less well defined. The widely conserved SpoIIIAH-SpoIIQ interaction is also required for engulfment efficiency, functioning like a ratchet to promote membrane migration around the forespore. Here, we screened for additional factors required for engulfment using transposon sequencing in Bacillus subtilis mutants with mild engulfment defects. We discovered that YrvJ, a peptidoglycan hydrolase, and the MurA paralog MurAB, involved in peptidoglycan precursor synthesis, are required for efficient engulfment. Cytological analyses suggest that both factors are important for engulfment when the DMP complex is compromised and that MurAB is additionally required when the SpoIIIAH-SpoIIQ ratchet is abolished. Interestingly, despite the importance of MurAB for sporulation in B. subtilis, phylogenetic analyses of MurA paralogs indicate that there is no correlation between sporulation and the number of MurA paralogs and further reveal the existence of a third MurA paralog, MurAC, within the Firmicutes. Collectively, our studies identify two new factors that are required for efficient envelop remodeling during sporulation and highlight the importance of peptidoglycan precursor synthesis for efficient engulfment in B. subtilis and likely other endospore-forming bacteria. IMPORTANCE In bacteria, cell envelope remodeling is critical for cell growth and division. This is also the case during the development of bacteria into highly resistant endospores (spores), known as sporulation. During sporulation, the developing spore becomes internalized inside the mother cell through a phagocytic-like process called engulfment, which is essential to form the cell envelope of the spore. Engulfment involves both the synthesis and hydrolysis of peptidoglycan and the stabilization of migrating membranes around the developing spore. Importantly, although peptidoglycan synthesis has been implicated during engulfment, the specific genes that contribute to this molecular element of engulfment have remained unclear. Our study identifies two new factors that are required for efficient envelope remodeling during engulfment and emphasizes the importance of peptidoglycan precursor synthesis for efficient engulfment in the model organism Bacillus subtilis and likely other endospore-forming bacteria. Finally, our work highlights the power of synthetic screens to reveal additional genes that contribute to essential processes during sporulation.

Inflammation-associated nitrate facilitates ectopic colonization of oral bacterium Veillonella parvula in the intestine.

Colonization of the intestine by oral microbes has been linked to multiple diseases such as inflammatory bowel disease and colon cancer, yet mechanisms allowing expansion in this niche remain largely unknown. Veillonella parvula, an asaccharolytic, anaerobic, oral microbe that derives energy from organic acids, increases in abundance in the intestine of patients with inflammatory bowel disease. Here we show that nitrate, a signature metabolite of inflammation, allows V. parvula to transition from fermentation to anaerobic respiration. Nitrate respiration, through the narGHJI operon, boosted Veillonella growth on organic acids and also modulated its metabolic repertoire, allowing it to use amino acids and peptides as carbon sources. This metabolic shift was accompanied by changes in carbon metabolism and ATP production pathways. Nitrate respiration was fundamental for ectopic colonization in a mouse model of colitis, because a V. parvula narG deletion mutant colonized significantly less than a wild-type strain during inflammation. These results suggest that V. parvula harness conditions present during inflammation to colonize in the intestine.

FtsK and SpoIIIE, coordinators of chromosome segregation and envelope remodeling in bacteria.

The translocation of DNA during bacterial cytokinesis is mediated by the SpoIIIE/FtsK family of proteins. These proteins ensure efficient chromosome segregation into sister cells by ATP-driven translocation of DNA and they control chromosome dimer resolution. How FtsK/SpoIIIE mediate chromosome translocation during cytokinesis in Gram-positive and Gram-negative organisms has been the subject of debate. Studies on FtsK in Escherichia coli, and recent work on SpoIIIE in Bacillus subtilis, have identified interactions between each translocase and the division machinery, supporting the idea that SpoIIIE and FtsK coordinate the final steps of cytokinesis with completion of chromosome segregation. Here we summarize and discuss the view that SpoIIIE and FtsK play similar roles in coordinating cytokinesis with chromosome segregation, during growth and differentiation.

Chromosome Segregation and Peptidoglycan Remodeling Are Coordinated at a Highly Stabilized Septal Pore to Maintain Bacterial Spore Development.

Asymmetric division, a hallmark of endospore development, generates two cells, a larger mother cell and a smaller forespore. Approximately 75% of the forespore chromosome must be translocated across the division septum into the forespore by the DNA translocase SpoIIIE. Asymmetric division also triggers cell-specific transcription, which initiates septal peptidoglycan remodeling involving synthetic and hydrolytic enzymes. How these processes are coordinated has remained a mystery. Using Bacillus subtilis, we identified factors that revealed the link between chromosome translocation and peptidoglycan remodeling. In cells lacking these factors, the asymmetric septum retracts, resulting in forespore cytoplasmic leakage and loss of DNA translocation. Importantly, these phenotypes depend on septal peptidoglycan hydrolysis. Our data support a model in which SpoIIIE is anchored at the edge of a septal pore, stabilized by newly synthesized peptidoglycan and protein-protein interactions across the septum. Together, these factors ensure coordination between chromosome translocation and septal peptidoglycan remodeling to maintain spore development.

The effect of loading dose of magnesium sulfate on uterine, umbilical, and fetal middle cerebral arteries Doppler in women with severe preeclampsia: A case control study.

UNLABELLED: SYNOPSIS IV MgSO4 administration in women with severe preeclampsia resulted in a decrease in umbilical artery, uterine artery, and fetal middle cerebral artery Doppler indices. OBJECTIVE: To evaluate Doppler parameters of the umbilical artery (UmA), uterine artery (UA), and fetal middle cerebral artery (MCA) before and after MgSO4 administration in women with severe preeclampsia. METHODS: A case control study included 100 pregnant women with severe preeclampsia. Umbilical artery, uterine artery, and fetal middle cerebral artery Doppler were measured before and 20 minutes after intravenous administration of 6 g of magnesium sulfate. RESULTS: There was a significant difference between maternal systolic blood pressure (173.20 ± 22.72 vs. 156.60 ± 19.18), diastolic blood pressure (109.60 ± 9.14 vs. 101.90 ± 10.05), and heart rate (80.52 ± 11.52 vs. 88.48 ± 12.08) before and after administration of MgSO4 in the studied patients (p value < 0.001). There was a significant difference between umbilical artery, middle cerebral artery, and uterine artery Doppler parameters before and after administration of MgSO4 in the studied patients (p value < 0.001). There was no significant difference between umbilical artery/middle cerebral artery with regard to RI and PI. However, there was significant difference with regard to the S/D ratio (p value < 0.001). The decrease in the values of Doppler parameters before and after administration of MgSO4 was more in the middle cerebral artery than in the umbilical artery. CONCLUSION: Intravenous administration of magnesium sulfate in pregnant women with severe preeclampsia resulted in a decrease in umbilical artery, uterine artery, and fetal middle cerebral artery Doppler indices with reduced resistance to blood flow in these vessels.

Pretreatment study of P53 overexpression for selection of candidates for pelvic lymphadenectomy in clinical stage I endometrial carcinoma: a randomized-controlled study.

PURPOSE: To study the value of pretreatment testing of P53 overexpression in selection of candidates for pelvic lymphadenectomy in clinical stage I endometrial carcinoma. PATIENTS AND METHODS: This prospective randomized clinical study included 38 patients with histologically confirmed endometrial carcinoma and staged clinically as stage I. Immunohistochemical staining of the tumor specimens obtained by dilatation and curettage with P53 monoclonal antibodies was done. The patients were randomized into two groups according to the planned surgical treatment: hysterectomy group and hysterectomy plus pelvic lymphadenectomy group. RESULTS: There was no significant difference in mean age, parity, medical status, surgical stage, histologic types, grade of differentiation, and myometrial invasion between the two groups. The survival rate in the hysterectomy group in our study was 82.4% and the recurrence rate was 17.6%, while in hysterectomy and lymphadenectomy group the survival rate was 81.0% and the recurrence rate was 19%. Adding pelvic lymphadenectomy was found to be associated with prolonged recurrence time in the P53-positive patients (24.07 vs. 17.8 months for group A). CONCLUSION: Pretreatment testing of P53 expression is recommended to help with other prognostic factors in the selection of candidates for pelvic lymphadenectomy in clinical stage I endometrial carcinoma.

The influence of baking fuel on residues of polycyclic aromatic hydrocarbons and heavy metals in bread.

The influence of fuel type used to bake bread on the spectrum and concentrations of some polycyclic aromatic hydrocarbons and heavy metals in baked bread was assessed. Bread samples were collected from different bakeries operated by either electricity, solar, mazot or solid waste and their residue content of PAHs and heavy metals was assessed. The total concentration of PAHs detected in mazot, solar, solid waste and electricity operated bakeries had an average of 320.6, 158.4, 317.3 and 25.5 microgkg(-1), respectively. Samples collected from mazot, solar and solid waste operated bakeries have had a wide spectrum of PAHs, in comparison to that detected in bread samples collected from electricity operated bakeries. Lead had the highest concentrations in the four groups of bread samples, followed by nickel, while the concentrations of zinc and cadmium were the least. The concentration of lead detected in bread samples produced from mazot, solar, solid waste and electricity fueled bakeries were 1375.5, 1114, 1234, and 257.3 microgkg(-1), respectively. Estimated daily intake of PAHs based on bread consumption were 48.2, 28.5, 80. 1, and 4.8 microg per person per day for bread produced in bakeries using mazot, solar, solid waste and electricity, respectively. Meanwhile, the estimated daily intake of benzo (a) pyrene were 3.69, 2.65, 8.1, and 0.81 microg per person per day for bread sample baked with mazot, solar, solid waste and electricity, respectively. The daily intake of lead, based on bread consumption was 291, 200.5, 222, and 46.31 microg per person per day for bread sample baked with mazot, solar, solid waste and electricity, respectively. The present work has indicated the comparatively high level of daily intake of benzo (a) pyrene and lead in comparison to levels reported from many other countries and those recommended by international regulatory bodies. It is probable that residues detected in bread samples are partially cereal-borne but there is strong evidence that the process of baking and the gases emitted are responsible for most of the contamination load.

Determination of malathion residues in some medicinal plants by liquid chromatography with gas chromatographic/mass spectrometric confirmation.

A method for determining malathion residues by reversed-phase liquid chromatography (LC) using methanol only as mobile phase is described. Malathion [diethyl(dimethoxyphosphinothiol)succinate] was applied on marjoram, mint, and chamomile. Residues were detected in fresh and dry crops by LC and confirmed by gas-LC/mass spectrometry. Average recovery of malathion was 85%. Residues detected in fresh marjoram, mint, and chamomile were 0.18, 0.23, and 0.083 mg/kg, respectively. Residues detected in dry marjoram and mint were 0.024 and 0.050 mg/kg, respectively. No malathion residues were detected in dry chamomile. The minimum detectable concentration with this method is 0.013 mg/kg. The study suggests it is safe to use malathion up to 2 sprays per season provided the crop is harvested not less than 3 weeks from the last spray.

Capillary gas chromatography determination of aliphatic hydrocarbons in fish and water from Oman.

Aliphatic hydrocarbon residues were monitored in two fish species, Indian mackerel (Rastrelliger Kanaguria) and Indian scad (Decapterus russelli) collected from local markets in three different cities in Oman. Residues were also monitored in water samples collected from two sites of the Gulf of Oman. Sampling was conducted twice, in July and again in February to have a thorough understanding of the dynamics of aliphatic hydrocarbon residues. Results indicated the presence of petrogenic aliphatic hydrocarbons ranging from C12-C28 in fish and water samples alike. Fish and water chromatograms were characterized by an unresolved complex mixture (UCM), a confirmatory sign of petrogenic origin of monitored hydrocarbons. Residue levels showed some variations related to sampling sites and time of sampling.

Feeding cyromazine to Luhmann hens: residues in tissues and effects on some biochemical constituents.

Cyromazine was fed to Luhmann hens at 0.15 ppm level supplemented the basal diet for 3 weeks. The build up of cyromazine residues in liver and muscles of hens up to 7th day, the balance between cyromazine intake and elimination had taken place between 7 and 10 days. After cyromazine was withdrawn from the diet its residues was depleted within 7 days. During the 3 weeks of feeding on the treated diet, the accumulated residues reduced the blood glucose and hepatic protein significantly up to 2 weeks, while the hepatic lipids was slightly increased on the 7th day. Also such residues had adverse effects on the activities of alkaline phosphatase (AP) and transaminases (GOT, GPT) and extend on red blood cells, white blood cells, hemoglobin content (Hb) and packed cell volume (PCV) compared with the untreated hens.

Perturbation of thyroid hormone homeostasis in the adult and brain function.

Although a critical role of thyroid hormones in mammalian brain development is well established and extensively documented, the adult CNS is often thought to be a thyroid hormone-insensitive organ. The presence in the adult brain of thyroid hormone, along with high levels of nuclear T3 receptors and the strict regulation of intracerebral T3 levels, coupled with overt psychomotor and cognitive dysfunctions in adult-onset dysthyroidism, casts doubt upon this assumption. We have therefore investigated the influence of thyroid hormones on the biochemistry, metabolism and molecular biology of adult rat brain regions and confluent neurons and astrocytes in culture. Our results and those in the literature show that brain nuclear T3 receptor and angiotensinogen mRNA levels and 5'D-II activity are dependent upon normal thyroid hormone concentrations. Several subfractions of cell signalling proteins (G protein alpha subunits) are compromised in hypo- and hyperthyroidism and the activities of protein kinases A and C are up-regulated in the hypothyroid state in a brain region-specific manner. The activities of acid phosphatase and aryl sulphatase A are compromised in the brain of hypothyroid rats, indicating a degree of lysosomal dysfunction, and several neurotransmitter metabolic enzymes and receptor systems are also affected. Metabolic experiments indicate that glutamate and acetate metabolism are compromised in the hypothyroid state, although glucose metabolism remains normal. Primary cultures of confluent neurons and astrocytes also strongly indicate a critical role for thyroid hormones in the control of amino acid uptake, protein synthesis, glycoprotein synthesis and 2-deoxyglucose uptake, in a cell-specific manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypothyroidism in the adult rat causes brain region-specific biochemical dysfunction.

The influence of hypothyroidism in the adult rat on brain biochemistry was investigated. Hypothyroidism was induced in 6-month-old male rats by partial thyroidectomy coupled with the administration of 6-n-propyl-2-thiouracil (0.005%, w/v) in the drinking water. Age-matched euthyroid males served as the controls. Hypothyroidism resulted in brain region-specific changes in certain catabolic enzyme activities. Acid phosphatase activity was reduced in the cerebellum (by 34%) and the medulla (by 38%), whereas alkaline phosphatase activity was decreased in the midbrain (by 37%) and the subcortex (by 49%). A differential response was also observed in the case of aryl sulphatase activity: aryl sulphatase A (myelin-degradative activity) was diminished in the cerebellum (by 56%), whereas aryl sulphatase B remained unchanged in all regions. Acetylcholine esterase activity was reduced in the cerebellum (by 45%), the medulla (by 34%) and the subcortex (by 45%), whereas monoamine oxidase activity was affected in only one region, the cerebellum, where it was increased by (61%). The compromise of myelin and neurotransmitter degradative enzyme activities may place severe restrictions on normal brain function. The vulnerability of the adult rat cerebellum to the effects of thyroidectomy is commensurate with the known clinical signs of cerebellar dysfunction in adult hypothyroid man. These findings raise the possibility of an important role for the thyroid hormones in the mature brain.

High performance liquid chromatography determination of DDT residues in some commercial brands of milk in Ismailia, Egypt.

A high performance liquid chromatography method was employed to detect DDT-type residues in milk samples collected from Ismailia governorate. o,p-DDT and p,p-DDE were the most frequent residues detected. In none of the testet samples the total DDT residues exceeded the maximum residue limit (MRL) for DDT complex.