Miracle-dz/UniFAR-FTUs huggingface dataset:
Immune responses to Mycobacterium tuberculosis membrane-associated antigens including alpha crystallin can potentially discriminate between latent infection and active tuberculosis disease

Changes in expression of membrane antigens may accompany the transition of Mycobacterium tuberculosis (Mtb) from ‘dormant’ to ‘active’ states. We have determined whether antibody and T cell responses to Mtb membrane (MtM)-associated antigens, especially the latency-induced protein alpha crystallin (Acr), can discriminate between latent tuberculosis infection (LTBI) and active TB (ATB) disease. Study subjects comprised a previously described cohort of healthcare workers (HCWs, n = 43) and smear-positive ATB patients (n = 10). HCWs were further categorized as occupational contacts (OC, n = 30), household contacts of TB (HC, n = 8) and cured TB (CTB, n = 5). Levels (ΔOD) of serum antibody isotypes (IgG, IgA and IgM) were determined by ELISA and blood T cell proliferative responses were determined by flow cytometry using Ki67 protein as marker for DNA synthesis. Antibodies to MtM and Acr were predominantly IgG and their levels in HCWs and ATB did not differ significantly. However, HCWs showed a significantly higher level of anti-MtM IgM and a significantly lower level of anti-Acr IgA antibodies than the ATB patients. Also, a larger proportion of HCWs showed a high (>1) ΔODAcr/ΔODMtM ratio for IgG. HCWs also showed a higher, though not significantly different from ATB, avidity of anti-MtM (IgG) antibodies. A higher proportion of HCWs (35% of OC, 62.5% of HC and 20% of CTB), compared with ATB (10%) showed a positive T cell response to Acr along with significant difference (P <0.05) between HC and ATB. A significant correlation (r = 0.60, P <0.0001) was noted between T cell responses of HCWs towards Acr and MtM (reported earlier by us) and both responses tended to decline with rising exposure to the infection. Even so, positive responses to Acr (38.5%) were significantly lower than to MtM (92%). Neither antibody nor T cell responses to either antigen appeared affected by BCG vaccination or reactivity to tuberculin. Results of the study suggest that the levels of IgM antibodies to MtM, IgA antibodies to Acr and proliferative T cell responses to both the antigens can potentially discriminate between LTBI and active TB disease. They also underscore the necessity of SOPs for antibody assays.
Epidemiological Analysis of Leptospirosis in Guangxi Zhuang Autonomous Region from 2007 to 2011

Objective To survey the epidemiological features of leptospirosis in Guangxi Zhuang Autonomous Region from 2007 to 2011 so as to provide a scientific basis for developing effective prevention and control measures.Methods Descriptive epidemiological and medical statistical methods were used to statistically analyze and evaluate the data about leptospirosis in Guangxi Zhuang Autonomous Region during the period of 2007-2011.Results Altogether,259 cases of leptospirosis were reported during the period of 2007-2011.There were 9 cases of death,with the mortality of 3.47%. The average annual incidence rate was 0.11/100,000.The prevalence season for leptospirosis was from June to September per year,with a peak in August and 69.11% cases occurred in the prevalence season.In the case of occupation distribution,farmers and students were the most commonly involved,accounting for 83.01% of the total cases.Male cases were more than female ones,and the ratio of male to female was 2.28:1.The main infection bacterial colony in the patients was jaundice bleeding group and the type of paddy-field was the dominant infection type.Conclusions Implementing comprehensive measures,including infection source control and management,health education and immunization,is the key to leptospirosis prevention and control.
Evaluation and management of abdominal sepsis.

PURPOSE OF REVIEW The review focuses on the evaluation and management of abdominal sepsis. RECENT FINDINGS A multitude of surgical approaches towards abdominal sepsis are practized in the world and may be associated with significant morbidity and mortality rates. Despite decades of sepsis research, no specific therapies for sepsis have emerged. Without specific therapies, the management of abdominal sepsis is based on the control of the infection and organ support. SUMMARY Early clinical diagnosis, adequate source control to stop ongoing contamination, appropriate antibiotic therapy dictated by patient and infection risk factors, and prompt resuscitation are the cornerstones of its management.
P2X7 receptor activation increases expression of caveolin-1 and formation of macrophage lipid rafts, thereby boosting CD39 activity

ABSTRACT Macrophages are tissue-resident immune cells that are crucial for the initiation and maintenance of immune responses. Purinergic signaling modulates macrophage activity and impacts cellular plasticity. The ATP-activated purinergic receptor P2X7 (also known as P2RX7) has pro-inflammatory properties, which contribute to macrophage activation. P2X7 receptor signaling is, in turn, modulated by ectonucleotidases, such as CD39 (also known as ENTPD1), expressed in caveolae and lipid rafts. Here, we examined P2X7 receptor activity and determined impacts on ectonucleotidase localization and function in macrophages primed with lipopolysaccharide (LPS). First, we verified that ATP boosts CD39 activity and caveolin-1 protein expression in LPS-primed macrophages. Drugs that disrupt cholesterol-enriched domains – such as nystatin and methyl-β-cyclodextrin – decreased CD39 enzymatic activity in all circumstances. We noted that CD39 colocalized with lipid raft markers (flotillin-2 and caveolin-1) in macrophages that had been primed with LPS followed by treatment with ATP. P2X7 receptor inhibition blocked these ATP-mediated increases in caveolin-1 expression and inhibited the colocalization with CD39. Further, we found that STAT3 activation is significantly attenuated caveolin-1-deficient macrophages treated with LPS or LPS+BzATP. Taken together, our data suggest that P2X7 receptor triggers the initiation of lipid raft-dependent mechanisms that upregulates CD39 activity and could contribute to limit macrophage responses restoring homeostasis. Summary: P2X7 receptor activation triggers the initiation of lipid raft-dependent regulatory pathways that upregulate CD39 activity, contributing to limit macrophage responses and inflammation.
Preoperative Mental Health Component Scoring is Related to Patient Reported Outcomes Following Lumbar Fusion.

STUDY DESIGN Retrospective cohort review. OBJECTIVE The objective of this study was to identify depression using the Mental Component Score (MCS-12) of the Short Form-12 (SF-12) survey and to correlate with patient outcomes. SUMMARY OF BACKGROUND DATA The impact of preexisting depressive symptoms on health-care related quality of life (HRQOL) outcomes following lumbar spine fusion is not well understood. METHODS Patients undergoing lumbar fusion between one to three levels at a single center, academic hospital were retrospectively identified. Patients under the age of 18 years and those undergoing surgery for infection, trauma, tumor, or revision, and less than one-year follow-up were excluded. Patients with depressive symptoms were identified using an existing clinical diagnosis or a score of MCS-12 ≤ 45.6 on the preoperative SF-12 survey. Absolute HRQOL scores, the recovery ratio (RR) and the percent of patients achieving MCID between groups were compared, and a multiple linear regression analysis was performed. RESULTS A total of 391 patients were included in the total cohort, with 123 (31.5%) patients reporting symptoms of depression based on MCS-12 and 268 (68.5%) without these symptoms. The low MCS-12 group was found to have significantly worse preoperative ODI, VAS Back and VAS Leg pain scores, and postoperative PCS-12, ODI, VAS Back, and VAS Leg pain scores (p < 0.05) than the non-depressed group. Finally, multiple linear regression analysis revealed preoperative depression to be a significant predictor of worse outcomes after lumbar fusion. CONCLUSION Patients with depressive symptoms, identified with an MCS-12 cutoff below 45.6, were found to have significantly greater disability in a variety of HRQOL domains at baseline and postoperative measurement, and demonstrated less improvement in all outcome domains included in the analysis compared to patients without depression. However, while the improvement was less, even the low MCS-12 cohort demonstrated statistically significant improvement in all HRQOL outcome measures after surgery. LEVEL OF EVIDENCE 3.
Does early palliative identification improve the use of palliative care services?

Purpose To evaluate whether the early identification of patients who may benefit from palliative care impacts on the use of palliative, community and acute-based care services. Methods Between 2014 and 2017, physicians from eight sites were encouraged to systematically identify patients who were likely to die within one year and would were thought to benefit from early palliative care. Patients in the INTEGRATE Intervention Group were 1:1 matched to controls selected from provincial healthcare administrative data using propensity score-matching. The use of palliative care, community-based care services (home care, physician home visit, and outpatient opioid use) and acute care (emergency department, hospitalization) was each evaluated within one year after the date of identification. The hazard ratio (HR) in the Intervention Group was calculated for each outcome. Results Of the 1,185 patients in the Intervention Group, 951 (80.3%) used palliative care services during follow-up, compared to 739 (62.4%) among 1,185 patients in the Control Group [HR of 1.69 (95% CI 1.56 to 1.82)]. The Intervention Group also had higher proportions of patients who used home care [81.4% vs. 55.2%; HR 2.07 (95% CI 1.89 to 2.27)], had physician home visits [35.5% vs. 23.7%; HR 1.63 (95% CI 1.46 to 1.92)] or had increased outpatient opioid use [64.3% vs. 52.1%); HR 1.43 (95% CI 1.30 to 1.57]. The Intervention Group was also more likely to have a hospitalization that was not primarily focused on palliative care (1.42 (95% CI 1.28 to 1.58)) and an unplanned emergency department visit for non-palliative care purpose (1.47 (95% CI 1.32 to 1.64)). Conclusion Physicians actively identifying patients who would benefit from palliative care resulted in increased use of palliative and community-based care services, but also increased use of acute care services.
Wogonin glucuronidation in liver and intestinal microsomes of humans, monkeys, dogs, rats, and mice

Abstract Wogonin, one of the flavonoids isolated from Scutellaria baicalensis, exhibits some beneficial bioactivities, including anti-inflammatory and anticancer effects, and is metabolized into glucuronide by UDP-glucuronosyltransferase (UGT) enzymes in humans. In the present study, wogonin glucuronidation was examined in the liver and intestinal microsomes of humans, monkeys, dogs, rats, and mice using a kinetic analysis. The kinetics of wogonin glucuronidation by liver microsomes followed the biphasic model in all species examined. CLint values (x-intercept) based on v versus V/[S] plots were rats > humans ≈ monkeys > mice > dogs. The kinetics of intestinal microsomes fit the Michaelis–Menten model for humans, monkeys, rats, and mice and the substrate inhibition model for dogs. CLint values were rats > monkeys > mice > dogs > humans. The tissue dependence of CLint values was liver microsomes > intestinal microsomes for humans, dogs, and rats, and liver microsomes ≈ intestinal microsomes for monkeys and mice. These results demonstrated that the metabolic abilities of UGT enzymes toward wogonin in the liver and intestines markedly differ among humans, monkeys, dogs, rats, and mice, and suggest that species differences are closely associated with the biological effects of wogonin.
Macrophyte Diversity and Complexity Reduce Larval Mosquito Abundance

Abstract The role of aquatic arthropod diversity and community interactions of larval mosquitoes are important for understanding mosquito population dynamics. We tested the effects of aquatic macrophyte diversity and habitat structural complexity in shaping the predator and competitor invertebrate communities associated with mosquito larvae. Experimental mesocosms were planted with live aquatic macrophytes and allowed to be naturally colonized by local invertebrates. Results indicated a positive effect of macrophyte diversity on competitor diversity and a negative effect on predator diversity. In turn, predator diversity negatively impacted mosquito abundance through a direct effect, while competitor diversity showed an indirect negative effect on mosquito larval abundance through its positive effect on predator diversity. The enhancement of aquatic macrophyte diversity and structural complexity has practical applications for the reduction of mosquito populations in managed systems where complete source elimination is not possible.
Do estimated 24-h pulse pressure components affect outcome? The Ohasama study.

OBJECTIVE Twenty-four-hour ambulatory pulse pressure (PP) is a powerful predictor of outcome. We attempted to apply the recently described PP components, an elastic (elPP), and systolic stiffening (stPP) components from 24-h ambulatory blood pressure (BP) monitoring (AMBP), and examine their influence on outcome in the Ohasama study population. DESIGN AND METHODS Included were participants of the Ohasama study without history of cardiovascular disease (CVD), who were followed-up for total and CVD mortality, and for stroke morbidity. The PP components were derived from 24-h SBP and DBP using a model based on the nonlinear pressure--volume relationship in arteries expressing pressure stiffness relationship. Outcome predictive power was estimated by Cox regression models; hazard ratio with 95% confidence interval (CI), applied to elPP, and stPP, adjusted for age, sex, BMI, smoking, alcohol drinking, diabetes mellitus, total cholesterol, antihypertensive treatment, and mean arterial pressure (MAP), whenever appropriate. RESULTS Of 1745 participants (age 61.4 ± 11.6, 65% women), 580 died, 212 of CVD, and 290 experienced a stroke during 17 follow-up years. PP was strongly correlated with elPP (r = 0.89) and less so with stPP (r = 0.58), and the correlation between the two components was weak (r = 0.15). After the adjustment, hazard ratio of PP per 1 SD increment for total mortality, CVD mortality, and stroke morbidity were 1.095 (95% CI 0.973-1.232), 1.207 (1.000-1.456), and 0.983 (0.829-1.166), respectively. Corresponding hazard ratios and 95% CIs were nonsignificant for elPP, and stPP. However, among participants with median pulse rate 68.5 bpm or less (median, n = 872), total (327 deaths) and CVD (131 deaths) mortality were predicted by elPP (per 1 SD increment), hazard ratio 1.231 (95% CI, 1.082-1.401), and 1.294 (95% CI, 1.069-1.566), respectively. In the subgroup of treated participants with hypertension and pulse rate 68.5 or less bpm (n = 309), total (177 deaths) and CVD (77 deaths) mortality were predicted by elPP, hazard ratio of 1.357 (95% CI, 1.131-1.628), and 1.417 (95% CI, 1.092-1.839), respectively. Stroke morbidity was not predicted by either PP or the PP components. CONCLUSION In a rural Japanese population, elPP but not stPP was predictive of total and CVD mortality even when adjusted for MAP and conventional risk factors in the subpopulation with slower pulse rate. This was mostly among the treated hypertensive patients.
Finding solutions for HIV's lost generation: adolescents and young adults

V o l u m e 1 5 , N o . 2 • F a l l 2 0 1 0 • I S S N 1 5 2 0 8 7 4 5 Interviews with: Patricia M. Flynn, MD: Understanding antiretroviral adherence, HIV stigma, and HIV prevention in adolescents Bill G. Kapogiannis, MD: Preventing HIV acquisition and transmission—and improving identification and management of HIV—in youth Finding solutions for HIV’s lost generation: adolescents and young adults
Functional analysis of Clostridium difficile sortase B reveals key residues for catalytic activity and substrate specificity

Most of Gram-positive bacteria anchor surface proteins to the peptidoglycan cell wall by sortase, a cysteine transpeptidase that targets proteins displaying a cell wall sorting signal. Unlike other bacteria, Clostridium difficile, the major human pathogen responsible for antibiotic-associated diarrhea, has only a single functional sortase (SrtB). Sortase's vital importance in bacterial virulence has been long recognized, and C. difficile sortase B (Cd-SrtB) has become an attractive therapeutic target for managing C. difficile infection. A better understanding of the molecular activity of Cd-SrtB may help spur the development of effective agents against C. difficile infection. In this study, using site-directed mutagenesis, biochemical and biophysical tools, LC-MS/MS, and crystallographic analyses, we identified key residues essential for Cd-SrtB catalysis and substrate recognition. To the best of our knowledge, we report the first evidence that a conserved serine residue near the active site participates in the catalytic activity of Cd-SrtB and also SrtB from Staphylococcus aureus. The serine residue indispensable for SrtB activity may be involved in stabilizing a thioacyl-enzyme intermediate because it is neither a nucleophilic residue nor a substrate-interacting residue, based on the LC-MS/MS data and available structural models of SrtB–substrate complexes. Furthermore, we also demonstrated that residues 163–168 located on the β6/β7 loop of Cd-SrtB dominate specific recognition of the peptide substrate PPKTG. The results of this work reveal key residues with roles in catalysis and substrate specificity of Cd-SrtB.
Structural basis for interorganelle phospholipid transport mediated by VAT-1

Eukaryotic cells are compartmentalized to form organelles, whose functions rely on proper phospholipid and protein transport. Here we determined the crystal structure of human VAT-1, a cytosolic soluble protein that was suggested to transfer phosphatidylserine, at 2.2 Å resolution. We found that VAT-1 transferred not only phosphatidylserine but also other acidic phospholipids between membranes in vitro. Structure-based mutational analyses showed the presence of a possible lipid-binding cavity at the interface between the two subdomains, and two tyrosine residues in the flexible loops facilitated phospholipid transfer, likely by functioning as a gate to this lipid-binding cavity. We also found that a basic and hydrophobic loop with two tryptophan residues protruded from the molecule and facilitated binding to the acidic-lipid membranes, thereby achieving efficient phospholipid transfer.
Preparation and Standardization of Polyherbomineral Formulation

Standardization of herbal formulation is essential in order to assess the quality of drugs. The present paper reports preparation and standardization of a herbomineral formulation which contains Zingiber officinalis (rhizome), Piper longum (fruit), Piper nigrum (fruit), Emblica officinalis (fruit,seed), Terminalia chebula (mature fruit), Terminalia belerica (pericarp of ripe fruit), Piper retrofractum (stem), Coriander sativum (fruit), Cuminum cyminum (fruit), Mercury, sulphur, loh bhasam, abharak bhasam. This Ayurvedic formulation is used to treat cold and cough. Here we discussed and focused about Morphology, Microscopy, Total ash, Acid insoluble ash, Water soluble and Alcohol soluble extractive value, bulk density, tapped density, Carr’s index, Hausner ratio, phytochemical tests, and Thin layer chromatography (TLC) etc. These parameters are required for authentication of any herbal drug and its Herbo-mineral formulation.
Clinical Management of Squamous Cell Carcinoma of the Conjunctiva

Patient: Female, 33-year-old Final Diagnosis: Conjunctival squamous cell carcinoma Symptoms: Tumorous lesion on the nasal bulbar conjunctiva • red eye Medication: — Clinical Procedure: The conjunctival tumor was excised. The histopathological diagnosis suggested a conjunctival squamous cell carcinoma. A treatment with topical MMC was admistered Specialty: Ophthalmology Objective: Rare disease Background: Conjunctival squamous cell carcinoma is the most common non-pigmented malignancy of the ocular surface. This report illustrates the clinical management of squamous cell carcinoma of the conjunctiva. Case Report: A 33-year-old female was referred to our eye hospital with a tumorous lesion on the nasal bulbar conjunctiva of the right eye. A topical therapy with antibiotic and corticosteroid eye drops did not change the lesion. The conjunctival tumor was widely resected. The histopathological diagnosis suggested a squamous cell carcinoma. After resection, a treatment with topical mitomycin C (MMC) 0.02% eye drops were started 4 times daily for 14 days. Two cycles of treatment were done with a 2-week interval during which only artificial tears eye drops were administered. At the 12-month follow-up, there was no sign of recurrence. Conclusions: This case illustrates the effective and successful clinical management of squamous cell carcinoma of the conjunctiva with excision and postoperative treatment with MMC 0.02% eye drops.
The epilepsy and intellectual disability-associated protein TBC1D24 regulates the maintenance of excitatory synapses and animal behaviors

Perturbation of synapse development underlies many inherited neurodevelopmental disorders including intellectual disability (ID). Diverse mutations on the human TBC1D24 gene are strongly associated with epilepsy and ID. However, the physiological function of TBC1D24 in the brain is not well understood, and there is a lack of genetic mouse model that mimics TBC1D24 loss-of-function for the study of animal behaviors. Here we report that TBC1D24 is present at the postsynaptic sites of excitatory synapses, where it is required for the maintenance of dendritic spines through inhibition of the small GTPase ARF6. Mice subjected to viral-mediated knockdown of TBC1D24 in the adult hippocampus display dendritic spine loss, deficits in contextual fear memory, as well as abnormal behaviors including hyperactivity and increased anxiety. Interestingly, we show that the protein stability of TBC1D24 is diminished by the disease-associated missense mutation that leads to F251L amino acid substitution. We further generate the F251L knock-in mice, and the homozygous mutants show increased neuronal excitability, spontaneous seizure and pre-mature death. Moreover, the heterozygous F251L knock-in mice survive into adulthood but display dendritic spine defects and impaired memory. Our findings therefore uncover a previously uncharacterized postsynaptic function of TBC1D24, and suggest that impaired dendritic spine maintenance contributes to the pathophysiology of individuals harboring TBC1D24 gene mutations. The F251L knock-in mice represent a useful animal model for investigation of the mechanistic link between TBC1D24 loss-of-function and neurodevelopmental disorders.
AMPA receptor structure and auxiliary subunits

Fast excitatory synaptic transmission in the mammalian brain is largely mediated by AMPA‐type ionotropic glutamate receptors (AMPARs), which are activated by the neurotransmitter glutamate. In synapses, the function of AMPARs is tuned by their auxiliary subunits, a diverse set of membrane proteins associated with the core pore‐forming subunits of the AMPARs. Each auxiliary subunit provides distinct functional modulation of AMPARs, ranging from regulation of trafficking to shaping ion channel gating kinetics. Understanding the molecular mechanism of the function of these complexes is key to decoding synaptic modulation and their global roles in cognitive activities, such as learning and memory. Here, we review the structural and molecular complexity of AMPAR–auxiliary subunit complexes, as well as their functional diversity in different brain regions. We suggest that the recent structural information provides new insights into the molecular mechanisms underlying synaptic functions of AMPAR–auxiliary subunit complexes.