Miracle-dz/UniFAR-FTUs huggingface dataset:
Allosteric Block of KCa2 Channels by Apamin*

Activation of small conductance calcium-activated potassium (KCa2) channels can regulate neuronal firing and synaptic plasticity. They are characterized by their high sensitivity to the bee venom toxin apamin, but the mechanism of block is not understood. For example, apamin binds to both KCa2.2 and KCa2.3 with the same high affinity (KD ∼ 5 pm for both subtypes) but requires significantly higher concentrations to block functional current (IC50 values of ∼100 pm and ∼5 nm, respectively). This suggests that steps beyond binding are needed for channel block to occur. We have combined patch clamp and binding experiments on cell lines with molecular modeling and mutagenesis to gain more insight into the mechanism of action of the toxin. An outer pore histidine residue common to both subtypes was found to be critical for both binding and block by the toxin but not for block by tetraethylammonium (TEA) ions. These data indicated that apamin blocks KCa2 channels by binding to a site distinct from that used by TEA, supported by a finding that the onset of block by apamin was not affected by the presence of TEA. Structural modeling of ligand-channel interaction indicated that TEA binds deep within the channel pore, which contrasted with apamin being modeled to interact with the channel outer pore by utilizing the outer pore histidine residue. This multidisciplinary approach suggested that apamin does not behave as a classical pore blocker but blocks using an allosteric mechanism that is consistent with observed differences between binding affinity and potency of block.
Expression of a Germination-Specific Amidase, SleB, of Bacilli in the Forespore Compartment of Sporulating Cells and Its Localization on the Exterior Side of the Cortex in Dormant Spores

ABSTRACT A germination-specific amidase of bacilli is a major spore-lytic enzyme that is synthesized with a putative signal sequence and hydrolyses spore cortex in situ. The sleB gene encoding this amidase in Bacillus subtilis and Bacillus cereus was expressed in the forespore compartment of sporulating cells under the control of ςG, as shown by Northern blot and primer extension analyses. The forespore-specific expression ofB. subtilis sleB was further indicated by the forespore-specific accumulation of a SleB-green fluorescent protein fusion protein from which a putative secretion signal of SleB was deleted. Immunoelectron microscopy with anti-SleB antiserum and a colloidal gold-immunoglobulin G complex showed that the enzymes from both Bacillus species are located just inside the spore coat layer in the dormant spore, and in the dormant spore, the amidases appear exist in a mature form lacking a signal sequence. These results indicate that SleB is translocated across the forespore’s inner membrane by a secretion signal peptide and is deposited in cortex layer synthesized between the forespore inner and outer membranes. The peripheral location of the spore-lytic enzymes in the dormant spore suggests that spore germination is initiated at the exterior of the cortex.
Aquaporin-4 antibody–negative neuromyelitis optica

Objective: To optimize aquaporin-4 (AQP4) antibody (Ab) detection and to assess the influence of the increased sensitivity of the assay on the demographic and disease-related characteristics of a group of AQP4-Ab–negative patients. Methods: Serum samples were obtained from patients included in the French NOMADMUS database with a definite diagnosis of neuromyelitis optica (NMO) (n = 87) and were compared with controls (n = 54). They were tested by indirect immunofluorescence and cell-based assays (CBAs) in various conditions and with several plasmids. Results: We identified the CBA on live cells transfected with the untagged AQP4-M23 isoform as the best method, with a sensitivity of 74.4% and a specificity of 100%. We demonstrated a direct relationship between improvement of the sensitivity of the detection method and the distinctiveness and characteristics of the AQP4-Ab–negative NMO group. Whereas with the classic indirect immunofluorescence or current AQP4-M1 CBA we found only slight differences between the 2 populations, using the AQP4-M23 CBA, we demonstrated that patients with AQP4-Ab–negative NMO expressed specific demographic and disease-related features. They were characterized by an equal male/female ratio (p < 0.001), a Caucasian ethnicity (p = 0.029), and an overrepresentation of simultaneous optic neuritis and transverse myelitis at first episode (p = 0.015). In terms of disability, they experienced a better visual acuity at last follow-up compared with seropositive NMO (p = 0.007). Conclusion: This raises the question of a distinct physiopathology for patients with AQP4-Ab–negative NMO and of their place in the spectrum of the disease.
Predictors of psychological distress in caregivers of older persons with wet age-related macular degeneration

Objectives: Several studies have investigated the biopsychosocial impacts of age-related macular degeneration (AMD) in regards to the older patient, little is known about the impacts associated with caring for individuals with AMD. We aimed to determine the predictors of subjective caregiver distress and other negative outcomes associated with caring for someone with advanced AMD. Methods: Cross-sectional, self-complete survey involving 500 caregivers of persons with advanced AMD. Respondents were identified from the Macular Disease Foundation of Australia client database. Logistic regression tested the independent effects of care recipient and caregiver characteristics on study outcomes, including: caregiver psychological well-being, participation in recreational/social activities and retirement plans. Results: Around one third of caregivers self-reported a high level of care recipient dependence. Over one in two caregivers reported a negative state of mind. Comorbid chronic illnesses in the care recipient were associated with the caregiver reporting psychological distress, multivariable-adjusted odds ratio, OR, 1.45 (95% confidence intervals, CI, 1.14–1.86). If the care recipient was highly dependent on the caregiver, there was 99% greater likelihood of caregiver distress, OR 1.99 (95% CI 1.01–3.93). Comorbid chronic conditions in the care recipient was associated with 49% and 31% higher odds of the caregiver reporting disruption to other areas of their life and retirement plans related to the caregiving experience, respectively. Conclusions: A high prevalence of caregiver distress related to caring for persons with advanced AMD was observed. Level of dependence on the caregiver and presence of comorbid chronic illnesses were independent predictors of the caregiver experiencing psychological distress.
Is transesophageal electrophysiologic study valuable in children with successful radiofrequency ablation of supraventricular tachycardia on follow-up for recurrence?

Objective: The aim of this study was to evaluate the efficacy of transesophageal electrophysiologic study (TEEPS) for the determination of supraventricular tachycardia (SVT) recurrences in symptomatic and asymptomatic children after successful radiofrequency ablation (RFA) for SVT. Methods: A total of 66 patients who underwent TEEPS after successful RFA were included. The demographic features, symptoms of the patients, and the characteristics of the recurrences induced by TEEPS were evaluated. The arrhythmia types induced during RFA were compared with those induced by TEEPS in terms of the compatibility of the diagnosis. Results: Forty-two (63.6%) girls and 24 (36.4%) boys with a mean age of 11.8±3.4 years were followed-up for 44.1±15.7 months. The average time between RFA and TEEPS was 5.2±5.9 months. The diagnoses during RFA were atrioventricular nodal reentrant tachycardia (AVNRT) in 47 of 66 patients, atrioventricular reentrant tachycardia (AVRT) in 18 of 66 patients, and ectopic atrial tachycardia in 1 of 66 patients. SVT was induced by TEEPS in 2 of 25 symptomatic and 5 of 41 asymptomatic patients. The SVT inducibility rate was 5.5% (1/18) and 12.7% (6/47) in patients with AVRT and AVNRT, respectively. In addition, 85.7% (6/7) of all recurrences occurred within 3.5 months. The recurrences as AVNRT in 2 of 25 symptomatic patients occurred in the first month after RFA. AVNRT in 4 of 41 and AVRT in 1 of 41 asymptomatic patients were induced within 3.5 months and 15 months, respectively. Conclusion: TEEPS seems to be a valuable screening and diagnostic method for the determination of recurrence in symptomatic and asymptomatic children who underwent successful RFA.
Acute respiratory distress syndrome caused by miliary tuberculosis: a multicentre survey in South Korea.

BACKGROUND Miliary tuberculosis (TB) is an unusual cause of acute respiratory distress syndrome (ARDS). OBJECTIVE To evaluate the clinical characteristics and outcomes of patients with ARDS caused by miliary TB admitted to the intensive care unit (ICU). DESIGN A total of 67 patients were enrolled during the period 1999-2008. RESULTS The median age of the patients was 56 years (range 17-81), 19 (28.4%) were aged >71 years, and 38 (56.7%) were male. All-cause mortality in the ICU and hospital were respectively 58.2% and 61.2%. Of the total number of enrolled patients, 49 (73.1%) were prescribed anti-tuberculosis medication within 3 days of hospital admission. On the day of ARDS diagnosis (10.0 ± 3.7 vs. 7.4 ± 3.5, P = 0.005), non-survivors had a significantly higher Sequential Organ Failure Assessment (SOFA) score than survivors. Multivariate analysis showed that SOFA score on the day of ARDS diagnosis was a significant predictor of survival (OR 0.809, 95%CI 0.691-0.946, P = 0.008). It was difficult to determine the efficacy of systemic corticosteroids on patient survival. CONCLUSION ARDS caused by miliary TB was associated with a high in-hospital mortality rate, with SOFA score on the day of ARDS diagnosis being a valuable prognostic indicator.
Adrenarche does not occur in treated patients with congenital adrenal hyperplasia resulting from 21‐hydroxylase deficiency

OBJECTIVE There have been few studies of adrenarche In patients with congenital adrenal hyperplasia (CAH). We have therefore sought to detect the onset of adrenarche In CAH patients and to investigate whether its evolution was influenced by the severity of the disease, the age at the onset of substitution therapy, or both.
Acclimating to Breast Cancer: A Process of Maintaining Self-integrity in the Pretreatment Period

Background:The period between diagnosis and initial treatment is one of the most stressful times for women with breast cancer. Unresolved distress may lead to future mental health and adjustment difficulties. Adjustment is facilitated by thoughts and behaviors that integrate a threatening event into a person's worldview. Few studies, however, have explored women's pretreatment thought processes. Objective:The purpose of this study was to develop a grounded theory of the pretreatment thought processes and behaviors of women diagnosed with breast cancer. Methods:Grounded theory method guided theoretical sampling of 18 women from a Midwestern, US breast center who were 37 to 87 years old, diagnosed with stage 0 to II breast cancer within the past 6 to 21 days and awaiting surgical treatment. Constant comparison of interview data and open, selective, and theoretical coding identified interrelated concepts and constructs that formed the grounded theory. Results:Threatened self-integrity was the main concern of women identified in the pretreatment period. Women addressed this problem through a continuous, nonlinear process of acclimating to breast cancer consisting of 3 stages: surveying the situation, taking action, and emerging self. Situational and personal factors influenced women's degree of engagement in 1 or more stages. Conclusions:Women's pretreatment response to breast cancer diagnosis involves integrated thought processes to maintain self-integrity influenced by situational and personal factors hypothesized to be amenable to interventions that facilitate adjustment. Implications for Practice:New insights provided by this theory can guide clinical practice and generate hypotheses to test pretreatment interventions to support psychological adjustment to breast cancer.
BIO-ASSAY OF CIRCULATING RENIN-LIKE PRESSOR MATERIAL BY ISOVOLEMIC CROSS CIRCULATION.

The renin-like pressor material present in blood under various experimental conditions was determined by isovolemic cross circulation using nephrectomized rats as assay animals and rats having different concentrations of renin in the kidney as "donor" animals. Cross circulation was established by connecting the femoral arteries of both animals with the corresponding femoral veins and maintaining a constant flow. In intact anesthetized rats, a "basic" concentration of renin-like pressor material is demonstrable in the blood which is not influenced by unilateral nephrectomy. In the rat made hypertensive by clamping one renal artery, leaving the other kidney untouched, an increase in circulating renin-like pressor material is demonstrable. In unilaterally nephrectomized rats in which the artery of the remaining kidney is clamped, the concentration of circulating pressor material is not elevated. In adrenalectomized rats, an increase of circulating pressor material coincides with an elevated concentration of renin in the kidneys. There is a good correlation between the concentration of renin in the kidney and of pressor material in the blood, while the level of circulating renin-like substance is not correlated with the height of blood pressure.
EFFECTS OF THE HALOPHYTES TECTICORNIA INDICA AND SUAEDA FRUTICOSA ON SOIL ENZYME ACTIVITIES IN A MEDITERRANEAN SABKHA

In the present work, we studied the effectiveness of the predominant halophytes of Soliman sabkha (Tecticornia indica and Suaeda fruticosa) to promote soil biological activities and ecosystem productivity. Soil Arylsulphatese ARY, β-glucosidase β-GLU, phosphatase PHO, invertase INV, urease URE, and dehydogenase DES activities in Extra- and Intra-tuft halophytes and plant productivity were assessed. Results revealed a high increase of microbial community and ARY, β-GLU, PHO, INV, URE and DES activities (+298%, +400%, +800%, +350%, +320%, +25% and +759%, respectively) in Intra-tuft rhizosphere as compared to Extra-tuft one, which is likely due to the significant decrease of salinity in the rhizosphere of Tecticornia indica and Suaeda fruticosa. Both perennial plants exhibited high productivities (7.4 t dry weight ha−1 and 2.2 t dry weight ha−1, respectively) and Na+-hyperaccumulating capacities (0.75 t Na+ ha−1 and 0.22 t Na+ ha−1, respectively), reducing salt constraint and favouring soil fertility. This constitutes a promising alternative to enhance productivity in such a salt-affected biotope by offering suitable microhabitat for annual glycophytes.
Functional Effects of Mutations at F35 in the NH2-terminus of Kir6.2 (KCNJ11), Causing Neonatal Diabetes, and Response to Sulfonylurea Therapy

Heterozygous mutations in the human Kir6.2 gene (KCNJ11), the pore-forming subunit of the ATP-sensitive K+ channel (KATP channel), cause neonatal diabetes. To date, all mutations increase whole-cell KATP channel currents by reducing channel inhibition by MgATP. Here, we provide functional characterization of two mutations (F35L and F35V) at residue F35 of Kir6.2, which lies within the NH2-terminus. We further show that the F35V patient can be successfully transferred from insulin to sulfonylurea therapy. The patient has been off insulin for 24 months and shows improved metabolic control (mean HbA1c 7.58 before and 6.18% after sulfonylurea treatment; P < 0.007). Wild-type and mutant Kir6.2 were heterologously coexpressed with SUR1 in Xenopus oocytes. Whole-cell KATP channel currents through homomeric and heterozygous F35V and F35L channels were increased due to a reduced sensitivity to inhibition by MgATP. The mutation also increased the open probability (PO) of homomeric F35 mutant channels in the absence of ATP. These effects on PO and ATP sensitivity were abolished in the absence of SUR1. Our results suggest that mutations at F35 cause permanent neonatal diabetes by affecting KATP channel gating and thereby, indirectly, ATP inhibition. Heterozygous F35V channels were markedly inhibited by the sulfonylurea tolbutamide, accounting for the efficacy of sulfonylurea therapy in the patient.
The Relationship Between Temperament and Impulsive Behaviors in Eating Disordered Subjects

To date, few studies have examined the personality characteristics and clinical predictors of impulsive behaviors in eating disorders (ED). The aim of this work was to study the prevalence of a wide range of impulsive behaviors in a sample of 554 ED subjects and to examine the predictors of these behaviors. Subjects were diagnosed according to DSM-IV criteria as having anorexia nervosa restricting type (ANR; n = 183), anorexia nervosa binge eating/purging type (ANBP; n = 65), bulimia nervosa purging type (BNP; n = 244), and bulimia nervosa nonpurging type (BNNP; n = 62). Nine different types of impulsive behaviors were assessed in these groups. About 55% of the whole sample reported at least one type of impulsive behavior, 35% more than one, and about 13% more than three. According to findings, impulsive and multi-impulsive subjects are characterized by the presence of purging behavior and by specific temperamental features such as high levels of novelty seeking and low persistence. The prediction of impulsive behavior is further improved by considering the presence of a history of childhood abuse, maternal psychiatric morbidity, and some specific psychological symptoms such as maturity fears, perfectionism, depression, and obsessive-compulsive symptoms. The presence of impulsive behavior appears to be associated with overall higher levels of psychiatric symptomatology and eating psychopathology, thus indicating that they are an important feature to be considered in the assessment and treatment of ED.
Outcomes Of Intensive Care Patients Having Septic Shock At A Tertiary Care Hospital Of Islamabad.

BACKGROUND Septic shock is defined as sepsis with circulatory, cellular and metabolic abnormalities which are associated with greater mortality more than 40%. The objective of this study was to identify shortcomings and act promptly and adequately. METHODS This case series included 32 patients over a period of 03 months, September to November 2016 done at ICU of KRL Hospital Islamabad. RESULTS The study only enrolled patients who fulfilled the criteria of septic shock. Mortality was as high as 50%. (UTI) was the most common infection (43.75%). In patients who died Pneumonia was commonest infection (43.75%). Mean TLC, CRP and lactate was 17.48×109/l, 29.28 mg/L and 6.81mmom/L respectively. Escherichia Coli (E. coli) was the most common isolated pathogen (31.25%) followed by Staphylococcus Aureus (12.5%). Mean initial MAP was 49.7 mmHg and mean MAP at end of 3-day period was 71.4 mmHg. Mean norepinephrine dose given on day 1, 2 & 3 was 0.90 μg/kg/min, 1.01 μg/kg/min & 1.28 μg/kg/min respectively. Mean hospital stay was 7.1 days. Six out of 08 (75%) patients who needed ventilator support died while 02 out of 08 (25%) patients survived. Acute Kidney Injury (AKI) was the most common End Organ Damage (EOD). CONCLUSIONS Mortality remains high in septic shock despite maximum efforts. In current study MAP, serum lactate level, hospital stay, need for ventilator support, comorbidities, need for newer generation antimicrobials were the important cofounders in differentiating patients who died and those who survived with significant p-values in the 1st four conditions.
Levels of serum immunoglobulin G specific to bacterial surface protein A of Tannerella forsythia are related to periodontal status.

BACKGROUND Tannerella forsythia (Tf) is a Gram-negative anaerobe implicated in the development of periodontal disease. Bacterial surface protein A (BspA) is a surface-expressed and -secreted protein that is recognized as an important virulence factor of Tf. This study was undertaken to determine whether Tf BspA induces an antibody response in periodontal disease. We hypothesized that serum immunoglobulin (Ig)G antibody levels against BspA correlate with the disease of patients. METHODS Sera were obtained from 100 patients with cardiac disorders and periodontal disease and 73 patients who experienced myocardial infarction but were periodontally healthy. Sera samples were assayed for anti-BspA antibody (total IgG and IgG subtypes) by enzyme-linked immunosorbent assay (ELISA). Antibody levels were measured in ELISA units by using an arbitrary patient as a standard. RESULTS A negative correlation was found with BspA-specific total IgG antibody titers and the severity of disease measured as the clinical attachment level (CAL) when healthy and diseased groups were analyzed separately (healthy group: [-0.23, correlation value] Student's t value [73 degrees of freedom] = 1.99; P = 0.05; diseased group: [-0.21] t [100 degrees of freedom] = 2.12; P = 0.03]). However, there was a positive correlation ([0.18 correlation value] Student's t value [173 degrees of freedom] = 2.39; P = 0.017) when healthy and diseased groups were combined. A strong positive correlation ([0.338 correlation value] Student's t value [173 degrees of freedom] = 4.69; P <0.0001) between the BspA-specific IgG titers and periodontal probing depth was observed when healthy and disease groups were combined. CONCLUSIONS Data demonstrated that antibodies to Tf BspA were elicited in patients with periodontal disease, and antibody levels were associated with the disease severity. Furthermore, data suggested that anti-BspA IgG might have a protective function in periodontal disease by minimizing the loss of tooth attachment tissue.
Dietary wolfberry ameliorates retinal structure abnormalities in db/db mice at the early stage of diabetes

Hyperglycemia-linked oxidative stress and/or consequent endoplasmic reticulum (ER) stress are the causative factors of pathogenesis of diabetic retinopathy. Dietary bioactive components which mitigate oxidative stress may serve as potential chemopreventive agents to prevent or slow down the disease progression. Wolfberry is a traditional Asian fruit consumed for years to prevent aging eye diseases in Asian countries. Here we report that dietary wolfberry ameliorated mouse retinal abnormality at the early stage of type 2 diabetes in db/db mice. Male mice at six weeks of age were fed the control diet with or without 1% (kcal) wolfberry for eight weeks. Dietary wolfberry restored the thickness of the whole retina, in particular the inner nuclear layer and photoreceptor layer, and the integrity of the retinal pigment epithelia (RPE), and the ganglion cell number in db/db mice. Western blotting of whole retinal cell lysates revealed that addition of wolfberry lowered expression of ER stress biomarkers binding immunoglobulin protein (BiP), protein kinase RNA-like ER kinase (PERK), activating transcription factor 6 (ATF6) and caspase-12, and restored AMP-activated protein kinase (AMPK), thioredoxin, Mn superoxide dismutase (Mn SOD) and forkhead O transcription factor 3 α (FOXO3α) activities. To determine if our observations were due to the high contents of zeaxanthin and lutein in wolfberry, additional studies using these carotenoids were conducted. Using the human adult diploid RPE cell line ARPE-19, we demonstrated that both zeaxanthin and lutein could mimic the wolfberry preventive effect on activation of AMPK, thioredoxin, Mn SOD, FOXO3α activities, normalize cellular reactive oxygen species and attenuate ER stress in ARPE-19 cells exposed to a high glucose challenge. The zeaxanthin preventive effect was abolished by small interfering RNA knockdown of AMPKα. These results suggested that AMPK activation appeared to play a key role in upregulated expression of thioredoxin and Mn SOD, and mitigation of cellular oxidative stress and/or ER stress by wolfberry and zeaxanthin and/or lutein. Taken together, dietary wolfberry on retinal protection in diabetic mice is, at least partially, due to zeaxanthin and/or lutein.