Effect of prothrombin and its activation fragments on calcium oxalate crystal growth and aggregation in undiluted human urine in vitro: relationship between protein structure and inhibitory activity.
In recent years there has been great interest in the putative role of prothrombin and its activation peptides, especially the urinary form of prothrombin fragment 1, in the pathogenesis of calcium oxalate (CaOx) urolithiasis. Previously, we showed that prothrombin and its activation peptides inhibit CaOx crystallization in inorganic conditions in vitro. The aim of the present study was to determine if this inhibitory activity is retained in undiluted human urine and, therefore, whether it is likely to have any influence under physiological conditions. A secondary objective was to assess the relationship between the structures of the proteins and their inhibitory activities. Prothrombin was purified from Prothrombinex-HT, cleaved with thrombin and the resulting fragment 1 (F1) and fragment 2 (F2) were purified. The purity of each protein was confirmed by SDS/PAGE, and their effects on CaOx crystallization in undiluted ultrafiltered human urine were determined at a final concentration 80.65 nmol/l using Coulter Counter and [(14)C]oxalate analysis. The precipitated crystals were visualized using scanning electron microscopy. The Coulter Counter data revealed that, whereas prothrombin and its activation peptides did not affect the urinary metastable limit and the size of the precipitated particles, F1 did significantly reduce the latter. These findings were corroborated with scanning electron microscopy which also revealed that the reduction in particle size caused by F1 resulted from a decrease in the degree of crystal aggregation, rather than in the size of the individual crystals. The [(14)C]oxalate data showed that none of the proteins added significantly inhibited the mineral deposition. It was concluded that with the exception of F1, which does inhibit CaOx crystal aggregation, prothrombin and its activation peptides do not alter the deposition and aggregation of CaOx crystals in ultrafiltered human urine in vitro. Also, the gamma-carboxyglutamic acid domain of prothrombin and F1, which is absent from thrombin and F2, is the region of the molecules that determines their potent inhibitory effects. The superior potency of F1, compared with prothrombin, probably results from the molecule's greater charge-to-mass ratio.


Morphology and unbiased stereology of the lateral superior olive in the short-beaked common dolphin, Delphinus delphis (Cetacea, Delphinidae).
In all mammals, the superior olivary complex (SOC) comprises a group of auditory brainstem nuclei that are important for sound localization. Its principal nuclei, the lateral superior olive (LSO) and the medial superior olive (MSO) process interaural time and intensity differences, which are the main cues for sound localization in the horizontal plane. Toothed whales (odontocetes) rely heavily on hearing and echolocation for foraging, orientation, and communication and localize sound with great acuity. The investigation of the SOC in odontocetes provides insight into adaptations to underwater hearing and echolocation. However, quantitative anatomical data for odontocetes are currently lacking. We quantified the volume, total neuron number, and neuron density of the LSO of six common dolphins (Delphinus delphis) using the Cavalieri principle and the unbiased stereology optical fractionator. Our results show that the LSO in D. delphis has a volume of 150 + (SD = 27) mm3 , which is on average 69 (SEM = 19) times larger than the LSO in human, or 37 (SEM = 11) times larger than the human LSO and MSO combined. The LSO of D. delphis contains 20,876 ± (SD = 3300) neurons. In comparison, data reported for the human brainstem indicate the LSO has only about ¼ that number but about the same number for the LSO and MSO combined (21,100). LSO neurons range from 21 to 25 μm (minor axis) and from 44 to 61 μm (major axis) in transverse sections. The LSO neuron packing density is 1080 ± (SD = 204) neurons/mm3 , roughly half of the LSO neuron density in human. SMI-32-immunohistochemistry was used to visualize projection neurons in the LSO and revealed the presence of principal, marginal, and multipolar neurons in transverse sections. The distinct morphology of the LSO likely reflects the common dolphin's superb sensitivity to ultra-high frequencies and ability to detect and analyze sounds and their location as part of its underwater spatial localization and echolocation tasks.


Mortality Risk and Etiologic Spectrum of Community-acquired Pneumonia in Hospitalized Adult Patients.
The etiology of community-acquired pneumonia (CAP) is specific to each region, as proved by numerous studies conducted so far. Knowledge of these data is essential in developing guidelines for antibiotic prescription. Assessment of severity of CAP patients is crucial in determining the risk of mortality and the site of care. Unusual bacterial etiologies may increase the risk of mortality. First outcome was the identification of pathogens in CAP patients requiring hospitalization and secondary to determine factors that correlate with increased risk of mortality. A prospective study of patients over 18 years of age hospitalized with CAP from whom pathological products were taken (mainly sputum) for bacteriological analysis (microscopy and culture). 120 patients were evaluated over a period of three years (2008-2010); we could identify a bacterial etiology in 33 cases (27.5%). The most commonly isolated were S. pneumoniae (11 cases), H. influenzae (9 cases) and Gram-negative enteric bacilli (12 cases). The mortality rate was 9.2%, significantly higher in the age group over 65 years and in patients with hypoxemia, impaired consciousness and high CURB 65 score, but the only independent factor for the mortality risk prediction was the presence of confusion on admission. S. pneumoniae, H. infuenzae and enteric Gram negative bacilli remain the most frequent cause of CAP in hospitalized patients in Romania and the first line of antibiotic treatment should be targeted. The only independent risk factor for mortality risk was the presence of disorders of consciousness on admission.


The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation incorporating both cystatin C and creatinine best predicts individual risk: a cohort study in 444 patients with chronic kidney disease.
The recently introduced CKD-EPIcreat-cys equation surpassed creatinine-based equations for GFR estimation in a large cross-sectional analysis. However, its performance to predict individual risk of CKD progression and death in patients with various underlying CKD etiologies is unknown. We recruited 444 patients with CKD GFR categories 2-4 (eGFR 15-89 mL/min/1.73 m2); baseline eGFR was estimated by the established MDRD and CKD-EPIcreat equations and by the novel CKD-EPIcreat-cys equation. Patients were followed for 2.7±1.2 years for the occurrence of the combined predefined endpoint event: death, need for renal replacement therapy or halving of eGFR. The endpoint occurred in 62 patients. Reclassification from MDRD determined categories to CKD-EPIcreat-cys categories yielded net reclassification improvements for those with the endpoint event (NRIevents) of 27.4% (95% CI: 16.7-40.0%) and for those without the event (NRInon-events) of -3.1% (-8.2 to 1.6%). Similarly, reclassification from CKD-EPIcreat categories to CKD-EPIcreat-cys categories yielded an NRIevents of 22.6% (10.2-34.3%) and NRInon-events of -11.3% (-15.9 to -6.5%). Addition of albuminuria to each eGFR equation increased the calculated risk of the outcome for a net 26-32% of those who subsequently reached the endpoint, and reduced the calculated risk in a net 21-23% in non-event patients, but only minimally. The CKD-EPIcreat-cys equation assigned patients who went on to have the event to more appropriate CKD risk categories than MDRD and CKD-EPIcreat, but patients without the event to less appropriate categories than CKD-EPIcreat. Addition of albuminuria marginally improved risk classification for those who had the event.


Metabolism in the globus pallidus after fetal implants in rats with nigral lesions.
The effect of fetal mesencephalic implants on glucose utilization in selected brain structures and on apomorphine-induced rotational behavior was measured in rats with a unilateral lesion of the substantia nigra. Ipsilateral, but not contralateral, implants decreased the rotational behavior induced by apomorphine. In addition, the nigral lesion decreased glucose utilization in the dorso- and ventrolateral quadrants of the striatum and in the entopeduncular nucleus but increased glucose utilization in the ipsilateral globus pallidus and lateral habenula. The increased metabolism in the globus pallidus was attenuated by ipsilateral, but not contralateral, mesencephalic implants which also decreased glucose utilization in the dorsomedial caudate nucleus. These results indicate that the ability of an ipsilateral mesencephalic graft to ameliorate the motor behavior in rats with nigral lesions is associated with changes in the functional activity of the ipsilateral globus pallidus.


Operative and Survival Outcomes of Robotic-Assisted Surgery for Colorectal Cancer in Elderly and Very Elderly Patients: A Study in a Tertiary Hospital in South Korea.
Data of all patients ≥75 years who underwent a robotic-assisted curative resection in Korea University Anam Hospital, Seoul, South Korea, between January 2007 and January 2021 were extracted from a prospectively maintained colorectal cancer database. Patients were subdivided into the three groups according to the age: youngest-old (YO: 75-80 years), middle-old (MO: 81-85), and oldest-old (OO: ≥86 years). Intraoperative findings, postoperative, and oncological outcomes were compared between the groups. Seventy-six consecutive patients (female 52.6%) were included; mean age was 80 years (SD 0.33); mean body mass index (BMI), 23.8 20.9 kg/m2 (SD 3.58); mean total operative time, 279 min (SD 80.93); mean blood loss, 186 ml (SD 204.03); mean postoperative length of stay, 14 days (SD 12.03). Major complications were seen in 2.1% of patients. The 30-day mortality rate was 0%. Average number of lymph node harvested was 20.9 (SD 12.33). Postoperative complications were not statistically different between the groups. Mean follow-up time for cancer-specific survival (CSS) was 99.28 months for the YO, 72.11 months for MO, and 31.25 months for OO groups (p = 0.045). The CSS rates at 5 years were 27.0%, 21.0%, and 0%, respectively. Recurrence risk was 10.50 times higher in the OO group than the others (adjusted HR, 95% CI 1.868-59.047, p = 0.008). In the multivariable analysis, TNM stage was not a risk factor for CSS in all groups. The number of the harvested nodes was a protective factor for recurrence (HR of 0.932, 95% CI 0.875-0.992, p = 0.027) and CSS (HR of 0.928, 95% CI 0.861-0.999, p = 0.047) in elderly patients. Robotic surgery is highly feasible in elderly and very elderly colorectal cancer patients, providing a favorable operative safety profile and an acceptable cancer-specific survival outcome.


Providing physicians with feedback on how they supervise students during patient contacts.
In this descriptive study an instrument is presented that has been developed to provide physicians with feedback about their strengths and weaknesses in facilitating student learning during patient contacts. The instrument is strongly theory based, i.e. it is based on current general theories of context-bound learning environments, and forms of facilitation promoting transfer of knowledge to actual professional practice. In addition, it has been developed in cooperation with physicians supervising students during patient contacts. The authors have shown how physicians can be provided with individualized feedback on their performance in supervising students during patient contacts.


Allele quantification using molecular inversion probes (MIP).
Detection of genomic copy number changes has been an important research area, especially in cancer. Several high-throughput technologies have been developed to detect these changes. Features that are important for the utility of technologies assessing copy number changes include the ability to interrogate regions of interest at the desired density as well as the ability to differentiate the two homologs. In addition, assessing formaldehyde fixed and paraffin embedded (FFPE) samples allows the utilization of the vast majority of cancer samples. To address these points we demonstrate the use of molecular inversion probe (MIP) technology to the study of copy number. MIP is a high-throughput genotyping technology capable of interrogating >20 000 single nucleotide polymorphisms in the same tube. We have shown the ability of MIP at this multiplex level to provide copy number measurements while obtaining the allele information. In addition we have demonstrated a proof of principle for copy number analysis in FFPE samples.


Inhibition of Soybean Cell Growth by the Adsorption of Rhizobium japonicum.
Soybean cells in suspension culture were inhibited in their growth by mixed culture with Rhizobium japonicum 5033. Rhizobium cells had the ability to adsorb on the surface of soybean cells. Cell envelope prepared from Rhizobium by sonic oscillation inhibited the growth of soybean cells. The growth-inhibiting activity of the cell envelope was depressed by beta-glucosidase, KIO(4), urea, sodium cholate, and Triton X-100, but was stable on heating at 120 C for 15 minutes. Adsorption of the cell envelope on soybean cells was depressed by only beta-glucosidase. The sodium cholate-soluble fraction of the cell envelope had the growth-inhibiting activity. Results in this paper suggest that components of the Rhizobium cell surface cause the inhibition of soybean cell growth after the adsorption of the Rhizobium cell to the soybean cell.


Comparison of Cepheid Xpert Flu/RSV XC and BioFire FilmArray for Detection of Influenza A, Influenza B, and Respiratory Syncytial Virus.
The Xpert Flu/RSV XC was compared to the FilmArray respiratory panel for detection of influenza (Flu) A, Flu B, and respiratory syncytial virus (RSV), using 128 nasopharyngeal swabs. Positive agreements were 100% for Flu A and RSV and 92.3% for Flu B. The Xpert may be useful in clinical situations when extensive testing is not required and may serve an important role in laboratories already performing broader respiratory panel testing.


Regio- and stereoselective monoepoxidation of dienes using methyltrioxorhenium: synthesis of allylic epoxides.
Methyltrioxorhenium (MTO) complexed with pyridine was shown to be a highly effective catalyst for the regioselective monoepoxidation of conjugated di- and trienes using 30% H2O2 at or below room temperature. The resultant allylic epoxides, and the triols derived from them, are versatile synthetic intermediates as well as substructures present in many bioactive natural products. The site of epoxidation was dependent upon olefin substitution, olefin geometry (Z vs E), and the presence of electron-withdrawing substituents on adjacent carbons. For 1-acyl(silyl)oxypenta-2,4-dienes, epoxidation of the distal olefin was generally favored in contrast to the adjacent regioselectivity characteristic of Sharpless, peracid, and other directed epoxidations of hydroxylated dienes.


Contemporary European practice in transcatheter aortic valve implantation: results from the 2022 European TAVI Pathway Registry.
A steep rise in the use of transcatheter aortic valve implantation (TAVI) for the management of symptomatic severe aortic stenosis occurred. Minimalist TAVI procedures and streamlined patient pathways within experienced Heart Valve Centres are designed to overcome the challenges of ever-increasing procedural volume. The 2022 European TAVI Pathway Survey aims to describe contemporary TAVI practice across Europe. Between October and December 2022, TAVI operators from 32 European countries were invited to complete an online questionnaire regarding their current practice. Responses were available from 147 TAVI centres in 26 countries. In 2021, the participating centres performed a total number of 27,223 TAVI procedures, with a mean of 185 TAVI cases per centre (median 138; IQR 77-194). Treatment strategies are usually (87%) discussed at a dedicated Heart Team meeting. Transfemoral TAVI is performed with local anaesthesia only (33%), with associated conscious sedation (60%), or under general anaesthesia (7%). Primary vascular access is percutaneous transfemoral (99%) with secondary radial access (52%). After uncomplicated TAVI, patients are transferred to a high-, medium-, or low-care unit in 28%, 52%, and 20% of cases, respectively. Time to discharge is day 1 (12%), day 2 (31%), day 3 (29%), or day 4 or more (28%). Reported adoption of minimalist TAVI techniques is common among European TAVI centres, but rates of next-day discharge remain low. This survey highlights the significant progress made in refining TAVI treatment and pathways in recent years and identifies possible areas for further improvement.


Tapping of Granular Packs: A Model Based on Local Two-Level Systems.
Two-level systems are known to be important for the low-temperature properties of glasses. We suggest here that they might explain some remarkable properties of powders under repeated tapping, as discovered by the Chicago group. Following the ideas of S. F. Edwards, the relevant variables here are (1) the volumes V(alpha) (V(beta)) occupied in the states alpha, beta (including distant reorganizations); (2) the magnitude B of the "activated volume" during a transition from alpha to beta; (3) the analog of temperatures, i.e., the compactivity (or free volume) v. Tapping induces alpha-->beta transitions, and these in turn reduce the compactivity. At low tapping strengths GammaGamma>Gamma(*)), the system freezes before reaching the alpha-beta equilibrium, and the density grows with the observed logarithmic law. At higher tapping strengths (Gamma<Gamma(*)) the beta<--beta equilibrium may be approached and competes with freezing (because the free volume is expected to increase with Gamma). The scenarios are discussed here for two limits; (a) a well-defined difference Delta=V(alpha)-V(beta), (b) a flat distribution of Delta values, which gives rather different predictions. Copyright 2000 Academic Press.


A new insight into subinteractomes of functional antagonists: Thromboxane (CYP5A1) and prostacyclin (CYP8A1) synthases.
The current article aims to summarize all possible spectrum of protein-protein interactions for thromboxane A synthase (CYP5A1) and prostacyclin synthase (CYP8A1). These enzymes metabolize the same substrate (prostaglandin H2 ) and can participate in cardiovascular, inflammatory, immune processes, and apoptosis modulation, as well as significantly influence the risk of cancers. Binary protein-protein and multiprotein complexes are of great importance in enzyme-regulating and signal-transduction pathways. However, protein partners of CYP5A1 and CYP8A1 are not yet fully identified, although both synthases are considered as prospective drug targets. At least 36 novel protein partners of CYP5A1 and CYP8A1 were revealed from different tissue types using an approach based on affinity isolation and mass spectrometry. Enrichment analysis showed that these proteins have different molecular functions: folding (refolding), unfolded protein and chaperon binding, protein transport (export/import), posttranslational modification, protein domain-specific binding, antioxidant activity, and glutathione homeostasis. A significant part of them, belonging to molecular chaperones, were common partners for CYP5A1 and CYP8A1, while other proteins were unique with the tissue-dependent distribution. New aspects of CYP5A1 and CYP8A1 interactomics and hetero-complex formation with different protein partners, including cytochrome P450s are discussed.


Video-assisted Port-Access surgery for radical myxoma resection.
The curative treatment of choice for myxomas is surgical removal. Most of the patients are young and active and are focused on postoperative comfort, cosmesis and a fast track to complete rehabilitation, all of which is related to the degree of invasiveness of the intervention. We report our first experience with video-assisted Port-Access surgery for atrial myxoma. From February 1997 until April 2000, nine patients (3M/6F)) had an atrial myxoma resection with the Heartport Endo-CPB and Endo-aortic clamp system. Mean age was 54 +/- 21.9 years. Most of the patients were symptomatic and had good LV function. Two patients had a combined procedure: one mitral valve replacement and one vascular shunt for dialysis. Mean aortic cross clamp time was 69 +/- 32.8 min and mean perfusion time was 103 +/- 42.7 min. There were no conversions to sternotomy. Three patients had minor complications. Mean ICU and hospital stay were 1 +/- 1.4 and 6 +/- 3.9 days respectively. No thromboembolic or peripheral ischaemic complications were observed. There were no hospital deaths. No recurrent tumors have been identified. The Port-Access approach for myxoma resection constitutes a invaluable alternative to sternotomy with the same gold standards of results and quality.


Cholesterol crystal embolization in a Saudi patient after cardiac surgery--a case report.
An eroded atheromatous aorta may be a source of cholesterol crystal embolism(CCE). Embolization of atheromatous material accounts for obstruction of distal arterioles around which a foreign-body giant cell granuloma inflammatory reaction develops. The diagnosis is often delayed or un recognized because of varying or misleading clinical signs, such as renal insufficiency, digestive or neurological symptoms, or both or unexplained multiple-system disease. Although CCE can occur spontaneously, it has been increasingly recognized as an iatrogenic complication from an invasive vascular procedure, such as manipulation of the aorta during angiography or vascular surgery. It has also been reported to occur following anticoagulant therapy or thrombolysis. Patients undergoing coronary artery bypass grafting (CABG) often experience a combination of these factors: anticoagulation, intra-arterial angiographic procedures and intraoperative aortic cross-clamping. These multiple factors could account for the acute and severe postoperative clinical and biological findings observed in the case reported here. A 65-year-old Saudi man was admitted to our hospital on July 9, 2008 due to chest pain at rest. He had suffered from type 2 diabetes mellitus on Oral hypoglycemics, hypertension on treatment, impaired renal functions and hypercholesterolemia, he was an ex-smoker with history of diagnosed pulmonary interstitial fibrosis. He had Coronary angiography in another hospital on May 2008 showing a left main lesion 60%, Left anterior descending lesion 90%, circumflex lesion 80% and Right coronary lesion 70%, three weeks later an acute on top of chronic deterioration in renal chemistry was observed for which conservative treatment was chosen.


The neighbourhood environment and profiles of the metabolic syndrome.
There is a dearth of studies on how neighbourhood environmental attributes relate to the metabolic syndrome (MetS) and profiles of MetS components. We examined the associations of interrelated aspects of the neighbourhood environment, including air pollution, with MetS status and profiles of MetS components. We used socio-demographic and MetS-related data from 3681 urban adults who participated in the 3rd wave of the Australian Diabetes, Obesity and Lifestyle Study. Neighbourhood environmental attributes included area socio-economic status (SES), population density, street intersection density, non-commercial land use mix, percentages of commercial land, parkland and blue space. Annual average concentrations of NO2 and PM2.5 were estimated using satellite-based land-use regression models. Latent class analysis (LCA) identified homogenous groups (latent classes) of participants based on MetS components data. Participants were then classified into five metabolic profiles according to their MetS-components latent class and MetS status. Generalised additive mixed models were used to estimate relationships of environmental attributes with MetS status and metabolic profiles. LCA yielded three latent classes, one including only participants without MetS ("Lower probability of MetS components" profile). The other two classes/profiles, consisting of participants with and without MetS, were "Medium-to-high probability of high fasting blood glucose, waist circumference and blood pressure" and "Higher probability of MetS components". Area SES was the only significant predictor of MetS status: participants from high SES areas were less likely to have MetS. Area SES, percentage of commercial land and NO2 were associated with the odds of membership to healthier metabolic profiles without MetS, while annual average concentration of PM2.5 was associated with unhealthier metabolic profiles with MetS. This study supports the utility of operationalising MetS as a combination of latent classes of MetS components and MetS status in studies of environmental correlates. Higher socio-economic advantage, good access to commercial services and low air pollution levels appear to independently contribute to different facets of metabolic health. Future research needs to consider conducting longitudinal studies using fine-grained environmental measures that more accurately characterise the neighbourhood environment in relation to behaviours or other mechanisms related to MetS and its components.


Ultrastructure investigation of the secondary insemination system of the gamasid mite Hattena cometis domrow (Acari: Anactinotrichida: Ameroseiidae).
Many gamasid mites, mainly of the taxon Dermanyssina, possess a secondarily evolved insemination system that is generally described as occurring in two types, the laelapid and the phytoseiid-type, which are structurally considerably different. Considering that Dermanyssina represent the most recent and most diverse group of gamasid mites, it was expected that a greater diversity of insemination system than reflected by the two types could be present and could give an idea of its evolution within the taxon. Here, the authors present a description of the fine-structure of the female secondary insemination system in the dermanyssine mite Hattena cometis. The system consists of a pair of sperm induction pores (solenostomes) and short sperm access ducts (tubules) which end in a syncytium. The syncytial strands of both sides meet medially under the ovary s.str., where they form a spherical syncytial spermatheca. Mature sperm cells of a modified ribbon type were seen in the syncytial parts of the system. The insemination system of Hattena cometis is regarded as a modification of the laelapid type. However, it is much simpler than that of Varroa destructor, the only other gamasid mite with the laelapid type studied ultrastructurally until now, and shows also some structural differences (e.g., no presence of an unpaired sperm duct). Hence, the present study suggests that some intermediate types might be revealed in future ultrastructure studies representing steps in the evolution of the insemination system in the Dermanyssina.


Systems Biology Approach Identifies Prognostic Signatures of Poor Overall Survival and Guides the Prioritization of Novel BET-CHK1 Combination Therapy for Osteosarcoma.
Osteosarcoma (OS) patients exhibit poor overall survival, partly due to copy number variations (CNVs) resulting in dysregulated gene expression and therapeutic resistance. To identify actionable prognostic signatures of poor overall survival, we employed a systems biology approach using public databases to integrate CNVs, gene expression, and survival outcomes in pediatric, adolescent, and young adult OS patients. Chromosome 8 was a hotspot for poor prognostic signatures. The MYC-RAD21 copy number gain (8q24) correlated with increased gene expression and poor overall survival in 90% of the patients (n = 85). MYC and RAD21 play a role in replication-stress, which is a therapeutically actionable network. We prioritized replication-stress regulators, bromodomain and extra-terminal proteins (BETs), and CHK1, in order to test the hypothesis that the inhibition of BET + CHK1 in MYC-RAD21+ pediatric OS models would be efficacious and safe. We demonstrate that MYC-RAD21+ pediatric OS cell lines were sensitive to the inhibition of BET (BETi) and CHK1 (CHK1i) at clinically achievable concentrations. While the potentiation of CHK1i-mediated effects by BETi was BET-BRD4-dependent, MYC expression was BET-BRD4-independent. In MYC-RAD21+ pediatric OS xenografts, BETi + CHK1i significantly decreased tumor growth, increased survival, and was well tolerated. Therefore, targeting replication stress is a promising strategy to pursue as a therapeutic option for this devastating disease.


[Analysis of Wumei Pills in treating chronic digestive system diseases with concept of "treating different diseases with same method" based on network pharmacology and molecular docking].
The present study explored the material basis and underlying mechanism of Wumei Pills in the treatment of ulcerative colitis(UC), diabetic enteropathy(DE), and irritable bowel syndrome(IBS) based on network pharmacology and molecular docking.The active components and targets of Wumei Pills were obtained and screened out from TCMSP, and the target names were standardized by UniProt.The related targets of UC, DE, and IBS were searched from GeneCards, DisGeNET, DrugBank, and OMIM.The Venn dia-gram was constructed using the Venny 2.1 online analysis tool to obtain the common targets of the drug and diseases.The "drug-active ingredient-target" network was constructed by Cytoscape 3.7.2.Gene Ontology(GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of common targets were carried out by DAVID.The main active components and targets were docked by AutoDock.The therapeutic mechanism of Wumei Pills was presumedly related to the regulation of the cancer pathway, TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, NF-κB signaling pathway, Toll-like receptor signaling pathway, JAK-STAT signaling pathway, etc.The results of molecular docking showed that the main active components could bind to the core targets, possessing stable conformation.The therapeutic effects of Wumei Pills against three diseases involved a variety of compounds such as flavonoids, sterols, and alkaloids in the prescriptions, which acted on key targets through multiple organs and participated in multiple signaling pathways such as apoptosis and immune inflammation, thereby exerting the therapeutic action on different diseases with the same method.This study explained the underlying mechanism of Wumei Pills in "treating different diseases with same method", and is expected to provide a theoretical basis for further understanding the mechanism of Wumei Pills and exploring the new clinical application.


CT assessment of CNS complications of AIDS.
Although acquired immunodeficiency syndrome (AIDS) is not directly fatal, individuals with the disease are susceptible to a host of life-threatening opportunistic infections and complications. This article focuses on the central nervous system (CNS) complications of HIV/AIDS and computed tomography's role in diagnosing these conditions. After completing the article, readers will know the signs and symptoms, causes or proposed causes and computed tomographic (CT) appearance of 4 important CNS complications of HIV/AIDS: Progressive multifocal leukoencephalopathy (PML). Toxoplasmosis. CNS lymphoma. AIDS dementia complex (ADC).


Energetics of stochastic resonance.
In this paper, we discuss the motion of a Brownian particle in a double-well potential driven by a periodic force in terms of energies delivered by the periodic and the noise forces and energy dissipated into the viscous environment. It is shown that, while the power delivered by the periodic force to the Brownian particle is controlled by the strength of the noise, the power delivered by the noise itself is independent of the amplitude and frequency of the periodic force. The implications of this result for the mechanism of stochastic resonance in an equilibrium system is that it is not energy from the noise force which enhances a small periodic force, but rather an increase of energy delivered by the periodic force, regulated by the strength of the noise. We further re-evaluate the frequency dependence of stochastic resonance in terms of energetic terms including efficiency.


[Technical considerations of a system of phosphor digital radiography and its cost-effectiveness in a radiology center].
The authors report the technical-applicative characteristics of a storage phosphor system (ADC 70, Ag-fa), experimentally used at the Department of Radiology of the University of Modena (Azienda Ospedaliera Policlinico) and analyze its effects on the center budget. The system was applied to urologic, osteoarticular and thoracic diagnoses, with bedside exams in the latter case. An automatic system (chest changer, Dupont) was used for hospitalized walking patients and for nonhospitalized patients. The data relative to the consumption of films and chemical products and the relative cost were analyzed and It. L. 84,284,782 appeared to have been saved on the annual budget. The data extrapolated from the practical experience of the Modena Radiology Department showed an average 900 exams a month, with 2,019 films being used for conventional radiography versus 918 with the ADC system. Reusing the same evaluation system, the implementation of the same system was simulated in another hospital with different characteristics (Azienda USL Imola, Bologna). The final result was an estimated annual saving of about It L. 83,000,000. The total workload of X-ray rooms afferent to the developing ADC system was considered for both departments and the cost of the conventional system compared with that of the digital system with laser print: about 197 square meters of film were used monthly with the conventional system, versus 55 after the implementation of the ADC system. The estimated figures were about 424 versus 235 for the implementation of the same ADC system in the second hospital. 9-10% was the estimated saving of the ADC system versus the conventional one thanks to fewer of the so-called refuses-i.e., exams that must be repeated; 63-81% chemical products were also saved because fewer films were developed. The cost-effectiveness of the ADC system in the budget of the two centers is stressed, with about 40% total saving. In particular, using the transfer price system for intermediate departments by Regione Emilia Romagna, the annual full cost per exam (weight = 1) decreased from It. L. 4,343 to It. L. 4,120 before and after the ADC system implementation, respectively.


Selective detection of NADPH oxidase in polymorphonuclear cells by means of NAD(P)H-based fluorescence lifetime imaging.
NADPH oxidase (NOX2) is a multisubunit membrane-bound enzyme complex that, upon assembly in activated cells, catalyses the reduction of free oxygen to its superoxide anion, which further leads to reactive oxygen species (ROS) that are toxic to invading pathogens, for example, the fungus Aspergillus fumigatus. Polymorphonuclear cells (PMNs) employ both nonoxidative and oxidative mechanisms to clear this fungus from the lung. The oxidative mechanisms mainly depend on the proper assembly and function of NOX2. We identified for the first time the NAD(P)H-dependent enzymes involved in such oxidative mechanisms by means of biexponential NAD(P)H-fluorescence lifetime imaging (FLIM). A specific fluorescence lifetime of 3670 +/- 140 picoseconds as compared to 1870 picoseconds for NAD(P)H bound to mitochondrial enzymes could be associated with NADPH bound to oxidative enzymes in activated PMNs. Due to its predominance in PMNs and due to the use of selective activators and inhibitors, we strongly believe that this specific lifetime mainly originates from NOX2. Our experiments also revealed the high site specificity of the NOX2 assembly and, thus, of the ROS production as well as the dynamic nature of these phenomena. On the example of NADPH oxidase, we demonstrate the potential of NAD(P)H-based FLIM in selectively investigating enzymes during their cellular function.


Consumption of reused vegetable oil intensifies BRCA1 mutations.
Breast cancer (BC) is a foremost type of cancer in women globally with an increased mortality rate in developing countries. Information regarding hereditary factors, lifestyle, work environment, food habits, and personal history could be useful in diagnosing breast cancer. Among such food habits, the reuse of edible oil for preparing food is a common practice in any developing country. The repeated heating of oils enhances the oxidative degradation of oil to produce polyaromatic hydrocarbons (PAH) which could disrupt the redox balance and generate reactive oxygen species. These reactive toxic intermediates can lead to BRCA1 mutations that are responsible for breast cancer. Mutations in DNA are the main cause for the conversion of proto-oncogenes into oncogenes which leads to change in expression and an increase in cell proliferation wherein a normal cell gets transformed into a malignant neoplastic cell. This review summarizes the possible mechanism involved in the induction of breast cancer due to repeated heating of edible.


Enhanced thermal and ultrasonic stability of a fungal protease encapsulated within biomimetically generated silicate nanospheres.
Dendrimers are highly branched synthetic macromolecules with a globular shape. They have been successfully used for generation of nanospheres at mild conditions via biomimetic silicification. Encapsulation of enzyme molecules within these nanospheres during their synthesis is a promising method for rapid and efficient entrapment of several enzymes. However, encapsulation of proteolytic enzymes has been rarely done via biomimetic silicification. As well, the operational stability of encapsulated enzyme has not been systematically reported. A proteolytic enzyme, either alpha-Chymotrypsin or a fungal protease from Aspergilus Oryzea was encapsulated along with iron oxide nanoparticles within particles yielded via biomimetic silicification of different generations of polyamidoamine (PAMAM) dendrimers. Stability of encapsulated enzyme was compared to that of free enzyme during storage at room temperature. As well, their thermal and ultrasonic stabilities were measured. Scanning electron microscopy, transmission electron microscopy and optical microscopy were used to investigate the morphology of nanospheres. Determination of encapsulation efficiency revealed that approximately 85% of fungal protease with concentration 1.4mg mL(-1) stock solution was immobilized within particles yielded by generation 0. Based on microscopic images the generated particles interconnected with each other and had spherical morphologies independent of generation. Kinetic analysis of encapsulated fungal protease demonstrated that Mechaelis-Menten constant (K(m)) slightly increased. PAMAM dendrimer generation 0 could be effectively used for rapid encapsulation of a fungal protease from Aspegilus Oryzae. Encapsulation significantly enhances the thermal and ultrasonic stabilities of enzymes, suggesting a range of diverse applications for them.


[Common Troubles of Vacuum Components in Elekta Linear Accelerator and Fast Solutions].
The transportation of electron is inseparable from vacuum environment. The maintenance of the vacuum system of Elekta linear accelerator depends on two sputtering ionic pumps at the gun end and the target end. The traveling wave acceleration were used in Elekta linear accelerators. And the design of the electron gun filament is detachable. Because of these two reasons, the vacuum stability is relatively weak. Only two vacuum values are used to reflect the operation state of the whole vacuum system, which causes a few failures but will not trigger a the machine interlock. Considering the complexity of whole vacuum system, the problem of vacuum caused by the failure of various components in vacuum system is analyzed in this paper. It is hoped that some useful repairing experience and suggestions for the maintenance engineers of linear accelerator to solve the vacuum fault and rebuild the vacuum can be provided quickly.


Selection of Bacillus species for targeted in situ release of prebiotic galacto-rhamnogalacturonan from potato pulp in piglets.
We have previously shown that galacto-rhamnogalacturonan fibers can be enzymatically extracted from potato pulp and that these fibers have potential for exerting a prebiotic effect in piglets. The spore-forming Bacillus species are widely used as probiotics in feed supplements for pigs. In this study, we evaluated the option for further functionalizing Bacillus feed supplements by selecting strains possessing the enzymes required for extraction of the potentially prebiotic fibers. We established that it would require production and secretion of pectin lyase and/or polygalacturonase but no or limited secretion of galactanase and β-galactosidase. By screening a library of 158 Bacillus species isolated from feces and soil, we demonstrated that especially strains of Bacillus amyloliquefaciens, Bacillus subtilis, and Bacillus mojavensis have the necessary enzyme profile and thus the capability to degrade polygalacturonan. Using an in vitro porcine gastrointestinal model system, we revealed that specifically strains of B. mojavensis were able to efficiently release galacto-rhamnogalacturonan from potato pulp under simulated gastrointestinal conditions. The work thus demonstrated the feasibility of producing prebiotic fibers via a feed containing Bacillus spores and potato pulp and identified candidates for future in vivo evaluation in piglets.


Treatment of chronic low back pain with tropisetron.
Various pathophysiological processes can lead to chronic back pain, which necessitates a differentiated therapeutic approach. In addition, psychic and psychosocial processes may influence the clinical picture. Twenty-five patients with chronic back pain were enrolled in the study. Patients suffering from psychosocial stresses and depressions were excluded from the study. The patients with painful tendinopathies and myofascial pain syndromes were treated with local injections of 5-10 mg tropisetron, and patients with degenerative processes were treated for 5 days with an intravenous (i.v.) bolus injection of 5 mg tropisetron (Navoban). Before treatment and 7 and 14 days later, the visual analog pain scale was filled in. The long-term drug therapy could be continued. There was a highly significant pain reduction with a very potent effect both in the locally treated group and in the intravenously treated group. Most of the patients could discontinue or reduce their long-term therapy with non-steroidal anti-inflammatory drugs or analgesics. A marked improvement in pain could be achieved in an open study by treating back pain of a primarily somatic nature with the 5-HT3 receptor antagonist tropisetron. A reduction in pain of > or =50% was reported by 76% of the patients. These results should be substantiated by the corresponding randomized, placebo-controlled, double blind studies that are needed to investigate the true benefit of treating back pain with 5-HT3 receptor antagonists.


Microintaglio Printing for Soft Lithography-Based in Situ Microarrays.
Advances in lithographic approaches to fabricating bio-microarrays have been extensively explored over the last two decades. However, the need for pattern flexibility, a high density, a high resolution, affordability and on-demand fabrication is promoting the development of unconventional routes for microarray fabrication. This review highlights the development and uses of a new molecular lithography approach, called "microintaglio printing technology", for large-scale bio-microarray fabrication using a microreactor array (µRA)-based chip consisting of uniformly-arranged, femtoliter-size µRA molds. In this method, a single-molecule-amplified DNA microarray pattern is self-assembled onto a µRA mold and subsequently converted into a messenger RNA or protein microarray pattern by simultaneously producing and transferring (immobilizing) a messenger RNA or a protein from a µRA mold to a glass surface. Microintaglio printing allows the self-assembly and patterning of in situ-synthesized biomolecules into high-density (kilo-giga-density), ordered arrays on a chip surface with µm-order precision. This holistic aim, which is difficult to achieve using conventional printing and microarray approaches, is expected to revolutionize and reshape proteomics. This review is not written comprehensively, but rather substantively, highlighting the versatility of microintaglio printing for developing a prerequisite platform for microarray technology for the postgenomic era.


The Health Benefits of Dietary Fibre.
Dietary fibre consists of non-digestible forms of carbohydrate, usually as polysaccharides that originate from plant-based foods. Over recent decades, our diet within Westernised societies has changed radically from that of our hominid ancestors, with implications for our co-evolved gut microbiota. This includes increased ingestion of ultra-processed foods that are typically impoverished of dietary fibre, and associated reduction in the intake of fibre-replete plant-based foods. Over recent decades, there has been a transformation in our understanding of the health benefits of dietary fibre. To explore the current medical literature on the health benefits of dietary fibre, with a focus on overall metabolic health. We performed a narrative review, based on relevant articles written in English from a PubMed search, using the terms 'dietary fibre and metabolic health'. In the Western world, our diets are impoverished of fibre. Dietary fibre intake associates with overall metabolic health (through key pathways that include insulin sensitivity) and a variety of other pathologies that include cardiovascular disease, colonic health, gut motility and risk for colorectal carcinoma. Dietary fibre intake also correlates with mortality. The gut microflora functions as an important mediator of the beneficial effects of dietary fibre, including the regulation of appetite, metabolic processes and chronic inflammatory pathways. Multiple factors contribute to our fibre-impoverished modern diet. Given the plethora of scientific evidence that corroborate the multiple and varied health benefits of dietary fibre, and the risks associated with a diet that lacks fibre, the optimization of fibre within our diets represents an important public health strategy to improve both metabolic and overall health. If implemented successfully, this strategy would likely result in substantial future health benefits for the population.


Comparison of single-port vs. two-port VATS technique for primary spontaneous pneumothorax.
Video-assisted thoracoscopic surgery (VATS) has been used for thoracic surgery for about two decades. As the trend in VATS is to use fewer ports to decrease postoperative complications, we compared the results of our experience with single-port and two-port VATS for primary spontaneous pneumothorax (PSP). This is a non-randomized retrospective study. From January 2017 to December 2018, 104 patients with PSP underwent VATS. Fifty-six patients received single-port VATS and 48 patients received two-port VATS. Operation time, blood loss, number of staplers used, drainage time, postoperative hospital stay, complications, chest wall paresthesia, visual analog scale (VAS) pain scores, and patient satisfaction scale scores were compared between the two groups. There was no difference in age, gender, body mass index (BMI), smoking status, surgical indication, and involved side between the two groups. The procedures performed in the single-port group were similar to those performed in the two-port group. No significant difference was found in operation time, blood loss, number of staplers used, drainage time, and recurrence rate. The rate of chest wall paresthesia was lower in the single-port group than in the two-port group (28.6 vs. 52.1%, p = .014). The VAS scores in the single-port group were lower than those in the two-port group at 24 and 48 h (p = .032 and p = .004). Compared with two-port VATS, single-port VATS for PSP showed more favorable results in terms of postoperative paresthesia and pain. The single-port procedure may be considered a good alternative to the standard thoracoscopic treatment of PSP. Abbreviations: VATS: Video-assisted thoracic surgery; PSP: primary spontaneous pneumothorax.


Epitopes for thyroid-stimulating antibodies in Graves' sera: a possible link of heterogeneity to differences in response to antithyroid drug treatment.
To evaluate the extent and clinical relevance of epitope heterogeneity for stimulating TSH receptor antibodies (TSHRAbs), we measured the activity of IgG preparations from 66 untreated patients with Graves' disease using Chinese hamster ovary (CHO) cells transfected with wild-type human TSHR and two TSHR chimeras with residues 9-165 (Mc1 + 2) or 90-165 (Mc2) substituted by equivalent residues of the LH/CG receptor. IgG from 68% of patients lose all of the stimulating TSHRAb activity with the chimeras; IgG from 27% lose most of the activity. Thus, we show that 95% of patients have stimulating TSHRAbs that require epitopes on the N-terminal portion of the extracellular domain of the TSHR and demonstrate the importance of epitopes within residues 90-165 for the first time. Heterogeneous epitope distribution, residual activity with one or both chimeras, i.e. with epitopes other than on the N-terminus of the TSHR, occurred in 21 patients (group A). Forty-five patients with homogeneous epitope distribution (group B) had stimulating TSHRAbs that depended only on epitopes on the N-terminus of the TSHR. Patients in group A were more likely to become euthyroid during antithyroid drug therapy and to do so more quickly than group B patients. The CHO-human TSHR cell system described herein appears to be as effective as the FRTL-5 rat thyroid system in stimulating TSHRAb detection; however, the two systems appear to measure different antibody populations in about 30% of cases. Further, stimulating TSHRAb activities measured in the FRTL-5 system tend to correlate better with goiter size and 99mTc pertechnetate uptake, whereas stimulating activities measured in the CHO-human TSHR/chimera system correlate better with free T4 and T3 levels.


Stenosis of the axis and cervical myelopathy. Case report.
A rare case is described of marked segmental stenosis of the axis secondary to developmental hypertrophy of the posterior neural arch causing cervical myelopathy. The patient made a remarkable recovery following decompressive laminectomy.


Human red blood cell acetylcholinesterase inhibition as the appropriate and conservative surrogate endpoint for establishing chlorpyrifos reference dose.
Chlorpyrifos (O,O-diethyl O-(3,5, 6-trichloro-2-pyridinyl)- phosphorothioate) is an organophosphorus (OP) insecticide used for controlling insect pests. Currently, the reference dose (RfD) used by the Environmental Protection Agency (EPA) to establish acceptable human exposure tolerances for chlorpyrifos is based upon inhibition of blood butyrylcholinesterase (BuChE), which is not the target enzyme of chlorpyrifos, and does not play any role in cholinergic transmission. Data are presented showing that inhibition of acetylcholinesterase (AChE) associated with red blood cells (RBC), an enzyme similar to or identical with that in the nervous system, is a more appropriate endpoint on which to base the RfD. Basing an acceptable level of human exposure (e.g., RfD) on inhibition of RBC AChE provides a significant margin of safety, since it is 12- to 14-fold more sensitive as an indicator of chlorpyrifos exposure than the AChE in the most sensitive relevant neurological tissues (brain or retina). Inhibition of RBC AChE activity is consistently exhibited at lower dosages of chlorpyrifos than those required to result in clinical symptoms of OP toxicity, or alterations in cognitive functional responses. There is no unique sensitivity of the fetus or neonates to chlorpyrifos when administered by an appropriate oral dose. Thus, inhibition of RBC AChE activity is an appropriate surrogate measurement of chlorpyrifos exposure and provides a conservative endpoint for establishing appropriate margins of safety for both adults and infants.


Antioxidant activity of extracts from foxtail millet (Setaria italica).
The less explored, commercially available foxtail millet-milled fractions like whole flour & bran rich fraction were studied for its antioxidant potency. Phytochemicals like alkaloids, phenolics, reducing sugars and flavonoids were found only in methanolic & aqueous extracts, while tannins and terpenoids were present in all the solvent extracts of whole flour & bran rich fraction. Antioxidants were extracted using methanol, ethanol and water. Methanolic extracts of whole flour and bran rich fraction exhibited a significantly higher (P < 0.05) radical scavenging activity (44.62% & 51.80% respectively) using DPPH model system, and reducing power (0.381 & 0.455 respectively) at 2 mg, than the other solvents used for extraction. As bran rich fraction showed the highest antioxidant activity, suggesting the presence of antioxidant components in the bran layer.


Short-term response of macular oedema to intravitreal bevacizumab.
Bevacizumab has been shown to be an effective treatment of macular oedema. This study assesses the response of macular oedema to bevacizumab with specific focus on the first 24 h postinjection. Subjects with diabetic macular oedema (DMO) or exudative age-related macular degeneration (ARMD) received intravitreal bevacizumab injections. Early Treatment of Diabetic Retinopathy Study (ETDRS) visual acuity and OCT macular thickness measurements were obtained at baseline, 1, 3, 6, 24 and 48 h, 1 week and 1 month postinjection. The average baseline OCT was 452.91 microm (SD 182.96, range 249.00 to 784.00). After injection, there was a statistically significant decrease in OCT thickness within 2 h with a plateau phase out to 24 h, followed by a significant drop between 24 and 48 h, and a return towards baseline between 1 week and 1 month. Average changes in ETDRS visual acuity were not statistically significant, though many patients experienced a positive outcome. While there is an immediate pressure-related effect, it appears that the anti-VEGF effects of bevacizumab require approximately 24 h to become active and persist for 2-3 weeks. These results suggest that injections at 2-3-week intervals might provide improved clinical outcomes, compared with the currently typical 4-6-week interval of injections.


The possibility of a liquid superconductor.
All superconductors are solids in their superconducting state, this canonical electronic state of matter presently having only been observed well below the melting temperature of the solid. The discovery of high-temperature superconductivity in cuprates has widened significantly our horizons of the theoretical understanding of the physical phenomenon. A number of observations point to the possibility that superconductors with a high superconducting transition temperature may not be conventional Bardeen-Cooper-Schrieffer (BCS) superconductors, but rather derive from the Bose-Einstein condensation of real-space pairs. While BCS superconductors exist in the solid state (probably with the exception of metallic liquid hydrogen at ultrahigh pressures), we argue here that a superconducting charged Bose liquid may be found in a true liquid state of condensed matter at ambient pressure. An experimental scenario is outlined in fluid metal-ammonia solutions for stabilizing and observing a high-temperature superconducting liquid (ca. 230 K) or at least a vitreous superconductor in the corresponding quenched solutions (ca. 160 K).


A novel fluorescent label based on organic dye-doped silica nanoparticles for HepG liver cancer cell recognition.
In this paper, we report a method for the recognition of HepG liver cancer cells with the use of a novel fluorescent label based on organic dye-doped fluorescent silica nanoparticles. The novel organic dye-doped silica nanoparticles are prepared with a water-in-oil microemulsion technique. The silica network is produced by the controlled synchronous hydrolysis of tetraethoxysilane and 3-amino-propyltriethoxysilane (APTES). The organic dye fluorescein isothiocyanate is doped inside as a luminescent signaling element, through covalent bonding to the amino group of APTES. The organic dye-doped core-shell nanoparticles are highly luminescent and exhibit minimal dye leaching and excellent photostability. A novel fluorescent label method based on biological fluorescent nanoparticles has been developed. The dye-doped fluorescent silica nanoparticles are covalently immobilized with anti-human liver cancer monoclonal antibody HAb18. We have used antibody-labeled fluorescent nanoparticles to recognize HepG liver cancer cells. It has been observed that the bioassay based on the organic dye-doped nanoparticles can identify the target cells selectively and efficiently. The fluorescent nanoparticle label also exhibits high photostability.


Termination and suppression of idiopathic left ventricular tachycardia by diltiazem.
Idiopathic left ventricular tachycardia is known to be responsive to verapamil in many cases. However, the role of other calcium-channel blockers, such as diltiazem, in treating this specific type of ventricular tachycardia is unknown. We report a case of idiopathic left ventricular tachycardia in a patient with a structurally normal heart, which was terminated and suppressed in the electrophysiology laboratory by a single dose of diltiazem intravenously, and was subsequently suppressed long-term with sustained-release diltiazem. Our finding suggests that idiopathic left ventricular tachycardia may be managed effectively with diltiazem in both the acute and chronic settings.


Changes in crossbridge and non-crossbridge energetics during moderate fatigue of frog muscle fibres.
1. The effect of sarcomere length (SL) during a fatiguing series of isometric tetani of frog muscle fibres was investigated. Tetani at 2.3 microns SL were more fatiguing than tetani at 3.2 microns SL, in that force declined twice as much as relaxation became much slower. 2. In a second set of experiments the force and heat production were measured during a series of fatiguing tetani. Heat was separated into two components: (a) crossbridge heat which is dependent on filament overlap and interaction, and (b) non-crossbridge heat which is independent of filament overlap and due to Ca2+ turnover. 3. In a series of fifty tetani, force, crossbridge heat and non-crossbridge heat each declined by 25-30% of its initial value. 4. The 25% reduction in non-crossbridge heat occurred completely during the first few tetani of the fatiguing series while force declined by less than 3%. This may be due to a reduction in Ca2+ binding to parvalbumin and to Ca2+ remaining bound during the remainder of the fatigue series. 5. After the first few tetani of the fatigue series the non-crossbridge heat hardly changed as force declined by a further 25% of its initial value. Continuing reduction of force with constant Ca2+ turnover indicates a reduction in the Ca2+ sensitivity of the filaments, and/or a reduction in the average force per attached crossbridge. 6. At the start of the fatiguing series, as force declines by about 7.5% there is a much larger decline of crossbridge heat (17%). The reason for this is unknown. Later in the series, force declined more rapidly than heat. This is probably due to a progressive accumulation of inorganic phosphate which acts by depressing force more than it depresses ATP breakdown.


Pure laparoscopic liver resection versus percutaneous radiofrequency ablation for small hepatocellular carcinoma: a propensity score and multivariate analysis.
In treatment of hepatocellular carcinoma (HCC), both laparoscopic liver resection (LLR) and radiofrequency ablation (RFA) provided similar short-term advantages. However, there was no robust clinical trial comparing the efficacy of LLR and RFA especially for small HCC. This study aimed to compare the short-term and long-term outcomes of LLR and RFA for patients with small HCC using a propensity score matching analysis to minimize potential selection bias. Factors affecting survival were then identified with multivariate analysis. All patients underwent RFA or LLR for small HCC [defined as Barcelona Clinic Liver Cancer (BCLC) stage 0 or A, size ≤3 cm, ≤3 nodules on contrast CT scan or MRI with no evidence of macrovascular invasion] from April 2005 to August 2020 were included. Propensity score matching was conducted to match patients in the LLR group and RFA group. Prognostic indicators, i.e., age, gender, tumor size, tumor number, Child's grading, albumin, bilirubin, platelet count, international normalized ratio, alpha-fetoprotein level and presence of cirrhosis on imaging were chosen for propensity score calculation. The demographic data, tumor characteristics, operative data, post-operative outcomes and survival data of the two groups were compared. A multivariate analysis based on Cox regression was used to identify factors associated with survival. Median follow-up was 34 months. LLR and RFA had similar overall survival (91.8% vs. 79.2% at 5-year, P=0.060); while the LLR had a significantly better disease-free survival (49.0% vs. 30.3% at 5-year, P=0.002) and local recurrence-free survival (96.0% vs. 63.7% at 5-year, P<0.001) when compared with the RFA. Multivariate analysis showed that treatment received by patient (LLR vs. RFA), prothrombin time and platelet counts were significantly associated with disease-free survival. On the other hand, the only factor associated with local recurrence-free survival was the treatment received by patient. Both RFA and LLR are safe and feasible treatment options for patients with small HCC. LLR should be considered for patients with preserved liver function with a better disease-free survival; while RFA offered a comparable overall survival with less surgical trauma and shorter hospital stay.


Efficacy of dual lumen jugular venous catheter hemodialysis when venous lumen is used as arterial lumen.
In 12 patients who underwent hemodialysis by a dual lumen jugular venous catheter, urea recirculation rate was measured during conventional treatment under normal conditions (R1), as well as when the venous lumen of the catheter was used as arterial lumen and the arterial as venous lumen (R2). Although the mean value of R2 was, as expected, higher than R1 (8.25 +/- 2.7 versus 4.25 +/- 1.00; p = 0.0004), it was still within the acceptable rate. We conclude that during hemodialysis by a dual lumen jugular venous catheter, efficient treatment can be provided when the venous is used as arterial lumen.


Oligodendrocyte precursor cell maturation: role of adenosine receptors.
Oligodendrocyte-formed myelin sheaths allow fast synaptic transmission in the brain and their degeneration leads to demyelinating diseases such as multiple sclerosis. Remyelination requires the differentiation of oligodendrocyte progenitor cells into mature oligodendrocytes but, in chronic neurodegenerative disorders, remyelination fails due to adverse environment. Therefore, a strategy to prompt oligodendrocyte progenitor cell differentiation towards myelinating oligodendrocytes is required. The neuromodulator adenosine, and its receptors (A1, A2A, A2B and A3 receptors: A1R, A2AR, A2BR and A3R), are crucial mediators in remyelination processes. It is known that A1Rs facilitate oligodendrocyte progenitor cell maturation and migration whereas the A3Rs initiates apoptosis in oligodendrocyte progenitor cells. Our group of research contributed to the field by demonstrating that A2AR and A2BR inhibit oligodendrocyte progenitor cell maturation by reducing voltage-dependent K+ currents necessary for cell differentiation. The present review summarizes the possible role of adenosine receptor ligands as potential therapeutic targets in demyelinating pathologies such as multiple sclerosis.


[Effects of reinfusion of the remaining blood filtered by leukocyte depletion filter on postoperative cellar immune function after cardiopulmonary bypass].
To evaluate effects of reinfusion of the remaining blood filtered by leukocyte depletion filter on postoperative cellular immune function after cardiopulmonary bypass (CPB). Forty patients who underwent selective cardiac valve replacement surgery with CPB in department of anesthesiology of Haikou Municipal Hospital from January to June in 2018 were enrolled. All the patients were divided into the control group and experimental group according to the random number table method, with 20 patients in each group. In the experimental group, patients received residual pump blood transfusion which had been filtered by leukocyte depletion filter and stored in sterile blood collection bags. In the control group, patients received residual pump blood transfusion which was stored in sterile blood collection bags without being filtered. The remaining blood was reinfused after CPB in two groups. Blood samples were taken before CPB (T1), 2 hours following CPB (T2), and 1, 3, 5 days after reinfusion of the remaining blood (T3, T4, T5), the levels of T lymphocyte subsets CD3+, CD4+, CD8+ and natural killer cells (NK cells) were detected by flow cytometer, and CD4+/CD8+ ratio was calculated. The levels of plasma tumor necrosis factor-α (TNF-α), interleukins (IL-2, IL-6, IL-8) were measured by enzyme linked immunosorbent essay (ELISA). The duration of mechanical ventilation, the length of intensive care unit (ICU) stay, the length of hospital stay, and incidence of wound and pulmonary infection after surgery were compared between two groups. Among 40 patients, there were 22 males and 18 females; with an age of (47.88±12.29) years old; and with 25 cases of American Society of Anesthesiologists (ASA) physical status II, and 15 cases of ASA III. There was no statistical difference in the volume of the remaining blood between the two groups (mL: 959.00±116.84 vs. 971.50±115.68, P > 0.05). Compared with T1, the levels of T lymphocyte subsets CD3+, CD4+, CD8+, NK cells and plasma levels of IL-2 were significantly decreased from T2, the CD4+/CD8+ ratio was significantly decreased from T3 in two groups, but there was no statistical difference in CD3+, CD4+, CD8+, NK cells, CD4+/CD8+ ratio or plasma level of IL-2 at each time between the two groups. Compared with T1, the plasma levels of TNF-α, IL-6 and IL-8 were significantly increased at T2 in two groups and then decreased gradually. The plasma levels of TNF-α, IL-6 and IL-8 from T3 in experimental group were lower than those in control group [TNF-α (ng/L): 28.49±4.66 vs. 33.82±4.30, IL-6 (ng/L): 25.98±4.51 vs. 31.38±5.42, IL-8 (ng/L): 38.98±4.67 vs. 45.76±5.33, all P < 0.05], they restored to the level of T1 at T5. In addition, compared with control group, the duration of mechanical ventilation, the length of ICU stay in experimental group were significantly decreased (hours: 8.07±1.30 vs. 9.16±1.52, 28.22±2.78 vs. 31.25±3.18, both P < 0.05), and there was no statistical difference in the length of hospital stay (days: 20.65±2.76 vs. 22.45±3.22), incidence of wound and pulmonary infection (25.0% vs. 15.0%, 5.0% vs. 15.0%) between the two groups (all P > 0.05). Reinfusion of the remaining blood filtered by leukocyte depletion filtercan inhibit inflammatory responses and don't affect the function of cellular immunity, and don't increase the incidence of infection.


Diabetic Neuropathic Cachexia in a Young Woman.
Profound weight loss with painful symmetrical peripheral neuropathy in diabetic patients was first described as diabetic neuropathic cachexia more than 4 decades ago. It is a distinct type of diabetic peripheral neuropathy that occurs in the absence of other microvascular and autonomic complications of diabetes. The mechanism and precipitating cause are unknown. It was reported to have good prognosis with spontaneous recovery within months to 2 years. However, it was frequently missed by clinicians because the profound weight loss is the most outstanding complaint, rather than the pain, numbness, or weakness. This often leads to extensive investigation to exclude more sinister causes of weight loss, particularly malignancy. We report a case of a young woman with well-controlled diabetes who presented with profound unintentional weight loss (26 kg), symmetrical debilitating thigh pain, and clinical signs of peripheral neuropathy. As the disease entity may mimic an inflammatory demyelinating cause of neuropathy, she was treated with a trial of intravenous immunoglobulin, which failed to give any significant benefit. However, she recovered after 6 months without any specific treatment, other than an antidepressant for the neuropathic pain and ongoing rehabilitation.


Metabolomics Study of Serum from a Chronic Alcohol-Fed Rat Model Following Administration of Defatted Tenebrio molitor Larva Fermentation Extract.
We have previously showed that defatted mealworm fermentation extract (MWF) attenuates alcoholic liver injury by regulating lipid, inflammatory, and antioxidant metabolism in chronic alcohol-fed rats. The current metabolomics study was performed to monitor biochemical events following the administration of MWF (daily for eight weeks) to a rat model of alcoholic liver injury by gas chromatography-tandem mass spectrometry (GC-MS/MS). The levels of 15 amino acids (AAs), 17 organic acids (OAs), and 19 free fatty acids (FFAs) were measured in serum. Analysis of variance (ANOVA), principal component analysis (PCA), and partial least squares discriminant analysis (PLS-DA) were used to compare the levels of 51 metabolites in serum. In particular, 3-hydroxybutyric acid (3-HB), pyroglutamic acid (PG), octadecanoic acid, and docosahexaenoic acid (DHA) were evaluated as high variable importance point (VIP) scores and PCA loading scores as determined by PLS-DA and PCA, and these were significantly higher in the MWF and silymarin groups than in the EtOH group. MWF showed a protective effect from alcohol-induced liver damage by elevating hepatic β-oxidation activity, and serum 3-HB levels were significantly higher in the MWF group than in the EtOH control group. Glycine levels were higher in the MWF group than in the EtOH group, and PG levels (related to glutathione production) were also elevated, indicating a reduction in alcohol-related oxidative stress. In addition, MWF is protected from alcohol-induced inflammation and steatosis by increasing serum DHA, palmitic, and octadecanoic acid levels as compared with the EtOH group. These results suggest that MWF might attenuate alcoholic liver disease, due to its anti-inflammatory and antioxidant effects by up-regulating hepatic β-oxidation activity and down-regulating liver FFA uptake.


Occupational Exposure to Talc Increases the Risk of Lung Cancer: A Meta-Analysis of Occupational Cohort Studies.
Talc is widely used in industrial applications. Previous meta-analyses of carcinogenic effects associated with inhaled talc included publications before 2004, with a lack of data in China, the largest talc-producing country. The safety of workers exposed to talc was unclear due to limited evidence. The objective of this study was to reevaluate the association between inhaled talc and lung cancer. A meta-analysis was performed to calculate the meta-SMR of lung cancer. We searched the MEDLINE, EMBASE, CNKI, and Wanfang Data databases through March 2017. Data from observational studies were pooled using meta-analysis with random effects models. Fourteen observational cohort studies (13 publications) were located via literature search. The heterogeneity of the included data was high (I-squared = 72.9%). Pooling all the cohorts yielded a meta-SMR of 1.45 (95% CI: 1.22-1.72, p < 0.0001) for lung cancer among the study subjects exposed to talc. Subgroup analysis for asbestos contamination showed no significant difference in lung cancer death between subjects exposed to talc with and without asbestos (p = 0.8680), indicating that this confounding factor may have no significance. This study provides evidence that nonasbestiform talc might still increase the risk of lung cancer. Further epidemiological studies are required to evaluate the safety of workers with occupational talc exposure.


The influence of personality, measured by the Karolinska Scales of Personality (KSP), on symptoms among subjects in suspected sick buildings.
The aim was to study possible relationships between personality traits as measured by the Karolinska Scales of Personality (KSP), a self-report personality inventory based on psychobiological theory, and medical symptoms, in subjects with previous work history in suspected sick buildings. The study comprised 195 participants from 19 consecutive cases of suspected sick buildings, initially collected in 1988-92. In 1998-89, the KSP inventory and a symptoms questionnaire were administered in a postal follow-up study. There were 16 questions on symptoms, including symptoms from the eyes, nose, throat, skin, and headache, tiredness, and a symptom score (SC), ranging from 0 to 16, was calculated. The questionnaire also requested information on personal factors, including age, gender, smoking habits, allergy and diagnosed asthma. The KSP ratings in the study group did not differ from the mean personality scale norm scores, calculated from an external reference group. Females had higher scores for somatic anxiety (P < 0.01), muscular tension (P < 0.001), psychic anxiety (P < 0.01), psychasthenia (P < 0.05), indirect aggression (P < 0.05), and guilt (P < 0.05), while males scored higher on detachment (P < 0.001). Subjects with higher SC were found to display higher degree of somatic anxiety (P < 0.001), muscular tension (P < 0.001), psychic anxiety (P < 0.001), psychasthenia (P < 0.001), inhibition of aggression (P < 0.05), detachment (P < 0.05), suspicion (P < 0.01), indirect aggression (P < 0.01), and verbal aggression (P < 0.05). In addition, ocular, respiratory, dermal, and systemic symptoms (headache and tiredness) were significantly related to anxiety- and aggressivity-related scales. There were associations between personality scales and change of symptom score (SC) during the 9-year period. The associations between KSP personality traits and symptoms were more pronounced in females. In conclusion, there are gender differences in personality and SBS symptoms. Personality may play a role in the occurrence of symptoms studied in indoor environmental epidemiology. Our results support a view that measurement of personality could be of value in future studies and vulnerability to environmental stress. Personality and personal vulnerability should be considered in both indoor environmental epidemiology and practical handling of building with suspected indoor problem, especially when the technical investigations fail to identify any obvious technical malfunction. Moreover, personality aspects should be considered among subjects with possible vulnerable personality exposed to environmental stress, and personality diagnosis can be a complementary tool useful when assessing 'sick building patients' in the medical services. We found no evidence of severe personality pathology in among those working in workplaces with environmental problems so called 'sick buildings'.


A Qualitative Study on the Knowledge and Opinions of Syrian Women regarding Family Planning.
Whatever the reason, migration has negative effects on individuals in terms of their physical, social and psychological aspects. Syria has witnessed a significant level of migration since 2011. The study was conducted with refugee women who attended the Adana Gülpınar Family Health Center between the dates of May 15 and April 15, 2019-2020. The samples of the study were the women who applied to the Adana Gülpınar Family Health Center. 30 individuals, determined using the purposeful sampling method, were included in the study. Refugee women cannot make personal decisions regarding the family planning for reasons such as pressure from their spouses, cultural pressure, and the inferior status of women. For this reason, they lack the necessary information regarding the family planning, and they are unable to access the family planning solutions.


Carnitine palmitoyltransferase 1A is essential for decidualization in mice.
Decidualization accompanies with extensive stromal cell proliferation and differentiation, is a crucial step in early pregnancy. Aberrant decidualization is linked to infertility and miscarriage but the mechanisms remain unclear. Carnitine palmitoyltransferase 1A (CPT1A) is an enzyme catalyzing key steps in the fatty acid beta-oxidation pathway. The objective of this study was to investigate the role of CPT1A in decidualization during early pregnancy. An increased expression of CPT1A was found both in Days 6 and 7 as compared with in Days 1, 4 and 5. Further examination showed that on days 5-7 of pregnancy, the protein level of CPT1A was strongly up-regulated at implantation sites compared with inter-implantation sites, the location of CPT1A protein was distributed in the decidual zone. Upon further exploration, CPT1A expression was significantly increased in response to artificially induced decidualization both in vivo and in vitro. After down-regulating CPT1A expression by CPT1A-small interfering RNA (siCPT1A) in primary mouse endometrial stromal cells, expressions of decidualization markers and cell proliferation markers were decreased. After siCPT1A was transfected into the mouse uterus, decidualization impaired and then led to the loss of the implanted embryos. Thus, CPT1A is important for decidualization in mice and it may regulate the stromal cell proliferation progress. It is worth noting that the expression of CPT1A protein of human decidua was significantly decreased in spontaneous abortion groups compared to normal pregnancy groups. Collectively, CPT1A is essential for endometrium of early pregnant mice and humans.


Image Reconstruction for a Rotating Radiofrequency Coil (RRFC) Using Self-Calibrated Sensitivity From Radial Sampling.
The purpose of this study was to develop a practical magnetic resonance imaging (MRI) scheme for the latest rotating radiofrequency coil (RRFC) design at 9.4 T. The new prototype RRFC was integrated with an optical sensor to facilitate recording of its angular positions relative to the sequence timing. In imaging, the RRFC was used together with radial k-space trajectories. To recover the image, the radial spokes were grouped according to the coil locations. Using an Eigen-decomposition approach, an array of location-dependent sensitivity maps was extracted from the central regions of the segmented k-space, enabling parallel-imaging techniques for image recovery in a straightforward manner. When the RRFC angular velocity is carefully designed and accurately controlled according to the sequence timing, the encoding by means of varying RRFC sensitivity maps can be accurately calibrated for a faithful image recovery. Approximations were made to counteract the variations of the RRFC angular velocity, providing successful image reconstruction at 9.4 T. The current study demonstrated a new and practical imaging scheme for RRFC-MRI. It is able to extract the temporally varying sensitivity maps retrospectively from the k-space acquisition itself, without resorting to electromagnetic simulation or numerical interpolation. The proposed imaging scheme and the supporting engineering solutions of the RRFC prototype enable accurate image reconstructions. These new developments pave the way for routine applications of the RRFC, and bode well for its further development in providing simultaneous multinuclear imaging by incorporating, for example, independent X-nuclear coil elements into the rotating structure.


Thromboelastography parameters in chronic viral liver disease and liver resection: A retrospective study.
Thromboelastography (TEG) provides a global assessment of haemostasis and is potentially applicable to liver disease. The present study aimed to explore the utility of TEG for the evaluation of patients with chronic viral liver disease, which has previously not been investigated. Demographic characteristics and TEG parameters were collected before surgery. Child-Turcotte-Pugh (CTP) and model for end-stage liver disease (MELD) scores were used to categorise stages of liver cirrhosis. Liver resections were classified as low, medium and high complexity. A total of 344 patients were included. Results showed significantly longer K-time, smaller α-angle and lower maximum amplitude (MA) with increasing liver disease severity as measured by the CTP and MELD scores (P < 0.05 for all). After multivariable adjustment (including age, sex, liver disease aetiology, alanine aminotransferase [ALT], aspartate aminotransferase [AST], albumin, total bilirubin, haemoglobin and platelet count), TEG parameters (except R-times) were either weakly or inversely related to the severity of liver disease as defined by the MELD score (absolute r < 0.2 and P < 0.05 for all except R-times). R-times obtained before surgery were weakly correlated with perioperative blood loss (r < 0.2 and P < 0.05 for all). The correlation between TEG parameters and severity of liver disease was weak. In addition, R-times obtained before liver resection were weakly associated with perioperative blood loss after multivariable adjustments. TEG utility for haemostasis assessment and prediction of blood loss during liver resection should be further explored in high-quality studies.


Characterisation of Deficits and Sex Differences in Verbal and Visual Memory/Learning in Bipolar Disorder.
Cognitive impairment is consistently reported in bipolar disorder (BD), but few studies have characterised which memory component processes are affected. Further, it is unknown whether the component processes underlying memory impairment are moderated by sex. The present study examined diagnosis and sex differences in both verbal and visual memory/learning domains in patients with BD and psychiatrically healthy controls. Verbal and visual memory/learning were measured using the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R). 114 patients with BD (n = 50 males, n = 64 females), were compared to 105 psychiatrically healthy controls (n = 42 males, n = 63 females). Patients with BD had worse performance in verbal and visual immediate and total recall, verbal and visual delayed free recall, and verbal recognition discrimination scores, but there were no group differences in learning slopes and cumulative learning index scores. There were trends for BD females to outperform BD males in visual memory/learning free recall and cumulative learning, but these results did not survive multiple testing correction. These findings did not change in a secondary sensitivity analysis comparing only strictly euthymic BD patients to controls (n = 64). The present study found trait-like verbal and visual memory/learning impairment in BD that was attributable to deficient encoding and/or consolidation processes rather than deficits in learning. We did not find marked sex differences in either visual or verbal memory/learning measures, although some trend level effects were apparent and deserve exploration in future studies.


Assessing the Impact of Efalizumab on Nail, Scalp and Palmoplantar Psoriasis and on Quality of Life: Results from a Multicentre, Open-label, Phase IIIb/IV Trial.
This post-approval, open-label trial (n = 1266) assessed the efficacy of efalizumab, administered in accordance with the European label at that time, in patients with concomitant nail, scalp or palmoplantar psoriasis. Patients received subcutaneous efalizumab 1.0 mg/kg weekly for up to 20 weeks. By Week 12, an improvement from baseline of 50% or more was observed in 21.4% (181/844) of patients with nail psoriasis, 62.4% (718/1150) of patients with scalp psoriasis, and 51.4% (127/247) of patients with palmoplantar psoriasis. Quality of life improved throughout the trial, with a 50% median improvement in DLQI score after 12 weeks of treatment. Efalizumab showed promising efficacy in the treatment of nail, scalp and palmoplantar psoriasis, which was reflected in improvements in quality of life.


Measurement of serum steroid profiles by HPLC-tandem mass spectrometry.
Accurate investigations of adrenal hormone levels play a vital role in pediatric endocrinology for the detection of steroid-related disorders. In this study, we developed and validated a simultaneous assay for eight serum steroids, i.e., DHEA, androstenedione, testosterone, progesterone, 17‑hydroxyprogesterone, DHEA‑sulfate, pregnenolone‑sulfate and cholesterol-sulfate, using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Serum samples were prepared by liquid-liquid extraction with methyl t‑butyl ether. Quantitation by LC-MS/MS was performed in multiple reaction monitoring mode with an electrospray ionization source. The run time was 10 min. Analytical performance was evaluated, including imprecision, linearity, ion suppression, carry over and detection capabilities. Serum specimens from 59 children and 120 adults were analyzed to compare the distribution of steroid levels between the groups. All hormones were effectively extracted and separated using our method. The method was essentially free from potential interference and ion suppression. Within-run and between-run imprecision values were <20%. The lower limits of quantification varied from 0.025 to 10 ng/mL. The results were generally good and correlated with those obtained using immunoassay techniques. We developed the HPLC-MS/MS method for the simultaneous measurement of free and sulfated steroid hormones. The performance of the developed method was generally acceptable. Thus, this method may provide a novel approach to steroid profiling in children of age before adrenarche.


What Prompted the Adoption of Self-Protective Behaviors in Response to COVID-19? Evidence From Women Living in the Rural Areas of Western China.
Self-protective behaviors, such as handwashing and mask-wearing, are effective to reduce the spread of coronavirus disease (COVID-19), but few studies have focused on women living in rural areas who bear the brunt of the impacts of the pandemic due to their economic and social vulnerabilities. This study explores what prompted the adoption of self-protective behaviors in response to COVID-19 among women living in rural areas of western China. The study sample consisted of 1,524 women from 116 townships across 10 counties in rural western China. We collected data in May and August 2020 on women's socioeconomic characteristics, exposure to COVID-19-related information, psychological response to COVID-19, and adoption of self-protective behaviors. Structural equation modeling (SEM) analyses were conducted to analyze the relations among the variables. During the lockdown, 1,221 (80.12%) of the 1,524 women in the study sample reported wearing a mask every time when they went outside and 1,021 (66.99%) reported handwashing with soap every time after they came home. Perceived efficacy had the strongest association with self-protective behaviors (β = 0.38; p < 0.001). Receiving public health guidance (β = 0.18; p < 0.001) was indirectly associated with more self-protective behaviors via greater perceived efficacy. Higher socioeconomic status was also directly associated with increased adoption of self-protective behaviors (β = 0.24; p < 0.001). Other variables, such as receiving surveillance and risk information, communication channels, perceived risks, and fear, were indirectly associated with the adoption of self-protective behaviors with smaller effect sizes (all β were lower than 0.10). Not all women were able to adopt self-protective behaviors, such as mask-wearing and handwashing, during the COVID-19 pandemic in western China. To further encourage behavioral changes in response to public health crises, the government should develop clear and actionable guidelines and adopt targeted health communication strategies to reach the most disadvantaged groups of society. These findings may inform tailored responses to COVID-19 in other low- and middle-income countries.


A brain-specific isoform of mitochondrial apoptosis-inducing factor: AIF2.
Apoptosis-inducing factor (AIF) has important supportive as well as potentially lethal roles in neurons. Under normal physiological conditions, AIF is a vital redox-active mitochondrial enzyme, whereas in pathological situations, it translocates from mitochondria to the nuclei of injured neurons and mediates apoptotic chromatin condensation and cell death. In this study, we reveal the existence of a brain-specific isoform of AIF, AIF2, whose expression increases as neuronal precursor cells differentiate. AIF2 arises from the utilization of the alternative exon 2b, yet uses the same remaining 15 exons as the ubiquitous AIF1 isoform. AIF1 and AIF2 are similarly imported to mitochondria in which they anchor to the inner membrane facing the intermembrane space. However, the mitochondrial inner membrane sorting signal encoded in the exon 2b of AIF2 is more hydrophobic than that of AIF1, indicating a stronger membrane anchorage of AIF2 than AIF1. AIF2 is more difficult to be desorbed from mitochondria than AIF1 on exposure to non-ionic detergents or basic pH. Furthermore, AIF2 dimerizes with AIF1, thereby preventing its release from mitochondria. Conversely, it is conceivable that a neuron-specific AIF isoform, AIF2, may have been 'designed' to be retained in mitochondria and to minimize its potential neurotoxic activity.


Elemental characterization of Daphnia resting eggs by X-ray analytical microscopy.
Resting eggs of Daphnia, a key crustacean zooplankton of freshwater food chains, can remain viable for more than a century. These eggs are able to withstand freezing and drying, and can survive the harsh environment of a predator's digestive system. Until recently little was known about the chemical composition, microanatomy, and physical properties of the resting eggs. The current study utilized a physical technique, the X-ray analytical microscope, to identify and localize component elements of the Daphnia resting egg. The analysis demonstrated that phosphorus, sulfur, potassium, and calcium were detected as elemental components of the resting egg, and detection intensities of the four elements differed according to the position of the eggs. Phosphorus and calcium were mostly detected in regions of the eggshell that surrounded the two embryos. In addition, sulfur was distributed throughout the eggshell whereas potassium was localized to the areas that corresponded to where the embryos were encased. Through the use of X-ray analytical microscopy, the current study identifies elemental characteristics in relationship to the structure of the Daphnia resting eggs.


Osteoporosis: association of recent fractures with quantitative US findings.
To study the association of quantitative ultrasound (US) parameters and bone mineral density (BMD) in patients with and patients without recent fractures. The authors studied 4,698 women (69 years or older) who had sustained 1,363 new fractures, including 106 hip fractures, during the 7 years prior to the study. Broadband ultrasound attenuation (BUA) and other velocity parameters were measured by means of quantitative US of the calcaneus. BMD was measured at the spine, hip, and calcaneus. The standardized age-adjusted odds ratio for all fractures was 1.5 (95% confidence interval [CI] = 1.4, 1.7) for BUA and up to 1.6 (95% CI = 1.5, 1.7) for BMD. For hip fractures, the odds ratio was 1.9 (95% CI = 1.5, 2.4) for BUA and up to 2.6 (95% CI = 2.0,3.4) for BMD. Sensitivity and specificity with BUA, velocity parameters, and BMD were comparable. Results of multivariate analysis showed that both BUA and BMD were independently associated with fractures and that combined measurements improved sensitivity and specificity. Quantitative US parameters are strongly associated with risk of fracture and partly independent of BMD. This simple, low-cost, portable, and radiation-free approach may complement bone densitometry in assessing risk of osteoporotic fracture.


Rib length in experimental scoliosis induced by pinealectomy in chickens.
This study was designed to investigate the difference of rib length of idiopathic scoliosis using experimentally induced scoliosis by pinealectomy in chickens. To find whether the difference of rib length may play a role for the development of scoliosis in pinealectomized chickens. In experimental and clinical studies, asymmetric growth of the rib has been considered to be one of factors for the development of idiopathic scoliosis. Pinealectomy in chickens consistently produces scoliosis with lordosis, vertebral rotations, and rib humps, which have anatomic characteristics similar to those of human idiopathic scoliosis. A total of 30 chickens were divided into two groups: pinealectomy in 15 chickens and sham operation in 15 chickens served as control. The surgeries were performed on the second day after hatching. The chickens in both groups were killed at 3 months of age. The spines were examined radiologically for the presence of a scoliotic curve. Also, the ribs at each level were measured and compared between left and right sides. All pinealectomized chickens that developed scoliosis showed rib humps. In contrast, none of chickens in a sham operation developed scoliosis. In both groups, there were no significant asymmetries in the rib length. Our results indicated that rib length was not related to the experimental scoliosis examined in this study. Further study is encouraged to investigate if the asymmetric rib length plays a role in causing or promoting other types of scoliosis, especially in primate or human idiopathic scoliosis.


TRAP1 in Oxidative Stress and Neurodegeneration.
Tumor necrosis factor receptor-associated protein 1 (TRAP1), also known as heat shock protein 75 (HSP75), is a member of the heat shock protein 90 (HSP90) chaperone family that resides mainly in the mitochondria. As a mitochondrial molecular chaperone, TRAP1 supports protein folding and contributes to the maintenance of mitochondrial integrity even under cellular stress. TRAP1 is a cellular regulator of mitochondrial bioenergetics, redox homeostasis, oxidative stress-induced cell death, apoptosis, and unfolded protein response (UPR) in the endoplasmic reticulum (ER). TRAP1 has attracted increasing interest as a therapeutical target, with a special focus on the design of TRAP1 specific inhibitors. Although TRAP1 was extensively studied in the oncology field, its role in central nervous system cells, under physiological and pathological conditions, remains largely unknown. In this review, we will start by summarizing the biology of TRAP1, including its structure and related pathways. Thereafter, we will continue by debating the role of TRAP1 in the maintenance of redox homeostasis and protection against oxidative stress and apoptosis. The role of TRAP1 in neurodegenerative disorders will also be discussed. Finally, we will review the potential of TRAP1 inhibitors as neuroprotective drugs.


Effect of sodium alginate supplementation on weight management and reproductive hormones in polycystic females.
Dietary fiber is getting attention these days due to its tendency to improve the reproductive performance in human beings. Sodium alginate (SA) is one of the natural dietary fibers. The present study aimed to evaluate the effect of SA on serum insulin, blood sugar, lipid profile, estrogen and testosterone in polycystic (PCOS) females. A single in vivo trial was conducted on thirty adult PCOS females (25 ± 5 years old) with a body mass index (BMI) of 27.5 ± 3.5 kg m-2. Blood samples of all PCOS females were drawn for the initial biochemical analysis and considered as the negative control (NC). A complete randomized design was used to divide the NC group into three equal subgroups (n = 9) i.e. SA3: with 0.03 g; SA6: with 0.06 g per kg body weight per day of sodium alginate; the positive control (PC): metformin 500 mg day-1 for 60 days (two months). A significant reduction (p < 0.05) in the body weight, BMI, blood sugar, serum insulin, lipids and testosterone was observed, while a significant incremental effect (p < 0.05) was observed in the high-density lipoprotein level. The percentages of some physical parameters were also improved like obesity, menstrual cycle, physical activity, psychological issues and hirsutism. Therefore, the study concluded that SA exhibited therapeutic potential for weight management and the improvement of serum testosterone in PCOS females.