The effect of 12-week resistance exercise training on serum levels of cellular aging process parameters in elderly men.
Regular physical activity has a positive effect on the prevention of cellular aging. The present study investigated the effect of 12-week resistance training (RT) on serum levels of Sirtuin-1 (SIRT1), Sirtuin-3 (SIRT3), Sirtuin-6 (SIRT6), Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-α), and telomerase enzyme in elderly men. For this purpose, 30 elderly men (age 66.23 ± 0.57 years) were randomly divided into two groups: resistance training group (RET, n = 15) and control group (CTR, n = 15). Participants in RET performed RT protocols with intensity of 60% one-repetition maximum (3×/week, 4 sets of the six exercise circuits). Body composition, physical functioning and, blood samples were assessed before (pre-test) and after (post-test) a 12-week intervention. The results showed that there was a significant increase in serum levels of SIRT1 (P = 0.001), SIRT3 (P = 0.001), SIRT6 (P = 0.02), PGC1-α (P = 0.001), and telomerase enzyme (P = 0.001) in RET. Also, we found a significant difference between the RET and CTR in serum levels of SIRT1 (P = 0.001), SIRT3 (P = 0.001), SIRT6 (P = 0.037), PGC1-α (P = 0.007), and telomerase enzyme (P = 0.001). 12-Week RT increased the levels of proteins associated with the biological aging process in elderly men. It seems that the RT may have beneficial effects on cellular senescence and also improved impaired mitochondrial protein and enzymatic functional induced aging.


Evaluation of two commercial procedures for quantification of human immunodeficiency virus type 1 RNA with respect to HIV-1 viral subtype and antiviral treatment.
To determine the reliability of two commercial assays for quantifying the human immunodeficiency type 1 (HIV-1) RNA levels in patients infected with different HIV-1 subtypes and managed with various drug regimens, blind testing of 127 plasma samples from 57 patients infected with HIV-1 subtypes A, B, C and E was performed using the Amplicor HIV-1 Monitor Test (Roche) and Quantiplex HIV-1 RNA 3.0 Assay (Chiron). Included were time course studies in 7 patients in whom the virus load was correlated with CD4+ cell counts and therapy. Both assays were accurate and precise to measure standardized amounts of viral load and displayed high correlation coefficients that were independent of gender and treatment modality, even though some assay-specific differences may exist in the quantification of viral subtype RNA. Time course studies showed comparable inverse associations between the CD4+ count and viral load measured by the two assays. Hence, both the Amplicor HIV-1 Monitor Test and the Quantiplex HIV-1 RNA 3.0 Assay promise to be useful for the management of HIV-1 infected patients.


The impact of socio-medical factors and oral status on dietary intake in the eighth decade of life.
The impact of different background factors on dietary intake was studied in a representative sample of 94 men and 89 women (mean age 74.6 years). More women than men in the sample felt lonely, lived alone and felt ill. The women also had more frequent and more severe mandibular dysfunction problems. Many individuals showed an unsatisfactory dietary intake according to the Recommended Dietary Allowance in Sweden (RDA-S). A multivariate analysis showed that sex, age, education, general living conditions, anamnestical and clinical dysfunction indices and dental status influenced dietary intake. Subjective chewing problems were strongly connected with dental status and constituted one of the most important single variables explaining the differences in dietary intake. This study shows the importance of asking elderly patients about their living conditions and chewing problems, as well as evaluating dental status and function from a "masticatory performance perspective" and offering adequate dietary advice.


Microemulsion and microsuspension polymerization of methyl methacrylate in surfactant-free microemulsions (SFME).
This article presents a free-radical polymerization method in a mesostructured system - free of any surfactants, protective colloids, or other auxiliary agents. It is applicable for a large variety of industrially relevant vinylic monomers. The aim of this work is to study the impact of surfactant-free mesostructuring on the polymerization kinetics and the polymer derived. So-called surfactant-free microemulsions (SFME) were investigated as reaction media with a simple composition comprising water, a hydrotrope (ethanol, n-propanol, isopropanol, tert-butyl alcohol), and the monomer as the reactive oil phase (methyl methacrylate). Polymerization reactions were performed using oil-soluble, thermal- and UV-active initiators (surfactant-free microsuspension polymerization) and water-soluble, redox-active initiators (surfactant-free microemulsion polymerization). Structural analysis of the SFMEs used and the polymerization kinetics were followed by dynamic light scattering (DLS). Dried polymers were analyzed with regard to their conversion yield by mass balance, the corresponding molar masses were determined using gel permeation chromatography (GPC), and the morphology was investigated by light microscopy. All alcohols are suitable hydrotropes to form SFMEs, except for ethanol, which forms a molecularly disperse system. We observe significant differences in the polymerization kinetics and the molar masses of the polymers obtained. Ethanol leads to significantly higher molar masses. Within a system, higher concentrations of the other alcohols investigated give rise to less pronounced mesostructuring, lower conversions, and lower average molar masses. It could be demonstrated that the effective concentration of alcohol in the oil-rich pseudophases as well as the repulsive effect of the surfactant-free, alcohol-rich interphases constitute the relevant factors influencing polymerization. Concerning the morphology, the polymers derived range from powder-like polymers in the so-called "pre-Ouzo region" over porous-solid polymers in the bicontinuous region to dense, almost compacted, transparent polymers in unstructured regions, comparable to the findings for surfactant-based systems reported in the literature. Polymerizations in SFME comprise a new intermediate between well-known solution (i.e., molecularly dispersed) and microemulsion respectively microsuspension polymerization processes.


Structural and functional features of a broad-spectrum prophage-encoded enzybiotic from Enterococcus faecium.
Multidrug-resistant (MDR) bacteria have become a growing threat to public health. The gram-positive Enterococcus faecium is classified by WHO as a high-priority pathogen among the global priority list of antibiotic-resistant bacteria. Peptidoglycan-degrading enzymes (PDEs), also known as enzybiotics, are useful bactericidal agents in the fight against resistant bacteria. In this work, a genome-based screening approach of the genome of E. faecium allowed the identification of a putative PDE gene with predictive amidase activity (EfAmi1; EC 220.127.116.11) in a prophage-integrated sequence. EfAmi1 is composed by two domains: a N-terminal Zn2+-dependent N-acetylmuramoyl-L-alanine amidase-2 (NALAA-2) domain and a C-terminal domain with unknown structure and function. The full-length gene of EfAmi1 was cloned and expressed as a 6xHis-tagged protein in E. coli. EfAmi1 was produced as a soluble protein, purified, and its lytic and antimicrobial activities were investigated using turbidity reduction and Kirby-Bauer disk-diffusion assays against clinically isolated bacterial pathogens. The crystal structure of the N-terminal amidase-2 domain was determined using X-ray crystallography at 1.97 Å resolution. It adopts a globular fold with several α-helices surrounding a central five-stranded β-sheet. Sequence comparison revealed a cluster of conserved amino acids that defines a putative binding site for a buried zinc ion. The results of the present study suggest that EfAmi1 displays high lytic and antimicrobial activity and may represent a promising new antimicrobial in the post-antibiotic era.


Electro-clinical studies of epileptic seizures in Mongolian gerbils.
In 26 seizure-prone gerbils, with chronically implanted electrodes, the electro-clinical relationship of seizures was studied. The results are based on 70 EEG recordings of fully developed seizures resulting from: (1) moving the animal from its home cage to the testing area, i.e., the naturally occurring environmentally precipitated seizures (EPS); (2) electrically induced by stimulation of cortical electrodes (ICS); and (3) electrically induced by stimulation of hippocampal electrodes (IHS). The EPS were categorized into 4 electro-clinical phases: myoclonic, clonic-tonic, tonic, and clonic movements; usually preceded by an incipient period and followed by a post-seizure period. Usually the EPS were preceded by focal single spiking in the posterior part of the hemisphere, during which the animal's behavior was normal. This spiking turned to generalized epileptic discharges (incipient period without epileptic behavior) which were followed by the 4 phases of generalized myoclonic and clonic-tonic seizures. Post-seizure coma-like behavior was associated with EEG depression. The ICS were very similar to the EPS, but of course lacking the incipient phase. In contrast to the EPS and ICS, the IHS were very different both in terms of EEG and clinical manifestations. Moreover, the post-seizure depression was absent or negligible. We concluded that in the EPS in gerbils, the cortex is of primary importance as to the site of origin of the seizure, while the hippocampal involvement is secondary to it.


[Experimental udder infection with Escherichia coli. 3. Morphological changes directly to subepithelially situated structures in the area of the glands of the milk cistern and the large milk ducts].
Alterations were recorded from capillaries and connective tissue by means of optical light and electron microscopy in investigations of subepithelial structures, following experimental Escherichia coli infection. These alterations led to an impairment of the blood-udder barrier and thus to increased extravasation of cells (especially neutrophilic granulocytes). They were found to accumulate in subepithelial connective tissue and, eventually, to penetrate in high quantity the epithelium proper, and, consequently, to be considerably involved in alterations to the latter.


Development of West syndrome in a patient with Reye syndrome: a case study.
We report the case of a 3 month old female with a diagnosis of Reye Syndrome, confirmed with laboratory exams. Three months after apparently recovering from the acute clinical picture, the patient developed massive spasms and psychomotor delay with an EEG tracing typical of hypsarrythmia, the classic triade which suggests West Syndrome.


Long-term prognostic value of longitudinal measurements of blood neurofilament levels.
To assess the long-term prognostic value of an integral of longitudinal measurements of plasma neurofilament light chain levels (NfLlong) over 12 and 24 months vs single neurofilament light chain (NfL) measurements in patients with relapsing-remitting MS (RRMS) and its additional value when combined with clinical and MRI measures. This analysis included continuously fingolimod-treated patients with RRMS from the 24-month FTY720 Research Evaluating Effects of Daily Oral therapy in Multiple Sclerosis (FREEDOMS)/12-month Trial Assessing Injectable Interferon vs FTY720 Oral in Relapsing-Remitting Multiple Sclerosis (TRANSFORMS) phase 3 trials and their long-term extension, LONGTERMS. Patients were classified into high (≥30 pg/mL, n = 110) and low (<30 pg/mL, n = 164) NfL categories based on the baseline (BL) NfL value or the geometric mean NfLlong calculated over 12 and 24 months to predict disability-related outcomes and brain volume loss (BVL). The additional prognostic value of NfL was quantified using the area under the receiver operating characteristic (ROC) curve. A single high (vs low) NfL measure at BL was prognostic of a higher risk of reaching Expanded Disability Status Scale (EDSS) score ≥4 earlier (hazard ratio [HR] = 2.19; 95% CI = 1.21-3.97) and higher BVL over 120 months (difference: -1.12%; 95% CI = -2.07 to -0.17). When NfLlong was measured over 24 months, high NfL was associated with a higher risk of reaching EDSS score ≥4 (HR = 7.91; 95% CI = 2.99-20.92), accelerated 6-month confirmed disability worsening (HR = 3.14; 95% CI = 1.38-7.11), and 20% worsening in the Timed 25-Foot Walk Test (HR = 3.05; 95% CI = 1.38-6.70). Area under the ROC curve was consistently highest in models combining NfL with clinical and MRI measures. NfLlong had a higher prognostic value than single NfL assessments on long-term outcomes in RRMS. Combining it with clinical and MRI measures increased sensitivity and specificity to predict long-term disease outcomes. This study provides Class I evidence that NfLlong was more strongly associated with long-term outcomes than single NfL assessments in patients with RRMS.


[A case of complete response (CR) persisting for 2 years and 10 months from UFT-E in a patient with liver metastasis of gastric cancer].
A 63-year-old man was admitted to our hospital because of advanced gastric cancer associated with metastasis of the liver. He was treated with 300 mg/day of UFT-E from 18 days after total gastrectomy on July 14, 1997. The preoperative serum level of tumor marker, which had been increasing (CEA: 340 ng/ml, CA19-9: 9,094 U/ml), returned to the normal range 7 months after gastrectomy. CT scan on July 9, 1998 (1 year after gastrectomy) showed that the liver metastasis had changed to a scar (CR). As of May, 2001, 2 years and 10 months after inducing CR, we have been administering UFT-E to the patient, with no side effect or regrowth of the tumor.


Hemoglobin Grange-Blanche [beta 27(B9) Ala----Val], a new variant with normal expression and increased affinity for oxygen.
Hemoglobin Grange-Blanche [beta 27(B9) Ala----Val] is a new variant found in a Portuguese family. The carriers present moderate erythrocytosis. Upon isoelectric focusing, Hb Grange-Blanche was slightly more cathodic than Hb A. beta Grange-Blanche chain migrated like the G gamma chain when submitted to electrophoresis in the presence of urea-Triton X-100. The precentage of Hb Grange-Blanche was about 50% in the heterozygous state. Oxygen affinity was increased (P50 = 22 mmHg), but heme-heme interaction was normal. An abnormal tryptic peptide (beta T3) was isolated using HPLC. Its composition allowed us to deduce unambiguously the amino acid change. The latter is the third mutation found in position 27 of the beta-chain. Because of its normal expression and its elevated affinity for oxygen, Hb Grange-Blanche contrasts with Hb Knossos [beta 27(B9) Ala----Ser], a beta-thalassemic variant with low affinity.


Improved synthesis of substituted 6,7-dihydroxy-4-quinazolineamines: tandutinib, erlotinib and gefitinib.
The synthesis of three substituted 6,7-dihydroxy-4-quinazolineamines: tandutinib (1), erlotinib (2) and gefitinib (3) in improved yields is reported. The intermediates were characterized by NMR and the purities determined by HPLC.


Effects of post-operative furosemide in adult surgical patients: A systematic review and meta-analysis of randomised clinical trials.
Acute kidney injury (AKI) is associated with increased morbidity and mortality and may present as oliguria in the post-operative phase. Diuretics, including furosemide, are commonly used in post-operative patients. Accordingly, we aimed to assess the balance between benefits and harms of furosemide post-operatively in adult surgical patients. We conducted a systematic review with meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statements, the Cochrane Handbook and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. We included randomised clinical trials (RCTs) comparing post-operative treatment with furosemide vs no furosemide in adult surgical patients. Risk ratios (RR) with 95% confidence intervals (CI) were estimated by conventional meta-analysis and trial sequential analysis (TSA). Two thousand five hundred and sixty seven records were identified and four trials with 325 patients in total were included. All were adjudicated as having overall high risk of bias. We observed no statistically significant difference between furosemide- vs no furosemide-treated patients in any of the predefined outcome measures, including AKI (RR 1.07, 95% CI 0.43-2.65), all-cause mortality (RR 1.73, 95% CI 0.62-4.80, use of vasopressors post-operatively (RR 1.04, 95% CI 0.74-1.44) or need for renal replacement therapy (RR 3.87, 95% CI 0.44-33.99). TSA highlighted sparse data, and the overall quality of evidence was very low. In this systematic review, we found that the quantity and quality of evidence for using furosemide post-operatively in adult surgical patients were very low with no firm evidence for benefit or harm.


Allele-specific transcriptional activity at type 2 diabetes-associated single nucleotide polymorphisms in regions of pancreatic islet open chromatin at the JAZF1 locus.
Translation of noncoding common variant association signals into meaningful molecular and biological mechanisms explaining disease susceptibility remains challenging. For the type 2 diabetes association signal in JAZF1 intron 1, we hypothesized that the underlying risk variants have cis-regulatory effects in islets or other type 2 diabetes-relevant cell types. We used maps of experimentally predicted open chromatin regions to prioritize variants for functional follow-up studies of transcriptional activity. Twelve regions containing type 2 diabetes-associated variants were tested for enhancer activity in 832/13 and MIN6 insulinoma cells. Three regions exhibited enhancer activity and only rs1635852 displayed allelic differences in enhancer activity; the type 2 diabetes risk allele T showed lower transcriptional activity than the nonrisk allele C. This risk allele showed increased binding to protein complexes, suggesting that it functions as part of a transcriptional repressor complex. We applied DNA affinity capture to identify factors in the complex and determined that the risk allele preferentially binds the pancreatic master regulator PDX1. These data suggest that the rs1635852 region in JAZF1 intron 1 is part of a cis-regulatory complex and that maps of open chromatin are useful to guide identification of variants with allelic differences in regulatory activity at type 2 diabetes loci.


Did managers of long-term care facilities neglect the functionality of older adults? A survey during the COVID-19 pandemic.
Physical distancing impaired the health of older adults living in long-term care facilities (LTCF). This study aimed to assess the perception of managers of Brazilian LTCF about the loss of functionality of residents and strategies to prevent it. In this cross-sectional study, 276 managers of LTCF from all Brazilian regions responded to an online survey, following the Checklist for Reporting Results of Internet E-Surveys. The managers reported a loss of cognitive (60.2%) and physical (48.2%) functionality and more depressive symptoms (77.9%) and falls (16.3%) in residents. In addition, 73.2% of LTCFs reduced in-person activities, and 55.8% did not perform remote activities. Managers of LTCF neglected the functionality of residents. Thus, health surveillance, prevention, and care must be reinforced for this population.


The relationship between job-related burnout and depressive disorders--results from the Finnish Health 2000 Study.
Depression and burnout are common health problems in working populations today. They appear to be interrelated, and the need for their differential diagnosis has been highlighted in many reviews. We analysed the overlap of job-related burnout and depressive disorders, i.e., major depressive disorder, dysthymia, and minor depressive disorder. We used the population-based 'Health 2000 Study' in Finland. Our nationally representative sample comprised 3276 employees aged 30-64 years. Burnout was assessed with the Maslach Burnout Inventory-General Survey. Diagnoses of depressive disorders were based on the Composite International Diagnostic Interview. Burnout and depressive disorders were clearly related. The risk of depressive disorders, especially major depressive disorder (12-month prevalence), was greater when burnout was severe. Half of the participants with severe burnout had some depressive disorder. Those with a current major depressive episode suffered from serious burnout more often than those who had suffered a major depressive episode earlier. This study was cross-sectional. The concepts of burnout and depression complement each other and cover partly overlapping phenomena. Depressive disorders are related to job-related burnout, particularly when it is severe. A current major depressive episode is likely to be associated with the experience of burnout. When encountering working patients, it is recommended to assess both the occurrence of burnout and of depressive disorders.


Production of erythropoietin by BHK cells growing on the microcarriers trapped in alginate gel beads.
Baby hamster kidney (BHK) cells engineered to produce recombinant human erythropoietin (EPO) were cultured at high density on microcarriers entrapped by calcium alginate gel particles. In this system, the BHK cells proliferated not only on the microcarriers but also in vacant spaces in the alginate gel particles. These spaces contributed greatly to high-density cultivation of the cells and a high productivity of EPO.


Lower Formalin-Induced Pain Responses in Painless Diabetic Neuropathy Rat Correlate with the Reduced Spinal Cord NR2B Subunit of N-Methyl-D-Aspartate Receptor Activation.
Diabetic neuropathy (DN) is a late complication of diabetic mellitus and may rise into painful and painless variants. Limited studies have looked at nociceptive mechanisms of painless DN variant. The study aimed to determine phosphorylation and total NR2B subunit of N-methyl-D-aspartate receptor in the spinal cord of painless DN rat during early phase following formalin injection. Thirty-six Sprague-Dawley male rats were randomly assigned into three groups: control, painful, and painless DN (n = 12). The rats were developed into the early phase of DN for 2 weeks following diabetic induction. Two weeks later, the rats were injected with 5% formalin solution and flinching and licking responses were recorded for 60 min. The rats were sacrificed 3 days later, and the spinal cord enlargement region was collected. Immunohistochemistry and Western blot procedures were conducted to determine the phosphorylated and total NR2B subunit expressions. The results showed reduced flinching and licking responses in painless DN rats compared to control and painful DN groups, followed by a significant reduction in phosphorylated and total NR2B expression at both ipsilateral and contralateral regions of the spinal cord. In conclusion, reduced pain behavior responses in painless DN rats following formalin injection is possibly contributed by the reduced expression of phosphorylated and total NR2B subunit in the spinal cord.


Plasma-promoted dielectric heating in the microwave synthesis of spinels.
Comparison between the rates of synthesis of the spinel phases (MAl2O4, M = Mg, Zn, Ni; and MFe2O4, M = Mg, Zn, Mn) using an O2 microwave-induced plasma (MIP) and conventional (tube furnace) methods indicate that a MIP promotes microwave dielectric heating at elevated temperatures.


Flexible fiberoptic bronchoscopy with general anesthesia in the poor-risk patient.
A study is presented of seven poor-risk patients who had bronchoscopy with a flexible fiberoptic bronchoscope and balanced general anesthesia. The cardiorespiratory status, as evidenced by arterial blood gas determinations, electrocardiographic findings, and blood pressure measurements, was improved and stabilized in all patients. Flexible fibeoptic bronchoscopy, combined with general anesthesia, has proved to be a reliable and safe procedure useful for both diagnosis and treatment in poor-risk patients.


[Zygomaticomaxillary complex fractures with infraorbital nerve damage].
Zygomaticomaxillary complex (ZMC) fracture is a common type of maxillofacial fracture. In addition to facial depression and diplopia, paresthesia of the lower eyelid, malar regions, nose skin, upper lip skin, and mucous membranes occurs because of infraorbital nerve injury. This article reviewed the anatomy, diagnosis, assessment, treatment, and prognosis of ZMC fracture-related infraorbital nerve injury.


Radiotherapy Use in Muscle-Invasive Bladder Cancer: Review of the Guidelines and Impact of Increased Awareness in Patient Referral at a Tertiary Center in Belgium.
Pronounced underuse of radiotherapy (RT) in muscle-invasive bladder cancer (MIBC) is reported. This study aims to assess the awareness about the role of RT in different MIBC settings and see whether this has increased since 2017. We reviewed the bladder cancer guidelines of the EAU, ESMO, NCCN, NICE, and AUA/ASCO/ASTRO/SUO, focusing on the role of RT in MIBC. In 2017, we evaluated the use of RT in MIBC in Belgium. This raised awareness about the indications of RT in different MIBC settings. Here, we present a retrospective pattern of care analysis of the RT use for MIBC patients at our center from January 2012 until December 2021. Frequency of RT use, patient, disease and treatment characteristics were compared between two 5-year periods (2012-2016 and 2017-2021). Review of the guidelines suggested that RT can be used as a treatment option in most MIBC settings. However, differences between guideline recommendations existed and high-level evidence was often lacking. Overall, 221 unique MIBC patients received RT at our center. RT use for MIBC was 39% higher in the second 5-year period (Between the same periods, the number of new MIBC registrations increased with 26%). The most pronounced increase, ie, 529%, was observed in the primary setting and was in parallel with patient preference becoming the main indication for RT. Participation in clinical trials seems to have had an important impact on the frequency of RT use in the adjuvant and metastatic setting. We provide a critical overview of the RT indications in MIBC as recommended by the international guidelines. Increased awareness about RT as a treatment option in MIBC seems to have an impact on the treatment choice in clinical practice, as was observed in our tertiary center.


The effects of dimethylnitrosamine and allyl alcohol on primary maintenance cultures of adult rabbit hepatocytes.
Cultures of adult rabbit hepatocytes have been used to study the early toxic effects of 2 model hepatotoxins, dimethylnitrosamine and allyl alcohol. Leakage of glutamate oxaloacetate transaminase and glutamate pyruvate transaminase into the cell culture medium was a sensitive indicator of plasma membrane damage by these compounds and a dose-response relationship was observed. By contrast, gamma-glutamyltranspeptidase and alkaline phosphatase were insensitive markers. The effects of dimethylnitrosamine were slower to develop. Dimethylnitrosamine also produced a dose-related inhibition of protein synthesis after 4 h, a decrease in NADPH diaphorase and an increase in non-specific esterase after 20 h. Dimethylnitrosamine, unlike allyl alcohol, caused extensive disruption of ribosome association with the endoplasmic reticulum.


Risk factors for severe respiratory syncytial virus infection among Alaska native children.
The incidence of hospitalization for respiratory syncytial virus (RSV) infection among Alaska Native children is much higher than among non-Native populations in the United States. We conducted this study to better understand factors associated with hospitalization attributable to RSV infection in this high-risk population. Case-control study, including collection of cord blood for RSV-neutralizing antibody measurement. Remote region of southwest Alaska served by 1 regional hospital and 2 referral hospitals. Case-patients identified through surveillance for RSV infection and matched control subjects without acute respiratory infection hospitalization. Breastfeeding was associated with a lower risk of RSV hospitalization (odds ratio: 0.34), whereas underlying medical conditions (primarily prematurity) were associated with increased risk (odds ratio: 6.25). Environmental factors associated with a higher risk of hospitalization included household crowding (4 or more children in the household and crowding index > or =2). The level of maternal RSV-neutralizing antibody was not associated with the risk of hospitalization. In this region with extremely high risk of RSV hospitalization, several measures, such as encouraging breastfeeding and reducing household crowding, could reduce the risk of hospitalization attributable to RSV.


Constraint-induced movement therapy for children with neonatal brachial plexus palsy: a randomized crossover trial.
To determine if constraint-induced movement therapy (CIMT) is more effective than standard care in improving upper-limb activity outcomes in children with neonatal brachial plexus palsy (NBPP). Twenty-one children with NBPP (mean age 25mo, SD=10.3, range=17-48mo; 11 males, 10 females) were enrolled in a crossover trial and randomly allocated to first receive CIMT or standard care, each for 8 weeks. The intervention arm consisted of 3 weeks of casting the unaffected limb followed by 5 weeks of transference activities. The Assisting Hand Assessment (AHA) was used to measure bimanual activity performance at baseline, 8 weeks, and 16 weeks, scored by blinded raters. The Pediatric Motor Activity Log-Revised (PMAL-R) was used as a caregiver-reported secondary outcome measure. After concealed random allocation (n=21), there were no significant differences on demographics or baseline measures. CIMT was superior compared to control in terms of bimanual activity performance with a mean difference in AHA change score of 4.8 (SD=10.5, p=0.04, Cohen's δ=0.46). There were no significant differences between treatment conditions on the PMAL-R. CIMT is favored over standard care for bimanual activity performance. Future research should investigate a longer follow-up period, additional comparator interventions, and analyse differences by participant characteristics. Gains in bimanual activity performance were greater after constraint-induced movement therapy (CIMT) compared to no CIMT. Frequency and quality of movement were not significantly different between treatment groups.


Oral amiodarone loading for the rapid treatment of frequent, refractory, sustained ventricular arrhythmias associated with coronary artery disease.
To evaluate the efficacy and safety of oral amiodarone in the treatment of recurrent, sustained, refractory ventricular arrhythmias, rapid high-dose oral loading was used to treat 12 critically ill patients with frequent, sometimes incessant, sustained ventricular arrhythmias refractory to 2 to 6 antiarrhythmic agents. Presenting arrhythmias included sustained monomorphic ventricular tachycardia and ventricular fibrillation associated with cardiac arrests in 6 patients. Patients experienced 2 to 10 episodes (mean 5 +/- 2) of sustained ventricular arrhythmias over a mean period of 6.2 +/- 5.0 days (range 1 to 14) before oral amiodarone was initiated at 1,200 to 1,400 mg/day. This included at least 1 to 4 episodes (mean 2.2 +/- 1.1) within 24 hours before amiodarone. One to 4 antiarrhythmic drugs were administered concurrently during amiodarone loading. Sustained ventricular arrhythmias no longer occurred after a mean of 5.2 days (range 1 to 22) with amiodarone. Arrhythmias were controlled in 4 patients within 24 hours, 5 patients within 48 hours, 7 patients within 4 days and 10 patients within 6 days. Patients experienced a mean of 0.6 +/- 0.8 episodes within 24 hours after amiodarone. Nine patients survived to hospital discharge. No patient had significant adverse effects during high-dose loading. In conclusion, high-dose oral amiodarone loading, when added to previously unsuccessful conventional antiarrhythmic therapy, is safe and often rapidly effective for at least short-term control of frequent, refractory, sustained ventricular arrhythmias.


Spindle assembly checkpoint proteins are positioned close to core microtubule attachment sites at kinetochores.
Spindle assembly checkpoint proteins have been thought to reside in the peripheral corona region of the kinetochore, distal to microtubule attachment sites at the outer plate. However, recent biochemical evidence indicates that checkpoint proteins are closely linked to the core kinetochore microtubule attachment site comprised of the Knl1-Mis12-Ndc80 (KMN) complexes/KMN network. In this paper, we show that the Knl1-Zwint1 complex is required to recruit the Rod-Zwilch-Zw10 (RZZ) and Mad1-Mad2 complexes to the outer kinetochore. Consistent with this, nanometer-scale mapping indicates that RZZ, Mad1-Mad2, and the C terminus of the dynein recruitment factor Spindly are closely juxtaposed with the KMN network in metaphase cells when their dissociation is blocked and the checkpoint is active. In contrast, the N terminus of Spindly is ∼75 nm outside the calponin homology domain of the Ndc80 complex. These results reveal how checkpoint proteins are integrated within the substructure of the kinetochore and will aid in understanding the coordination of microtubule attachment and checkpoint signaling during chromosome segregation.


Isolation of a new cyclophilin-like protein from chickpeas with mitogenic, antifungal and anti-HIV-1 reverse transcriptase activities.
A protein designated chickpea cyclophilin-like antifungal protein (CLAP) was isolated from seeds of the chickpea (Cicer arietinum). Chickpea CLAP was characterized by a molecular weight of 18 kDa and an N-terminal sequence homologous to cyclophilins. The protein was isolated with a procedure involving affinity chromatography on Affi-gel blue gel and ion exchange chromatography on CM-Sepharose. In addition to an inhibitory effect on the growth of fungi including Rhizoctonia solani, Mycosphaerella arachidicola and Botrytis cinerea, the protein was capable of inhibiting human immunodeficiency virus-1 reverse transcriptase. Chickpea CLAP did not possess lectin and ribonuclease activities but it weakly inhibited translation in a rabbit reticulocyte lysate system. The protein stimulated 3H-thymidine incorporation by mouse splenocytes.


Fire Intumescent, High-Temperature Resistant, Mechanically Flexible Graphene Oxide Network for Exceptional Fire Shielding and Ultra-Fast Fire Warning.
Smart fire alarm sensor (FAS) materials with mechanically robust, excellent flame retardancy as well as ultra-sensitive temperature-responsive capability are highly attractive platforms for fire safety application. However, most reported FAS materials can hardly provide sensitive, continuous and reliable alarm signal output due to their undesirable temperature-responsive, flame-resistant and mechanical performances. To overcome these hurdles, herein, we utilize the multi-amino molecule, named HCPA, that can serve as triple-roles including cross-linker, fire retardant and reducing agent for decorating graphene oxide (GO) sheets and obtaining the GO/HCPA hybrid networks. Benefiting from the formation of multi-interactions in hybrid network, the optimized GO/HCPA network exhibits significant increment in mechanical strength, e.g., tensile strength and toughness increase of ~ 2.3 and ~ 5.7 times, respectively, compared to the control one. More importantly, based on P and N doping and promoting thermal reduction effect on GO network, the excellent flame retardancy (withstanding ~ 1200 °C flame attack), ultra-fast fire alarm response time (~ 0.6 s) and ultra-long alarming period (> 600 s) are obtained, representing the best comprehensive performance of GO-based FAS counterparts. Furthermore, based on GO/HCPA network, the fireproof coating is constructed and applied in polymer foam and exhibited exceptional fire shielding performance. This work provides a new idea for designing and fabricating desirable FAS materials and fireproof coatings.


Minimally Invasive Surgical Repair of Vertebral Artery Ostium Stenosis in Patients with Ischemic Stroke: A Single-Center Case Series.
Ischemic stroke is the second leading cause of death in North Macedonia. Posterior circulation disease, caused by vertebral artery (VA) ostium (VAo) stenosis, is a common cause of ischemic stroke. We established a treatment approach using surgical revascularization of posterior circulation disease. In the present observational study, we assessed the outcome after surgical revascularization of the posterior circulation ischemia caused by VAo stenosis. A retrospective analysis of 20 consecutive patients who had undergone surgery from January 2017 to December 2019. The VA was accessed through a 3-cm incision in the upper medial clavicle. The corrective procedures consisted of resection and anastomosis (15 of 20), VA to subclavian artery transposition (16 of 20), endarterectomy (10 of 20), vein graft interposition techniques (4 of 20), and vein graft bypass (1 of 20). The cohort included 9 acute cases. The mean patient age was 66.5 years (range 46-77). Of the 20 patients, 8 were women and 12 were men. Left-sided VA pathology was present in 75% of the cases. We observed rapid clinical improvement in 19 patients (95%). The total study period was 321 patient-months, with a median follow-up of 18 months (interquartile range, 5-24 months). One patient had died of an unknown cause after 12 months. During the follow-up period, 15 patients (75%) had reported permanent clinical improvement with no significant relapse of symptoms. Minimally invasive surgical revascularization of the posterior brain circulation is a clinically effective therapeutic approach to manage ischemia caused by VAo stenosis. It can be performed safely, promote long-lasting symptom relief, and prevent recurrent strokes.


Down syndrome in tribal population in India: A field observation.
Down syndrome (DS) is a prevalent genetic disorder in intellectual disability (ID) in India. Its prevalence in tribal population is not known. The study aimed to understand the profile of DS in a tribal population with an objective of finding the prevalence of DS among those with ID. This is a community-based study with a survey design. A door-to-door survey was conducted by trained, community-based rehabilitation workers under close supervision of multidisciplinary team to identify people with ID. A standardized screening instrument National Institute for Mentally Handicapped-Developmental Screening Schedule was used in the survey. All identified ID cases were evaluated by therapists in IDs for diagnosis of ID on developmental screening test and Vineland social maturity scale. Clinical examination was performed by medical doctors for DS on people identified as ID. Only two parents brought their children for further lab investigations at Ashagram Trust, Barwani. Descriptive statistics was applied manually to treat the data. The frequency of DS population in tribal population closely matches with DS prevalence in the USA. Mothers of DS children in the tribal community are relatively younger. Prevalence of DS in tribal population of India may greatly vary with that of the US data, but it is markedly associated with younger maternal age. Further studies are needed for prevalence and identification of potential correlates of this condition.


CAR T cell therapies for diffuse midline glioma.
Diffuse midline glioma (DMG) is a fatal pediatric cancer of the central nervous system (CNS). The location and infiltrative nature of DMG prevents surgical resection and the benefits of palliative radiotherapy are temporary; median overall survival (OS) is 9-11 months. The tumor immune microenvironment (TIME) is 'cold', and has a dominant immunosuppressive myeloid compartment with low levels of infiltrating lymphocytes and proinflammatory molecules. Because survival statistics have been stagnant for many decades, and therapies targeting the unique biology of DMG are urgently needed, this has prompted the clinical assessment of chimeric antigen receptor (CAR) T cell therapies in this setting. We highlight the current landscape of CAR T cell therapy for DMG, the role the TIME may play in the response, and strategies to overcome treatment obstacles.


Drop coating deposition Raman spectroscopy of liposomes: role of cholesterol.
Drop coating deposition Raman (DCDR) spectroscopy was used to study liposomes (DPPC and asolectin) with growing proportion of cholesterol. Deposited samples of both liposomes on special hydrophobic surface formed a dried drop with a circular shape with a ring of concentrated liposomes at the outer edge. The presence of cholesterol in liposome causes a diminishing of the drop size and an increasing in diameter of the ring, but DPPC with 20% of cholesterol forms the compact drop without the ring. Raman spectra contain characteristics of both lipids and cholesterol, liposomes do not change their initial phase state after drying. Spectral mapping shows that maximum Raman intensity originated from the inner part of the ring. Our results suggest that DCDR spectroscopy can be used for studying lipids containing cholesterol in situ.


Urinary tract endometriosis: clinical, diagnostic, and therapeutic aspects.
To describe our experience at La Paz University Hospital with 12 patients with urinary tract endometriosis, an uncommon pathologic finding, the most extensive series published by Spanish investigators to our knowledge. We performed a retrospective analysis of 12 cases of urinary tract endometriosis diagnosed from 1993 to 2008. The mean patient age was 37.75 years. Of the 12 patients, 5 had bladder involvement and 7 had ureteral involvement, 2 bilateral, 2 left, and 3 right. In those with bladder endometriosis, the diagnosis was made by cystoscopy and biopsy in 4 patients. Treatment consisted of laparoscopic hysterectomy and partial cystectomy in 1 patient and exploratory laparotomy, transvesical resection, and transurethral resection of the bladder in 3 patients. One of the patients who underwent transurethral resection of the bladder experienced 2 relapses. The first relapse was treated with transurethral resection of the bladder and the second with laparoscopic partial cystectomy. In the patients with ureteral endometriosis, the diagnosis was mainly established by magnetic resonance imaging. Treatment consisted of ureteroneocystostomy in 5 patients (bilateral in 1) and laparoscopic ureterolysis in 2, with later ureteral resection and end-to-end anastomosis in 1 of them. The patient who underwent bilateral ureteroneocystostomy finally required right autotransplantation because of early ureteral relapses. Urinary tract endometriosis is an uncommon pathologic finding. Surgery is the treatment of choice. We believe partial cystectomy should be considered as an initial option in selected cases, depending on the extent and location of lesions. For cases of ureteral endometriosis, the initial technique depends on the location and depth of the lesion.


Anticoagulation remains underused in prevention of stroke associated with atrial fibrillation: insights from two consecutive national surveys.
Atrial fibrillation (AF) is a major risk factor of ischemic stroke. We tested whether the adoption of the CHADS(2) score in clinical guidelines has impacted treatment strategies for stroke prevention, and examined how AF affects stroke outcome. In the setting of two national surveys [National Acute Stroke Israeli Surveys; all patients hospitalized for stroke in Israel during February-March 2004, and March-April 2007] data of patients with and without AF were analyzed with respect to patient characteristics, use of anticoagulation, stroke severity, clinical course, and long-term outcome. Of 3040 patients with acute ischemic stroke, 586 patients (19%) had a history of AF. Severe strokes on admission were significantly more frequent in patients with AF, as was the proportion of total anterior circulation strokes. Ischemic stroke associated with AF predicted poor outcome at discharge (adjusted OR 1.56; 95%CI 1.24-1.96) and higher mortality rates throughout follow-up. Among patients with a CHADS(2) score ≥ 2 prior to the index stroke and without known contraindications, 41% received anticoagulation. This proportion increased to only 62% after the index stroke, even after excluding patients with severe disability and no significant increase between 2004 and 2007 was detectable. Increasing age, in-hospital infectious complications, and unfavorable functional status at discharge were independently associated with decreased likelihood of receiving anticoagulation. In deviation from current recommendations and in spite of the introduction of CHADS(2) criteria, anticoagulation for stroke prevention remains underutilized, despite the particularly poor outcome of strokes associated with AF.


Bioabsorbable gelatin sheets latticed with polyglycolic acid can eliminate pericardial adhesion.
As an extension of our previous studies on bioabsorbable pericardial substitutes, we have created a new form of gelatin sheets latticed with bioabsorbable polyglycolic acid (PGA). This study was undertaken to evaluate the biomechanical property of the sheet and the preventive effect on pericardial adhesions after pericardial replacement in a canine model before its clinical applications. The mechanical property was assessed by measuring tension of suture pull-out at first break test. Fifteen dogs underwent partial pericardial replacement with the bioabsorbable sheets through a left thoracotomy. Macroscopic assessment for severity of adhesions and microscopic evaluation for histologic changes were made at 2, 4, 12, and 24 weeks postoperatively. The latticed sheets exhibited tenfold higher tension of disruption at the suturing margin compared to our previously developed gelatin sheets (619 +/- 141 versus 62 +/- 7 gf, p < 0.001), and demonstrated equivalent strength to that of clinically available expanded polytetrafluoroethylene membrane. During rethoracotomy, adhesions between the epicardium and the pericardial substitutes were moderate at the 4-week interval and resolved completely after 12 weeks postoperatively. Inflammatory reaction scores graded into 4 scales on histologic assessment were 2 +/- 0.0, 1.6 +/- 0.6, and 0.3 +/- 0.5 at 4, 12, and 24 weeks, respectively. Inflammatory reaction significantly decreased from the 4-week interval to the 24-week interval after the pericardial replacement (p < 0.05). The bioabsorbable gelatin sheets latticed with PGA gained improved mechanical properties compared with the previously reported gelatin sheets without impairing its bioabsorbability. The bioabsorbable sheet could eliminate pericardial adhesions after being replaced with regenerated tissue.


Renal haemodynamic effects of endothelin-1 and the ETA/ETB antagonist TAK-044 in anaesthetized rabbits.
The aim of this study was to test the effects of exogenous endothelin-1 (ET-1) on regional kidney blood flow and renal function, and the renal haemodynamic effects of endogenous ET, in anaesthetized rabbits. ET-1 was infused into the left renal artery at 2 ng/kg/min for 30 min, then at 1 ng/kg/min. Cumulative doses of TAK-044 (0.1-3 mg/kg, i.v.) or its vehicle were given at 30-min intervals. In other rabbits, an extracorporeal circuit was established to adjust renal arterial pressure (RAP) independently of systemic arterial pressure (MAP). RAP was set at 65 mmHg, and either TAK-044 (3 mg/kg, i.v.) or its vehicle was administered. In the infused kidney ET-1 (2 ng/kg/min) reduced renal blood flow (RBFprobe; 52+/-8%), cortical perfusion (37+/-7%), glomerular filtration rate (GFR; 49+/-8%), urine flow (47+/-14%) and sodium excretion (49+/-13%), but not medullary perfusion (5+/-6%). No effects of ET-1 on MAP or on the contralateral kidney were observed. TAK-044 dose-dependently reversed the effects of ET-1 on RBFprobe and cortical perfusion. TAK-044 also reduced MAP (by up to 11+/-3%) and increased effective renal blood flow in the contralateral kidney (by up to 46+/-27%). In the extracorporeal circuit model, TAK-044 decreased MAP by 12+/-2% and RAP by 10+/-3%, and increased RBF by 9+/-3%. Exogenous ET-1 reduces cortical more than medullary perfusion, and reduces GFR without affecting net tubular sodium and fluid reabsorption. TAK-044 antagonizes local renal vascular responses to ET-1. Endogenous ETs appear to contribute markedly to resting renal vasomotor tone and MAP.


The long term results of endoscopic surveillance of premalignant gastric lesions.
A large proportion of patients attending open access endoscopy have histological and gross pathological findings that are potentially premalignant. The proportion of these patients who go on to develop malignancies and the timescale over which this occurs are uncertain. This study aims to discover the incidence of gastric cancers in this "high risk" group and to examine the potential for their early diagnosis and treatment. A total of 1753 patients attended open access endoscopy. From these, 166 patients with dysplasia, intestinal metaplasia, atrophic gastritis, foveolar hyperplasia, regenerative changes, polyps, or ulcers who agreed to undergo annual surveillance endoscopy were studied. Patients were endoscoped annually. Additionally, patients with ulcers were re-examined at two monthly intervals until ulcer healing. Cancers detected were treated by gastrectomy. Twenty two of 1753 patients attending open access endoscopy had gastric cancer (1.3%). In the study population, 14 cancers were detected over 10 years (8.4 %). These were of an earlier stage than those detected at open access (stage I and II 67% v 23%; p<0.05) and five year survival was significantly higher (50% v 10%; p=0.006). In atrophic gastritis and intestinal metaplasia the risk of malignancy was 11%. In patients with atrophic gastritis or intestinal metaplasia, annual surveillance can detect most new tumours at an early stage with a major improvement in survival. Potential benefits of such a surveillance programme are large and warrant further investigation in a multicentre randomised controlled trial.


[Topical problems of the modern epidemiology (data for presentation at the all-Russian scientific conference "The problems of modern epidemiology. Perspective means and methods for the laboratory diagnosis and prevention of urgent infections")].
The strategic goal of preserving the nation's health, reducing mortality rates, and overcoming the demographic decline has been realized in Russia over the recent years. To decrease the incidence of infectious diseases is a substantial reserve for reducing mortality rates and increasing lifespan. The Russian Federation is augmenting the interaction in the problem of infectious diseases within the framework of the Shanghai Cooperation, CIS, EuroAsEC, etc. Our country implements hundreds of regional programs on the sanitary-and-epidemiological well-being of the population every year. Considerable progress has been made in reducing the incidence of infections controlled by specific preventive means. It is essential to implement a national priority health project on mass additional immunization against viral hepatitis B, measles, German measles, influenza, and poliomyelitis, and on the prevention and treatment of HIV/AID and viral hepatitis B and C.


Vitamin D in Head and Neck Cancer: a Systematic Review.
Observational studies have shown that serum 25-OH vitamin D [25(OH)D] is inversely associated with overall cancer risk in many malignancies. We performed a systematic literature review to determine whether vitamin D deficiency is related to head and neck cancer (HNC) etiology and outcome. The search yielded five prospective studies reporting 25(OH)D levels prior to cancer diagnosis and their effect on the risk of HNC. Eight studies were cross-sectional or case-control studies, in which 25(OH)D levels were only measured after cancer diagnosis. Two studies found an inverse association between 25(OH)D level and HNC risk, while two other prospective cohort studies demonstrated no connection between 25(OH)D and HNC risk. Several studies reported cancer patients to have significantly lower 25(OH)D levels than controls. Associations between 25(OH)D and prognosis and mortality were variable. The link between vitamin D and HNC has so far only been investigated in a few observational, prospective, and case-control studies. Vitamin D deficiency may be more common in HNC patients than in the healthy population. There is no evidence for a causal relationship. Further studies are needed to evaluate whether low 25(OH)D concentrations play a role in the development or outcome of HNCs.


Gastric juice MicroRNAs as potential biomarkers for the screening of gastric cancer.
MicroRNAs (miRNAs) play a crucial role in carcinogenesis; however, it largely remains unclear whether miRNAs in gastric juice, which is specific for gastric tissues, can be used as biomarkers for gastric cancer. The objective of the current study was to investigate the feasibility of using gastric juice miRNAs as potential biomarkers to assist in screening for gastric cancer. Gastric juice samples were collected from 141 patients who underwent upper gastrointestinal endoscopy examination between September 2010 and December 2011. Gastric cancer and adjacent normal biopsy specimens also were collected. The existence and stability of miRNAs in gastric juices were determined by real-time reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) and sequencing. miRNA levels in tissues and gastric juices were detected by RT-qPCR. A receiver operating characteristic (ROC) curve was constructed for differentiating gastric cancer from benign gastric diseases. Levels of miRNA-21 (miR-21) and miR-106a in gastric cancer tissues were significantly higher compared with the levels in adjacent tissues (P = .006 and P = .001, respectively). Patients who had gastric cancer had significantly different levels of gastric juice miR-21 and miR-106a compared with patients who had benign gastric diseases (both P < .001). There were significant correlations between miR-21/miR-106a levels and Borrmann types. miR-21 levels in intestinal type gastric cancer specimens were higher than that in diffuse (P = .003) or mixed (P < .001) gastric cancer types. The area under the ROC curve was up to 0.969 for miR-21 and 0.871 for miR-106a. The current results indicated that certain miRNAs in gastric juice are potential biomarkers that can assist in screening for gastric cancer.


Depolarization-induced release of ethanolamine from brain synaptic preparations in vitro.
The release of ethanolamine from mouse brain synaptosomes and synaptoneurosomes has been investigated. The depolarizing agents veratridine (50 microM), KCl (35 mM) and 4-aminopyridine (2 mM) enhanced the release of [3H]ethanolamine from preloaded synaptosomes under superfusion conditions. Tetrodotoxin (2 microM) strongly inhibited veratridine- and 4-aminopyridine-stimulated release of [3H]ethanolamine but had no effect on KCl-evoked or resting release. In the absence of calcium, a reduction in the resting release of [3H]ethanolamine occurred and release evoked by veratridine, and KCl was markedly reduced. Exposure of preloaded synaptosomes to 5 mM ethanolamine (but not 5 mM serine or 5 mM choline) calcium-dependently increased the efflux of [3H]ethanolamine, however, this was not accompanied by membrane depolarization. When these experiments were performed using synaptoneurosomes, qualitatively similar results were obtained. The resting and evoked release of [3H]ethanolamine was however approximately 2.5-fold higher compared to synaptosomes on a brain equivalent basis, suggesting that uptake and release occur at sites in addition to the nerve ending. Our data are consistent with the idea that a significant amount of ethanolamine accumulates presynaptically and undergoes calcium-dependent release upon depolarization possibly via classical exocytosis. In contrast, ethanolamine-induced release of [3H]ethanolamine likely involves mostly diffusional exchange across the neuronal membrane rather than base exchange. The present results add support to the concept that ethanolamine may play a role as a synaptic signaling molecule in mammalian brain.


The effect of a red background on location backward masking by structure.
It has been established that diffuse red light partially suppresses the magnocellular (M) visual pathway. Previous research reported that metacontrast masking is reduced (improved accuracy) with a red background, consistent with a reduction in M pathway response from the mask. In contrast, a recent study used location backward masking by noise and found that accuracy decreased with a red background--theoretically due to suppression of the M pathway's initial localization of the target. The present study provides the first report examining the effect of red light on performance in a location backward masking by structure task. Results revealed a main effect of a red (as opposed to a green) background on reducing masking (improved accuracy) with a medium effect size (eta2 = .23). This effect was strongest at the 47- and 60-msec stimulus onset asynchronies. Results suggest that red light primarily decreases interference from the mask in location backward masking by structure.


Acute leukemia of hybrid phenotype: T lymphoid and myelomonocytic markers.
Several unique phenotypical and functional characteristics were found together in a patient with acute poorly differentiated leukemia. The blast cells showed an unusual T-cell phenotype, forming spontaneous rosettes with sheep red blood cells and expressing the T11 antigen, but were negative for the other immature or mature T markers tested--Leu-1, 3A1, T3, T4, T8, T9, T10, T6, and TdT--and reacted with the monoclonal antibody OKM1 expressed by myeloid lineage cells and which is also present in natural killer (NK) cells. Furthermore, these cells were able to produce interleukin-2 (IL-2) after mitogenic stimulation and showed cytotoxic activity against K-562 target cells after incubation with an IL-2 supernatant. These features do not correspond to any known stage of the T-cell differentiation pathway and may represent the expansion of a pre-NK cell which may be poorly represented in normal tissues.


Cell-penetrating peptides as versatile vehicles for oligonucleotide delivery.
Short regulatory oligonucleotides (ONs) have a great therapeutic potential for the modulation of gene expression due to their high specificity and low toxicity. The major obstacles for in vivo clinical applications of ONs are the poor permeability of plasma membrane to nucleic acids and the sensitivity of ONs to enzymatic degradation. Hence, various delivery vehicles have been developed to ensure the transduction of ONs into cells. Among these, the cell-penetrating peptides (CPPs) have gained quickly broadening popularity as promising nonviral transmembrane delivery vectors. For coupling of nucleic acids to CPPs, two distinct strategies may be applied-covalent and noncovalent. The majority of earlier studies have used covalent coupling of CPPs to ONs. However, the number of studies demonstrating very high therapeutic potential of noncovalent complexes of ONs with novel CPP-based delivery vehicles is explosively increasing. In this review, the recent developments in the application of CPP-mediated oligonucleotide delivery by noncovalent strategy will be discussed.


Machine Learning Within Studies of Early-Life Environmental Exposures and Child Health: Review of the Current Literature and Discussion of Next Steps.
The goal of this article is to review the use of machine learning (ML) within studies of environmental exposures and children's health, identify common themes across studies, and provide recommendations to advance their use in research and practice. We identified 42 articles reporting upon the use of ML within studies of environmental exposures and children's health between 2017 and 2019. The common themes among the articles were analysis of mixture data, exposure prediction, disease prediction and forecasting, analysis of complex data, and causal inference. With the increasing complexity of environmental health data, we anticipate greater use of ML to address the challenges that cannot be handled by traditional analytics. In order for these methods to beneficially impact public health, the ML techniques we use need to be appropriate for our study questions, rigorously evaluated and reported in a way that can be critically assessed by the scientific community.


Active site mutants of human herpesvirus-6 proteinase.
Amino acid residues thought to comprise the catalytic triad of HHV-6 proteinase were changed by site-directed mutagenesis in the precursor form of the proteinase. By monitoring the ability of each mutant proteinase precursor to undergo autoprocessing, Ser116, His46 and His135 were identified as catalytically crucial. An attempt was made to mimic the catalytic triad arrangement of archetypal serine proteinases by replacement of the second histidine, His135, by an Asp. Instead of increasing the autoprocessing ability of the His135Asp mutant HHV-6 proteinase precursor, this mutation had a detrimental effect since the precursor persisted predominantly in its unprocessed form.


The effect of albinism on avian predator attack rates in eastern garter snakes.
Albinism is a conspicuous and distinctive phenotype arising from the absence of melanin in the integument that has been documented in all major vertebrate groups. With few exceptions, albinism is rare in natural populations, suggesting that it incurs significant fitness costs as compared to wild-type phenotypes. One possible explanation for this rarity is that albinos experience higher predation risk as compared to wild-type individuals. We tested this hypothesis by comparing rates of attack by avian predators on immobile clay model proxies that mimicked wild-type and albino eastern garter snakes (Thamnophis s. sirtalis) at Bond Swamp in central Georgia, USA; two mixed pattern treatments provided intermediate phenotypes for comparison. Surprisingly, we found no difference in attack rate across all four model treatments, nor among pairs of treatments (i.e., wild-type-like vs. albino-like models). This indicates that albino garter snakes are not subject to higher predation risk from birds due to coloration alone, and that other factors (correlated pathologies of albinism, thermoregulatory challenges, mate selection) are likely to be more important in explaining the rarity of albinism in snakes and perhaps other vertebrate groups.


Outcome and rehabilitation after childhood stroke.
In contrast to popular belief, the vascular stroke syndromes of childhood (arterial ischemic stroke, cerebral sinovenous thrombosis, and nontraumatic intracranial hemorrhage) result in appreciable mortality and significant morbidity in survivors. The specific nature and range of impairments is affected by the etiology and distribution of the lesion as well as the age of the child. However, no domain of function is universally spared. Impairments, in particular affecting cognitive function, may only emerge over time and therefore long-term vigilance is important. Current rehabilitation approaches in these children are rarely evidence based and are usually based on approaches used in management of congenital disorders such as cerebral palsy. The rehabilitation approach should be targeted to the observed pattern of impairment rather than the diagnosis - for example dystonia, rather than spasticity, is a far more common consequence of arterial ischemic stroke in children, whereas most conventional stroke rehabilitation approaches target spasticity. Age is likely to be an important factor in both determining the potential for natural recovery as well as the response to rehabilitation. New rehabilitation approaches such as constraint induced movement therapy and transcranial magnetic stimulation hold promise.


Isolation, identification and toxicological characterization of TSS 1, a new mycotoxin of the rosenane class.
11-β-hydroxy-7-deoxy-rosenonolactone (TSS1), a product of the pathogenic fungusTrichothecium roseum (Moniliaceae) was isolated from culture medium extracts and completely described in its structure by spectroscopical methods.TSS 1 was classified as a representative of the lactone series of the rosenane class and as a structural isomer to Rosenololactone (1) and Rosololactone (2, 3).TSS1 showed toxic effects in the growth inhibition test toE coli (EC 50: lOμg/mL) andB subtil is (EC 50: 17μg/mL), inhibited fermentation of yeast (EC 50: 2.8μg/mL) and suppressed motility ofAnemia satina larvae (EC 50: 45/μg/mL).Rosenonolactone, the best known representative of that mycotoxin class, showed only a very weak biological activity (EC 50: 200μg/mL), despite the high degree of structural similarity compared to TSS1. This investigation demonstrates that a small difference in the chemical structure between two metabolites of the same organism can strongly enhance the toxicity of a substance.


Visual information following object grasp supports digit position variability and swift anticipatory force control.
Anticipatory force control underlying dexterous manipulation has historically been understood to rely on visual object properties and on sensorimotor memories associated with previous experiences with similar objects. However, it is becoming increasingly recognized that anticipatory force control also relies on how an object is grasped. Experiments that allow unconstrained grasp contact points when preventing tilting an object with an off-centered mass show trial-to-trial variations in digit position and subsequent scaling of lift forces, all before feedback of object properties becomes available. Here, we manipulated the availability of visual information before reach onset and after grasp contact (with no vision during the reach) to determine the contribution and timing of visual information processing to the scaling of fingertip forces during dexterous manipulation at flexible contact points. Results showed that anticipatory force control was similarly successful, quantified as an appropriate compensatory torque at lift onset that counters the external torque of an object with a left and right center of mass, irrespective of the timing and availability of visual information. However, the way in which anticipatory force control was achieved varied depending on the availability of visual information. Visual information following grasp contact was associated with greater use of an asymmetric thumb and index finger grasp configuration to generate a compensatory torque and digit position variability, together with faster fingertip force scaling and sensorimotor learning. This result supports the hypothesis that visual information at a critical and functionally relevant time point following grasp contact supports variable and swift digit-based force control for dexterous object manipulation.NEW & NOTEWORTHY Humans excel in dexterous object manipulation by precisely coordinating grasp points and fingertip forces, highlighted in scenarios requiring countering object torques in advance, e.g., lifting a teacup without spilling will demand a unique digit force pattern based on the grip configuration at lift onset. Here, we show that visual information following grasp contact, a critical and functionally relevant time point, supports digit position variability and swift anticipatory force control to achieve a dexterous motor goal.


Daidzein Activates Akt Pathway to Promote the Proliferation of Female Germline Stem Cells through Upregulating Clec11a.
Female germline stem cells (FGSCs) have been successfully isolated and characterized from postnatal mammalian and human ovarian tissues. However, the effects and mechanisms of action of natural small-molecule compounds on FGSCs are largely unknown. Here, we found that daidzein promoted the viability and proliferation of FGSCs. To elucidate the mechanism underlying this, we performed RNA-Sequence in daidzein-treated FGSCs and controls. The results showed that there were 153 upregulated and 156 downregulated genes in daidzein treatment. We confirmed the expression of some genes related to cell proliferation in the sequencing results by RT-PCR, such as Type C lectin domain family 11 member a (Clec11a), Mucin1 (Muc1), Glutathione peroxidase 3 (Gpx3), and Tet methylcytosine dioxygenase 1 (Tet1). The high expression of Clec11a at the protein level after daidzein treatment was also confirmed by western blotting. Furthermore, recombinant mouse Clec11a (rmClec11a) protein was shown to promote the viability and proliferation of FGSCs. However, knockdown of Clec11a inhibited the viability and proliferation of FGSCs, which could not be rescued by the administration of daidzein. These results indicate that daidzein promoted the viability and proliferation of FGSCs through Clec11a. In addition, both daidzein and rmClec11a activated the Akt signaling pathway in FGSCs. However, Clec11a knockdown inhibited this pathway, which could not be rescued by daidzein administration. Taken together, our findings revealed that daidzein activates the Akt signaling pathway to promote cell viability and proliferation through upregulating Clec11a. This study should deepen our understanding of the developmental mechanism of FGSCs and female infertility.


Gliomatosis cerebri: report of a case presenting as a focal cerebral mass.
Gliomatosis cerebri (syn. astrocytomatosis cerebri) is a rare diffuse neoplastic condition affecting all parts of the brain. The clinical and pathological features of an unusually diffuse and histologically uniform case of gliomatosis cerebri are presented. Many tumour cells stained positively for glial fibrillary acid protein, confirming the astrocytic derivation of this neoplasm. Differing views on the nature of gliomatosis cerebri are briefly discussed.


Development and evaluation of multiplex real-time RT-PCR assays for seasonal, pandemic A/H1pdm09 and avian A/H5 influenza viruses detection.
Since the pandemic influenza A (H1N1) 2009 ((H1N1)pdm09) virus spread all over the world, the (H1N1)pdm09 virus has been circulating with seasonal influenza viruses. We developed rapid and sensitive one-step multiplex real-time RT-PCR assays (rRT-PCR) for simultaneous detection of influenza viruses currently circulating in humans, and the avian A/H5 virus. The detection limit of each assay was 4.8 to 1 copies per reaction and no cross-reactivity with other major respiratory pathogens was found. Analytical positive predictive value (PPV), negative predictive value (NPV) sensitivity and specificity were 100%, 94.1%, 93.7% and 100%, respectively. Clinical evaluation revealed that 1,976 (16.5%) of 11,963 throat swabs from patients with respiratory symptoms were confirmed as 1,651 (83.6%) A/H1pdm09, 308 (15.6%) A/H3 and 17 (0.8%) B virus during the 2010-2011 influenza season. Collectively, the multiplex rRT-PCR assays described here provide a practical tool for reliable implementation of influenza surveillance and diagnosis.


Murine H-2Dd-reactive monoclonal antibodies recognize shared antigenic determinant(s) on human HLA-B7 or HLA-B27 molecules or both.
We have evaluated the serological relationships between the murine H-2Dd and human HLA molecules using four H-2Dd-reactive monoclonal antibodies (mAbs) produced in the A.BY (KbIbDb) anti-A.TL (KsIkDd) combination. In the mouse, these reagents exhibited three distinct reactivity patterns: Dd, Ks, and H-2u (mAb 81.L); Dd, H-2p, and H-2u (mAb 81.R); and Dd, Kd, H-2p, H-2u, and H-2v (mAbs 97.G and 97.H). Sequential immunoprecipitation and cross-competitive mAb binding experiments revealed that these mAbs recognized determinants in two spatially distinct polymorphic domains on the H-2Dd molecule of B10.A(5R) cells (defined by mAbs 81.L and 81.R, 97.H, and 97.G, respectively). MAbs 81.R, 97.G, and 97.H, but not 81.L, also defined an HLA-linked polymorphism in the human, the main characteristics of which can be summarized as follows: (i) on B lymphoblastoid cell lines, mAbs 81.R and 97.H bound to cells expressing the HLA-B7, HL-B27 or Bw40 cross-reacting specificities, (ii) on peripheral blood lymphocyte (PBL) panel mAb 81.R exerted C dependent cytotoxicity to 118 of 400 cells tested, including almost all HLA-B7 or HLA-B27 cells or both (r: 0.952), (iii) the expression of the 81.R cross-reacting determinant segregated in an informative family with the parental haplotype carrying the HLA-B7 allele, and (iv) mAbs 81.R, 97.G, and 97.H recognized topologically related determinants on the same class I molecule(s) of the human B lymphoblastoid cells JY (HLA-A2,2, -B7,7). These data support the view that some, but not all H-2Dd allotopes have been conserved throughout evolution and are associated in the human with the HLA-B7, -B27 cross-reacting specificities.


Development of the perifollicular capillary network. Autoradiographic and morphometric studies in the rabbit ovary.
The published data give a report on systematic examinations on the development of the perifollicular capillary network in the theca interna in rabbit ovaries. The follicle size and the number of capillaries were investigated by means of morphometric methods. The extent of proliferation of granulosa and endothelial cells was studied autoradiographically by determining the labelling index (LI). The results show that the perifollicular capillary network is initiated only when the stratum granulosum has developed into a multilayered cell population. After that the number of capillaries increases linearly with increasing follicle size, independently of the oestrus cycle. During follicle growth at different times in the oestrus cycle the decrease and increase in the LI of granulosa cells is followed by a corresponding decrease and increase in the LI of endothelial cells several hours later. It should be noted, however, that the proliferation of endothelial cells in follicles with a diameter of 900 microns continues, although the decreasing LI of granulosa cells already indicates a reduced follicle growth. The number of labelled endothelial cells in atretic follicles decreases only after a decrease in proliferation of granulosa cells. In conclusion, it can be noted that the follicle growth and function is not influenced by variations in the number of capillaries in the theca interna. The curve of LI of granulosa and endothelial cells suggests that the granulosa cells have a certain regulatory function with respect to the growth of the capillary network in the theca interna.


Metformin inhibits cardiometabolic syndrome associated cognitive deficits in high fat diet rats.
Glucose intolerance and insulin resistance are hallmarks of metabolic syndrome and lead to Alzheimer's disease (AD). The purpose of this study is to elucidate the neuroprotective effect of metformin through insulin regulation with cardiometabolic and neurotransmitter metabolic enzyme regulation in high-fat, high-sucrose diet and streptozotocin (HFHS-STZ)-induced rats. Male Wistar rats were treated with metformin (180 mg/kg and 360 mg/kg). STZ (35 mg/kg i.p.) injection was performed on the 14th day of 42 days of HFHS diet treatment. Brain neurotransmitter metabolic enzymes (acetylcholinesterase and monoamine oxidase) were determined along with sodium-potassium ATPase (Na+K+-ATPase). Plasma lipids and homeostasis model assessment of insulin resistance (HOMA-IR) was performed. Mean arterial blood pressure, heart rate and electrocardiogram (QT, QTc and RR intervals) were analysed with PowerLab. Metformin treatment significantly (p < 0.001) reduced the HOMA-IR index and decreased neurotransmitter metabolic enzymes such as AChE and MAO (p < 0.01 and p < 0.05). The lipid profile was significantly (p < 0.001) controlled with cardiometabolic functions. Our investigation revealed that metformin has a remarkable role in regulating brain insulin, vascular system with monoaminergic metabolic enzymes and enhancing synaptic plasticity. Metformin may be a selective early therapeutic agent in metabolic syndrome associated with cognitive decline.


Application of nanoparticles in the diagnosis and treatment of chronic kidney disease.
With the development of nanotechnology, nanoparticles have been used in various industries. In medicine, nanoparticles have been used in the diagnosis and treatment of diseases. The kidney is an important organ for waste excretion and maintaining the balance of the internal environment; it filters various metabolic wastes. Kidney dysfunction may result in the accumulation of excess water and various toxins in the body without being discharged, leading to complications and life-threatening conditions. Based on their physical and chemical properties, nanoparticles can enter cells and cross biological barriers to reach the kidneys and therefore, can be used in the diagnosis and treatment of chronic kidney disease (CKD). In the first search, we used the English terms "Renal Insufficiency, Chronic" [Mesh] as the subject word and terms such as "Chronic Renal Insufficiencies," "Chronic Renal Insufficiency," "Chronic Kidney Diseases," "Kidney Disease, Chronic," "Renal Disease, Chronic" as free words. In the second search, we used "Nanoparticles" [Mesh] as the subject word and "Nanocrystalline Materials," "Materials, Nanocrystalline," "Nanocrystals," and others as free words. The relevant literature was searched and read. Moreover, we analyzed and summarized the application and mechanism of nanoparticles in the diagnosis of CKD, application of nanoparticles in the diagnosis and treatment of renal fibrosis and vascular calcification (VC), and their clinical application in patients undergoing dialysis. Specifically, we found that nanoparticles can detect CKD in the early stages in a variety of ways, such as via breath sensors that detect gases and biosensors that detect urine and can be used as a contrast agent to avoid kidney damage. In addition, nanoparticles can be used to treat and reverse renal fibrosis, as well as detect and treat VC in patients with early CKD. Simultaneously, nanoparticles can improve safety and convenience for patients undergoing dialysis. Finally, we summarize the current advantages and limitations of nanoparticles applied to CKD as well as their future prospects.


Industrial potential of the enzymatic synthesis of nucleoside analogs: existing challenges and perspectives.
Nucleoside phosphorylases have progressed from an enzymatic curiosity to a viable synthetic tool. However, despite the recent advances in nucleoside phosphorylase-catalyzed nucleoside synthesis, the widespread application of these enzymes in industrial processes is still lacking. We attribute this gap to three key challenges, which are outlined in this short review. To address these persistent obstacles, we believe that biocatalytic nucleoside synthesis needs to embrace interdisciplinary partnerships with the fields of organic chemistry, process engineering, and flow chemistry.


Predation-associated differences in sex linkage of wild guppy coloration.
Evolutionary theory predicts that the sex linkage of sexually selected traits can influence the direction and rate of evolutionary change, and also itself be subject to selection. Theory abounds on how sex-specific selection, mate choice, or other phenomena should favor different types of sex-linked inheritance, yet evidence in nature remains limited. Here, we use hormone assays in Trinidadian guppies to explore the extent to which linkage of male coloration differs among populations adapted to varying predation regimes. Results show there is consistently higher degree of X- and autosomal linkage in body coloration among populations adapted to low-predation environments. More strikingly, analyses of an introduced population of guppies from a high- to a low-predation environment suggest that this difference can change in 50 years or less.


Hypoalbuminemia Is Associated with Increased 30-Day Complications following Rectourethral Fistula Repair: A National Surgical Quality Improvement Program Study.
We sought to assess patient risk factors for 30-day postoperative complications among men undergoing surgical management of rectourethral fistula (RUF). The American College of Surgeons National Surgical Quality Improvement Program database was queried for all male patients who underwent RUF repair (2006-2018). Hypoalbuminemia was defined as preoperative serum albumin <3.5 gm/dL. Postoperative 30-day complications included wound infection, organ space surgical site infection, urinary tract infection, sepsis, venous thromboembolism, pneumonia, cerebrovascular accident, myocardial infarction, return to operating room and mortality. The association between pre-selected patient covariates and postoperative complications was investigated using logistic regression analysis. A total of 250 patients were identified. Concurrent procedures during RUF repair were bowel diversion in 43/250 patients (17.2%), bowel resection (34/250, 13.6%), cystectomy (20/250, 8.0%) and urethroplasty (37/250, 14.8%). Overall, median age was 66.0 years (IQR 59.0-72.0), body mass index 26.6 kg/m2 (IQR 23.7-29.5) and 247/250 patients (98.8%) were functionally independent. Comorbidities included hypertension (140/250, 56.0%), smoking (55/250, 22.0%), diabetes (17/250, 6.8%), chronic obstructive pulmonary disease (11/250, 4.4%) and congestive heart failure (1/250, 0.4%). Hypoalbuminemia (<3.5 gm/dL) was present in 25/126 patients (19.8%). Overall, 51/250 patients (20.4%) experienced a complication within 30 days of surgery including wound infection (14/250, 5.6%), sepsis (13/250, 5.2%), organ space infection (11/250, 4.4%), urinary tract infection (8/250, 3.2%), venous thromboembolism (8/250, 3.2%) and mortality (5/250, 2.0%). After adjusting for covariates, hypoalbuminemia was associated with increased odds of a 30-day complication (OR 2.49, 95% CI 1.06-5.86, p=0.036). Hypoalbuminemia was associated with increased odds of short-term complications after surgical management of RUF.


Neurophysiologic control of lower urinary tract.
Current concepts in neurophysiology are discussed, with emphasis on neurotransmitters and electrodiagnosis. Specific neuronal mechanisms governing urine storage and expulsion are presented followed by clinical considerations of various neuronal dysfunctions.


Characteristics of lip-mouth region in smiling position from 80 persons with acceptable faces and individual normal occlusions.
The characteristics of lip-mouth region including the soft and hard tissues in smiling position with frontal fixed position photographic computer-aided analysis were studied. The subjects were 80 persons (40 male and 40 females, age range: 17 to approximately 25 years) with acceptable faces and individual normal occlusions. The subjects were asked to take maximum smiling position to accept photographic measurement with computer-aided analysis. The maximum smile line could be divided into 3 categories: low smile line (16.25%), average smile line (68.75%), and high smile line (15%). The method adopting maximum smiling position to study the lip-month region is reproducible and comparable. This study would be helpful to provide a quantitative reference for clinical investigation, diagnosis, treatment and efficacy appraisal.


Disconnection of the ventilatory system does not prevent pleural lesions during sternotomy.
In previous studies pleurotomy has seldom been reported as a complication of sternotomy and, therefore, the incidence is unknown. Factors increasing or decreasing the risk of pleurotomy also have not been studied properly. In a prospective, randomized trial, performed during 14 consecutive months from 1988 until 1989, the incidence of pleurotomy and its possible risk factors were studied in 712 patients undergoing median sternotomy for cardiac and mediastinal procedures. The overall incidence of pleurotomy was 14.7%. Chronic obstructive pulmonary disease, the use of positive end-expiratory pressure, and continuation or discontinuation of the ventilatory system did not affect the incidence. A surgeon-related risk factor could be significantly identified (P < 0.001). In conclusion, disconnection of the ventilatory system during sternotomy has been shown to have no influence on the pleurotomy rate and its continued use is no longer valid.


Comparison of clinicopathological features and prognostic significance between synchronous multiple primary and solitary esophageal squamous cell carcinomas.
Synchronous multiple primary esophageal squamous cell carcinoma (S-MPESCC) refers to more than one primary esophageal carcinoma detected in a solitary patient at the time of initial presentation. The purpose of this study was to evaluate the clinicopathological features, appropriate surgical approaches and long-term survival in patients with S-MPESCC by comparing with those with solitary esophageal squamous cell carcinoma (SESCC). In total, 567 patients with esophageal squamous cell carcinoma surgically resected in Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2018 were screened for retrospective analysis (50 in the S-MPESCC group and 516 in the SESCC group). No significant difference was observed in terms of other characteristics except total alcohol consumption (P = 0.029). S-MPESCC had higher lymph node rate than SESCC (62.0% and 44.1%, respectively; P = 0.015) especially in upper mediastinal (32.0% and 18.6%, respectively; P = 0.023) and abdominal (38.0% and 22.8%, respectively; P = 0.017) regions. The survival was not different between the two groups, and the 5-year survival rates of S-MPESCC and SESCC were 46.2% and 50.8%, respectively (P = 0.507). But for patients with pT3-4 cancers, the survival in S-MPESCC was worse than that in SESCC (P = 0.033). In the multivariate analysis, pT stage of primary cancer was an important independent predictor of prognosis in patients with S-MPESCC (hazard ratio [HR], 3.968; 95% confidence interval [CI], 1.031 to 15.268; P = 0.045). S-MPESCC was significantly different from SESCC in terms of clinicopathological characteristics include alcohol intake and pattern of lymphatic metastasis. Furthermore, S-MPESCC showed worse long-term survival than SESCC with increasing depth of primary cancer infiltration.


A new approach to optimal control of conductance-based spiking neurons.
This paper presents an algorithm for solving the minimum-energy optimal control problem of conductance-based spiking neurons. The basic procedure is (1) to construct a conductance-based spiking neuron oscillator as an affine nonlinear system, (2) to formulate the optimal control problem of the affine nonlinear system as a boundary value problem based on Pontryagin's maximum principle, and (3) to solve the boundary value problem using the homotopy perturbation method. The construction of the minimum-energy optimal control in the framework of the homotopy perturbation technique is novel and valid for a broad class of nonlinear conductance-based neuron models. The applicability of our method in the FitzHugh-Nagumo and Hindmarsh-Rose models is validated by simulations.


Experiences of elderly patients regarding participation in their hospital discharge: a qualitative metasummary.
Ageing patients are discharged from the hospital 'quicker and sicker' than before, and hospital discharge is a critical step in patient care. Older patients form a particularly vulnerable group due to multimorbidity and frailty. Patient participation in healthcare is influenced by government policy and an important part of quality improvement of care. There is need for greater insights into the complexity of patient participation for older patients in discharge processes based on aggregated knowledge. The aim of this study was to review reported evidence concerning the experiences of older patients aged 65 years and above regarding their participation in the hospital discharge process. We conducted a qualitative metasummary. Systematic searches of Medline, Embase, Cinahl, PsycINFO and SocINDEX were conducted. Data from 18 studies were included, based on specific selection criteria. All studies explored older patients' experience of participation during the discharge process in hospital, but varied when it came to type of discharge and diagnosis. The data were categorised into themes by using thematic analysis. Our analysis indicated that participation in the discharge process varied among elderly patients. Five themes were identified: (1) complexity of the patients state of health, (2) management and hospital routines, (3) the norm and preference of returning home, (4) challenges of mutual communication and asymmetric relationships and (5) the significance of networks. Collaboration between different levels in the health systems and user-friendly information between staff, patient and families are crucial. The complexity of patient participation for this patient group should be recognised to enhance user involvement during discharge from hospital. Interventions or follow-up studies of how healthcare professionals can improve their communication skills and address the tension between client-centred goals and organisational priorities are requested. Organisational structure may need to be restructured to ensure the participation of elderly patients.


A new lignan glycoside from the rhizomes of Imperata cylindrica.
A new lignan glycoside, 6-acetyl-1-[1,3-(4,4'-dihydroxy-3,3'-dimethoxy-beta-truxinyl)-beta-d-fructofuranosyl]-alpha-d-glucopyranoside (1), named impecyloside, was isolated from the rhizomes of Imperata cylindrica. The structure of the compound was determined by spectroscopic data including FABMS, UV, IR, 1H NMR and 13C NMR (DEPT) and 2D NMR (COSY, HSQC, HMBC).


Concentration and total number of circulating primordial germ cells in Green-legged Partridgelike chicken embryos.
The Green-legged Partridgelike fowl is an old Polish indigenous breed of chicken. Primordial germ cells (PGCs) are one of the best sources of precursor cells that can be used for the conservation and proliferation of the endangered breeds of bird. Initially, the chicken PGCs colonize at the anterior extraembryonic region called "germinal crescent," and after the establishment of blood vascular circulation, they temporally circulate via the embryonic blood vascular system along with embryonic blood cells. They further colonize at the microcapillary networks of both right and left future gonadal regions. Subsequently, they migrate interstitially to reach gonadal anlages, where they begin to differentiate and eventually develop into the future ova or sperm. The basic knowledge regarding the concentration and the total number of circulating PGCs (cPGCs) throughout their circulating phase in the early embryonic stages is crucial for providing an insight into the mechanisms by which they circulate and colonize at the capillary networks of left and right future gonadal regions in each developmental stage. The present study aims to determine the most efficient developmental stage that is suitable to collect cPGCs. The concentration of cPGCs was directly measured, and total volume of embryonic blood was calculated based on the concentration of PKH26-stained embryonic blood cells which were injected 10 min before the blood sampling process in the same embryo during each stage of embryonic development from stage 13 Hamburger and Hamilton (HH; Hamburger and Hamilton, 1951) to 16 HH. Analysis of whole embryonic bloodstream revealed that at stage 14 HH of embryonic development, peak total number of cPGCs (386.3 cells/μL) and peak concentration of cPGCs (18.6 cells/μL) were observed. Later, there was a decrease in concentration, suggesting that the cPGCs might be trapped gradually by the capillary networks at the future gonadal regions after stage 15 HH.


The Multi-Cover Persistence of Euclidean Balls.
Given a locally finite X ⊆ R d and a radius r ≥ 0 , the k-fold cover of X and r consists of all points in R d that have k or more points of X within distance r. We consider two filtrations-one in scale obtained by fixing k and increasing r, and the other in depth obtained by fixing r and decreasing k-and we compute the persistence diagrams of both. While standard methods suffice for the filtration in scale, we need novel geometric and topological concepts for the filtration in depth. In particular, we introduce a rhomboid tiling in R d + 1 whose horizontal integer slices are the order-k Delaunay mosaics of X, and construct a zigzag module of Delaunay mosaics that is isomorphic to the persistence module of the multi-covers.


Cow culling patterns in eight commercial Estonian dairy herds and farmers' behaviour in reporting culling reasons.
The present study aimed to reveal the culling-related metrics, identify the culling reason patterns for cows by developing and implementing the cow culling form (CCF), and analyse the concordance of farmers' stated culling reasons with those identified based on the CCF. A CCF was developed to register the disease history and conditions of cows that were related to culling. CCFs were completed by farm managers and veterinarians in eight dairy herds over a one-year period for slaughtered (n = 686) and dead (n = 250) cows. Completed CCFs were interpreted by the study authors to identify underlying, intermediate, influential, and immediate culling reasons. The identified culling reasons were compared to those reported by producers. The mean annual cow culling rate of the study farms was 31.8%, and the average on-farm mortality was 9.3%. Of the 250 cows that died on the farms, 43.6% were euthanised. Only 2% of the cows were slaughtered due to low milk yield. In total, 260 and 119 unique three-reason culling codes were created for slaughtered and dead cows, respectively. Single disease or condition causing slaughter or death of cows was identified in 44.8% and 52.0% of the cases, respectively. Producers' reported culling reasons concurred with the underlying culling reason in 72.6% and 63.6% of slaughtered and dead cows, respectively. A high variety of agreements between the farmers' reported and CCF-based culling codes was identified across single culling reasons. Improved registration of culling reasons is required to support informed herd-based decisions.


Quantifying the contribution of local drivers to observed weakening of spring dust storm frequency over northern China (1982-2017).
Recent studies have suggested that spring dust storm (SDS) events in northern China (NC) have exhibited substantial decline over the past 30 years. However, it is unclear which local factors are most responsible for the decline in SDS events, and the contribution of each dominant factor remains to be determined. This study utilized high-density DS records and collocated homogenized surface meteorological observations from 1982 to 2017, in conjunction with land surface products, to examine the local drivers that influence the long-term variation in SDS frequency (SDSF) over the entire NC area and its three dust-source areas: northwestern China (NWC), north-central China (NCC), and northeastern China (NEC). Results indicated that the observed SDSF averaged over NC, NWC, NCC, and NEC has decreased by 144.4 %, 109.3 %, 166.4 %, and 92.2 %, respectively, during 1982-2017. The variation in SDSF is largely explained by variation in wind speed (WS), precipitation, volumetric soil moisture, and surface bareness. A multivariable linear regression model incorporating these local drivers accounted for 81.0 %, 74.0 %, and 46.9 % of the variance in SDSF in NWC, NCC, and NEC, respectively. Statistical analyses on the local drivers suggested that weakening of WS was the dominant factor in the reduction in SDSF over recent decades, contributing 76.9 %, 54.7 %, and 33.6 % of the variation in NWC, NCC, and NEC, respectively. More importantly, we revealed that the interannual variation in regional SDSF was not only controlled by local drivers, but also influenced by cross-regional transport of dust aerosols emitted from upstream source areas.


Active management of labor and operative delivery in nulliparous women.
There has been a fourfold increase in cesarean births in Canada in the last 20 years. The two main indications are dystocia and repeat cesarean section. Of all primary cesarean sections, about half are due to dystocia. This is largely confined to nulliparous women. Work from Ireland suggests that a policy of active management of labor may reduce dystocia. This involves a uniform policy of amniotomy once a diagnosis of labor is established, followed by oxytocin augmentation if labor is nonprogressive (less than 1 cm/hr). From October 1, 1985, to December 31, 1986, this policy was carried out on 552 consecutive normal nulliparous women in spontaneous labor at greater than or equal to 37 weeks' gestation with a single fetus in vertex presentation with no fetal distress. These results were compared with a control group of 533 similar nulliparous women delivered between January 1, 1984 and March 31, 1985. The cesarean section rate dropped to 4.3% from 13% (p less than 0.005) and the forceps delivery rate dropped to 19.4% from 29% (p less than 0.005). The duration of labor greater than 12 hours dropped to 7% from 20% (p less than 0.005). There was no increase in fetal morbidity or mortality.


Principles and recommendations for incorporating estimands into clinical study protocol templates.
Clinical study protocols are the foundation of good clinical studies. Prospective and multidisciplinary collaboration that pays attention to the design of all components of the study protocol can ensure that a clinical study will answer the research questions posed in a reliable manner that is meaningful for decision-makers and patients. The ICH E9(R1) addendum on estimands and sensitivity analysis in clinical trials provides a framework for clinical study planning to ensure alignment between study objectives, design, conduct, and analysis. The estimand or clinical question posed can be regarded as the backbone of the study and the clinical study protocol should reflect estimands accordingly. In practice, stakeholders are still learning how to embrace the estimand framework and how it impacts studies and study documents. In this paper, we anticipate that a protocol structure centred around estimands, or objectives rather than endpoints alone will prevail for all types of studies. To assist sponsors during this paradigm shift, this paper provides discussion and guidance for implementing the estimand framework in protocol templates.