Matrix metalloproteinase 2 may be a marker of microangiopathy in children and adolescents with type 1 diabetes mellitus.
Matrix metalloproteinases (MMPs) 2 and 9 are responsible for extracellular matrix breakdown and their abnormal circulating levels may pre-date clinical evidence of diabetic angiopathy. We detected by ELISA, plasma MMP-2 and MMP-9 levels and associated activity in 25 children and adolescents with T1DM. Thirteen male and 12 female patients were evaluated at the clinical diagnosis and onset of T1DM and again at a 5-year follow-up. Twelve patients had developed microangiopathic complications at the follow-up evaluation. MMP-2 and MMP-9 levels and activity were detected in samples obtained at T1DM diagnosis and at the 5-year follow-up. As controls, 19 healthy subjects who were the same age as the patients were also evaluated at baseline and again after 5 years. MMP-2 levels and activity were significantly higher in the patients than in the controls at disease onset. This was particularly evident when patients who developed microangiopathic complications were compared to controls and patients without complications. At the 5-year follow-up, a significant increase in MMP-2 levels and a significant decrease in MMP-2 activity were found only in the control group compared to the baseline levels. MMP-2 levels and activity were higher in patients with microangiopathy. MMP-9 levels and activity were increased in all groups compared to baseline levels. MMP-9 levels were lower in patients with microangiopathy compared to controls, but no difference was found between the two patient groups. It is well known that MMP-9 is an index of the severity and stability of macroangiopathy while our results allow us to postulate that MMP-2 may be a marker of microangiopathy.


Structural Adaptation of the Excitation-Contraction Coupling Apparatus in Calsequestrin1-Null Mice during Postnatal Development.
The precise arrangement and peculiar interaction of transverse tubule (T-tubule) and sarcoplasmic reticulum (SR) membranes efficiently guarantee adequate contractile properties of skeletal muscle fibers. Fast muscle fibers from mice lacking calsequestrin 1 (CASQ1) are characterized by the profound ultrastructural remodeling of T-tubule/SR junctions. This study investigates the role of CASQ1, an essential component of calcium release units (CRUs), in the postnatal development of muscle fibers. By using CASQ1-knockout mice, we examined the maturation of CRUs and the involvement of different junctional proteins in the juxtaposition of the membrane system. Our morphological investigation of both wild-type (WT) and CASQ1-null extensor digitorum longus (EDL) fibers, from 1 week to 4 months of age, yielded noteworthy findings. Firstly, we observed that the absence of CASQ1 hindered the full maturation of CRUs, despite the correct localization of key junctional components (ryanodine receptor, dihydropyridine receptor, and triadin) to the junctional SR in adult animals. Furthermore, analysis of protein expression profiles related to T-tubule biogenesis and organization (junctophilin 1, amphiphysin 2, caveolin 3, and mitsugumin 29) demonstrated delayed progression in their expression during postnatal development in the absence of CASQ1, suggesting the impaired maturation of CRUs. The absence of CASQ1 directly impacts the proper assembly of CRUs during development and influences the expression and coordination of other proteins involved in T-tubule biogenesis and organization.


"I was gonna ask you": How patients use agency framing to display engagement in primary care.
The message that patients should be responsible for their health is pervasive. Health promotion campaigns encourage patients to "ask your doctor" about potential illnesses and treatments, preventive medicine guidelines call for patients to self-monitor to avoid future health problems, and models like shared decision-making advocate for greater patient involvement in medical decisions. Research shows that patients can participate in medical dialogue by asking questions, but that doing so is difficult due to the structure and social norms of medical visits. In this article, we ask: how can patients participate more actively in medical care? Drawing on video recordings of older patients (aged 65 and older) and primary care physicians, we use conversation analysis to describe one practice that patients use to demonstrate personal responsibility for their health; agency framing. This involves prefacing questions to the doctor with phrases that project a prior intended action, such as "I was gonna ask you", "I was gonna tell you" or "I wanted to ask you". Patients use agency framing to cast their questions as 1) independently motivated, 2) well-informed, and 3) personally responsible. Consequently, patients exert agency within the confines of the medical visit structure to resist the potential interpretation that their question was responsive to the doctor or to the local interactional context. Rather, agency framing allows patients to show that their question was considered independently. Questions designed with agency framing work to portray the speaker as a responsible patient who is not only meeting the bare minimum of expected health maintenance, but is staying ahead of medical problems. This article discusses the particular importance of this practice among older patients, for whom demonstrating a willingness and ability to cope with medical problems may be significant for maintaining independence.


A review on the lignocellulosic derived biochar-based catalyst in wastewater remediation: Advanced treatment technologies and machine learning tools.
Wastewater disposal in the ecosystem affects aquatic and human life, which necessitates the removal of the contaminants. Eliminating wastewater contaminants using biochar produced through the thermal decomposition of lignocellulosic biomass (LCB) is sustainable. Due to its high specific surface area, porous structure, oxygen functional groups, and low cost, biochar has emerged as an alternate contender in catalysis. Various innovative advanced technologies were combined with biochar for effective wastewater treatment. This review examines the use of LCB for the synthesis of biochar along with its activation methods. It also elaborates on using advanced biochar-based technologies in wastewater treatment and the mechanism for forming oxidizing species. The research also highlights the use of machine learning in pollutant removal and identifies the obstacles of biochar-based catalysts in both real-time and cutting-edge technologies. Probable and restrictions for further exploration are discussed.


Consistent and reproducible staining of glia by a modified Golgi-Cox method.
Golgi-Cox staining is a powerful histochemical approach which has been used extensively to visualize the morphology of neurons and glia. However, its usage as a first-choice method is hindered by its uncertain nature, diminished consistency and lengthy staining duration. The FD Rapid GolgiStain™ Kit (FD Neurotechnologies, Inc., USA) has been developed by employing the Golgi-Cox approach. It is a simple, reliable and reproducible way of performing Golgi impregnation for the analysis of neuronal morphology. We report here simple modifications to the manufacturer's protocol which enable reproducible and reliable staining of glial cells. Exposure of brain tissue to 4% paraformaldehyde (PFA) during perfusion followed by postfixation with 8% glutaraldehyde in 4% PFA led to only glial cells being stained, whereas in the absence of postfixation both neurons and glia were stained with unclear morphology. Additionally, we found that impregnation at 26°C±1 was critical to attain uniform staining. Our modified Golgi-Cox approach is consistent and reproducible and affords uniform glial staining throughout the brain. As this protocol stains only a small percentage of cells, it is suitable for the analysis of individual cells.


Artificial syndactylisation for congenital crossed toes.
Congenital crossed toe is a common deformity which frequently causes disability. The fifth toe is affected and over-rides the fourth toe. Correction is carried out to relieve pain caused by pressure and to improve appearance. Methods of correction range from conservative manipulation and splintage to radical amputation. The method of syndactylisation is a plastic procedure which is simple, safe and reliable.


Characterization of [3H](+/-)L-364,718 binding to solubilized cholecystokinin (CCK) receptors of rat pancreas.
The binding of [3H](+/-)L-364,718 (3S(-)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepine-3-yl )-1H-indole-2-carboxamide), an extremely potent nonpeptide cholecystokinin (CCK) receptor antagonist, to digitonin-solubilized CCK receptors from rat pancreas was characterized. [3H](+/-)L-364,718 binding to digitonin-solubilized receptors was assayed using polyethylene glycol precipitation followed by rapid filtration to separate free and bound [3H](+/-)L-364,718. Specific [3H](+/-)L-364,718 binding to solubilized receptors was dependent on the digitonin and receptor concentration and, under optimal conditions, represented greater than 90% of the total binding. Scatchard analysis indicated a single class of binding sites with a Kd of 0.53 nM and a Bmax of 3.1 pmol/mg protein. Specific [3H](+/-)L-364,718 binding to solubilized CCK receptors was inhibited by both CCK receptor agonists and antagonists in a stereospecific manner. After solubilization, the affinities of various antagonists to displace specific [3H](+/-)L-364,718 binding were similar to those obtained with membrane-bound receptors; however, the affinities of CCK agonists were reduced 10-100 times. Collectively, the data presented indicate that [3H](+/-)L-364,718 represents a new antagonist ligand which has apparent advantages over the agonist ligand [125I]CCK in assaying digitonin-solubilized receptors. Gel filtration of the digitonin-solubilized CCK receptors followed by [3H](+/-)L-364,718 binding determinations revealed an estimated molecular weight of 400,000 daltons.


Control of the rubber anthracnose fungus Colletotrichum gloeosporioides using culture filtrate extract from Streptomyces deccanensis QY-3.
Colletotrichum gloeosporioides is a main cause of rubber anthracnose, which results in a huge loss for the natural rubber industry. In this study, an actinomycete strain QY-3 was isolated and had good antagonistic activity against C. gloeosporioides with an inhibition rate of 86.6%. Strain QY-3 was identified as Streptomyces deccanensis preliminarily. Millet medium was selected as the optimal fermentation broth for antifungal metabolites production by S. deccanensis QY-3. The culture filtrate extract (CFE) from the millet broth of S. deccanensis QY-3 exhibits broad-spectrum antifungal activity against plant pathogenic fungi, and its EC50 inhibiting the mycelial growth of C. gloeosporioides is 6.3 μg/mL. The CFE has good thermal and pH stabilities, and it can break the hyphae and inhibit the conidial germination of C. gloeosporioides. 100 μg/mL of CFE had an obvious control effect on rubber anthracnose, and the control efficacy was 63.7% on 5 days after inoculation. Two compounds with inhibitory effects on C. gloeosporioides, anthranilic acid and sangivamycin, were isolated from the CFE. The MICs of both compounds against C. gloeosporioides were 29.3 and 23.0 μg/mL respectively. In conclusion, the CFE from S. deccanensis QY-3 has great potential to be a promising fungicide for rubber anthracnose.


Signaling Pathways in Pregnancy.
We are pleased to present this Special Issue of Cells, entitled 'Signaling Pathways in Pregnancy' [...].


Effect of short term aerobic exercise on fasting and postprandial lipoprotein subfractions in healthy sedentary men.
Our goal was to investigate the effect of short term exercise on fasting and postprandial lipoprotein profile. Healthy sedentary men exercised 20 min for four days. The intensity of exercise was modulated to maintain 75-80 % of a calculated HRmax. Before and after the exercise program, fasting and postprandial (4 h after standard meal) concentrations of lipoprotein subfractions were measured by an electrophoresis in polyacrylamide gel and total concentrations of TAG, LDL and HDL by enzymatic colorimetric method. After 2 days of rest, fasting and postprandial concentrations of lipoprotein fractions and subfractions were measured to determine a persistency of a changes in the lipoprotein profile. 4 days of physical exercise led to statistically significant decrease of concentration of triacylglycerol in fasting (76.29 ± 20.07, 53.92 ± 10.90, p < 0.05) and postprandial state (139.06 ± 23.72, 96.55 ± 25.21, p < 0.05) VLDL in fasting (21.88 ± 3.87, 18.00 ± 3.93, p < 0.05) and postprandial state (23.88 ± 3.52, 19.25 ± 3.62, p < 0.05), total cholesterol in fasting (162.26 ± 23.38, 148.91 ± 17.72, p < 0.05) and postprandial state (163.73 ± 23.02, 150.08 ± 18.11, p < 0.05). Atherogenic medium LDL decreased also in fasting (9.89 ± 3.27, 6.22 ± 2.55, p < 0.001) and postprandial state (8.88 ± 6.51, 6.88 ± 5.57, p < 0.001). However decrease of large IDL (25.38 ± 3.54, 23.88 ± 3.91, p < 0.05) and large LDL particles (42.89 ± 11.40, 38.67 ± 9.30) was observed only in postprandial state. Total HDL concentration remained unchanged but we observed statistically significant decrease of small HDL particles in fasting (6.11 ± 2.89, 4.22, p < 0.05) and postprandial state (6.44 ± 3.21, 4.56 ± 1.33, p < 0.05). Concentration of these particles are associated with progression of atherosclerosis. All changes of fasting and postprandial lipoprotein profile disappeared after 2 days of rest. Just 4 daily settings of 20 min of physical exercise can lead to significant positive changes of fasting and postprandial lipoprotein profile.


HPV vaccination in Japan: results of a 3-year follow-up survey of obstetricians and gynecologists regarding their opinions toward the vaccine.
In Japan, the cervical cancer preventative HPV vaccination rate has dramatically declined, directly as a result of repeated broadcasts of so-called adverse events and the resulting suspension of the government's recommendation. Our previous survey of obstetricians and gynecologists in Japan regarding their opinions toward HPV vaccination revealed that these key specialists were as negatively influenced by the reports of purported negative events as were the general population. Here, we report a 3-year follow-up survey of these clinicians. We reused the same questionnaire format as used in our 2014 survey, but added new questions concerning opinions regarding a WHO statement and reports of a Japanese nation-wide epidemiological study related to the adverse events, released in 2015 and 2016, respectively. The response rate was 46% (259/567): 5 (16.1%) of 31 doctors had inoculated their own teenaged daughters during the time period since the previous survey, despite the continued suspension of the governmental recommendation, whereas in the previous survey none of the doctors had done so. Among the respondents, the majority claimed awareness of the recent pro-vaccine WHO statement (66.5%), and of the report of a Japanese epidemiological study (71.5%), and a majority affirmed they currently held positive opinions of the safety (72.7%) and effectiveness (84.3%) of the HPV vaccine. Our re-survey of Japan's obstetricians and gynecologists regarding their opinions about the HPV vaccine found that their opinions have changed, potentially leading to a more positive future re-engagement for HPV vaccination in Japan.


The utility of PET/CT with (68)Ga-DOTATOC in sarcoidosis: comparison with (67)Ga-scintigraphy.
This study was designed to compare the clinical efficacy of (68)Ga-DOTA-Tyr-octreotide (DOTATOC)-positron emission tomography (PET)/computed tomography (CT) with that of conventional (67)Ga-scintigraphy (GS), and to correlate quantitative parameters on DOTATOC-PET/CT with clinical data, in patients with sarcoidosis. Twenty patients who were histologically and/or clinically diagnosed with sarcoidosis and underwent both DOTATOC-PET/CT and GS were analyzed in this study. The numbers of patients with positive findings for each organ were determined. The total numbers of involved nodal areas in the chest, as determined by DOTATOC-PET and gallium single-photon emission tomography (Ga-SPECT), were compared. The correlations between quantitative parameters on PET and clinical laboratory data were evaluated. DOTATOC-PET/CT was positive in 19 patients, being negative in only one patient with chronic inactive sarcoidosis, whereas GS was positive in 17 patients. DOTATOC-PET/CT visualized more lesions in lymph nodes, uvea, and muscles than did Ga-scintigraphy and identified more involved areas than did GS-SPECT (p < 0.0001). Whole-body active lesion volume showed a significant, but moderate correlation with angiotensin-converting enzyme level (ρ = 0.64, p = 0.0044). PET/CT with DOTATOC may be superior to conventional GS in detecting sarcoidosis lesions, especially in lymph nodes, uvea, and muscles. Volumetric parameters in DOTATOC-PET/CT may be helpful in estimating the activity of sarcoidosis.


Pharmacokinetics of ganciclovir in pediatric renal transplant recipients.
Ganciclovir (GCV) is effective in preventing and treating cytomegalovirus (CMV) infection in solid organ transplant recipients. The aims of the present study were to determine the pharmacokinetics of GCV administered intravenously (IV) and orally (p.o.) as pre-emptive anti-CMV therapy in pediatric renal transplant recipients and to monitor trough levels and side-effects during pre-emptive therapy. Eleven pediatric renal transplant recipients (aged 11.0+/-3.9 years) were included. The diagnosis of CMV infection, based on two positive pp-65 CMV blood antigen tests at 1 week apart, was made at 39+/-12 days post renal transplantation. They received IV GCV at a dose of 5.0+/-0.3 mg/kg per 12 h for 15 days, followed by GCV p.o. at a dose of 46.7+/-8.2 mg/kg per 12 h for 3 months. Pharmacokinetics (PK) were studied at steady state and GCV plasma concentrations were measured by high-performance liquid chromatography. After IV GCV administration, PK parameters were: C(0)=0.84+/-0.66 microg/ml; C(max)=11.77+/-2.82 microg/ml; AUC(0-12 h)=42.29+/-17.57 microg/ml per hour; Cl=0.13+/-0.05 l/h per kg. After p.o. GCV administration, PK parameters were: C(0)=1.08+/-0.68 microg/ml; C(max)=2.70+/-1.07 microg/ml; AUC(0-12 h)=18.97+/-9.36 microg/ml per hour; Cl/F=2.97+/-1.42 l/h per kg. Bioavailability (F) was 4.9+/-1.2%. Pre-dose concentrations (C(0)) measured under p.o. GCV (n=51) were 1.29+/-0.80 microg/ml (8 C(0) values were below 0.5 microg/ml). Pp-65 CMV blood antigen tests became negative after 16+/-11 days of treatment. GCV was well tolerated. Because of the limited bioavailability, the recommended high doses of p.o. GCV (50 mg/kg per 12 h) were administered and were associated with trough levels over 0.5 microg/ml. In 1 patient who received an erroneously low dosage p.o., CMV resistance to GCV appeared, requiring foscarnet.


The unrecognized effects of the volume and composition of the resuscitation fluid used during the administration of blood products.
Recent publications have reported the severe adverse events associated with blood products but have not considered the effect of the volume and composition of the resuscitative fluids infused with the blood products. Injury leads to cellular reaction characterized by insulin resistance during which glucose cannot enter muscle and fat cells. In all cells, mitochondrial pyruvate dehydrogenase activity is decreased during insulin deficiency leaving cells deficient in substrates needed to power the Krebs cycle and make ATP. d-β-Hydroxybutyrate, a normal ketone body metabolite, enters cells on the monocarboxylate transport mimicking the action of insulin and bypassing the enzymatic block at PDH. Metabolism of ketone bodies increases efficiency of mitochondrial energy production and cellular ATP level. Infusion of 250 ml of 600 mM Na d-β-hydroxybutyrate solution, with the same osmotic strength as the hypertonic NaCl solution currently being used, would correct insulin resistance, provide energy substrates for cells to produce ATP, correct the tendency of injured tissue to swell due to decreased energy of ionic gradients and correct acidosis observed in hemorrhage.


Helminth parasites of beef cattle in the East Kimberley and Victoria River Districts of Northern Australia.
An investigation into the helminth species present in cattle in the East Kimberley and Victoria River Districts of Northern Australia was conducted over a 2-year period based on bi-monthly total and differential worm counts in weaner cattle as well as on a post mortem survey of adult cattle sent for slaughter. The most important species found in young cattle were Haemonchus placei and Cooperia spp. Only small numbers of Bunostomum phlebotomum, Nematodirus spathiger, Oesophagostomum radiatum and Moniezia benedini were present. Calicophoron calicophorum and nodules of Onchocerca spp. and Oe. radiatum were recorded in adult cattle. Seasonal fluctuations in helminth parasite burdens are discussed in relation to temperature and rainfall and the results are interpreted in relation to the effects of helminthosis on present and future beef production in this area.


Key internal factors leading to the variability in CO2 fixation efficiency of different sulfur-oxidizing bacteria during autotrophic cultivation.
Variability in the apparent CO2 fixation yield of four aerobic sulfur-oxidizing bacteria (Halothiobacillus neapolitanus DSM 15147, Thiobacillus thioparus DSM 505, Thiomonas intermedia DSM 18155, and Starkeya novella DSM 506) in autotrophic culturing was studied, and mutual effects of key intrinsic factors on CO2 fixation were explored. DSM 15147 and DSM 505 exhibited much higher CO2 fixation yields than DSM 18155 and DSM 506. The differences in CO2 fixation yield were determined not only by cbb gene transcription, but also by cell synthesis rate, which was determined by rRNA gene copy number; the rRNA gene copy number had a more significant effect than cbb gene transcription on the apparent CO2 fixation yield. Moreover, accumulation of EDOC was observed in all four strains during chemoautotrophic cultivation, and the proportion of EDOC accounting for total fixed organic carbon (TOC; EDOC/TOC ratio) was much higher in DSM 18155 and DSM 506 than in DSM 15147 and DSM 505. The accumulation of EDOC led to a significant decrease in the cbb gene transcription efficiency during cultivation, and a further feedback inhibitory effect on CO2 fixation.


Comparison of different EEG features in estimation of hypnosis susceptibility level.
Hypnosis has long been known to be associated with heightened control over physical processes and researchers put it under consideration because of its usage as a therapeutic tool in many medical and psychological problems. Determination of hypnosis susceptibility level is important before prescribing any hypnotic treatment. In this study different features are introduced to classify hypnotizability levels. These features were extracted from electroencephalogram (EEG) signals which were recorded from 32 subjects during hypnosis suggestion. Based on the obtained result, a method was suggested to estimate the hypnosis susceptibility level from hypnosis EEG signals instead of using traditional clinical subjective tests.


Monoclonal antibodies to leucine enkephalin.
Monoclonal antibodies to leucine enkephalin have been produced after fusion of mouse myeloma cells with spleen cells from hyper-immune mice. Hybrid clones 2D1 and SL1 were characterised using radioimmunoassay and an enzyme-linked immunosorbent assay. The antibody 2D1 was of low affinity and showed a maximum sensitivity of 0.1ng. The antibody binds equally well to the sulphated leucine enkephalin and to methionine enkephalin. It does not cross-react with dynorphin, methionine enkephalin-arg-phe or oxidised methionine enkephalin. The hybrid clone SL1 appears to be specific for leucine enkephalin. Preliminary immunocytochemical studies have shown that both antibodies bind specifically to leucine enkephalin in defined areas of the central nervous system.


Pathobiological behavior and molecular mechanism of signet ring cell carcinoma and mucinous adenocarcinoma of the stomach: a comparative study.
To elucidate the distinctive pathobiological behavior between signet ring cell carcinoma (SRC) and mucinous adenocarcinoma of the stomach. Based on the histological growth patterns and cell-functional differentiation classifications of stomach carcinoma, we conducted a series of comparative studies. All paraffin-embedded and frozen blocks were collected from the files of Cancer Institute of China Medical University. On the basis of histopathological observation, we applied enzymatic and mucous histochemistry, immunohistochemistry, flow cytometry (FCM) and molecular biology to compare these two categories of gastric cancers in terms of the DNA ploidy, proliferative kinetics, the expression of gastric carcinoma associated gene product and instabilities of mitochondrial DNA (mtDNA). Gastric SRC was commonly seen in females below 45 years, mostly presenting diffuse growth and ovary or uterine cervix metastasis. The majority of SRC were absorptive and mucus-producing functional differentiation type (AMPFDT), which growth relied on estrogen. Meanwhile, stomach mucinous adenocarcinomas were mostly observed in males over 50 years, prone to massive growth or nest growth and extensive peritoneal infiltration, showing two categories of cell-functional differentiation types: AMPFDT and mucus-secreting functional differentiation type (MSFDT). Expressions of ER, enzyme c-PDE and 67kDaLN-R in SRC were evidently higher than that in mucinous adenocarcinoma, while expressions of LN, CN-IV, CD44v6, and PTEN protein were obviously lower in SRC than that in mucinous adenocarcinoma (P<0.05). There was no statistic significance in VEGF, ECD and instabilities of mtDNA (P>0.05) between the above two gastric carcinomas. Though SRC and mucinous adenocarcinoma were both characterized by abundant mucus-secretion, they were quite different in morphology, ultrastructure, cell-functional differentiation and protein expression, indicating different mechanisms of carcinogenesis. We concluded that combining histological growth patterns, cell-functional differentiation type with tumor related markers might be significant in early diagnosis and prognosis assessment for SRC and mucinous adenocarcinoma of the stomach.


Ureteral blockage by Candida in a patient with urinary derivation type Camey.
A study of ureteral blockage by Candida in a patient suffering from urinary derivation is presented. It has been favourably resolved by medical treatment and nephrostomy. The increasing medical importance of urinary infections by fungi, especially in weak patients and catheter carriers, makes it important to employ more aggressive treatment. Regarding urinary derivation and Candida infection, in the case of urinary blockage the possibility must be considered that blockage may be due to fungi, since it can be successfully treated medically without the need of surgery.


Longer Time Interval from Neoadjuvant Chemoradiation to Surgery is Associated with Poor Survival for Patients Without Clinical Complete Response in Oesophageal Cancer.
The optimal interval between neoadjuvant therapy and oesophagectomy for oesophageal cancer remains controversial. Patients with locally advanced oesophageal squamous cell carcinoma (ESCC) who received neoadjuvant chemoradiotherapy followed by oesophagectomy between June 2017 and December 2020 were prospectively enrolled and retrospectively analysed. Patients were divided into two groups: timely (group A; < 10 weeks) and delayed (group B; ≥ 10 weeks) surgery groups. Survival was the primary outcome, and tumour response and post-operative complications were the secondary outcomes. Overall, 224 patients were recruited; 116 patients (51.8%) underwent timely surgery within 10 weeks (group A), and 108 patients (49.2%) underwent delayed surgery over 10 weeks (group B) after chemoradiotherapy. In patients with clinical complete response (cCR), two groups had no significant difference of survival benefit (P = 0.618). However, in patients without cCR, delayed surgery was associated with poor survival (P = 0.035) and cancer progression (P = 0.036). A total of 40 patients (34.5%) in group A and 54 patients (50.0%) in group B achieved pCR (P = 0.019). pCR rates were significantly different across the four groups and increased over time (P = 0.006). Patients with a prolonged time interval from neoadjuvant chemoradiation to surgery had higher pCR rates. For patients with cCR to neoadjuvant chemoradiation, the time interval to surgery can be safely prolonged for at least 10 weeks. However, for patients with non-cCR to neoadjuvant chemoradiation, delayed surgery is associated with poor survival, and surgery should be performed within 10 weeks of neoadjuvant chemoradiation.


Synergistic effects of detergents and organic solvents on protein refolding: control of aggregation and folding rates.
This paper presents the synergistic enhancement of the refolding yield of denatured and reduced lysozyme by using detergents as aggregation inhibitors and water-miscible organic cosolvents as modulators for the detergents. Adding only cetyltrimethylammonium bromide (CTAB) led to a slight increase in the refolding yield (up to 13%). Further addition of dimethylsulfoxide (DMSO) with CTAB drastically increased the refolding yield up to 35%, a value which was higher than the simple sum of the refolding yields in the presence of only CTAB or DMSO. The synergistic enhancement was also observed in the coexistence of other detergents, such as polyethylene glycol monooleyl ether (n = 50) and N-tetradecyl-N,N-dimethyl-3-ammonio-1-propanesulfonate, and cosolvents, such as N,N-dimethylformamide and N,N-dimethylacetamide. Experimental data and a kinetic analysis revealed the guideline for selecting a couple of additives; detergents which can adequately inhibit the aggregation of proteins by binding to hydrophobic surfaces of refolding intermediates should be employed as an aggregation inhibitor, and cosolvents which can properly prevent both protein-protein and protein-detergent interactions act as effective modulators for the aggregation inhibitor, resulting in a desirable balance between folding and aggregation rates.


Metabolism of 1-methyladenosine.
1-[methyl-8-14C] Adenosine was synthesized and its metabolic fate was determined in intact rat. It was found that approximately 57% of 1-[methyl-8-14C] adenosine administered iv was excreted unchanged in the urine and 33% of the excreted radioactivity in the urine was associated with the major metabolite 1-methyl-hypoxanthine and about 4.5% was associated with 1-methylinosine. Very little adenosine or N6-methyladenosine was formed. It is concluded that 1-methyladenosine is initially deaminated by adenosine deaminase to 1-methylinosine which is then cleaved by nucleoside phosphorylase to 1-methylhypoxanthine.


Behavioral and neural predictors of upcoming decisions.
Although it is widely known that brain regions such as the prefrontal cortex, the amygdala, and the ventral striatum play large roles in decision making, their precise contributions remain unclear. Here, we used functional magnetic resonance imaging and principles of reinforcement learning theory to investigate the relationship between current reinforcements and future decisions. In the experiment, subjects chose between high-risk (i.e., low probability of a large monetary reward) and low-risk (high probability of a small reward) decisions. For each subject, we estimated value functions that represented the degree to which reinforcements affected the value of decision options on the subsequent trial. Individual differences in value functions predicted not only trial-to-trial behavioral strategies, such as choosing high-risk decisions following high-risk rewards, but also the relationship between activity in prefrontal and subcortical regions during one trial and the decision made in the subsequent trial. These findings provide a novel link between behavior and neural activity by demonstrating that value functions are manifested both in adjustments in behavioral strategies and in the neural activity that accompanies those adjustments.


Nursing team's conceptions about the families of hospitalized children.
to describe nursing team care and discuss the nursing team's conception of companion families of hospitalized children. The study was based on the theoretical framework of Collière's theory of nursing care identity. this was a qualitative study with 14 members of a nursing team, conducted through an unstructured group interview. Thematic data analysis was employed. habitual and repair care was delegated to families, regardless of the child's clinical condition. the team's official discourse about the families of hospitalized children, as recommended by the literature, refers to the family's alterity and participation in care provision, with sights on discharge and defending family participation as beneficial to children. In practice, however, the nursing staff makes concessions about the presence of chaperoning families and delegates care. descrever os cuidados da equipe de enfermagem e discutir as concepções da equipe de enfermagem frente à família acompanhante da criança hospitalizada. O referencial teórico está vinculado à identidade do cuidado de enfermagem de Collière. Estudo qualitativo com quatorze membros da equipe de enfermagem, utilizando a técnica de entrevista não diretiva em grupo. Foi realizada análise temática dos dados. os cuidados habituais e de reparação prestados à criança estão sendo delegados à família, independentemente da situação clínica da criança. o discurso oficial da equipe de enfermagem frente à família acompanhante da criança hospitalizada, preconizado pela literatura, refere-se à alteridade e à participação da família nos cuidados à criança, prevendo sua alta e justificando a participação como benéfica para a criança. Em contrapartida, na prática, a enfermagem faz concessões sobre a permanência da família e delega os cuidados.


The ubiquitin ligase dTopors directs the nuclear organization of a chromatin insulator.
Chromatin insulators are gene regulatory elements implicated in the establishment of independent chromatin domains. The gypsy insulator of D. melanogaster confers its activity through a protein complex that consists of three known components, Su(Hw), Mod(mdg4)2.2, and CP190. We have identified a factor, Drosophila Topoisomerase I-interacting RS protein (dTopors) that interacts with the insulator protein complex and is required for gypsy insulator function. In the absence of Mod(mdg4)2.2, nuclear clustering of insulator complexes is disrupted and insulator activity is compromised. Overexpression of dTopors in the mod(mdg4)2.2 null mutant rescues insulator activity and restores the formation of nuclear insulator bodies. dTopors associates with the nuclear lamina, and mutations in lamin disrupt dTopors localization as well as nuclear organization and activity of the gypsy insulator. Thus, dTopors appears to be involved in the establishment of chromatin organization through its ability to mediate the association of insulator complexes with a fixed nuclear substrate.


Neuropathological lesions in the brains of goats in North-Western Nigeria: possible impact of artisanal mining.
Indiscriminate small-scale artisanal gold mining activities were reported to have caused anthropogenic heavy metal environmental pollution in Zamfara State, north-western Nigeria. There is little or no information on the neurotoxic effects and related neuropathological lesions due to environmental pollution in the animal population. Therefore, this work investigated the concentration of heavy metal and associated lesions in the brain of goats around an artisanal mining site in Zamfara. Brain samples were collected from 40 goats at slaughter slabs in Bagega (Zamfara State) while 15 goats with the same demography but without a history of environmental exposure at the time of this study served as controls. The concentration of lead and cadmium in brain tissue and histopathologic changes were assessed using atomic absorption spectrophotometry, histology and immunohistochemistry. The metal concentrations were significantly higher in exposed goats than in the unexposed animals. Cresyl violet staining and glial fibrillary acidic protein (GFAP) immunohistochemistry indicated chromatolysis and increased astrocytic activity respectively in the exposed goats. This study is of epidemiological importance as it shows a generalised increase of the metal concentrations in the brain of goats exposed to artisanal mining in Zamfara, north-western Nigeria. This could have health effects on the animals associated with nervous co-ordination, growth and development and as a good sentinel for pathogenesis of the heavy metal exposure.


Crystal structures of the N-terminal kinase domain of human RSK1 bound to three different ligands: Implications for the design of RSK1 specific inhibitors.
The p90 ribosomal S6 kinases (RSKs) also known as MAPKAP-Ks are serine/threonine protein kinases that are activated by ERK or PDK1 and act as downstream effectors of mitogen-activated protein kinase (MAPK). RSK1, a member of the RSK family, contains two distinct kinase domains in a single polypeptide chain, the regulatory C-terminal kinase domain (CTKD) and the catalytic N-terminal kinase domain (NTKD). Autophosphorylation of the CTKD leads to activation of the NTKD that subsequently phosphorylates downstream substrates. Here we report the crystal structures of the unactivated RSK1 NTKD bound to different ligands at 2.0 A resolution. The activation loop and helix alphaC, key regulatory elements of kinase function, are disordered. The DFG motif of the inactive RSK1 adopts an "active-like" conformation. The beta-PO(4) group in the AMP-PCP complex adopts a unique conformation that may contribute to inactivity of the enzyme. Structures of RSK1 ligand complexes offer insights into the design of novel anticancer agents and into the regulation of the catalytic activity of RSKs.


Simultaneous bilateral total knee arthroplasty has higher in-hospital complications than both staged surgeries: a nationwide propensity score matched analysis of 38,764 cases.
To investigate (1) healthcare utilization, (2) in-hospital metrics and (3) total in-hospital costs associated with simultaneous versus staged BTKA while evaluating staged BTKA as a single process consisting of two combined episodes. The national readmissions database was reviewed for simultaneous and staged (two primary unilateral TKAs12 months apart) BTKA patients (2016-2017). A total of 19,382 simultaneous BTKAs were identified, and propensity score matched (1:1) to staged BTKA patients (19,382 patients; 38,764 surgeries) based on demographics, comorbidities, and socioeconomic determinants. Outcomes included healthcare utilization [length of stay (LOS) and discharge disposition], in-hospital periprosthetic fractures, non-mechanical complications, and costs. Staged BTKA was evaluated as one process consisting of two episodes. For each staged patient, continuous outcomes were evaluated via the sum of both episodes. Categorical outcomes were added, and percents were expressed relative to total number of surgeries (n = 38,764). Simultaneous BTKA had longer LOS (5.0 days ± 4.7 vs. 4.5 days ± 3.5; p < 0.001), higher non-home discharge [36.9% (n = 7150/19,382) vs. 13.6% (n = 5451/38,764)], in-hospital periprosthetic fractures [0.13% (26/19,382) vs. 0.08% (31/38,764); p = 0.049], any non-mechanical complication [33.76% (6543/19,382) vs.15.93% (6177/38,764); p < 0.0001], hematoma/seroma formation [0.11% (22/19,382) vs. 0.05% (20/38,764); p = 0.0088], wound disruption [0.08% (16/19,382) vs. 0.04% (16/38,764); p = 0.0454], and any infection [1.13% (219/19,382) vs. 0.50% (194/38,764); p < 0.0001]. Average in-hospital costs for the two staged BTKA episodes combined were $5006 higher than those of simultaneous BTKA ($28,196 ± $18,488 vs. $33,202 ± $15,240; p < 0.001). Simultaneous BTKA had higher healthcare utilization and in-hospital complications than both episodes of staged BTKA combined, with a minimal in-hospital cost savings. Future studies are warranted to further explore patient selection who would benefit from BTKA.


Silibinin (Legalon-70) enhances the motility of human neutrophils immobilized by formyl-tripeptide, calcium ionophore, lymphokine and by normal human serum.
Experiments reported here were designed to investigate the effect of silibinin (extracted from Silybum marianum) on human polymorphonuclear leukocyte (PMN) motility and on leukocyte immobilizing activity of lymphokine (leukocyte inhibitory factor, LIF), formyl-Met-Leu-Phe (fMLP), calcium ionophore A-23187 and human sera inactivated by heat (HI-S). In the in vitro experiments, silibinin (1-10 micrograms/ml) failed to influence the random motility of unstimulated PMNS in agarose droplet assay, but enhanced the motility of the PMNs immobilized by fMLP, calcium ionophore, LIF or by autologous human sera. In the in vivo study, silibinin (Legalon-70) two hours after the administration was effective in enhancing spontaneous motility of leukocytes obtained from health volunteers which action could be regarded as a consequence of the decrease of leukocyte immobilizing activity being present in normal human plasma.


Arteriovenous fistula complicating an inferior gluteal artery perforator flap donor site.
We report the case of a 59-year-old woman who developed an arteriovenous fistula in her right buttock following a right inferior gluteal artery perforator flap for breast reconstruction.


The alkynyl moiety as a donor for donor-acceptor cyclopropanes.
The first trans-selective [3 + 2]-cycloaddition of a new type of donor-acceptor cyclopropane with aldehydes is presented. 2,2-Disubstituted cyclopropanes, bearing an alkyne moiety as the sole donor entity, were transformed to highly substituted tetrahydrofurans in the presence of a catalytic amount of Ca(NTf2)2/Bu4NPF6. The protocol allows for an easy access to tetrahydrofurans bearing a versatile alkyne substituent at the quarternary 2-position under very mild reaction conditions.


The less you see it, the faster it moves: shortening the "on-time" speeds up apparent motion.
The apparent motion (AM) created by two spots illuminated in alteration looks faster when there is dark temporal interval (ISI) between the offset of one spot and the onset of the other than when the spots are presented immediately after one another (no ISI), even though the temporal frequency and the spatial separation between spots are held constant. AMISI looks 18.6% faster than AMnoISI at temporal frequencies between 1.5 and 4.5 Hz. Reducing the duty cycle from 0.5 to 0.05 increases the apparent speedup to 30%. This difference in subjective speed is not due to differential saturation of velocity detectors, nor to the apparent spatial separation between spots, nor to differences in the time-averaged luminance of the stimuli. It is the "on-time", the time for which the spot is visible in one position, that determines the subjective speed. The longer the on-time, the slower the spot appears to move.


SUF12 suppressor protein of yeast. A fusion protein related to the EF-1 family of elongation factors.
Mutations at the suf12 locus were isolated in Saccharomyces cerevisiae as extragenic suppressors of +1 frameshift mutations in glycine (GGX) and proline (CCX) codons, as well as UGA and UAG nonsense mutations. To identify the SUF12 function in translation and to understand the relationship between suf12-mediated misreading and translational frameshifting, we have isolated an SUF12+ clone from a centromeric plasmid library by complementation. SUF12+ is an essential, single-copy gene that is identical with the omnipotent suppressor gene SUP35+. The 2.3 x 10(3) base SUF12+ transcript contains an open reading frame sufficient to encode a 88 x 10(3) Mr protein. The pattern of codon usage and transcript abundance suggests that SUF12+ is not a highly expressed gene. The linear SUF12 amino acid sequence suggests that SUF12 has evolved as a fusion protein of unique N-terminal domains fused to domains that exhibit essentially co-linear homology to the EF-1 family of elongation factors. Beginning internally at amino acid 254, homology is more extensive between the SUF12 protein and EF-1 alpha of yeast (36% identity; 65% with conservative substitutions) than between EF-1 alpha of yeast and EF-Tu of Escherichia coli. The most extensive regions of SUF12/EF-1 alpha homology are those regions that have been conserved in the EF-1 family, including domains involved in GTP and tRNA binding. It is clear that SUF12 and EF-1 alpha are not functionally equivalent, since both are essential in vivo. The N-terminal domains of SUF12 are unique and may reflect, in part, the functional distinction between these proteins. These domains exhibit unusual amino acid composition and extensive repeated structure. The behavior of suf12-null/SUF12+ heterozygotes indicates that suf12 is co-dominantly expressed and suggests that suf12 allele-specific suppression may result from functionally distinct mutant proteins rather than variation in residual wild-type SUF12+ activity. We propose a model of suf12-mediated frameshift and nonsense suppression that is based on a primary defect in the normal process of codon recognition.


Melanocytes freshly isolated from normal human skin express the cell membrane receptor for the adhesive glycoprotein thrombospondin.
Thrombospondin (TSP) is an adhesive protein with multiple binding sites, which is able to mediate several cell-to-cell and cell-to-matrix interactions, particularly through its cell membrane receptor (TSP-R). Because human keratinocytes are able to synthesize and express TSP, and as TSP is also localized at the dermal-epidermal junction in normal human skin, we questioned whether epidermal cells are able to bind available TSP, that is, to express TSP-R. To investigate this, we employed gold immunoelectron microscopy on epidermal cells freshly isolated from normal human skin; the TSP-R was detected by OKM5 monoclonal antibody. Epidermal cells showing ultrastructural characteristics of melanocytes were gold-stained on their plasma membrane, whereas keratinocytes, Langerhans cells and lymphocytes were unstained. Although functional studies are clearly necessary to clarify the role(s) played by the TSP-R on the cell surface of melanocytes, it is tempting to speculate that the TSP-R may be important for melanocyte adhesion to the dermal-epidermal junction and to keratinocytes. Such adhesion may not only subserve the steric localization of melanocytes, but also have important implications for those functional activities of melanocytes which have been shown to require close contact between these cells and adjacent keratinocytes and/or basement membrane components.


Synthesis of D- and L-apio nucleoside analogues with 2'-hydroxyl group as potential anti-HIV agents.
The present work describes the asymmetric synthesis of D- and L-apio-2',3'-dideoxynucleoside analogues, 4 and 5 with 2'-hydroxyl group via a common intermediate 9, starting from D-galactose. Stereoselective dihydroxylation and deoxygenation through radical inversion were successfully employed to synthesize the key intermediate 12 with D-apio structure, while stereoselecetive hydroboration-oxidation was used for the synthesis of another key intermediate 18 with L-apio structure.


Expert review of global real-world data on COVID-19 vaccine booster effectiveness and safety during the omicron-dominant phase of the pandemic.
COVID-19 vaccines have been highly effective in reducing morbidity and mortality during the pandemic. However, the emergence of the Omicron variant and subvariants as the globally dominant strains have raised doubts about the effectiveness of currently available vaccines and prompted debate about potential future vaccination strategies. Using the publicly available IVAC VIEW-hub platform, we reviewed 52 studies on vaccine effectiveness (VE) after booster vaccinations. VE were reported for SARS-CoV-2 symptomatic infection, severe disease and death and stratified by vaccine schedule and age. In addition, a non-systematic literature review of safety was performed to identify single or multi-country studies investigating adverse event rates for at least two of the currently available COVID-19 vaccines. Booster shots of the current COVID-19 vaccines provide consistently high protection against Omicron-related severe disease and death. Additionally, this protection appears to be conserved for at least 3 months, with a small but significant waning after that. The positive risk-benefit ratio of these vaccines is well established, giving us confidence to administer additional doses as required. Future vaccination strategies will likely include a combination of schedules based on risk profile, as overly frequent boosting may be neither beneficial nor sustainable for the general population.


Low-risk HLA genotype in Type 1 diabetes is associated with less destruction of pancreatic B-cells 12 months after diagnosis.
The role of human leukocyte antigen (HLA) genes in the susceptibility to Type 1 diabetes (T1DM) is well known. However, we do not know whether the degree of pancreatic B-cell destruction depends on different HLA genetic risk. The aim of this study was to analyse the influence of DRB1* and DQB1* genes on the rate of pancreatic B-cell loss in a prospective series of 120 consecutive newly diagnosed T1DM subjects in the first 12 months after diagnosis. Patients were typed for HLA-DRB1* and DQB1* loci by a reverse line blot assay using an array of immobilized sequence-specific oligonucleotide probes. C-peptide, insulin requirement and glycated haemoglobin (HbA(1c)) were determined at diagnosis and every 3 months for 12 months. The variance of C-peptide as evidence of B-cell loss during follow-up was analysed using the general linear model for repeated-measures procedure. Fasting C-peptide in T1DM subjects with low HLA genetic risk was significantly higher when compared with subjects with moderate or high HLA genetic risk from time of diagnosis up to 12 months (P = 0.007 and P = 0.0002, respectively). Nonetheless, the changes in C-peptide levels over a 12-month period did not differ significantly between T1DM subjects with different HLA genetic risks. Low-risk HLA genotype in T1DM is associated with less destruction of pancreatic B-cells up to 12 months after diagnosis. These results are useful when designing trials for therapies aimed to prevent the progression of B-cell destruction in recent-onset T1DM.


Preparation of Stereo-Divergent Compounds from the Natural Product Drupacine Based on Complexity-to-Diversity Strategy.
The Complexity-to-Diversity (CtD) strategy was applied to synthesize a 23-member compound collection from the natural product drupacine, including 21 novel compounds. An unusual benzo [d] cyclopenta [b] azepin skeleton was constructed by Von Braun reaction to cleave C-N bond of drupacine. Moreover, compound 10 has potential cytotoxicity to human colon cancer cells with low toxicity to the normal human colon mucosal epithelial cell lines.


The effect of activity and face masks on exhaled particles in children.
Despite the high burden of respiratory infections among children, the production of exhaled particles during common activities and the efficacy of face masks in children have not been sufficiently studied. To determine the effect of type of activity and mask usage on exhaled particle production in children. Healthy children were asked to perform activities that ranged in intensity (breathing quietly, speaking, singing, coughing, and sneezing) while wearing no mask, a cloth mask, or a surgical mask. The concentration and size of exhaled particles were assessed during each activity. Twenty-three children were enrolled in the study. Average exhaled particle concentration increased by intensity of activity, with the lowest particle concentration during tidal breathing (1.285 particles/cm3 [95% CI 0.943, 1.627]) and highest particle concentration during sneezing (5.183 particles/cm3 [95% CI 1.911, 8.455]). High-intensity activities were associated with an increase primarily in the respirable size (≤ 5 µm) particle fraction. Surgical and cloth masks were associated with lower average particle concentration compared to no mask (P = 0.026 for sneezing). Surgical masks outperformed cloth masks across all activities, especially within the respirable size fraction. In a multivariable linear regression model, we observed significant effect modification of activity by age and by mask type. Similar to adults, children produce exhaled particles that vary in size and concentration across a range of activities. Production of respirable size fraction particles (≤ 5 µm), the dominant mode of transmission of many respiratory viruses, increases significantly with coughing and sneezing and is most effectively reduced by wearing surgical face masks.


A Sustainable Alternative for Postharvest Disease Management and Phytopathogens Biocontrol in Fruit: Antagonistic Yeasts.
Postharvest diseases of fruits caused by phytopathogens cause losses up to 50% of global production. Phytopathogens control is performed with synthetic fungicides, but the application causes environmental contamination problems and human and animal health in addition to generating resistance. Yeasts are antagonist microorganisms that have been used in the last years as biocontrol agents and in sustainable postharvest disease management in fruits. Yeast application for biocontrol of phytopathogens has been an effective action worldwide. This review explores the sustainable use of yeasts in each continent, the main antagonistic mechanisms towards phytopathogens, their relationship with OMIC sciences, and patents at the world level that involve yeast-based-products for their biocontrol.


Presence and induction of the enzyme NAD(P)H: quinone oxidoreductase 1 in the central nervous system.
NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyzes a reductive detoxification that is thought to protect cells against the adverse effects of quinones and related compounds. NQO1 activity is present in all tissues. Absence of the enzyme produces abnormalities in the redox state and seizures, suggesting an important role of the protein in the central nervous system. Immunohistochemical analysis showed that the protein was found throughout the brain of the adult rat and mouse, with complete absence of the protein in brains from NQO1-/- mice. NQO1 was not seen in any neuronal population, but was localized to Bergmann glial in the cerebellum and a subset of the oligodendrocytes throughout the brain. Prolonged seizures induced in adult rats with kainic acid resulted in an increase in activity of the enzyme throughout the brain, most prominently in the cerebellum, but immunoreactivity did not appear in neurons. Comparison of the axons in the corpus callosum from a wild-type mouse to a knockout mouse showed that myelin is produced in the absence of NQO1, but there appears to be more small-diameter axons in the knockout animal. These results suggest that NQO1 has a role in myelination in the central nervous system or in the insulating/wrapping function of glial cells.


Chronic experimental autoimmune encephalomyelitis in the guinea pig. Presence of anti-M2 antibodies in central nervous system tissue and the possible role of M2 autoantigen in the induction of the disease.
Experimental autoimmune encephalomyelitis (EAE) can be transferred adoptively with T cells sensitized to the basic protein of myelin (BP). However, in the guinea pig, the chronic form of EAE has not been found to be inducible with BP alone, nor has it been adoptively transferred. An antibody response to the central nervous system (CNS) myelin autoantigens was looked for in serum and target CNS tissue in S13 guinea pigs with isologous CNS tissue-induced chronic EAE. Antibody activity was estimated by an immunoenzymatic technique and by autoradiography, using immunoprecipitated and electrophoresed relevant radiolabelled antigens. In serum, IgG antibody response to BP and M2 reached its maximum level 30 to 40 d after immunization and then declined progressively until it became undetectable. On the other hand, while anti-BP antibodies were seldom detected in CNS tissue acid extract, anti-M2 IgG antibodies were always present in CNS tissue of chronic EAE animals, and the amount of these antibodies were related to the severity of symptoms and lesions. No antibody response to proteolipid or to galactocerebroside was detected in serum or CNS tissue. BP-immunized controls showed no chronic EAE and no response to M2 in their serum or CNS tissue. Inasmuch as M2 has been shown to be a glycoprotein of CNS myelin, and anti-M2 antibodies to have a demyelinating property, the latter would be responsible for CNS tissue demyelination in chronic EAE. A shared role of BP and M2 in the induction of chronic EAE in the guinea pig is suggested.


[The role of atherogenic dyslipidaemia in clinical practice guidelines].
Atherogenic dyslipidaemia is underdiagnosed, undertreated, and under-controlled. The aim of the present study was to assess the positioning of clinical guidelines as regards atherogenic dyslipidaemia. The major clinical guidelines of scientific societies or official agencies issued between January 1, 2012 and March 31, 2015 were collected from the MEDLINE database. High-density lipoprotein (HDL) cholesterol, triglycerides, atherogenic dyslipidaemia, non-HDL cholesterol, and apolipoprotein (apo) B were gathered from the 10 selected guidelines, and it was assessed whether these parameters were considered a cardiovascular risk factor, a therapeutic target, or proposed a pharmacological strategy. American guidelines, except the National Lipid Association (NLA), do not consider HDL cholesterol and triglycerides in cardiovascular prevention. The NLA emphasises the relevance of atherogenic dyslipidaemia. The Canadian guidelines introduced non-HDL cholesterol and ApoB as alternative targets, and proposes non-statin treatment in the presence of low HDL cholesterol and hypertriglyceridaemia. The International Atherosclerosis Society (IAS) and National Institute for Health and Care Excellence (NICE) guidelines promote the importance of non-HDL cholesterol. European, Brazilian and Japanese guidelines highlight HDL cholesterol and triglycerides, but with the limitation that the main evidence comes from sub-analysis of clinical studies. The clinical guidelines analysed do not consider, or unconvincingly address, the importance of atherogenic dyslipidaemia.


Allocation of provincial carbon emission allowances under China's 2030 carbon peak target: A dynamic multi-criteria decision analysis method.
To balance China's socio-economic development and emission reduction goals, a fair and effective provincial carbon emission allowance (CEA) allocation is necessary. By considering the implied emissions of inter-provincial power transfer, this study designed a dynamic multi-criteria CEA allocation model based on four criteria-egalitarianism, historical responsibility, emission reduction capability, and emission efficiency-to calculate the provincial CEA year by year before 2030. The efficiency and fairness of the CEA scheme were evaluated through the Data envelopment analysis (DEA) model, the environmental Gini coefficient, and its grouped decomposition method. The national overall CEA, the results revealed, will peak during the 15th Five-Year Plan (FYP) period. Specifically, the CEA for eastern and central China is expected to peak first during the 14th FYP period, while the northeast region's CEA remains stable and that of the western region continues to grow. Provinces with high carbon emissions, high carbon emission intensity and high per capita carbon emissions and provinces with particularly high carbon emissions will face great pressure regarding emission reduction, and their CEA peaks are expected to arrive before 2025 and 2030 respectively. The CEA of the less-developed provinces will have a surplus. In terms of time, the high-emission provinces face greater emission reduction pressure during the 15th FYP period than during the 14th FYP period. In terms of scheme evaluation, the scheme achieved a double improvement in fairness and efficiency compared with the current actual emissions of various provinces. Reducing the differences in per capita CEA between the different regions and provinces in the western and eastern regions will help improve the scheme's fairness. This study overcomes the existing researches' shortcomings on the large differences in the distribution of emission reduction pressures in key provinces and is more feasible in practice.


Congenital ureteral valves: two new cases and a review of the literature.
Ureteral valves are a rare clinical finding. Frequently they are associated with other urological anomalies such as complete or incomplete renal duplication, ectopic ureter, vesicoureteral reflux and horseshoe kidney. Hydronephrosis is the most common clinical sign. We report two cases of ureteral valves recently encountered at the Surgical Department of Sant Joan de Dèu Hospital in Barcelona, and discuss the diagnosis and surgical treatment with a review of the literature from 1926.


The anatomy lesson of Dr. Nicolaes Tulp by Rembrandt (1632): a comparison of the painting with a dissected left forearm of a Dutch male cadaver.
Rembrandt's The Anatomy Lesson of Dr. Nicolaes Tulp (1632) is considered a masterpiece and is a group portrait of the Amsterdam Guild of Surgeons in the form of an anatomy lesson. Dr. Nicolaes Tulp, Doctor of Medicine and Praelector Anatomiae to the Amsterdam Guild of Surgeons, showed an anatomic dissection of a forearm on the corpse of an executed criminal. The anatomic accuracy in Rembrandt's famous painting has been discussed in the literature for decades without any general consensus. In 2006, on the 400th anniversary of Rembrandt's birth, a forearm dissection of a cadaver and a comparison with the anatomy in the painting are presented to analyze the anatomic accuracy of Rembrandt's famous painting.


The prenatal triad: The importance of provider-patient communication with expectant fathers throughout the prenatal care process.
Previous research has primarily focused on the relationship between providers and expectant mothers as a key element of quality prenatal care. Significantly less attention has been directed toward expectant fathers and the importance of their communication with prenatal care providers and involvement in the prenatal care process. Much of this limited existing literature emphasizes the health benefits including fathers would bring for mom and baby, but rarely is the potential benefit to fathers' health included in the conversation. This discussion aims to highlight the value of this line of research for both communication and medical researchers and consider potential avenues for studying and promoting father engagement in prenatal care.


Views and experiences of healthcare practitioners supporting people with COPD who have used activity monitors: "More than just steps".
Activity monitors (apps and wearables) are increasingly used by the general population, including people with Chronic Obstructive Pulmonary Disease (COPD). There is potential for activity monitors to support increases in physical activity for people with COPD and healthcare practitioners (HCPs) are likely to be key in supporting their use, but little is currently known about HCPs' views or experiences. This qualitative research aimed to explore HCPs' views and experiences of supporting people with COPD who have used activity monitors. Seventeen semi-structured telephone or online interviews were conducted with HCPs between September 2020 and May 2021. HCPs included two nurses, an occupational therapist, a physician, and 13 physiotherapists. Participants were recruited via social media advertisements. They all had experience of supporting people with COPD who had used activity monitors. Interviews were analysed using reflexive thematic analysis. Four themes were developed highlighting the challenges and benefits of HCPs supporting patients with using activity monitors and utilising patient-collected activity data; 1) Skills and experience are needed to increase accessibility and engagement, 2) Objectively monitored physical activity can support exercise prescription, 3) Applications of activity monitors vary across different settings, and 4) Support is needed for future use of activity monitors. HCPs recognised the potential for activity monitors to impact patients' ability to self-manage their COPD. However, there is a lack of guidance and information to support integration within practice. Future research is needed to co-develop information and guidelines for people with COPD and HCPs.


Monogenic diabetes characteristics in a transnational multicenter study from Mediterranean countries.
Diagnosis of monogenic diabetes has important clinical implications for treatment and health expenditure. However, its prevalence remains to be specified in many countries, particularly from South Europe, North Africa and Middle-East, where non-autoimmune diabetes in young adults is increasing dramatically. To identify cases of monogenic diabetes in young adults from Mediterranean countries and assess the specificities between countries. We conducted a transnational multicenter study based on exome sequencing in 204 unrelated patients with diabetes (age-at-diagnosis: 26.1 ± 9.1 years). Rare coding variants in 35 targeted genes were evaluated for pathogenicity. Data were analyzed using one-way ANOVA, chi-squared test and factor analysis of mixed data. Forty pathogenic or likely pathogenic variants, 14 of which novel, were identified in 36 patients yielding a genetic diagnosis rate of 17.6%. The majority of cases were due to GCK, HNF1A, ABCC8 and HNF4A variants. We observed highly variable diagnosis rates according to countries, with association to genetic ancestry. Lower body mass index and HbA1c at study inclusion, and less frequent insulin treatment were hallmarks of pathogenic variant carriers. Treatment changes following genetic diagnosis have been made in several patients. Our data from patients in several Mediterranean countries highlight a broad clinical and genetic spectrum of diabetes, showing the relevance of wide genetic testing for personalized care of early-onset diabetes.


Myocardial surgical revascularization after streptokinase treatment for acute myocardial infarction.
Eighty-six patients admitted with evolving myocardial infarction within 6 hours of symptom onset were treated with streptokinase. Thirty-nine received intracoronary streptokinase, and 47 received intravenous streptokinase. There were no streptokinase-related complications. Twenty-three patients treated with intracoronary streptokinase and 28 patients receiving intravenous streptokinase underwent coronary artery bypass grafting. On admission, 16 patients receiving intracoronary streptokinase had electrocardiographic evidence of anterolateral evolving myocardial infarction and seven had evidence of inferior evolving myocardial infarction. Time from first symptom to intracoronary streptokinase was 4.4 +/- 1.6 hours. In seven patients, intracoronary streptokinase failed to open the obstructed coronary. All developed severe left ventricular hypokinesia in the area supplied by that coronary artery. In spite of recanalization, nine of 14 patients developed severe hypokinesia in the supplied area, and one an apical aneurysm. Four patients developed mild to moderate hypokinesia, and one had no left ventricular damage. On admission, 14 patients receiving intravenous streptokinase had electrocardiographic evidence of anterolateral evolving myocardial infarction and four had evidence of inferior evolving myocardial infarction. Time from first symptom to intravenous streptokinase was 3.2 +/- 1.5 hours. In seven patients, intravenous streptokinase failed to open the coronary, and all developed severe hypokinesia of the supplied area, with formation of apical left ventricular aneurysm in three. In 21 patients, intravenous streptokinase opened the artery. Eighteen angiographies performed 9.6 +/- 7.9 days after therapy showed a normal left ventricle in eight patients, moderate hypokinesia in seven, and severe hypokinesia in three. Time from first symptom to therapy was shorter in the patients receiving intravenous therapy (p less than 0.01). Coronary artery bypass grafting and four resections after left ventricular aneurysm were performed without operative death. Two patients receiving intracoronary therapy died in the hospital, and one died 2 months later from arrhythmias. Freedom from angina and rehabilitation (New York Heart Association Class I) were achieved in 69.5% of patients receiving intracoronary streptokinase and in 75% of patients receiving intravenous streptokinase. Thus streptokinase-induced thrombolysis salvages myocardium, and the intravenous route seems as effective as the intracoronary. Advantages of the former are earlier administration that might increase myocardial salvage, no invasive procedure, and lesser cost.


Platelet dynamics in the early phase of postischemic liver in vivo.
In liver surgery, ischemia/reperfusion injury occasionally leads to liver failure by activating Kupffer cells (KCs) and leukocytes. However, few reports have demonstrated a relationship between KCs and platelets in vivo. This study investigated the relationship between these cells using intravital microscopy. Male Wistar rats were divided into two groups: (1) KC+ group, receiving 1 mL saline; and (2) KC- group, intravenously injected with liposome-encapsulated dichloromethylene disphosphonate for elimination of KCs. At 48 h after administration, 20 min of total normothermic hepatic ischemia was induced. Rhodamine-6G-labeled platelets and sinusoidal alterations were monitored using intravital microscopy up to 120 min after reperfusion. P-selectin, accumulated leukocytes and morphological damage, and alanine aminotransferase were evaluated. In the KC+ group, numbers of adherent platelets increased significantly within 30 min after reperfusion. Endothelial cells of sinusoids in which KCs were mainly located were destroyed and the sinusoids were significantly constricted after reperfusion. Conversely, in the KC- group, adherent platelets in sinusoids were suppressed, and sinusoidal perfusion, endothelial cell damage and serum alanine aminotransferase levels were significantly improved. P-selectin on sinusoidal endothelial cells was not observed up to 120 min after reperfusion in either group. Adherent platelets appear to reflect activation of KCs and lead to leukocyte accumulation, resulting in sinusoidal perfusion disturbance and liver failure. Evaluation of adherent platelets in the microcirculation offers an important marker of hepatic injury.


A Snapshot of European Children's Eating Habits: Results from the Fourth Round of the WHO European Childhood Obesity Surveillance Initiative (COSI).
Consuming a healthy diet in childhood helps to protect against malnutrition and noncommunicable diseases (NCDs). This cross-sectional study described the diets of 132,489 children aged six to nine years from 23 countries participating in round four (2015-2017) of the WHO European Childhood Obesity Surveillance Initiative (COSI). Children's parents or caregivers were asked to complete a questionnaire that contained indicators of energy-balance-related behaviors (including diet). For each country, we calculated the percentage of children who consumed breakfast, fruit, vegetables, sweet snacks or soft drinks "every day", "most days (four to six days per week)", "some days (one to three days per week)", or "never or less than once a week". We reported these results stratified by country, sex, and region. On a daily basis, most children (78.5%) consumed breakfast, fewer than half (42.5%) consumed fruit, fewer than a quarter (22.6%) consumed fresh vegetables, and around one in ten consumed sweet snacks or soft drinks (10.3% and 9.4%, respectively); however, there were large between-country differences. This paper highlights an urgent need to create healthier food and drink environments, reinforce health systems to promote healthy diets, and continue to support child nutrition and obesity surveillance.


Psychometric properties of the HIV-Related Fatigue Scale.
The HIV-Related Fatigue Scale (HRFS) was developed to address the specific aspects of fatigue experienced by people who are HIV-positive and are not measured in any commonly used fatigue scale. The necessity for a new scale was determined after analysis of a qualitative study to explore HIV-related fatigue in which it was found that HIV-related fatigue has components related to intensity, circumstances, and consequences that must be included in the measurement of fatigue for this population. The HRFS has 56 items, most of which are on a 1-to-10 scale, drawn from five existing fatigue scales and the data from this qualitative study. The items were deemed content valid, easy to understand, and not fatiguing to complete by people with HIV-related fatigue. Cronbach's alpha for the entire tool was .94; internal consistency for each of the three preliminary subscales is reported as well. Test-retest reliability was moderate at r = .43. Further testing needs to be done, but the HRFS has the potential to be a valuable addition to the measurement of fatigue in seropositive persons.


Training needs, practices and barriers in the work of community reproductive health workers in Masindi district, Uganda.
Community reproductive health workers play a valuable role in family planning counselling and the distribution of contraceptive methods in rural communities. However, they face stigma, misconceptions and a lack of support. Regular supervision by health workers and support from community leaders can help address these issues.


Nicotine inhibits activation of microglial proton currents via interactions with α7 acetylcholine receptors.
Alpha 7 subunits of nicotinic acetylcholine receptors (nAChRs) are expressed in microglia and are involved in the suppression of neuroinflammation. Over the past decade, many reports show beneficial effects of nicotine, though little is known about the mechanism. Here we show that nicotine inhibits lipopolysaccharide (LPS)-induced proton (H+) currents and morphological change by using primary cultured microglia. The H+ channel currents were measured by whole-cell patch clamp method under voltage-clamp condition. Increased H+ current in activated microglia was attenuated by blocking NADPH oxidase. The inhibitory effect of nicotine was due to the activation of α7 nAChR, not a direct action on the H+ channels, because the effects of nicotine was cancelled by α7 nAChR antagonists. Neurotoxic effect of LPS-activated microglia due to inflammatory cytokines was also attenuated by pre-treatment of microglia with nicotine. These results suggest that α7 nAChRs in microglia may be a therapeutic target in neuroinflammatory diseases.


Primary lymphoma of the aorta presenting as a descending thoracic aortic aneurysm.
We describe a case of primary lymphoma of the thoracic aorta that presented as an aneurysm of the descending thoracic aorta. The aortic tumor was successfully resected with 2-year disease-free survival.


Is duplex surveillance of value after leg vein bypass grafting? Principal results of the Vein Graft Surveillance Randomised Trial (VGST).
The purpose of this study was to assess the benefits of duplex compared with clinical vein graft surveillance in terms of amputation rates, quality of life, and healthcare costs in patients after femoropopliteal and femorocrural vein bypass grafts. This was a multicenter, prospective, randomized, controlled trial. A total of 594 patients with a patent vein graft at 30 days after surgery were randomized to either a clinical or duplex follow-up program at 6 weeks, then 3, 6, 9, 12, and 18 months postoperatively. The clinical and duplex surveillance groups had similar amputation rates (7% for each group) and vascular mortality rates (3% versus 4%) over 18 months. More patients in the clinical group had vein graft stenosis at 18 months (19% versus 12%, P=0.04), but primary patency, primary assisted patency, and secondary patency rates, respectively, were similar in the clinical group (69%, 76%, and 80%) and the duplex group (67%, 76%, and 79%). There were no apparent differences in health-related quality of life, but the average health service costs incurred by the duplex surveillance program were greater by 495 pound sterling (95% CI 83 pound sterling to 807 pound sterling) per patient. Intensive surveillance with duplex scanning did not show any additional benefit in terms of limb salvage rates for patients undergoing vein bypass graft operations, but it did incur additional costs.


DNA damage and biological responses induced by Boron Neutron Capture Therapy (BNCT).
Boron Neutron Capture Therapy (BNCT) is a tumor cell selective high LET (linear energy transfer) particle beam therapy. The patient is administrated a boron (10B) compound via intravenous injection or infusion, and when 10B is sufficiently accumulated in the tumor, neutron beams containing epithermal neutrons as the main component are irradiated. Epithermal neutrons lose energy in the body and become thermal neutrons. The captured 10B undergoes a (n, α) reaction with thermal neutrons, and the resulting α particles and 7Li nuclei have short ranges of 9-10μm and 4-5μm, respectively, and do not reach the surrounding cells in normal tissues. Therefore, these high LET-heavy charged particles can selectively kill cancer cells. The cell-killing effect of these heavy charged particles is thought to be triggered by DNA damage. It is known that DNA damage caused by heavy charged particles is more serious and difficult to repair than DNA damage caused by Low LET radiation such as X-rays and γ-rays. This review focuses on DNA damage, e.g., DNA strand breaks and DNA damage repair caused by BNCT and describes the resulting biological response.


DUPLICATE: Cinnarizine: A Promising Agent for Migraine Prevention You May Never Get the Chance to Use.
The Publisher regrets that this article is an accidental duplication of an article that has already been published, http://dx.doi.org/10.1016/j.pediatrneurol.2014.07.002. The duplicate article has therefore been removed. The full Elsevier Policy on Article Removal can be found at http://www.elsevier.com/locate/withdrawalpolicy.


Direct NMR detection of the "invisible" alkali metal cations tightly bound to G-quadruplex structures.
We report the first direct solution NMR detection of the alkali metal cations (23Na+, 39K+, and 87Rb+) residing inside G-quadruplex channel structures formed by guanosine 5'-monophosphate and a DNA oligomer, d(TG4T). In solution, these channel alkali metal cations are tightly bound to the G-quadruplex structure and have been considered to be "invisible" to NMR spectroscopy for many years. Our finding that it is possible to directly observe these alkali metal cations by NMR spectroscopy provides a new tool for studying cation binding affinity and dynamics in G-quadruplex DNA.


Network Pharmacology and Molecular Docking Approaches to Investigating the Mechanism of Action of Zanthoxylum bungeanum in the Treatment of Oxidative Stress-induced Diseases.
Zanthoxylum bungeanum Maxim., a traditional Chinese herbal medicine, has been reported to possess therapeutic effects on diseases induced by oxidative stress (DOS), such as atherosclerosis and diabetes complication. However, the active components and their related mechanisms are still not systematically reported. The current study was aimed to explore the main active ingredients and their molecular mechanisms of Z. bungeanum for treating DOS using network pharmacology combined with molecular docking simulation. The active components of Z. bungeanum pericarps, in addition to the interacting targets, were identified from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. These components were filtered using the parameters of oral bioavailability and drug-likeness, and the targets related to DOS were obtained from the Genecards and OMIM database. Furthermore, the overlapping genes were obtained, and a protein-protein interaction was visualized using the STRING database. Next, the Cytoscape software was employed to build a disease/drug/component/target network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed using R software. Finally, the potential active compounds and their related targets were validated using molecular docking technology. A total of 61 active compounds, 280 intersection genes, and 105 signaling pathways were obtained. Functional enrichment analysis suggested that DOS occurs possibly through the regulation of many biological pathways, such as AGE-RAGE and HIF-1 signaling pathways. Thirty of the identical target genes showed obvious compact relationships with others in the STRING analysis. Three active compounds, quercetin, diosmetin, and beta-sitosterol, interacting with the four key targets, exhibited strong affinities. The findings of this study not only indicate the main mechanisms involving in oxidative stress-induced diseases but also provide the basis for further research on the active components of Z. bungeanum for treating DOS.


The role of a monoclonal antibody 11C8B1 as a diagnostic marker of IDH2-mutated sinonasal undifferentiated carcinoma.
IDH2 R172 mutations occur in >80% sinonasal undifferentiated carcinomas ("SNUC") and ~80% of these are R172S and R172T variants. We examined the utility of the monoclonal antibody 11C8B1 to IDH2 R172S in IDH2 R172-mutated tumors to establish an immunohistochemistry protocol as a surrogate method for IDH2 R172S mutation detection. Eighty-eight formalin-fixed paraffin-embedded tumors including 42 sinonasal tumors and a variety of IDH1/2-mutated malignancies were tested by immunohistochemistry. The IDH1/2 mutation status was determined in 86 cases by a targeted massively parallel sequencing MSK-IMPACTTM assay. Interestingly, monoclonal antibody 11C8B1 was reactive with all IDH2 R172S (N = 15) mutated tumors including 12 sinonasal carcinomas, 2 high-grade sarcomas and one intrahepatic cholangiocarcinoma, and with all R172T (N = 3) mutated sinonasal carcinomas displaying a distinct granular cytoplasmic labeling in all R172S/T mutated malignancies. 11C8B1 immunohistochemistry was also positive in 2 of 6 IDH1 R132S-mutated tumors, including one intrahepatic cholangiocarcinoma and one chondrosarcoma showing a smooth homogeneous cytoplasmic staining pattern. All IDH2 R172G/K/M/W (N = 22) and IDH1 132H/C/G/L (N = 15) mutated tumors, and all IDH1/2-wild-type tumors (N = 25), including a histologic variety of 23 sinonasal tumors, were immunonegative. Importantly, 11 sinonasal undifferentiated carcinomas (N = 14, 79%) and 3 (100%) high-grade neuroendocrine carcinomas, large cell type were 11C8B1 immunopositive. Literature search revealed a virtual absence of IDH2 R172 and IDH1 R132S mutations in >1000 cases of 8 different malignancies included in the differential diagnosis of sinonasal undifferentiated carcinoma. Our study suggests that positive IDH2 11C8B1 immunohistochemistry in sinonasal carcinomas would be highly predictive of the presence of IDH2 R172S/T mutations and could serve as a reliable adjunct diagnostic marker of sinonasal undifferentiated carcinomas in >70% cases.


Feedback regulation through myosin II confers robustness on RhoA signalling at E-cadherin junctions.
Actomyosin at the epithelial zonula adherens (ZA) generates junctional tension for tissue integrity and morphogenesis. This requires the RhoA GTPase, which establishes a strikingly stable active zone at the ZA. Mechanisms must then exist to confer robustness on junctional RhoA signalling at the population level. We now identify a feedback network that generates a stable mesoscopic RhoA zone out of dynamic elements. The key is scaffolding of ROCK1 to the ZA by myosin II. ROCK1 protects junctional RhoA by phosphorylating Rnd3 to prevent the cortical recruitment of the Rho suppressor, p190B RhoGAP. Combining predictive modelling and experimentation, we show that this network constitutes a bistable dynamical system that is realized at the population level of the ZA. Thus, stability of the RhoA zone is an emergent consequence of the network of interactions that allow myosin II to feedback to RhoA.


Nitric oxide: an overview.
Nitric oxide (NO), a paracrine-acting gas enzymatically synthesized from L-arginine, is a unique biologic mediator that has been implicated in a myriad of physiologic and pathophysiologic states. It is an important regulator of vascular tone and may be the mediator of the hemodynamic changes involved in sepsis and cirrhosis. In addition, there is increasing evidence that NO is involved in coagulation, immune function, inhibitory innervation of the gastrointestinal tract, protection of gastrointestinal mucosa, and the hepatotoxicity of cirrhosis. It has already been speculated that NO may represent a point of control or intervention in a number of disease states. The purpose of this paper is to provide the surgeon with a broad overview of the scientific and clinical aspects of this important molecule.


Approximation of smooth functionals using deep ReLU networks.
In recent years, deep neural networks have been employed to approximate nonlinear continuous functionals F defined on Lp([-1,1]s) for 1≤p≤∞. However, the existing theoretical analysis in the literature either is unsatisfactory due to the poor approximation results, or does not apply to the rectified linear unit (ReLU) activation function. This paper aims to investigate the approximation power of functional deep ReLU networks in two settings: F is continuous with restrictions on the modulus of continuity, and F has higher order Fréchet derivatives. A novel functional network structure is proposed to extract features of higher order smoothness harbored by the target functional F. Quantitative rates of approximation in terms of the depth, width and total number of weights of neural networks are derived for both settings. We give logarithmic rates when measuring the approximation error on the unit ball of a Hölder space. In addition, we establish nearly polynomial rates (i.e., rates of the form exp-a(logM)b with a>0,0<b<1) when measuring the approximation error on a space of analytic functions.


Increased prostacyclin content in gastric mucosa of cirrhotic patients with portal hypertensive gastropathy.
Plasma levels and gastric mucosal contents of prostaglandin (PG) E2 and prostacyclin were determined in cirrhotic patients with portal hypertensive gastropathy (PHG), in cirrhotic patients without PHG and in healthy controls. PGE2 and 6-keto-PGF1 alpha (a stable metabolite of prostacyclin) levels were measured in 30 cirrhotic patients and 10 controls, using radioimmunoassay. Of 30 cirrhotics, 13 had PHG of the fundus and the corpus. Plasma concentrations of 6-keto-PGF1 alpha in the cirrhotic patients were significantly higher than in the controls (p < 0.01), but there was no significant difference between cirrhotics and controls with regard to plasma levels of PGE2. The gastric mucosal contents of 6-keto-PGF1 alpha in the fundus was significantly higher in cirrhotics with PHG than those without PHG (p < 0.05) and controls (p < 0.01). However, the gastric mucosal contents of PGE2 in the fundus were not significantly different in cirrhotics with and without PHG. The gastric mucosal contents of 6-keto-PGF1 alpha significantly correlated to the plasma levels (r = 0.37, p < 0.05), but there was no significant correlation between plasma levels and gastric mucosal contents of PGE2. Since prostacyclin has vasodilator and gastric acid inhibitory effects, we speculate that high contents of prostacyclin in the gastric mucosa may have some role in the pathogenesis of PHG.


The relationship between regional blood flow and contractile function in normal, ischemic, and reperfused myocardium.
During normoperfusion, both myocardial blood flow and contractile function are heterogeneously distributed throughout the left ventricle, in that midwall segment shortening is higher at the apex than at the base of the left ventricle, and greater in the anterior than in the posterior wall. Also, transmural heterogeneity of myocardial deformation exists with greater segment shortening and wall thickening occurring in inner than in outer myocardial layers. A transmural heterogeneity of myocardial blood flow-with greater inner as compared to outer wall perfusion-exists which is not simply related to temporal fluctuations since the heterogeneous flow pattern is stable over at least a few minutes. While an increase in myocardial contractile function will lead to a metabolically mediated increase in myocardial blood flow, an increase in regional coronary perfusion within or above the autoregulatory range does not increase regional myocardial contractile function. During hypoperfusion, the reduction in subendocardial blood flow is more pronounced than that in subepicardial blood flow, and contractile function in the inner myocardial layers ceases more rapidly than in the outer myocardial layers. The reduced regional myocardial contractile function is closely matched to the reduced regional myocardial blood flow; however, such a coupling between reduced flow and function is lost when ischemia is prolonged for several hours in that function for a given flow is further reduced. During reperfusion, regional myocardial contractile function remains depressed for a prolonged period of time, depending on the severity, duration, and location of the preceding ischemic episode, while regional myocardial blood flow is restored to almost normal. Recovery of contractile function in the outer myocardial layers is faster than in the inner myocardial layers.


Experimental study on the effects of bismuth subgallate on the inflammatory process and angiogenesis of the oral mucosa.
Bismuth subgallate is a salt derived from heavy metal. The aim of this study was to evaluate the effect of this salt on some phases of healing. To assess the effect of subgallate on mucosa and to evaluate the association between the use of bismuth subgallate and neogenesis of vessels in oral mucosal wounds. This was a prospective and experimental study. This study used sixty rats, which were divided into control and experimental groups. The animals were submitted to a surgical procedure, which caused oral mucosal injury. A saline solution was applied on the wound of the control group, and in the experimental group, a solution of bismuth subgallate was administrated. The experimental group showed greater inflammatory reaction with increasing monomorphic proliferation. There was increased vessel proliferation in the control group. Bismuth subgallate had a negative influence on the healing process, delaying the rate of new vessel formation and optimal wound healing.


Competency assessment of the medical interns and nurses and documenting prevailing practices to provide family planning services in teaching hospitals in three states of India.
The objectives of the study were to assess the knowledge and skills of medical interns and nurses regarding family planning (FP) services, and document the prevailing FP practices in the teaching hospitals in India. A cross-sectional study was conducted in three states (Delhi, Rajasthan, and Maharashtra) of India, among randomly selected 163 participants, including medical interns (n = 81) and in-service nurses (n = 82), during 2017. The semi-structured, pre-tested interview schedule, was used to assess the knowledge and status of training received; and objective structured clinical examination (OSCE) based checklist was used to evaluate the skills. About 60% of the interns and 48% of the nurses knew more than five contraceptives that could be offered to the clients. About 22% (11.1% interns and 33.3% nurses) respondents believed that contraceptives should not be given to a married woman coming alone, and 31.9% (17.3% interns and 46.3% nurses) respondents reported that it was illegal to provide contraceptives to unmarried people. Nearly 43.3% interns and 69.5% nurses refused to demonstrate intrauterine contraceptive device (IUCD) insertion in the dummy uterus as per OSCE, and among those who did, 12.3% interns and 18.3% nurses had failed. About 63% interns and 63.4% of nurses had observed IUCD insertion, and 12.3% interns and 17.1% had performed IUCD insertion, during their training. Knowledge and skills of interns and nurses regarding FP services were inadequate. The medical training during graduation or internship, and during the job, was found to be inadequate to provide quality FP services as per guidelines of nursing/medical council of India and Government of India on FP.


Migrated T lymphocytes into malignant pleural effusions: an indicator of good prognosis in lung adenocarcinoma patients.
The presence of leukocyte subpopulations in malignant pleural effusions (MPEs) can have a different impact on tumor cell proliferation and vascular leakiness, their analysis can help to understand the metastatic microenvironment. We analyzed the relationship between the leukocyte subpopulation counts per ml of pleural fluid and the tumor cell count, molecular phenotype of lung adenocarcinoma (LAC), time from cancer diagnosis and previous oncologic therapy. We also evaluated the leukocyte composition of MPEs as a biomarker of prognosis. We determined CD4+ T, CD8+ T and CD20+ B cells, monocytes and neutrophils per ml in pleural effusions of 22 LAC and 10 heart failure (HF) patients by flow cytometry. Tumor cells were identified by morphology and CD326 expression. IFNγ, IL-10 and IL-17, and chemokines were determined by ELISAs and migratory response to pleural fluids by transwell assays. MPEs from LAC patients had more CD8+ T lymphocytes and a tendency to more CD4+ T and CD20+ B lymphocytes than HF-related fluids. However, no correlation was found between lymphocytes and tumor cells. In those MPEs which were detected >1 month from LAC diagnosis, there was a negative correlation between pleural tumor cells and CD8+ T lymphocytes. CXCL10 was responsible for the attraction of CD20+ B, CD4+ T and CD8+ T lymphocytes in malignant fluids. Concentrations of IL-17 were higher in MPEs than in HF-related effusions. Survival after MPE diagnosis correlated positively with CD4+ T and CD8+ T lymphocytes, but negatively with neutrophils and IL-17 levels. In conclusion, lymphocyte enrichment in MPEs from LAC patients is mostly due to local migration and increases patient survival.


Tympanoplasty: cartilage prostheses--a report of 564 cases.
We reviewed 564 tympanoplasties operated upon over an eight year period at the Otologic Medical Group in which tragal cartilage was used to re-establish the sound pressure transfer mechanism. Eighty-six percent of the cases were revisions, and half of these were planned second stage procedures. In the majority of cases the stapes crural arch was missing. The conductive deficit in these cases was reduced to 20 db or less in 67% and 10 db or less in 40%. The commonest single cause of failure was a short prosthesis. There were no instances of cartilage resorption. Extrusion occurred in one case. Tragal cartilage has been more satisfactory than ossicular tissue in many situations. Recently we have been using plastic prosthesis (TORP and PORP) in combination with tragal cartilage and believe that the results will be even better.


Are there specialized junctions in the pars maculata of the distal tubule?
In the present study the tight junctions at the macula densa were compared to those of the adjacent straight and convoluted segments of the distal tubule using freeze fracturing and thin sectioning techniques. Only insignificant differences were found in the number of strands and the apico-basal depth of the tight junctions in the three distal tubular segments of rat, dog and tree shrew. In experiments with horseradish peroxidase on mice and tree shrews, the tracer did not penetrate the apical junctions in any of the distal tubular segments. Our findings do not support the concept of considerably higher permeability of the tight junctions at the macula densa, as previously reported. Gap junctions were never observed in the distal nephron. The present results suggest that the glomerulo-tubular feedback is more likely to be mediated by transcellular resorption of solutes than by passive diffusion through a leaky paracellular shunt pathway.


Urinary bisphenol a concentration and thyroid function in Chinese adults.
Bisphenol A (BPA) is an endocrine disruptor that in animal studies can bind to the thyroid hormone receptor and affect thyroid function. Relevant epidemiologic studies are limited and results are inconsistent. We explored the relationship between urinary BPA and thyroid function in a Chinese population. The study population included 3394 subjects age 40 years or older who were enrolled in a population-based study from Songnan Community, Baoshan District, Shanghai, China, from June through August 2009. We analyzed the association between urinary BPA and thyroid function using multivariate linear regression. Participants were further divided according to thyroid function status, and logistic regression was applied to determine the relationship between urinary BPA and thyroid function. Each one-quartile increase in BPA was related to an increase of 0.068 pmol/l (95% confidence interval = 0.065- 0.071) in free triiodothyronine and a 0.084 μIU/ml decline (-0.099 to -0.069) in thyroid-stimulating hormone (TSH) in men. For women, there was a 0.10 pmol/l (0.09 to 0.11) increase in free triiodothyronine and a 0.13 μIU/ml decline (-0.14 to -0.11) in TSH. High urinary BPA level was associated with increased thyroid function (adjusted odds ratio= 1.71 [1.26 to 2.32]). Our results support previous reports of associations between BPA exposure and altered thyroid hormones in animal models and epidemiologic studies. Because our study is cross-sectional, no causal relationships can be established.


[Substance P as a factor in resistance to emotional stress].
The effect of substance P--an endogenous brain peptide--on the resistance to chronic emotional stress was studied in rats. A single administration of the peptide (125 or 250 mkg/kg) elicits a highly significant increase of rats resistance to chronic emotional stress and reduces the raise of adrenals weight, hemodynamic fluctuations and emotional reactivity.