Factitious extension contracture of the elbow: case report.
A case report of factitious extension contracture of the elbow due to injection-induced fibrous myopathy of the triceps is presented. Crystalline material was demonstrated in muscle biopsies preserved in absolute alcohol and surgical section of the triceps resulted in correction of the deformity. A review of the literature and differentiation between Weber-Christian systemic panniculitis and factitial panniculitis is discussed.


A novel non-invasive blood pressure waveform measuring system compared to Millar applanation tonometry.
The accurate, non-invasive, measuring of the continuous arterial blood pressure waveform faces some difficulties and an innovative blood pressure measurement technology is urgently needed. However, the arterial blood pressure waveform plays an essential role in health care by providing diagnostic information and base for calculating several heart function parameters. The aim of this study is to introduce a novel non-invasive measuring system that can measure the arterial blood pressure waveform with high accuracy in comparison to an applanation tonometry system. The applied measuring device utilizes a new measurement strategy enabled by the OptoForce 3D force sensor, which is attached to the wrist at the radial artery. To validate the accuracy, 30 simultaneous measurements were taken with a Millar tonometer. For the simultaneously recorded non-invasive signals, the similarity was high (the average correlation was [Formula: see text]). The differences in the systolic and the diastolic blood pressure measured by the two systems are small. The average differences ([Formula: see text]) for simultaneously recorded systolic, diastolic, mean arterial and incisura pressures were: [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text], respectively. These results satisfy the AAMI criteria. Based on our results, this new system requires further development and validation against invasive arterial blood pressure monitoring in order to prove its usefulness in patient monitoring, emergency care, and pulse diagnosis.


Voice change after thyroidectomy without vocal cord paralysis: Analysis of 2,297 thyroidectomy patients.
Some patients experience long-term voice change after thyroidectomy. One of the most common symptoms of voice change is pitch lowering, which is closely related to unfavorable voice quality. Here we observed voice outcomes for 6 months of follow-up after thyroidectomy to identify factors closely related to low-pitched voice. We retrospectively reviewed the records of 2,297 patients who underwent thyroidectomy between January 2014 and December 2017. All the patients had their vocal status examined using videostroboscopy, acoustic voice analyses, aerodynamic study, and Thyroidectomy-Related Voice Questionnaire scores. We stratified patients into 2 groups (low-pitched voice versus favorable voice) according to pitch lowering (reduction in speaking fundamental frequency ≥12 Hz 1 month after thyroidectomy compared to the preoperative value). We compared preoperative data with postoperative data collected 1, 3, and 6 months after thyroidectomy to identify factors contributing to low-pitched voice. Univariate logistic regression analyses showed that factors related to low-pitched voice were female sex, older age, low body weight, short stature, and a high positive lymph node ratio. Multivariate analyses showed that female sex and older age were significantly associated with a negative prognosis for low-pitched voice 1 month after thyroidectomy (odds ratios 0.41 and 1.04, respectively; P < .001). Receiver operating characteristic curves for predicting sustained low-pitched voice during 6 months showed that speaking fundamental frequency ≥12.48 Hz 1 month after thyroidectomy was the optimal cutoff value, with 87.9% sensitivity and 95.8% specificity (P < .001). Female sex and older age are strongly associated with increased risk for low-pitched voice after thyroidectomy. Speaking fundamental frequency ≥12.48 Hz 1 month after thyroidectomy can be used to predict sustained low-pitched voice after thyroidectomy.


Complications related to veno-arterial extracorporeal membrane oxygenation in patients with acute myocardial infarction: VA-ECMO complications in AMI.
Among various mechanical support devices, veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is the last resort for acute myocardial infarction (AMI) patients complicated with refractory cardiogenic shock or cardiac arrest. The purpose of this study was to investigate the V-A ECMO-related complications in AMI patients who underwent percutaneous coronary intervention (PCI), and to find the association between complications and in-hospital death in that population. We retrospectively included 101 AMI patients who received V-A ECMO and underwent PCI to the culprit lesion, and divided them into the survivor group (n=43) and the in-hospital death group (n=58). We compared the clinical characteristics and outcomes including complications between the 2 groups, and performed multivariate logistic regression analysis to find factors associated with in-hospital death and major bleeding. The incidence of major bleeding including V-A ECMO site bleeding and intracranial hemorrhage was higher in the in-hospital death group (34.5%) than in the survivor group (7%) (p=0.001). Multivariate logistic regression analysis revealed that final thrombolysis in myocardial infarction (TIMI) flow grade ≤2 (OR 4.453, 95% CI1.427-13.894, p=0.010) and major bleeding (OR 4.986, 95% CI1.277-19.466, p=0.021) were significantly associated with in-hospital death. Out-of-hospital cardiac arrest (OHCA) was significantly associated with major bleeding (OR 3.881, 95% CI 1.358-11.089, p=0.011). In AMI patients who received V-A ECMO and underwent PCI, final TIMI flow grade ≤2 and major bleeding were associated with in-hospital death. OHCA was closely associated with major bleeding.


Chronic administration tetrahydroxystilbene glucoside promotes hippocampal memory and synaptic plasticity and activates ERKs, CaMKII and SIRT1/miR-134 in vivo.
Polygonum multiflorum Thunb is a traditional Chinese medicine with anti-aging effect. 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is generally considered as the main active component in Polygonum multiflorum Thunb. However, the effect of TSG on memory in adult is unclear till now. 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside (TSG) is a polyphenols compound from Polygonum multiflorum Thunb. The present study aimed to evaluate the effect of chronic administration of TSG on hippocampal memory in normal mice. Behavioral test, electrophysiology and golgi staining were used to evaluate the effect of TSG on hippocampus-dependent memory and synaptic plasticity. Western blotting was used to determine the expression of ERK1/2, CaMKII, and SIRT1. Real-time quantitative PCR was explored to measure miR-134. It was found that TSG enhanced hippocampus-dependent contextual fear memory and novel object recognition, facilitated hippocampal LTP and increased dendrite spine density in the CA1 region of hippocampus. TSG obviously promoted the phosphorylations of ERK1/2, CaMKII, CREB and the expression of BDNF in the hippocampus, with upregulation of silent information regulator 1 (SIRT1) and downregulation of miR-134. Chronic administration of TSG promotes hippocampal memory in normal mice, suggesting that supplementary of TSG might serve as an enhancement of memory.


Differential expression analysis of genes and long non-coding RNAs associated with KRAS mutation in colorectal cancer cells.
KRAS mutation is responsible for 40-50% of colorectal cancers (CRCs). RNA-seq data and bioinformatics methods were used to analyze the transcriptional profiles of KRAS mutant (mtKRAS) in comparison with the wild-type (wtKRAS) cell lines, followed by in-silico and quantitative real-time PCR (qPCR) validations. Gene set enrichment analysis showed overrepresentation of KRAS signaling as an oncogenic signature in mtKRAS. Gene ontology and pathway analyses on 600 differentially-expressed genes (DEGs) indicated their major involvement in the cancer-associated signal transduction pathways. Significant hub genes were identified through analyzing PPI network, with the highest node degree for PTPRC. The evaluation of the interaction between co-expressed DEGs and lncRNAs revealed 12 differentially-expressed lncRNAs which potentially regulate the genes majorly enriched in Rap1 and RAS signaling pathways. The results of the qPCR showed the overexpression of PPARG and PTGS2, and downregulation of PTPRC in mtKRAS cells compared to the wtKRAS one, which confirming the outputs of RNA-seq analysis. Further, significant upregualtion of miR-23b was observed in wtKRAS cells. The comparison between the expression level of hub genes and TFs with expression data of CRC tissue samples deposited in TCGA databank confirmed them as distinct biomarkers for the discrimination of normal and tumor patient samples. Survival analysis revealed the significant prognostic value for some of the hub genes, TFs, and lncRNAs. The results of the present study can extend the vision on the molecular mechanisms involved in KRAS-driven CRC pathogenesis.


Transforming growth factor-β and epithelial-mesenchymal transition are associated with pulmonary metastasis in adenoid cystic carcinoma.
Adenoid cystic carcinoma (ACC) is one of the most common malignancies of salivary glands, characterized by poor prognosis, particularly due to pulmonary metastasis. We previously reported that transforming growth factor (TGF)-β1 promoted ACC cell migration and invasion via the Smad pathway in vitro. The aim of this study was to establish the underlying mechanisms. TGF-β1, phospho-Smad2 and β-catenin expression in ACC tissues derived from patients was evaluated by immunohistochemistry. The role of TGF- β1 on the invasive capacity of ACC cells was determined by transwell assays in SACC-83 cells transfected with TGF-β1 and TGF-β type II dominant-negative receptor (TβRIIDN) plasmids or silenced by TGF-β1 siRNA. Expression of the epithelial-mesenchymal transition (EMT) markers, β-catenin, E-cadherin and Nectin-1, was determined by real-time PCR and immunochemistry. In vivo investigations were performed by inoculating nude mice with the transfected ACC cells and examining metastasis in bilateral lung tissues by immunohistochemistry. Overexpression of TGF-β1 and phospho-Smad2, and reduced expression of membrane β-catenin, were closely associated with lung metastasis in ACC. Furthermore, the EMT markers were downregulated. In vitro, cells transfected with TGF-β1 exhibited altered morphology and increased invasive capacity compared to TβRIIDN-transfected cells or TGF-β1 siRNA silenced cells. In vivo, mice inoculated with TGF-β1 transfected ACC cells exhibited more metastases than other cells. TGF-β1, phospho-Smad2 and β-catenin were significantly correlated with ACC metastasis. Blockade of TGF-β signaling by TβRIIDN or siRNA may offer potential gene therapies against pulmonary metastasis in patients with ACC.


Discordance of exocrine and endocrine growth after 90% pancreatectomy in rats.
As we have previously shown, by 8 wk after 90% pancreatectomy (PX) in the rat, there is considerable regeneration of both exocrine and endocrine pancreas. In this study we examine the growth of both the exocrine and endocrine tissue 3, 7, 14, and 21 days after PX by following the pancreatic content of insulin, glucagon, and amylase as well as the mitotic indices for exocrine and islet beta-cells. By 7 days the pancreatic remnant weighed more than the anatomically equivalent tissue in the sham, the remnant equivalent. The growth of the exocrine tissue and the endocrine beta-cells was discordant during these initial weeks after PX, as shown by the mitotic index. The mitotic index, measured as accumulated mitotic figures after a 4-h colchicine treatment, for both the exocrine and beta-cells in the sham animals was low and unchanging at the different time points (approximately 0.5%). At 3 and 7 days after PX, both the exocrine and beta-cells had mitotic indices three- to fourfold that of the sham animals. At 14 days after PX, the exocrine cells had a slightly, albeit significantly, elevated mitotic index, whereas that of the beta-cells was still double that of the shams. By 21 days there was no difference in mitotic index for exocrine tissue, but the beta-cells on the PX animals had a mitotic index still double that of the shams. Another index of growth, the cell birthrate, was estimated at 7 days from the slope of regression lines of the mitotic frequency accumulated 1, 2, 3, and 4 h after colchicine.(ABSTRACT TRUNCATED AT 250 WORDS)


Muscle and plasma amino acids after injury: the role of inactivity.
The amino acid pattern following total hip replacement is characterized by increases in muscle of the branched chain amino acids (leucine, isoleucine and valine), the aromatics (phenylalanine and tyrosine) as well as methionine. The nonessential amino acids in muscle tend to decline, glutamine having the most marked change. Plasma levels of the essential amino acids increase while the nonessentials tend to decrease. This pattern differs from that observed in other catabolic states (uremia, starvation, untreated diabetes) and is significantly different from the effects of inactivity and starvation combined. This suggests that injury can be characterized by a unique pattern of muscle and plasma amino acids.


Dietary Intervention to Increase Fruit and Vegetable Consumption in Breastfeeding Women: A Pilot Randomized Trial Measuring Inflammatory Markers in Breast Milk.
Diets rich in fruits and vegetables (F/V) can reduce the inflammatory profile of circulating cytokines and potentially decrease the risk of breast cancer. However, the extent to which a diet rich in F/V alters cytokine levels in breast tissue remains largely unknown. Breast milk provides a means of assessing concentrations of secreted cytokines in the breast microenvironment and is a potential tool for studying the effects of diet on inflammation in breast tissue and breast cancer risk. The aim of this pilot randomized trial was to test the feasibility of increasing F/V intake in breastfeeding women and of measuring changes in markers of inflammation in breast milk. Participants randomized to the intervention (n=5) were provided weekly boxes of F/V, along with dietary counseling, to increase consumption of F/V to 8 to 10 daily servings for 12 consecutive weeks. Controls (n=5) were directed to the US Department of Agriculture's "ChooseMyPlate" diet for pregnancy and breastfeeding. Ten breastfeeding women consuming fewer than five servings of F/V per day, as estimated by the National Institutes of Health "All-Day" Fruit and Vegetable Screener (F/V Screener), were recruited through flyers and a lactation consultant between February and May 2016 in the Western Massachusetts area. Baseline demographic and F/V intake data were collected during enrollment. At week 1 and week 13 (final) home visits, participants provided milk samples and anthropometric measurements were recorded. Participants completed F/V screeners at baseline and at study end. Adiponectin, leptin, C-reactive protein, and 11 additional cytokines were measured in breast milk collected at weeks 1 and 13. F/V consumption at baseline and after the final visit, and between controls and intervention groups, was compared with dependent and independent t tests, respectively. Differences between cytokine levels at weeks 1 and 13 were assessed with a mixed-effects repeated-measures model. All women in the intervention increased F/V intake and were consuming more servings than controls by week 13; daily serving of F/V at baseline and final visit: controls=1.6 and 2.0, diet=2.6 and 9.9. Most cytokines were detected in the majority of milk samples: 12 were detected in 90% to 100% of samples, one was detected in 75% of samples, and one was detected in 7.5% of samples; coefficients of variation were below 14% for 11 of the cytokines. These preliminary findings indicate that it is feasible to significantly increase F/V intake in breastfeeding women and provide support for conducting a larger diet intervention study in breastfeeding women, in which longer-term benefits of the intervention are assessed.


Phase II trial of neoadjuvant chemotherapy with docetaxel followed by epirubicin in stage II/III breast cancer.
In most neoadjuvant chemotherapy regimens, the taxane is administered either in combination with an anthracycline or after an anthracycline-containing regimen. We sought to test the feasibility, safety, and determine the pathological complete response (pCR) rate of administering docetaxel first followed by epirubicin as neoadjuvant chemotherapy in women with clinical stage II, III breast cancer. Twenty-five women with newly diagnosed clinical stage IIB (n = 10), IIIA (n = 5), or IIIB (n = 10) received 3 cycles of docetaxel 100 mg/M2 intravenously (IV) every 3 weeks followed by 3 cycles of epirubicin 100 mg/M2 IV every 3 weeks. pCR was defined as the absence of invasive cancer in the breast at definitive surgery. The median primary tumor size was 6 cm (range 1-12 cm), and 13 (52%) women had clinically palpable axillary lymph nodes. Patients received 149 of the 150 planned cycles of docetaxel and epirubicin without treatment delays, and only 3 (12%) patients had a dose reduction of docetaxel. Seven (28%) patients experienced febrile neutropenia, and 9 (36%) patients had grade 3 non-hematological toxicities with diarrhea being the most frequent in 3 (12%) patients. Six (24%) patients had pCR in the breast. Analysis of pre- and post-docetaxel biopsies from a subset of patients documented taxane-induced activation of mitogen-activated and stress-activated protein kinase pathways. Neoadjuvant docetaxel followed by epirubicin is well tolerated and active in breast cancer. To our knowledge, this is first description of docetaxel-induced activation of mitogen-activated and stress-activated protein kinase pathways in human breast cancer.


Phase I study of suramin given by intermittent infusion without adaptive control in patients with advanced cancer.
Suramin is a promising agent for the treatment of hormone-refractory metastatic prostate cancer. However, questions about the relationship of severe neurotoxicity to sustained peak plasma concentrations greater than 300 micrograms/mL raised concerns that this drug could not be safely administered without adaptive control. To test the adaptive-control hypothesis, we designed a phase I study that relied on clinical end points, using a fixed dosing scheme that did not rely on adaptive control. In a phase I dose-escalation study using fixed dosing without adaptive control, gradually decreasing doses of suramin were administered to 63 patients on days 1 (loading dose), 2, 8, and 9 of a 28-day cycle. Fifty-four patients with hormone-refractory metastatic prostate cancer and nine patients with other solid tumors have been treated. Doses of 400 mg/m2 to 2,080 mg/m2 on the first day have been administered. The mean peak plasma concentration following the loading dose at a dose level of 1,730 mg/m2 was 933 micrograms/mL (26% coefficient of variation), and the mean trough concentration was 139 micrograms/mL (40% CV) on day 1 of cycle 2 [corrected]. At 1,730 mg/m2, five of 13 patients experienced dose-limiting toxicity (DLT), including malaise, neurotoxicity, pericardial effusion, and coagulopathy. At 2,080 mg/m2, three of five patients experienced DLT. Two patients treated at this dose level died while on study. One of these patients died of a subdural hematoma sustained after a fall and had a prolonged prothrombin time at the time of his death. One patient developed classic suramin neurotoxicity, which led to respiratory failure, for which the patient refused intubation. No significant associations were noted between peak or trough concentrations during either cycles 1 or 2 and the occurrence of neurotoxicity. (1) Suramin can be safely administered without adaptive control, (2) suramin on this schedule may exhibit significant activity against hormone-refractory metastatic prostate cancer, and (3) based strictly on toxicity considerations, we recommended that a day-1 dose of 1,440 mg/m2 be used in subsequent clinical trials, with a maximum of three cycles. Further studies to establish the optimal empiric dosing regimen are needed.


[Ferritin. Radioimmunological determination in serum and clinical significance (author's transl)].
Ferritin is an iron storage protein which has been shown to be present in blood serum only recently. An immunoradiometric determination of ferritin in 324 subjects with different iron stores is reported. In healthy men and women a ferritin concentration of 131 microgram/l (SD: 1,59) and 67 microgram/l (SD: 1,79) was found respectively. In male and female blood donors as well as patients with iron deficiency and iron overload significant differences of serum ferritin concentration could be demonstrated. In clinical practice the determination of serum ferritin is a valuable method for the estimation of body iron stores.


Role of surfactants in improving release from higher drug loading amorphous solid dispersions.
Amorphous solid dispersion formulations (ASD) are increasingly being used as a formulation strategy to improve bioavailability of poorly soluble drugs. One of the limitations of ASDs, in particular for high glass transition temperature (Tg) compounds, is the drug loading threshold (termed the limit of congruency, LoC) below which rapid, complete and congruent release of drug and polymer is achieved. In this study, several ionic and non-ionic surfactants were added to atazanavir-copovidone ASDs with the main goal of increasing the limit of congruency. Atazanavir (ATZ) is a relatively high Tg compound with a LoC of 5 % drug loading (DL). Surface normalized dissolution studies revealed that addition of 5 % w/w of surfactant, sodium dodecyl sulfate (SDS) or cetrimonium bromide (CTAB), to the binary copovidone-based ASD doubled the LoC (from 5 to 10 % DL), resulting in a more than 30-fold increase in total release compared to the corresponding binary ASD. Moreover, addition of 5 % of Span®80 increased the LoC to 15 % DL. ASD Tg was found to decrease upon addition of surfactants and water sorption extent was found to increase. We speculate that surfactants act as plasticizers, which may facilitate polymer release from ASDs containing a high Tg drug, providing a possible explanation for the observed enhancement in drug release from ternary ASDs and the increase in LoC.


The round-ear incision in full face-lifting.
Several techniques for face-lifting have been described, all aimed at achieving a youthful appearance with a hidden scar. The authors are concerned about the conspicuous horizontal scar that travels all the way through the hairless skin behind the ears, which they consider very unpleasant and totally unnecessary. They are able to achieve a normal-appearing face with a safer technique that minimizes the visible scars such as the postauricular one, yet still has good and lasting results. In the past 9 years, 202 patients, men and women ages 38 to 86 years, have undergone surgery using the round-ear face-lifting technique, most of them with local anesthesia and sedation. The authors were able to achieve good and lasting results with a minimum of complications and to change the unaesthetic postauricular scar to a retroauricular one (with contouring of the concha) using a new design of marking the skin incisions. A new face-lifting incision is described. The procedure is suitable and safer for all patients requiring facial rejuvenation. The main advantage of this technique is the absence of visible postauricular scars.


Early environmental exposures influence schizophrenia expression even in the presence of strong genetic predisposition.
There are few studies of environmental factors in familial forms of schizophrenia. We investigated whether childhood adversity or environmental factors were associated with schizophrenia in a familial sample where schizophrenia is associated with the NOSA1P gene. We found that a cumulative adversity index including childhood illness, family instability and cannabis use was significantly associated with narrow schizophrenia, independent of NOSA1P risk genotype, previously measured childhood trauma, covariates and familial clustering (adjusted odds ratio (95% confidence interval)=1.55 (1.01, 2.38)). The results provide further support that early environmental exposures influence schizophrenia expression even in the presence of strong genetic predisposition.


Choroid plexus structure and function in young rats on a high-potassium diet.
Rats, 20 days old, were fed a diet containing 20% KCl for 10 days. At 30 days these rats had lower body, brain and choroid plexus weights than matched controls and plasma [K+] was increased to 7.5 mM compared to 4.1 mM for controls. Cerebrospinal fluid (CSF) [K+] and bulk fluid secretion were not changed by the high K+ diet but there was a mild metabolic acidosis. The fourth ventricle choroid plexus was prepared for transmission electron microscopy and the structure of the epithelium analysed by quantitative stereology. The high K+ rats had a large increase in the mitochondrial volume fraction of the epithelium due to a 36% increase in individual mitochondrial volume. The high-K+ rats also had a decrease in the apical surface density of the epithelium due to a 41% decrease in the height of the microvilli. It is concluded that the increase in mitochondrial volume may provide the additional energy required for the increased transport of K+ out of the CSF in hyperkalaemia. The reduction in height of the microvilli could be a means for maintaining a normal CSF bulk secretion rate despite the increase in K+ transport required to maintain normal CSF [K+] in hyperkalaemia.


Detection of Fukushima Daiichi nuclear power plant accident radioactive traces in Monaco.
Daily air monitoring of radionuclides in the Principality of Monaco (43°73'N, 7°43'E) after the Fukushima Daiichi nuclear power plant accident showed that only Iodine-131 ((131)I) and Caesium isotopes ((134)Cs and (137)Cs) were detected. The peak of (131)I varied and reached its maximum between March 29th and April 5th, meanwhile both peaks of (134)Cs and (137)Cs arrived later and attained a maximum between April 1st and 4th. Their maximum activity concentrations in air were 354, 30, and 37 μBq m(-3) respectively. The (134)Cs to (137)Cs activity ratio was close to 1, which is different from that one observed after the Chernobyl accident (around 0.54). Up to 95% of caesium isotopes were washed out by wet scavenging during 27-28th of March, where the maximum deposition rates of (134)Cs and (137)Cs (13.7 and 19.1 mBq m(-2) day(-1), respectively) were observed. The significant input of (134)Cs and (137)Cs into the Mediterranean seawater column (30 m depth) was detected later, on the 24th of May. Radioisotopes of caesium and iodine were found far above the applied detection limits, but still with no concern for harmful radiation exposure and public health. The contamination gradually decreased in air and activity concentrations returned to background values after one or two months.


Exosomes derived from schwann cells alleviate mitochondrial dysfunction and necroptosis after spinal cord injury via AMPK signaling pathway-mediated mitophagy.
Although spinal cord injury (SCI) represents a primary etiology of disability, currently, there are exist limited viable therapies modalities. Acquiring comprehension of the diverse pathways that drive mitochondrial aberration may facilitate the identification of noteworthy targets for ameliorating the deleterious consequences precipitated by SCI. Our objective was to determine the efficiency of exosomes produced from Schwann cells (SCDEs) in protecting against mitochondrial dysfunction. This evaluation was conducted using a rat model of compressed SCI and in vitro experiments involving rat pheochromocytoma cells (PC12) exposed to oxygen-glucose deprivation (OGD). The conducted experiments yielded evidence that SCDEs effectively mitigated oxidative stress (OS) and inflammation subsequent to SCI, while concurrently diminishing necroptosis. Subsequent in vitro inquiry assessed the impact of SCDEs on PC12, with a specific emphasis on mitochondrial functionality, necrotic cell prevalence, and mitophagy. The study findings revealed that SCDEs enhanced mitophagy in PC12 cells, leading to a decrease in the generation of reactive oxygen species (ROS) and inflammatory cytokines (CK) provoked by OGD-induced injury. This, in turn, mitigated mitochondrial dysfunction and necroptosis. Mechanistically, SCDEs facilitated cellular mitophagy through activation of the AMPK signaling pathway. In conclusion, our data strongly support the notion that SCDEs hold considerable promise as a therapeutic approach for managing SCI. Furthermore, our investigation serves to elucidate the pivotal role of AMPK-mediated mitophagy in reducing cell damage, thereby unveiling novel prospects for enhancing neuro-pathological outcomes following SCI.


Temporal host-parasite relationships of the wild rabbit, Oryctolagus cuniculus (L.) as revealed by stable isotope analyses.
Natural abundances of the stable isotopes, 15N/14N (delta15N) and 13C/12C (delta13C), were used to study temporal host-parasite relationships of the wild rabbit, Oryctolagus cuniculus (L.). During the 12-month sampling period, temporal isotopic shifts in delta15N were noted for dietary vegetation, host rabbit faeces and fur, but not for muscle or stomach contents. delta15N varied temporally for the parasitic cestode species, Mosgovoyia pectinata but not for Cittotaenia denticulata. Similarly, intestinal parasitic nematodes had apparent species-specific delta15N patterns. Only rabbit fur and intestinal parasitic nematodes did not exhibit temporal shifts in delta13C. Overall, host faeces and stomach contents were isotopically indistinct as a likely consequence of coprophagy. Relative to their host, parasitic nematodes were 15N-enriched, consistent with an increase in trophic level status. Conversely, cestodes were 15N-depleted. Isotopically, each parasite reflected a species-specific relationship with their rabbit host. This technique could be utilized to integrate parasites into food-web studies.


[Effect of sudden decompression on tissue pressure in the brain and the cerebrospinal fluid pressure].
Extracranial hypertension was produced in cats by means of epidural compression with a baloon. After 2 hours of compression sudden decompression was performed and tissue pressure was compared at symmetrical sites of cerebral hemispheres with cerebrospinal fluid pressure measured in the cisterna magna. It was found that symmetrical tissue pystem, which was due probably to early oedema developing in the compressed area.


Fentanyl intoxication caused by abuse of transdermal fentanyl.
Fentanyl has an analgesic effect 100 times greater than that of morphine; therefore, transdermal administration of fentanyl has been widely used to control pain. Due to misconceptions regarding the proper use of fentanyl, its simple method of administration, and the absence of regulatory rules regarding its use, both medical providers and non-medical providers have abused fentanyl. We report on three cases of fentanyl intoxication and suggest solutions to prevent its abuse in the future. Three patients were intoxicated by transdermal fentanyl, which resulted in respiratory depression. Two of these cases were attributed to non-medical use of the drug and the other occurred while using fentanyl as directed by medical personnel. Physicians should use transdermal fentanyl only to control chronic pain, and rules should be established to prevent abuse of fentanyl that occurs due to its ease of use and the absence of any established policy regarding the prescription and disposal of this drug.


Self-Assembly of Novel Thiophene-Based BODIPY RuII Rectangles: Potential Antiproliferative Agents Selective Against Cancer Cells.
Novel Ru (2+2) rectangles were designed and synthesized by self-assembly of a new thiophene-functionalized dipyridyl BODIPY ligand, BDPS, and ruthenium(II) precursors. The complexes exhibited dose-dependent antiproliferative activities against cancer cells, in which some compounds selectively kill cancer cells. The net fluorescence due to BODIPY allowed us to visualize their location inside cancer cells. Moreover, the metalla-rectangles displayed substantial propensity to bind with biomolecules.


SARS-CoV-2 Infections Among Children in the Biospecimens from Respiratory Virus-Exposed Kids (BRAVE Kids) Study.
Children with SARS-CoV-2 infection typically have mild symptoms that do not require medical attention, leaving a gap in our understanding of the spectrum of illnesses that the virus causes in children. We conducted a prospective cohort study of children and adolescents (<21 years of age) with a SARS-CoV-2-infected close contact. We collected nasopharyngeal or nasal swabs at enrollment and tested for SARS-CoV-2 using a real-time PCR assay. Of 382 children, 289 (76%) were SARS-CoV-2-infected. SARS-CoV-2-infected children were more likely to be Hispanic (p<0.0001), less likely to have a history of asthma (p=0.009), and more likely to have an infected sibling contact (p=0.0007) than uninfected children. Children ages 6-13 years were frequently asymptomatic (38%) and had respiratory symptoms less often than younger children (30% vs. 49%; p=0.008) or adolescents (30% vs. 59%; p<0.0001). Compared to children ages 6-13 years, adolescents more frequently reported influenza-like (61% vs. 39%; p=0.002), gastrointestinal (26% vs. 9%; p=0.003), and sensory symptoms (43% vs. 9%; p<0.0001), and had more prolonged illnesses [median (IQR) duration: 7 (4, 12) vs. 4 (3, 8) days; p=0.004]. Despite the age-related variability in symptoms, we found no differences in nasopharyngeal viral load by age or between symptomatic and asymptomatic children. Hispanic ethnicity and an infected sibling close contact are associated with increased SARS-CoV-2 infection risk among children, while a history of asthma is associated with decreased risk. Age-related differences in the clinical manifestations of SARS-CoV-2 infection must be considered when evaluating children for COVID-19 and in developing screening strategies for schools and childcare settings.


Covalent transfer of chemical gradients onto a graphenic surface with 2D and 3D control.
Control over the functionalization of graphenic materials is key to enable their full application in electronic and optical technologies. Covalent functionalization strategies have been proposed as an approach to tailor the interfaces' structure and properties. However, to date, none of the proposed methods allow for a covalent functionalization with control over the grafting density, layer thickness and/or morphology, which are key aspects for fine-tuning the processability and performance of graphenic materials. Here, we show that the no-slip boundary condition at the walls of a continuous flow microfluidic device offers a way to generate controlled chemical gradients onto a graphenic material with 2D and 3D control, a possibility that will allow the sophisticated functionalization of these technologically-relevant materials.


[Upstream migration of Philopotamus montanus (Trichoptera)].
Imagines of Philopotamus montanus were sampled by light-traps and by hand at four sites along the Kaltisjokk in Swedish-Lappland. The samples were quantitatively and qualitatively analysed and compared. They differed in the following points: 1. There were many more imagines at the mouth of the stream than in the upper reaches. 2. At the mouth of the stream the percentage of the females was about one third compared with the samples from the upper reaches. Most of these females were immature, whereas most of the females from the upper parts had already laid their eggs. Mature females, which were ready for the first oviposition were distributed uniformly along the stream. 3. The proportion of mature females caught in the light-traps was twice that caught by hand. Immature females and females which had already laid their eggs were less numerous in the light-traps than in the hand-catches. 4. During the ten-day period of the investigation the differences between the samples from the four sites decreased. 5. With the light-traps most of the insects were caught during the day-time (6-22h). The sex ratio changed with the time of day. In the morning males dominated the catch, and in the afternoon females. 6. The reliability of the methods is discussed and the hypothesis is put forward that mature, egg-bearing females migrate upstream.


Biotechnological potential of fungi from a mangrove ecosystem: Enzymes, salt tolerance and decolorization of a real textile effluent.
The mangrove is an ecosystem bounded by the line of the largest tide in size that occurs in climatic and subtropical regions. In this environment, microorganisms and their enzymes are involved in a series of transformations and nutrient cycling. To evaluate the biotechnological potential of fungi from a mangrove ecosystem, samples from mangrove trees were collected at the Paranaguá Estuarine Complex in Brazil and 40 fungal isolates were obtained, cultivated, and screened for hydrolytic and ligninolytic enzymes production, adaptation to salinity and genetic diversity. The results showed a predominance of hydrolytic enzymes and fungal tolerance to ≤ 50 g L-1 sodium chloride (NaCl) concentration, a sign of adaptive halophilia. Through morphological and molecular analyses, the isolates were identified as: Trichoderma atroveride, Microsphaeropsis arundinis, Epicoccum sp., Trichoderma sp., Gliocladium sp., Geotrichum sp. and Cryphonectria sp. The ligninolytic enzymatic potential of the fungi was evaluated in liquid cultures in the presence and absence of seawater and the highest activity of laccase among isolates was observed in the presence of seawater with M. arundinis (LB07), which produced 1,037 U L-1. Enzymatic extracts of M. arundinis fixed at 100 U L-1 of laccase partially decolorized a real textile effluent in a reaction without pH adjustment and chemical mediators. Considering that mangrove fungi are still few explored, the results bring an important contribution to the knowledge about these microorganisms, as their ability to adapt to saline conditions, biodegradation of pollutants, and enzymatic potential, which make them promising candidates in biotechnological processes.


Facilitation of amphetamine-induced rotation by muscarinic antagonists is correlated with M2 receptor affinity.
This study examined the relationship between the affinity of cholinergic drugs for muscarinic receptor subtypes and their potency in potentiating or inhibiting amphetamine-induced rotation. The ascending nigrostriatal dopaminergic pathway was unilaterally lesioned in male Wistar rats using 6-hydroxydopamine. In these rats, ipsiversive rotation induced by amphetamine sulphate (1 mg/kg, s.c.) was dose-dependently inhibited by the cholinergic agonists oxotremorine, RS86 and pilocarpine and by the acetylcholinesterase inhibitor physostigmine. In contrast the cholinergic antagonists scopolamine, secoverine and dicyclomine facilitated amphetamine-induced rotation. Agonist and antagonist potencies were then compared with M1 and M2 binding site affinities estimated by displacing [3H]pirenzepine from forebrain and [3H]QNB from brainstem homogenates. The data suggest a relationship between antagonist potency and M2 binding site affinity.


Targetted correction of a mutant HPRT gene in mouse embryonic stem cells.
Two recent developments suggest a route to predetermined alterations in mammalian germlines. These are, first, the characterization of mouse embryonic stem (ES) cells that can still enter the germline after genetic manipulation in culture and second, the demonstration that homologous recombination between a native target chromosomal gene and exogenous DAN can be used in culture to modify specifically the target locus. We here use gene targetting functionally to correct the mutant hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene in the ES cell line which has previously been isolated and used to produce an HPRT-deficient mouse. This modification of a chosen gene in pluripotent ES cells demonstrates the feasibility of this route to manipulating mammalian genomes in predetermined ways.


A method for the determination of minoxidil in hair-regrowth formulations by micellar electrokinetic capillary chromatography.
A method based on micellar electrokinetic capillary chromatography (MEKC) was developed for determination of minoxidil in Rogaine and competing products. The original intent of the work was to offer an orthogonal means to HPLC for testing illicit imitations of Rogaine. However, because the patent has since expired, we offer the procedure as a confirmatory measure to HPLC for assay of generic minoxidil products. The MEKC procedure complements an earlier method based on free solution capillary electrophoresis (FSCE), designed to the same end. Validation was carried out on both a Dionex CES-1, which utilizes gravity injection, and a PE-ABI 270HT, which employs vacuum injection. The procedure was validated for both active pharmaceutical ingredient and for minoxidil solutions. The run buffer is pH 7.0, 20 mM sodium phosphate, 20 mM sodium dodecyl sulfate, with 10% isopropanol; the internal standard is dl-tryptophan. The method bears the attributes of simplicity, ease of use, and short analysis time (12 min). It is selective with respect to known process and degradation impurities. High efficiency was achieved on the CES-1, with a plate count exceeding 200,000 for minoxidil at an elution time of 9 min. Although slight differences in performance were noted across the two instruments, results on both were in conformance with modern day validation expectations. Comparison of MEKC with HPLC resulted in slightly higher values for the former, but all results met registration specifications and internal targets.


Identifying rare variants using a Bayesian regression approach.
Recent advances in next-generation sequencing technologies have made it possible to generate large amounts of sequence data with rare variants in a cost-effective way. Statistical methods that test variants individually are underpowered to detect rare variants, so it is desirable to perform association analysis of rare variants by combining the information from all variants. In this study, we use a Bayesian regression method to model all variants simultaneously to identify rare variants in a data set from Genetic Analysis Workshop 17. We studied the association between the quantitative risk traits Q1, Q2, and Q4 and the single-nucleotide polymorphisms and identified several positive single-nucleotide polymorphisms for traits Q1 and Q2. However, the model also generated several apparent false positives and missed many true positives, suggesting that there is room for improvement in this model.


Immune function, autoimmunity, and selective immunoprophylaxis in the aged.
Many changes occur in the immune system with age. The involution of the thymus plays a major role in immune senescence. Related to this event are the altered ratio of helper to suppressor T-lymphocyte subsets, decrease in immune response by both cell-mediated and humoral branches of the immune system, and increase in autoimmune activity. The clinical implications of these changes are the elderly person's increased susceptibility to infections such as pneumococcal pneumonia, influenza A, and tetanus as well as increased autoimmune activity, reflected by pernicious anemia. Other changes may be increased susceptibility to neoplasms and perhaps acceleration of the aging process. A high index of suspicion should be present for the diagnosis of pernicious anemia in the elderly population. Knowledge of the many autoantibodies that might be present without illness is important when evaluating for disease processes. The relationship of the senescent immune system to the aging process is still unknown. Investigations of this matter, as well as of the function of immune system components and their relationship to disease processes, are continuing. Most methods proposed for enhancing the immune system are still experimental. However, immunizations have been proved to be an effective means of reducing morbidity and mortality from certain infectious diseases in the elderly. Therefore, it is strongly recommended that all elderly persons who are at risk for pneumococcal pneumonia, influenza, and tetanus receive the proper immunizations.


Universal lymph node detection in T2 MRI using neural networks.
Identification of lymph nodes (LNs) that are suspicious for metastasis in T2 Magnetic Resonance Imaging (MRI) is critical for assessment of lymphadenopathy. Prior work on LN detection has been limited to specific anatomical regions of the body (pelvis, rectum). Therefore, an approach to universally detect both benign and metastatic nodes in T2 MRI studies of the body is highly desirable. We developed a Computer Aided Detection (CAD) pipeline to universally identify LN in T2 MRI. First, we trained various neural networks for detecting LN: Faster RCNN with and without Hard Negative Example Mining (HNEM), FCOS, FoveaBox, VFNet, and Detection Transformer (DETR). Next, we show that VFNet with Adaptive Training Sample Selection (ATSS) outperformed Faster RCNN with HNEM. Finally, we ensembled models that surpassed a 45% mAP threshold. Experiments on 122 test studies revealed that VFNet achieved a 51.1% mAP and 78.7% recall at 4 false positives (FP) per volume, while the one-stage model ensemble achieved a mAP of 52.3% and sensitivity of 78.7% at 4FP. We found that VFNet and the one-stage model ensemble can be interchangeably used in the CAD pipeline. Our CAD pipeline universally detected both benign and metastatic nodes in T2 MRI studies, resulting in a sensitivity improvement of [Formula: see text]14% over the current LN detection approaches (sensitivity of 78.7% at 4 FP vs. 64.6% at 5 FP per volume).


Purification and determination of antibody drugs in bio-samples by EGFR/cell membrane chromatography method.
With the rapid development of therapeutic monoclonal antibody drugs, it is increasingly difficult to meet clinical needs using traditional antibody purification techniques. In this study, epidermal growth factor receptor (EGFR)-SNAP-tag was expressed in HEK293 cells. Then we captured the EGFR-SNAP-tag from the cell membrane suspension onto a O6-benzylguanine-modified silica gel to prepare a new EGFR stationary phase as a bioactive material, which could specifically recognize its antibody in bio-samples. The EGFR stationary phase was systematically characterized via scanning electron microscopy, transmission electron microscopy, X-ray photoelectron spectroscopy, and fourier transform infrared spectroscopy. Then we used EGFR stationary phase to establish a new EGFR cell membrane chromatography (CMC) model. The EGFR/CMC-online-ion exchange chromatography (IEC)/high performance liquid chromatography (HPLC) was established for the efficient purification and specific identification of cetuximab, nituzumab, and panizumab from cell culture medium and human serum. The results show that the EGFR stationary phase prepared by one-step immobilized technique can maintain biological activity and stability like EGFR in cell membrane. The EGFR/CMC-online-IEC/HPLC method has a high specificity, accuracy and sensitivity. Therefore, it will present a valuable method for the purification, identification, and analysis of monoclonal antibody drugs.


Prevention of IOP-rise following Nd-YAG laser capsulotomy with pre-operative timolol eye-drops and 1 tablet acetazolamide 250 mg systematically.
Short-term observation following Nd-YAG laser capsulotomy indicates that serious elevation of intra-ocular pressure may occur, unrelated to the amount of energy used. In this study the IOP in 3 groups of 10 pseudophakic patients undergoing Nd-YAG laser posterior capsulotomy was measured before capsulotomy and 2 and 4 hours afterwards, using the fellow-eye as control. The first group received no medication, the second received timolol 1/2% eyedrops preoperatively, the third group a combination of timolol 1/2% and 1 tablet of acetazolamide 250 mg systemically. Pretreatment with timolol 0.5% minimizes IOP-rise but does not give complete protection. The combination of timolol 0.5% with 1 tablet of acetazolamide 250 mg proves to be a safe procedure for the prevention of IOP-rise after YAG laser capsulotomy. To prevent other complications it is advisable to make a small capsulotomy of 2-3 mm diameter using as little energy as possible. Also a defocussing system in the laser is a great advantage. Indomethacin drops during a period of 6 weeks after Nd-YAG laser capsulotomy should prevent cystoid macular edema.


A comparative double blind study of ketoconazole and griseofulvin in dermatophytosis.
The merits of oral ketoconazole and griseofulvin in dermatophytosis have been compared in a double blind study on 74 patients with 152 infected sites. The initial daily doses were 200 mg and 500 mg respectively, but these were doubled after 3 months if there was an inadequate clinical response. Treatment was continued either until clinical and mycological remission was achieved or a year of therapy had been given. Seventy-five per cent (total 80) and 74% (total 72) of all infected sites treated with ketoconazole and griseofulvin respectively were cleared of infection. However, in toe nail infections the respective cure rates were only 21% and 17%. Ketoconazole appeared to act more rapidly in curing tinea corporis or tinea cruris due to Trichophyton rubrum, whereas griseofulvin was superior in T. interdigitale infections. No serious side-effects were encountered in either treatment group. In view of the slight risk of drug-induced hepatitis, ketoconazole is best reserved as a second-line drug for toe nail infections unless there are specific indications, such as griseofulvin intolerance. In these cases liver function tests should be monitored regularly throughout therapy.


Educating healthcare providers in geriatric oncology - A call to accelerate progress through identifying the gaps in knowledge.
The majority of patients with cancer are over the age of 65. This patient population often has unique care needs. Thus, clinicians require additional competencies and skills to care for this population. Most clinicians, however, receive little to no training in geriatrics. There has been increasing recognition of the importance of learning about geriatric oncology. However, teaching of geriatric oncology principles is not standard or widespread. Here we highlight educational work and scholarship accomplished thus far in the field of geriatric oncology and identify gaps in knowledge that need to be addressed in order to help accelerate the development, implementation, integration, and dissemination of geriatric oncology curricula. These, in turn, will hopefully help improve the knowledge and skills of clinicians caring for older adults with cancer globally.


Reverse end-diastolic umbilical artery velocity in a case of intrauterine fetal death at 14 weeks' gestation.
A case of intrauterine fetal death at 14 week's gestation in a mother with systemic lupus erythematosus is described. Doppler ultrasonography performed within 24 hours before fetal death showed reverse end-diastolic flow velocities on umbilical artery velocity waveforms. The placental alteration causing this early gestation is discussed.


[Investigation of Coptis chinensis on jaundice of glucose-6-phosphate dehydrogenase (G6PD) deficient neonates from Guigang, Guangxi province].
To investigate the effect of Coptis chinensis on jaundice of G6PD deficient neonates. 122 G6PD deficient neonates with jaundice who were in People' s Hospital of Guigang of Guangxi province from January 1999 to October 2004 were divided into two groups: C. chinensis group (62 neonates with C. chinensis administration before jaundice' s appearance) and none C. chinensis group (60 neonates without C. chinensis administration before jaundice' s appearance). The initial time, duration of jaundice, hemoglobin and serum bilirubin level and the incidence of kernicterus were analyzed between the two groups. The initial time of jaundice is significantly later and the duration of jaundice is markedly shorter in the neonates with C. chinensis than that without C. chinensis. Simultaneously, the level of hemoglobin is significantly increased, and there is a low tendency of serum total bilirubin and direct bilirubin level in C. chinensis group as compared to that in none C. chinensis group. Moreover, there is no kernicterus in C. chinensis group and no difference in the treating result out of hospital between the two groups. Our results do not support the view that C. chinensis could aggravate jaundice of G6PD deficient neonates.


Application of the Human Well-Being Index to Sensitive Population Divisions: A Children's Well-Being Index Development.
The assessment of community well-being is critical as an end-point measure that will facilitate decision support and assist in the identification of sustainable solutions to address persistent problems. While the overall measure is important, it is equally vital to distinguish variations among groups within the population who may be impacted in a different manner. The U.S. Environmental Protection Agency (US EPA) developed the Human Well-Being Index (HWBI), as a way of measuring these outcomes and assessing community characteristics. The HWBI approach produces a suite of indicators, domains and a final composite index appropriate for characterizing well-being of a population. While generalized approaches are needed, it is important to also recognize variations in well-being across community enclaves. This paper presents an adaption of the HWBI for child populations to test the applicability of the index framework to specific community enclaves. First, an extensive literature review was completed to ensure the theoretical integrity of metric and indicator substitutions from the original HWBI framework. Metric data were then collected, refined, imputed where necessary and evaluated to confirm temporal and spatial availability. A Children's Well-Being Index (CWBI) value, representing the same indicators and domains of well-being as the original HWBI, was calculated for the population under age 18 across all US counties for 2011. Implications of this research point to an effective, holistic end-point measure that can be tracked over time. Similarly, there is great potential for the application of the original HWBI method to other statistical population segments within the greater US population. These adaptations could help identify and close gaps in equity of resource distribution among these groups.


Longitudinal multimodal functional macular analysis after half-dose photodynamic therapy for central serous chorioretinopathy.
Half-dose photodynamic therapy (HD-PDT) has been widely used for central serous chorioretinopathy (CSC) with good anatomical results. However, long-term functional outcomes after this treatment remain uncertain. This study aimed a longitudinal multimodal macular assessment, correlating functional and anatomical outcomes. This is a retrospective study performed in a tertiary referral center including 111 eyes from 95 CSC patients. Data on best corrected visual acuity (BCVA), central macular thickness (CMT), central retinal sensitivity (CRS) using microperimetry (MP) and multifocal electroretinography (mfERG) at baseline and 3, 6, 12, 18, 24, 36, 48 and 60 months after treatment were registered. A correlation analysis was performed. Mean follow-up was 34.5 ± 26.3 months. A significant improvement in BCVA and CMT was registered in all the visits. CRS significantly improved until 24 months (p < 0.001 at 12 months, p < 0.05 at 24 months), worsening afterwards. The mfERG amplitude of N1 and P1 waves significantly improved in the first 12 months, aggravating afterwards. The implicit time improved until 24 months, deteriorating after 48 months. This long-term decline was also described in some inactive untreated fellow eyes CONCLUSIONS: A multimodal longitudinal analysis of CSC patients after HD-PDT shows that, after the first 12 to 24 months, the significant sustained improvement in BCVA and CMT is not paired by a sustained improvement in macular sensitivity or electrical response. This long-term functional deterioration might result from the disease itself and not directly from the treatment .


The effect of hypothalamic hemi-islands on compensatory adrenal growth.
Unilateral hypothalamic disconnections were made with a Halász knife in young male rats to determine the effects of these lesions on adrenal weight, and the response to unilateral adrenalectomy. Rats were unilaterally adrenalectomized or sham-adrenalectomized 5-7 days after the hypothalamic surgery. No lesion affected adrenal weight in sham-adrenalectomized rats. Compensatory adrenal growth 3 days after unilateral adrenalectomy is prevented by a unilateral hypothalamic hemi-island on the side ipsilateral, not contralateral, to the first removed adrenal (P less than 0.01). Portions of the ipsilateral hemi-island were examined to determine which interrupted the compensatory adrenal growth response. The anterior 90 degrees portion enhanced compensatory adrenal growth (P less than 0.01). The posterior 90 degrees portion only partially inhibited compensatory adrenal growth (P less than 0.05), while the posterolateral portion completely inhibited the response (P less than 0.01). Plasma ACTH and corticosterone levels at the time of sacrifice were unaffected by unilateral adrenalectomy, but were slightly elevated by the hypothalamic cuts. These studies provide further evidence that compensatory adrenal growth is mediated neurally.


Discovery of new 2-phenyl-1H-benzo[d]imidazole core-based potent α-glucosidase inhibitors: Synthesis, kinetic study, molecular docking, and in vivo anti-hyperglycemic evaluation.
In the present study, a series of 2-phenyl-1H-benzo[d]imidazole-based α-glucosidase inhibitors were synthesized and evaluated for their in vitro and in vivo anti-diabetic potential. Screening of an in-house library revealed a moderated α-glucosidase inhibitor, 6a with 3-(1H-benzo[d]imidazol-2-yl)aniline core, and then the structural optimization was performed to obtain more efficient derivatives. Most of these derivatives showed increased activity than 6a, and the most promising inhibitors were found to be compounds 15o and 22d with IC50 values of 2.09 ± 0.04 and 0.71 ± 0.02 µM, respectively. Fluorescence quenching experiment confirmed the direct binding of compounds 15o and 22d with α-glucosidase. Kinetic study revealed that both compounds were non-competitive inhibitors, that was consistent with the result of molecular docking studies where they located at the allosteric site of the enzyme. Cell viability evaluation demonstrated the non-cytotoxicity of 15o and 22d against LO2 cells. Furthermore, the in vivo pharmacodynamic study revealed that compound 15o showed significant hypoglycemic activity and improved oral sucrose tolerance, comparable to the positive control acarbose.


Differentiation between metabolic incorporation and covalent binding in the labeling of macromolecules in the rat nasal mucosa and bone marrow by inhaled [14C]- and [3H]formaldehyde.
The mechanisms of labeling of macromolecules (DNA, RNA, and protein) in the respiratory and olfactory mucosa, and in the bone marrow (femur) of male Fischer-344 rats exposed to [14C]- and [3H]formaldehyde [( 14C]- and [3H]CH2O) were investigated. Animals were exposed for 6 hr to atmospheres containing [14C]- and [3H]CH2O at concentrations of 0.3, 2, 6, 10, or 15 ppm, 1 day following a single pre-exposure to the same concentration of unlabeled CH2O. The major route of nucleic acid labeling at all concentrations and in all tissues was metabolic incorporation; protein labeling in the respiratory mucosa was mainly due to covalent binding at the higher CH2O concentrations. Incorporation of [14C]CH2O into DNA in the respiratory mucosa was maximal at 6 ppm but decreased at higher concentrations, whereas labeling of DNA in the olfactory mucosa and bone marrow increased monotonically with concentration. Evidence for covalent binding of CH2O to respiratory mucosal DNA was obtained at CH2O concentrations equal to or greater than 2 ppm. The concentration of CH2O covalently bound to DNA at 6 ppm was 10.5-fold higher than at 2 ppm, indicating significant nonlinearity of DNA binding with respect to the inhaled formaldehyde concentration under these conditions. Covalent binding to proteins increased in an essentially linear manner with increases in the airborne concentration. No evidence was obtained for the formation of covalent adducts with macromolecules in the olfactory mucosa or bone marrow. The nonlinear increase in covalent binding to respiratory mucosal DNA with increasing CH2O concentrations may be explained either by a decrease in the efficiency of defense mechanisms or by an increase in the availability of reaction sites on the DNA resulting from increased cell turnover.


Cycles of juvenile hormone esterase activity during the juvenile hormone-driven cycles of oxygen consumption in pupal diapause of flesh flies.
During diapause O2 consumption in fly pupae is a cyclic event (4-day periodicity at 25 degrees C) driven by cycles of juvenile hormone activity. Levels of juvenile hormone esterase activity change systematically during the cycle, with highest activity observed at the nadir of the O2 consumption cycle.


Association between major depression, depressive symptoms and personal income in US adults with diabetes.
Although the association between diabetes and depression outcomes has been well studied, very little is known about the association between depression and personal income in adults with diabetes. We examined the association between major depression, number of depressive symptoms and personal income among individuals with diabetes. We used the two-stage Heckman procedure to estimate adjusted personal income by major depression status and number of depressive symptoms for 1818 adults with diabetes from the nationally representative 2006 Medical Expenditure Panel Survey. STATA V.10 was used for statistical analysis to account for the complex survey design. In a fully adjusted model with major depression as a binary variable, major depression was associated with $2838 lower personal income. In a separate model with depressive symptoms as a continuous variable, each additional symptom was associated with $1235 lower personal income. Compared with being white/non-Hispanic, being black/non-Hispanic (-$4640) was associated with decreased personal income. Compared with excellent health status, fair health status (-$12,172) and poor health status (-$13,835) were associated with lower income. Relative to private insurance, public insurance only (-$8413) and being uninsured (-$9600) were associated with decreased income. Among adults with diabetes, major depression and depressive symptoms are associated with lower personal income, after adjusting for relevant confounders. This finding suggests that aggressively diagnosing and treating depression as well as keeping people free of depressive symptoms can have huge human capital savings over the employment lifetime of individuals with diabetes and depression.


[Model of social exclusion of the elderly people in Siberian Regions].
An article presents results of the construction and approbation of a theoretical model of social exclusion of population of elderly age groups in Siberian regions. It bases on the results of sociological research (2016) in three Russian regions: Altai region, Trans-Baikal region and Kemerovo oblast (n=779 age of respondents from 55 (women) and 60 (men) years and older). In theory, the model lays on the following: in is determined by economic (material) deprivation, deprivation of social rights (access to social institutes and services) and deprivation of security (safe environment), deprivation of social participation, cultural (normative) disintegration and social autism; the above named components are specific for the group of elderly people, that is a priori a high risk of exclusion; social exclusion, as a condition and situation of exclusion can be estimated straightly through the manifestation of its dimensions; the model has a one-way causality, i.e. the manifestation of one of its dimensions can lead to the high manifestation of the social exclusion. Basing on dimensions, operationalized in questionnaire, we calculated as an index of components of the social exclusion, as the total social exclusion index for elderly people including its regional correlations. By the results of a posteriori testing of the suggested model, we proved a good correlation between theoretical and empirical models of social exclusion of elderly people.


Effects of empagliflozin on estimated extracellular volume, estimated plasma volume, and measured glomerular filtration rate in patients with heart failure (Empire HF Renal): a prespecified substudy of a double-blind, randomised, placebo-controlled trial.
SGLT2 inhibitors are a promising treatment option in patients with heart failure and reduced ejection fraction. We aimed to investigate the effects of empagliflozin on estimated extracellular volume, estimated plasma volume, and measured glomerular filtration rate (GFR) in patients with heart failure and reduced ejection fraction. Empire HF Renal was a prespecified substudy of the investigator-initiated, double-blind, randomised, placebo-controlled Empire HF trial. The study was done at Herlev and Gentofte University Hospital (Herlev, Denmark), with patients recruited from four Danish heart failure outpatient clinics. Patients with New York Heart Association class I-III symptoms, with a left ventricular ejection fraction of 40% or lower, and on guideline-directed heart failure therapy were randomly assigned (1:1) to receive either oral empagliflozin 10 mg or matched placebo once daily for 12 weeks. The allocation sequence was computer-generated. Patients and study investigators were masked to treatment allocation. The coprimary prespecified renal outcomes were the between-group difference in the changes in estimated extracellular volume, estimated plasma volume, and measured GFR from baseline to 12 weeks. All analyses were done in the intention-to-treat population (apart from safety analyses, which were done in patients who received at least one dose of study drug), with no interim analyses done during the trial. The Empire HF trial is registered with ClinicalTrials.gov, NCT03198585, and EudraCT, 2017-001341-27. Between June 29, 2017, and July 15, 2019, we assessed 391 patients for eligibility, of whom 120 (31%) were randomly assigned to empagliflozin or placebo, including 105 (88%) without diabetes. In intention-to-treat analyses, 60 (100%) patients in the empagliflozin group and 59 (98%) patients in the placebo group were included for estimated extracellular volume and estimated plasma volume, and 59 (98%) patients in the empagliflozin group and 58 (97%) patients in the placebo group were included for measured GFR. Empagliflozin treatment resulted in reductions in estimated extracellular volume (adjusted mean difference -0·12 L, 95% CI -0·18 to -0·05; p=0·00056), estimated plasma volume (-7·3%, -10·3 to -4·3; p<0·0001), and measured GFR (-7·5 mL/min, -11·2 to -3·8; p=0·00010) compared with placebo. Five (8%) of 60 patients in the empagliflozin group and three (5%) of 60 patients in the placebo group had one or more serious adverse events. In patients with heart failure and reduced ejection fraction, empagliflozin reduced estimated extracellular volume, estimated plasma volume, and measured GFR after 12 weeks. Fluid volume changes might be an important mechanism underlying the beneficial clinical effects of SGLT2 inhibitors. Research Council at Herlev and Gentofte University Hospital, Research and Innovation Foundation of the Department of Cardiology at Herlev and Gentofte University Hospital, Capital Region of Denmark, Danish Heart Foundation, and AP Møller Foundation for the Advancement of Medical Science.


In Vitro Testing of Voltage Indicators: Archon1, ArcLightD, ASAP1, ASAP2s, ASAP3b, Bongwoori-Pos6, BeRST1, FlicR1, and Chi-VSFP-Butterfly.
Genetically encoded voltage indicators (GEVIs) could potentially be used for mapping neural circuits at the plane of synaptic potentials and plateau potentials-two blind spots of GCaMP-based imaging. In the last year alone, several laboratories reported significant breakthroughs in the quality of GEVIs and the efficacy of the voltage imaging equipment. One major obstacle of using well performing GEVIs in the pursuit of interesting biological data is the process of transferring GEVIs between laboratories, as their reported qualities (e.g., membrane targeting, brightness, sensitivity, optical signal quality) are often difficult to reproduce outside of the laboratory of the GEVI origin. We have tested eight available GEVIs (Archon1, ArcLightD, ASAP1, ASAP2s, ASAP3b, Bongwoori-Pos6, FlicR1, and chi-VSFP-Butterfly) and two voltage-sensitive dyes (BeRST1 and di-4-ANEPPS). We used the same microscope, lens, and optical detector, while the light sources were interchanged. GEVI voltage imaging was attempted in the following three preparations: (1) cultured neurons, (2) HEK293 cells, and (3) mouse brain slices. Systematic measurements were successful only in HEK293 cells and brain slices. Despite the significant differences in brightness and dynamic response (ON rate), all tested indicators produced reasonable optical signals in brain slices and solid in vitro quality properties, in the range initially reported by the creator laboratories. Side-by-side comparisons between GEVIs and organic dyes obtained in HEK293 cells and brain slices by a "third party" (current data) will be useful for determining the right voltage indicator for a given research application.


Pneumonia.
Essential facts: An infection of the lung tissue, pneumonia is common and has a high mortality rate. According to the National Institute for Health and Care Excellence (NICE), between 0.5% and 1% of adults will develop community-acquired pneumonia (CAP) every year. It is diagnosed in 5-12% of those who present to GPs with lower respiratory tract infection, with 22% to 42% admitted to hospital, where the mortality rate is between 5% and 14%. Hospital-acquired pneumonia is estimated to increase hospital stay by about eight days, and has a reported mortality rate ranging from 30% to 70%.


Value of Toxoplasma gondii detection in one hundred thirty-three placentas for the diagnosis of congenital toxoplasmosis.
The placenta examination by polymerase chain reaction and mouse inoculation increased the sensitivity of the diagnosis of congenital toxoplasmosis at birth from 60% (use of serologic techniques on the newborn's blood only) to 75% (both serologic techniques and placental analysis). The specificity of Toxoplasma gondii detection in the placenta was 94.7%.


Patellofemoral articular cartilage damage is associated with poorer patient-reported outcomes following isolated medial patellofemoral ligament reconstruction.
The purpose of this study was to investigate the impact of articular cartilage damage on outcomes following medial patellofemoral ligament (MPFL) reconstruction. Record review identified 160 patients who underwent isolated MPFL reconstruction at a single institution between 2008 and 2016. Patient demographics, patellofemoral articular cartilage status at surgery, and patient anatomical measures from imaging were obtained via chart review. Patients were contacted and outcomes assessed through collection of Norwich Patellar Instability (NPI) score, Knee injury and Osteoarthritis Outcome Score (KOOS), and Marx activity score as well as an assessment for recurrent patellar dislocation. Outcomes of patients with grade 0-II patellofemoral cartilage damage were compared to those of patients with grade III-IV cartilage damage. One hundred twenty-two patients (76%) with a minimum of one year follow-up were contacted at a mean of 4.8 years post-operatively. A total of 63 patients (52%) had grade III or IV patellofemoral chondral damage at the time of surgery. The majority of the defects was on the medial patella (46 patients-72%) and the mean patellar defect size was 2.8 cm2. Among 93 patients who completed patient-reported outcome scores, the 52 with grade III or IV chondral damage reported a significantly poorer KOOS Quality of Life than the 44 patients with grade 0 to II chondral damage (p = 0.041), controlling for patient age, sex, BMI, and anatomical factors. Patients with grade III or IV articular cartilage damage of the patellofemoral joint at the time of MPFL reconstruction demonstrated poorer KOOS knee-related quality of life than patients without grade III or IV articular cartilage damage at a mean of 4.8 years following isolated MPFL reconstruction. Level II.


Factors associated with radiologic-pathologic discordance in magnetic resonance imaging after neoadjuvant chemotherapy for breast cancer.
Although breast MRI is known to be the best imaging modality for assessing the response after neoadjuvant chemotherapy (NAC), discordance still remains between MRI findings and final pathology findings. To evaluate imaging and clinicopathologic factors associated with radiologic-pathologic discordance in breast cancer patients after NAC. This retrospective study included 104 breast cancer patients (mean age: 50.2 years) who underwent breast MRI examinations before and after NAC between June 2015 and December 2019. Radiologic complete response (rCR) was defined as equal or lesser enhancement compared with breast tissue in post-NAC MRI. Pathologic CR (pCR) was defined as absence of invasive cancer in final pathology. Imaging and clinicopathologic factors associated with radiologic-pathologic discordance were analyzed with logistic regression analysis. Overall rCR and pCR rates were 37.5% (39/107) and 40.2% (43/107), respectively. Multivariate analysis revealed that the presence of non-mass enhancement (odds ratio [OR], 3.6; 95% confidence interval [CI], 1.1-11.2; P = 0.03) and multicentric lesions on pre-NAC MRI (OR, 4.2; 95% CI, 1.2-14.9; P = 0.03) were independently associated with radiologic-pathologic discordance. False-positive rate for predicting residual tumor was the most prevalent in HER2-positive cancers (86.7%). When determining rCR, the presence of non-mass enhancement and multicentric lesions on pre-NAC MRI, and HER2-positive cancers should be interpreted with caution.


Genotyping and phylogenetic analysis of Acanthamoeba isolates associated with keratitis.
We examined a partial SSU-rDNA sequence from 20 Acanthamoeba isolates associated with keratitis infections. The phylogenetic tree inferred from this partial sequence allowed to assign isolates to genotypes. Among the 20 isolates examined, 16 were found to be of the T4 genotype, 2 were T3, 1 was a T5, and 1 was a T2, confirming the predominance of T4 in infections. However, the study highlighted other genotypes more rarely associated with infections, particularly the T2 genotype. Our study is the second one to detect that this genotype is associated with keratitis. Additionally, the phylogenetic analyses showed five main emerging clusters, T4/T3/T11, T2/T6, T10/T12/T14, T13/T16, and T7/T8/T9/T17, regularly obtained whichever method was used. A similar branching pattern was found when the full rDNA sequence was investigated.


Studies on antiviral glycosides. II. Mode of action for virucidal effects on Sendai virus.
Treatment of Sendai virus with p-(sec-butyl)-phenyl-6-chloro-6-deoxy-beta-D-glucopyranoside, followed by freezing and thawing resulted in a loss of hemolytic and cell fusion activities as well as infectivity without affecting hemagglutinating and neuraminidase activities. The anti-hemolytic activity of this compound was reversed by the addition of phosphatidyl choline to the virus samples. p-Azidophenyl-6-chloro-6-deoxy-beta-D[3H]glucopyranoside was successfully used for photoaffinity labeling of a specific virion site, and we confirmed the affected site of the glucoside to be the lipid components in the viral envelopes.


Health as an independent predictor of the 2017 French presidential voting behaviour: a cross-sectional analysis.
It has been suggested that poor health has influenced vote for Brexit and the US presidential election. No such research has been published regarding the 2017 French presidential election. We performed a cross-sectional analysis using a comprehensive set of socioeconomic and health indicators, to be compared with voting outcome at the first round of the 2017 French presidential election. The 95 French departments were selected as the unit of analysis. Data were obtained from publicly available sources. The linear model was used for both univariate and multivariate analysis to investigate the relation between voting patterns and predictors. Sensitivity analyses were done using the elastic-net regularisation. Emmanuel Macron and Marine Le Pen arrived ahead. When projected on the first factorial plane (~ 60% of the total inertia), Emmanuel Macron and Marine Le Pen tended to be in opposite directions regarding both socioeconomic and health factors. In the respective multivariate analyses of the two candidates, both socio-economic and health variables were significantly associated with voting patterns, with wealthier and healthier departments more likely to vote for Emmanuel Macron, and opposite departments more likely to vote for Marine Le Pen. Mortality (p = 0.03), severe chronic conditions (p = 0.014), and diabetes mellitus (p < 0.0001) were among the strongest predictors of voting pattern for Marine Le Pen. Sensitivity analyses did not substantially change those findings. We found that areas associated with poorer health status were significantly more likely to vote for the far-right candidate at the French presidential election, even after adjustment on socioeconomic criteria.


Clinical profile and predictors of renal failure in emergency department patients at a tertiary level hospital, a cross sectional study.
Since establishment of the emergency departments (ED) in the country, there is lack of information on clinical profile of patients admitted to the ED and predictors of renal failure in these patients. Renal failure is prevalent in critical patients and a cause of significant mortality and morbidity. The aim of this study was to assess the clinical profile and predictors of renal failure in admissions to the ED. This was a cross-sectional study that was conducted at a tertiary level hospital in Zambia from January to December, 2019 among admissions to the ED after ethical approval. The primary outcome of the study was to describe the clinical profile of admissions to the ED and proportion of renal failure defined as estimated glomerular filtration rate (eGFR) < 60 mls/1.72 m2. The final analysis includes 152 patients, 7 excluded for missing key data. The median age was 43.5 years (IQR 32.5-59.5) and 94.7% of patients were medical. Nearly 70.0% of the patients were triaged as emergency (red) or very urgent (orange). The reason for admission to the ED were sepsis and/or sepsis shock in 25.0%, diabetic hyperglycaemia emergencies in 20.0%, hypertensive crisis in 10.5%, respiratory failure (9.9%), severe malaria (7.9%) and poisoning (5.0%). The prevalence of renal failure was 36.1% and proteinuria was observed in 23.0%. Oliguria and hypertension were 5.9-fold and 1.7-fold independent predictors of renal failure in the ED. Patients with renal failure were likely older, hypertensive, oliguric and anaemic compared to those without. During admission to the ED, 19.1% died. Sepsis and diabetic and hypertensive emergencies accounted for nearly half of ED admissions. Hypertension and oliguria were key predictors of renal failure. Early diagnosis, management and follow-up of hypertension including urine output monitoring for high-risk patients is key in surveillance and prevention of renal failure.


Insertion/deletion polymorphism of the angiotensin-converting enzyme gene and preeclampsia in Japanese patients.
To clarify whether the homozygous deletion (DD) genotype of angiotensin-converting enzyme gene ( ACE) is a genetic risk factor for preeclampsia in Japanese women, we performed ACE genotyping in patients with preeclampsia and healthy pregnant women, and analyzed the relationship between preeclampsia and ACE genotype, taking into account some well-known contributing factors for preeclampsia, such as primiparity, positive family history of hypertension, prepregnancy body mass index < 24, and heterozygosity and homozygosity of T235 (MT+TT) genotypes of the angiotensinogen ( AGT) gene. Among all of the subjects, the frequency of the DD genotype was not different between patients with preeclampsia and controls (16% and 12%, respectively). Regarding primiparity, prepregnancy body mass index < 24, and MT+TT genotypes of AGT, no significant differences in the frequency of the DD genotype of ACE were found between patients with preeclampsia and controls, although in a subgroup positive for family history of hypertension, the frequency of the DD genotype tended to be higher in patients with preeclampsia (25%) than in controls (8%; p = 0.061). Carrying the DD genotype may have some influence on the pathogenesis of preeclampsia, perhaps through effects on placental hypoxia or the interaction of hypertensive disease and atherosclerosis, although this influence may not be strong. Additional studies using a larger number of patients and analyses that include other genetic and environmental factors will be necessary to confirm these results.


Straw-derived biochar for the removal of antibiotics from water: Adsorption and degradation mechanisms, recent advancements and challenges.
Antibiotics, a kind of containments with the properties of widely distributed and difficult to degrade, has aroused extensive attention in the world. As a prevalent agricultural waste, straws can be utilized to prepare biochar (straw-derived biochar, SBC) to remove antibiotics from aquatic environment. To date, although a number of review papers have summarized and discussed research on biochar application in wastewater treatment and soil remediation, there are few reviews on SBC for antibiotic removal. Due to the limitations of poor adsorption and degradation performance of the pristine SBC, it is necessary to modify SBC to improve its applications for antibiotics removal. The maximum antibiotic removal capacity of modified SBC could reach 1346.55 mg/g. Moreover, the adsorption mechanisms between modified SBC and antibiotics mainly involve π-π interactions, electrostatic interactions, hydrophobic interactions, and charge dipole interactions. In addition, the modified SBC could completely degrade antibiotics within 6 min by activating oxidants, such as PS, PDS, H2O2, and O3. The mechanisms of antibiotic degradation by SBC activated oxidants mainly include free radicals (including SO4•-, •OH, and O2•-) and non-free radical pathway (such as, 1O2, electrons transfer, and surface-confined reaction). Although SBC and modified SBC have demonstrated excellent performance in removing antibiotics, they still face some challenges in practical applications, such as poor stability, high cost, and difficulties in recycling. Therefore, the further research directions and trends for the development of SBC and biochar-based materials should be taken into consideration.


A Pharmacokinetic Modeling Approach to Predict the Contribution of Active Metabolites to Human Efficacious Dose.
A preclinical drug candidate, MRK-1 (Merck candidate drug parent compound), was found to elicit tumor regression in a mouse xenograft model. Analysis of samples from these studies revealed significant levels of two circulating metabolites, whose identities were confirmed by comparison with authentic standards using liquid chromatography-tandem mass spectrometry. These metabolites were found to have an in vitro potency similar to that of MRK-1 against the pharmacological target and were therefore thought to contribute to the observed efficacy. To predict this contribution in humans, a pharmacokinetic (PK) modeling approach was developed. At the mouse efficacious dose, the areas under the plasma concentration time curves (AUCs) of the active metabolites were normalized by their in vitro potency compared with MRK-1. These normalized metabolite AUCs were added to that of MRK-1 to yield a composite efficacious unbound AUC, expressed as "parent drug equivalents," which was used as the target AUC for predictions of the human efficacious dose. In vitro and preclinical PK studies afforded predictions of the PK of MRK-1 and the two active metabolites in human as well as the relative pathway flux to each metabolite. These were used to construct a PK model (Berkeley Madonna, version 8.3.18; Berkeley Madonna Inc., University of California, Berkeley, CA) and to predict the human dose required to achieve the target parent equivalent exposure. These predictions were used to inform on the feasibility of the human dose in terms of size, frequency, formulation, and likely safety margins, as well as to aid in the design of preclinical safety studies.


LBL deposition of chitosan and silk fibroin on nanofibers for improving physical and biological performance of patches.
Pelvic floor dysfunction diseases (PFD) become more prevalent with the increase of elderly population, and complications of pelvic floor reconstructive surgery (e.g. infection and exposure of mesh) have been troubling to patients and gynecologists. In this study, the nanofibrous mats were prepared by alternately depositing chitosan (CS) and silk fibroin (SF) on Nylon6 (N6) nanofibrous mats via layer-by-layer (LBL) technique. The as-prepared mats were characterized. The results showed that CS and SF molecules were successfully assembled on the nanofibers. Additionally, after LBL modification, the hydrophilicity of the nanofibrous mats was reduced and the mechanical properties were improved. Furthermore, the antibacterial activity of the LBL-structured mats reached >95% inhibiting Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The in vitro cell co-culture experiments indicated that LBL-structured mats had smaller toxic effects and more excellent biocompatibility to L929 fibroblasts, especially the mats with 15 bilayers coated films. Hence, the LBL-structured mats are promising materials for pelvic floor reconstruction to reduce postoperative pelvic complication rates.


Ten-year follow-up of skin-sparing mastectomy followed by immediate breast reconstruction.
The oncological safety of skin-sparing mastectomy (SSM) followed by immediate breast reconstruction (IBR) is debated owing to a presumed compromise in the completeness of mastectomy. Current evidence is poor as it is based mostly on short-term follow-up data from highly selected patients. A prospectively maintained institutional database was searched to identify patients who underwent SSM and IBR between 1995 and 2000. A retrospective review of medical records was carried out, including only patients with ductal carcinoma in situ and invasive breast cancer. During this time all patients treated with mastectomy were offered IBR regardless of tumour stage. Follow-up data from 253 consecutive patients with IBR were reviewed. Patients with incomplete follow-up data and those undergoing SSM for recurrent disease following previous lumpectomy were disregarded, leaving 207 for analysis. Offering IBR to all women requiring mastectomy resulted in a large proportion of patients with advanced disease. During a median follow-up of 119 months, 17 (8·2 per cent) locoregional, six (2·9 per cent) local and 22 (10·6 per cent) distant recurrences were detected; the overall recurrence rate was 39 (18·8 per cent). Overall recurrence rate was associated with axillary lymph node metastasis (P = 0·009), higher stage (P < 0·001) and higher tumour grade (P = 0·031). The breast cancer-specific survival rate was 90·8 per cent (19 of 207 women died from recurrence). Based on these long-term follow-up data, SSM combined with IBR is an oncologically safe treatment option regardless of tumour stage.


Role of endogenous somatostatin in the secretion of parathyroid hormone and calcitonin.
Our previous in vitro and in vivo studies demonstrated that exogenous somatostatin inhibited secretion of both parathyroid hormone (PTH) and calcitonin (CT). This study evaluates the possible role of endogenous somatostatin in PTH and CT secretion. Rats receiving somatostatin antiserum i.v. had significantly greater circulating levels of serum immunoreactive PTH (iPTH) and CT (iCT) than rats receiving normal rabbit serum. In in vitro studies with bovine parathyroid tissue, the addition of somatostatin antiserum to the medium significantly increased PTH secretion from basal, low calcium-stimulated and high calcium-suppressed parathyroid tissue. These combined observations strongly suggest that endogenous somatostatin must have a suppressive effect on PTH and CT secretion. The in vitro observations with isolated parathyroid tissue suggest that somatostatin is synthesized by cells within this tissue. These data strongly suggest that somatostatin is a locally-synthesized hormone that has a role in modulation of both PTH and CT secretion.


[The stratum corneum].
Epidermal differentiation is a continuous process, constituting and renewing a protective layer at the skin surface: the stratum corneum, composed of cornified keratinocytes that is a barrier to water diffusion. Massive loss of physiologic liquids is one of the severest consequences of extensive burns. The stratum corneum also protects the subjacent tissues from xenobiotic aggression, ultraviolet radiation (70 p. cent of UVB absorption) and from mechanic aggression. The integrity of the stratum corneum depends on three elements: 1) the physico-chemical quality of the cornified cells, 2) the persistence of mechanical junctions uniting these cells and 3) the organization and composition of the lipid "mortar" in the intercellular spaces. Since all these components are issued from the keratinocyte differentiation process, any perturbation may, in time, induce modifications in the "barrier" function of the epidermis. The barrier quality varies, depending on its localization (soles of the feet, palms of the hands and transitional epidermis of the lips), during skin healing (priority to keratinocyte proliferation to the detriment of maturation) under the influence of treatment (retinoids, vitamin D derivatives), in the course of aging and diseases: ichtyosis and other keratinization genodermatoses, benign (including psoriasis) and malignant hyperproliferative diseases. Furthermore, the relative impermeability of the stratum corneum is an important factor limiting the penetration and diffusion of allergens, but also local drugs delivered with local and systemic trans-epidermal treatments. Further knowledge is required on the function of the epidermal barrier and the mechanism regulating cohesion/desquamation of the stratum corneum to understand certain hereditary diseases, improve efficacy of topical therapeutic products and optimize cosmetic formulations.


Behavioural and endocrine fear responses in Japanese quail upon presentation of a novel object in the home cage.
Most tests used to study fear in birds involve transferring them to a novel environment, which constitutes a bias in studies aiming at identifying the neural correlates of a specific fear-inducing situation. In order to investigate fear in birds with minimum interference by humans, behavioural and endocrine responses to the presentation of a novel object in the home cage were investigated in two lines of Japanese quail divergently selected for long or short duration of tonic immobility, a behavioural index of fear. Presentation of the novel object induced typical fear responses (avoidance of the object, increased pacing and increased plasma corticosterone levels) that were similar in the two lines of quail. Presentation of a novel object in the home cage thus appears to be a suitable stimulus to induce fear reactions in quail, with minimum interference from other motivational systems. The fact that quail of both lines reacted similarly in this test, while they are known to differ greatly in their behavioural responses to other fear-inducing tests, illustrates the multidimensional nature of fear.


Empagliflozin reverses obesity and insulin resistance through fat browning and alternative macrophage activation in mice fed a high-fat diet.
We reported previously that empagliflozin-a sodium-glucose cotransporter (SGLT) 2 inhibitor-exhibited preventive effects against obesity. However, it was difficult to extrapolate these results to human subjects. Here, we performed a therapeutic study, which is more relevant to clinical situations in humans, to investigate antiobesity effects of empagliflozin and illustrate the mechanism underlying empagliflozin-mediated enhanced fat browning in obese mice. After 8 weeks on a high-fat diet (HFD), C57BL/6J mice exhibited obesity, accompanied by insulin resistance and low-grade chronic inflammation. Cohorts of obese mice were continued on the HFD for an additional 8-week treatment period with or without empagliflozin. Treatment with empagliflozin for 8 weeks markedly increased glucose excretion in urine, and suppressed HFD-induced weight gain, insulin resistance and hepatic steatosis. Notably, empagliflozin enhanced oxygen consumption and carbon dioxide production, leading to increased energy expenditure. Consistently, the level of uncoupling protein 1 expression was increased in both brown and white (WAT) adipose tissues of empagliflozin-treated mice. Furthermore, empagliflozin decreased plasma levels of interleukin (IL)-6 and monocyte chemoattractant protein-1, but increased plasma levels of IL-33 and adiponectin in obese mice. Finally, we found that empagliflozin reduced M1-polarized macrophage accumulation, while inducing the anti-inflammatory M2 phenotype of macrophages in the WAT and liver, thereby attenuating obesity-related chronic inflammation. Treatment with empagliflozin attenuated weight gain by increasing energy expenditure and adipose tissue browning, and alleviated obesity-associated inflammation and insulin resistance by alternative macrophage activation in the WAT and liver of obese mice.


Comparison of outcomes following radiological reduction of intussusception with or without sedation.
Non-operative radiological reduction (NORR) is usually the first line treatment in pediatric ileo-colic intussusception. The aim of our study was to compare outcomes of NORR with or without sedation. All patients undergoing to contrast enema NORR for intussusception between 01.01.2015 to 31.12.2020 in two hospitals were included: in one centre patients were sedated (A) while in the other patients were awake (B). Primary outcome was the rate of radiological reduction. Secondary outcomes were length-of-stay, complications and recurrence rate. Seventy-seven and 49 patients were included in group A and B respectively. Successful reduction rate was 72.7% in group A and 61.2% in group B (P>0.05). There were no complications related to the procedure among the 2 groups. Adverse events to sedation were observed in 3 patients. NORR has similar success rate when performed under sedation or awake, despite the former being graved by additional anesthesiologic risks and thus warrant careful indications.


Template directed formation of nanoparticle decorated multi-walled carbon nanotube bundles with uniform diameter.
Bundles of multi-walled carbon nanotubes of uniform diameter decorated with Ni nanoparticles were synthesized using mesoporous silicates as templates. The ordered morphology and the narrow pore size distribution of mesoporous silicates provide an ideal platform to synthesize uniformly sized carbon nanotubes. In addition, homogeneous sub-10 nm pore sizes of the templates allow in situ formation of catalytic nanoparticles with uniform diameters which end up decorating the carbon nanotubes. The resulting carbon nanotubes are multi-walled with a uniform diameter corresponding to the pore diameter of the template used during the synthesis that are decorated with the catalysts used to synthesize them. They have a narrow size distribution which can be used in many energy related fields of research.