Ambulatory blood pressure-lowering effects of valsartan and enalapril after a missed dose in previously untreated patients with hypertension: a prospective, randomized, open-label, blinded end-point trial.
Approximately 3 days a month, some 15% to 20% of patients with hypertension do not recall having taken their antihypertensive medication. Individuals with this frequency of missed doses may be at increased risk for a cardiovascular event and may have a poorer long-term prognosis. This study used ambulatory blood pressure monitoring (ABPM) to compare the blood pressure (BP)-lowering effects of valsartan and enalapril over the 24 hours after missing 1 dose in previously untreated patients with mild to moderate essential hypertension. This was a prospective, randomized, open-label, parallel-group, blinded end-point trial in previously untreated patients (age >18 years) with mild to moderate essential hypertension (European Society of Hypertension-European Society of Cardiology guidelines: systolic BP 140-179 mm Hg or diastolic BP 90-109 mm Hg). Patients were randomly assigned to receive 16 weeks of treatment with valsartan 160 mg/d or enalapril 20 mg/d, taken on waking. ABPM was conducted for 48 consecutive hours at baseline and again after 16 weeks of therapy. Patients took a dose of their assigned treatment at the beginning of the final session of ABPM and were instructed to skip the next daily dose. The study enrolled 148 Spanish patients (84 men, 64 women; mean [SD] age, 45.8 [10.7] years) with previously untreated hypertension. At the end of treatment, there were significant differences between groups during the first 24 hours of ABPM, starting in the final 6 hours of the dosing interval (P < 0.001). There was no significant change in BP reduction between the first and second 24-hour periods of ABPM with valsartan (-2.1/-1.4 mm Hg), whereas enalapril was associated with a significant increase in BP over this period (5.5/3.8 mm Hg; P < 0.001 vs first 24 hours; P = 0.032 vs valsartan). In this study in previously untreated patients with mild to moderate essential hypertension, valsartan was associated with a sustained BP-lowering effect beyond the initial 24 hours after dosing, whereas enalapril was not. There was no significant change in the efficacy of valsartan in the 24 hours after a missed dose. At the doses tested, valsartan was more effective than enalapril, both during active treatment and after a missed dose.


An assessment of the Cardiovascular Health Education Program in primary health care.
Primary health care is an effective means of improving health for all while at the same time containing rising health care costs. In an effort to improve the health of one community, the Cardiovascular Health Education Program (CHEP) was implemented in a study of 44 eighth-grade adolescents. The purpose of this study was to assess the influence of the CHEP on adolescents' cardiovascular health knowledge. It was found that participants' knowledge improved significantly, whereas a control group showed no comparable improvement. This study showed that community-based health education programs for targeted populations can influence health knowledge.


[Flow cytometry-pathology combined study of breast cancer].
To study the relation between histopathologic grading and some of the cytogenetic and molecular biology characteristics of breast cancer. On the basis of estrogen receptor (ER) expression, DNA content, S-phase fraction (SPF), bcl-2 and mutant p53 protein (mtp53) expression were examined by FCM in 121 breast cancer patients. In 66 patients with invasive ductal breast cancer, histopathologic grading was also examined. The aneuploidy rate and DNA index (DI) were significantly different in grade I, II and III breast cancer. SPF and mtp53 expression significantly increased with increase in histopathologic grading (P < 0.05), but bcl-2 did not show this trend. SPF and mtp53 expression were significantly more in breast cancer with negative ER than in those with positive ER (P < 0.05). Again, no such differences in bcl-2 regardless of ER expression. Correlations existed between DI vs SPF, DI vs mtp53, and SPF vs mtp53 expressions (P < 0.01) but bcl-2 did not correlate with any one of them. Cytogenetic and molecular biology studies on the basis of histopathologic grading may provide more information in prognostic prediction of breast cancer.


[Peripheral regulation of the cholinergic mediator process in the smooth muscles of the rat small intestine].
A physiologically active substance (X-factor) is released from smooth muscle fibers of rat's small intestine-donor under the effect of acetylcholine. This substance which seems to be a macroergic nature strengthens the spontaneous activity of isolated piece of rat's small intestine-recipient and increases its sensitivity to acetylcholine almost twofold. Participation of the X-factor in the control of cholinoreceptor activity of smooth muscle fibers of rat's small intestine following the pattern of positive feedback, is discussed.


Pediatric death: guidelines for the grieving anesthesiologist.
This essay examines the effects of unexpected pediatric death on anesthesiology house staff, and offers a discussion of normal and abnormal patterns of grieving. The increased incidence of substance abuse and suicide among anesthesiologists is discussed, and the relationship of stress following patient death and appropriate coping skills is explored. A blueprint for managing stress is given based on a military combat stress model, and recommendations for residency training programs are made.


High blood pressure is one of the symptoms of paraquat-induced toxicity in rats.
This study investigated whether paraquat (Pq)-induced lipidic peroxidation (LP) is accompanied by changes in blood pressure and heart rate (HR) in rats. Groups of adult male Wistar rats were studied 2 and 12 h after Pq (35 mg/kg, i.p.) administration. The LP was evaluated by monitoring thiobarbituric acid reactive substances (TBARS) in the kidneys, liver and lungs, and validated by including a group treated with an antioxidant, superoxide dismutase (CuZnSOD 50,000 IU/kg), in the study. The TBARS levels were significantly higher (p<0.05) in the kidneys of the rats studied 2 h after Pq than in their respective controls. Similarly, systolic and diastolic blood pressure (DBP) were higher (p<0.05), while HR was lower (p<0.05) than basal levels 2 and 12 h after Pq administration. In contrast, the group treated simultaneously with Pq and CuZnSOD exhibited lower levels of TBARS (p<0.05) in all studied organs compared to the control group, while the mean arterial pressure and HR did not differ from those seen in the control group. These findings indicate that acute Pq poisoning symptoms include high blood pressure.


A rapidly growing benign intrathoracic neurofibroma after lung lobectomy.
A 67-year-old male underwent a right upper lung lobectomy for lung cancer in January 1993. Follow-up chest X-rays revealed a progressive and rapidly growing intrathoracic mass in the right thorax. The mass, however, did not resemble a tumor recurrence, and the patient complained only of shortness of breath. Computerized tomography and magnetic resonance imaging confirmed the presence of the intrathoracic mass and its associated compression of the residual lung. A right thoracotomy was performed in January 1998, and a mass found arising from the sympathetic nerve trunk was resected. Microscopic examination revealed stellate or spindle-shaped cells in myxoid stroma with sparsely distributed collagen fibers. Immunohistochemically, the cells were positive for neuron-specific enolase, and the tumor was identified as neurofibroma. The patient did not suffer from von Recklinghausen's disease, and there was no family history of the disease. After resection of the neurofibroma, the compressed lung was able to re-expand, and the patient's shortness of breath disappeared. At one year postoperative, the patient remains well, and there is no evidence of recurrence.


Chemical composition and bioactive compounds of garlic (Allium sativum L.) as affected by pre- and post-harvest conditions: A review.
Garlic (Allium sativum L.) is considered one of the twenty most important vegetables, with various uses throughout the world, either as a raw vegetable for culinary purposes, or as an ingredient of traditional and modern medicine. Furthermore, it has also been proposed as one of the richest sources of total phenolic compounds, among the usually consumed vegetables, and has been highly ranked regarding its contribution of phenolic compounds to human diet. This review aims to examine all the aspects related with garlic chemical composition and quality, focusing on its bioactive properties. A particular emphasis is given on the organosulfur compounds content, since they highly contribute to the effective bioactive properties of garlic, including its derived products. The important effects of pre-harvest (genotype and various cultivation practices) and post-harvest conditions (storage conditions and processing treatments) on chemical composition and, consequently, bioactive potency of garlic are also discussed.


Endoscopic Management of Esthesioneuroblastoma.
Esthesioneuroblastoma is a rare malignant tumor of sinonasal origin. These tumors typically present with unilateral nasal obstruction and epistaxis, and diagnosis is confirmed on biopsy. Over the past 15 years, significant advances have been made in endoscopic technology and techniques that have made this tumor amenable to expanded endonasal resection. There is growing evidence supporting the feasibility of safe and effective resection of esthesioneuroblastoma via an expanded endonasal approach. This article outlines a technique for endoscopic resection of esthesioneuroblastoma and reviews the current literature on esthesioneuroblastoma with emphasis on outcomes after endoscopic resection of these malignant tumors.


Pros and cons of the nonsurgical treatments for gallbladder stones.
Dissolution of gallbladder stones is usually possible if the cholesterol content of the stones is high. Oral treatment with chenodiol or ursodiol is least invasive, but also least effective and slow. methyl tert-butyl ether requires delivery by percutaneous transhepatic catheter, but is rapidly effective. Extracorporeal shock wave lithotripsy enhances dissolution by oral bile acids, but is highly effective only for solitary stones less than or equal to 20 mm in diameter. Percutaneous cholecystostomy is most invasive, but effective regardless of stone composition. Stones will probably recur in 50 percent of patients with a patent cystic duct and intact gallbladder.


Mulching practices alter soil microbial functional diversity and benefit to soil quality in orchards on the Loess Plateau.
To improve our understanding about the responses of microbial functional diversity to different mulching practices, this study used a metagenomic approach to reveal soil microbial functional specificity under four tillage regimes: conventional tillage (CT), organic mulch practices with ryegrass (Lolium perenne L.) intercropping cover (RE) and cornstalk mulch (CS), and inorganic mulching with black ground fabric (BF) in a 7-year field experiment in an apple orchard of the Loess Plateau in China. Enzyme activity and soil physicochemical properties were measured. A redundancy analysis showed that the RE and CS treatments had positive effects on soil nutrient and enzyme activity compared to that of the BF and CT treatments. The CS and RE treatments increased β-glucosidase, cellobiohydrolase, and β-xylosidase activities. In addition, the CS treatment significantly enhanced the β-N-acetylglucosaminidase and urease activities compared to that under CT treatment. However, the activity of these enzyme was reduced in the BF treatment compared with that of the CT treatment. The results also indicated that the enzymes activities were not completely consistent with the changing trends of the genes encoding these enzymes. In addition, the RE and CS treatments also increased the abundance of genes encoding carbohydrate enzymes. It is interesting that the RE and CS treatments had more pathway genes associated with the carbon cycle, nitrogen cycle, and amino acid metabolism compared with the BF treatment. Remarkably, RE and CS treatments effectively increased the abundance of carbon fixation gene cbbL compared to CT treatment. In summary, organic mulching practices increased the soil microbiological functional diversity related to the carbon and nitrogen cycle, while inorganic mulching practice reduced them. This study enhanced our understanding of how mulching practices may alter soil microbial functional diversity and benefit soil quality.


Potential anticancer activity of Mn (II) complexes containing arginine dithiocarbamate ligand on MCF-7 breast cancer cell lines.
Cancer refer to genetic changes in the DNA structure accompanied by abnormal growth of normal cells, and resulting in the death of these structures, and is a disease currently recognized as a major cause of mortality globally. Chemotherapy plays important role in breast cancer management. Non-toxic metals have been developed to replace the highly toxic cisplatin, an example being Manganese. Furthermore, Ligands have displayed great capabilities in the determination of anticancer properties, and an essential agent exploited in drug development is arginine dithiocarbamate. Therefore, this study was conducted to examine the anticancer potentials of Mn (II) arginine dithiocarbamate. The synthesis and spectroscopic analysis of the Mn (II) Arginine dithiocarbamate complex was successfully carried out. Then, the complexes were characterized through the employment of the UV-Vis, FT-IR, as well as the melting point tests, and subsequently analyzed for anticancer activities through in vitro means. The compound was produced from UV-Vis spectrum at 246 and 385 nm wavelengths and IR spectrum at wave numbers 354-499 cm-1. The results revealed the cytotoxicity of Mn (II) Arginine dithiocarbamate against the MCF-7 cell line, observed from a significant change in the morphology of the cancer cells with IC50 value of 211.53 μg/mL. The compound, Mn (II) Arginine dithiocarbamate has effective anticancer potentials against MCF-7 cancer cells.


Preoperative concomitant boost intensity-modulated radiotherapy with oral capecitabine in locally advanced mid-low rectal cancer: a phase II trial.
We aimed to assess the safety and efficacy of preoperative intensity-modulated radiotherapy (IMRT) with oral capecitabine in patients with locally advanced mid-low rectal cancer using a concomitant boost technique. Patients with resectable locally advanced mid-low rectal cancer (node-negative ≥T3 or any node-positive tumor) were eligible. The eligible patients received IMRT to 2 dose levels simultaneously (50.6 and 41.8 Gy in 22 fractions) with concurrent capecitabine 825 mg/m(2) twice daily 5 days/week. The primary end point included toxicity, postoperative complication, and pathological complete response rate (ypCR). The secondary endpoints included local recurrence rate, progression-free survival (PFS), and overall survival (OS). Sixty-three eligible patients were enrolled; five patients did not undergo surgery. Of the 58 patients evaluable for pathologic response, the ypCR rate was 31.0% (95% CI 19.1-42.9). Grade 3 toxicities included diarrhea (9.5%), radiation dermatitis (3.2%), and neutropenia (1.6%). There was no Grade 4 toxicity reported. Four (6.9%) patients developed postoperative complications. Two-year local recurrence rate, PFS, and OS were 5.7%, 90.5%, and 96.0%, respectively. The design of preoperative concurrent boost IMRT with oral capecitabine could achieve high rate of ypCR with an acceptable toxicity profile.


Rat oligodendroblasts in vitro as a long-term cell line.
A stable line of oligodendrocyte-like cells has been derived by passaging methods from initial explant cultures of postnatal Lewis rat cerebellum. These cells resemble oligodendrocytes by both light and electron microscopy. However, their ultrastructure suggests immaturity, and they express no galactocerebroside at their surfaces. They do express surface tetrasialoganglioside. They contain no intermediate filaments, and show none of the ultrastructural characteristics of astrocytes. It is suggested that they represent immediate precursors to oligodendrocytes, or "oligodendroblasts". In addition, the cell line contains a small minority of astrocytes, and interactions between these and the oligodendroblasts are suggested to account for the highly differentiated ultrastructure maintained by the oligodendroblasts over hundreds of cell generations in vitro, as well as, possibly, the high proliferative rate of the oligodendroblasts. Conversely, the failure of the oligodendroblasts to mature is related to the absence of neurons.


Tetrabromobenzotriazole (TBBt) and tetrabromobenzimidazole (TBBz) as selective inhibitors of protein kinase CK2: evaluation of their effects on cells and different molecular forms of human CK2.
The development of selective cell-permeable inhibitors of protein kinase CK2 has represented an important advance in the field. However, it is important to not overlook the existence of discrete molecular forms of CK2 that arise from the presence of distinct isozymic forms, and the existence of the catalytic CK2 subunits as free subunits and in complexes with the regulatory CK2beta subunits and, possibly, other proteins. This review examines two recently developed, and presently widely applied, CK2 inhibitors, 4,5,6,7-tetrabromobenzotriazole (TBBt) and the related 4,5,6,7-tetrabromobenzimidazole (TBBz), the latter of which was previously shown to discriminate between different molecular forms of CK2 in yeast. We have shown, by spectrophotometric titration, that TBBt, with a pK(a) approximately 5, exists in solution at physiological pH almost exclusively (>99%) as the monoanion; whereas TBBz, with a pKa approximately 9, is predominantly (>95%) in the neutral form, both of obvious relevance to their modes of binding. In vitro, TBBt inhibits different forms of CK2 with Ki values ranging from 80 to 210 nM. TBBz better discriminates between CK2 forms, with Ki values ranging from 70 to 510 nM. Despite their general similar in vitro activities, TBBz is more effective than TBBt in inducing apoptosis and, to a lesser degree, necrosis, in transformed human cell lines. Finally, development of shRNA strategies for the selective knockdown of the CK2alpha and CK2alpha' isoforms reinforces the foregoing results, indicating that inhibition of CK2 leads to attenuation of proliferation.


Development and validation of a PCR-RFLP assay to evaluate TVB haplotypes coding receptors for subgroup B and subgroup E avian leukosis viruses in White Leghorns.
The cellular receptor of subgroup B avian leukosis virus (ALVB) is encoded by a gene at the tumour virus B (TVB) locus. TVB alleles encode specific receptors permitting infection by exogenous ALVB or avian leukosis virus subgroup D (ALVD) as well as endogenous avian leukosis virus subgroup E (ALVE), and thus susceptibility is dominant to resistance. Two single nucleotide polymorphisms at the TVB locus have been reported distinguishing three TVB alleles (TVB*S1, TVB*S3 and TVB*R). We have developed a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay using the two single nucleotide polymorphisms to define three observed allelic haplotypes and to identify the six possible TVB genotypes consisting of the three haplotypes in defined laboratory strains of chickens. One additional potential allelic haplotype and four genotypes were also briefly discussed. Chickens from parents heterozygous for different TVB alleles were challenged with Rous sarcoma viruses of subgroup ALVB and ALVE to induce wing-web tumours. Tumour incidences were evaluated between chickens of the genotypes determined with this newly developed PCR-RFLP assay. Importantly, chickens typed with this assay as TVB*S3/*S3 were resistant to infection by ALVE only, and those TVB*R/*R were resistant to both ALVE and ALVB. Furthermore, a vast majority of chickens with the susceptible TVB*S1/- genotypes developed a tumour. This PCR-RFLP assay enables a relatively rapid assessment of all six anticipated TVB genotypes in experimental strains of chickens undergoing segregation for TVB*S1, TVB*S3, and TVB*R alleles. This non-infectious assay should be further evaluated for the capacity to select and breed commercial chickens for genetic resistance to infections by ALVB, ALVD and ALVE.


Plethysmographic features of calf pump failure in chronic venous obstruction and reflux.
Calf pump failure (CPF) is a common concept in chronic venous disease. Dorsal vein pressures were originally used to define the pathophysiology. More recently, an abnormal ejection fraction (EF) and residual volume fraction (RVF) with air plethysmography (APG) have been substituted for its diagnosis. The relationship between reflux and calf pump function has been studied extensively. Reflux is thought to be the main cause of CPF, although other mechanisms may play a secondary role. Data mining in our dataset revealed that CPF is frequently found in nonrefluxive limbs-an unexpected finding. We analyzed the APG features of CPF in nonrefluxive limbs of a large cohort of patients investigated for chronic venous disease in our clinic. Data from refluxive limbs (control) seen over the same period was included for comparison. Venous obstructive pathology was variably present in both subsets. Iliac vein stent outcome in CPF limbs from both subsets is included. The role of obstruction in CPF is currently unknown. Records of 13,234 limbs in 8813 patients evaluated for suspected chronic venous disease over a 22-year period were analyzed. Prestent and poststent data in 406 CPF limbs (129 nonrefluxive; 277 refluxive) that underwent iliac vein stenting to correct associated stenosis are included. This is a single-center retrospective analysis of prospectively collected data. Duplex and APG data were available for included limbs. A RVF of more than 50% was defined as CPF. A reflux time of greater than 1 second elicited with automated cuffs in the erect position was defined as reflux. There were 7780 (59%) limbs with reflux and 5454 (41%) that were nonrefluxive. Supine venous pressure, an index of venous obstruction, was elevated in both subsets. The incidence of CPF was 25% in refluxive limbs and 16% in nonrefluxive limbs totaling 2790 limbs. Venous volume and venous filling index were significantly elevated (P = .0001) in refluxive limbs compared to nonrefluxive limbs. The EF was diminished (<50%) in all CPF limbs except in a small fraction (n = 427 [3%]). Stent correction of iliac vein stenosis corrected CPF, normalizing the RVF in both subsets. CPF frequently occurs in nonrefluxive limbs with incidence only slightly less than in refluxive limbs. An RVF of more than 50% seems to be a practical definition of a CPF; an EF of less than 50% is associated with a RVF of greater than 50% in 97% of analyzed limbs. Prospective identification of CPF in limbs with chronic venous disease may allow more detailed investigation of its cause (preload, afterload, neuromuscular pathology or joint immobility, etc) and direct more targeted treatment than currently practiced.


Avulsion of common bile duct after blunt abdominal injury: a review of the literature.
Injury to the common bile duct following blunt injury of the abdomen has been reported in 82 previous cases in the literature that we have reviewed. An additional rare case of complete avulsion of the common bile duct at its junction with the pancreas is presented here. Diagnosis has usually been late, peritonitis has commonly been present and 33 per cent of the cases ended fatally. Although diagnosis is often late, there have been many attempts at primary repair; we describe a new technique of delayed repair, which involved intermittent closure of the common duct and was successful in increasing its diameter by the time of the second operation. The initial injury was treated by a cutaneous choledochostomy and 2 jejunostomy tubes, one for decompression and drainage and the other for feeding and replacement of bile. The final repair consisted of a choledochojejunostomy, jejunojejunostomy and T-tube drainage of the common juct. The patient is completely well after two years.


A modular approach to map out the conformational landscapes of unbound intrinsically disordered proteins.
Intrinsically disordered proteins (IDPs) fold upon binding to select/recruit multiple partners, morph around the partner's structure, and exhibit allostery. However, we do not know whether these properties emerge passively from disorder, or rather are encoded into the IDP's folding mechanisms. A main reason for this gap is the lack of suitable methods to dissect the energetics of IDP conformational landscapes without partners. Here we introduce such an approach that we term molecular LEGO, and apply it to NCBD, a helical, molten globule–like IDP, as proof of concept. The approach entails the experimental and computational characterization of the protein, its separate secondary structure elements (LEGO building blocks), and their supersecondary combinations. Comparative analysis uncovers specific, yet inconspicuous, energetic biases in the conformational/folding landscape of NCBD, including 1) strong local signals that define the three native helices, 2) stabilization of helix–helix interfaces via soft pairwise tertiary interactions, 3) cooperative stabilization of a heterogeneous three-helix bundle fold, and 4) a dynamic exchange between sets of tertiary interactions (native and nonnative) that recapitulate the different structures NCBD adopts in complex with various partners. Crucially, a tug of war between sets of interactions makes NCBD gradually shift between structural subensembles as a conformational rheostat. Such conformational rheostatic behavior provides a built-in mechanism to modulate binding and switch/recruit partners that is likely at the core of NCBD's function as transcriptional coactivator. Hence, the molecular LEGO approach emerges as a powerful tool to dissect the conformational landscapes of unbound IDPs and rationalize their functional mechanisms.


Interplay of nitric oxide metabolites and markers of endothelial injury, inflammation, and vascular disease in the spectrum of advanced chronic kidney disease.
Chronic kidney disease is linked to cardiovascular morbidity; therefore, relevant biomarkers are widely investigated. We aimed to assess the relationship between nitric oxide (as measured by its metabolites, NOx), a key endothelial molecule, with markers of endothelial dysfunction, inflammation, antioxidant status, and mineral disorders as well as histologically assessed vascular calcification in uremic and hemodialysis patients with chronic kidney disease. Plasma and serum samples were obtained from 62 patients with renal failure. NOx was assessed by the Griess method, while the other biomarkers were measured by the immunoenzymatic assay. Morphological analysis of arterial calcification was performed in a blinded, semiquantitative manner. Common carotid intima‑media thickness and atherosclerotic plaques were assessed by ultrasonography. In the simple analysis, NOx levels correlated positively with the parameters of renal function, mineral metabolism, endothelial injury, and inflammation. NOx predicted carotid intima‑media thickness in simple (P = 0.014) and multiple analysis (P = 0.036) adjusted for the Framingham risk score, C‑reactive protein, serum creatinine, and parathormone. The occurrence of atherosclerotic plaques in the common carotid artery was correlated with higher NOx concentrations (P = 0.021). In chronic renal failure, NOx is associated with surrogate markers of atherosclerosis, even after adjustment for traditional cardiovascular risk factors, inflammation, and renal function, but not with the presence or grade of medial arterial calcification. Endothelial injury, inflammation, and mineral metabolism markers are associated with NOx levels, though a causal link requires further study.


Validation of the Mini Nutritional Assessment-Short Form in a Population of Frail Elders without Disability. Analysis of the Toulouse Frailty Platform Population in 2013.
To assess the validity of the Mini Nutritional Assessment-Short Form (MNA-SF) in elderly patients from the Toulouse Frailty Platform. Overall, 267 patients aged 65 and over, without severe cognitive impairment (i.e. Mini Mental Status Examination > 20 and CDR<1), no physical disability (i.e. Activities of Daily Living ≥ 5) and no active cancer history (over the past 12 months) were included in 2013. Receiver operating characteristic (ROC) analyses were used to assess the predictive validity of the French version of the MNA-SF for good nutritional status (defined as a full MNA score≥24/30). Analyses were conducted in the overall sample and then in subgroups of frail and pre-frail subjects according to the frailty phenotype. Optimal cut-off points were determined to obtain the best sensitivity/specificity ratio and the highest number of correctly classified subjects. Among 267 patients, mean age=81.5±5.8; women=67.0%; 138 (51.7%) were frail, 98 (36.7%) were pre-frail and 31 (11.6%) were robust. Given their MNA-SF scores, 201 (75.3%) had a good nutritional status, 61 (22.8%) were at risk of malnutrition and 5 (1.9%) were malnourished. In the overall sample, but also in subgroups of pre-frail or frail elders, the areas under ROC curves were 0.954, 0.948 and 0.958 respectively. The 11 points cut-off provided the best correct classification ratio (91.4%); sensitivity=94.0%, specificity=83.3%. The MNA-SF appeared to be a validated and effective tool for malnutrition screening in frail elders. Implementing this tool in clinical routine should contribute to improving the screening of malnourished frail individuals.


Space-Confined Guest Synthesis to Fabricate Sn-Monodispersed N-Doped Mesoporous Host toward Anode-Free Na Batteries.
Severe issues including volume change and dendrite growth on sodium metal anodes hinder the pursuit of applicable high-energy-density sodium metal batteries. Herein, an in situ reaction approach is developed that takes metal-organic frameworks as nano-reactor and pore-former to produce a mesoporous host comprised of nitrogen-doped carbon fibers embedded with monodispersed Sn clusters (SnNCNFs). The hybrid host shows outstanding sodiophilicity that enables rapid Na infusion and ultralow Na nucleation overpotential of 2 mV. Its porous structure holds a high Na content and guides uniform Na deposition. Such host provides favorable Na plating/stripping with an average Coulombic efficiency of 99.96% over 2000 cycles (at 3 mA cm-2 and 3 mA h cm-2 ). The Na-infused SnNCNF anode delivers extreme Na utilization of 86% in symmetric cells (at 10 mA cm-2 and 10 mA h cm-2 ), outstanding rate capability and cycle life in Na-SnNCNF||Na3 V2 (PO4 )3 full cells (at 1 A g-1 for over 1000 cycles with capacity retention of 92.1%). Furthermore, high-energy/power-density anode-less and anode-free Na cells are achieved. This work presents an effective heteroatom-doping approach for fabricating multifunctional porous carbon materials and developing high-performance metal batteries.


Preclinical drug development paradigms for chemopreventives.
Preclinical screening studies and animal efficacy testing models currently are used by the National Cancer Institute's chemoprevention drug discovery program to assess and identify chemical agents and natural products that may have the potential to prevent human cancer. Identification of potential cancer preventing agents begins by subjecting each compound to a sequential series of short-term, in vitro prescreens of mechanistic, biochemical assays to provide quantitative data to help establish an early indication of chemopreventive efficacy and to assist in prioritizing agents for further evaluation in longer-term, in vitro transformation bioassays and whole animal models. Promising chemical agents or combinations of agents that work through different inhibitory mechanisms subsequently are tested in well-established, chemically induced, animal tumor models, which include models of the lung, bladder, mammaries, prostate, and skin. These preclinical bioassays afford a strategic framework for evaluating agents according to defined criteria, and not only provide evidence of agent efficacy, but also serve to generate valuable dose-response, toxicity, and pharmacokinetic data required prior to phase I clinical safety testing. Based on preclinical efficacy and toxicity screening studies, only the most successful agents considered to have potential as human chemopreventives progress into clinical chemoprevention trials.


Spatio-temporal activities in the antennal lobe analyzed by an optical recording method in the male silkworm moth Bombyx mori.
Optical recordings with a voltage-sensitive dye showed that the spatio-temporal pattern of depolarizing responses evoked by electrical stimulation of antennal nerve (AN) was non-homologously distributed in the antennal lobe (AL) of the male silkworm moth, Bombyx mori. Time courses of postsynaptic activities and GABAergic inhibitory potentials of AL neurons were individually demonstrated by pharmacological experiments, i.e. Ca2+ free and bicuculline conditions. GABAergic inhibitory potentials began with a ca. 3 ms delay from the beginning of the postsynaptic activities. Intensity of the postsynaptic activities and GABAergic inhibitory potentials were non-homologously distributed in the AL. Relatively strong postsynaptic activities and GABAergic inhibitory potentials were consistently observed in some parts of the macroglomerular complex (MGC) and/or in some ordinary glomeruli (Gs) in the medial and ventral part of the AL.


Minimal ovarian stimulation combined with elective single embryo transfer policy: age-specific results of a large, single-centre, Japanese cohort.
The two main complications associated with the use of assisted reproduction techniques, ovarian hyperstimulation syndrome and multiple pregnancies, could be eliminated by milder ovarian stimulation protocols and the increased use of a single embryo transfer (SET) policy. A retrospective, cohort study was performed in private infertility centre to evaluate the embryological and clinical results of a large exclusively SET program according to patient age (lower or equal 29, 30-34, 35-39, 40-44 and equal or higher 45 years). A total of 7,244 infertile patients have undergone 20,244 cycles with a clomiphene-based minimal stimulation or natural cycle IVF protocol during 2008. Following oocyte retrieval, fertilization and embryo culture a total of 10,401 fresh or frozen single embryo transfer procedures were performed involving cleavage-stage embryos or blastocysts. Successful oocyte retrieval rate (78.0 %) showed no age-dependent decrease until 45 years. Fertilization (80.3 %) and cleavage (91.1 %) rates were not significantly different between age groups. Blastocyst formation (70.1 % to 22.8 %) and overall live birth rates (35.9 % to 2 %) showed an age-dependent decrease. Frozen-thawed blastocyst transfer cycles gave the highest chance of live birth per embryo transfer (41.3 % to 6.1 %). High fertilization and cleavage rates were obtained regardless of age whereas blastocyst formation and live birth rates showed an age-dependent decrease. An elective single embryo transfer program based on a minimal ovarian stimulation protocol yields acceptable live birth rates per embryo transfer in infertile patients up until their mid-forties. However in very advanced age patients (equal or higher 45 years old) success rates fall below 1 %.


On the use of ultraviolet resonance Raman intensities to elaborate molecular force fields: application to nucleic acid bases and aromatic amino acid residues models.
Normal modes analyses for different molecules with biological interest have been performed and checked via the calculation of resonance Raman intensities. For this purpose, molecular orbital calculations were used to determine bond order changes in the lowest-lying electronic transitions. These bond order changes were used to calculate resonance Raman intensities in order to obtain correct vibrational assignments and reliable force fields.


Estimating contact-adjusted immunity levels against measles in South Korea and prospects for maintaining elimination status.
Measles has been reemerging in South Korea since December 2018 resulting in 185 cases by September 2019. We calculated contact-adjusted immunity levels against measles in South Korea using national seroprevalence data in 2014, vaccination uptake rates, and an age-specific contact matrix. We further explored options to achieve a contact-adjusted immunity level of 93% for herd immunity. The assessed contact-adjusted immunity level has increased from 86% in 2014 to 92% in 2018. Herd immunity could be achieved with immunizing 50% of susceptibles among birth cohorts 1999-2003 in 2018. Contact-adjusted immunity levels against measles have increased recently in South Korea, although they might not yet be high enough to guarantee herd immunity.


Regulation of expression of aminopeptidase N in fetal rat lung by dexamethasone and epidermal growth factor.
Aminopeptidase N (EC 188.8.131.52) (APN) is an ectopeptidase expressed in lung at the apical surface of alveolar type II epithelial cells. Its expression is up-regulated during fetal lung development. Recently several ectopeptidases have been recognized as possible regulators of growth and cell differentiation through their role in hydrolysis of autocrine and paracrine peptides that influence these processes. The studies reported here describe effects of factors known to promote lung development and differentiation of the alveolar epithelium on expression of aminopeptidase N during fetal lung development in organ culture. Fetal rat lung was placed in organ culture at the 15th gestational day and cultured for 6 days in the presence or absence of the synthetic glucocorticoid hormone dexamethasone or epidermal growth factor (EGF). Steady-state levels of APN mRNA increased approximately 10-fold during the 6-day culture. During this time the lung alveolar epithelium developed to the point where immature alveolar type II cells were recognized by the presence of lamellar bodies. Dexamethasone or EGF increased the levels of APN mRNA in the fetal lung 2-to 3-fold over control cultures by the third day in culture and concurrently accelerated the morphological development of the alveolar epithelium. Differences in treated and control cultures diminished after 6 days in culture when the epithelium appeared more mature, suggesting that the immature epithelium was more responsive to the treatments.


Childhood identification and prophylaxis of antisocial personality disorder.
Physiological and psychological characteristics show considerable similarity between children with attention deficit disorder with hyperactivity (ADDH) and adults with antisocial personality disorder (ASPD). Prospective studies of ADDH children, with or without conduct disorder (CD), show a high outcome of ASPD. Recently, other forms of treatment have been added to the traditional psychopharmacological agents used for ADDH. If medication and new treatment modalities are administered for a period of three years, a recent controlled study indicates that the mean number of arrests for felony offenses and the mean number of institutionalizations are reduced at a p less than 0.0001 level (1.32 versus 0.19 and 0.49 versus 0.00, respectively).


Proapoptotic peptide-mediated cancer therapy targeted to cell surface p32.
Antiangiogenic therapy is a promising new treatment modality for cancer, but it generally produces only transient tumor regression. We have previously devised a tumor-targeted nanosystem, in which a pentapeptide, CGKRK, delivers a proapoptotic peptide into the mitochondria of tumor blood vessel endothelial cells and tumor cells. The treatment was highly effective in glioblastoma mouse models completely refractory to other antiangiogenic treatments. Here, we identify p32/gC1qR/HABP, a mitochondrial protein that is also expressed at the cell surface of activated (angiogenic) endothelial cells and tumor cells, as a receptor for the CGKRK peptide. The results demonstrate the ability of p32 to cause internalization of a payload bound to p32 into the cytoplasm. We also show that nardilysin, a protease capable of cleaving CGKRK, plays a role in the internalization of a p32-bound payload. As p32 is overexpressed and surface displayed in breast cancers, we studied the efficacy of the nanosystem in this cancer. We show highly significant treatment results in an orthotopic model of breast cancer. The specificity of cell surface p32 for tumor-associated cells, its ability to carry payloads to mitochondria, and the efficacy of the system in important types of cancer make the nanosystem a promising candidate for further development.


Nutrient/TOR-dependent regulation of RNA polymerase III controls tissue and organismal growth in Drosophila.
The nutrient/target-of-rapamycin (TOR) pathway has emerged as a key regulator of tissue and organismal growth in metazoans. The signalling components of the nutrient/TOR pathway are well defined; however, the downstream effectors are less understood. Here, we show that the control of RNA polymerase (Pol) III-dependent transcription is an essential target of TOR in Drosophila. We find that TOR activity controls Pol III in growing larvae via inhibition of the repressor Maf1 and, in part, via the transcription factor Drosophila Myc (dMyc). Moreover, we show that loss of the Pol III factor, Brf, leads to reduced tissue and organismal growth and prevents TOR-induced cellular growth. TOR activity in the larval fat body, a tissue equivalent to vertebrate fat or liver, couples nutrition to insulin release from the brain. Accordingly, we find that fat-specific loss of Brf phenocopies nutrient limitation and TOR inhibition, leading to decreased systemic insulin signalling and reduced organismal growth. Thus, stimulation of Pol III is a key downstream effector of TOR in the control of cellular and systemic growth.


Enzymatic formation of carbohydrate rings catalyzed by single-walled carbon nanotubes.
Macrocyclic carbohydrate rings were formed via enzymatic reactions around single-walled carbon nanotubes (SWNTs) as a catalyst. Cyclodextrin glucanotransferase, starch substrate and SWNTs were reacted in buffer solution to yield cyclodextrin (CD) rings wrapped around individual SWNTs. Atomic force microscopy showed the resulting complexes to be rings of 12-50 nm in diameter, which were highly soluble and dispersed in aqueous solution. They were further characterized by Raman and Fourier transform infrared spectroscopy and molecular simulation using density functional theory calculation. In the absence of SWNT, hydrogen bonding between glucose units determines the structure of maltose (the precursor of CD) and produces the curvature along the glucose chain. Wrapping SWNT along the short axis was preferred with curvature in the presence of SWNTs and with the hydrophobic interactions between the SWNTs and CD molecules. This synthetic approach may be useful for the functionalization of carbon nanotubes for development of nanostructures.


A general method for detecting protease activity via gelation and its application to artificial clotting.
A modular system for detecting protease activity via enzyme-triggered gel formation is described. Protease-specific recognition sequences are utilized to achieve enzyme specificity. Artificial blood clotting is demonstrated by activating endogenous thrombin to trigger gelation in fibrinogen-deficient blood plasma.


In vitro and in vivo mutagenicity studies with airborne particulate extracts.
The contribution of nitro compounds to airborne particulate mutagenicity was studied with Salmonella typhimurium strains TA98, TA98NR, TA98/1,8DNP6. The results obtained indicate that nitropyrenes play a minor role in air particulate mutagenicity. Seasonal variations indicate a relatively greater contribution of nitro compounds to the mutagenicity of spring and summer samples. Fractionation of extracts into acidic, neutral and basic components shows that neutral compounds account for about two-thirds of the total mutagenic activity. Attempts to extract mutagens adsorbed onto particulate matter with aqueous media were almost completely negative. No significant mutagenicity was detected in urine and faecal extracts and in plasma samples of Sprague-Dawley rats treated with air particulate extracts at 80 mg/kg either per os or by i.p. injection. Negative results were obtained in the micronucleus test with Swiss mice treated at 200 and 400 mg/kg (twice by i.p. injection). A significant decrease in liver aminopyrine-N-demethylase was observed in Swiss mice injected with air particulate extracts or its basic and neutral fractions. In vitro experiments suggest a direct interaction of test materials with microsomal cytochrome P-450.


Some factors affecting mother-child relationships following low birthweight delivery in a Nigerian sociocultural environment.
Twenty mothers with low birthweight babies, cared for in neonatal unit and kept in incubators (as index group) and 20 mothers with full-term babies (as control group) were studied to determine the extent of maternal separation and deprivation following delivery and the effects of these on mother-child relationships. The population was prospectively sampled and an interview method using a structured questionnaire, was adopted to obtain the information for the study. The result showed a delayed post-partum contact, negative reactions and some delays in maternal attachment in mothers of premature infants. Nevertheless, some degree of adjustment in the mother-child relationship, as shown by some positive perceptions of the infants, took place 6 months after leaving hospital. Other social and cultural factors that may contribute to the negative reactions of the mothers to premature delivery are highlighted.


Presynaptic control of dopamine metabolism in the nucleus accumbens. Lack of effect of buspirone as demonstrated using in vivo voltammetry.
Buspirone is a non-benzodiazepine drug with anxiolytic properties. It has been reported to induce a marked increase in the metabolism of dopamine in the striatum and the nucleus accumbens which is similar to that induced by neuroleptics. It has been suggested that the effect observed in the striatum reflects an action of buspirone on dopaminergic autoreceptors in both terminals and cell bodies. In the present study, presynaptic effects of buspirone on dopaminergic metabolism in the nucleus accumbens were investigated, and they were compared to the effects of the classical neuroleptic, haloperidol. Dopaminergic terminals were isolated by infusion of tetrodotoxin into the median forebrain bundle in order to evaluate the effects of buspirone and haloperidol on presynaptic receptors. Changes in dopamine metabolism were determined by in vivo voltammetry. Buspirone administered after interruption of the impulse flow did not affect dopamine metabolism. In contrast haloperidol treatment led to an increase in metabolism of dopamine. It is concluded that buspirone did not act at the presynaptic level and furthermore on dopaminergic autoreceptors.


Effects of independent lung ventilation and lateral position on cytokine markers of inflammation after unilateral lung acid injury in dogs.
The aim of this study was to compare the effects of conventional ventilation, lateral (non-injured lung-dependent) position, asynchronous and synchronous independent lung ventilation on inflammatory markers in an animal model of unilateral lung acid injury. Twenty-eight dogs underwent unilateral endobronchial instillation with hydrochloric acid and randomly received (n = 7 in each group) conventional ventilation in the supine (group I) or lateral position (group II), and independent lung ventilation in asynchronous (group III) or synchronous (group IV) modes. Arterial blood gases and serum cytokine levels were assessed at baseline, and 5 min and 4 h after mechanical ventilation. At the end of the study, cytokine levels were measured in individual lung lavage fluid. In three animals per group, differential lung perfusion was detected using a dual-head gamma camera. Unilateral acid injury alone worsened oxygenation as determined by the ratio of PaO(2) to fraction of inspired oxygen (PaO(2)/FiO(2)) and increased serum cytokine levels. Mean oxygenation (SD) was significantly preserved in group II, 338 (26); group III, 396 (28); and group IV, 395 (22) compared with group I, 173 (18) (all P < 0.01). Serum IL-8, left-lung lavage IL-8 and matrix metalloproteinase-9 levels were significantly lower in groups II-IV (all P < 0.05). Only group I showed significantly different left and right lung lavage fluid cytokine levels. Groups III and IV showed slightly decreased left lung perfusion. Cytokine levels and oxygenation were similar in groups III and IV. In this model of unilateral lung acid injury, lateral position and independent lung ventilation preserved oxygenation and attenuated the inflammatory response in serum and injured lung BAL fluid.


Characterization of the substance P receptor in rat brain cortex membranes and the inhibition of radioligand binding by guanine nucleotides.
Rat brain cortex membranes bind to a conjugate of substance P and 125I-labeled Bolton-Hunter reagent, and this binding can be inhibited by a low concentration of substance P (Kd = 1.2 +/- 0.4 X 10(-8) M). This binding is reversible and saturable (0.5 +/- 0.1 pmol of binding sites/mg of protein). Fragments of substance P as small as the carboxyl-terminal hexapeptide can inhibit the binding although their potency decreases with the decrease in the length of the peptides. The binding affinities of smaller peptides or peptides in which the carboxyl-terminal amide or amino acids are removed are drastically reduced. Biologically active analogs of substance P, physalaemin, eledoisin, substance P methyl ester, [D-Ala0]hepta(5-11)substance P, kassinin, and the eledoisin-related hexapeptide also can inhibit the binding. However, the binding is not inhibited by polypeptides structurally unrelated to substance P or by amine hormones/neurotransmitters. The binding affinities of biologically active peptides to rat brain cortex membranes are almost identical with their affinities for rat parotid cells which we previously determined. Furthermore, the recently described substance P antagonist, [D-Pro, D-Trp]substance P, inhibits the binding of the 125I-labeled substance P derivative to brain cortex membranes and to parotid cells equally well. These results suggest that the substance P receptors in the brain cortex and the parotid gland are similar. The brain cortex membrane binding of the 125I-labeled substance P derivative can be inhibited by micromolar concentrations of GTP, GDP, and their analogs. ITP and IDP were less active. Adenine and pyridine nucleotides were inactive.


Intrauterine rectovaginal tear during a manual attempt to rotate a neonate.
Intrauterine rectovaginal tears in neonates are a rare and life-threatening complication of abnormal presentation during labor. Two previous cases have been presented in the literature, of which one had a fatal outcome. The authors present a third case of a severe rectovaginal intrauterine tear that had a favorable outcome.


The Intersection of Metabolomics and Data Science.
Metabolomics generates a vast amount of data and heavily relies on data science for biological interpretation [...].


Ablative facial resurfacing.
Ablative resurfacing is a powerful tool for rejuvenation of the aging face and for the treatment of a wide array of skin lesions. In the proper hands, it is a safe and effective way to treat many of the problems of photodamaged skin that surgery or nonablative methods cannot address. This article discusses the three most common modalities used in ablative facial resurfacing: chemical peels, dermabrasion, and laser resurfacing. Indications, mechanism of action, techniques, results, and complications all are reviewed.


A comprehensive database of Nature-Inspired Algorithms.
These data contain a comprehensive collection of all Nature-Inspired Algorithms. This collection is a result of two corresponding surveys, where all Nature-Inspired Algorithms that have been published to-date were gathered and preliminary data acquired. The rapidly increasing number of nature-inspired approaches makes it hard for interested researchers to keep up. Moreover, a proper taxonomy is necessary, based on specific features of the algorithms. Different taxonomies and useful insight into the application areas that the algorithms have coped with is given through these data. This article provides a detailed description of the above mentioned collection.


Is radial shortening useful for Litchman stage 3B Kienbock's disease?
Treatment of Litchman stage 3 Kienböck's disease is still controversial. In this study our aim was to evaluate the effectiveness of radial shortening on stage 3B Kienböck's disease in comparison with stage 3A cases. Radial shortening was performed for 23 patients who had stage 3A (group I, n = 13) and 3B (group II, n = 10) Kienböck's disease between 1994 and 2004. The radial osteotomy was performed 4.5 cm proximal to the distal articular surface. The mean shortening was 2.6 mm (range 2 to 4.5). The average follow-up period was 85 months (range 26-147). Based on the modified Nakamura system, the mean clinical points were 14.3 in group I and 13.3 in group II. There was no statistical difference between both groups with regard to clinical points (P = 0.483). The extension-flexion arc showed significant improvement in both groups. Based on the results of this long-term follow-up study, we concluded that radial shortening osteotomy can be performed in the treatment of type 3B Kienböck's disease as reliably as type 3A, despite the lack of evident radiological improvement.


The Dead with No Wake, Grieving with No Closure: Illness and Death in the Days of Coronavirus in Spain.
The pandemic caused by the spread of Covid-19 is giving rise to an exceptional social situation because of the great speed of propagation of the illness and the high level of mortality it has occasioned in a very short time. Moreover, the lockdown measures decreed in Spain prohibit the holding of wakes to avoid contagion, and limit funerals to three people plus the officiant. Thus, coronavirus is robbing people of the opportunity of a final farewell, stripping the dead of their dignity and worsening the grief of the living. This article investigates the situation and the social and cultural impact it has provoked. The method used takes the line of critical dialogue analysis (CDA) applied to information contained in the mass media, employing qualitative material from a related small-scale study. The results show that in countries like Spain where there is a strong Roman Catholic tradition the importance of these rituals is unquestionable. Although the country has become laicized over recent years, many traditions around death are still maintained. Hence, the impossibility of holding funerals is triggering a large number of social and personal conflicts. Furthermore, they indicate that lockdown, and the lack of rituals and of accompaniment constitute some of the most crucial stressors in the epidemic. Grief in solitude has become widespread and all the more fundamental in a society that values social support from close friends and family members. The conclusions show that the social distancing imposed by the epidemic is especially hard to bear when relatives are passing into death.


Magnitude of central obesity and associated factors among adult patients attending public health facilities in Adama town, Oromia region, Ethiopia, 2022.
Central obesity is excessive accumulation of fat around the abdomen, which is associated with the risk of coronary heart and cerebrovascular diseases. This study determined the magnitude of central obesity among adult patients using the waist-to-hip ratio, which has a superior capacity to measure the risk of developing non-communicable diseases compared to the body mass index used in previous studies in Ethiopia. Institutional-based cross-sectional study was conducted among a sample of 480 adults from April 1 to May 30, 2022. A systematic random sampling technique was used to select the study participants. Data were collected by using interviewer-administered structured questionnaires and anthropometric measurements. The data were entered into EPI INFO version 7 and analyzed by Statistical Software for Social Science Version 25. The associations between independent and dependent variables were checked using bivariate and multivariate logistic regression analyses. Adjusted odds ratio and 95% confidence interval were used to measure the strengths of the association. Statistical significance was declared at a P value of less than 0.05. The magnitude of central obesity in this study was 40% (51.2% and 27.4% among females and males, respectively (95% CI 36-44%)). Being a female (AOR = 9.5, 95% CI 5.22-17.9), age range 35-44 (AOR = 7.0, 95% CI 2.9-16.7), 45-64 years (AOR = 10.1, 95% CI4.0-15.2), married (AOR = 2.5, 95% CI 1.3-4.7), high monthly income (AOR = 3.3, 95% CI 1.5-7.3), high consumption of milk and milk products (AOR = 0.3, 95% CI 0.1-0.6), family history of obesity (AOR = 1.8, 95% CI 1.1-3.2) were significantly associated with central obesity among the study participants. The magnitude of central obesity was higher in the study area. Sex, age, marital status, monthly income, consumption of milk and milk products, and family history of obesity were independent determinants of central obesity. Therefore, it is important to raise awareness about central obesity through behavior change communication that targets the high-risk population.


Purification and characterization of four antibacterial peptides from protamex hydrolysate of Atlantic mackerel (Scomber scombrus) by-products.
Proteins from fish by-product sources are valuable source of bioactive peptides and show promise as functional foods ingredients. The objective of the present study was to isolate and characterize antibacterial peptides from protamex hydrolysates of Atlantic mackerel (Scomber scombrus) by-products. Four sequences SIFIQRFTT (P4), RKSGDPLGR (P8.1), AKPGDGAGSGPR (P8.2) and GLPGPLGPAGPK (P11) were identified in peptide fractions separated using RP-HPLC. At 200 μg mL(-1), while peptides P8.1, P8.2 and P11 exhibited partial inhibition, P4 totally inhibited tested Gram-positive (Listeria innocua) and Gram-negative (Escherichia coli) bacterial strains. These results suggest that the protein hydrolysate derived from mackerel by-products could be used as an antimicrobial ingredient in both functional food and nutraceutical applications.


Burst abdomen and incisional hernia after major gastrointestinal operations--comparison of three closure techniques.
To compare the incidence of burst abdomen and incisional hernia after three different techniques of closure of the abdominal wall after major gastrointestinal operations. Prospective, randomised, controlled trial. University hospital, Norway. 599 adults who underwent major operations for gastrointestinal conditions between December 1990 and February 1992. Patients were randomised in three groups for abdominal wall closure by continuous mass polyglyconate (Maxon) double suture with loop, continuous mass polyglactin 910 (Vicryl), and interrupted polyglactin 910 (Vicryl) (layered for transverse and mass for midline incisions). Burst abdomen during the postoperative period, and incisional hernia after one year follow up. The incidence of wound dehiscence was 2% and of incisional hernia at one year 7%. There were no differences in the rate of dehiscence among the groups, but there were significantly more hernias in the polyglyconate group (19/164, 12%) compared with the two in which polyglactin 910 was used (16/327, 5%). Wound infections developed in 84/583 of our patients (14%) and the incidence was closely associated with emergency operations and contamination. Wound complications were not associated with the closure technique. Wound infection is the most important single factor in the development of burst abdomen and incisional hernia. The continuous closure technique is quicker, cheaper, and as safe as the interrupted technique.


Corrigendum to "One pot sets another boiling: A case of social learning perspective about leader self-serving behaviour and followers self-serving counterproductive work behaviour" [Heliyon 9 (3), March 2023, Article e14611].
[This corrects the article DOI: 10.1016/j.heliyon.2023.e14611.].


Cortrak feeding tube placement: interpretation agreement of the 'GI flexure' system versus X-ray.
Blind (unguided) feeding tube placement results in 0.5% of patients suffering major complications mainly due to lung misplacement detected prior to feeding. Electromagnet-guided (Cortrak) tube placement could pre-empt such complications but undetected misplacements still occur due to incorrect trace interpretation. By identifying gastrointestinal (GI) flexures from the trace, 'the GI flexure system', it has been proposed that tube position can be interpreted. To audit agreement between standards of interpreting tube position: the Cortrak 'GI flexure' system versus X-ray. In 185 primary nasointestinal tube placements tube position determined by Cortrak trace interpretation (GI flexure) was retrospectively compared with radiological position in a blinded study. Radiological and Cortrak interpretation agreed in 92.2-98.3% of placements at different GI flexures. Discrepancy mainly occurred because some radiological images were unclear or did not cover all anatomical points. The GI flexure method of Cortrak interpretation appears safe but would necessitate prospective radiological investigation to definitively test equivalence.


The role of human endogenous retroviruses (HERVs) in Multiple Sclerosis and the plausible interplay between HERVs, Epstein-Barr virus infection, and vitamin D.
Multiple Sclerosis (MS) is one of the chronic inflammatory diseases with neurological disability in the central nervous system (CNS). Although the exact cause of MS is still largely unknown, both genetic and environmental factors are thought to play a role in disease risk. Human Endogenous Retroviruses (HERVs) are endogenous viral elements of the human genome whose expression is associated with MS. HERVs are normally silenced or expressed at low levels, although their expression is higher in MS than in the healthy population. Several studies highlighted the plausible interaction between HERVs and other MS risk factors, including viral infection like Epstein-Barr viruses and vitamin D deficiency which may lead to high expression of HERVs in these patients. Understanding how HERVs act in this scenario can improve our understanding towards MS etiology and may lead to the development of antiretroviral therapies in these patients. Here in this review, we try to examine the different HERVs expression implicated in MS and their association with EBV infection and vitamin D status.


The Drosophila circadian phase response curve to light: Conservation across seasonally relevant photoperiods and anchorage to sunset.
Photic history, including the relative duration of day versus night in a 24-hour cycle, is known to influence subsequent circadian responses to light in mammals. Whether such modulation is present in Drosophila is currently unknown. To date, all photic phase-response curves (PRCs) generated from Drosophila have done so with animals housed under seasonally agnostic equatorial photoperiods with alternating 12-hour segments of light and darkness. However, the genus contains thousands of species, some of which populate high and low-latitude habitats (20-50° north or south of the Equator) where seasonal variations in the light-dark schedule are pronounced. Here, we address this disconnect by constructing the first high-resolution Drosophila seasonal atlas for light-induced circadian phase-resetting. Testing the light responses of over 4,000 Drosophila at 120 timepoints across 5 seasonally-relevant rectangular photoperiods (i.e., LD 8:16, 10:14, 12:12, 14:10, and 16:8; 24 hourly intervals surveyed in each), we determined that many aspects of the fly circadian PRC waveform are conserved with increasing daylength. Surprisingly though, irrespective of LD schedule, the start of the PRCs always remained anchored to the timing of subjective sunset, creating a differential overlap of the advance zone with the morning hours after subjective sunrise that was maximized under summer photoperiods and minimized under winter photoperiods. These data suggest that there may be differences in flies versus mammals as to how the photoperiod modulates the waveform and amplitude of the circadian PRC to light. On the other hand, they support the possibility that the lights-off transition determines the phase-positioning of photic PRCs across seasons and across species. More work is necessary to test this claim and whether it might factor into the timing of seasonal light responses in humans.


Sample Preparation and Choice of Fluorophores for Single and Dual Color Photo-Activated Localization Microscopy (PALM) with Bacterial Cells.
Photo-activated localization microscopy (PALM) is one of the light microscopy techniques providing highest resolution. Single photo-activatable or photo-switchable fluorescent molecules are stochastically excited. The point spread function of this event is recorded and the exact fluorophore position is calculated. This chapter describes how bacterial samples can be prepared for PALM to achieve routinely a resolution of ≤30 nm using fluorophores such as mNeonGreen, Dendra2, and PAmCherry. It is also explained how to perform multicolor PALM and combine it with total internal reflection (TIRF) microscopy to increase resolution.


The increasing atmospheric CO2 over India: Comparison to global trends.
Atmospheric CO2 is the key Greenhouse Gas in terms of its global warming potential and anthropogenic sources. Therefore, it is important to analyze the changes in the concentration of atmospheric CO2 to monitor regional and global climate change. Here, we use ground-based and satellite measurements for the 2002-2020 period to assess CO2 over India. The average CO2 trend over India is about 2.1 ppm/yr, and the highest trends are in agreement with the increase in total energy consumption during the period, and the highest trends are found in the areas of mines and refineries in the west and east India. The estimated CO2 trends for India are comparable to that of global tropical and mid-latitude regions. The increasing CO2 implies serious anthropogenic global warming and thus, calls for mitigation measures and continuous monitoring for timely policy interventions.


R848, a toll-like receptor 7 agonist, inhibits osteoclast differentiation but not survival or bone-resorbing function of mature osteoclasts.
R848, also known as resiquimod, acts as a ligand for toll-like receptor 7 (TLR7) and activates immune cells. In this study, we examined the effects of R848 on differentiation, survival, and bone-resorbing function of osteoclasts. R848 inhibited osteoclast differentiation of mouse bone marrow-derived macrophages (BMMs) and human peripheral blood-derived monocytes induced by receptor activator of NF-κB ligand in a dose-dependent manner. In addition, it inhibited mouse osteoclast differentiation induced in cocultures of bone marrow cells and osteoblasts in the presence of dihydroxyvitamin D(3) [1,25(OH)(2)D(3)]. However, R848 did not affect the survival or bone-resorbing activity of mouse mature osteoclasts. R848 also upregulated the mRNA expression levels of interleukin (IL)-6, IL-12, interferon (IFN)-γ, and inducible nitric oxide synthase in mouse BMMs expressing TLR7. IFN-β was consistently expressed in the BMMs and addition of neutralizing antibodies against IFN-β to the cultures partially recovered osteoclast differentiation inhibited by R848. These results suggest that R848 targets osteoclast precursors and inhibits their differentiation into osteoclasts via TLR7.


Purification and properties of a phospholipase C that has high activity toward sphingomyelin from Aspergillus saitoi.
An enzyme hydrolyzing sphingomyelin was purified from extracts of solid cultures of Aspergillus saitoi 7041 by fractionation with isopropanol followed by successive column chromatographies on DEAE-Sepharose CL-6B, butyl-Toyopearl 650 M, and phenyl-Sepharose CL-4B. The preparation of purified enzyme was homogeneous and had an activity increased 81-fold over that of the isopropanol fraction. The yield was about 65%. The molecular weight was estimated to be 54,000 by sodium dodecyl sulfate-gel electrophoresis. The enzyme solution had a violet color and contained iron atoms. The enzyme catalyzed the hydrolysis of sphingomyelin to N-acylsphingosine and phosphorylcholine. The optimum pH for hydrolytic activity was around 3.5. The Km values for sphingomyelin and 2-hexadecanoylamino-4-nitrophenylphosphorylcholine were 0.11 and 0.33 mM, respectively. The enzyme also catalyzed the hydrolysis of other phospholipids; the order of its hydrolytic activity at a substrate concentration of 2.5 mM was phosphatidylcholine greater than or equal to sphingomyelin = phosphatidylethanolamine = lysophosphatidylethanolamine greater than phosphatidyl DL-glycerol = phosphatidyl L-serine greater than phosphatidylinositol. From these results, this enzyme appears to be a new type of phospholipase C(phosphatidylcholine cholinephosphohydrolase, EC 184.108.40.206).


Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance.
Clinically acquired resistance to MAPK inhibitor (MAPKi) therapies for melanoma cannot be fully explained by genomic mechanisms and may be accompanied by co-evolution of intra-tumoral immunity. We sought to discover non-genomic mechanisms of acquired resistance and dynamic immune compositions by a comparative, transcriptomic-methylomic analysis of patient-matched melanoma tumors biopsied before therapy and during disease progression. Transcriptomic alterations across resistant tumors were highly recurrent, in contrast to mutations, and were frequently correlated with differential methylation of tumor cell-intrinsic CpG sites. We identified in the tumor cell compartment supra-physiologic c-MET up-expression, infra-physiologic LEF1 down-expression and YAP1 signature enrichment as drivers of acquired resistance. Importantly, high intra-tumoral cytolytic T cell inflammation prior to MAPKi therapy preceded CD8 T cell deficiency/exhaustion and loss of antigen presentation in half of disease-progressive melanomas, suggesting cross-resistance to salvage anti-PD-1/PD-L1 immunotherapy. Thus, melanoma acquires MAPKi resistance with highly dynamic and recurrent non-genomic alterations and co-evolving intra-tumoral immunity.


Morbidity and mortality of surgically treated pathologic humerus fractures compared to native humerus fractures.
Despite an increasing prevalence of patients sustaining pathologic fractures of neoplastic origin, few studies have investigated 30-day postoperative complication profiles after surgical treatment of pathologic humerus fractures. The purposes of this study were to use a large nationally representative database to determine short-term complication profiles after surgical treatment of pathologic humerus fractures and assess how these complications compared with more commonly studied native humerus fractures. Using the National Surgical Quality Improvement Program database, we identified 30,866 patients who underwent surgical treatment for either pathologic (n = 449) or native humerus fractures (n = 30,417) from 2007 to 2017. Thirty-day postoperative complication profiles were ascertained and compared between the 2 groups using χ2 analyses. Three logistic regression models were then performed to determine which complications were primarily attributable to the pathologic fracture itself vs. the increased comorbidity burden faced by these patients. Patients with pathologic humerus fractures experienced significantly higher rates of death (6.0% vs. 0.3%, P < .001), serious adverse events (12.2% vs. 3.7%, P < .001), minor complications (15.8% vs. 4.8%, P < .001), extended postoperative lengths of stay (42.3% vs. 21.3%, P < .001), discharge to facilities (22.3% vs. 13.5%, P < .001), and readmissions (14.8% vs. 3.4%, P < .001) compared with patients with native humerus fractures. With respect to specific complications, patients with pathologic fractures were at significantly higher risk of pulmonary complications (1.3% vs. 0.3%, P < .001), renal complications (0.7% vs. 0.2%, P = .007), thromboembolic complications (1.6% vs. 0.6%, P = .01), and transfusions (15.1% vs. 4.1%, P < .001). After surgical treatment, patients with pathologic humerus fractures had significantly higher complication rates compared with native humerus fractures, suggesting that guidelines and treatment algorithms for native humerus fractures may not be generalizable for those of pathologic origin. These findings have significant implications for preoperative patient counseling and may be used to negotiate higher reimbursement rates for these patients given a significantly higher morbidity and mortality than was previously described in literature. Postoperatively, orthopedic surgeons should closely monitor patients with pathologic humerus fractures for deep vein thrombosis, renal complications, and pulmonary complications, use blood-sparing techniques, and employ a multidisciplinary approach to help manage and prevent a more heterogeneous profile of postsurgical complications.


Biomechanics and early sac regression after endovascular aneurysm repair of abdominal aortic aneurysm.
Sac regression after endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms (AAA) is regarded as a marker of successful response to treatment. Several factors influence sac behavior after EVAR, yet little is known about the value of preoperative biomechanics. The aim of this study was to investigate the difference in aortic biomechanics between patients with and without sac regression. Patients treated with standard EVAR for infrarenal AAA at the Karolinska University Hospital between 2009 and 2012 with one preoperative and a minimum of two postoperative computed tomography angiography (CTA) scans were considered for inclusion in this single-center retrospective cohort study. Biomechanical indices such as AAA wall stress and wall stress-strength ratio as well as intraluminal thrombus (ILT) thickness and stress were measured preoperatively in A4ClinicRE (VASCOPS GmbH). AAA diameter and volume were analyzed on preoperative, 30-day, and 1-year CTAs. Patients were dichotomized based on sac regression, defined as a ≥ 5 mm decrease in maximal AAA diameter between the first two postoperative CTA scans. Multivariable logistic regression was used for analysis of factors associated with early sac regression. Of the 101 patients treated during the inclusion period, 64 were included. Thirty-nine (61%) demonstrated sac regression and 25 (39%) had a stable sac or sac increase. The mean patients age (73 years vs 76 years), male sex (85% vs 96%), and median AAA diameter (58 mm vs 58.5 mm) did not differ between patients with and without sac regression. Although no difference in preoperative biomechanics was seen between the groups, multivariable logistic regression revealed that a larger AAA diameter (odds ratio [OR], 1.27; 95% confidence interval [CI], 1.06-1.51; P = .009) and smoking (OR, 22.1; 95% CI, 2.78-174; P = .003) were positively associated with sac regression. In contrast, the lumen diameter (OR, 0.87; 95% CI, 0.77-0.98; P = .023), ILT thickness (OR, 0.85; 95% CI, 0.75-0.97; P = .013), aspirin or direct-acting oral anticoagulant use (OR, 0.11; 95% CI, 0.02-0.61; P = .012), and mean ILT stress (OR, 0.35; 95% CI, 0.14-0.87; P = .024) showed a negative association. Patients with sac regression had fewer reinterventions (log-rank P = .010) and lower mortality (log-rank P = .012) at the 5-year follow-up. This study, characterizing preoperative biomechanics in patients with and without sac regression, demonstrated a negative association between mean ILT stress and ILT thickness with a change in sac diameter after EVAR. Given that the ILT is a highly dynamic entity, further studies focusing on the role of the thrombus are needed. Furthermore, patients presenting with early sac regression had improved outcomes after EVAR.


Theoretical study of water oxidation by the ruthenium blue dimer. II. Proton relay chain mechanism for the step [bpy2(HOO)Ru(IV)ORu(IV)(OH)bpy2]4+ → [bpy2(O2(–))Ru(IV)ORu(III)(OH2)bpy2]4+.
The oxidation of water to O2 by the oxidized species [L2(O)Ru(V)ORu(V)(O)L2]4+ of the Ru blue dimer catalyst (L = bpy, bipyridine) is examined using density functional theory with model ligands and explicit solvent approaches. Following our earlier study of the initial O–O formation by addition of water (step I) ( J. Phys. Chem. A 2011, 115, 8003), we report calculations on the subsequent, penultimate step in the superoxide production (denoted step II), involving proton transfer from the reactant [L2(HOO)Ru(IV)ORu(IV)(OH)L2]4+ to form [L(O2(–))Ru(IV)ORu(III)(H2O)L2]4+. The reaction profile of step II commences with a rearrangement of the HOO and OH groups and associated solvent relaxation in the complex, accompanied by a barrier of ~9 kcal/mol and a free-energy change of +3 kcal/mol. Subsequently, a water molecule connecting these two groups mediates a double proton transfer in a proton relay chain that proceeds spontaneously with a free-energy decrease of 8 kcal/mol to form step II's product. Comparison with other calculations is made, and the implications for the overall water oxidation to O2 are discussed.


The role of intensity-modulated radiotherapy in the treatment of parotid tumors.
To compare intensity-modulated radiotherapy (IMRT) treatment plans with three-dimensional conformal radiotherapy (3D-CRT) plans to investigate the suitability of IMRT for the treatment of tumors of the parotid gland. One 3D-CRT treatment plan and 10 IMRT treatment plans with differing beam arrangements were produced for each of nine patient data sets. The plans were compared using regret analysis, dose conformity, dose to organs at risk, and uncomplicated tumor control probability (UTCP). The target dose was comparable in the 3D-CRT and IMRT plans, although improvements were seen when seven and nine IMRT fields were used. IMRT reduced the mean dose to the contralateral parotid gland and the maximum doses to the brain and the spinal cord, but increased the ipsilateral lens dose in some cases. Each IMRT arrangement produced a higher UTCP than the 3D-CRT plans; the largest absolute difference was 9.6%. IMRT is a suitable means for treating cancer of the parotid, and a five-field class solution is proposed. It produced substantial sparing of organs at risk and higher UTCPs than 3D-CRT and should enable dose escalation.


Hospital contact for mental disorders in survivors of childhood cancer and their siblings in Denmark: a population-based cohort study.
Survivors of childhood cancer are known to be at risk for long-term physical and mental effects. However, little is known about how cancers can affect mental health in the siblings of these patients. We aimed to assess the long-term risks of mental disorders in survivors of childhood cancer and their siblings. Hospital contact for mental disorders was assessed in a population-based cohort of 7085 Danish children treated for cancer by contemporary protocols between 1975 and 2010 and in their 13 105 siblings by use of data from the Danish Psychiatric Central Research Registry. Hazard ratios (HRs) for first hospital contact were calculated using a Cox proportional hazards model. We compared these sibling and survivor cohorts with two population-based cohorts who were not childhood cancer survivors or siblings of survivors. Survivors of childhood cancer were at increased risk of hospital contact for mental disorders, with HRs of 1·50 (95% CI 1·32-1·69) for males and 1·26 (1·10-1·44) for females. Children younger than 10 years at diagnosis had the highest risk, and increased risks were seen in survivors of CNS tumours, haematological malignancies, and solid tumours. Survivors had higher risk of neurodevelopmental, emotional, and behavioural disorders than population-based comparisons and siblings, and male survivors had higher risk for unipolar depression. Overall, siblings had no excess risk for mental disorders. However, our data suggest that siblings who were young at the time of cancer diagnosis of the survivor were at increased risk for mental disorders, whereas those older than 15 years at diagnosis were at a lower risk than the general population. Childhood cancer survivors should be followed up for mental late effects, especially those diagnosed in young age. Further, clinicians should also be aware that siblings who were young at the time of cancer diagnosis might be at increased risk for mental health disorders.


Rivaroxaban and apixaban for the treatment of suspected or confirmed heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is an adverse hematologic drug reaction that results in thrombocytopenia. This potentially life-threatening event is due to the administration of heparin products, such as unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH). The incidence of HIT occurs in <0.1%-7% of hospitalized patients treated with heparin products, with a risk of thrombosis as high as 50%. In 2018, the American Society of Hematology (ASH) recommended the utilization of direct oral anticoagulants (DOACs) in clinically stable patients at average bleeding risk with HIT. The objective of this study was to evaluate the prescribing patterns of rivaroxaban and apixaban for the treatment of suspected or confirmed HIT. This was a retrospective chart review from January 2013 through October 2019 at the University of Chicago Medicine. Twelve patients were identified to have received a DOAC for suspected or confirmed HIT. Rivaroxaban was utilized in seven (58%) patients, six of whom received argatroban prior to starting rivaroxaban. Five (71%) of these patients were started on the recommended dose of rivaroxaban for VTE. Apixaban was utilized in five (42%) patients; four patients were started on argatroban and transitioned to apixaban. One patient was started on the suggested dose of apixaban for VTE. After starting DOACs for suspected HIT, no patients had new thrombosis during hospitalization. Eight patients (67%) followed up at our institution within 6 months of their discharge date. No subsequent thrombi formation were identified for any of these patients. The results of this study add to the expanding literature regarding the safety and efficacy of DOAC use in HIT, and indicate DOACs are being increasingly utilized for the treatment of confirmed or suspected HIT.


Effects of probiotic litchi juice on immunomodulatory function and gut microbiota in mice.
Development new functional foods containing probiotics had gained much attention during the past two decades. In this study, probiotic litchi juice was developed, and its effects on immunomodulatory function and gut microbiota were evaluated. Firstly, the litchi juice was fermented with Lactobacillus casei, which increased total phenolic, total flavone, and exopolysaccharide contents of the litchi juice. Hence, the immunomodulatory influence of fermented litchi juice (FL) was investigated in cyclophosphamide-induced mice. The results showed that FL enhanced immune organs indexes (spleen, thymus) and antioxidant capacity, improved the secretions of cytokines (IL-2, IL-6) and immunoglobulins (IgA, IgG, SIgA), and protected the intestinal tract. Finally, the effect of FL on gut microbiota was analyzed by high-throughput sequencing analysis. The changes in the relative abundance of dominant microbe were investigated at phylum and genus levels, respectively. After treatment with FL, the relative abundance of Firmicutes phylum was dramatically increased, as well as the genera of Faecalibaculum, Lactobacillus, and Akkermansia. These findings indicated that probiotic litchi juice could alleviate immune dysfunction and modify gut microbiota structure of mice, which provide a potential functional food to improve the host health.


The impact of infliximab induction therapy on mucosal healing and clinical remission in Polish pediatric patients with moderate-to-severe Crohn's disease.
To assess the clinical efficacy and the impact of infliximab (IFX) induction therapy on mucosal healing in Polish children with Crohn's disease (CD). A total of 66 children (29 boys and 37 girls) aged 14.06 ± 3.59 years with CD diagnosed at the mean age of 8.4 ± 7.3 years were included in the study. Patients received IFX (5 mg/kg) in three repeated infusions at 0, 2, and 6 weeks. The clinical activity of the disease was assessed using the Pediatric Crohn's Disease Activity Index (PCDAI) and the endoscopic activity was scored using the Simple Endoscopic Score for Crohn's disease at baseline and at week 10. Twenty-two (33%) of the studied patients reached clinical remission (PCDAI ≤ 10), 26 (39%) showed a clinical response (PCDAI between 15 and 30), and 18 (28%) did not respond to the therapy. When comparing data at baseline and at week 10, significant decreases were observed in the median PCDAI, C-reactive protein, and platelet count. In addition, a significant increase in BMI was noted. A significant decrease in the Simple Endoscopic Score for CD was observed between the initial and the control colonoscopies. Fifteen out of 66 patients (22.7%) had score 0 in the control endoscopy at week 10. No adverse events leading to therapy termination were observed. Biological therapy with IFX enables mucosal healing in pediatric patients with CD. Induction therapy with infliximab was found to be clinically effective in 72% of Polish pediatric patients with CD and induced a remission in 33% of them. Induction therapy with infliximab helps to increase BMI.


Influence of the mesonephros on the development of fetal mouse ovaries following transplantation into adult male and female mice.
We previously reported that fetal mouse ovaries frequently develop testicular structure following transplantation into adult male mice. The mechanism involved in gonadal sex reversal of ovarian grafts is not known. In the present study, we examined the influence of the adjacent mesonephros on development of the ovarian grafts. The results show that (1) when fetal ovaries were transplanted with the attached mesonephros, the frequency of ovotestis development was higher in male hosts than in female hosts, (2) the fetal ovaries that had been separated from mesonephros developed testicular structures more frequently than those with the mesonephros, and the incidence of ovotestis development was comparable in male and female hosts, (3) removal of the cranial or caudal half of the mesonephros resulted in a similar frequency of ovotestis development, and (4) when fetal ovaries were separated and reattached to the mesonephros, they developed testicular structures at a frequency similar to that of ovaries left attached to the mesonephros, and the sex of mesonephroi reattached to ovarian grafts did not influence the incidence of ovotestis development. These findings suggest that fetal ovaries can develop testicular structures after transplantation regardless of the sex of host, and that the adjacent mesonephros protects ovarian grafts from masculinizing stimuli more efficiently in female host than male hosts.


Mercury contamination in farmed fish setup on former garimpo mining areas in the Northern Mato Grosso State, Amazonian region, Brazil.
The garimpo gold mining activity has released about 2.500 tons of mercury in the Brazilian Amazonian environment in the 1980-1995 period. The northern region of Mato Grosso State, an important gold mining and trading area during the Amazonian gold rush is now at a turning point regarding its economic future. Nowadays, the activities related to gold mining have only a low relevance on its economy. Thus, the local communities are looking for economic alternatives for the development of the region. Cooperative fish farming is one of such alternatives. However, some projects are directly implemented on areas degraded by the former garimpo activity and the mercury left behind still poses risks, especially by its potential accumulation in fish. The objective of the present study was to evaluate the levels of mercury contamination in two fish farming areas, Paranaíta and Alta Floresta, with and without records of past gold-washing activity, respectively. Data such as mercury concentration in fish of different trophic level, size, and weight as well as the water physical and chemical parameters were measured and considered. These preliminary data have shown no significant difference between these two fish farming areas, relatively to mercury levels in fish.


Discovery of HIV-1 integrase inhibitors: pharmacophore mapping, virtual screening, molecular docking, synthesis, and biological evaluation.
HIV-1 integrase enzyme plays an important role in the life cycle of HIV and responsible for integration of virus into human genome. Here, both computational and synthetic approaches were used to design and synthesize newer HIV-1 integrase inhibitors. Pharmacophore mapping was performed on 20 chemically diverse molecules using DISCOtech, and refinement was carried out using GASP. Ten pharmacophore models were generated, and model 2, containing four features including two donor sites, one acceptor atom, and one hydrophobic region, was considered the best model as it has the highest fitness score. It was used as a query in NCI and Maybridge databases. Molecules having more than 99% Q(fit) value were used to design 30 molecules bearing pteridine ring and were docked on co-crystal structure of HIV-1 integrase enzyme. Among these, six molecules, showing good docking score compared with the reference standards, were synthesized by conventional as well as microwave-assisted methods. All compounds were characterized by physical and spectral data and evaluated for in vitro anti-HIV activity against the replication of HIV-1 (IIIB) in MT-4 cells. The used approach of molecular docking and anti-HIV activity data of designed molecules will provide significant insights to discover novel HIV-1 Integrase Inhibitors.


Tethered Function Assays as Tools to Elucidate the Molecular Roles of RNA-Binding Proteins.
Dynamic regulation of RNA molecules is critical to the survival and development of cells. Messenger RNAs are transcribed in the nucleus as intron-containing pre-mRNAs and bound by RNA-binding proteins, which control their fate by regulating RNA stability, splicing, polyadenylation, translation, and cellular localization. Most RBPs have distinct mRNA-binding and functional domains; thus, the function of an RBP can be studied independently of RNA-binding by artificially recruiting the RBP to a reporter RNA and then measuring the effect of RBP recruitment on reporter splicing, stability, translational efficiency, or intracellular trafficking. These tethered function assays therefore do not require prior knowledge of the RBP's endogenous RNA targets or its binding sites within these RNAs. Here, we provide an overview of the experimental strategy and the strengths and limitations of common tethering systems. We illustrate specific examples of the application of the assay in elucidating the function of various classes of RBPs. We also discuss how classic tethering assay approaches and insights gained from them have been empowered by more recent technological advances, including efficient genome editing and high-throughput RNA-sequencing.


Morphological differences in the central nervous system and organs of monkeys inoculated intracerebrally with virulent and attenuated strains of mumps virus.
The degree of attenuation of mumps virus was studied in intracerebrally inoculated Macaca mulatta monkeys. The virulent Leningrad-3 strain and its attenuated variant as well as the attenuated Sophia-6 strain were used. The nature of pathological alterations in the neurons pointed to neurotropism of only the virulent strain. Morphological changes caused by attenuated and virulent strains in the brain structures, in the epithelium and glandular structures of the salivary glands differed considerably and may be used as a kind of markers of neurovirulence and the degree of attenuation of mumps virus strains.


Expanding the conceptualisation of the Art of Caring.
To analyze the concept Art of Caring and expand its conceptualization in the Nursing discipline. A conceptual analysis in Spanish and English was developed based on the steps proposed by Walker and Avant. Five principal historical stages of development of the concept were identified. Attributes, antecedents, consequences, and cases are provided. An analogy is proposed to illustrate this concept through the representation of a four-dimensional figure (tesseract). Art of Caring embeds the core disciplinary nursing knowledge. Exploring this concept leads to a broad perspective of Nursing and the act of caring, with the potential of uniting the discipline globally. With the increasing use of Nursing knowledge in different languages, the global understanding of its foundations is key for advancement of the discipline. This concept analysis provides tools to help nurses to understand and be understood regardless of linguistic differences.


Cytochrome C Oxidase Assembly Factor 1 Homolog Predicts Poor Prognosis and Promotes Cell Proliferation in Colorectal Cancer by Regulating PI3K/AKT Signaling.
Colorectal cancer (CRC) is one of the most common malignancies in the world. The prognosis of advanced CRC is still poor. The purpose of this study was to identify a gene expression profile associated with CRC that may contribute to the early diagnosis of CRC and improve patient prognosis. Five pairs of CRC tissues and paracancerous tissues were used to identify causative genes using microarray assays. The prognostic value of Cytochrome C Oxidase Assembly Factor 1 Homolog (COA1) in CRC was assessed in 90 CRC patients. Loss-of-function assays, cell proliferation assays using Celigo and MTT, colony formation assays, a subcutaneous xenograft mouse model, and apoptosis assays were used to define the effects of downregulation of COA1 in CRC cells in vitro and in vivo. The underlying molecular mechanisms of COA1 in CRC were also investigated. The causative gene COA1 was identified through microarray analysis. COA1 expression in CRC was notably associated with pathologic differentiation, tumor size, and tumor depth. COA1 expression may act as an independent prognostic factor for overall survival of CRC. Knockdown of COA1 inhibited the proliferation of CRC cells in vitro and the tumorigenicity of CRC cells in vivo. Decreased COA1 expression induced apoptosis of CRC cells. Based on the microarray assay results comparing HCT116 cells transfected with lentivirus encoding anti-COA1 shRNA or negative control shRNA, ingenuity pathway analysis (IPA) revealed that the PI3K/AKT signaling pathway was significantly enriched. Moreover, CCND1, mTOR, AKT1, and MDM2 were identified as the downstream genes of COA1. These findings demonstrate that COA1 promotes CRC cell proliferation and inhibits apoptosis by regulating the PI3K/AKT signaling pathway. Our results implicate COA1 as a potential oncogene involved in tumor growth and progression of CRC.


Risk of squamous cell carcinoma and methoxsalen (psoralen) and UV-A radiation (PUVA). A meta-analysis.
To assess the risk of squamous cell carcinoma (SCC) and the relation of dose to risk among groups of patients with psoriasis exposed to psoralen-UV-A (PUVA). Four electronic databases were searched from 1984 to 1998. In addition to the PUVA Follow-up Study, we included all English-language studies from the United States and Europe with at least 150 patients enrolled, who were followed up for at least 5 years as identified from our bibliographic search. A custom-designed questionnaire was used to extract data from each of the articles. For each study, if possible, we determined the incidence of basal cell carcinomas and SCCs and the incidence rate ratio of SCC among patients exposed to low-dose (we defined as < 100 treatments or 1000 J/cm2) compared with high-dose PUVA (> 200 treatments or 2000 J/cm2). Exact methods were used to calculate the incidence rate ratios. In addition to our study, we identified and reviewed 8 other studies. Overall, the incidence among patients exposed to high-dose PUVA was 14-fold higher than among patients with low-dose exposure (95% confidence interval, 8.3-24.1); a greater dose-dependent increase in risk than that observed in the PUVA Follow-up Study. Although the incidence of SCC reported among groups of PUVA-treated patients followed up for at least 5 years varies greatly, compared with the risk in low-dose patients, long-term high-dose exposure to PUVA was consistently observed to significantly increase the risk of SCC in all studies reviewed.


Single-molecule magnet behavior with a single metal center enhanced through peripheral ligand modifications.
Bis(imino)pyridine pincer ligands in conjunction with two isothiocyanate ligands have been used to prepare two mononuclear Co(II) complexes. Both complexes have a distorted square-pyramidal geometry with the Co(II) centers lying above the basal plane. This leads to significant spin-orbit coupling for the d(7) Co(II) ions and consequently to slow relaxation of the magnetization that is characteristic of Single-Molecule Magnet (SMM) behavior.