Multidetector computed tomography findings of abdominal aortic aneurysm and its complications: a pictorial review.
Abdominal aortic aneurysms (AAAs) are defined as abnormal dilatation of the abdominal aorta and are potential to catastrophic complications. With the advent of multidetector computed tomography (MDCT), this diagnostic modality has virtually replaced conventional angiography in many circumstances and has become an integral part of the evaluation of AAA. Its ability to assess the peri-aortic soft tissue and the exact extension of aneurysm as well as its excellent vascular opacification and multiplanar reconstruction make computed tomography angiography the best suited imaging modality for not only detecting AAA but also evaluating its various complications. In this pictorial essay, we intend to demonstrate the spectrum of MDCT findings in AAA and its various consequences including impending rupture, contained rupture, rupture, aorto-caval fistula, aorto-left renal vein fistula, aorto-enteric fistula, and infection. Familiarity with the characteristic imaging features of AAA is essential for clinical radiologists and also referring physicians for the prompt diagnosis of life-threatening complications.


Expression of capsules by Haemophilus influenzae in mixed infections.
The pathogenicity of eight clinical isolates of non-type b Haemophilus influenzae was investigated by inoculating them subcutaneously into mice, alone or mixed with viable or non-viable bacteria of certain other species. Three of the H. influenzae isolates were non-capsulated while five were slightly capsulated (less than 1% of organisms had capsules). The other strains of bacteria tested were four isolates of capsulated and four isolates of non-capsulated pigmented strains of Prevotella sp. and Porphyromonus sp. as well as a capsulate Klebsiella pneumoniae ("helpers"). None of the non-capsulated strains induced an abscess when inoculated alone. Following co-inoculation of viable or non-viable "helpers" with H. influenzae, abscesses were formed in all instances in which the "helper" had a capsule. Profusely capsulated cells of H. influenzae were recovered, however, only from abscesses induced with the five slightly capsulated strains of H. influenzae. These capsulated organisms were found serologically to be of type b and induced abscesses when inoculated alone. Our findings illustrate the ability of non-capsulated strains of H. influenzae to produce progeny of capsulated type b organisms after co-inoculation with certain other species.


Overexpression of the ATP-dependent helicase RecG improves resistance to weak organic acids in Escherichia coli.
Increased resistance to several weak organic acids was conferred on Escherichia coli by overexpression of the ATP-dependent helicase RecG and, to a lesser extent, by overexpressing the helicase RuvAB. This property of helicases was identified by reproducible selection of recG-bearing clones from genomic libraries of the acetate-resistant species Acetobacter aceti and Staphylococcus capitis. We show that overexpression of RecG from both species, but also from E. coli, increased the maximum biomass concentration attained by E. coli cultures that were grown in the presence of various weak organic acids and uncouplers. Furthermore, overexpression of RecG from A. aceti significantly improved the maximum growth rates of E. coli under weak organic acid challenge. Based on the known role of RecG in DNA replication/repair, our data provide a first indication that weak organic acids negatively affect DNA replication and/or repair, and that these negative effects may be counteracted by helicase activity.


Regulatory roles of miRNAs 16, 133a, and 223 on osteoclastic bone destruction caused by breast cancer metastasis.
Osteolytic bone metastasis leads to skeletal‑related events, resulting in a decline in the patient activities and survival; therefore, it is important to understand the mechanism underlying bone metastasis. Recent studies have suggested that microRNAs (miRNAs or miRs) are involved in osteoclast differentiation and/or osteolytic bone metastasis; however, the roles of miRNAs have not been elucidated. In the present study, the roles of miRNAs in bone destruction caused by breast cancer metastasis were investigated in vitro and in vivo. miR‑16, miR‑133a and miR‑223 were transfected into a human breast cancer cell line, MDA‑MB‑231. The expression of osteolytic factors in conditioned medium (miR‑CM) collected from the culture of transfected cells was assessed. To evaluate the effects of miRNAs on osteoclast differentiation and activities, tartrate‑resistant acid phosphatase (TRAP) staining and bone resorptive assays were performed in osteoclasts following miR‑CM treatment. To create in vivo bone metastasis models for histological and morphometric evaluation, miRNA‑transfected MDA‑MB‑231 cells were transplanted into the proximal tibia of nude mice. Expression of osteolytic factors, including receptor activator for nuclear factor‑κB ligand (RANKL), interleukin (IL)‑1β, IL‑6, parathyroid hormone‑related protein (PTHrP), and tumor necrosis factor (TNF), was increased in miR‑16‑CM, whereas it was decreased in both miR‑133a‑CM and miR‑223‑CM. TRAP staining and bone resorptive assays revealed that osteoclast function and activities were promoted by miR‑16‑CM treatment, whereas they were suppressed by miR‑133a‑CM and miR‑223‑CM. Consistent with in vitro findings, in vivo experiments revealed that the overexpression of miR‑16 increased osteoclast activities and bone destruction in MDA‑MB‑231 cells, whereas the opposite results were observed in both miR‑133a‑ and miR‑223‑transfected MDA‑MB‑231 cells. Our results indicated that miR‑16 promoted osteoclast activities and bone destruction caused by breast cancer metastasis in the bone microenvironment, whereas miR‑133a and miR‑223 suppressed them. These miRNAs could be potential biomarkers and therapeutic targets for breast cancer bone metastasis.


CFTR drives Na+-nHCO-3 cotransport in pancreatic duct cells: a basis for defective HCO-3 secretion in CF.
Pancreatic dysfunction in patients with cystic fibrosis (CF) is felt to result primarily from impairment of ductal HCO-3 secretion. We provide molecular evidence for the expression of NBC-1, an electrogenic Na+-HCO-3 cotransporter (NBC) in cultured human pancreatic duct cells exhibiting physiological features prototypical of CF duct fragments (CFPAC-1 cells) or normal duct fragments [CAPAN-1 cells and CFPAC-1 cells transfected with wild-type CF transmembrane conductance regulator (CFTR)]. We further demonstrate that 1) HCO-3 uptake across the basolateral membranes of pancreatic duct cells is mediated via NBC and 2) cAMP potentiates NBC activity through activation of CFTR-mediated Cl- secretion. We propose that the defect in agonist-stimulated ductal HCO-3 secretion in patients with CF is predominantly due to decreased NBC-driven HCO-3 entry at the basolateral membrane, secondary to the lack of sufficient electrogenic driving force in the absence of functional CFTR.


[Change in the functional indices of animals during prolonged inhalation of acetic acid].
Laboratory animals inhaled acetic acid vapors at a concentration of 86 to 27 mg/m3 for 3 to 35 days. It was found that the dose 36 mg/m3 inhaled for as long as 22 days constituted the minimal acting dose. The most sensitive parameters to be used in detecting the toxic effect of acetic acid were: treadmill run duration, open field activity, and ethylene, acetaldehyde and acetone concentrations in the exhaled air.


Description of larval instars of Dryinus tarraconensis Marshall, 1868 and <br />Gonatopus baeticus (Ceballos, 1927) (Hymenoptera: Chrysidoidea: Dryinidae), parasitoids of the genus Dictyophara Germar (Hemiptera: Auchenorrhyncha: Dictyopharidae).
The last immature stage and the mature larva of Dryinus tarraconensis Marshall, 1868 and Gonatopus baeticus (Ceballos, 1927) are described for the first time. Features of immature and mature larvae of both species are discussed in the context of their implications for characterizing the subfamilies Dryininae and Gonatopodinae.


Calculation of mutational free energy changes in transition states for protein folding.
Recent advances in experimental and computational methods have made it possible to determine with considerable accuracy the structures whose formation is rate limiting for the folding of some small proteins-the transition state ensemble, or TSE. We present a method to analyze and validate all-atom models of such structures. The method is based on the comparison of experimental data with the computation of the change in free energy of the TSE resulting from specific mutations. Each mutation is modeled individually in all members of an ensemble of transition state structures using a method originally developed to predict mutational changes in the stability of native proteins. We first apply this method to six proteins for which we have determined the TSEs with a technique that uses experimental mutational data (Phi-values) as restraints in the structure determination and find a highly significant correlation between the calculated free energy changes and those derived from experimental kinetic data. We then use the procedure to analyze transition state structures determined by molecular dynamics simulations of unfolding, again finding a high correlation. Finally, we use the method to estimate changes in folding rates of several hydrophobic core mutants of Fyn SH3. Taken together, these results show that the procedure developed here is a tool of general validity for analyzing, assessing, and improving the quality of the structures of transition states for protein folding.


Total Gastrectomy for CDH-1 Mutation Carriers: An Institutional Experience.
Gastric cancer is a leading cause of cancer-related death across the world. A subset of gastric cancers demonstrates an inherited genetic predisposition. Individuals with germline mutations in the CDH1 gene incur a lifetime risk for diffuse gastric cancer and benefit from prophylactic gastrectomy. The results for this operative intervention remain relatively undescribed in the literature, despite guidelines supporting its use. We present a single-institution series of patients with confirmed CDH1 mutations who underwent gastrectomy. We describe their presenting symptoms, preoperative screening, clinicopathologic features, and outcomes. Focal outcomes of interest are weight loss and postoperative morbidity. Between 2010 and 2018, ten patients with a confirmed CDH1 mutation underwent total gastrectomy with intestinal pouch reconstruction at our institution. Two patients had clinical gastric cancer at the time of their operation at 21 and 60 y of age. Eight patients had prophylactic gastrectomy. All prophylactic patients had undergone prior endoscopic screening without detection of cancer; however, three had occult gastric cancer on pathological examination. Median weight loss after gastrectomy was 10 kg at 6 mo and 11 kg at 1 y. Postoperative morbidity was limited to one anastomotic leak, one hematoma, and one case of pneumonia. All patients remain disease-free with median follow-up of 19 mo. Total gastrectomy for patients with a CDH1 mutation is a cancer-preventing operation for a high-risk population. For this series, jejunal pouch reconstruction was performed with encouragingly low postoperative morbidity, weight loss, and good subjective function.


An improved needle holder for scleral buckling surgery.
A new needle holder was designed to provide the surgeon with a stout-angled jaw and a round locking handle. It is useful for holding large needles commonly used in scleral buckling surgery.


Cost-effectiveness analysis of patent foramen ovale closure versus medical therapy alone after cryptogenic stroke.
Closure of a patent foramen ovale reduces the risk of recurrent stroke compared with medical therapy alone in young patients with cryptogenic strokes revealed by randomized control trials. Some cost-effectiveness analyses outside Japan have shown that patent foramen ovale closure is cost-effective, but no studies have examined cost-effectiveness in Japan. The objective of this study is to assess cost-effectiveness, from the perspective of a Japanese healthcare payer, of patent foramen ovale closure versus medical therapy alone for patients with patent foramen ovale related to cryptogenic strokes. A cost-effectiveness study was conducted by developing a decision tree and a Markov model. Probabilities and a 5.9-year time horizon followed the RESPECT study. Utilities and costs were based upon published studies and assumptions. All assumptions were assessed by experts, including a cardiologist and a statistical expert. The target population comprised patients with cryptogenic stroke and patent foramen ovale, aged 60 years or younger. The model was discounted at 2.0% and its cycle was one month. A willingness-to-pay threshold is set at $50,000 / quality-adjusted life years (QALYs). Incremental cost-effectiveness ratio was evaluated. Then one-way sensitivity analyses as deterministic sensitivity analysis, and probabilistic sensitivity analyses were performed to assess data robustness. Incremental quality-adjusted life years, incremental costs, and incremental cost-effectiveness ratio were 0.464, $13,562, and $29,208 per QALY gained, respectively. One-way sensitivity analysis showed that the stable state utility score difference between patent foramen ovale closure and medical therapy had the largest impact on incremental cost-effectiveness ratio. Patent foramen ovale closure is cost-effective at a stable state utility score difference of >0.051, compared with medical therapy. Probabilistic sensitivity analyses demonstrated that patent foramen ovale closure was 50.3% cost-effective. Patent foramen ovale closure was cost-effective compared with medical therapy for Japanese patients with cryptogenic stroke who were ≤60 years.


Outcomes in rectal cancer patients undergoing laparoscopic or robotic low anterior resection compared to open: a propensity-matched analysis of the NCDB (2010-2015).
Minimally invasive resection of rectal cancer is controversial due to concerns of the oncologic efficacy and the difficulties of a laparoscopic total mesorectal excision (TME). Using the National Cancer Database (NCDB), for the period 2010-2015, perioperative outcomes and overall survival (OS) in patients with rectal cancer who underwent laparoscopic or robotic low anterior resection (LLAR or RLAR) were compared to open LAR (OLAR) after propensity score matching. 26,047 patients underwent LAR: 4062 (16%) RLAR, 9236 (35%) LLAR, and 12,749 (49%) OLAR. Patient and clinical tumor characteristics were similar between groups after matching. The conversion rates among patients undergoing LLAR and RLAR were 15% and 8%, respectively. In matched OLAR and LLAR patients, longitudinal and circumferential resection margins (CRM) were positive in 5.4% and 3.2% (p < 0.001) and 5.5% and 4.1% (p < 0.001); length of stay was 6 and 5 days, (p < 0.001); readmission was required in 6.5% and 7.0% (p = 0.112); OS at 1, 3, and 5 years were 95.5%, 83.7%, and 72.0% and 95.9%, 86.3%, and 76.4%, respectively (p < 0.001). In matched OLAR and RLAR patients, longitudinal and CRM were positive in 5.4% and 3.2% (p < 0.001) and 5.5% and 3.9% (p < 0.001); length of stay was 6 and 5 days (p < 0.001); readmission was required in 6.1% and 7.9%, (p = 0.010); and OS at 1, 3, and 5 years were 96.2%, 86.5%, and 77.1% and 97.5%, 89.4%, and 79.7%, respectively (p = 0.001). In this national sample of propensity matched patients with rectal cancer who underwent open, laparoscopic, or robotic sphincter-saving rectal resection, only small differences in terms of resection margin status, length of stay, readmission, and overall survival were revealed. With acknowledgement of the limitations introduced by selection bias, our data indicate that each of the evaluated operative techniques results in acceptable outcomes for patients with rectal cancer.


Togavirus RNA: reversible effect of urea on genomes and absence of subgenomic viral RNA in Kunjin virus-infected cells.
Electrophoretic analyses showed that no RNase-sensitive RNA smaller than the genome was specified by the flavivirus Kunjin in infected Vero cells during the period of maximum RNA and protein synthesis. In contrast, RNA extracted from Sindbis virus-infected cells under similar conditions included the expected 42S RNA (equivalent to the genome) and the smaller 26S (interjacent) RNA. Treatment of the genome of both togaviruses with 12 M urea produced a reversible (possibly conformational) change; measurement of the molecular weights of the treated RNAs by co-electrophoresis with fully denatured ribosomal RNA markers in SDS-polyacrylamide gels yielded a value of 2.1 X 10(6) if 8 M urea was incorporated in the gels and 4.2 X 10(6) if urea was omitted from the gels. These results indicate that flavivirus messenger RNA is represented solely by the intact genome of m.wt. 4.2 X 10(6).


Purification of duck growth hormone and cloning of the complementary DNA.
Duck growth hormone (GH) was isolated and purified from duck pituitaries by salt precipitation and HPLC on reverse-phase C18 columns. The duck GH was homogeneous as shown by SDS-polyacrylamide gel electrophoresis with a molecular weight of 22,000. The cDNA was synthesized and cloned in Escherichia coli using EcoRI linkers and pBR322 as vector. The positive clones were selected and sequenced. The full-length duck GH cDNA contains 820 nucleotide pairs with an open reading frame coding for the precursor form duck GH of 216 amino-acid residues. The partial amino-acid sequence from the protein completely agrees with that derived from the cDNA, with Phe as the first residue in mature duck GH preceded by a 27-residue hydrophobic signal peptide. The duck GH is almost completely homologous to the chicken GH, with only three conservative substitutions (Ser for Thr, His for Tyr and Lys for Arg) and one deletion (Ala) in the duck GH sequence. Comparison of amino-acid sequence of duck GH with that of various species reveals 56%, 73% and 40% homologies with GHs of human, rat and salmon, respectively.


Personal recollections on the early development of taxol.
All of us who have worked with taxol in the laboratory and the clinic, and the many patients all over the world who have benefited from the drug, owe a great debt of gratitude to Monroe Wall, Mansukh Wani, and their colleagues for the initial isolation and characterization of this compound.


Comparing the effect of aromatherapy with breast milk, Lavandula stoechas, and Rosa damascena on venipuncture pain in preterm infants.
Since preterm infants frequently undergo painful diagnostic and therapeutic procedures, pain management, especially through non-pharmacological methods, will be extremely beneficial. Accordingly, the present study aimed to compare the effects of aromatherapy with breast milk, Lavandula stoechas, and Rosa damascena on venipuncture pain in preterm infants. In this interventional study, preterm infants were randomly divided into four groups of aromatherapy with breast milk (25 infants), Lavandula stoechas (25 infants), Rosa damascena (25 infants), and sham (25 infants). One minute before, during, and two minutes after venipuncture, the Neonatal Infant Pain Scale (NIPS) as well as heart rate and SPO2 were measured. The results indicated that pain intensity was significantly lower during and after venipuncture in all the aromatherapy methods compared with the sham group (P < 0.001). Breast milk odor decreased the pain more than the other two odors during and after venipuncture (P < 0.001); however, there was no significant difference between Lavandula stoechas and Rosa damascena (P = 0.94). SPO2 was significantly higher in infants in the Lavandula stoechas (P < 0.001) and Rosa damascena (P = 0.03) groups compared with the sham infants. All three aromatherapy methods were effective in decreasing preterm infants' venipuncture pain. Since no study on the effect of aromatherapy with Rosa damascena was found in this regard, the effectiveness of aromatherapy with Rosa damascena is of great importance, and future studies are recommended to analyze this topic in greater depth.


Risk factors for squamous cell carcinoma, a study by the National Dermatology Centre of Colombia.
Nonmelanoma skin cancer is the most common malignancy in white individuals. The risk factors for squamous cell carcinoma, which belongs to the family of nonmelanoma skin cancers, have not been studied in Colombia. To determine the risk factors for squamous cell carcinoma in patients at a national referral center for skin diseases in Colombia. We conducted a case-control study that evaluated sociodemographic, epidemiological, and clinical factors among 332 individuals. Risk was calculated as odds ratio (ORs) using the multivariate conditional logistic regression analysis method. The following risk factors were identified: family history of skin cancer (OR, 6.55; 95% CI, 1.4-28.9), living in a rural area after the age of 30 years (OR, 3.13; 95% CI, 1.3-7.2), a lifetime working outdoors (OR, 2.98; 95% CI, 1.5-5.7), smoking more than 10 cigarettes a day (OR, 2.96; 95% CI, 1.3-6.5), actinic conjunctivitis (OR, 2.68; 95% CI, 1.2-5.9), poikiloderma of Civatte (OR, 3.29; 95% CI, 1.7-6.1), numerous facial actinic keratoses (OR, 9.23; 95% CI, 4.9-17.1), and numerous freckles (OR, 3.68; 95% CI, 1.3-10.1). We have documented clinical characteristics and personal history factors that should guide the physician in making decisions on the preventive and follow-up measures to be adopted for individuals at risk of squamous cell carcinoma. These findings may help guide policy for controlling the disease using local information.


Efficacy of a bacterial siderophore, pyoverdine, to supply iron to Solanum lycopersicum plants.
Active uptake of ferric iron in microorganisms is based on siderophores. During iron deficiency, Pseudomonas fluorescens synthesizes siderophores, called pyoverdine, which have a high affinity for ferric iron. Strategy I plants generally cannot synthesize pyoverdine or take up ferric iron. We assessed the effect of pyoverdine chelated to ferric iron on iron nutrition in Solanum lycopersicum. Weight and photosynthetic pigment concentrations in the plants supplemented with the pyoverdine and ferric iron were restored to the rates of plants supplemented with ferrous iron. Leaves and roots accumulated significant iron after pyoverdine and ferric iron supplementation than when supplemented with ferric iron alone. When leaves and roots were supplemented with pyoverdine and ferric iron, the SlFRO1 expression level was suppressed to 20% and 50% relative to those decreased with ferric iron alone, respectively. The level of SlIRT1 in roots supplemented with pyoverdine and ferric iron decreased to 50% compared with the level in roots supplemented with ferric iron alone. These results suggest that SlFRO1 and SlIRT1 expression levels were suppressed and that iron content was restored by pyoverdine and ferric iron supplementation. Thus, the downregulation may have occurred because of negative feedback on mRNA expression. Pyoverdine-mediated ferric iron uptake by tomato is suggested to be a useful strategy to increase iron uptake from the environment.


Ochratoxin A induced TNFα release from the isolated and blood- free perfused rat liver.
Ochratoxin A (OTA) a naturally occuring mycotoxin is nephrotoxic, hepatotoxic, teratogenic, embryotoxic, genotoxic, cancerogenic and immunosuppressive. Focussing on the immunemodulating effects, we found that OTA induces cytokine release from the isolated and bloodfree perfused rat liver. In the present study, we have characterized the liberation of tumor necrosis factor alpha (TNFα) by OTA and we described interactions with various mycotoxins andE.coli lipopolysaccharide (LPS).


[Implementation of the recommendations for psychotherapy after psychiatric inpatient treatment : Results of the PAKT study Part II].
Waiting periods for inpatient or outpatient psychotherapeutic treatment are generally considerable. For patients treated in a psychiatric day-clinic or hospital, implementation of a recommended subsequent psychotherapeutic treatment might be difficult. In part II of the psychotherapy after hospital or day clinic (PAKT) study, we examined how the recommendation for psychotherapy can be implemented after psychiatric treatment. Three months after discharge from one of four psychiatric hospitals in southern Germany, we interviewed 306 patients who received a recommendation for psychotherapeutic treatment after their hospital stays if the recommendation was implemented successfully. Only about 12 % of the patients in the follow-up group were unable to implement the general recommendation for psychotherapy after psychiatric stay despite motivation for psychotherapeutic treatment. In the case of recommendation for outpatient psychotherapy, 20 % were unsuccessful. Predictors for successful implementation were education and employment, whereas variables like age, gender, diagnosis, or severity of disorder did not play a significant role. The relatively small percentage of unimplemented psychotherapeutic treatment is surprising at a first glance. However, the proportion recommended for psychotherapy after psychiatric stay was less than 10 %, as shown in the first part of the study (see PAKT Study Part I, doi:s00115-016-0107-z).


The control of oscillatory movements of the forearm.
The patterns of EMG activity in the biceps and triceps muscles were recorded during horizontal oscillatory movements of the forearm. Subjects showed increased frequency of oscillation as they voluntarily reduced movement amplitude. EMG burst duration was significantly correlated with wavelength of oscillation in every case. In almost half the cases burst intensity was also positively correlated with wavelength. Subjects seemed to be using one or both these methods to control amplitude. A model was developed in three stages which satisfactorily accounted for the data.


Long-term improvement in efficacy and safety after switching to ziprasidone in stable outpatients with schizophrenia.
The long-term efficacy and tolerability of treatment with ziprasidone following a switch from prior antipsychotics was evaluated in outpatients with schizophrenia or schizoaffective disorder in three open-label, flexible-dose, 1-year extension studies. These studies enrolled completers of 6-week trials in which subjects were switched to ziprasidone from conventional antipsychotics, olanzapine, or risperidone. Identical study designs and the small number of patients entering the extensions supported pooling of the data. Of 185 pooled subjects entering the extension studies, 72 completed 58 weeks of treatment. Median treatment duration was 34.6 weeks; median dose was 120 mg/day at endpoint. The intent-to-treat population showed significant improvement in Positive and Negative Syndrome Scale (PANSS) total scores (-4.3 [P< or =.01]), PANSS negative scores (-2.4 [P< or =.0001]), and Clinical Global Impression of severity score (-0.3 [P< or =.001]). Completers showed significant improvement in mean PANSS total scores (-10.2 [P<.0001]), PANSS positive scores (-2.7 [P< .0001]), PANSS negative scores (-2.7 [P< .001]), and Clinical Global Impression of severity scores (-0.6 [P< .0001]). Ziprasidone was well tolerated, and patients demonstrated significant improvement in metabolic parameters and in all movement disorder assessments. Insomnia and somnolence were the only adverse events with an incidence >10% in pooled subjects. No subject had a corrected QT interval > or =500 msec.


Lack of association between three serotonin genes and suicidal behavior in Chinese psychiatric patients.
Suicide is a significant health problem throughout the world. The serotoninergic system is believed to be involved in suicidal behavior and there is evidence of biological abnormalities of two serotonin receptors (HTR2A, HTR2C) and one serotonin transporter (5HTT) in suicide victims. Rs6313 (T102C) of HTR2A and rs6318 (Cys23Ser) of HTR2C have been investigated in suicide behavior in other studies. Here, we investigated rs6313 and rs6318 and other 10 randomly chosen SNPs, of those three genes in a study of 329 psychiatric patients who had never attempted suicide and 297 patients who had attempted suicide. No associations were found for the 12 SNPS. Our results do not support the involvement of HTR2A, 5HTT or HTR2C in suicidal behavior in Han Chinese subjects.


Design, synthesis and ex vivo evaluation of colon-specific azo based prodrugs of anticancer agents.
Colon-specific azo based prodrugs of anticancer agents like methotrexate (6), gemcitabine (7) and analogue of oxaliplatin (RTB-4) (8) were synthesized and characterized by modern analytical techniques. The prepared prodrugs were stable in acidic (pH 1.2) and basic (pH 7.4) buffers which showed their stability in upper GIT environment. Further, an assay was performed which demonstrated the presence of azoreductase enzyme in the rat fecal material, rat cecum content and other parts of intestinal content which reduce specifically the azo bond and release the drug. The in vitro cytotoxicity assay was also performed which clearly indicated that these azo based prodrugs are active against human colorectal cancer cell lines (COLO 205, COLO 320 DM and HT-29). The release behavior of prodrugs (10, 11 and 15) was 60-70% after 24h incubation at 37°C. Therefore, the synthesized azo linked prodrugs of methotrexate, gemcitabine and RTB-4 are the potential candidates for colon targeted drug delivery system with minimal undesirable side effects.


Impact of atrial fibrillation on the risk of ischemic stroke in patients on hemodialysis: BOREAS-HD3 Study.
Atrial fibrillation (AF) is an established risk factor for ischemic stroke in a general population. However, its impact in patients on hemodialysis (HD), a group with a high risk for stroke, is still controversial. Here we examined this issue in a Japanese cohort. This study was designed as a multicenter cohort study. HD patients (n = 1,067) were enrolled from 22 institutes in January 2009 and followed up for 3 years. Patients with missing data (n = 196) or kidney transplantation (n = 4) were excluded, and 867 patients contributed to the analysis of the risk of new-onset of ischemic stroke. At baseline, AF was observed in 123 patients (14.2%, AF group) and not in the others (n = 744: 85.8%, non-AF group). During a follow-up period of 31.3 months, the cumulative incidence rate for ischemic stroke was significantly higher in the AF group than in the non-AF group (6.5% vs. 2.9%, p < 0.05). In Cox regression analysis, AF was a significant independent risk factor for new-onset of ischemic stroke after adjustment for age, sex, prior history of ischemic stroke, use of warfarin, dialysis vintage, comorbidity of diabetic nephropathy, and interdialytic weight gain (hazard ratio 2.17-2.68). Present analyses using comprehensive adjustment for multiple confounders, including prior history of ischemic stroke, indicated that AF independently increases the risk of new-onset of ischemic stroke by more than twofold in Japanese HD patients.


Pre-treatment soluble PD-L1 as a predictor of overall survival for immune checkpoint inhibitor therapy: a systematic review and meta-analysis.
Immune checkpoint inhibitors (ICI) such as anti-PD-L1 and anti-PD-1 agents have been proven to be effective in various cancers. However, the rate of non-responders is still high in all cancer entities. Therefore, the identification of biomarkers that could help to optimize therapeutic decision-making is of great clinical importance. Soluble PD-L1 (sPD-L1) and PD-1 (sPD-1) are emerging blood-based biomarkers and were previously shown to be prognostic in various clinical studies. We aimed to evaluate the prognostic relevance of sPD-L1 and sPD-1 in patients with different tumor entities who underwent ICI therapy. We searched for articles in PubMed via Medline, Embase, Scopus, and Cochrane databases. The primary outcome was overall survival (OS) and progression-free survival (PFS); furthermore, we analyzed on-treatment serum level changes of sPD-L1 and sPD-1 during ICI therapy. We synthesized the data of 1,054 patients with different cancer types from 15 articles. Pooled univariate analysis showed that elevated levels of sPD-L1 were significantly associated with inferior OS (HR = 1.67; CI:1.26-2.23, I2 = 79%, p < 0.001). The strongest association was found in non-small cell lung cancer, whereas weaker or no association was observed in melanoma as well as in renal cell and esophageal cancers. Pooled multivariate analysis also showed that elevated levels of sPD-L1 correlated with worse OS (HR = 1.62; CI: 1.00-2.62, I2 = 84%, p = 0.05) and PFS (HR = 1.71; CI:1.00-2.94, I2 = 82%, p = 0.051). Furthermore, we observed that one or three months of anti-PD-L1 treatment caused a strong (27.67-fold) elevation of sPD-L1 levels in malignant mesothelioma and urothelial cancer. We found significantly inferior OS in ICI-treated cancer patients with elevated pre-treatment sPD-L1 levels, but this association seems to be tumor type dependent. In addition, sPD-L1 increases during anti-PD-L1 therapy seems to be therapy specific.


Topically applied levobunolol does not cause changes in the corneal endothelium.
The corneal endothelium was examined in ten patients suffering from ocular hypertension before, during and after four months of topical levobunolol treatment. The untreated fellow eye served as a control. The number of endothelial cells, determined with a McIntyre eyepiece and an Eisner's contact lens, was not affected by levobunolol therapy. In addition, the morphology of the cell did not appear to be affected by the drug.


Thyroxine suppressive therapy of benign solitary thyroid nodules: a prospective randomized study.
Patients with solitary thyroid nodules that are benign on aspiration biopsy are often treated nonsurgically. To find out if thyroxine therapy is effective, 74 patients were randomized to receive levothyroxine treatment or nothing. There were 8 males and 66 females. Their mean age was 39 years. The mean nodule size was 3.6 cm and the mean nodule duration was 11 months. All patients had normal serum thyroxine and thyroid stimulating hormone (TSH) levels, and positive thyrotropin releasing hormone (TRH) tests. The dose of thyroxine was adjusted until the TRH test was negative. Patients were followed at 6-month intervals in the first 2 years and yearly thereafter, with measurement of the nodule diameter. The mean follow-up period was 1.5 years. In the 37 patients receiving thyroxine therapy, 8 had disappearance of nodules, 6 had greater than 50% reduction in nodule size. In 19, the nodules were unchanged and in 4, the nodules were enlarged. In the 37 patients receiving no drug, 8 had disappearance of nodules, 5 had greater than a 50% reduction in nodule size, 17 had nodules unchanged, and 7 had enlarged nodules (p greater than 0.9). The mean reduction in nodule diameter at various follow-up periods was greater in the thyroxine group, but the difference did not reach statistical significance. Carcinoma was found in 1 patient in each group and both of them experienced nodule enlargement. We conclude that an adequate suppressive dose of levothyroxine does not alter the natural course of benign solitary thyroid nodules. An enlargement of the nodule or a change in its consistency should be further investigated to exclude malignancy.


The free swimming Pipa larvae, with a review of pipid larvae and pipid phylogeny (Anura: Pipidae).
This paper describes the morphology of the free swimming Pipa larvae, compares them with Xenopus, Hymenochirus, and to some extent, Rhinophrynus larvae, and presents a morphological diagnosis of pipid larvae. Pipa and Xenopus have very similar chondrocrania. Hymenochirus is superficially different but has the same diagnostic features. The differences appear related to its small size and predatory habitus. Other aspects of anatomy, especially the filter apparatus are very different in each genus. The filter apparatus of Pipa is somewhat reduced and seems modified for the retention of relatively large (20+ microns) particles. Similar adaptations may have been annectant to predations in Hymenochirus, which lacks a filter apparatus. However, varying states of seven character complexes, which cut across the varying ecology, show that there are two basic pipid lineages, each currently confined to Africa or South America, respectively. Recent finds of fossil South American Xenopus indicate that these two lineages separated before the continents did. This does not warrant the recognition of two subfamilies because Xenopus and Hymenochirus are too different. Pseudhymenochirus is not an intermediate between them; it is primitive Hymenochirus. Eight character states separate pipid and rhynophrynid larvae.


Neuronal Calcium Imaging, Excitability, and Plasticity Changes in the Aldh2-/- Mouse Model of Sporadic Alzheimer's Disease.
Dysregulated signaling in neurons and astrocytes participates in pathophysiological alterations seen in the Alzheimer's disease brain, including increases in amyloid-β, hyperphosphorylated tau, inflammation, calcium dysregulation, and oxidative stress. These are often noted prior to the development of behavioral, cognitive, and non-cognitive deficits. However, the extent to which these pathological changes function together or independently is unclear. Little is known about the temporal relationship between calcium dysregulation and oxidative stress, as some reports suggest that dysregulated calcium promotes increased formation of reactive oxygen species, while others support the opposite. Prior work has quantified several key outcome measures associated with oxidative stress in aldehyde dehydrogenase 2 knockout (Aldh2-/-) mice, a non-transgenic model of sporadic Alzheimer's disease. Here, we tested the hypothesis that early oxidative stress can promote calcium dysregulation across aging by measuring calcium-dependent processes using electrophysiological and imaging methods and focusing on the afterhyperpolarization (AHP), synaptic activation, somatic calcium, and long-term potentiation in the Aldh2-/- mouse. Our results show a significant age-related decrease in the AHP along with an increase in the slow AHP amplitude in Aldh2-/- animals. Measures of synaptic excitability were unaltered, although significant reductions in long-term potentiation maintenance were noted in the Aldh2-/- animals compared to wild-type. With so few changes in calcium and calcium-dependent processes in an animal model that shows significant increases in HNE adducts, Aβ, p-tau, and activated caspases across age, the current findings do not support a direct link between neuronal calcium dysregulation and uncontrolled oxidative stress.


Use of the 1,2,5-thiadiazolidin-3-one 1,1 dioxide and isothiazolidin-3-one 1,1 dioxide scaffolds in the design of potent inhibitors of serine proteinases.
The attachment of a phosphate leaving group to the 1,2,5-thiadiazolidin-3-one 1,1 dioxide and isothiazolidin-3-one 1,1 dioxide scaffolds was found to yield highly potent, time-dependent inhibitors of human leukocyte elastase (HLE).


Insight into the genome of Aspergillus fumigatus: analysis of a 922 kb region encompassing the nitrate assimilation gene cluster.
Aspergillus fumigatus is the most ubiquitous opportunistic filamentous fungal pathogen of human. As an initial step toward sequencing the entire genome of A. fumigatus, which is estimated to be approximately 30 Mb in size, we have sequenced a 922 kb region, contained within 16 overlapping bacterial artificial chromosome (BAC) clones. Fifty-four percent of the DNA is predicted to be coding with 341 putative protein coding genes. Functional classification of the proteins showed the presence of a higher proportion of enzymes and membrane transporters when compared to those of Saccharomyces cerevisiae. In addition to the nitrate assimilation gene cluster, the quinate utilisation gene cluster is also present on this 922 kb genomic sequence. We observed large scale synteny between A. fumigatus and Aspergillus nidulans by comparing this sequence to the A. nidulans genetic map of linkage group VIII.


Will the COVID-19 pandemic slow down in the Northern hemisphere by the onset of summer? An epidemiological hypothesis.
The COVID-19 pandemic has affected most countries of the world. As corona viruses are highly prevalent in the cold season, the question remains whether or not the pandemic will improve with increasing temperatures in the Northern hemisphere. We use data from a primary care registry of almost 15,000 patients over 20 years to retrieve information on viral respiratory infection outbreaks. Our analysis suggests that the severity of the pandemic will be softened by the seasonal change to summer.


Forensic applications of the determination of benzodiazepines in blood samples by microcolumn cleanup and high-performance liquid chromatography with reductive mode electrochemical detection.
Recently described microcolumn cleanup and high-performance liquid chromatography with electrochemical reductive mode detection have facilitated the determination of benzodiazepines in contaminated and degraded blood samples. Examples from an extensive application of the procedure to British forensic science casework are given here.


Defibrillation Threshold Testing: Who Doesn't Get It?
Defibrillation testing has been routinely performed as part of the implantable cardioverter-defibrillator (ICD) implantation procedure, and is currently supported by practice guidelines; however, more recently, this practice has been called into question. Such testing is safe, and serious complications are rare. With modern ICD systems, physicians will rarely encounter a patient in whom defibrillation will fail. This article reviews the literature regarding the utility, necessity, complications, and cost of routine operative and follow-up defibrillation testing, and, it is hoped, clarifies the issue of "Who doesn't get it?"


Case report: Traumatic lingual hematoma.
We describe a case of traumatic lingual hematoma in a patient on dual antiplatelet therapy. After securing the airway, bilateral lingual artery embolization successfully halted expanding hematoma formation. Patient subsequently required tracheostomy for continued airway edema. Although patient course was wrought with postoperative complications, we review this case to illustrate how prompt hematoma evacuation and embolization can resolve significant vasovagal bradycardia and hypotension secondary to expansile lingual hematoma.


Inhibition of sexual behavior in female rats by intracerebral injections of Met-enkephalin in combination with an inhibitor of enkephalin degrading enzymes.
Injection of Met-enkephalin, either subcutaneously (10 or 100 microgram, s.c.), intracerebroventricularly (100 ng or 1 microgram, i.c.v.) or into the mesencephalic central gray (100 ng), had no inhibitory effect on sexual behavior in female rats. If combined with [(R)-3-(N-hydroxy)-carboxamido-2-benzylpropanoyl]-L-alanine (kelatorphan, 5 micrograms i.c.v.; 1.5 micrograms in the central gray; 200 micrograms s.c.), an inhibitor of enkephalin degrading enzymes, however, i.c.v. or central gray (100 ng), but not s.c. (100 micrograms), injection of Met-enkephalin suppressed the behavior. Injection of Leu-enkephalin, s.c. or i.c.v. alone or in combination with kelatorphan, had no inhibitory effect. Peptidases may rapidly inactivate Met-enkephalin after intracerebral injection and prevent the behavioral effect. Inhibition of sexual behavior by Met-enkephalin may occur during lactation, a physiological state when the behavior is suppressed by an opioid peptide.


Effects of dehydroevodiamine exposure on glutamate release and uptake in the cultured cerebellar cells.
Dehydroevodiamine has been reported to have neuroprotective and antiamnesic effects. This study examined the effects of dehydroevodiamine on glutamate release and uptake in cultured cerebellar cells. Chronic dehydroevodiamine exposure decreased the viability of granule cells. The basal and N-methyl-D-aspartate (NMDA)-induced release of glutamate from granule cells were decreased (26 and 14%) by dehydroevodiamine. The NMDA-induced release of glutamate was concentration-dependently inhibited in the granule cells. The basal and NMDA-induced releases of glutamate in chronically dehydroevodiamine-preexposed granule cells were unaffected by dehydroevodiamine. Glutamate uptake in the glial cells incubated without and with cAMP was inhibited (31% and 8%, respectively) by dehydroevodiamine. In the chronically dehydroevodiamine-preexposed glial cells, glutamate uptake was increased (8%) in the cAMP-coexposed glial cells by dehydroevodiamine but was unaffected in the naive cells. In addition, dehydroevodiamine potentiated (from 20% to 34%) the inhibition of L-pyrollidine-2,4-dicarboxylic acid (PDC) on glutamate uptake in naive glial cells, but this inhibition was reduced (from 41% to 26%) in cAMP-coexposed glial cells. These results suggest that dehydroevodiamine inhibits glutamate uptake and release. Furthermore, the results suggest that the characteristics of glutamate release and uptake in granule and glial cells may be altered by chronic exposure to dehydroevodiamine.


Outcomes of Fracture Surgery in Patients With Escalating Hemoglobin A1C in the Setting of Unmanaged Diabetes.
To determine whether there is a threshold of elevated hemoglobin A1C (HbA1c) above which the complication risk is so high that fracture fixation should be avoided. Retrospective cohort study. Academic Level I trauma center. A cohort of 187 patients with HbA1c values >7 and operatively treated extremity fractures. Surgical fixation of extremity fractures. Rate of major orthopaedic complication (loss of reduction, nonunion, infection, and need for salvage procedure). 34.8% demonstrated HbA1c > 9% and 12.3% with HbA1c > 11. Major complications occurred in 31.4%; HbA1c values were not predictive. We found no evidence of a clinically or statistically significant relationship between HbA1c and risk of major complication. The odds ratio for a one-point increase in HbA1c was 1.006 ( P = 0.9439), and the area under the receiver operating characteristic curve, which reflects the average probability that someone with a major complication will have a higher HbA1c than someone without, was 0.51 (95% confidence interval 0.42-0.61), equivalent to random chance. Diabetic patients with fracture demonstrated an extremely high overall rate of complications, with 30.5% experiencing a major complication. However, patients with extreme diabetic neglect did not have higher complication rates after extremity fracture fixation when compared with patients with controlled and uncontrolled diabetes. There was no correlation between rate of complication and level of HbA1c. In addition, there was no difference in complication rate between upper and lower extremity fractures or between fractures treated with open or percutaneous fixation. This suggests that fracture treatment decision-making should not be altered for patients with poor diabetic control, and that surgery is not contraindicated in patients with an extremely high HbA1c. Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Evolution and diversification of mitochondrial protein import systems.
More than 95% of mitochondrial proteins are encoded in the nucleus, synthesised in the cytosol and imported into the organelle. The evolution of mitochondrial protein import systems was therefore a prerequisite for the conversion of the α-proteobacterial mitochondrial ancestor into an organelle. Here, I review that the origin of the mitochondrial outer membrane import receptors can best be understood by convergent evolution. Subsequently, I discuss an evolutionary scenario that was proposed to explain the diversification of the inner membrane carrier protein translocases between yeast and mammals. Finally, I illustrate a scenario that can explain how the two specialised inner membrane protein translocase complexes found in most eukaryotes were reduced to a single multifunctional one in trypanosomes.


A two-step approach improves the diagnosis of Clostridium difficile infection.
Clostridium difficile infection (CDI) is a major cause of health care-associated diarrhea. The aim of the present study was to evaluate a two-step approach for the diagnosis of CDI. The two-step procedure consisted of GDH-toxin A/B EIA (Enzyme immunoassay targeting enterotoxin A and Cytotoxin B), followed by PCR detecting toxigenic C. difficile. Results indicate that EIAs provide a rapid screening assay for the laboratory diagnosis of CDI but, in GDH-positive and toxins-negative samples, EIA should be always followed by PCR to distinguish toxigenic vs nontoxigenic strains. GDH-toxin A/B EIA-rapid test has high specificity but low sensitivity to detect CDI. The implementation of a two-step procedure significantly increases the diagnostic accuracy to detect CDI and provides a toxigenic type characterization of C. difficile isolates.


Analysis of Doppler-obtained velocity curves in functional evaluation of mechanical prosthetic valves in the mitral and aortic positions.
A total of 145 patients with 160 mechanical prostheses of the Björk-Shiley or Starr-Edwards type (15 with double mitral plus aortic valves) underwent clinical and Doppler echocardiography analysis. In the mitral position (85 valves) 10 patients with valve-related symptoms, calculated prosthetic area less than or equal to 1 cm2, or mean transprosthetic gradient greater than 10 mm Hg by Doppler echocardiography were predefined as abnormal. Seven patients had operations, and prosthetic obstruction was confirmed in all. All patients had higher pulmonary pressures (p less than 0.001) before valve replacement. Clinical presentation was variable; however, all those with proved prosthetic thrombosis had a fulminant course and distinctive velocity curves on Doppler. In the 75 patients predefined as normal, calculated valve area (2.3 +/- 0.6 cm2, mean +/- SD, range 1.3 to 3.7 cm2) and mean gradient (4.9 +/- 1.7 mm Hg, range 1.5 to 9.5 mm Hg) were widely spread and were independent of prosthetic size greater than or equal to 27 mm. Clinically 37 of 75 patients were moderately to severely limited. Mean gradient above 5 mm Hg was associated with a higher incidence of chronic atrial fibrillation (p less than 0.05), significant tricuspid regurgitation, failure of the right side of the heart, and significant functional limitation (p less than 0.02 for all). In the aortic position (75 valves) peak gradients were 28.2 +/- 15 mm Hg (8 to 80 mm Hg). Mean gradients were 18 +/- 9.6 mm Hg (6.5 to 46.5 mm Hg). Averaged gradients derived from the average of peak and late systolic gradients were 22.4 +/- 12.7 mm Hg (6 to 62 mm Hg). In all five abnormal patients (two with endocarditis and three with hemodynamic decompensation) but also in 18 of 70 clinically normal valves, peak gradients were greater than or equal to 36 mm Hg (ranges 36 to 65 mm Hg in both). Gradients were unrelated to symptoms or to the duration of the valve in situ (3 weeks to 20 years). Gradients correlated with prosthetic size (r = 0.57) and were higher (p less than 0.001) across small (19 to 23 mm) versus large (25 to 31 mm) valves. Regurgitation was present in 40% of the mitral prostheses. It was detected in 32% of the mitral prostheses defined as normal and was estimated as mild in most. Aortic regurgitation was present in all five abnormal aortic prostheses, significant in four, and in 26 of the valves (37%) defined as normal, significant in two.(ABSTRACT TRUNCATED AT 400 WORDS)


Materials chemistry: macroporous crystalline vanadium oxide foam.
Porous inorganic solids can be synthesized in complex forms, and here we describe a simple method to create an ultralight, macroporous, crystalline vanadium oxide foam by bubbling oxygen gas produced in situ through a viscous vanadium oxide gel. This foaming process could be extended to other metal oxides.


An improvement on the maximum likelihood reconstruction of pedigrees from marker data.
Many methods have been proposed to reconstruct the pedigree of a sample of individuals from their multilocus marker genotypes. These methods, like those in other fields of statistical inferences, may suffer from both type I (falsely related) and type II (falsely unrelated) errors. In sibship reconstruction, type I errors come from the spurious fusion of two or more small sibships into a single sibship, and type II errors originate from the spurious splitting of a large sibship into two or more small sibships. In this study I investigate the tendencies of both types of errors made by the likelihood methods in sibship reconstruction, using both analytical and simulation approaches. I propose an improvement on the likelihood methods to reduce sibship splitting, and thus type II errors by downscaling the number of inferred siblings sharing the same genotype at a locus. Simulations are then conducted to compare the accuracy of the original and improved likelihood methods in sibship reconstruction of a large sample of individuals in full-sib families of the same small size, the same large size and highly variable sizes, using a variable number of loci with a variable number of alleles per locus. The methods were also applied to the analysis of a salmon data set. I show that my scaling scheme prevents effectively the splitting of large sibships, and reduces type II errors greatly with little increase in type I errors. As a result, it improves the overall accuracy of sibship assignments, except when sibships are expected to be uniformly small or marker information is unrealistically scarce.


The role of race in pediatric legal intervention as a cause of injury.
Previous studies have assessed the prevalence and nature of traumatic injuries due to legal intervention in adults. The purpose of this study is to characterize and understand legal intervention trauma in children. The National Trauma Data Bank (NTDB) was queried from 2007 to 2015. Patients (0-18 years old) who sustained injuries due to legal intervention were compared to those injured from other causes in the general NTDB population. Descriptive statistics were used to characterize the study population. Multivariate logistic regression models were utilized to predict firearm trauma and mortality. 622 patients sustained injuries involving legal intervention. Compared to general NTDB pediatric population, those who sustained legal intervention injuries were more likely to be older (age 16.5 vs. 10.6, p < 0.01), male (91.96% vs. 34.95%, p < 0.01), test positive for illegal drugs (64.64% vs. 38.35%, p < 0.01) or alcohol (26.36% vs. 17.25%, p < 0.01), and be African-American (44.37% vs. 17.00%, p < 0.01), Latino (22.82% vs. 15.10%, p < 0.01), or Native American (0.96% vs.. 0.94%, p < 0.01). Logistic regression models identified an 11% increased odds (95% CI 1.02-1.21, p = 0.02) of death among African-Americans when compared to other racial groups receiving legal intervention trauma. African-American status was associated with a 12% increased odds (95% CI 1.02-1.22, p = 0.01) of firearm trauma when compared to other racial groups receiving legal intervention trauma. Legal intervention-related pediatric trauma disproportionately affects the African-American population. This is particularly pronounced in cases of firearm related injuries. III.


Refractive-index and element-spacing effects on the spectral behavior of infrared frequency-selective surfaces.
Transmission and reflection characteristics of inductive-mesh frequency-selective surfaces were measured in the 4-12-microm range. Specific issues investigated include the effect of interelement spacing on the location and width of the resonance and the influence of superstrate and substrate refractive indices on the spectral response of the structure.


Ablation plus Transarterial Embolic Therapy for Hepatocellular Carcinoma Larger than 3 cm: Science, Evidence, and Future Directions.
Thermal ablation is widely regarded as definitive therapy for early-stage hepatocellular carcinoma, but its efficacy decreases in tumors greater than 3 cm. Extensive clinical studies have supported improved outcomes provided through combining transarterial embolic therapy with ablation in the treatment of larger tumors. This article will provide a survey of the science and data for combination therapy in both thermal and nonthermal ablation modalities, as well as describe emerging applications.


Taking snapshots of a quantum thermalization process: Emergent classicality in quantum jump trajectories.
We investigate theoretically the emergence of classical statistical physics in a finite quantum system that is either totally isolated or otherwise subjected to a quantum measurement process. We show via a random matrix theory approach to nonintegrable quantum systems that the set of outcomes of the measurement of a macroscopic observable evolve in time like stochastic variables, whose variance satisfies the celebrated Einstein relation for Brownian diffusion. Our results show how to extend the framework of eigenstate thermalization to the prediction of properties of quantum measurements on an otherwise closed quantum system. We show numerically the validity of the random matrix approach in quantum chain models.


Effects of manganese, calcium, magnesium and lithium on the ouabain-induced seizure.
The effects of the intraventricularly administered cations (Mn2+, Ca2+, Mg2+ and Li+) against the seizure induced by ouabain (3 microgram) were investigated. Mn2+, Ca2+ and Mg2+ caused definite sedation and decreased locomotor activity. But Li+ was without significant behavioral effect at the doses applied. Among the cations used, Mn2+, Ca2+ and Mg2+ showed significant anticonvulsive effect on the ouabain-induced seizure. In comparison, on the dose and molar-to-molar basis, the potency of anticonvulsive action was in the following order: Mn2+ greater than Ca2+ greater than Mg2+. On the contrary, the higher dose of Li+ potentiated the ouabain-induced seizure. The importance of the increased Ca2+ level in the extracellular space or the inhibition of Ca2+ uptake as the anticonvulsive effect of Ca2+, Mn2+ and Mg2+ was discussed.


Development and evaluation of a single tube nested PCR based approach (STNPCR) for the diagnosis of plague.
The performance of a single-tube nested-PCR (STNPCR) technique was evaluated for plague diagnosis in comparison to conventional (one step) and two step nested PCR (NPCR). Assays were carried out with primers targeting the gene caf1 that encodes the Yersinia pestis F1 antigen. For STNPCR inner primers were immobilized onto the inside of the microtube caps and after the first amplification they were eluted by inversion of the tube. This procedure avoids opening the tube, reducing the risks of false-positive results by cross-contamination. The immobilized primers are stable for several months at -20 degrees C, thus, the tubes can be prepared beforehand and stored until use. STNPCR was more sensitive than conventional PCR, and less sensitive than NPCR. This drawback is compensated by a lower risk of cross-contamination. The experiments with infected animals showed that NPCR and STNPCR were able to produce positive results in all samples tested, despite contamination with other organisms. In contrast, conventional PCR yielded positive results in a smaller number of samples. Three out of 62 culture-negative rodents from plague areas, were positive by STNPCR. In conclusion, the PCR approaches evaluated, particularly NPCR and STNPCR have potential to be used as alternative tools in epidemiological surveys of plague. Furthermore, as the results can be obtained quickly (less than 24 hour), these techniques could be useful in emergency situations in which the rapidity in diagnosis is essential for adoption of immediate measures of control.


Early Gastrointestinal Complications After Open Thoracoabdominal Aortic Aneurysm Repair.
The present study was done to examine the incidence, predictors, and impact of early gastrointestinal (GI) complications after open thoracoabdominal aortic aneurysm repair. We retrospectively analyzed data from 3587 open thoracoabdominal aortic aneurysm repairs performed at our center from 1986 to 2019. We used univariate analyses and multivariable logistic regression to identify risk factors associated with GI complications, including bleeding, ischemia, obstruction, and acute pancreatitis. Adverse event was defined as operative death or persistent stroke, paraplegia, paraparesis, or renal failure necessitating dialysis. Gastrointestinal complications developed after 213 repairs (5.9%). Gastrointestinal complications less often developed after extent I repair than after repairs that involved infrarenal abdominal aortic segments (ie, extent II to IV repairs; P = .003). Patients who had GI complications more often underwent endarterectomy, stenting, or bypass of visceral arteries (51.2% vs 42.2%; P = .01). Use of selective visceral perfusion did not differ between groups. Patients who had GI complications had higher rates of operative mortality (34.3% vs 6.6%) and adverse events (44.1% vs 13.2%) and had longer hospitalization (29 vs 11 days; P < .001 for all). Independent predictors of GI complications included incidental splenectomy, rupture, non-extent I repair, older age, and longer aortic cross-clamp time. Short-term, midterm, and long-term survival were poorer for patients who had GI complications (P < .001). Although uncommon, early GI complications after open thoracoabdominal aortic aneurysm repair are associated with significant early and late morbidity and mortality. Development of perioperative strategies to mitigate these complications is warranted.


Modulation of natural killer (NK) cells by autologous neutrophils and monocytes.
Although natural killer (NK) cell activity is remarkably stable in healthy individuals, the number and cytotoxicity of the cells fluctuate in disease. In man, regulatory mechanisms are virtually unexplored but depressed NK cell function accompanies most chronic diseases. A suppressive role of monocytes/macrophages has been reported. Since neutrophils (PMN) and monocytes (M) often respond reciprocally to pathologic stimuli, experiments were designed to investigate whether increments in PMN and M per se could influence NK cell function. Peripheral blood NK cells obtained by Percoll gradient centrifugation were either cocultured with various concentrations of autologous PMN or M or they were exposed to diffusates of these granulocytes in Millipore chambers. The treated NK cells were washed and then mixed with melanoma target cells in various effector:target cell ratios. It was observed that PMN diffusates augmented cytotoxicity whereas monocyte diffusates decreased the killing function of NK cells markedly and in a dose dependent fashion (P less than 0.001). The stimulatory effect of PMN diffusates was heat labile and not attributable to interferon. The inhibitory effect of M diffusates was heat stable, not due to prostaglandins or lysozyme, and irreversible within 6 hr of observation. Binding of effector to target cells was enhanced by PMN-media, and significantly inhibited by monocyte diffusates . It is therefore possible that factors elaborated by neutrophils and monocytes in vivo could also influence NK cell function.


Endoscopic management of carpal tunnel syndrome.
This article describes a subcutaneous endoscopic operative procedure for carpal tunnel syndrome and analyzes its effectiveness using electrophysiological data. Subcutaneous transverse carpal ligament release under universal subcutaneous endoscope (USE) was performed using local anesthesia without pneumotourniquet in 54 hands of 45 patients since June 1986. The mean follow-up period was 13.8 months. Sensory disturbances began to subside immediately after the operation and disappeared within 2 months in all cases. After the disappearance of sensory disturbances, we performed postoperative electrophysiological studies in 27 patients (33 hands). Postoperative electrophysiological data were significantly improved in all cases. Patients did not suffer from any serious complications such as motor branch injuries of the median nerve, hypesthesia of the palm, or injuries of the superficial palmar arch. From these results, we conclude that the transverse carpal ligament can be safely incised by this procedure.


CIRSE Standards of Practice on Bronchial Artery Embolisation.
This CIRSE Standards of Practice document is aimed at interventional radiologists and provides best practices for performing bronchial artery embolisation to effectively treat haemoptysis. It has been developed by an expert writing group established by the CIRSE Standards of Practice Committee.


Microsurgical anatomy of the Adamkiewicz artery-anterior spinal artery junction.
The aim of this study is to describe the anterior spinal artery-Adamkiewicz artery (ASA-AKA) junction and establish a classification allowing defining the neurological risk in either thoracoabdominal aorta aneurysm treatment and in anterior or transforaminal thoracolumbar spine surgery. Fifteen spinal cords of fresh cadavers were dissected. Both lumbar arteries and ASA were injected with strongly diluted red-colored silicon. The dural crossing of AKA was located on the left side in 86 % of cases, between T8 and T10 in 73.33 % of cases and L1-L2 in 26.67 % of cases. The average diameter of the ascending branch of AKA was 1.10 mm (range 0.8-1.9 mm), and its average length was 30.27 mm (range 12.3-60 mm). The AKA's arch average diameter was 11.3 mm (range 9-20 mm) with an open downward angle average of 20.1° (range 11°-30°). The descending branch of AKA which was a continuation of ASA had an average diameter of 1.33 mm (range 0.8-1.86 mm). The ASA at the top of the arch had an average diameter of 0.74 mm (range 0.2-1.77 mm). According to these findings, we have proposed a new classification with two types of junctions. The type I and its variant correlated to high neurological risk were present in 93.33 % of cases. The type II, correlated to medium or low neurological risk, was present in 6.67 % of cases. These anatomical findings allow a planning of the neurological risk before thoracoabdominal aorta aneurysm or thoracolumbar anterior or transforaminal spine surgery.


The taenia of the rabbit colon, an elastic visceral muscle.
The longitudinal musculature (taeniae) of the rabbit proximal colon was studied by phase contrast and electron microscopy. The taenia coli of the rabbit has several structural features which are not found in other visceral muscles of this or other species, and which, on the other hand, are common in certain vascular muscles. Among the characteristics of taenia coli are: highly corrugated muscle cell profiles (even when the muscle is fixed in a resting condition), very high surface-to-volume ratio (1 micron m2/0.5 micron m3), large percentage volume of the extracellular space (about 40%), absence of intramuscular septa, and very large number of elastic fibres, which run mainly longitudinally in broad meshworks parallel to the serosal surface. Several points of contact between elastic fibres and muscle cell membrane occur at all levels along the length of the cells, often involving 11-nm microfibrils; these contacts, and others involving collagen fibrils, are regarded as cell-to-stroma junctions. The taenia coli is virtually devoid of intramuscular blood vessels, including capillaries. The possibility that the lack of capillaries is related to the abundance of elastic material is discussed.


Giant Benign Prostatic Hyperplasia in a Pakistani Patient.
"Giant hyperplasia" of the prostate is a rare pathology of the prostate gland. We report one such case, in which a successful retropubic prostatectomy was performed on an elderly male patient in Pakistan. The weight of the resected prostate was 700 g, which is the eighth largest prostate with benign prostatic hyperplasia reported.


Four-year weight loss Roux-Y gastric bypass: anastomotic reinforcement not additive.
There were 133 morbidly obese patients who received a Roux-Y gastric bypass in which a 12-mm gastrojejunostomy was sutured with multifilament steel (72 patients) for reinforcement or with interrupted silk (61 patients). Weight loss through 4 years was not different between the two patient groups. Moreover, weight loss in patients whose gastric stomas enlarged up to 16 mm was not different from those in whom the stomas remained at 12 mm. Stoma reinforcement with noncompliant steel did not add to long-term weight loss.


Dystrophin abnormalities in Duchenne and Becker dystrophy carriers: correlation with cytoskeletal proteins and myosins.
Characterization with a panel of six antibodies revealed abnormal dystrophin expression in 6 of 20 Duchenne muscular dystrophy (DMD) carriers examined, and in 5 of 12 Becker muscular dystrophy (BMD) carriers examined. The immunocytochemistry of muscle fibres was normal with five of the antibodies in two BMD carriers, but some muscle fibres were negative to the antibody directed against a portion of the dystrophin rod domain. Mosaicism was detected with all six antibodies in the other three BMD (but in only a small number of fibres) and in all DMD carriers muscles. Spectrin, vinculin and talin were immunolocalized in the same muscle specimens in order to assess membrane cytoskeletal integrity and to correlate their expression with that of dystrophin. These proteins, including vinculin, which was previously reported to be reduced in DMD patient muscles, were normally present on the surface of all dystrophin-deficient fibres. Muscle fibre types were characterized using monoclonal antibodies against fetal myosin and adult fast and adult slow myosin heavy chains. In both the DMD and BMD carriers, a significant reduction in type 2B fibres, as well as an increase in type 2C and fetal myosin-containing fibres was found - as has also been reported in DMD patients. Altered dystrophin expression was observed more frequently in type 2 than type 1 fibres. Dystrophin deficiency was found in a high percentage of type 2C fibres as well as in all fibres expressing fetal myosin; this suggests that dystrophin-deficient fibres are more susceptible to degeneration, leading to regeneration.


Carnosic acid as a major bioactive component in rosemary extract ameliorates high-fat-diet-induced obesity and metabolic syndrome in mice.
In this study, we investigated the preventive effects of carnosic acid (CA) as a major bioactive component in rosemary extract (RE) on high-fat-diet-induced obesity and metabolic syndrome in mice. The mice were given a low-fat diet, a high-fat diet or a high-fat diet supplemented with either 0.14% or 0.28% (w/w) CA-enriched RE (containing 80% CA, RE#1L and RE#1H), or 0.5% (w/w) RE (containing 45% CA, RE#2), for a period of 16 weeks. There was the same CA content in the RE#1H and RE#2 diets and half of this amount in the RE#1L diet. The dietary RE supplementation significantly reduced body weight gain, percent of fat, plasma ALT, AST, glucose, insulin levels, liver weight, liver triglyceride, and free fatty acid levels in comparison with the mice fed with a HF diet without RE treatment. RE administration also decreased the levels of plasma and liver malondialdehyde, advanced glycation end products (AGEs), and the liver expression of receptor for AGE (RAGE) in comparison with those for mice of the HF group. Histological analyses of liver samples showed decreased lipid accumulation in hepatocytes in mice administrated with RE in comparison with that of HF-diet-fed mice. Meanwhile, RE administration enhanced fecal lipid excretion to inhibit lipid absorption and increased the liver GSH/GSSG ratio to perform antioxidant activity compared with HF group. Our results demonstrate that rosemary is a promising dietary agent to reduce the risk of obesity and metabolic syndrome.


Comparison of the healing capacities of sucralfate and cimetidine in the short-term treatment of duodenal ulcer: a double-blind randomized trial.
Fifty-nine outpatients with endoscopically proven duodenal ulcer were evaluated for 4-8 wk in a randomized, double-blind trial comparing sucralfate, a sulfated disaccharide, (1 g, 0.5 h before each meal and at bedtime) with cimetidine (300 mg, 0.5 h before each meal and at bedtime). Ulcer symptoms and their relief were recorded by patients in a diary, along with data on cigarette, alcohol, coffee, and drug intake. Duodenoscopy was performed after 4 wk to assess healing, and was repeated after 8 wk if healing had not occurred by the 4-wk evaluation. Twenty-four of 30 patients taking sucralfate (80.0%) and 22 of 29 patients taking cimetidine (75.9%) had their ulcer completely healed after 4 wk. The overall healing rates after 8 wk for the sucralfate and cimetidine groups were 90.0% (27 of 30 patients) and 86.2% (25 of 29 patients), respectively. There were no significant differences between the two treatment groups in ulcer healing, symptom relief, and side effects. Symptoms were relieved equally with respect to time and efficacy. Minor adverse experiences were reported in each treatment group. None of these experiences were serious enough to warrant discontinuation of treatment. These results suggest tha sucralfate is as effective as cimetidine in the short-term treatment of duodenal ulcer.


Face mask application as a tool to diminish the particulate matter mediated heavy metal exposure among citizens of Lucknow, India.
Traffic related fine particulate emissions, enriched in metal contents, are directly linked to respiratory disorders in human subjects. In view of the growing traffic related emissions in India, the present study was undertaken to estimate the heavy metal exposure among non-occupationally exposed two vehicle riders of Lucknow City and related health effects via application of face masks (FMs) fitted with cellulose nitrate filters and measuring the peak respiratory flow rate (PEFR). Carefully selected 200 volunteers (asymptomatic n=154 and symptomatic n=46) were advised to use FMs during their deriving time for 30 days and PEFR test was conducted on each subject at the beginning, i.e. 0 day, and at end of the study period, i.e. 30 days. On completion of the prescribed study period, filters from the used FMs were collected, acid leached and analyzed for Fe, Mn, Cu, Zn, Pb, Ni, Cr and Cd. Asymptomatic and symptomatic subject groups were further divided into two age groups of 15-40 years and 41-68. Pb, Cu and Cd were significantly higher in lower age group (15-40) of symptomatic group and Cr was in asymptomatic group. Negative associations were observed between metals viz. Pb (r=-0.39, p<0.001), Cd (r=-0.26, p<0.001), Fe (r=-0.37, p<0.001), Mn (r=-0.15, p<0.05) and the lung functioning. 30 days PEFR of all subjects were higher by nearly 10% than 0 day in all 200 samples irrespective of age and symptomatic nature of the subject. The improvement could also be due to metals and other organic species, not analyzed herein. Nevertheless the results indicate that FM usage has a role to play for immediate, if not ultimate, improvement in public health and need further studies.


Human fetal spinal cord xenografts survive in the eye of athymic nude rat hosts.
Human fetal spinal cord tissue was recovered from elective abortions and grafted to the anterior chamber of the eye of adult athymic nude rats. The transplants slowly became vascularized from the host iris during the first months. There was a clear cut stage-dependent survival and growth along a more "human" time-table. Fetal spinal cord tissue from embryos younger than gestational week 8 showed a much better survival and growth than tissue from older stages. Using laminin immunohistochemistry blood vessels could be visualized in the grafts. The pattern of vascularization was, however, clearly abnormal; there were fewer vessels which had abnormally thick walls as compared to those in the normal spinal cord. Similar to rat spinal cord allografts the human spinal cord xenografts displayed a relative gliosis and were surrounded by a glial layer visualized with antibodies against glial fibrillary acidic protein. Neurofilament-immunoreactive fibres were found inside the glial layer. A variety of neurons were found including large polygonal motoneuron-shaped cells, albeit with CGRP and AChE negative cell bodies. Both Substance P and enkephalin-immunoreactive cells and fibres were found. It is concluded that xenografted fetal human spinal cord survives, grows and may provide a useful model for experimental studies of human spinal cord development and connectivity.


Expression of NF-κB and osteopontin of synovial fluid of patients with knee osteoarthritis.
To explore the significance of osteopontin and nuclear factor κB (NF-κB) expression in patients with knee osteoarthritis. RT-PCR and enzyme-linked immunosorbent assay were used to measure the Osteopontin (OPN) and NF-κB concentration of knee joint synovial fluid of patients with knee osteoarthritis and trauma fractures, and analyze the relationship between the expressiones of them. OPN and NF-κB expression at the mRNA and protein levels of patients with knee osteoarthritis were significantly higher than the control group. the result showed statistical significance (P<0.05). There was a positive correlation between the OPN levels in synovial fluid of patients with knee osteoarthritis and NF-κB expression levels (P<0.05). The high expression of OPN and NF-κB are closely related to occurrence and development of knee osteoarthritis.


Disturbed prefrontal and temporal brain function during emotion and cognition interaction in criminal psychopathy.
Impaired emotional responsiveness has been revealed as a hallmark of psychopathy. In spite of an increasing database on emotion processing, studies on cognitive function and in particular on the impact of emotion on cognition in psychopathy are rare. We used pictures from the International Affective Picture Set (IAPS) and a Simon Paradigm to address emotion-cognition interaction while functional and structural imaging data were obtained in 12 healthy controls and 10 psychopaths. We found an impaired emotion-cognition interaction in psychopaths that correlated with a changed prefrontal and temporal brain activation. With regard to the temporal cortex, it is shown that structure and function of the right superior temporal gyrus is disturbed in psychopathy, supporting a neurobiological approach to psychopathy, in which structure and function of the right STG may be important.


DNA polymerases δ and λ cooperate in repairing double-strand breaks by microhomology-mediated end-joining in Saccharomyces cerevisiae.
Maintenance of genome stability is carried out by a suite of DNA repair pathways that ensure the repair of damaged DNA and faithful replication of the genome. Of particular importance are the repair pathways, which respond to DNA double-strand breaks (DSBs), and how the efficiency of repair is influenced by sequence homology. In this study, we developed a genetic assay in diploid Saccharomyces cerevisiae cells to analyze DSBs requiring microhomologies for repair, known as microhomology-mediated end-joining (MMEJ). MMEJ repair efficiency increased concomitant with microhomology length and decreased upon introduction of mismatches. The central proteins in homologous recombination (HR), Rad52 and Rad51, suppressed MMEJ in this system, suggesting a competition between HR and MMEJ for the repair of a DSB. Importantly, we found that DNA polymerase delta (Pol δ) is critical for MMEJ, independent of microhomology length and base-pairing continuity. MMEJ recombinants showed evidence that Pol δ proofreading function is active during MMEJ-mediated DSB repair. Furthermore, mutations in Pol δ and DNA polymerase 4 (Pol λ), the DNA polymerase previously implicated in MMEJ, cause a synergistic decrease in MMEJ repair. Pol λ showed faster kinetics associating with MMEJ substrates following DSB induction than Pol δ. The association of Pol δ depended on RAD1, which encodes the flap endonuclease needed to cleave MMEJ intermediates before DNA synthesis. Moreover, Pol δ recruitment was diminished in cells lacking Pol λ. These data suggest cooperative involvement of both polymerases in MMEJ.


Ramsey waits: allocating public health service resources when there is rationing by waiting.
The optimal allocation of a public health care budget across treatments must take account of the way in which care is rationed within treatments since this will affect their marginal value. We investigate the optimal allocation rules for public health care systems where user charges are fixed and care is rationed by waiting. The optimal waiting time is higher for treatments with demands more elastic to waiting time, higher costs, lower charges, smaller marginal welfare loss from waiting by treated patients, and smaller marginal welfare losses from under-consumption of care. The results hold for a wide range of welfarist and non-welfarist objective functions and for systems in which there is also a private health care sector. They imply that allocation rules based purely on cost effectiveness ratios are suboptimal because they assume that there is no rationing within treatments.


Immunocrossreactivity of antisera against grain prolamines of wheat, rye, barley and oats.
Prolamines extracted from wheat (gliadin), rye (secalin), barley (hordein) and oats (avenin) were used to raise antibodies in rabbits. The four prolamines were separated by SDS-PAGE and blotted onto nitrocellulose. The immunocrossreactivity of the separated prolamines with the four antisera was studied. The close botanical relationship between wheat and rye, and to a lesser extent barley, is clearly established. The crossreactivity of gliadin, secalin and hordein with anti-avenin serum was found to be weak. In contrast, avenin shows a strong crossreactivity with anti-gliadin serum.


SEL1L preserves CD8+ T-cell survival and homeostasis by fine-tuning PERK signaling and the IL-15 receptor-mediated mTORC1 axis.
SEL1L-mediated endoplasmic reticulum-associated degradation (ERAD) plays critical roles in controlling protein homeostasis by degrading misfolded or terminal unfolded proteins. However, it remains unclear how SEL1L regulates peripheral T-cell survival and homeostasis. Herein, we found that SEL1L deficiency led to a greatly reduced frequency and number of mature T cells, which was further validated by adoptive transfer experiments or bone marrow chimera experiments, accompanied by the induction of multiple forms of cell death. Furthermore, SEL1L deficiency selectively disrupted naïve CD8+ T-cell homeostasis, as indicated by the severe loss of the naïve T-cell subset but an increase in the memory T-cell subset. We also found that SEL1L deficiency fueled mTORC1/c-MYC activation and induced a metabolic shift, which was largely attributable to enhanced expression of the IL-15 receptor α and β chains. Mechanistically, single-cell transcriptomic profiling and biochemical analyses further revealed that Sel1l-/- CD8+ T cells harbored excessive ER stress, particularly aberrant activation of the PERK-ATF4-CHOP-Bim pathway, which was alleviated by supplementing IL-7 or IL-15. Importantly, PERK inhibition greatly resolved the survival defects of Sel1l-/- CD8+ T cells. In addition, IRE1α deficiency decreased mTORC1 signaling in Sel1l-/- naïve CD8+ T cells by downregulating the IL-15 receptor α chain. Altogether, these observations suggest that the ERAD adaptor molecule SEL1L acts as an important checkpoint for preserving the survival and homeostasis of peripheral T cells by regulating the PERK signaling cascade and IL-15 receptor-mediated mTORC1 axis.


Efficacy of Dapagliflozin in Black Versus White Patients With Heart Failure and Reduced Ejection Fraction.
This study sought to investigate the efficacy and safety of dapagliflozin in Black and White patients with heart failure (HF) with reduced ejection fraction (HFrEF) enrolled in DAPA-HF (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure). Black patients may respond differently to certain treatments for HFrEF than White patients. Patients with New York Heart Association functional class II to IV with an ejection fraction of ≤40% and elevated N-terminal pro-B-type natriuretic peptide were eligible for DAPA-HF. Because >99% of Black patients were randomized in the Americas, this post hoc analysis considered Black and White patients enrolled only in North and South America. The primary outcome was the composite of a worsening HF event (HF hospitalization or urgent HF visit requiring intravenous therapy) or cardiovascular death. Of the 4,744 patients randomized in DAPA-HF, 1,494 (31.5%) were enrolled in the Americas. Of these, 1,181 (79.0%) were White, and 225 (15.1%) were Black. Black patients had a higher rate of worsening HF events, but not mortality, compared with White patients. Compared with placebo, dapagliflozin reduced the risk of the primary endpoint similarly in Black patients (HR: 0.62; 95% CI: 0.37-1.03) and White patients (HR: 0.68; 95% CI: 0.52-0.90; P-interaction = 0.70). Consistent benefits were observed for other prespecified outcomes, including the composite of total (first and repeat) HF hospitalizations and cardiovascular death (P-interaction = 0.43) and Kansas City Cardiomyopathy Questionnaire total symptom score. Study drug discontinuation and serious adverse events were not more frequent in the dapagliflozin group than in the placebo group in either Black or White patients. Dapagliflozin reduced the risk of worsening HF and cardiovascular death, and it improved symptoms, similarly in Black and White patients without an increase in adverse events. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).


[(Un)Forgotten Neugebauer-Le Fort operation. Paramedian closure of the vagina--safe and effective surgical procedure for treating of pelvic organ prolapse in older women].
The aim of the study is to present data concerning Neugebauer-Le Fort operations performed at the Gynecologic Oncology Clinic, Polish Mother's Health Center Research Institute in Lodz between 2000-2009, including the effects of the surgeries on improving quality of life. Our research included all patients (90 women) operated due to total pelvic organ prolapse (stage IV of POP-Q) in Gynecologic Oncology Clinic. The data was collected retrospectively from medical records. Results of the treatment were evaluated based upon surveys and control checkups. The p-value of 0.05 was considered statistically significant. Mean patient age was 76.5 years. The analysis of medical records showed that 35% of the subjects had a BMI index >30. Out of 90 patients, 53%, 30% and 4% of the women had 2, 3, and 4 natural deliveries, respectively whereas 16% had forceps delivery Of the 65 operated patients, in more than 92% all the symptoms connected with pelvic organ prolapse disappeared. Problems with the urinary tract (urinary incontinence 'de novo', urinary tract infections) emerged in 13% and constipation in 5% of the women. As far as improved quality of life after the surgery is concerned, 93% of the subjects answered 4 and 5 (in a scale from 1 to 5). Neugebauer-Le Fort surgery is characterized by high effectiveness both, in objective research and subjective ratings of the operated patients. A high safety profile constitutes a great advantage of the surgery as was confirmed in our study In carefully selected group of patients with stage IV of POP-Q, Neugebauer-Le Fort surgery is a safe and effective procedure.


Identification of serosal invasion and extramural venous invasion on review of Dukes' stage B colonic carcinomas and correlation with survival.
To determine whether serosal invasion (SI) and/or extramural venous invasion (VI) could be more frequently identified on review of Dukes' stage B colonic carcinoma resection specimens and whether the revised findings correlated with clinical outcome. The original histology slides from 82 patients with Dukes' stage B colonic carcinoma were reviewed specifically to identify tumours showing SI and/or VI. All tumours were initially reported to be negative for both pathological parameters. The selected cases included 35 patients who died of carcinoma within 5 years of surgery and 47 patients with a minimum of 5-years' postoperative survival. The review was blinded to the original histopathology reports and to clinical follow-up data. SI and/or VI were identified in 26 cases (32%). Fourteen of 18 patients with SI, 8/12 patients with VI and all four patients with both adverse histological features died of carcinoma. Review of routinely sampled and stained colonic carcinoma resection specimens increased the proportion of cases classified as positive for SI and/or VI. The revised assessment correlated with patient outcome. Reliable identification of these features may permit stratification of high-risk patients with Dukes' stage B colonic cancer who could benefit from adjuvant treatment.


Capitalisation of multiple ecosystems on property prices in Auckland, New Zealand.
Ecosystems and their associated services have become essential in policymaking as they often have implications for the welfare of those who live nearby. Coupled with the shift toward integrating green infrastructure, ecosystem services, and nature-based solutions in urban and environmental planning, ecosystems may capitalise on property prices. But a potential phenomenon in applications of hedonic prices models is the offsetting between amenities and disamenities values, which may result in insignificant marginal effects. Some strategies to mitigate this phenomenon involve introducing a greater categorisation of open spaces and housing submarkets typology. Hence, this paper explores the capitalisation patterns of 14 terrestrial and aquatic ecosystems across the housing market segments of Auckland, New Zealand's largest city. We used a dataset of 274 thousand sales transactions between January 2011 and December 2019. Models are estimated via OLS and unconditional quantile regressions (UQR) to account for heterogeneity, outliers and heavy-tailed distributions. UQR produce more accurate estimates of the implicit prices and lead to more effective policy recommendations. We find multiple capitalisation patterns across the prices distribution and confirm offsetting effects when ecosystems are not controlled as separate variables. This paper informs land-use decisions involving the preservation or creation of natural spaces in residential areas and improves our understanding of the interaction between their economic valuation and regional diversity.


Decreased serum netrin-1 is associated with ischemic stroke: A case-control study.
Netrin-1 was a laminin-related protein involved in neurovascular protection, and we previously discovered that decreased serum netrin-1 was associated with poor prognosis of ischemic stroke. However, the relationship between serum netrin-1 level and the risk of ischemic stroke remains unclear. The aim of this study was to investigate the association between netrin-1 level and risk of ischemic stroke. A case-control study including 591 ischemic stroke patients and 591 age- and sex-matched healthy individuals was conducted, and serum netrin-1 concentrations were quantitatively determined via enzyme-linked immunosorbent assay for all participants. The serum netrin-1 levels were significantly lower in the ischemic stroke patients than those in matched controls (median, 496.4 vs 652.1 pg/mL; P < 0.001). After adjustment for potential confounders, the odds ratio of ischemic stroke associated with the highest quartile of netrin-1 was 0.07 (95% CI: 0.01-0.65; Ptrend = 0.018) compared with the lowest quartile of netrin-1. Each 1-standard deviation increase of log-transformed netrin-1 was associated with a lower odds of ischemic stroke (odds ratio: 0.45, 95% CI: 0.22-0.94; P = 0.032), and a dose-response relationship between serum netrin-1 and ischemic stroke was observed (Plinearity = 0.003). Incorporating netrin-1 to conventional risk factors improved the discriminatory power for ischemic stroke (net reclassification index = 98.0%, P < 0.001; integrated discrimination improvement = 0.28%, P = 0.027). Serum netrin-1 was decreased in patients with ischemic stroke compared with healthy controls, suggesting that there was a potential role of netrin-1 in the pathogenesis of ischemic stroke.


Recent progress in Fenton/Fenton-like reactions for the removal of antibiotics in aqueous environments.
The frequent use of antibiotics allows them to enter aqueous environments via wastewater, and many types of antibiotics accumulate in the environment due to difficult degradation, causing a threat to environmental health. It is crucial to adopt effective technical means to remove antibiotics in aqueous environments. The Fenton reaction, as an effective organic pollution treatment technology, is particularly suitable for the treatment of antibiotics, and at present, it is one of the most promising advanced oxidation technologies. Specifically, rapid Fenton oxidation, which features high removal efficiency, thorough reactions, negligible secondary pollution, etc., has led to many studies on using the Fenton reaction to degrade antibiotics. This paper summarizes recent progress on the removal of antibiotics in aqueous environments by Fenton and Fenton-like reactions. First, the applications of various Fenton and Fenton-like oxidation technologies to the removal of antibiotics are summarized; then, the advantages and disadvantages of these technologies are further summarized. Compared with Fenton oxidation, Fenton-like oxidations exhibit milder reaction conditions, wider application ranges, great reduction in economic costs, and great improved cycle times, in addition to simple and easy recycling of the catalyst. Finally, based on the above analysis, we discuss the potential for the removal of antibiotics under different application scenarios. This review will enable the selection of a suitable Fenton system to treat antibiotics according to practical conditions and will also aid the development of more advanced Fenton technologies for removing antibiotics and other organic pollutants.


Adherence of Mycoplasma mycoides subspecies mycoides to cultured endothelial cells.
The LC- and SC-type strains of Mycoplasma mycoides subspecies mycoides were examined for adherence to guinea pig erythrocytes and bovine and caprine endothelial cells. The LC-type strains but not the SC-type strains adsorbed guinea pig erythrocytes and caprine endothelial cells. Difference in cytoadherence was observed between strains of the LC-type. The interaction between the most adherent LC-type strain and caprine endothelial cells was examined by transmission and scanning electron microscopy.


Thermosensitive Polypeptide Hydrogels as a Platform for ROS-Triggered Cargo Release with Innate Cytoprotective Ability under Oxidative Stress.
Reactive oxygen species (ROS) play important roles in cell signaling pathways, while increased production of ROS may disrupt cellular homeostasis, giving rise to a series of diseases. Therefore, materials responding to ROS at physiological levels are of great significance. In this work, a novel ROS-responsive thermogelling hydrogel based on methoxy poly(ethylene glycol)-poly(l-methionine) diblock copolymers is designed and synthesized. The mechanism for solution-to-hydrogel (sol-gel) phase transitions of the copolymer aqueous solutions is studied. Incubation of the hydrogels in the presence of peroxide hydrogen (H2 O2 ) displays a H2 O2 -responsive degradation process. The hydrogels containing Rhodamine 6G exhibit sustained release profiles that are accelerated in response to H2 O2 . An innate cytoprotective ability of the hydrogels is revealed by incubation of L929 cells with the hydrogels under oxidative stress, which reduces H2 O2 -mediated cell death. ROS produced by activated macrophages can accelerate the erosion of the hydrogel, suggesting that the hydrogel is also responsive to pathological level of H2 O2 . Meanwhile, the poly(l-methionine)-based hydrogels degrade within 6 weeks after subcutaneous injection into rats, with a good biocompatibility in vivo. Overall, the injectable, ROS-responsive hydrogels may serve as promising platforms for sustained drug delivery and cell-based therapies in treatment of diseases with local oxidative stress.


Involvement of subtype 1 metabotropic glutamate receptors in apoptosis and caspase-7 over-expression in spinal cord of neuropathic rats.
The effect of the non-selective, 1-aminoindan-1,5-dicarboxylic acid (AIDA), and selective (3,4-dihydro-2H-pyrano[2,3-b]quinolin-7-yl)-(cis-4-methoxycyclohexyl) methanone (JNJ16259685), metabotropic glutamate subtype 1 (mGlu1) receptor antagonists, on rat sciatic nerve chronic constrictive injury (CCI)-induced hyperalgesia, allodynia, spinal dorsal horn apoptosis, and gliosis was examined at 3 and 7 days post-injury. RT-PCR analysis showed increased expression of bax, apoptotic protease-activating factor-1 (apaf-1), nestin, GFAP, and caspase-7 mRNA in the dorsal horn spinal cord by 3 days post-CCI. At 7 days post-CCI, only over-expression of bcl-2, nestin and GFAP mRNA was observed. Administration of AIDA reduced thermal hyperalgesia and mechanical allodynia at 3 and 7 days post-CCI; administration of JNJ16259685 reduced thermal hyperalgesia at 3 and 7 days post-CCI, but not mechanical allodynia. AIDA decreased the mRNA levels of bax, apaf-1, GFAP and caspase-7 genes. JNJ16259685 increased the mRNA levels of bcl-2 and GFAP gene, and decreased APAF-1 and caspases-7 genes. Inhibiting mGlu1 receptors also reduced TUNEL-positive profiles and immunohistochemical reactivity for caspase-7. We report here that despite inhibiting CCI-induced over-expression of pro-apoptotic genes in the spinal cord dorsal horn, the selective mGlu1 receptor antagonist JNJ16259685 exerted only a slight and transient allodynic effect. Moreover, JNJ16259685, but not the non-selective AIDA, increased astrogliosis which may account for its decreased analgesic efficacy. This study provides evidence that the contemporary and partial blockade of group I and likely ionotropic glutamate receptors may be a more suitable therapy than selective blockade of mGlu1 subtype receptors condition to decrease neuropathic pain symptoms.