Detection of Leishmania DNA in Sand Flies (Diptera: Psychodidae) From a Cutaneous Leishmaniasis Outbreak Area in Northeastern Brazil.
Cutaneous leishmaniasis (CL) by Leishmania braziliensis Vianna (Kinetoplastida: Trypanosomatidae) is a widespread disease in the western hemisphere and Brazil is the country reporting the majority of the human cases each year. Several phlebotomine sand flies have been regarded as putative or proven vectors of L. braziliensis and multiple vectors may be involved in the transmission of this parasite in the same endemic foci. In this study, we tested a subset of female phlebotomine sand flies collected in the frame of a previous study conducted in a military training camp, where outbreaks of CL by L. braziliensis have sporadically been reported. In total, 1,807 female phlebotomine sand flies were tested (individually or in pools) by real-time PCR and a minimum infection rate of 0.9% (95% CI: 0.6-1.5%) was detected. Positive females belonged to the species Psychodopygus complexus (Mangabeira) or Psychodopygus wellcomei Fraiha, Shaw & Lainson (females of these species are morphologically indistinguishable), Trichopygomyia longispina (Mangabeira), and Sciopemyia sordellii (Shannon & Del Ponte) (Diptera: Psychodidae). By restriction enzyme analysis, 13 samples (nine of Ty. longispina, two of Ps. complexus/wellcomei, and two of Sc. sordellii) presented a HaeIII restriction profile identical to L. braziliensis. The results of this study reinforce the notion that multiple vectors may be involved in the transmission of L. braziliensis in a single focus, ultimately making the epidemiological picture more complex than currently recognized.


Breast reconstruction with immediate autologous free tissue transfer in a peri-operative COVID-19 positive patient: A case report illustrating feasibility of aftercare.
Globally, there has been a measured response to rationalise elective operating during the Coronavirus disease 2019 (COVID-19) pandemic. In terms of breast cancer care, this has led to a restricted provision of reconstruction with autologous free tissue transfer. A primary concern is the risk of mortality in elective surgery patients who develop COVID-19. The aim of this report is to describe the observed physiological impact of the virus on our patient, and to address how outpatient care after autologous free tissue transfer can be delivered to COVID-19 positive patients. In March 2020, we performed a bilateral breast reconstruction with a deep inferior epigastric perforator flap and a superficial inferior epigastric perforator flap. The patient became symptomatic on day three post-operatively, tested positive for COVID-19 and was discharged home. Drain and dressing management was continued through the use of telemedicine. Two weeks following the operation, a breast seroma formed that was drained semi-electively in the COVID-19 positive area of the Emergency Department. The patient visited the dressing clinic twice in total and healed after three weeks. Despite undergoing complex surgery and having pre-operative chemotherapy, our patient suffered a mild form of the virus limited to upper respiratory symptoms. Physiologically we did not see any significant difference to that of the normal post-operative course. This case demonstrates the possibility of managing autologous breast reconstruction patients using telemedicine. Although COVID-19 can complicate, or even be fatal, in the perioperative course, our patient thankfully suffered no discernable negative outcome from her infection.


The effectiveness of home-based phototherapy for vitiligo: A systematic review of randomised controlled trials.
Vitiligo may be treated with hospital-based phototherapy, but this requires long-term frequent appointments. Self-treatment using home-based phototherapy is a convenient alternative, which may improve adherence and results, but evidence is limited, and so it is not routinely recommended. This systematic review aims to assess the effectiveness and safety of home-based phototherapy for vitiligo. Searches were conducted on Medline, Scopus and The Cochrane Library for randomised controlled trials comparing home-based phototherapy with institution-based phototherapy or placebo/no phototherapy for vitiligo. The primary outcome was treatment effectiveness. CASP criteria were used for quality assessment. Data were synthesised in a meta-analysis where appropriate. Three studies (195 participants) were included: two compared home-based with institution-based phototherapy, and one compared home-based phototherapy with placebo. Studies were of mixed quality. Therapy regimes varied across studies. Findings on effectiveness were contradictory across studies with variable rates of repigmentation. There was no significant difference in repigmentation rates between the groups, although adherence to treatment schedules was significantly better in home-based groups. Adverse effects were significantly higher in home-based groups. No long-term data were reported on maintenance of treatment benefits. Although adherence to treatment was significantly better with home-based phototherapy, data were insufficient to form conclusions on effectiveness. Home-based phototherapy had a significantly higher risk of adverse effects, making it difficult to recommend in clinical practice. However, as it offers logistical advantages for patients, its effectiveness alongside additional safety measures should be explored further in large-scale, good-quality RCTs, with standardised outcome measures, including patient-reported outcomes.


Three-year randomized clinical evaluation of a low-shrinkage silorane-based resin composite in non-carious cervical lesions.
The clinical suitability of low-shrinkage resin composites for class V cavities has not been investigated in vivo. The purpose of this double-blind randomized clinical trial was to compare the clinical performances of low-shrinkage resin composite Filtek silorane and nanoceramic resin composite Ceram X mono in non-carious cervical lesions (NCCLs) over 36 months. Two calibrated operators restored 144 NCCLs in 24 patients by using Filtek silorane with silorane system adhesive (FS/SSA) and Ceram X mono with Clearfil SE (CXM/CSE) or XP bond (CXM/XPB). Then, two blinded, calibrated evaluators assessed the restorations at the baseline and 6, 12, 24, and 36 months thereafter by using the modified US Public Health Service criteria. Data were analyzed with the Freidman and Wilcoxon signed-rank tests at a significance level of 5 % (P < 0.05). No restoration was associated with postoperative sensitivity or secondary caries. Further, no group showed significant changes until 12 months. The retention rates of the FS/SSA (97.5 %), CXM/CSE (97.5 %), and CXM/XPB (92.31 %) restorations did not differ significantly (P > 0.05). Six (4 CXM/XPB, 1 FS/SSA, and 1 CXM/CSE) of the 121 restorations evaluated at 36 months were completely lost. However, no significant intergroup differences were observed in the other evaluation criteria. The 3-year clinical performances of the restorative materials in NCCLs were not significantly different. Filtek silorane is suitable for restoring NCCLs.


Individual Differences in the Affective Response to Pandemic-Related Stressors in COVID-19 Health Care Workers.
We investigated the evolving prevalence of mood and anxiety symptoms among health care workers from May 2020 to January 2021, risk factors for adverse outcomes, and characteristic modes of affective responses to pandemic-related stressors. A total of 2307 health care workers (78.9% female, modal age 25-34 years) participated in an online survey assessing depression (Patient Health Questionnaire-9) and anxiety (Generalized Anxiety Disorder-7 scale) symptoms, demographic variables, and self-reported impact of pandemic-related stressors. A total of 334 subjects were reassessed ∼6 months later. The prevalence of clinically significant depression and anxiety was 45.3% and 43.3%, respectively, and a majority (59.9%-62.9%) of those individuals had persistent significant symptoms at 6-month follow-up. Younger age, female gender, and specific occupations (support staff > nurses > physicians) were associated with increased depressive and anxiety symptoms. The most important risk factors were social isolation and fear of contracting COVID-19. The prevalence of clinically significant mood and anxiety symptoms increased by 39.8% from May 2020 to January 2021. Patient Health Questionnaire-9 and Generalized Anxiety Disorder-7 scores were highly correlated and associated with nearly identical risk factors, suggesting that they are not capturing independent constructs in this sample. Principal component analysis identified seven orthogonal symptom domains with unique risk factors. Clinically significant mood and anxiety symptoms are highly prevalent and persistent among health care workers, and are associated with numerous risk factors, the strongest of which are related to pandemic stressors and potentially modifiable. Interventions aimed at reducing social isolation and mitigating the impact of fear of infection warrant further study.


(Tris{2-[2-(2,3,5,6-tetra-fluoro-4-iodo-phen-oxy)eth-oxy]eth-yl}amine)-potassium iodide.
The title adduct, [K(C30H24F12I3NO6)]I, gives an extended tape of cations linked through I⋯I(-) halogen bonds (XBs), two of them being quite short and one quite long. In the structure, the cation is hosted in a cavity formed by the arms of the podand which presents a closed conformation wherein two tetra-fluoro-iodo-benzene rings are near parallel [dihedral angle = 15.8 (4)°; centroid-centroid distance = 3.908 (5) Å] and the third ring is closer to orthogonal [dihedral angles = 66.28 (14) and 75.20 (19)°] to the other two rings. The coordination sphere of the K(+) cation is composed of the six O atoms, the N atom and an F atom in the ortho position of one of the rings.


A later menopausal age is associated with a lower prevalence of physical frailty in community-dwelling older adults: The Korean Frailty and Aging Cohort Study (KFACS).
The aim of this study was to determine whether age at menopause is associated with physical frailty. This was a cross-sectional study that included 1264 women (70-84 years) from the Korean and Aging Cohort Study (KFACS) who had records of their ages at menarche and their ages at menopause and had experienced a natural menopause. We used Fried criteria to assess physical frailty status. The ages at menopause and menarche were collected using self-reported questionnaires. The prevalence of physical frailty decreased by 5.3 % with each year of increase in age at menopause after adjusting for age, marital status, years of education, diabetes mellitus, hypertension, polypharmacy, hospitalizations, falls, and hormone replacement therapy (p = 0.005). The prevalence of frailty significantly decreased by 4.1 % when the reproductive span increased by a year (p = 0.019). This study found that a later menopausal age was associated with a lower risk of frailty using Fried criteria. In addition, it showed that a longer reproductive span was associated with a lower prevalence of frailty.


A sandwich method of enzyme-immunoassay. II. Quantification of rheumatoid factor.
A sandwich enzyme-immunoassay (EIA) has been applied to the determination of the rheumatoid factor (RF). This non-competeitive assay comprises 3 steps: 1) the RF to be assayed is extracted for the biological medium by an immunosorbent of aggregated IgG linked to cellulose; 2) the solid phase is then incubated with the enzyme-labeled aggregated IgG; 3) the enzymatic activity of the immunosorbent is then measured with a suitable chromogenic reagent. This activity is a direct function of the amount of RF to be assayed. This assay gave reproducible results in the range 0.5-50.0 IU/ml. A good agreement was obtained between the EIA and the Waaler-Rose test but no correlation was obtained with the latex slide-test. This assay permits a quantitation of RF with a good reproducibility (coefficient of variation in the range of 10% for moderately elevated values) and thus allows a closer follow-up of patients. The results do not depend on the interpretation of the technician performing the test, which can be easily automated. Finally, it may detect some RF devoid of agglutinating activity.


Non-AUG translation: a new start for protein synthesis in eukaryotes.
Although it was long thought that eukaryotic translation almost always initiates at an AUG start codon, recent advancements in ribosome footprint mapping have revealed that non-AUG start codons are used at an astonishing frequency. These non-AUG initiation events are not simply errors but instead are used to generate or regulate proteins with key cellular functions; for example, during development or stress. Misregulation of non-AUG initiation events contributes to multiple human diseases, including cancer and neurodegeneration, and modulation of non-AUG usage may represent a novel therapeutic strategy. It is thus becoming increasingly clear that start codon selection is regulated by many trans-acting initiation factors as well as sequence/structural elements within messenger RNAs and that non-AUG translation has a profound impact on cellular states.


Determination of phthalate esters from food-contacted materials by on-line microdialysis and liquid chromatography.
Phthalates (endocrine disrupters) released from food-contacted plastics into aqueous solution during microwave conditioning were measured with microdialysis enrichment on-lined high-performance liquid chromatography. The released phthalates in aqueous solution were diffused through a cellular dialysis membrane into the perfusion stream and thus enriched prior to HPLC analysis. Conditions for obtaining optimum enrichment such as the hollow dialysis fiber, flow-rate and polarity modifier in perfusion stream, pH, added-salt and stirring rate in sample solution, as well as chromatographic conditions were investigated. Experimental results indicated that microdialysis enrichment with a 20-cm polysulfone hollow dialysis fiber and heptane as the perfusate at 0.10-microL/min flow-rate to collect phthalates from aqueous sample in 0.5M KCl matrix (optional pH) at 250 rpm stirring offered the optimum enriched efficiency. The dimethyl phthalate (DMP), diethyl phthalate (DEP) and dibutyl phthalate (DBP) were well separated within 16 min by a C-18 column and eluted gradient from 40 to 90% aqueous acetonitrile (at pH 6.0) and 1.0 to 1.5 mL/min flow-rate. Detection was carried out with an UV detector at 225 nm. The enrichment factors were 14, 140 and 201 (at 0.10-microL/min perfusate flow-rate) for DMP, DEP and DBP, respectively, with less than 4% RSD. The proposed method provided a very simple, fast and eco-friendly enriched procedure to determine the extent of phthalates migration from disposable plastic materials into drinking soup.


Transplantation of mouse embryonic stem cells into the cochlea of an auditory-neuropathy animal model: effects of timing after injury.
Application of ouabain to the round window membrane of the gerbil selectively induces the death of most spiral ganglion neurons and thus provides an excellent model for investigating the survival and differentiation of embryonic stem cells (ESCs) introduced into the inner ear. In this study, mouse ESCs were pretreated with a neural-induction protocol and transplanted into Rosenthal's canal (RC), perilymph, or endolymph of Mongolian gerbils either 1-3 days (early post-injury transplant group) or 7 days or longer (late post-injury transplant group) after ouabain injury. Overall, ESC survival in RC and perilymphatic spaces was significantly greater in the early post-injury microenvironment as compared to the later post-injury condition. Viable clusters of ESCs within RC and perilymphatic spaces appeared to be associated with neovascularization in the early post-injury group. A small number of ESCs transplanted within RC stained for mature neuronal or glial cell markers. ESCs introduced into perilymph survived in several locations, but most differentiated into glia-like cells. ESCs transplanted into endolymph survived poorly if at all. These experiments demonstrate that there is an optimal time window for engraftment and survival of ESCs that occurs in the early post-injury period.


Effects of rifampicin on the peripheral turnover kinetics of thyroid hormones in mice and in men.
The induction of mixed function hepatic oxygenases by rifampicin is known to increase the metabolic clearance rate (MCR) of T4. By performing T3 and rT3 kinetics we have shown that rifampicin also increases the MCR of T3 and rT3. Using the fall of serum T4 during TSH suppression as an indirect marker of the production rate (PR) of T4, we have demonstrated that there was no major change in monodeiodination nor any shift to either 5'- or 5-monodeiodination. Rifampicin stimulates in mice the mixed function hepatic oxygenases. However, we were unable to increase hepatic deiodinase activity (deiodinase type I) in this species. It is therefore possible that the increased MCR of T4 in man is not mediated by an increased conversion rate either. As mixed function hepatic oxygenases are known to increase hepatic conjugation it is suggested that rifampicin increases the biliary excretion of iodothyronine conjugates.


Care-seeking decisions for worsening symptoms in heart failure: a qualitative metasynthesis.
Over 50 % of heart failure (HF) patients delay seeking help for worsening symptoms until these reach acute levels and require emergency hospitalisation. This metasynthesis aimed to identify and explore factors influencing timely care-seeking in patients with HF. Electronic databases searched were MEDLINE, Embase, and CINAHL. Studies were included if they were peer-reviewed journal articles, written in English, and reported perspectives of HF patients following qualitative data collection and analysis. Forty articles underwent analysis following the approach of Thomas and Harden. Leventhal's self-regulatory model (SRM) was used to organise the literature. Much of the literature fits within the SRM; however, this model did not account for all factors that influence patients' care-seeking for worsening symptoms. Factors not accounted for included patients' appraisals of previous care-seeking experiences, perceived system and provider barriers to accessing care, and the influence of external appraisals. When added to factors already represented in the model, such as misattribution of symptoms, not identifying with HF diagnosis, cognitive status, lack of understanding information provided, adaptation to symptoms, and emotional responses, a more comprehensive account of patients' decision-making was revealed. This metasynthesis identified factors, as yet unaccounted for, in a prominent model, and has suggested a more comprehensive framework for addressing care-seeking in HF patients. This information can be used to tailor education, communication, and service initiatives to improve HF patients' responses to worsening symptoms and target those most at risk of delay.


Correction to: One decade of glioblastoma multiforme surgery in 342 elderly patients: what have we learned?
There was a typo in the third author's name in the initial online publication.


Enhancing digestive fistula healing by the off-label use of a thermoresponsive vessel occluder polymer associated with esophageal stent placement: A case report.
This case report relates to the first-in-man use of a vessel occluder gel medical device as a fistula occluder in a repurposing strategy. A patient with chronic colocutaneous fistula received an off-label treatment with a thermoresponsive Poloxamer 407 gel (20%) via percutaneous administration and injected under endoscopic control. Treatment consisted in the association of esophageal stent placement and gel injection. The product was administered just after the stent placement at<20°C in its liquid form, gelling at body temperature to form a fistula plug. However, the stent was removed at day 26 because of major pain and the fistula was still present. Treatment was continued a total of 14 administrations of thermoresponsive Poloxamer 407 gel during 7 weeks via the external fistula orifice. The treatment reduced fistula orifice diameter from 4.0±0.5 to 1mm and fistula daily output decreased from 425±65 to 23±4mL, when comparing the months before and after treatment. Gel administration was not associated with any toxic effects. The therapeutic outcome remained stable 1 year after treatment. The external fistula diameter and the fistula output were similar to what was observed after the last Poloxamer 407 gel administration.


Diagnosis, prognosis and therapeutic role of circulating miRNAs in cardiovascular diseases.
Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in the world. Although much progress has been made for cardiovascular diseases in diagnosis, treatment and prognosis during the past two decades, the clinical need for a novel diagnostic biomarker and new therapeutic interventions to decrease the cardiovascular disease incidence is ongoing. MicroRNAs (miRNAs) are endogenous, small (∼22 nucleotides), single-stranded, non-coding RNAs that regulate gene expression and are detectable in whole blood, serum, plasma, urine and other body fluids in a highly stable form. Accumulating evidence suggests that miRNAs are potential novel biomarkers with high sensitivity for early diagnosis and modern treatment for cardiovascular diseases. Altered circulating miRNAs expressions have been reported in acute myocardial infarction (AMI), acute coronary syndrome (ACS), stable coronary artery disease, heart failure, atherosclerosis, essential hypertension and stroke. In the present review, we examine more recent data regarding circulating miRNAs and their potential roles in diagnosis, prognosis and therapeutic strategies for cardiovascular diseases. In addition, we briefly present our own recent experience in detecting circulating miRNAs, and the significance of these miRNAs in AMI prognosis.


Automatic Classification of Marine Mammals with Speaker Classification Methods.
We present an automatic acoustic classifier for marine mammals based on human speaker classification methods as an element of a passive acoustic monitoring (PAM) tool. This work is part of the Protection of Marine Mammals (PoMM) project under the framework of the European Defense Agency (EDA) and joined by the Research Department for Underwater Acoustics and Geophysics (FWG), Bundeswehr Technical Centre (WTD 71) and Kiel University. The automatic classification should support sonar operators in the risk mitigation process before and during sonar exercises with a reliable automatic classification result.


Transanal total mesorectal excision of giant villous tumor of the lower rectum with McKittrick-Wheelock syndrome: a case report of a novel surgical approach.
McKittrick-Wheelock syndrome (MKWS) is caused by a villous tumor of the rectosigmoid colon with hypersecretion of mucus containing electrolytes. Complete resection of the tumor is needed to cure this disease. Transanal total mesorectal excision (TaTME) is currently a promising treatment for lower rectal tumor because of the reliability of its resection margin especially in bulky tumor. We present this first case report of a TaTME for MKWS with a lower rectal tumor. An 81-year-old woman was admitted to our hospital with diarrhea and acute renal failure. Computed tomography and magnetic resonance imaging examinations revealed an 80-mm-sized enhanced tumor located in her lower rectum without lymph node swelling and distant metastasis. A giant villous tumor secreting mucus was seen in the lower rectum to the anal canal during colonoscopy. The result of tumor biopsy was adenocarcinoma. To preserve the anal function and ensure distal margin, we chose TaTME for curative resection. After improving the electrolyte imbalance, TaTME was performed successfully and R0 resection was achieved. There was no sign of recurrence or electrolyte depletion for 1 year after the surgery. TaTME could be a promising surgical approach for giant villous tumor with MKWS in the lower rectum.


TaqMan real-time PCR assay for specific detection of Opisthorchis viverrini DNA in Thai patients with hepatocellular carcinoma and cholangiocarcinoma.
The aim of this study was to develop TaqMan real-time PCR assay that detected Opisthorchis viverrini DNA from 18 normal and 18 tumor tissue specimens from Thai patients with hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), who underwent liver resection from October 2005 to May 2006. Control liver specimens were seven non-primary liver cancers. A conserved probe representing 100% sequence homology was used as a reference for O. viverrini-specific probe. Five of six tumors (83%) and all six normal tissues from CCA group; and seven of twelve tumors (58%) and ten of twelve normal tissues (83%) from HCC group were found to have O. viverrini DNA. The O. viverrini DNA detection among HCC and CCA patients were not associated (p=0.193; 90%CI). This RT-PCR will be a useful tool for investigating the relationship between cancer type and presence of the parasite and also for conducting epidemiological surveys.


Flexible CO2 laser and submucosal gel injection for safe endoluminal resection in the intestines.
The CO(2) laser's unique wavelength of 10.6 μm has the advantage of being readily absorbed by water but historically limited it to line-of-sight procedures. Through recent technological advances, a flexible CO(2) laser fiber has been developed and holds promise for endoluminal surgery. We examined whether this laser, along with injection of a water-based gel in the submucosal space, will allow safe dissection of the intestines and enhance the potential of this tool for minimally invasive surgery. Using an ex vivo model with porcine intestines, spot ablation was performed with the flexible CO(2) laser at different power settings until transmural perforation. Additionally, excisions of mucosal patches were performed by submucosal dissection with and without submucosal injection of a water-based gel. With spot ablation at 5 W, none of the specimens was perforated by 5 min, which was the maximum recorded time. The time to perforation was significantly shorter with increased laser power, and gel pretreatment protected the intestines against spot ablation, increasing the time to perforation from 6 to 37 s at 10 W and from 1 to 7 s at 15 W. During excision of mucosal patches, 56 and 83% of untreated intestines perforated at 5 and 10 W, respectively. Gel pretreatment prior to excision protected all intestines against perforation. These specimens were verified to be intact by inflation with air to over 100 mmHg. Furthermore, excision of the mucosal patch was complete in gel-pretreated specimens, whereas 22% of untreated specimens had residual islands of mucosa after excision. The flexible CO(2) laser holds promise as a precise dissection and cutting tool for endoluminal surgery of the intestines. Pretreatment with a submucosal injection of a water-based gel protects the intestines from perforation during ablation and mucosal dissection.


Cloning and ontogenetic expression of the uncoupling protein 1 gene UCP1 in sheep.
The uncoupling protein 1 (UCP1) is an indicator of brown adipocytes and is involved in the control of body temperature and regulation of energy balance. It abundantly expresses in newborns and has important functions in adults. However, little information was known on UCP1 gene expression in young and adolescent sheep. In this study, we cloned and identified the full-length DNA and cDNA sequences of the ovine UCP1 gene, which were 6659 bp and 1621 bp, respectively, and predicted the location of the gene on chromosome 17. Forty-eight animals with an equal number of males and females each for both Guangling Large Tail sheep (GLT) and Small Tail sheep Han (STH) sheep were used to study the ontogenetic expression of UCP1 mRNA in eight adipose tissues by quantitative real-time polymerase chain reaction (PCR). The results showed that the mRNA was expressed in all tissues studied and at all stages from 2 to 12 months of age. Nevertheless, the mRNA in perirenal fat was expressed significantly higher than that in other tissues and lower in superficial fat than in deep deposits. The highest expression was observed in animals at 2 months of age and then decreased gradually with age. Global expression in GLT was significantly higher than that in STH. Interactions between tissue and breed and age also influenced the mRNA expression significantly. In addition, the mRNA expression was associated with the single nucleotide polymorphism (SNP) haplotypes detected in the cDNA of the gene.


Antimycobacterial activity of novel N-(substituted)-2-isonicotinoylhydrazinocarbothioamide endowed with high activity towards isoniazid resistant tuberculosis.
Various isonicotinoylhydrazinocarbothioamides were prepared by reacting isonicotinoyl hydrazide (INH) with appropriate potassium salt of substituted phenyl thiocarbamate and were tested for their antimycobacterial activity in vitro against Mycobacterium tuberculosis H(37)R(v) and INH resistant M. tuberculosis using the agar dilution method. Among the synthesized compounds, 2-isonicotinoyl-N-[2-(trifluoromethyl)phenyl]hydrazinecarbothioamide (4i) was found to be the most potent compound with minimum inhibitory concentration of 0.58 microM against M. tuberculosis H(37)R(v) and INH resistant M. tuberculosis. When compared to INH, 4i was found to be 1.24 and 157 times more active against M. tuberculosis H(37)R(v) and INH resistant M. tuberculosis respectively, with a selectivity index of >218.


Coarctation of the aorta in infants: which operation?
In this series, 178 infants (age, less than or equal to 3 months old) underwent repair of aortic coarctation. Pure coarctation was present in 63 patients (Group 1), 47 infants had additional ventricular septal defects (Group 2), and 68 patients had associated complex heart disease (Group 3). Subclavian flap angioplasty was used in 26 patients, limited resection and end-to-end anastomosis in 45 patients, extended resection and end-to-end anastomosis in 99 patients, and miscellaneous procedures in 8 infants. The early mortality was 8% for the first group, 11% for the second group, and 37% for the third group (p less than 0.001). Mean follow-up was 32 months and included 97% of patients. Actuarial survival at five years was 90% for the first group, 84% for the second group, and 40% for the third group. Recoarctation occurred in 15 operative survivors (11%); 7 necessitated reoperation. Freedom from recoarctation at five years was 89% after subclavian flap angioplasty, 81% after end-to-end anastomosis, and 86% following extended resection and end-to-end anastomosis. Early mortality and late results were not influenced by the type of coarctation repair but were determined by the clinical status and the presence of associated major cardiac anomalies. These results suggest that the surgical procedure should be individualized for each infant to optimize the aortic anatomy.


Transplant-associated microangiopathy (TAM) in recipients of allogeneic hematopoietic stem cell transplants.
We studied occurrence, risk factors and outcome of patients with transplant-associated microangiopathy (TAM) after allogeneic stem cell transplantation (HSCT). A total of 221 consecutive patients were transplanted between 1995 and 2002. TAM is defined as evidence of hemolysis and schistocytes in the first 100 days. Outcomes analyzed included TAM and overall survival. Of 221 patients, 68 had TAM. The cumulative incidence was 31 (25-38)% at 100 days. Patients with TAM had higher LDH, higher bilirubin, higher creatinine and more often neurologic symptoms. TAM was not associated with stem cell source, cyclosporine levels and was not more frequent in recent years. In multivariate analysis, risk factors for TAM included donor type, age, gender, ABO-incompatibility and acute graft-versus-host disease (aGvHD). In patients with TAM, 1-year survival was lower than in patients without TAM (27 +/- 18% for TAM with high schistocyte counts; 53 +/- 15% for TAM with low schistocyte counts; vs 78 +/- 7% in patients without TAM; P<0.0001). TAM was independently associated with mortality adjusting for donor type, age and aGvHD occurrence and severity. TAM is frequent after HSCT and is associated with mortality even after adjustment for aGvHD grade. Risk factors of TAM are similar to aGvHD. TAM may represent endothelial damage driven by donor-host interactions.


Microwave ablation of ex vivo human liver and colorectal liver metastases with a novel 14.5 GHz generator.
This study assessed the relationship between time, power and ablation size using a novel high-frequency 14.5 GHz microwave applicator in ex vivo human hepatic parenchyma and colorectal liver metastases. Previous examination has demonstrated structurally normal but non-viable cells within the ablation zone. This study aimed to further investigate how ablation affects these cells, and to confirm non-viability. Ablations were performed in ex vivo human hepatic parenchyma and tumour for a variety of time (10-180 s) and power (10-50 W) settings. Histological examination was performed to assess cellular anatomy, whilst enzyme histochemistry was used to confirm cellular non-viability. Transmission electron microscopy was used to investigate the subcellular structural effects of ablation within these fixed cells. Preliminary proteomic analysis was also performed to explore the mechanism of microwave cell death. Increasing time and power settings led to a predictable and reproducible increase in size of ablation. At 50 W and 180 s application, a maximum ablation diameter of 38.8 mm (±1.3) was produced. Ablations were produced rapidly, and at all time and power settings ablations remained spherical (longest:shortest diameter <1.2). Routine histological analysis using haematoxylin-eosin (H&E) confirmed well preserved cellular anatomy despite ablation. Transmission electron microscopy demonstrated marked subcellular damage. Enzyme histochemistry showed complete absence of viability in ablated tissue. Large spherical ablation zones can be rapidly and reproducibly achieved in ex vivo human hepatic parenchyma and colorectal liver metastases using a 14.5 GHz microwave generator. Despite well preserved cellular appearance, ablated tissue is non-viable.


Effects of defensin and lactoferrin on functional activity of endothelial cells in vitro.
We studied the effects of antibacterial peptides and proteins (defensins and lactoferrins) on functional activity of endothelial cells in vitro: proliferative activity and adhesion of human endothelial ECV-304 cells to the matrix were evaluated, alpha-Defensin (NP-2) from rabbit neutrophils, total alpha-defensin (HNP 1-3) from human neutrophils, and lactoferrins from porcine neutrophils and human milk were studied. Defensins stimulated and lactoferrin in doses of 1-10 microg/ml inhibited proliferation and adhesion of endothelial cell. The stimulatory effect of defensins on proliferation and adhesion was reproduced in fibroblast culture. Lactoferrins did not modify proliferation of fibroblasts, but suppressed their adhesion. These data suggest that antibiotic proteins and peptides are prospective objects for the creation of drugs regulating angiogenesis.


How predictive is PK/PD for antibacterial agents?
The pharmacodynamic (PD) parameters most often used in studies of antibiotic effect include the following relationships between the antibiotic concentration curve in serum as a surrogate marker for the antibiotic concentration at the infection site, the peak/minimal inhibitory concentration (MIC) ratio, the area under the curve (AUC)/MIC ratio and the duration of time the concentration exceeds the MIC (T(>MIC)). The MIC plays an important role also as a PD marker, and its precision in this respect is discussed. The predictive role of T(>MIC) is important for drugs showing minimal concentration dependent effect such as the beta-lactam antibiotics, the macrolides and others. The time can be calculated as the chronological time measured or as the (cumulative) per cent of the dosing interval covered by the dose. Several clinical studies have confirmed this relationship. It can be deduced from experimental as well as clinical studies that there is a minimal effective time (MET), which needs to be covered by the antibiotic concentration at the site of infection in order to achieve cure. Dosing according to this MET will result in the least antibiotic needed for the shortest duration. In several cases a single dose will suffice to cover the MET. If this is not possible the antibiotic should be dosed in a way, that each dose will surpass the MIC for at least 40-50% of the dosing interval. For antibiotics with a clear concentration-dependent bacterial killing effect the most important pharmacokinetic/pharmacodynamic (PK/PD) index is the peak/MIC ratio (or the AUC/MIC ratio). This is the case for aminoglycosides and fluoroquinolones, and for both classes a peak/MIC ratio of at least 10 within the first 24 h of treatment has been shown to result in around 90% bacteriological as well as clinical cure. One consequence of clinical dosing has been the once-a-day (OD) dosing for aminoglycosides, which is the standard mode of therapy in many countries. Clinical studies in the field of antibacterial PD are still relatively scarce, and much information is needed to enable relevant dosing strategies for all types of antibiotics against all common infections and micro-organisms.


Micromanipulation in assisted reproductive technology.
Micromanipulation describes a set of tools and techniques for cellular microsurgery and manipulation. Micromanipulation techniques have played an important role in basic research and the development of clinical techniques in assisted reproductive technology. This work provides a review of the development and current practices involving micromanipulation in the human clinical assisted reproduction laboratory.


Materials for hydrogen storage: current research trends and perspectives.
Storage and transport of hydrogen constitutes a key enabling technology for the advent of a hydrogen-based energy transition. Main research trends on hydrogen storage materials, including metal hydrides, porous adsorbents and hydrogen clathrates, are reviewed with a focus on recent developments and an appraisal of the challenges ahead. .


Comparison of intravenous ibuterol (KWD 2058), a new bronchodilator, and terbutaline.
The selectivity of the recently developed beta-stimulating drug ibuterol, a terbutaline ester which is rapidly hydrolyzed to terbutaline in vivo, was tested by comparing it with terbutaline after intravenous infusion. Dose-response curves for both drugs for FEV, heart rate, blood pressure, and tremor were recorded. The two drugs had equal bronchodilator effect. Ibuterol caused significantly less increase in heart rate, tremor ratio, and pulse amplitude when doses causing equal bronchodilation were infused. This is probably due to inequality of distribution. The lower tremorogenic activity of ibuterol can also be caused by differences in the concentration of tissue esterases in lung and skeletal muscle. It is concluded that ibuterol is more selective for the bronchi than terbutaline.


[Blind spot enlargement syndrome in acute zonal occult outer retinopathy with detection of autoantibodies against the retinal antigens CRALBP and S-Ag].
Acute zonal occult outer retinopathy (AZOOR) is a rare disease and is part of the white dot syndrome occurring bilaterally and often asymmetrically in young healthy myopic women. Characteristic findings are distinct focal lesions of the outer segments (OS) of the photoreceptor (PR) layer and abnormalities in fundus autofluorescence (FAF) within the lesions. Currently there is a lack of defined disease criteria, such as specific laboratory findings. Also no effective therapy is known which makes it difficult to diagnose, differentiate and treat AZOOR. Supplementation of antioxidants may become part of therapeutic options in AZOOR. A 19-year-old myopic woman presented with unilaterally reduced visual acuity. Due to the clinical features and with the help of FAF, spectral domain optical coherence tomography (SD-OCT) and perimetry the diagnosis of blind spot enlargement syndrome in AZOOR was made. Identification of autoantibodies specific for two retinal antigens (CRALBP and S-Ag) supports the concept of an autoimmunological origin of the disease. Systemic steroids were given but stopped almost 6 weeks later as no improvement was seen. In follow-up controls over 12 months the clinical picture remained unchanged without any further therapy.


Feasibility of developing children's Pill School within a UK hospital.
We assessed the feasibility of introducing an intervention (children's Pill School-PS) within a UK hospital to provide swallowing training for children, identified the proportion of children who can be switched from oral liquid medicines to pills and assessed children/parents' opinions about the PS training. 30 inpatient children (aged 3-18 years; taking oral liquid medicines; their liquid medications assessed suitable for switching to pills; can (and their parents) speak/understand English were included. Training sessions were delivered using hard sweets of different sizes. 87% (26) of children successfully learnt how to swallow pills after one training session (mean duration 14.5 min), and 92% (24) were discharged on pills. 75 prescribed oral liquid medications were deemed suitable for switching to pills. Of these, 89% (67) were switched successfully. Children as young as 3 years were successful in swallowing pills after training. Providing children PS training session within hospital is feasible and acceptable to children and their parents.


Fecundity in relation to wing-morph of three closely related species of the melanocephalus group of the genus Calathus (Coleoptera: Carabidae).
In two successive years the fecundity of the carabid beetles Calathus (Neocalathus) cinctus, C. (N.) melanocephalus and C. (N.) mollis was studied in relation to wing-morph and temperature. Differences were found between the three species in both egg production and timing and length of the oviposition period. In all species the fecundity of laboratory bred beetles was significantly higher than that of females collected in the field. Long-winged females of both cinctus and melanocephalus had significantly higher egg production than short-winged females, and they also tended to produce eggs over a longer period. In mollis only the fecundity of the long-winged morph was established. The observed lower relative fitness of the short-winged morph in both cinctus and melanocephalus contradicts the supposed increase of the frequency of this morph in ageing, more or less isolated, populations of these species. The loss of long-winged genotypes, resulting from flight activities, is considered the most plausible cause of the increase of short-winged beetles in ageing populations. The higher fecundity of macropterous females makes them especially suited for (re)establishing populations.


Optimal treatment of chronic constipation in managed care: review and roundtable discussion.
Prevalence studies estimate that chronic constipation affects 12%-19% of Americans. This prevalence rate exceeds that of many highly publicized chronic conditions, including diabetes and asthma. Identifying the etiology of each patient's constipation is essential for determining treatment and management plans. The etiology of chronic constipation falls into 2 broad categories: primary or idiopathic constipation caused by physical and functional problems, and secondary constipation resulting from a variety of organic conditions as well as the use of certain medications. Patients may have more than one cause of their constipation. Treatment options may be based not only on the cause but may be dictated by a patient's health care coverage and the inclusion criteria of different health care plans. To (a) present key information on the causes, diagnosis, and treatment recommendations for patients with chronic constipation; (b) describe how chronic constipation impacts quality of life; and (c) describe how all providers can work to improve the quality of care and health outcomes for patients with chronic constipation. Chronic constipation is a prevalent condition that disproportionately affects women and the elderly. Most agents are available over-the-counter, although their efficacy has not been extensively tested. Few prescription agents are currently available, and they are more costly; therefore, managed care plans may restrict these products for patients who fail traditional treatments. A lack of evidence-based algorithms leaves many providers to treat patients empirically. Practitioners can assist patients seeking recommendations and provide information on treatment options.


Effect of olivocochlear bundle transection on choline acetyltransferase activity in the rat cochlear nucleus.
Using a microdissection and quantitative microassay approach, choline acetyltransferase activities were mapped in the cochlear nuclei of rats having complete transections of the olivocochlear bundle on one side in the brain stem. In rats in which the trapezoid body was not significantly damaged by the lesion, consistent reductions of choline acetyltransferase activity in subregions of the lesion-side cochlear nucleus, as compared to the control side, averaged about 20%. Nevertheless, a profound lesion-side reduction of choline acetyltransferase activity was found in a branch connection from the olivocochlear bundle to the cochlear nucleus. The results suggest that branches from the olivocochlear bundle are cholinergic, but contribute a relatively minor proportion of the cholinergic synapses in all regions of the rat cochlear nucleus. In the light of previous results with more extensive lesions, it can be proposed that synapses in all regions of the rat cochlear nucleus. In the light of previous results with more extensive lesions, it can be proposed that most cholinergic input into the rat cochlear nucleus enters by a ventral route along the trapezoid body. It is noted that this represents a quantitatively somewhat different situation from that in the cat.


790 Kb microduplication in chromosome band 17p13.1 associated with intellectual disability, afebrile seizures, dysmorphic features, diabetes, and hypothyroidism.
We report a patient with a moderate mental retardation, afebrile seizure, mild dysmorphic features and type 2 diabetes mellitus with mild obesity and metabolic syndrome. Array-CGH analysis revealed a de novo 790-830 kb duplication on chromosome 17p13.1, not reported so far. Among the approximately 50 genes involved in the rearrangement, neuroligin 2 (NLGN2) and ephrin B3 (EFNB3) are candidates for the mental retardation phenotype. NLGN2 may therefore be a novel candidate gene for mental retardation or autistic spectrum disorder, joining other members of the neurexin/neuroligin network. Moreover, GLUT4, a member of the solute carrier family 2, may play a role in the patient's type 2 diabetes.


Pollution source identification and abatement for water quality sections in Huangshui River basin, China.
Accurately obtaining the pollution sources and their contribution rates is the basis for refining watershed management. Although many source analysis methods have been proposed, a systematic framework for watershed management is still lacking, including the complete process of pollution source identification to control. We proposed a framework for identification and abatement of pollutants and applied in the Huangshui River Basin. A newer contaminant flux variation method based on a one-dimensional river water quality model was used to calculate the contribution of pollutants. The contributions of various factors to the over-standard parameters of water quality sections at different spatial and temporal scales were calculated. Based on the calculation results, corresponding pollution abatement projects were developed, and the effectiveness of the projects was evaluated through scenario simulation. Our results showed that the large scale livestock and poultry farms and sewage treatment plants were the largest sources of total nitrogen (TP) in Xiaoxia bridge section, with contribution rates of 46.02% and 36.74%, respectively. Additionally, the largest contribution sources of ammonia nitrogen (NH3-N) were sewage treatment plants (36.17%) and industrial sewage (26.33%). Three towns that contributed the most to TP were Lejiawan Town (14.4%), Ganhetan Town (7.3%) and Handong Hui Nationality town (6.6%), while NH3-N mainly from the Lejiawan Town (15.9%), Xinghai Road Sub-district (12.4%) and Mafang Sub-district (9.5%). Further analysis found that point sources in these towns were the main contributor to TP and NH3-N. Accordingly, we developed abatement projects for point sources. Scenario simulation indicated that the TP and NH3-N could be significantly improved by closing down and upgrading relevant sewage treatment plants and building facilities for large scale livestock and poultry farms. The framework adopted in this study can accurately identify pollution sources and evaluate the effectiveness of pollution abatement projects, which is conducive to the refined water environment management.


Solid-state analysis of amorphous solid dispersions: Why DSC and XRPD may not be regarded as stand-alone techniques.
Amorphous solid dispersions (ASDs) are single-phase amorphous systems, where drug molecules are molecularly dispersed (dissolved) in a polymer matrix. The molecular dispersion of the drug molecules is responsible for their improved dissolution properties. Unambiguously establishing the phase behavior of the ASDs is of utmost importance. In this paper, we focused on the complementary nature of (modulated) differential scanning calorimetry ((m)DSC) and X-ray powder diffraction (XRPD) to elucidate the phase behavior of ASDs as demonstrated by a critical discussion of practical real-life examples observed in our research group. The ASDs were manufactured by either applying a solvent-based technique (spray drying), a heat-based technique (hot melt extrusion) or mechanochemical activation (cryo-milling). The encountered limiting factors of XRPD were the lack of sensitivity for small traces of crystallinity, the impossibility to differentiate between distinct amorphous phases and its impossibility to detect nanocrystals in a polymer matrix. In addition, the limiting factors of (m)DSC were defined as the well-described heat-induced sample alteration upon heating, the interfering of residual solvent evaporation with other thermal events and the coinciding of enthalpy recovery with melting events. In all of these cases, the application of a single analytical technique would have led to erroneous conclusions, whilst the combination of (m)DSC and XRPD elucidated the true phases of the ASD.


An IFN-γ and TNF-α dual release fluorospot assay for diagnosing active tuberculosis.
Currently available interferon (IFN)-γ-release assays (IGRA) cannot discriminate active tuberculosis (TB) from latent TB infection (LTBI), and so have limited clinical utility for diagnosing active TB. Since numbers of tumour necrosis factor (TNF)-α-producing T cells are highly correlated with active TB, we hypothesized that detecting IFN-γ- and/or TNF-α-producing T cells would overcome this limitation of IGRA. This study evaluated the diagnostic performances of the IFN-γ and TNF-α dual release fluorospot assay for active TB. Adult patients with suspected TB including recent TB exposers were prospectively enrolled over a 28-month period. In addition to the conventional IGRA test (i.e. QuantiFERON-In-Tube), a fluorospot assay for detecting IFN-γ- and TNF-α-producing T cells was performed. The final diagnoses were classified by clinical category. Patients with confirmed or probable TB were regarded as active TB, and patients with not active TB were further classified as having not active TB with and without LTBI, based on the QuantiFERON-In-Tube results. A total of 153 patients including 45 with active TB and 108 with not active TB (38 LTBI vs. 70 not LTBI) were finally analysed. The sensitivity and specificity of the QuantiFERON-In-Tube assay for active TB were 84% (95% confidence interval (CI), 70-93) and 70% (95% CI 61-79), respectively. The IFN-γ/TNF-α dual release assay by fluorospot had substantially higher diagnostic specificity (94%) for diagnosing active TB than the IFN-γ single release assay (72%, p < 0.001), without compromising sensitivity (84% vs. 89%, p 0.79). The fluorospot-based IFN-γ/TNF-α dual release assay appears to be a simple and useful test for diagnosing active TB.


Nicotine increases alcohol self-administration in non-dependent male smokers.
Alcohol and tobacco are commonly co-administered, yet little is known about the effects of acute nicotine administration on alcohol consumption in humans. This study sought to determine how nicotine delivered by tobacco smoke influences alcohol intake in humans using a double-blind placebo controlled repeated measures design. During two randomized 120 min sessions 15 male occasional smokers smoked four nicotine-containing or four de-nicotinized cigarettes at 30 min intervals. Throughout the session, subjects could earn units of their preferred alcoholic beverage and glasses of water using a progressive-ratio (PR) task. Wilcoxon signed-rank tests indicated that nicotine increased alcohol self-administration in a significant proportion of participants (P<or=0.03) without affecting water consumption (P>or=0.16). A two-way ANOVA supported this observation further, and, compared to de-nicotinized cigarettes, the nicotine-containing cigarettes increased PR breakpoints for alcohol but not water, as reflected by a Cigarettex Beverage interaction (P<or=0.055). The present data suggest that acute nicotine administration increases alcohol consumption in at least a subset of smokers.


Fear of recurrence, symptom burden, and health-related quality of life in men with prostate cancer.
To examine the contributions of fear of recurrence and the more commonly examined treatment-related symptoms to the health-related quality of life (HRQOL) of men treated for localized prostate cancer. A total of 730 men with localized disease were identified from the Cancer of the Prostate Strategic Urologic Research Endeavor, a national, prospective study of men with prostate cancer. Pre- to post-treatment changes in fear of recurrence, treatment-specific symptoms and burden, comorbidities at diagnosis, number of new symptoms, and post-treatment HRQOL data were analyzed. Linear regression, adjusted for clinical and demographic characteristics, showed that improved fear of recurrence (P <0.01), higher number of post-treatment symptoms (P <0.01), and improved bowel function (P <0.01) significantly predicted better mental health scores. For physical health, improved urinary bother (P <0.01) and lower number of post-treatment symptoms (P <0.01) were associated with better physical health. Understanding men's fears about cancer recurrence and how these fears influence physical and mental health are important components of providing care to this growing population.


The use of bisphosphonate in the treatment of osteonecrosis of the femoral head: a meta-analysis of randomized control trials.
This meta-analysis revealed that bisphosphonates could not provide a better clinical outcome in the treatment of osteonecrosis of the femoral head (ONFH) when compared with placebo. Bisphosphonates have been recommended to treat ONFH. However, the exact clinical outcomes after treatment are still controversial. A comprehensive search of PubMed, Embase, and Web of Science databases was undertaken, and only randomized control trials were included. The clinical outcomes consisted of progression to collapse, total hip arthroplasty (THA) incidence, and improvement of Harris hip score (HHS). The heterogeneities between the trials were assessed with the I (2) statistic, and random effects models were used for the meta-analysis. Five eligible trials were identified involving 329 subjects with 920.9 patient-years of follow-up. The clinical outcomes of patients with ONFH was not significantly improved by bisphosphonate therapy (progression to collapse: risk ratio = 0.71 (0.41, 1.24), p = 0.23; THA incidence: risk ratio = 0.61 (0.33, 1.15), p = 0.13; HHS improvement: mean difference = 3.26 (-5.12, 11.64), p = 0.45). The I (2) statistic showed the existence of considerable heterogeneity (all I (2) ≥ 50 %), which was explained by one trial where bisphosphonate alone was used with no additional therapy. However, when this trial was excluded, the clinical outcomes after bisphosphonate therapy were still not significantly improved compared with placebo. The current analysis does not support the use of bisphosphonates for ONFH. As potential serious adverse effects are associated with these drugs, only limited use can be recommended.


Effectiveness of cognitive-behavioural therapy for post-disaster distress in post-traumatic stress symptoms after Chilean earthquake and tsunami.
This is the first time that the effectiveness of cognitive-behavioural therapy for post-disaster stress (CBT-PD) in symptoms of posttraumatic stress disorder (PTSD) has been tested outside the United States of America. Quasi-experiment with three groups. In the quasi-control group, complete CBT-PD was applied even though its members did not have PTSD; in quasi-experimental conditions, participants received complete treatment because they had this diagnosis; and in the third group, participants with PTSD received an abbreviated treatment (double sessions) due to organisational requirements. Primary health care workers in Constitución (Chile), city exposed to earthquake and tsunami; public department workers in Talca (city exposed only to earthquake) and teachers from a school (Constitución). A total of 13 of the 91 people diagnosed with PTSD participated. In addition, 16 people without diagnosis voluntarily participated. The treatment was completed by 29 participants. There were no dropouts. Only 1 of the 9 participants in the quasi-experimental group did not respond to treatment. CBT-PD is a group therapy (10-12 sessions) that includes psychoeducation, breathing retraining, behavioural activation and cognitive restructuring. CBT-PD (complete and abbreviated) was applied between September and December 2010. Short Posttraumatic Stress Disorder Rating Interview (SPRINT-E) was used to measure PTSD symptoms before and after treatment. The group that received the complete treatment and was diagnosed with PTSD showed a significant decrease in the total symptoms to below dangerous levels (IGAAB: 31.556; p<0.01; 95%CI: 0.21-2.01]; η2=0.709). The effectiveness and benefits of incorporating CBT-PD in the health network after events like disasters were discussed.


Cellular Microenvironment Stiffness Regulates Eicosanoid Production and Signaling Pathways.
Pathological changes in the biomechanical environment are implicated in the progression of idiopathic pulmonary fibrosis (IPF). Stiffened matrix augments fibroblast proliferation and differentiation and activates TGF-β1 (transforming growth factor-β1). Stiffened matrix impairs the synthesis of the antifibrogenic lipid mediator prostaglandin E2 (PGE2) and reduces the expression of the rate-limiting prostanoid biosynthetic enzyme cyclooxygenase-2 (COX-2). We now show that prostaglandin E synthase (PTGES), the final enzyme in the PGE2 biosynthetic pathway, is expressed at lower levels in the lungs of patients with IPF. We also show substantial induction of COX-2, PTGES, prostaglandin E receptor 4 (EP4), and cytosolic phospholipase A2 (cPLA2) expression in human lung fibroblasts cultured in soft collagen hydrogels or in spheroids compared with conventional culture on stiff plastic culture plates. Induction of COX-2, cPLA2, and PTGES expression in spheroid cultures was moderately inhibited by the p38 mitogen-activated protein kinase inhibitor SB203580. The induction of prostanoid biosynthetic enzyme expression was accompanied by an increase in PGE2 levels only in non-IPF-derived fibroblast spheroids. Our study reveals an extensive dysregulation of prostanoid biosynthesis and signaling pathways in IPF-derived fibroblasts, which are only partially abrogated by culture in soft microenvironments.


GameTag: A New Sequence Tag Generation Algorithm Based on Cooperative Game Theory.
Sequence tag-based peptide search is a critical technology in proteomics for the characterization of proteins from tandem mass spectrometry data. However, the main reason for hindering the full application of such an approach lies that accurately extracting sequence tags responsible for each experimental spectrum. Toward that end, GameTag, a novel cooperative game framework for sequence tag generation is proposed, which includes a tag generator and a tag discriminator to collaboratively generate sequence tags. Specifically, the tag generator works to extract as many correct tag candidates as possible and the tag discriminator serves to determine the correctness of tag candidates and reduce the total number of output tags simultaneously. Through the dynamic two-player game, the number of extracted tags is decreased while the number of correct tags gets boosted. The performance of the proposed method is also investigated under various hyperparameter and structure settings. Extensive experiments on a wide variety of data sets from different species demonstrate that GameTag outperforms previous state-of-the-art methods, InsPecT, PepNovo+, DirecTag, and the existing tag-extraction method in Open-pFind, increasing by at least 10% the number of spectra extracted more than one correct tag.


Medical students' perceptions of the elements of effective inpatient teaching by attending physicians and housestaff.
Most studies of effective inpatient teaching have focused on teaching by attending physicians. To identify and compare medical students' perceptions of behaviors associated with teaching effectiveness of attending physicians and housestaff (residents and interns). Third-year students who spent 4 weeks on a general internal medicine inpatient service during academic year 2003-2004 completed surveys using a 5-point Likert-type scale. Students evaluated numerous teaching behaviors of attendings and housestaff and then evaluated their overall teaching effectiveness. Each behavior was correlated with the perceived teaching effectiveness in univariate and regression analyses. Seventy-two students were taught by 23 attendings and 73 housestaff. Of 144 possible teaching evaluations, they completed 142 (98.6%) for attendings and 128 (88.9%) for housestaff. The mean rating for perceived teaching effectiveness was 4.48 (SD 0.82) for attendings and 4.39 (SD 0.80) for housestaff. For attending physicians, teaching effectiveness correlated most strongly with enthusiasm for teaching (R(2)=63.6%) but was also associated with inspiring confidence in knowledge and skills, providing feedback, and encouraging students to accept increasing responsibility. Housestaff teaching effectiveness correlated most strongly with providing a role model (R(2)=61.8%) but was also associated with being available to students, performing effective patient education, inspiring confidence in knowledge and skills, and showing enthusiasm for teaching. Regression models explained 79.7% and 73.6% of the variance in evaluations of attendings and housestaff, respectively. Students' perceptions of effective teaching behaviors differ for attending physicians and housestaff, possibly reflecting differences in teaching roles or methods.


Primary endometrioid adenocarcinoma of the large intestine arising in colorectal endometriosis.
Three cases of endometrioid adenocarcinoma arising in colorectal endometriosis are described with discussion of their macroscopic and microscopic pathology and diagnosis, using immunohistochemistry. Three middle-aged women presented with symptoms and signs of colorectal mass effect. Two had a preceding history of gynaecological endometriosis and all three had either been on hormone replacement therapy or had functioning ovaries prior to presentation with colorectal disease. Each underwent resection of tumours of the distal large intestine. The definitive diagnosis was dependent on histological examination and immunohistochemistry, which was used to demonstrate an origin in endometriotic tissue. Endometrioid adenocarcinoma is a rare complication of colorectal endometriosis, this report contributing to a total of 25 cases in the literature. Definitive diagnosis, aided by immunohistochemical studies, is important to enable the identification of the optimal management for this uncommon condition.


Differential effects of estrogen treatment on bone mineral density of the spine, hip, wrist and total body in late postmenopausal women.
It is commonly believed that estrogen is effective only in preventing menopause-related loss of bone mineral. However, recent studies found significant increases in bone mineral density (BMD) of the spine in response to estrogen, particularly in older women. The degree to which estrogen can restore BMD of the hip is uncertain. In the present study, changes in BMD of the lumber spine (L2-4), hip (neck, trochanter and Ward's triangle), wrist (ultradistal) and total body in response to 1 year of hormone replacement therapy (HRT) were evaluated by dual-energy X-ray absorptiometry (DXA) in women 10 or more years past menopause. Twelve women, aged 61-74 years, received conjugated estrogens 0.625 mg and cyclic medroxyprogesterone acetate 5 mg; 12 women who did not receive HRT were controls. Calcium intake was adjusted to approximately 1500 mg/day in all subjects. There were no differences between the groups in BMD prior to treatment. Increases in BMD of the lumbar spine (mean +/- SD, 0.041 +/- 0.030 g/cm2), hip (neck, 0.019 +/- 0.018 g/cm2; trochanter, 0.017 +/- 0.012 g/cm2; Ward's triangle, 0.026 +/- 0.029 g/cm2) and total body (0.013 +/- 0.016 g/cm2) occurred in response to HRT, and these changes were significantly different from those in controls (spine, 0.005 +/- 0.020 g/cm2; neck, -0.007 +/- 0.026 g/cm2; trochanter, 0.002 +/- 0.014 g/cm2; Ward's triangle, 0.003 +/- 0.019 g/cm2; total body, -0.001 +/- 0.017 g/cm2). HRT appears to be most effective at weight-bearing sites that have a high cancellous bone content.(ABSTRACT TRUNCATED AT 250 WORDS)


Platelet concentrates: past, present and future.
Platelets play a crucial role in hemostasis and wound healing, platelet growth factors are well known source of healing cytokines. Numerous techniques of autologous platelet concentrates have been developed and applied in oral and maxillofacial surgery. This review describes the evolution of the first and second generation of platelet concentrates (platelet rich plasma and platelet rich fibrin respectively) from their fore runner-fibrin sealants.


COVID-19 highlights the pitfalls of reliance on the carceral system as a response to addiction.
People who are incarcerated are likely to meet criteria for at least one substance use disorder and need access to treatment. Access to such interventions was limited prior to the COVID-19 pandemic and has almost certainly been restricted further due to implementation of procedures intended to stop the spread of the virus. In this brief commentary, we discuss how COVID-19 has revealed the already tenuous access that people who are incarcerated have to behavioral health services, and the pitfalls of reliance on the U.S. carceral system as a response to addiction.


Identification of an estrogenic hormone receptor in Caenorhabditis elegans.
Changes in both behavior and gene expression occur in Caenorhabditis elegans following exposure to sex hormones such as estrogen and progesterone, and to bisphenol A (BPA), an estrogenic endocrine-disrupting compound. However, only one steroid hormone receptor has been identified. Of the 284 known nuclear hormone receptors (NHRs) in C. elegans, we selected nhr-14, nhr-69, and nhr-121 for analysis as potential estrogenic hormone receptors, because they share sequence similarity with the human estrogen receptor. First, the genes were cloned and expressed in Escherichia coli, and then the affinity of each protein for estrogen was determined using a surface plasmon resonance (SPR) biosensor. All three NHRs bound estrogen in a dose-dependent fashion. To evaluate the specificity of the binding, we performed a solution competition assay using an SPR biosensor. According to our results, only NHR-14 was able to interact with estrogen. Therefore, we next examined whether nhr-14 regulates estrogen signaling in vivo. To investigate whether these interactions actually control the response of C. elegans to hormones, we investigated the expression of vitellogenin, an estrogen responsive gene, in an nhr-14 mutant. Semi-quantitative RT-PCR showed that vitellogenin expression was significantly reduced in the mutant. This suggests that NHR-14 is a C. elegans estrogenic hormone receptor and that it controls gene expression in response to estrogen.


Occupational Activity After Renal Transplantation vs Quality of Life, Personality Profile, and Stress Coping Styles.
Kidney transplantation (KT) increases the quality of life (QoL) of patients with chronic kidney disease. Employment is one the objective indicators of KT success. The aim of the presented study was to assess the psychological predispositions of KT and hemodialysis (HD) patients, such as stress coping styles, chosen personality features, and their relationship with employment and QoL. One hundred and sixty-one persons were examined, 101 after KT, and 60 HD patients. The following methods were applied: NEO-FFI Personality Inventory; Coping Inventory for Stressful Situations (CISS); WHOQoL-BREF; and general survey, measuring sociodemographic data and work experience. In the KT group, 58 persons were employed and 43 were unemployed. HD patients were mostly unemployed, with only 15 persons working. Significant differences were identified between the results of the following variables: WHOQoL environmental scale (employed m= 16.8, standard deviation [SD] = 3; unemployed m= 15, SD = 2.8); extraversion (employed m = 6.7, SD = 2; unemployed m = 5.6, SD = 2); somatic WHOQoL scale (HD m = 12.2, SD = 2.7; KT m = 14.2, SD = 3.5). In the KT group, the following correlations were identified: extraversion with contact seeking strategy (r = 0.553), agreeableness (r = 0.245), and conscientiousness (r = 0.384); agreeableness with conscientiousness (r = 0.336). In the HD group, the following correlations were identified: task-oriented style with conscientiousness (r = 0.474); avoidance-oriented style with conscientiousness (r = -0.466); contact seeking with extraversion (r = 0.402) and agreeableness (r = 0.469). The following conclusions were reached: Social competence, such as seeking and maintaining contacts, positively translates to features connected with occupational activity. Social skills strengthen the organization of healthier environment and increase QoL. Employed patients have higher social skills and QoL.


Carboxylterminal deletion mutants of ribulosebisphosphate carboxylase from Rhodospirillum rubrum.
The carboxylterminal octapeptide of ribulosebisphosphate carboxylase from Rhodospirillum rubrum, which lacks small subunits, shows homology to a highly conserved region near the amino terminus of the small subunits of hexadecameric ribulosebisphosphate carboxylases, which are composed of large and small subunits. Truncations of the R. rubrum enzyme, which partially or completely deleted the region of homology, demonstrated that the region is not an important determinant of the catalytic efficiency of the enzyme. A further truncation, which replaced the carboxylterminal 19 amino acid residues with a single terminal leucyl residue, yielded a Rubisco whose substrate-saturated catalytic rate resembled that of the wild-type enzyme but which had weaker affinities for ribulose-P2 and CO2.


The effects of leg crossing and applied tension on blood donor return.
Repeated isometric muscle tension (applied tension) during blood donation reduces vasovagal symptoms in many donors. Experiencing vasovagal symptoms has been found to reduce blood donor return. However, does practicing applied tension improve blood donor return? Follow-up results from a randomized controlled trial are presented. Data were collected in mobile clinics held in several colleges and universities. During the baseline donation, participants either (1) practiced 'standard' applied tension consisting of repeated 5 s cycles of whole-body isometric muscle tension in the donation chair (N = 133), (2) practiced tension with legs crossed (N = 131), or (3) gave blood as usual (N = 140). Subsequent blood donations in the following 2 years were determined. Applied tension had no effect on immediate (at the end of the baseline blood donation) rating of intention to give blood or the dichotomous measure of whether or not the participant gave blood again in the following 2 years. However, men asked to practice applied tension with legs crossed gave approximately one unit more during the follow-up period compared with men in the control group (F1,106 = 5·32, P = 0·023). This was associated significantly with adherence - men assigned to the applied tension with legs crossed condition who did not practice as instructed were no more likely to return than controls. The results provide modest support for the idea that applied tension may increase subsequent blood donation though the results were limited to men who practiced the technique as instructed.


Potential role of a mismatched HLA-specific CTL clone developed pre-transplant in graft rejection following cord blood transplantation.
Graft rejection is a serious complication in cord blood transplantation (CBT), but little is known about the mechanism of rejection. To investigate the potential role of T lymphocytes in graft rejection, we isolated a CD8(+) cytotoxic T lymphocyte (CTL) clone of recipient origin from blood obtained from a patient with graft rejection after CBT from an HLA-mismatched unrelated donor. The isolated CTL clone specifically recognized an HLA-B( *)1501 molecule as an alloantigen, which was expressed in donor cells but not in recipient cells. The results of a microchimerism analysis specific for HLA-B( *)1501 and a polymerase chain reaction assay specific for the T cell receptor on DNA from pretransplant peripheral blood mononuclear cells revealed that the patient was exposed to HLA-B( *)1501 prior to CBT, and that the CTL clone was in the patient's blood prior to transplantation. The present study demonstrates a potential role for pretransplant CTL in graft rejection following CBT.


Position of chromosomes 18, 19, 21 and 22 in 3D-preserved interphase nuclei of human and gorilla and white hand gibbon.
Even though comparative nuclear architecture studies in hominoids are sparse, nuclear chromosome architecture was shown to be conserved during hominoid evolution. Thus, it is suspected that yet unknown biological mechanisms must underlie this observation. Here for the first time a combination of multicolor banding (MCB) and three-dimensional analysis of interphase cells was used to characterize the position and orientation of human chromosomes #18, #19, #21 and #22 and their homologues in primate B-lymphocytic cells. In general, our data is in concordance with previous studies. The position of the four studied human chromosomes and their homologues were conserved during primate evolution. However, comparison of interphase architecture in human B-lymphocytic cells and sperm revealed differences of localization of acrocentric chromosomes. The latter might be related to the fact that the nucleolus organizing region is not active in sperm. Studies in different tissue types may characterize more - potentially biologically relevant differences in nuclear architecture.


Nutrition and burrowing energetics of the Cape mole-rat Georychus capensis.
At 22°C the resting oxygen consumption of G. capensis is 1.13±0.05 cm3O2·g-1·h-1 (mean± S.E.). In loose sandy soil the burrowing metabolic rate was approximately three times that of resting (3.41±0.19 cm3O2·g-1· h-1). Rate of oxygen consumption while burrowing bears a linear relationship with rate of burrowing. The equation of the regression line describing this relationship was used to construct a model for calculating energy expenditure of burrowing in free-living mole-rats. The diet of G. capensis consists of some green plant material and geophyte corms. The latter has a mean gross energy content of 16.36 kJ·g-1 dry weight. The digestibility coefficient for captive G. capensis fed on sweet potato, was 97.42±0.41%. Data collected from an excavated burrow system revealed that the total energetic cost of constructing the burrow amounted to 79% of the estimated digestible energy available from geophyte corms in the area. A food store in the same burrow system was sufficient to meet the maintenance requirements of an adult G. capensis, resting at 22°C, for approximately 80-85 days. Soil samples taken at random adjacent to the burrow contained corms with a mean estimated digestible energy value of 2084 kJ per m3 of soil. A comparison of energetic cost of burrowing and randomly available digestible energy in the field suggests that foraging patterns are not random.


Neurogenic Pulmonary Edema Following a Seizure: A Case Report and Literature Review.
Acute pulmonary edema is one of the frequent causes of dyspnea encountered in everyday practice. It is broadly attributed to be either cardiogenic or noncardiogenic. It is usually treated with diuretics in addition to other medications depending on the underlying pathology. Here, we report a case of a female patient who presented with shortness of breath after developing a seizure. Further investigations excluded cardiogenic etiology and showed critically low phenytoin level. It improved within 48 h of supportive care without giving diuretics favoring the diagnosis of neurogenic pulmonary edema as the primary pathology. The goal of our case report is to keep neurogenic pulmonary edema in mind, and hence provide the appropriate management, when dealing with similar cases.


A simplified procedure for the quantitative measurement of neurological deficits after forebrain ischemia in mice.
This study describes a comprehensive method to assess neurological deficits after brain ischemia produced by sequential common carotid artery sectioning (SCAS) in aged mice, and a scale to determine the degree of functional incapacity of ischemic animals. The method involves an initial phase of undisturbed observation and a later manipulative phase during which each animal is subjected to a sequence of very simple manipulations. Sham-operated animals demonstrated 96% survival throughout the study period (72 h), whereas the 24, 48 and 72 h survival rates of SCAS-mice were 48, 38 and 36%, respectively. In the surviving SCAS-mice, we detected a total of 23 neurological alterations throughout the observation period (72 h); the most frequent alterations were: motor incoordination, abnormal body position, hypomobility, decreased body tone and muscular strength, tremor, hunched back, passivity, forelimb flexion and ataxic gait. Based on these alterations, we used a global scale that comprises 10 progressive grades beyond 0 (normal), extending to status 10 (death due to SCAS), with higher scores indicating greater deficit. The median neurological scores for sham-operated animals were 1.36, 1.48 and 1.32 at 24, 48 and 72 h, respectively, whereas total neurological scores in SCAS-mice of 6.1, 6.8 and 7.4, at 24, 48 and 72 h, respectively, were substantially greater than those observed in sham-operated animals. The simplicity of the procedure, herein described, to measure the functional neurological condition of ischemic animals, and the remarkable level of functional impairment produced by SCAS offer the possiblity to test the efficacy of putative stroke therapies and to monitor progress of deficits over time in groups of animals.


Mortality trends among Alaska Native people: successes and challenges.
Current mortality rates are essential for monitoring, understanding and developing policy for a population's health. Disease-specific Alaska Native mortality rates have been undergoing change. This article reports recent mortality data (2004-2008) for Alaska Native/American Indian (AN/AI) people, comparing mortality rates to US white rates and examines changes in mortality patterns since 1980. We used death record data from the state of Alaska, Department of Vital Statistics and SEER*Stat software from the National Cancer Institute to calculate age-adjusted mortality rates. Annual age-adjusted mortality from all-causes for AN/AI persons during the period 2004-2008 was 33% higher than the rate for US whites (RR = 1.33, 95% CI 1.29-1.38). Mortality rates were higher among AN/AI males than AN/AI females (1212/100,000 vs. 886/100,000). Cancer remained the leading cause of death among AN/AI people, as it has in recent previous periods, with an age-adjusted rate of 226/100,000, yielding a rate ratio (RR) of 1.24 compared to US whites (95% CI 1.14-1.33). Statistically significant higher mortality compared to US white mortality rates was observed for nine of the ten leading causes of AN/AI mortality (cancer, unintentional injury, suicide, alcohol abuse, chronic obstructive pulmonary disease [COPD], cerebrovascular disease, chronic liver disease, pneumonia/influenza, homicide). Mortality rates were significantly lower among AN/AI people compared to US whites for heart disease (RR = 0.82), the second leading cause of death. Among leading causes of death for AN/AI people, the greatest disparities in mortality rates with US whites were observed in unintentional injuries (RR = 2.45) and suicide (RR = 3.53). All-cause AN/AI mortality has declined 16% since 1980-1983, compared to a 21% decline over a similar period among US whites. Mortality rates and trends are essential to understanding the health of a population and guiding policy decisions. The overall AN/AI mortality rate is higher than that of US whites, although encouraging declines in mortality have occurred for many cause specific deaths, as well as for the overall rate. The second leading cause of AN/AI mortality, heart disease, remains lower than that of US whites.


Cloning and expression of the genes for xylose isomerase and xylulokinase from Klebsiella pneumoniae 1033 in Escherichia coli K12.
The genes xylA and xylB were cloned together with their promoter region from the chromosome of Klebsiella pneumoniae var. aerogenes 1033 and the DNA sequence (3225 bp) was determined. The gene xylA encodes the enzyme xylose isomerase (XI or XylA) consisting of 440 amino acids (calculated M(r) of 49,793). The gene xylB encodes the enzyme xylulokinase (XK or XylB) with a calculated M(r) of 51,783 (483 amino acids). The two genes successfully complemented xyl mutants of Escherichia coli K12, but no gene dosage effect was detected. E. coli wild-type cells which harbored plasmids with the intact xylAKp 5' upstream region in high copy number (but lacking an active xylB gene on the plasmids) were phenotypically xylose-negative and xylose isomerase and xylulokinase activities were drastically diminished. Deletion of 5' upstream regions of xylA on these plasmids and their substitution by a lac promoter resulted in a xylose-positive phenotype. This also resulted in overproduction of plasmid-encoded xylose isomerase and xylulokinase activities in recombinant E. coli cells.


Enhanced winter soil frost reduces methane emission during the subsequent growing season in a boreal peatland.
Winter climate change may result in reduced snow cover and could, consequently, alter the soil frost regime and biogeochemical processes underlying the exchange of methane (CH4 ) in boreal peatlands. In this study, we investigated the short-term (1-3 years) vs. long-term (11 years) effects of intensified winter soil frost (induced by experimental snow exclusion) on CH4 exchange during the following growing season in a boreal peatland. In the first 3 years (2004-2006), lower CH4 emissions in the treatment plots relative to the control coincided with delayed soil temperature increase in the treatment plots at the beginning of the growing season (May). After 11 treatment years (in 2014), CH4 emissions were lower in the treatment plots relative to the control over the entire growing season, resulting in a reduction in total growing season CH4 emission by 27%. From May to July 2014, reduced sedge leaf area coincided with lower CH4 emissions in the treatment plots compared to the control. From July to August, lower dissolved organic carbon concentrations in the pore water of the treatment plots explained 72% of the differences in CH4 emission between control and treatment. In addition, greater Sphagnum moss growth in the treatment plots resulted in a larger distance between the moss surface and the water table (i.e., increasing the oxic layer) which may have enhanced the CH4 oxidation potential in the treatment plots relative to the control in 2014. The differences in vegetation might also explain the lower temperature sensitivity of CH4 emission observed in the treatment plots relative to the control. Overall, this study suggests that greater soil frost, associated with future winter climate change, might substantially reduce the growing season CH4 emission in boreal peatlands through altering vegetation dynamics and subsequently causing vegetation-mediated effects on CH4 exchange.


Identification and Validation of the Prognostic Impact of Metastatic Prostate Cancer Phenotypes.
Castration-sensitive metastatic prostate cancer is heterogeneous. Our objective is to identify metastatic prostate cancer phenotypes and their prognostic impact on survival. The National Cancer Database was queried. The Surveillance, Epidemiology, and End Results database was used for validation. Patterns were split into: nonregional lymph node, bone only, and visceral (any brain/liver/lung). Hazard ratios (HR) with 95% confidence intervals (CI) were calculated for the univariate and multivariate Cox proportional hazards regression models, odds ratios were calculated, Kaplan-Meier curves were generated, and a nomogram of the multivariate regression model was created. The training set included 13,818 men; bone only was most common (n = 11,632, 84.2%), then nonregional lymph node (n = 1388, 10.0%), and any visceral (brain/liver/lung; n = 798, 5.8%). Risk of death was increased by metastases to a visceral organ versus nonregional lymph node (HR = 2.26; 95% CI [2.00, 2.56]), bone only metastases versus nonregional lymph node (HR = 1.57; 95% CI [1.43, 1.72]), T-stage 4 versus 1 (HR = 1.27; 95% CI [1.17, 1.36]), Grade Group 5 versus 1 (HR = 1.93; 95% CI [1.61, 2.31]), PSA > 20 ng/mL versus < 10 ng/mL (HR = 1.32; 95% CI [1.23, 1.42]), and age ≥ 80 versus < 50 (HR = 1.96; 95% CI [1.69, 2.29]). On internal validation, the model had C-indices 20.5%, 22.7%, and 14.6% higher than the current staging system for overall survival, 1-year, and 5-year survival, respectively. We developed and validated prognostic metastatic prostate cancer phenotypes that can assist risk stratification to potentially personalize therapy. Our nomogram (https://tinyurl.com/prostate-met) may be used to predict survival.


A possible mechanism for atherosclerosis induced by polycyclic aromatic hydrocarbons.
Polycyclic aromatic hydrocarbons (PAHs), aryl hydrocarbon receptor (AHR) ligands, induce atherogenesis. Liver X receptor (LXR) alpha is known to be involved in the control of cholesterol homeostasis. Thus, the purpose of this study was to investigate the effects of 3-methlycholanthrene (MC), one of the PAHs, on LXRalpha-mediated signal transductions. We found that expression of mRNAs for ATP binding cassette A1, sterol regulatory element binding protein 1c (SREBP-1c), fatty acid synthase, and stearoyl-CoA desaturase was suppressed by treatment of HepG2 cells with MC. A luciferase reporter assay revealed that LXRalpha- and SREBP-1c-mediated transactivations were inhibited by MC via AHR. Based on these lines of evidence, we propose that down-regulation of the LXRalpha-regulated genes by PAHs is one of the causes responsible for atherosclerosis induced by PAHs.


Efficacy and safety of transgastric closure in natural orifice transluminal endoscopic surgery using the OTSC system and T-bar sutures: a survival study in a porcine model.
In natural orifice transluminal endoscopic surgery (NOTES), procedures are performed with an endoscope passed through a natural orifice. One of the most important factors that will determine the future of transgastric NOTES is obtaining a reliable closure of the access site. The aim of this study was to determine the efficacy and safety of transgastric closure using the over-the-scope clip (OTSC) system or T-bar sutures. We performed a survival study that included 15 pigs. A standardized transgastric approach to the peritoneal cavity and a peritoneoscopy were performed. The gastrotomy was closed using the OTSC system or T-bar sutures. The gastrotomy closure was tested for leaks with the methylene blue test. All animals were observed for 2 weeks before they were sacrificed and necropsy was performed. Histopathological examination of tissue samples retrieved from the access sites was performed. There were no perioperative complications. The methylene blue test did not demonstrate any leakage of fluid. Necropsy after 2 weeks confirmed completeness of gastric closure in all animals with full-thickness healing and no spillage of gastric contents into the peritoneal cavity. No differences between the OTSC system and T-bar sutures were observed. We observed no differences between the efficacy and safety of the OTSC system and those of T-bar sutures used in closing gastric incisions in NOTES. Both methods are safe and effective.


Methotrexate-Related Liver Cirrhosis in Psoriatic Arthritis: A Case Report and Review of the Literature.
Methotrexate is an anchor-drug for the treatment of inflammatory arthritides affecting peripheral joints, such as rheumatoid and psoriatic arthritis (PsA), but also for other immune-mediated diseases like psoriasis. Although it is generally a well-tolerated drug, adverse effects often occur. Reversible derangement of liver function test is the most common laboratory adverse event. However, in some cases, liver cirrhosis and/or fibrosis can occur. Besides, many of these diseases like PsA and psoriasis are closely linked with clinical conditions and risk factors that also contribute to liver damage/cirrhosis, such as increased body mass index, dyslipidaemia and diabetes mellitus (DM). It has been hypothesised that the aforementioned risk factors along with methotrexate usage can act synergistically, causing liver damage in these patients. Herein, we describe a PsA patient with DM who developed fatal liver cirrhosis after 10 years of treatment with MTX. We also review the literature about the liver toxicity of MTX in the context of PsA and psoriasis, describing concurring risk factors and histopathological findings. PubMed and Scopus were searched, without date limits. The keywords "methotrexate" AND "psoriatic arthritis" OR "psoriasis" AND "Liver damage" OR "liver fibrosis" OR "cirrhosis" were used. We found that although fibrosis/cirrhosis is present in about 10-25% of the patients, MTX can rarely cause liver damage itself. However, it can exert its effect when other factors, like increased alcohol consumption and obesity coexist. Prospective studies are needed, specifically examining the hepatotoxicity of MTX in individuals with immune-mediated diseases.


Ovarian cancer antigen CA125: a prospective clinical assessment of its role as a tumour marker.
Serum CA 125, quantified by an immunoradiometric assay employing the monoclonal antibody 0C125 was found to be elevated in 48/58 (83%) of patients with established ovarian cancer. All histological types of carcinoma were antigen positive and there was a positive correlation between the frequency and level of serum CA125 and body burden of tumour. Twenty patients undergoing chemotherapy had serial CA125 estimations following a prospective protocol. Variation in CA125 level reflected disease progression or regression in 21/23 instances. Three of 9 patients tested showed an acute elevation of CA125 in the first week following chemotherapy and this effect predicted a good response to treatment. The natural half-life of CA125 in serum was estimated at approximately 4.8 days, sufficiently short to allow changes in tumour volume to be rapidly reflected by a change in circulating antigen level. Although none of 15 patients with non-Hodgkin lymphoma demonstrated antigen levels outside the normal range, 11/27 patients with non-ovarian adenocarcinoma showed elevated CA125 levels, a specificity of 58% for this latter group. The value of CA125 in the management of ovarian malignancy is discussed.


Executive control, ERP and pro-inflammatory activity in emotionally exhausted middle-aged employees. Comparison between subclinical burnout and mild to moderate depression.
Burnout is a syndrome occurring mainly in individuals with long-term stressful work. The main complaints are emotional exhaustion and reduced performance. Burnout also largely overlaps with depression. Both are characterized by increased incidence of infections due to dysregulation of the immune system, overexpression of pro-inflammatory cytokines and cognitive deficits, particularly related to executive functions. To distinguish between burnout and depression already at the pre-clinical stage, the present double-blinded study compared immunological and cognitive parameters in seventy-six employees from emotionally demanding occupations who were post-hoc subdivided into two groups scoring low (EE-) and high (EE+) in emotional exhaustion and low (DE-) and high (DE+) in depression. Immunological parameters were measured from blood samples. Executive functions were studied by analyzing event-related brain potentials (ERPs) and performance during a task switching paradigm. Psychosocial job parameters were measured with standardized questionnaires. Burnout and mild to moderate depression largely overlapped. However, several subjects showed burnout without depressive symptoms. Higher levels of the pro-inflammatory cytokines IL-6 and IL-12 were correlated with burnout severity and depressive symptoms in male individuals. In the switch task a trend for lower performance in the EE+ vs. EE- group and no difference between DE+ and DE- groups were found. In the ERPs, however, differences were observed which distinguished between subclinical burnout and depression: the terminal contingent negative variation (CNV), indicating preparatory activity and the P3b, related to allocation of cognitive resources were generally reduced in EE+ vs. EE-, whereas no differences were found in the DE+ vs. DE- groups. The frontal P3a was selectively reduced in switch trials in the EE+ vs. EE- group and showed only a trend in DE+ vs. DE-, indicating impairment of executive control in subclinical burnout. Taken together, the results unveil specific immunological changes and declines in brain functions in employees with subclinical burnout that are not apparent in persons with moderate depression. Hence, the combination of immunological, behavioral and ERP methods renders a promising method for distinguishing both syndromes and for improving an early diagnosis of burnout before a clinical stage is reached.


Effect of environmental pollutants on the C-reactive protein of a freshwater major carp, Catla catla.
C-reactive proteins (CRP) have been affinity purified to electrophoretic homogeneity from the sera of major carp, Catla catla before and after exposure to environmental pollutants. Exposure to these pollutants elevate the levels of circulating CRPs to 2.8-3.5 times the normal values. Kinetic studies of metal intoxication indicate that a unique molecular variant of CRP is present in the serum at the peak level of acute phase induction, and this variant coexists with normal CRPs. Carbohydrate analysis and lectin binding reveals that these CRPs are glycoproteins differing significantly in total carbohydrate contents. Their electrophoretic mobilities in native gel are different but become identical on desialylation and deglycosylation implying that the molecular variants vary in the glycan parts. All these forms of CRP contain two nonidentical subunits of Mr 22 and 29 kDa. Examination of their immunological crossreactivity demonstrate their similarity in overall molecular topology but their differences in the quantitative extent of binding are reflected.


Lignocellulosic waste valorisation strategy through enzyme and biogas production.
Lignocellulosic wastes are generally pre-treated to facilitate the hydrolysis stage during the anaerobic digestion process. A process consisting of solid state fermentation carried out by white rot fungi and anaerobic digestion was evaluated on corn stover to produce ligninolytic enzymes and biogas. The enzyme production was quantified every 3d for a month at 30°C, and three fungal strains and two particle sizes of waste were compared. Of the main outcomes, Pleurotus eryngii produced the highest laccase enzyme activity compared with Pleurotus ostreatus and Trametes versicolor. Furthermore, this activity was improved by 16% when copper was used as an enzyme inducer. On the other hand, most of the conditions studied showed a decrease in maximum biogas production compared with untreated waste, the addition of copper decreased biogas production by 20%. Despite the above, Pleurotus eryngii showed promising results allowing a 19% increase of biogas production and high enzyme production values.