Systematic review and network meta-analysis of hydrosalpinx treatment before in vitro fertilization.

OBJECTIVES: To compare different methods to treat hydrosalpinx, based on both ablative and non-ablative approaches, in infertile patients before undergoing IVF-ET. METHODS: Systematic review and network meta-analysis (NMA) of comparisons between different treatments of hydrosalpinx in infertile patients undergoing IVF. DATA SOURCES: structured searches in common citation databases. Study inclusion criteria: peer-reviewed randomized trials (RCT) or cohort studies comparing effects of salpingectomy, laparoscopic proximal tubal occlusion (LTO), insertion of intratubal device (ITD), sclerotherapy, ultrasound-guided aspiration and no treatment, on live birth, ongoing pregnancy, clinical pregnancy as main outcomes, considering also miscarriage, ectopic pregnancy and complications as secondary outcomes. Principal NMA included RCT, and aggregated NMA of RCT and observational studies was carried out. Pooled effects have been estimated by Odds Ratio (OR) and its 95% confidence interval (CI) for direct and indirect-mixed comparisons, derived from random-effects models. Imprecision and heterogeneity of NMA estimations was assessed by comparison of its 95% CI with predefined intervals for clinically relevant size of effect (OR <0.9 or >1.1). Surface under the cumulative ranking curve (SUCRA) were used to predict treatment rankings for each outcome. RESULTS: Nine RCT were included in main analysis, plus 17 additional observational studies in additional analysis. NMA of RCT did not identify significant differences in the effect of compared treatments on live birth rate, and LTO was the option with the highest value of SUCRA (0.92, mean rank: 1.2). Salpingectomy and US-aspiration associated to a significant increase of ongoing pregnancy rate compared to no treatment, according to NMA results (NMA OR: 4.35; 95% CI: 1.7, 11.14 and 2.8; 95% CI: 1.03, 7.58 respectively). Salpingectomy had the highest SUCRA value (0.88, mean rank: 1.4). NMA estimated significant increase of clinical pregnancy rate for salpingectomy compared with no treatment (NMA OR: 2.24; 95% CI: 1.3, 3.86) as well as for LTO versus no treatment (NMA OR: 2.55; 95% CI: 1.2, 5.41). Both comparisons were affected by a high grade of heterogeneity. For clinical pregnancy, LTO was the intervention with highest SUCRA (0.85; mean rank: 1.6). Regarding secondary outcomes, feasible NMA estimates did not support significant differences between treatments effects. According to aggregated NMA including randomized and observational studies, sclerotherapy showed significant beneficial effects on live birth rate compared to no treatment (NMA (OR: 4.6; 95% CI: 1.21, 17.46). Compared with untreated patients, the aggregated NMA estimates a higher ongoing pregnancy rate in patients treated with salpingectomy (NMA OR: 3.35; 95% CI: 2.12, 5.12), US-aspiration (NMA OR: 2.16; 95% CI: 1.28, 3.65) and LTO (NMA OR: 2.46; 95% CI: 1.11, 5.43). Salpingectomy and LTO produced a higher beneficial effect compared to ITD, based on both direct and indirect comparisons. Salpingectomy obtained the highest SUCRA value in rank of effects on ongoing pregnancy (0.94; mean rank: 1.2). NMA found significant effects on clinical pregnancy for comparisons between the different active management procedures compared with no treatments, with the exception of ITD insertion. LTO had more increasing effect on clinical pregnancy rate compared with US-aspiration (NMA OR: 2.04; 95% CI: 1.05, 3.97), while for the rest of the comparisons between procedures no significant differences were identified. NMA ranked LTO as the treatment with a highest SUCRA value (0.91; mean rank: 1.5). NMA prediction models identified LTO as best intervention to reduce miscarriage (SUCRA value: 0.84; mean rank: 1.8), as sclerotherapy as safer option in terms of ovarian response to IVF stimulation. CONCLUSIONS: The present NMA fails to support the effectiveness of any option to treat hydrosalpinx before IVF in order to improve live birth rates, although the beneficial effect of salpingectomy and US aspirations on ongoing pregnancy rates and of both salpingectomy and LTO on clinical pregnancy rates emerges from our analysis, which reinforces current recommendations. Based on the aggregated analyses, sclerotherapy could be a promising alternative to conventional laparoscopic techniques, combined with a favorable safety profile. This article is protected by copyright. All rights reserved.

Serological study of healthcare workers in four different hospitals in Madrid (Spain) with no previous history of COVID-19.

OBJECTIVES: Healthcare workers (HCWs) have been one of the most severely affected groups during the COVID-19 pandemic, though few studies have sought to determine the rate of undiagnosed cases among this population. In this study, we aim to determine the rate of undetected infection in HCWs, a potential source of nosocomial infection. METHODS: Serological screening for IgG and IgM antibodies against SARS-CoV-2 was carried out among HCWs from four different hospitals in Madrid, Spain, from 6 April to 25 April 2020; HCWs with a previous diagnosis of infection based on real-time reverse transcriptase-PCR assay performed after presenting compatible symptoms were excluded. Prevalence of IgG and IgM antibodies was calculated among HCWs to obtain the rate of COVID-19 presence of antibodies in each hospital. RESULTS: Of the 7121 HCWs studied, 6344 (89.09%) had not been previously diagnosed with COVID-19. A total of 5995 HCWs finally participated in the study, resulting in a participation rate of 94.49%. A positive IgM or IgG test against COVID-19 was revealed in 16.21% of the HCWs studied (n=972). CONCLUSION: This study reveals the importance of early detection of SARS-CoV-2 infection among HCWs to prevent nosocomial infection and exposure of patients, visitors and workers and the spread of COVID-19 in the overall community.

Evaluation of a phased pneumococcal conjugate vaccine introduction in Mongolia using enhanced pneumonia surveillance and community carriage surveys: a study protocol for a prospective observational study and lessons learned.

BACKGROUND: Streptococcus pneumoniae causes substantial morbidity and mortality among children. The introduction of pneumococcal conjugate vaccines (PCV) has the potential to dramatically reduce disease burden. As with any vaccine, it is important to evaluate PCV impact, to help guide decision-making and resource-allocation. Measuring PCV impact can be complex, particularly to measure impact on one of the most common and significant diseases caused by the pneumococcus, namely pneumonia. Here we outline the protocol developed to evaluate the impact of 13-valent PCV (PCV13) on childhood pneumonia in Mongolia, and a number of lessons learned in implementing the evaluation that may be helpful to other countries seeking to undertake pneumonia surveillance. METHODS: From 2016 PCV13 was introduced in a phased manner into the routine immunisation programme with some catch-up by the Government of Mongolia. We designed an evaluation to measure vaccine impact in children aged 2-59 months with hospitalised radiological pneumonia as a primary outcome, with secondary objectives to measure impact on clinically-defined pneumonia, nasopharyngeal carriage of S. pneumoniae among pneumonia patients and in the community, and severe respiratory infection associated with RSV and/or influenza. We enhanced an existing hospital-based pneumonia surveillance system by incorporating additional study components (nasopharyngeal swabbing using standard methods, C-reactive protein, risk factor assessment) and strengthening clinical practices, such as radiology as well as monitoring and training. We conducted cross-sectional community carriage surveys to provide data on impact on carriage among healthy children. DISCUSSION: Establishing a robust surveillance system is an important component of monitoring the impact of PCV within a country. The enhanced surveillance system in Mongolia will facilitate assessment of PCV13 impact on pneumonia, with radiological confirmed disease as the primary outcome. Key lessons arising from this evaluation have included the importance of establishing a core group of in-country staff to be responsible for surveillance activities and to work closely with this team; to be aware of external factors that could potentially influence disease burden estimates; to be flexible in data collection processes to respond to changing circumstances and lastly to ensure a consistent application of the pneumonia surveillance case definition throughout the study period.

Comparative features between recombinant lipases CALA-like from U. maydis and CALA from C. antarctica in thermal stability and selectivity.

OBJECTIVES: Ustilago maydis lipase A (UMLA) expressed in Pichia pastoris was compared with Candida antarctica lipase A (CALA) to study its biochemical properties such as thermostability and selectivity. RESULTS: UMLA had similar behavior to its homologue CALA regarding the effect of pH and temperature on enzymatic activity, substrate preference and selectivity. Both lipases were active on insoluble triglycerides as well as natural oils and hydrolyzed preferably esters with short and medium acyl and alkyl chains. Both enzymes were slightly selective for the (S)-glycidyl butyrate enantiomer and had a remarkable preference for the sn-2 position of triglycerides. The optimal activity was 40 and 50 °C for UMLA and CALA, respectively. However, temperature had a greater effect on the stability of UMLA compared to CALA, observing a half-life at 50 °C of 2.07 h and 12.83 h, respectively. CONCLUSIONS: UMLA shares some biochemical properties with CALA such as the sn-2 preference on triglyceride hydrolysis and transesterification. However, the high thermostability attributed to CALA was not observed in UMLA; this can be due to the lack of stabilization via AXXXA motifs in helices and fewer proline residues at the surface.

[Relationship between perineal characteristics and symptoms and pelvic girdle pain: A literature review]. / Caractéristiques et symptômes pelvi-périnéaux dans les douleurs de la ceinture pelvienne : une revue de la littérature.

INTRODUCTION: Pelvic girdle pain (PGP) is characterized by the presence of pain in the posterior pelvic area, distally and laterally to the fifth lumbar vertebra, and/or at the pubic symphysis. PGP is a very common pain condition in women, especially during pregnancy and postpartum. After delivery, pain prevalence decreases to 7 % in the first three months. The current literature describes an association between pelvic girdle pain and different perineal characteristics and symptoms. OBJECTIVES: A better understanding of perineal structures influence on PGP could assist towards the management of this condition. The aim of this review is to describe the peer-reviewed literature about perineal function in patients with PGP. METHODS: A bibliographic search on PubMed was conducted. The key words used were: pelvic girdle pain, pregnacy-related low back pain, lumbopelvic pain, posterior pelvic pain, peripartum pelvic pain, pelvic girdle relaxation, pelvic joint instability, peripartum pelvic pain, sacroiliac joint pain, sacroiliac joint dysfunction, sacroiliac-joint related pelvic pain and pelvic floor. Two hundred and twenty-one (221) articles were identified. Out of them, a total of nine articles were selected. The level of evidence was determined using Oxford's scale. RESULTS: Patients with PGP showed increased activity of the pelvic floor muscles (P=0.05) (LE3), decreased urogenital hiatus area (PGP 12.4 cm2±2.7, control 13.7 cm2±2.8, P=0.015) (LE3), shorter endurance time (PGP 17.8 s; control 54.0 s, P=0.00) (LE3), significantly later onset time during affected side leg elevation (PGP 25ms, control -129ms, P=0.01) (LE3), levator ani and obturator internus tenderness (PGP 25/26; control 5/25, P<0.001) (LE3) and a higher prevalence of vesico-sphincteric disorders compared to asymptomatic subjects (LE3). CONCLUSION: This review confirms that subjects suffering PGP present particular perineal characteristics regarding morphology and biomechanics. It would be interesting to develop clinical research concerning pelvic floor release effect in PGP.

BRI2 ectodomain affects Aß42 fibrillation and tau truncation in human neuroblastoma cells.

Alzheimer's disease (AD) is pathologically characterized by the presence of misfolded proteins such as amyloid beta (Aß) in senile plaques, and hyperphosphorylated tau and truncated tau in neurofibrillary tangles (NFT). The BRI2 protein inhibits Aß aggregation via its BRICHOS domain and regulates critical proteins involved in initiating the amyloid cascade, which has been hypothesized to be central in AD pathogenesis. We recently detected the deposition of BRI2 ectodomain associated with Aß plaques and concomitant changes in its processing enzymes in early stages of AD. Here, we aimed to investigate the effects of recombinant BRI2 ectodomain (rBRI276-266) on Aß aggregation and on important molecular pathways involved in early stages of AD, including the unfolded protein response (UPR), phosphorylation and truncation of tau, as well as apoptosis. We found that rBRI276-266 delays Aß fibril formation, although less efficiently than the BRI2 BRICHOS domain (BRI2 residues 113-231). In human neuroblastoma SH-SY5Y cells, rBRI276-266 slightly decreased cell viability and increased up to two-fold the Bax/Bcl-2 ratio and the subsequent activity of caspases 3 and 9, indicating activation of apoptosis. rBRI276-266 upregulated the chaperone BiP but did not modify the mRNA expression of other UPR markers (CHOP and Xbp-1). Strikingly, rBRI276-266 induced the activation of GSK3ß but not the phosphorylation of tau. However, exposure to rBRI276-266 significantly induced the truncation of tau, indicating that BRI2 ectodomain can contribute to NFT formation. Since BRI2 can also regulate the metabolism of Aß, the current data suggests that BRI2 ectodomain is a potential nexus between Aß, tau pathology and neurodegeneration.

Antibiotic prophylaxis in elective cholecystectomy: Protocol adequacy and related outcomes in a retrospective single-centre analysis.

BACKGROUND: Antibiotic prophylaxis is an effective tool to reduce surgical infection rates. However, antibiotic prophylaxis in cholecystectomy is controversial when non-high risk patients are considered. This research aims to evaluate the adherence with antibiotic prophylaxis protocol in patients undergoing cholecystectomy, and its impact in the outcomes of surgical infection. METHODS: This single-center observational and retrospective study analyzed all elective cholecystectomy procedures carried out at the Fundación Alcorcón University Hospital in the period 2007-2014. Data were recovered from hospital records; rates of adherence to the available hospital protocols were evaluated for choice, initiation, duration, administration route and dosages of antibiotics, and the starting and duration of the prophylaxis. RESULTS: The overall adequacy rate to protocol was 72%. The adherence rates in both the administration route and dose were 100%. The most common violations of the protocol included the choice of antibiotic agent (19%), followed by the moment of initiating its administration (8.9%). The overall wound infection rate was lower in case of laparoscopy than in laparotomy cholecystectomy (1.4% vs. 4.3%, p < 0.05; odds rate [OR] 0.29, 95% confidence interval [CI] 0.1-0.6). No relationship between adequacy of antibiotic prophylaxis and surgical infection rate was documented, neither considering overall gallbladder surgeries (crude OR 0.26, 95% CI 0.1-2.0), nor laparoscopy vs. open surgery (MH adjusted OR 0.24, 95% CI 0.2-2.1). CONCLUSIONS: The overall adequacy rate to antibiotic prophylaxis protocol recommended for elective cholecystectomy in our hospital was high (72%). No significant association between the adequacy or antibiotic prophylaxis and surgical infection was found.

Analysis of the long control region of bovine papillomavirus type 1 associated with sarcoids in equine hosts indicates multiple cross-species transmission events and phylogeographical structure.

Papillomaviruses are a family of slowly evolving DNA viruses and their evolution is commonly linked to that of their host species. However, whilst bovine papillomavirus-1 (BPV-1) primarily causes warts in its natural host, the cow, it can also cause locally aggressive and invasive skin tumours in equids, known as sarcoids, and thus provides a rare contemporary example of cross-species transmission of a papillomavirus. Here, we describe the first phylogenetic analysis of BPV-1 in equine sarcoids to our knowledge, allowing us to explore the evolutionary history of BPV-1 and investigate its cross-species association with equids. A phylogenetic analysis of the BPV-1 transcriptional promoter region (the long control region or LCR) was conducted on 15 bovine and 116 equine samples from four continents. Incorporating previous estimates for evolutionary rates in papillomavirus implied that the genetic diversity in the LCR variants was ancient and predated domestication of both equids and cattle. The phylogeny demonstrated geographical segregation into an ancestral group (African, South American and Australian samples), and a more recently derived, largely European clade. Whilst our data are consistent with BPV-1 originating in cattle, we found evidence of multiple, probably relatively recent, cross-species transmission events into horses. We also demonstrated the high prevalence of one particular sequence variant (variant 20), and suggest this may indicate that this variant shows a fitness advantage in equids. Although strong host specificity remains the norm in papillomaviruses, our results demonstrate that exceptions to this rule exist and can become epidemiologically relevant.

Characterization of hepatitis C infection in tuberculosis patients in an urban city in the USA.

The impact of hepatitis C virus infection (HCI), the most common bloodborne virus infection in the USA, on outcome of active tuberculosis (TB) treatment is largely unknown. We aimed to describe characteristics of TB patients with hepatitis C virus infection (TB-HCI) in King County, Washington, including TB treatment duration and outcome. We reviewed 1510 records of patients treated for active TB at the Public Health - Seattle & King County Tuberculosis Control Program between 2000 and 2010, and identified 53 with HCI. Advanced age, being born in the USA, HIV infection, homelessness and injection drug use were independently associated with HCI in TB cases. Independent factors associated with increased treatment duration included HIV infection, excess alcohol use, extrapulmonary TB, and any drug-resistant TB disease. Our findings suggest that TB-HCI patients can be successfully treated for active TB without extending treatment duration.

Impacts of urbanization on groundwater hydrodynamics and hydrochemistry of the Toluca Valley aquifer (Mexico).

The Toluca Valley is located on the high plains of Mexico, where there are significant industrial zones and large populations. Water needs are almost exclusively met by groundwater, which has brought about intense exploitation of the aquifer and indication of some contamination. The present study investigates the effect of urbanization, related to industrialization of the region, on groundwater in the central portion of the Toluca Valley aquifer--a zone with high population density and where the largest industrial park is located. A general decline in the groundwater level has been found over the years, at a rate of as much as 2.5 m/year. The appearance of a large drawdown cone was identified, indicating changes in the direction of groundwater flow. Also identified was the presence of several ground fissures, the location of which coincided with the drawdown cone. In hydrochemical terms, the water type is sodium-magnesium bicarbonate and this characteristic has not changed over time, although it has been possible to detect the presence of larger quantities of sulfates (up to 117 mg/L) and nitrates (up to 47 mg/L) in recent years, likely associated with contamination from industrial and urban wastewater. Factor analysis made it possible to identify ions that would characterize natural processes involving the acquisition of salts (HCO3 (-), Na(+), Mg(2+), and Si), as well as anthropic activities (SO4 (2-), NO3 (-), Cl(-), Ca(2+), and K(+)).

Impact of congenital uterine anomalies on obstetric and perinatal outcomes: systematic review and meta-analysis.

Background: Congenital uterine anomalies (CUA) can be associated with impairments of early and late pregnancy events. Objective: To assess the impact of CUA on reproductive outcomes in pregnancies conceived spontaneously or after assisted reproduction. Materials and Methods: Systematic review and meta-analysis of cohort studies comparing patients with CUA versus women with normal uterus. A structured literature search was performed in leading scientific databases to identify prospective and retrospective studies. The Newcastle-Ottawa scale, adapted to AHRQ standards, was used to assess the risk of bias. Pooled odds ratios (OR) were calculated. Publication bias and statistical heterogeneity were assessed, and meta-regression was used to analyse the heterogeneity. Main outcome measures: Miscarriage, ectopic pregnancy, placental abruption, term, and premature rupture of membranes (PROM), malpresentation at delivery, preterm delivery prior to 37, 34 and 32 weeks, caesarean delivery, intrauterine growth restriction/small for gestational age, foetal mortality and perinatal mortality. Results: 32 studies were included. CUAs increased significantly the risk of first/second trimester miscarriage (OR:1.54;95%CI:1.14-2.07), placental abruption (OR:5.04;3.60-7.04), PROM (OR:1.71;1.34-2.18), foetal malpresentation at delivery (OR:21.04;10.95-40.44), preterm birth (adjusted OR:4.34;3.59-5.21), a caesarean delivery (adjusted OR:7.69;4.17-14.29), intrauterine growth restriction/small for gestational age (adjusted OR:50;6.11-424), foetal mortality (OR:2.07;1.56-2.73) and perinatal mortality (OR:3.28;2.01-5.36). Conclusions: CUA increases the risk of complications during pregnancy, delivery, and postpartum. Complications most frequent in CUA patients were preterm delivery, foetal malpresentation, and caesarean delivery. What is new?: Bicornuate uterus was associated with the highest number of adverse outcomes, followed by didelphys, subseptate and septate uterus.

Application of Unmanned Aerial Vehicle (UAV) Sensing for Water Status Estimation in Vineyards under Different Pruning Strategies.

Pruning determines the plant water status due to its effects on the leaf area and thus the irrigation management. The primary aim of this study was to assess the use of high-resolution multispectral imagery to estimate the plant water status through different bands and vegetation indexes (VIs) and to evaluate which is most suitable under different pruning management strategies. This work was carried out in 2021 and 2022 in a commercial Merlot vineyard in an arid area of central Spain. Two different pruning strategies were carried out: mechanical pruning and no pruning. The stem water potential was measured with a pressure chamber (Ψstem) at two different solar times (9 h and 12 h). Multispectral information from unmanned aerial vehicles (UAVs) was obtained at the same time as the field Ψstem measurements and different vegetation indexes (VIs) were calculated. Pruning management significantly determined the Ψstem, bunch and berry weight, number of bunches, and plant yield. Linear regression between the Ψstem and NDVI presented the tightest correlation at 12 h solar time (R2 = 0.58). The red and red-edge bands were included in a generalised multivariable linear regression and achieved higher accuracy (R2 = 0.74) in predicting the Ψstem. Using high-resolution multispectral imagery has proven useful in predicting the vine water status independently of the pruning management strategy.

MLL2 mutation detection in 86 patients with Kabuki syndrome: a genotype-phenotype study.

Recently, pathogenic variants in the MLL2 gene were identified as the most common cause of Kabuki (Niikawa-Kuroki) syndrome (MIM#147920). To further elucidate the genotype-phenotype correlation, we studied a large cohort of 86 clinically defined patients with Kabuki syndrome (KS) for mutations in MLL2. All patients were assessed using a standardized phenotype list and all were scored using a newly developed clinical score list for KS (MLL2-Kabuki score 0-10). Sequencing of the full coding region and intron-exon boundaries of MLL2 identified a total of 45 likely pathogenic mutations (52%): 31 nonsense, 10 missense and four splice-site mutations, 34 of which were novel. In five additional patients, novel, i.e. non-dbSNP132 variants of clinically unknown relevance, were identified. Patients with likely pathogenic nonsense or missense MLL2 mutations were usually more severely affected (median 'MLL2-Kabuki score' of 6) as compared to the patients without MLL2 mutations (median 'MLL2-Kabuki score' of 5), a significant difference (p < 0.0014). Several typical facial features such as large dysplastic ears, arched eyebrows with sparse lateral third, blue sclerae, a flat nasal tip with a broad nasal root, and a thin upper and a full lower lip were observed more often in mutation positive patients.

[Evaluation of the physical and psychosocial consequences of the diastasis of the rectus abdominis and its interference in health: A mixed study]. / Evaluación de las consecuencias físicas y psicosociales de la diástasis de rectos abdominales y su interferencia en la salud: un estudio mixto.

INTRODUCTION: Diastasis rectus abdominis (DRA) is defined as the separation of the rectus abdominis along the linea alba. This condition can occur in both sexes, being frequent in women during pregnancy and pospartum. There is little evidence on the consequences of DRA on the quality of life of women. OBJECTIVE: The analysis of the perception of the symptoms of and its repercussion on a physical, psychological and social level in women affected by this condition. PATIENTS AND METHODS: Observational study through a semi-structured online survey, composed of 30 closed questions and 2 open ones. The inclusion criteria were adult Spanish-speaking women who had given birth and who presented abdominal diástasis. The data were analyzed quantitatively and the qualitative information was obtained through a content analysis of the open questions. RESULTS: 319 women with DRA were included. The results showed a negative effect of DRA on quality of life, functional capacities, and urogynecological and digestive health. Likewise, a negative impact was evidenced at an emotional level, on body image and poor self-perceived health. CONCLUSION: DRA has a negative impact on women's health. Women with DRA present an impairment of the quality of life and functional capacities, an alteration in body image, feelings of abandonment by health institutions, shame, sadness, powerlessness, lack of self-esteem, resignation and social pressure.

High resolution melting analysis for the identification of novel mutations in DKC1 and TERT genes in patients with dyskeratosis congenita.

Dyskeratosis congenita (DC) is a rare inherited bone-marrow failure syndrome with high clinical heterogeneity. Cells derived from DC patients present short telomeres at early ages, as a result of mutations in genes encoding components of the telomerase complex (DKC1, TERC, TERT, NHP2 and NOP10), or the shelterin complex (TINF2). However, mutations have been identified only in around 50% of the cases, indicating that other genes could be involved in the development of this disease. Indeed, mutations in TCBA1 or chromosome segment C16orf57 have been described recently. We have used HRM technology to perform genetic analysis in the above mentioned genes, in Spanish patients showing both, some clinical features of DC and short telomeres. The mutations have been identified by PCR amplification of DC genes followed by high resolution melting (HRM) and direct DNA sequencing analysis. We have identified seven new families with DC, three with X-linked DC and four with autosomal dominant DC, in which we have found two novel mutations in DKC1 (p.His68Arg and p.Lys390del) and four novel mutations in TERT gene (p.Pro530Leu, p.Arg698Trp, p.Arg971His and p.Arg698Gln). The results show that the use of HRM analysis enables a rapid and inexpensive identification of mutations in dyskeratosis congenita associated genes.

Equine sarcoids: Bovine Papillomavirus type 1 transformed fibroblasts are sensitive to cisplatin and UVB induced apoptosis and show aberrant expression of p53.

Bovine papillomavirus type 1 infects not only cattle but also equids and is a causative factor in the pathogenesis of commonly occurring equine sarcoid tumours. Whilst treatment of sarcoids is notoriously difficult, cisplatin has been shown to be one of the most effective treatment strategies for sarcoids. In this study we show that in equine fibroblasts, BPV-1 sensitises cells to cisplatin-induced and UVB-induced apoptosis, a known cofactor for papillomavirus associated disease, however BPV-1 transformed fibroblasts show increased clonogenic survival, which may potentially limit the therapeutic effects of repeated cisplatin treatment. Furthermore we show that BPV-1 increases p53 expression in sarcoid cell lines and p53 expression can be either nuclear or cytoplasmic. The mechanism and clinical significance of increase/abnormal p53 expression remains to be established.

Consumers' willingness to pay for beef direct sales. A regional comparison across the Pyrenees.

Willingness to pay (WTP) for direct market of beef is investigated in two Spanish and two French regions located on both sides of the Pyrenees. Given the novelty of this distribution system, especially in Spain, a contingent valuation approach is undertaken, and a double-bounded model is estimated. Different patterns of awareness, use and WTP are found across regions. Likewise, the profile of current and potential users of direct sale chains is investigated. Experience in the different stages involved from choice to final consumption of beef, intensity of varied beef consumption, familiarity with direct market of food in general, and beef in particular, are some of the relevant factors to explain WTP and the probability of getting engaged into a direct distribution system of beef.

A randomised controlled trial for the effectiveness of intra-articular Ropivacaine and Bupivacaine on pain after knee arthroscopy: the DUPRA (DUtch Pain Relief after Arthroscopy)-trial.

PURPOSE: In this double-blinded, randomised clinical trial, the aim was to compare the analgesic effects of low doses of intra-articular Bupivacaine and Ropivacaine against placebo after knee arthroscopy performed under general anaesthesia. METHODS: A total of 282 patients were randomised to 10 cc NaCl 0.9%, 10 cc Bupivacaine 0.5% or 10 cc Ropivacaine 0.75%. Patients received the assigned therapy by intra-articular injection after closure of the portal. Pain and satisfaction were measured at one, 4 h and 5-7 days after arthroscopy with Numerical Rating Scale (NRS) -scores. NSAID consumption was also recorded. RESULTS: One-h NRS-scores at rest were higher in the NaCl group compared with the Bupivacaine group (P < 0.01), 1 h NRS-scores in flexion were higher in the NaCl group compared with the Bupivacaine (P < 0.01) and Ropivacaine (P < 0.01) groups. NRS-satisfaction at 4 h was higher for the Bupivacaine group compared with the NaCl group (P = 0.01). Differences in NRS-scores were significant but low in magnitude. NSAID consumption was lower in the Bupivacaine group compared with the NaCl group (P < 0.01). CONCLUSIONS: The results of this randomised clinical trial demonstrate improved analgesia after administration of low doses of intra-articular Bupivacaine and Ropivacaine after arthroscopy of the knee. Considering reports of Bupivacaine and Ropivacaine being chondrotoxic agents and the relatively small improvement on patient comfort found in this trial, it is advised to use systemic anaesthetic instead of intra-articular Bupivacaine or Ropivacaine for pain relief after knee arthroscopy.

Structural, dynamic, and hydration properties of quercetin and its aggregates in solution.

Quercetin is a flavonoid present in the human diet with multiple health benefits. Quercetin solutions are inhomogeneous even at very low concentrations due to quercetin's tendency to aggregate. We simulate, using molecular dynamics, three systems of quercetin solutions: infinite dilution, 0.22 M, and 0.46 M. The systems at the two highest concentrations represent regions of the quercetin aggregates, in which the concentration of this molecule is unusually high. We study the behavior of this molecule, its aggregates, and the modifications in the surrounding water. In the first three successive layers of quercetin hydration, the density of water and the hydrogen bonds formations between water molecules are smaller than that of bulk. Quercetin has a hydrophilic surface region that preferentially establishes donor hydrogen bonds with water molecules with relative frequencies from 0.12 to 0.46 at infinite dilution. Also, it has two hydrophobic regions above and below the planes of its rings, whose first hydration layers are further out from quercetin (≈0.3 Å) and their water molecules do not establish hydrogen bonds with it. Water density around the hydrophobic regions is smaller than that of the hydrophilic. Quercetin molecules aggregate inπ-stacking configurations, with a distance of ≈0.37 nm between the planes of their rings, and form bonds between their hydroxyl groups. The formation of quercetin aggregates decreases the hydrogen bonds between quercetin and the surrounding water and produces a subdiffusive behavior in water molecules. Quercetin has a subdiffusive behavior even at infinite dilution, which increases with the number of molecules within the aggregates and the time they remain within them.

Trajectories of prenatal alcohol exposure and behavioral outcomes: Findings from a community-based sample.

OBJECTIVE: To characterize patterns of prenatal alcohol exposure (PAE), and determine whether PAE trajectories were associated with behavior from a community-based sample of first-grade children. METHODS: Using data collected as part of the Collaboration of Fetal Alcohol Spectrum Disorders Prevalence study (n = 1663), we performed longitudinal cluster analysis on prenatal alcohol use reported for four time points around conception and pregnancy. From the sample, 638 respondents reported any alcohol use in pregnancy and were included in trajectories for average daily and maximum drinks per drinking day (max DDD). We then estimated the association with behavioral problems measured by the Child Behavior Checklist (CBCL) and Teacher Report Form (TRF) with multivariable linear regression. The reference group had 1025 children with no reported PAE. RESULTS: Five trajectories were selected to describe max DDD patterns: very low/discontinuing (n = 186), low/discontinuing (n = 111), very low/continuing (n = 47), med/high (n = 245), and high (n = 49). Six trajectories best described average daily alcohol use: very low/discontinuing (n = 378), very low/continuing (n = 98), low/continuing (n = 56), low/discontinuing (n = 37), medium/high (n = 35), and high (n = 31). When assessing max DDD trajectories for both the CBCL and TRF, individuals with PAE in the two highest trajectories and the very low/continuing trajectory had more behavioral problems relative to children with no PAE, although confidence intervals for most estimates included the null. PAE modeled as average drinks per day did not predict behavior in any consistent pattern. CONCLUSIONS: In this community-based sample, select PAE trajectories were associated with behavior, even at relatively low levels of PAE that continued later in gestation.