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Improved and cheaper molecular diagnostics allow the shift from "one size fits all" therapies to personalised treatments targeting the individual tumor. However, the wealth of potential targets based on comprehensive sequencing remains a yet unsolved challenge that prevents its routine use in clinical practice. Thus, we designed a workflow that selects the most promising treatment targets based on multi-omics sequencing and in silico drug prediction. In this study we demonstrate the workflow with focus on bladder cancer (BLCA), as there are, to date, no reliable diagnostics available to predict the potential benefit of a therapeutic approach. Within the TCGA-BLCA cohort, our workflow identified a panel of 21 genes and 72 drugs that suggested personalized treatment for 95% of patients-including five genes not yet reported as prognostic markers for clinical testing in BLCA. The automated predictions were complemented by manually curated data, thus allowing for accurate sensitivity- or resistance-directed drug response predictions. We discuss potential improvements of drug-gene interaction databases on the basis of pitfalls that were identified during manual curation.

Different methodologies for determining the dissociation equilibrium constant (K i ) of protein tight binding inhibitors are frequently found in the scientific literature. Taking into account that the K i value is the main parameter characterizing the inhibition strength, its determination often represents the first step during the characterization of a potential drug. The purpose of this review is to summarize the current information related to tight binding inhibitors K i values determination and discuss about the importance of different factors as the enzyme concentration, the inhibitor concentration dilution series, the enzyme-inhibitor incubation time and the dose-response data mathematical fitting. For this aim, the bi-functional SmCI protease inhibitor is used as a tool for exemplifying the experimental and mathematical steps performed during tight binding inhibitors K i values determination. In addition, the natural and the different recombinant forms of SmCI were used to go deeply into the comparison of some mathematic approaches that are frequently used in the literature. Finally, other biochemical techniques that could be potentially used for tight binding inhibitors K i values determination are also commented., Competing Interests: Declaration of Competing interest All authors declare there are not conflict of interest., (Copyright © 2020 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.)

Several plants from South America show strong antitumoral properties based on anti-proliferative and/or pro-apoptotic activities. In this work we aimed to identify selective cytotoxic compounds that target BRCA1-deficient cancer cells by Synthetic Lethality (SL) induction. Using a high-throughput screening technology developed in our laboratory, we analyzed a collection of extracts from 46 native plant species from Argentina using a wide dose-response scheme. A highly selective SL-induction capacity was found in an alkaloidal extract from Zanthoxylum coco (Fam. Rutaceae). Bio-guided fractionation coupled to HPLC led to the identification of active benzophenanthridine alkaloids. The most potent SL activity was found with the compound oxynitidine, which showed a remarkably low relative abundance in the active fractions. Further validation experiments were performed using the commercially available and closely related analog nitidine, which showed SL-induction activity against various BRCA1-deficient cell lines with different genetic backgrounds, even in the nanomolar range. Exploration of the underlying mechanism of action using BRCA1-KO cells revealed AKT and topoisomerases as the potential targets responsible of nitidine-triggered SL-induction. Taken together, our findings expose an unforeseen therapeutic activity of alkaloids from Zanthoxylum -spp. that position them as novel lead molecules for drug discovery., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Garcia, Pansa, Pacciaroni, García, Gonzalez, Oberti, Bocco, Carpinella, Barboza, Nicotra and Soria.)

Background: The Afirma gene expression classifier (GEC) has been used to aid in the diagnosis and management of thyroid nodules having Bethesda category III fine-needle aspiration cytologic diagnosis (B3 nodules). The American Thyroid Association sonographic risk stratification system for thyroid nodules (ATA-US) may stratify B3 nodules and aid in the decision to order a molecular test. The aim of this study was to assess the association between ATA-US and GEC as well as to determine their individual and combined diagnostic performances when applied to B3 nodules. Methods: A retrospective single-center study included B3 nodules that had undergone evaluation by GEC. Each ultrasound was reviewed by three radiologists, and nodules were classified using the 2015 ATA sonographic risk categories. Nodules were determined to be benign or malignant based on surgical pathology or minimum 11 months of follow-up. Positive predictive values (PPV) and negative predictive values (NPV) were calculated for GEC, ATA-US, and GEC across all ATA-US categories. Results: One hundred twenty-six B3 nodules with GEC results were included and deemed benign or malignant based on final pathology or follow-up. Prevalence of malignancy was 32%. The rate of malignancy was similar in the ATA-US high suspicion (HS) and intermediate suspicion (IS) categories at 42% and 38%, respectively; and lower in nodules with low suspicion sonography (LS) and very low suspicion sonography (VLS) at 23% and 11%, respectively. The PPV and NPV of ATA-US was calculated by designating HS or IS sonography as a "positive" test and the lower risk categories as "negative." ATA-US had a PPV of 40% and NPV of 79%. The GEC PPV was 40% and NPV was 83%. The PPV of GEC was 50% in nodules with HS or IS ATA-US and lower at 28% and 20%, respectively, in LS and VLS nodules. The NPV of GEC was 80% in HS, 77% in IS, 84% in LS, and 100% in VLS sonography categories. Conclusions: In B3 nodules, ATA-US and GEC have similar diagnostic performance. The PPV of GEC varies across ATA-US categories, while the NPV remains similar. These data support the need for future prospective studies.

Purpose: To survey risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) practice and advice regarding hormone replacement therapy (HRT) in women with Lynch syndrome., Methods: We conducted a survey in 31 contributing centers from the Prospective Lynch Syndrome Database (PLSD), which incorporates 18 countries worldwide. The survey covered local policies for risk-reducing hysterectomy and BSO in Lynch syndrome, the timing when these measures are offered, the involvement of stakeholders and advice regarding HRT., Results: Risk-reducing hysterectomy and BSO are offered to path _ MLH1 and path_MSH2 carriers in 20/21 (95%) contributing centers, to path_MSH6 carriers in 19/21 (91%) and to path_PMS2 carriers in 14/21 (67%). Regarding the involvement of stakeholders, there is global agreement (~90%) that risk-reducing surgery should be offered to women, and that this discussion may involve gynecologists, genetic counselors and/or medical geneticists. Prescription of estrogen-only HRT is offered by 15/21 (71%) centers to women of variable age range (35-55 years)., Conclusions: Most centers offer risk-reducing gynecological surgery to carriers of path_MLH1 , path_MSH2 and path_MSH6 variants but less so for path_PMS2 carriers. There is wide variation in how, when and to whom this is offered. The Manchester International Consensus Group developed recommendations to harmonize clinical practice across centers, but there is a clear need for more research.

Satellite cells are the myogenic stem and progenitor population found in skeletal muscle. These cells typically reside in a quiescent state until called upon to support repair, regeneration, or muscle growth. The activities of satellite cells are orchestrated by systemic hormones, autocrine and paracrine growth factors, and the composition of the basal lamina of the muscle fiber. Several key intracellular signaling events are initiated in response to changes in the local environment causing exit from quiescence, proliferation, and differentiation. Signals emanating from Notch, wingless-type mouse mammary tumor virus integration site family members, and transforming growth factor-β proteins mediate the reversible exit from growth 0 phase while those initiated by members of the fibroblast growth factor and insulin-like growth factor families direct proliferation and differentiation. Many of these pathways impinge upon the myogenic regulatory factors (MRF), myogenic factor 5, myogenic differentiation factor D, myogenin and MRF4, and the lineage determinate, Paired box 7, to alter transcription and subsequent satellite cell decisions. In the recent past, insight into mouse transgenic models has led to a firm understanding of regulatory events that control satellite cell metabolism and myogenesis. Many of these niche-regulated functions offer subtle differences from their counterparts in livestock pointing to the existence of species-specific controls. The purpose of this review is to examine the mechanisms that mediate large animal satellite cell activity and their relationship to those present in rodents., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Covalent organic frameworks (COFs) are commonly synthesized under harsh conditions yielding unprocessable powders. Control in their crystallization process and growth has been limited to studies conducted in hazardous organic solvents. Herein, we report a one-pot synthetic method that yields stable aqueous colloidal solutions of sub-20 nm crystalline imine-based COF particles at room temperature and ambient pressure. Additionally, through the combination of experimental and computational studies, we investigated the mechanisms and forces underlying the formation of such imine-based COF colloids in water. Further, we show that our method can be used to process the colloidal solution into 2D and 3D COF shapes as well as to generate a COF ink that can be directly printed onto surfaces. These findings should open new vistas in COF chemistry, enabling new application areas.

Objective: To report our clinical experience with bevacizumab in a cohort of Hereditary Hemorrhagic Telangiectasia (HHT) patients with severe hepatic involvement and/or refractory anemia., Methods: Observational, ambispective study of the Institutional Registry of HHT at Hospital Italiano de Buenos Aires. Patients were treated with bevacizumab due to iron deficiency refractory anemia secondary to nasal/gastrointestinal bleeding and/or high output cardiac failure. We describe basal clinical data, bevacizumab schedules, efficacy outcomes and adverse events. Wilcoxon signed ranks test and longitudinal analysis were conducted., Results: Twenty adult patients were included from July 2013 to June 2019. Clinical indications were: 13 for anemia, 4 for heart failure and 3 for both. In the anemia group, median pretreatment hemoglobin was 8.1 g/dl [IQR: 7.2-8.4] and median transfusion requirement was 4 units [2-6]. In heart failure group, pretreatment median cardiac index was 4.5 L/min/m2 [4.1-5.6] and cardiac output was 8.3 L/min [7.5-9.2]. Bevacizumab 5 mg/kg/dose every 2 weeks for 6 applications was scheduled. By the end of induction, median hemoglobin at 3 months was 10.9 g/dl [9.5-12.8] (p = 0.01) and median transfusion requirement 0 units [0-1] (p<0.01), and this effect was more or less sustained during a year. Regarding heart failure group, two patients had complete hemodynamic response and achieved liver transplantation and two had partial response. No serious adverse events were registered., Conclusion: Bevacizumab is a promising line of treatment for HHT patients with refractory anemia. For patients with high output cardiac failure, bevacizumab may be useful as bridge therapy awaiting for liver transplantation., Competing Interests: The authors have declared that no competing interests exist.

Objective: The aim of this study is to describe the clinical manifestations and treatment options of patients having dural sinus malformation with giant pouch (DSMGP) in a tertiary pediatric center., Introduction: Dural sinus malformation with giant pouch (DSMGP) is a rare vascular malformation affecting fetuses, newborns, and infants. It is characterized by a dilated dural sinus frequently thrombosed with arteriovenous fistula (AVF) in its wall. There is a few information about symptoms, best treatment, and prognosis of the disease., Material and Methods: Medical charts of cases of DSMGP were retrospectively analyzed from January 2010 to January 2019. Our hospital is a pediatric tertiary center. An adult patient managed by the authors in another institution was added to the series., Results: Eight pediatric patients from 0 to 9 months were managed, four were males. The adult patient was a 40-year-old male. Symptoms were mass effect in 4 pediatric cases. Exophthalmos was present in the pediatric case and adult case. Both cases had venolymphatic malformation of the orbit. Congestive heart failure (CHF), epistaxis and facial vein engorgement, and intracranial hemorrhage (ICH) were the symptoms in other 3 cases. A child has spontaneous resolution of the disease., Discussion: Transverse sinus and superior sagittal sinus are affected more commonly. Patients with totally thrombosed pouch had mass effect symptoms. These cases were managed by surgical excision. When AVFs are present, clinical manifestations were secondary to cerebral venous hypertension or cardiac overload. If cavernous sinus drained the shunt (capture), epistaxis and facial veins engorgement could be present. AVFs are amenable to embolization, achieving the control of venous hypertension in most cases. Cavernous malformation could be present and must be controlled because its enlargement could be a sign of uncontrolled venous hypertension. On the other hand, DSMGP can be accompanied by venolymphatic malformation conforming a cerebral venous metameric syndrome.

Purpose: Pathogenic variants affecting MLH1, MSH2, MSH6, and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific cancer risks according to gene and gender and to determine survival after cancer., Methods: We conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 follow-up years., Results: There were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate. Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Ten-year crude survival was over 80% following colon, endometrial, or ovarian cancer., Conclusion: Management guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers.

Postexercise skeletal muscle repair is dependent on the actions of satellite cells (SCs). The signal(s) responsible for activation of these normally quiescent cells in the horse remain unknown. The objective of the experiment was to determine whether submaximal exercise or tributyrin (TB) supplementation is sufficient to stimulate SC activation. Adult geldings were fed a control diet (n = 6) or a diet containing 0.45% TB (n = 6). After 30 d, the geldings performed a single bout of submaximal exercise. Middle gluteal muscle biopsies and blood were collected on days -1, 1, 3, and 5 relative to exercise. Diet had no effect on any parameter of physical performance. Total RNA isolated from the gluteal muscle of TB fed geldings contained greater (P < 0.05) amounts of myogenin mRNA than controls. Satellite cell isolates from TB supplemented horses had a greater (P = 0.02) percentage of proliferating cell nuclear antigen immunopositive (PCNA+) SC than controls after 48 h in culture. Submaximal exercise was sufficient to increase (P < 0.05) the percentage of PCNA(+) cells in all isolates obtained during recovery period. No change in the amount of gluteal muscle Pax7 mRNA, a lineage marker of SCs, occurred in response to either diet or exercise. Our results indicate that both submaximal exercise and TB prime SCs for activation and cell cycle reentry but are insufficient to cause an increase in Pax7 expression during the recovery period., (© The Author(s) 2019. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We aimed to assess the current genetics practice to manage patients with Lynch syndrome (LS) across Latin America. A Latin American LS survey was sent out to 52 centres/registries, comprising a total of 12 countries from the region. Overall, 33 centres completed the survey, of which the oldest LS registry was established in 1992 in Sao Paulo (Brazil), and the youngest this year in San Jose (Costa Rica). In total, 87% (26/30) of the participating centres/registries belonging to the nine countries are performing genetic testing. Overall, 1352 suspected families were sequenced. Pathogenic variants were identified in 34% of the families, with slightly differing distribution of variants between females and males. Path&#95;MLH1 variants were identified in 39% of females and 50% of males (p = 0.023), while path&#95;MSH2 were identified in 37% of females and males, followed by path&#95;PMS2 in 11% of females and 8% of males, path&#95;MSH6 in 13% of females and 3% of males (p < 0.001) and path&#95;EPCAM in 0.3% of females and 2% of males. In Latin America, 9 of 12 (75%) participating countries had implemented healthcare for LS. LS screening is inconsistently applied within Latin America healthcare systems because of structural differences in the healthcare systems between the countries., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path&#95;MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path&#95;MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path&#95;MSH6 and path&#95;PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path&#95;MLH1 and path&#95;MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%-80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency., (© 2018 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Aims: Current available data on cytokeratin 7 (CK7) immunostaining pattern in the clear cell renal cell carcinoma (RCC) spectrum is conflicting. The aim of this study was to assess CK7 immunoreactivity within the spectrum of clear cell renal neoplasms, including clear cell RCC, multicystic renal neoplasm of low malignant potential and clear cell papillary RCC-like tumours., Methods and Results: We analysed two clones of CK7 and two tumour blocks for a total of 75 cases divided into five distinct groups: (i) low-grade clear cell RCC, (ii) high-grade clear cell RCC, (iii) multicystic renal neoplasm of low malignant potential, (iv) clear cell RCC with cystic changes and (v) clear cell papillary RCC-like tumours. We found the highest CK7 reactivity in low-grade clear cell RCC, multicystic renal neoplasm of low malignant potential and clear cell papillary RCC-like groups, ranging from 60% to 93%., Conclusions: Our findings show that CK7 immunoreactivity in clear cell RCC is variable, and the extent of staining depends on the grade and architectural growth patterns of the tumours., (© 2018 John Wiley & Sons Ltd.)

Telehealth can overcome access and availability barriers that often impede receiving needed mental health services. This case report describes an interdisciplinary approach to treatment for an individual with chronic physical health conditions and comorbid mental health concerns, which resulted in high utilization (and associated costs) of preventable emergency services. The report describes clinical case progression on anxiety symptoms and emergency service utilization while concurrently highlighting telehealth-specific practice implications, especially as they pertain to training settings., (© 2018 Wiley Periodicals, Inc.)

Purpose: Pre-eclampsia is a multisystem disorder characterized by new-onset hypertension and proteinuria during pregnancy. Pre-eclampsia remains a major cause of maternal death in low-income countries. Vitamin D has a very diverse biological role in cardiovascular diseases. This study will evaluate the association of vitamin D levels and relevance to pre-eclampsia., Methods: We conducted a case-control study of women recruited from the GenPE (Genetics and Pre-eclampsia) Colombian registry. This is a multicenter case-control study conducted in eight Colombian cities. 25-Hydroxyvitamin D (25(OH)D) concentration was measured using liquid-chromatography-tandem mass spectrometry from 1013 women with pre-eclampsia and 1015 mothers without pre-eclampsia (controls)., Results: Fifty-two percent of women with pre-eclampsia were vitamin D deficient. The 25(OH)D concentrations were significantly lower in the pre-eclampsia (mean 29.99 ng/mL; 95% CI: 29.40-30.58 ng/mL) group compared to controls (mean 33.7 ng/mL; 95% CI: 33.20-34.30 ng/mL). In the unadjusted model, maternal vitamin D deficiency, defined by maternal 25(OH)D concentration <30 ng/mL, was associated with an increased probability of suffering from pre-eclampsia (OR 2.10; 95% CI, 1.75-2.51). After adjusting for covariates, a similarly increased probability of having pre-eclampsia was observed (OR 2.18; 95% CI, 1.80-2.64) among women with vitamin D deficiency, relative to controls., Conclusion: Although the results suggest that low maternal concentrations of 25(OH)D increase pre-eclampsia risk, this evidence may not be indicative of a causal association. Future studies are needed to confirm a definite causal relationship between concentrations of vitamin D and the risk of pre-eclampsia, by means of powered clinical trials., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Hepatocyte growth factor (HGF) signals mediate mouse skeletal muscle stem cell, or satellite cell (SC), reentry into the cell cycle and myoblast proliferation. Because the athletic horse experiences exercise-induced muscle damage, the objective of the experiment was to determine the effect of HGF on equine SC (eqSC) bioactivity. Fresh isolates of adult eqSC were incubated with increasing concentrations of HGF and the initial time to DNA synthesis was measured. Media supplementation with HGF did not shorten (P > 0.05) the duration of G0/G1 transition suggesting the growth factor does not affect activation. Treatment with 25 ng/mL HGF increased (P < 0.05) eqSC proliferation that was coincident with phosphorylation of extracellular signal-regulated kinase (ERK)1/2 and AKT serine/threonine kinase 1 (AKT1). Chemical inhibition of the upstream effectors of ERK1/2 or AKT1 elicited no effect (P > 0.05) on HGF-mediated 5-ethynyl-2'-deoxyuridine (EdU) incorporation. By contrast, treatment of eqSC with 2 µm Gö6983, a pan-protein kinase C (PKC) inhibitor, blocked (P < 0.05) HGF-initiated mitotic activity. Gene-expression analysis revealed that eqSC express PKCα, PKCδ, and PKCε isoforms. Knockdown of PKCδ with a small interfering RNA (siRNA) prevented (P > 0.05) HGF-mediated EdU incorporation. The siPKCδ was specific to the kinase and did not affect (P > 0.05) expression of either PKCα or PKCε. Treatment of confluent eqSC with 25 ng/mL HGF suppressed (P < 0.05) nuclear myogenin expression during the early stages of differentiation. These results demonstrate that HGF may not affect activation but can act as a mitogen and modest suppressor of differentiation., (© The Author(s) 2018. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

We aimed to compare the mortality risk between patients with affective disorders and dementia under treatment with antipsychotics. To do this, a matched-cohort study based on an electronic database of a tertiary teaching hospital in Argentina was performed. Antipsychotic exposure was defined as any antipsychotic drug initiated by the patient. Primary outcome was defined as all-cause mortality during the 5-year follow-up period. To estimate the association between baseline diagnosis (affective disorders vs. dementia) and all-cause mortality, we used a multivariate generalized linear model with robust standard errors. Of 1008 eligible patients, 114 age-matched pairs were included in the present study. The primary event occurred in 23 patients (20%) and 17 patients (15%) in the dementia and affective disorder group respectively. In the adjusted model, the risk of all cause mortality for the affective disorders group was 0.92 times the risk for the dementia group (95%CI, 0.54-1.59, p = 0.77). In conclusion, older patients with affective disorders starting antipsychotic treatment presented with a similar risk of all-cause mortality during the 5-year follow-up when compared to older patients with dementia who were also initiating either typical or atypical antipsychotic medications. Closer medical attention to older patients with mental conditions under antipsychotic treatment remains warranted., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Introduction: Patients with haemophilia may have lower levels of bone mineral density (BMD) compared with the general population. Moreover, haemophilic patients have increased risk factors for low bone mineral density (LBMD) such as arthropathy and resulting immobility, increasing their risk for osteoporosis and fractures., Aim: To assess the prevalence of LBMD and associated risk factors among a group of Colombian haemophilic patients., Methods: In this case-control study, 90 patients with haemophilia A and B, over the age of five, were recruited. Controls were healthy participants matched by age, gender, body mass index (BMI), socioeconomic status, and race. All participants underwent dual energy X-ray absorptiometry (DXA) and the Global Physical Activity Questionnaire. Blood tests were collected to evaluate LBMD determinants in cases., Results: BMD was lower in cases than in the control group. BMD of femoral necks was 0.907 g/cm 2 in cases vs. 1.020 g/cm 2 in controls (P = .019), and BMD of hips 0.930 g/cm 2 in cases vs. 1030 g/cm 2 in controls (P = .019). The greater the severity of haemophilia, the lower BMD in spine, femoral neck, and hips. Elevated C-protein levels were found in 44.1% of patients with LBMD and 14.8% with normal BMD (P = .003). The study found an adjusted prevalence ratio of 2.11, indicating that haemophilic patients are two times more likely to have LBMD (CI95% = 1.43-3.11 P < .001)., Conclusion: Results from the present study showed that haemophilia was associated with a higher frequency of LBMD. Severity of haemophilia, haemophilic arthropathy, and elevated C-reactive protein levels was directly associated with LBMD., (© 2018 John Wiley & Sons Ltd.)

Inactivating mutations in the MLH1 gene cause the cancer predisposition Lynch syndrome, but for small coding genetic variants it is mostly unclear if they are inactivating or not. Nine such MLH1 variants have been identified in South American colorectal cancer (CRC) patients (p.Tyr97Asp, p.His112Gln, p.Pro141Ala, p.Arg265Pro, p.Asn338Ser, p.Ile501del, p.Arg575Lys, p.Lys618del, p.Leu676Pro), and evidence of pathogenicity or neutrality was not available for the majority of these variants. We therefore performed biochemical laboratory testing of the variant proteins and compared the results to protein in silico predictions on structure and conservation. Additionally, we collected all available clinical information of the families to come to a conclusion concerning their pathogenic potential and facilitate clinical diagnosis in the affected families. We provide evidence that four of the alterations are causative for Lynch syndrome, four are likely neutral and one shows compromised activity which can currently not be classified with respect to its pathogenic potential. The work demonstrates that biochemical testing, corroborated by congruent evolutionary and structural information, can serve to reliably classify uncertain variants when other data are insufficient., (© 2018 Wiley Periodicals, Inc.)

Purpose: The purpose of this study was to answer the following clinical question: among patients who have their third molars (M3s) removed, do those who receive only postoperative antibiotics compared with those who receive no perioperative antibiotics have a lower frequency of postoperative inflammatory complications?, Materials and Methods: The authors designed and implemented a prospective cohort study and enrolled a sample of patients who had at least 1 M3 removed in an ambulatory private practice setting from June 2011 through May 2012 by oral and maxillofacial surgeons participating in a practice-based research collaborative. The predictor variable was postoperative antibiotic use categorized as postoperative antibiotics alone or no antibiotics. The primary outcome variable was the presence or absence of an inflammatory complication (ie, alveolar osteitis or surgical site infection) after M3 removal. Descriptive, bivariate, and multiple logistic regression statistics (adjusted for clustering within surgical practices) were computed to measure the association between postoperative antibiotic use alone and inflammatory complications after M3 removal, with statistical significance set at a P value less than or equal to .05., Results: The study sample was composed of 1,877 patients having 5,631 M3s removed, of which 61% received postoperative antibiotics only. The overall inflammatory complication frequencies in the groups receiving postoperative antibiotic only and no antibiotic were 4.3 and 7.5%, respectively (P = .003). After adjusting for differences between the 2 study groups and clustering of patients within surgical practices, postoperative antibiotic use was associated with a 40% decreased risk of developing postoperative inflammatory complications (P = .04) with marginal statistical significance., Conclusions: The results of this study suggest that postoperative antibiotic therapy is associated with a statistically meaningful decreased risk of inflammatory complications after M3 removal compared with no antibiotic therapy., (Copyright © 2017 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Introduction: Ultrasound is increasingly used as an adjunct in the diagnosis of neuromuscular disease by measuring muscle thickness and echointensity (EI). Reproducibility is limited because of variations in scanning technique and proprietary algorithms that alter EI values., Methods: We developed a standardized scanning protocol and a portable machine without any postimaging processing. Ten subjects underwent scanning of 6 muscles by 3 sonographers on 2 separate days. One of the sonographers repeated the protocol with 4 different machine/transducer combinations. Gray-scale values were measured from each image with the use of a region of interest (ROI) box., Results: Combined intraclass correlation coefficients were 0.92 (intra-rater), 0.88 (inter-rater), and 0.96 (inter-system). The biceps had the highest variability (coefficient of variance [COV] 12.7%), and the medial gastrocnemius had the lowest variability (COV 7.4%)., Conclusions: We demonstrate excellent reliability of a reproducible ultrasound system for gray-scale analysis of muscle that has potential applicability as a screening tool for neuromuscular disease. Muscle Nerve 56: 408-412, 2017., (© 2016 Wiley Periodicals, Inc.)

Background: Dermatopathology is considered the gold standard for melanoma diagnosis, but a subset of cases is difficult to diagnose by histopathology., Objective: The goals of this study were to measure the accuracy of histopathologic features in difficult-to-diagnose melanocytic tumors and the interobserver agreement of those features., Methods: This is a case-control study of histopathologic features of melanoma in 100 difficult-to-diagnose melanocytic neoplasms (40 melanomas and 60 nevi). Slides were blindly evaluated by 5 dermatopathologists. Frequencies, predictive values, and interobserver agreement were calculated. Univariate and multivariate logistic regression analyses were performed to identify the most influential features in arriving at a diagnosis of melanoma., Results: Asymmetry, single-cell melanocytosis, solar elastosis, pagetoid melanocytosis, and broad surface diameter were most influential in arriving at a diagnosis of melanoma. Asymmetry and single-cell melanocytosis were most predictive of melanoma. Fleiss kappa was <0.6 for interobserver agreement in 9/10 histopathologic features of melanoma., Limitations: This study is limited by the small sample size, selection bias, and binary classification of melanocytic lesions., Conclusion: Our results indicate histopathologic features of melanoma in difficult-to-diagnose lesions vary in accuracy and reproducibility., (Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To analyse pelvic floor muscle strength (PFMS) and urinary and anal incontinence (UI and AI) in the postpartum period., Method: Cross-sectional study carried out with women in their first seven months after child birth. Data were collected through interviews, perineometry (Peritron™), and the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF)., Results: 128 women participated in the study. The PFMS mean was 33.1 (SD=16.0) cmH2O and the prevalence of UI and AI was 7.8% and 5.5%, respectively. In the multiple analyses, the variables associated with PFMS were type of birth and cohabitation with a partner. Newborn's weight, previous pregnancy, UI during pregnancy, and sexual activity showed an association with UI after child birth. Only AI prior to pregnancy was associated with AI after childbirth., Conclusion: Vaginal birth predisposes to the reduction of PFMS, and caesarean section had a protective effect to its reduction. The occurrence of UI during pregnancy is a predictor of UI after childbirth, and women with previous pregnancies and newborns with higher weights are more likely to have UI after childbirth.AI prior to pregnancy is the only risk factor for its occurrence after childbirth. Associations between PFMS and cohabitation with a partner, and between UI and sexual activity do not make possible to conclude that these variables are directly associated., Objetivo: Analisar a força dos músculos do assoalho pélvico e a incontinência urinária e anal no período pós-parto., Método: Estudo transversal realizado com mulheres nos primeiros 7 meses após o parto. Os dados foram coletados por meio de entrevista, da perineometria (Peritron™) e do International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF)., Resultados: Participaram do estudo 128 mulheres. A média da força dos músculos do assoalho pélvico foi 33,1 (d.p.=16,0) cmH2O e a prevalência de incontinência urinária e incontinência anal foi de 7,8% e 5,5%, respectivamente. Na análise múltipla, as variáveis associadas à força dos músculos do assoalho pélvico foram tipo de parto atual e coabitação com o parceiro. Peso do recém-nascido, gestação anterior, incontinência urinária na gestação e atividade sexual mostraram associação. Apenas a incontinência anal prévia à gestação associou-se à incontinência anal após o parto., Conclusão: O parto vaginal predispõe à redução da força dos músculos do assoalho pélvico, e a cesariana exerce função protetora à sua redução. A ocorrência de incontinência urinária na gestação é preditora da incontinência urinária após o parto, e as mulheres com gestação anterior e recém-nascido de maior peso têm maior propensão em apresentar incontinência urinária após o parto. Incontinência anal prévia à gestação é o único fator de risco para sua ocorrência após o parto. As associações entre força dos músculos do assoalho pélvico e coabitação com o parceiro e entre incontinência urinária e atividade sexual não permitem concluir que essas variáveis estejam diretamente relacionadas.

Objective: To implement care practices for perineal trauma prevention and repairing in normal birth., Method: Quasi-experimental study conducted at Hospital da Mulher Mãe-Luzia, in Macapá, AP, Brazil. Seventy-four (74) nurses and obstetricians and 70 post-partum women were interviewed and the records of 555 patients were analyzed. The study was conducted in three stages: pre-audit and baseline audit (phase 1); educational intervention and implementation of best practices (phase 2); post-implementation audit (phase 3). Data was analyzed by comparison of the results of phases 1 and 3., Results: Following the educational intervention, a lower number of health professionals encouraged directed pushing, performed episiotomies and repaired first-degree lacerations; more women reported lithotomy position; more patient records indicated the use of Vicryl™ to suture the perineal mucosa and skin., Conclusion: The educational intervention improved birth care and perineal outcomes. Nevertheless, gaps were identified in the implementation of evidence, as well as inappropriate perineal care management.

Purpose: The role of antibiotic use in third molar (M3) surgery is controversial. The purpose of this study was to measure the association between antibiotic use and postoperative inflammatory complications after M3 surgery in the community office-based ambulatory private practice setting., Materials and Methods: The authors designed and implemented a prospective cohort study and enrolled a sample composed of patients who had at least one M3 removed in a private practice setting by oral and maxillofacial surgeons participating in a practice-based research collaborative from June 2011 through May 2012. The predictor variable was antibiotic use of any type, categorized as yes or no. The primary outcome variable was the presence or absence of an inflammatory complication, specifically surgical site infection (SSI) or alveolar osteitis (AO), after M3 removal. Descriptive, bivariate, and multiple logistic regression statistics were computed to measure the association between antibiotic use and inflammatory complications after M3 removal, with statistical significance set at a P value less than or equal to .05., Results: The study sample was composed of 2,954 patients. Three fourths (75.2%) of the sample received antibiotics in some form. The overall inflammatory complication (AO or SSI) frequencies in the antibiotic and nonantibiotic groups were 5.0 and 7.5%, respectively (P = .012). After adjusting for differences between the two groups, statistical significance between the groups persisted., Conclusions: The results of this study suggest that antibiotic therapy, regardless of type, dose, frequency, or pattern of delivery, is associated with a decreased risk of inflammatory complications after M3 removal., (Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

After decades of unawareness about Lynch syndrome, the medical community in South America is increasingly interested and informed. The visits and support of mentors like H. T. Lynch had been crucial to this awakening. Several countries have at least one registry with skilled personnel in genetic counseling and research. However, this only represents a very restricted resource for the region. According to the GETH, there are 27 hereditary cancer care centers in South America (21 in Brazil, 3 in Argentina, 1 in Uruguay, 1 in Chile and 1 in Peru). These registries differ in fundamental aspects of function, capabilities and funding, but are able to conduct high quality clinical, research and educational activities due to the dedication and personal effort of their members, and organizational support. More support from the governments as well as the participation of the community would boost the initiatives of people leading these groups. Meantime, the collaboration among the South American registries and the involvement of registries and leaders from developed countries will allow to maximize the efficiency in caring for affected patients and their families. The aim of this article is to describe how the knowledge of LS began to be spread in South America, how the first registries were organized and to summarize the current state of progress. In addition, we will provide an update of the clinical and molecular findings in the region.

Adenomyoepithelioma (AME) is a biphasic neoplasm of epithelial and myoepithelial cells. It is most commonly found in the breast, although rare cases have been reported from the lung, salivary glands, and skin. There are 5 well-documented cases of cutaneous AME in the literature. We report a new case of cutaneous AME. Our case was commingled with apocrine hidrocystoma. This is the first report of cutaneous AME in a male patient and the first to describe SOX10 immunostaining in cutaneous AME. We review the literature on cutaneous AME and note the greater than chance colocalization with other adnexal tumors. We speculate that AME may represent localized overgrowth of myoepithelial cells within a pre-existent sweat gland tumor. Histopathologists should be aware of the potential of SOX10-positive myoepithelial neoplasms to mimic nodular melanocytic proliferations.

Purpose: To evaluate the safety of midazolam and diazepam for adolescents during third molar extraction and whether any differences in perioperative complications exist when using the 2 benzodiazepines alone or in combination., Materials and Methods: A prospective study was performed in adolescents (<21 yr old) who underwent at least 1 third molar extraction by an oral and maxillofacial surgeon in the ambulatory setting from January 2001 through December 2010 using the Oral and Maxillofacial Surgery Outcomes System. The primary predictor variable was type of benzodiazepine used, divided into the total number of patients who received diazepam with or without midazolam. The outcome of interest was adverse complications resulting from anesthesia. Multivariable logistic regression was applied to measure the association between benzodiazepine type and adverse complications., Results: Patients in the diazepam group (n = 4,213) and in the combination group (n = 426) had a complication rate of 1.4%, whereas those in the midazolam group (n = 13,451) had a complication rate of 1.0% (P = .027). Multiple logistic regression analysis showed a 50% increased odds of adverse complications in patients receiving diazepam (adjusted odds ratio = 1.50; 95% confidence interval, 1.05 to 2.16; P = .027)., Conclusions: Adolescent patients who received intravenous diazepam during third molar procedures had an increased odds of anesthesia-related complications compared with those given midazolam., (Copyright © 2016 The American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: Benchmark statistics are used in quality assurance/quality improvement processes. The purposes of the present report are to 1) review the rationale for a new specialty-specific benchmark study, 2) summarize the methods to create a practice-based research collaborative (P-BRC) designed for collecting data to create benchmarks, and 3) describe the characteristics of the P-BRC surgeon participants., Materials and Methods: The study was designed as a prospective cohort study. We created a P-BRC composed of randomly selected American Association of Oral and Maxillofacial Surgeons (AAOMS) members in private practice in the United States, who agreed to enroll patients scheduled to receive anesthesia of any type in the office-based ambulatory setting. The study variables included clinician demographics and their P-BRC status, grouped as 1) invited, active participants, 2) invited, inactive participants, and 3) uninvited AAOMS members. The P-BRC participants collected data for dozens of variables from their patients related to anesthesia. If the procedure was third molar (M3) surgery, additional M3 procedure-specific data were collected. Data analyses were composed of computing descriptive and bivariate statistics. Preliminary sample size estimates suggested that the P-BRC should include 300 surgeons to produce estimates with a ±5% error., Results: During the 1-year study interval, 642 surgeons (11.8%) were invited to join the P-BRC from a population of 5,455 eligible AAOMS members. The 124 active participants in the P-BRC contributed 6,344 subjects to the anesthesia data set and 2,978 subjects who had had 9,207 M3s removed to the M3 data set. The active participants in the P-BRC were younger and more likely to be board-certified than were the inactive participants (P < .05). Details of the anesthesia and M3 variables will follow in future reports., Conclusions: Despite vigorous efforts, we did not achieve our stated goal of creating a P-BRC composed of a random sample of 300 AAOMS members. With the current P-BRC sample, variables with very high (>93%) or very low (<7%) frequency estimates will produce estimates with the desired range of ±5% error. The P-BRC includes a sample of self-selected, not random, participants and is well-characterized in terms of age, gender, board-certification status, academic degrees, and geographic distribution., (Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: To examine the complications resulting from moderate sedation versus deep sedation/general anesthesia for adolescent patients undergoing third molar extraction and determine whether any differences in complication risks exist between the 2 levels of sedation., Materials and Methods: We performed a prospective study of the Oral and Maxillofacial Surgery Outcomes System from January 2001 to December 2010. The primary predictor variable was the level of sedation, divided into 2 groups: moderate sedation versus deep sedation/general anesthesia. The primary outcome was the incidence of adverse complications resulting from the sedation level. Differences in the cohort characteristics were analyzed using the independent samples t test, χ(2) test, and analysis of variance, as appropriate. Multivariable logistic regression was used to measure the effect the level of sedation had on the adverse complication rate., Results: Patients in the moderate sedation group had a complication rate of 0.5%, and patients in the deep sedation/general anesthesia group had a complication rate of 0.9%. Compared with moderate sedation, deep sedation/general anesthesia did not pose a significantly increased risk of adverse anesthesia complications (adjusted odds ratio 1.63, 95% confidence interval 0.95 to 2.81; P = .077)., Conclusions: The results of our study have shown that the risk of adverse anesthesia complications is not increased when choosing between moderate and deep sedation/general anesthesia for adolescent patients undergoing third molar extraction., (Copyright © 2016 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Purpose: To review outcomes of continuous motor/somatosensory-evoked potential (MEP/SSEP) monitoring, cerebrospinal fluid drainage, and selective use of iliofemoral conduits in patients undergoing endovascular repair of descending thoracic aneurysm (DTA) and thoracoabdominal aortic aneurysms (TAAAs)., Methods: The clinical data of 49 patients (mean age 75±8 years; 38 men) who underwent endovascular repair of DTA and TAAAs (2011-2014) were reviewed. All patients had cerebrospinal fluid drainage, permissive hypertension (mean arterial pressure ≥80 mm Hg), and MEP/SSEP monitoring. There were 44 (90%) patients with TAAAs and 5 (10%) with DTA. Types I and II TAAAs were repaired in staged procedures. Iliofemoral conduits were used for small iliac arteries and to minimize time of lower extremity ischemia in patients with difficult anatomy. In patients with changes in MEP/SSEPs, a standardized protocol was employed to optimize spinal cord perfusion and restore lower extremity blood flow. Endpoints were mortality, spinal cord injury (SCI), and lower extremity ischemic complications., Results: Sixteen (33%) patients had staged TAAA repair. A total of 163 visceral arteries were targeted by fenestrations and branches (mean 3.7±1.0 vessels/patient). Temporary iliofemoral conduits were used in 16 limbs/14 patients. A stable MEP/SSEP was achieved in all patients. Thirty-one (63%) patients had a ≥75% decrease in MEP/SSEP amplitude in 50 limbs starting on average 75±28 minutes after obtaining vascular access. MEP/SSEP amplitude improved with maneuvers in 12 (39%) patients and returned to baseline with restoration of lower extremity flow in all except 1 patient who developed immediate SCI. Thirty-day mortality was 4%. Three (6%) patients had SCI, 2 permanent and 1 temporary at 14 days. There were no lower extremity ischemic complications., Conclusion: Neuromonitoring predicted immediate SCI and allowed use of a protocol to optimize spinal cord and lower extremity perfusion during complex endovascular aortic repair. Larger clinical experience is needed to evaluate the efficacy of neuromonitoring to prevent SCI., (© The Author(s) 2015.)

E-learning has been widely used in the infection control field and has been recommended for use in hand hygiene (HH) programs by the World Health Organization. Such strategies are effective and efficient for infection control, but factors such as learner readiness for this method should be determined to assure feasibility and suitability in low- to middle-income countries. We developed a tailored, e-learning, Spanish-language HH course based on the WHO guidelines for HH in healthcare settings for the pediatric cancer center in Guatemala City. We aimed to identify e-readiness factors that influenced HH course completion and evaluate HCWs' satisfaction. Pearson's chi-square test of independence was used to retrospectively compare e-readiness factors and course-completion status (completed, non-completed, and never-started). We surveyed 194 HCWs for e-readiness; 116 HCWs self-enrolled in the HH course, and 55 responded to the satisfaction survey. Most e-readiness factors were statistically significant between course-completion groups. Moreover, students were significantly more likely to complete the course if they had a computer with an Internet connection (P=0.001) and self-reported comfort with using a computer several times a week (p=0.001) and communicating through online technologies (p=0.001). Previous online course experience was not a significant factor (p=0.819). E-readiness score averages varied among HCWs, and mean scores for all e-readiness factors were significantly higher among medical doctors than among nurses. Nearly all respondents to the satisfaction survey agreed that e-learning was as effective as the traditional teaching method. Evaluating HCWs' e-readiness is essential while integrating technologies into educational programs in low- to middle-income countries.

Objective: Presenting methodology for transferring knowledge to improve maternal outcomes in natural delivery based on scientific evidence., Method: An intervention study conducted in the maternity hospital of Itapecerica da Serra, SP, with 50 puerperal women and 102 medical records from July to November 2014. The PACES tool from Joanna Briggs Institute, consisting of pre-clinical audit (phase 1), implementation of best practice (phase 2) and Follow-up Clinical Audit (phase 3) was used. Data were analyzed by comparing results of phases 1 and 3 with Fisher's exact test and a significance level of 5%., Results: The vertical position was adopted by the majority of puerperal women with statistical difference between phases 1 and 3. A significant increase in bathing/showering, walking and massages for pain relief was found from the medical records. No statistical difference was found in other practices and outcomes. Barriers and difficulties in the implementation of evidence-based practices have been identified. Variables were refined, techniques and data collection instruments were verified, and an intervention proposal was made., Conclusion: The study found possibilities for implementing a methodology of practices based on scientific evidence for assistance in natural delivery.

Context: Physicians overestimate survival in patients with advanced cancer. Patient-reported outcomes could provide another way to estimate survival. We previously reported four prognostic groups based on Karnofsky Performance Status, Functional Assessment of Cancer Therapy physical well-being subscale, and Memorial Symptom Assessment Scale-Short Form physical symptom distress subscale scores., Objectives: To determine the validity of these four prognostic groups., Methods: We performed prospective surveys. Data from a total of 880 Veterans Affairs Medical Center patients, 417 in the First Cohort and 463 in the Validation Cohort, were analyzed. Both inpatients and outpatients were prospectively recruited in Institutional Review Board-approved studies from August 1999 to September 2009. Survival was measured from the date of entry until death or December 1, 2009. Patients completed self-assessments with the Functional Assessment of Cancer Therapy and Memorial Symptom Assessment Scale-Short Form. Analysis of variance was used to test differences between groups in continuous variables; a generalized Wilcoxon test was used for differences between groups for survival., Results: The average age in the Validation Cohort was 66.5 years and 98% were men. The majority of patients had metastatic cancer (90%), with lung (28%) and prostate (26%) cancers being predominant. The median Karnofsky Performance Status was 70. Median survival was 33, 46.5, 124, and 209.5 days for the four prognostic groups (P < 0.0001, all pair-wise comparisons P < 0.02)., Conclusion: The four prognostic groups remained distinct in the prospective cohort. Small differences in patient-reported physical well-being can halve survival estimates. Patient-reported outcomes can correct for physician overestimate of prognosis. This study provides a way to use patient-reported outcomes for prognosis in patients with advanced cancer, with important implications for assessment., (Published by Elsevier Inc.)

Purpose: The American Association of Oral and Maxillofacial Surgeons Board of Trustees mandated monitoring using capnography during moderate sedation (MS) and deep sedation or general anesthesia (DS/GA) delivered in the office setting effective January 1, 2014. The purpose of this study was to estimate the frequency of capnography use and to identify variables associated with a clinician's choice to use capnography before the mandate., Materials and Methods: To address the research purpose, the authors designed a prospective cohort study and enrolled 2 samples: 1) American private practicing oral and maxillofacial surgeons (OMSs) and 2) all eligible patients for whom these OMSs delivered MS or DS/GA. The predictor variables were categorized as surgeon or patient demographics, anesthesia risk factors, procedure-related variables, and anesthetic medications. The outcome variable was capnography use during MS or DS/GA. Descriptive, bivariate, and forward stepwise multiple logistic regression statistics were computed to evaluate the association between the predictor variables and capnography use, with statistical significance set at a P value less than or equal to .05., Results: The surgeon sample was composed of 95 OMSs and 13.7% reported using capnography. The patient sample included 3,495 patients with a mean age of 30.6 years (standard deviation, 17.8 yr), 43.5% were men, and 5.6% were monitored using capnography. Based on bivariate analyses, 17 variables were associated with capnography use. Forward stepwise regression modeling identified 9 variables statistically associated with capnography use. These variables were patient's age, Mallampati airway score, alcohol consumption, board certification, sevoflurane use, number of monitoring methods, electrocardiogram use, precordial stethoscope use, and number of personnel in operating suite., Conclusions: Although this study might be of historical interest at this time, the results offer insight into OMSs' practice patterns before the mandatory requirement to use capnography. As more OMSs comply with the capnography mandate, their practice patterns involving variables found to statistically correlate with capnography use might become more similar to those of early adopters of this technology., (Copyright © 2015 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: to analyze the Pelvic Floor Muscle Strength (PFMS) of pregnant women with one or more vaginal or cesarean deliveries; to compare the PFMS of these with pregnant women with the PFMS of primiparous women., Methods: cross-sectional study with women up to 12 weeks pregnant, performed in Itapecerica da Serra, São Paulo state, from December 2012 to May 2013. The sample consisted of 110 pregnant women with one or more vaginal deliveries or cesarean sections and 110 primigravidae. The PFMS was evaluated by perineometry (Peritron(tm)) and vaginal digital palpation (modified Oxford scale)., Results: the average PFMS in pregnant women with a history of vaginal delivery or cesarean section was 33.4 (SD=21.2) cmH2O. From the Oxford scale, 75.4% of the pregnant women with previous vaginal or cesarean deliveries presented grade ≤ 2, and 5.5% grade ≥ 4; among the primiparae, 39.9% presented grade ≤ 2, and 50.9% grade ≥ 4, with a statistically significant difference (p<0.001). From the perineometry, there was no statistically significant difference between the PFMS and age, type of delivery, parity, body mass index, and genitourinary tract symptoms, however, there was a statistically significant difference between the pregnant women with and without a history of episiotomy (p=0.04). In the palpation, none of the variables showed a statistically significant difference., Conclusion: pregnancy and childbirth can reduce the PFMS.

Background: Endocannabinoids and temperament traits have been linked to both physical activity and body mass index (BMI) however no study has explored how these factors interact in females. The aims of this cross-sectional study were to 1) examine differences among distinct BMI groups on daytime physical activity and time spent in moderate-vigorous physical activity (MVPA), temperament traits and plasma endocannabinoid concentrations; and 2) explore the association and interaction between MVPA, temperament, endocannabinoids and BMI., Methods: Physical activity was measured with the wrist-worn accelerometer Actiwatch AW7, in a sample of 189 female participants (43 morbid obese, 30 obese, and 116 healthy-weight controls). The Temperament and Character Inventory-Revised questionnaire was used to assess personality traits. BMI was calculated by bioelectrical impedance analysis via the TANITA digital scale. Blood analyses were conducted to measure levels of endocannabinoids and endocannabinoid-related compounds. Path-analysis was performed to examine the association between predictive variables and MVPA., Results: Obese groups showed lower MVPA and dysfunctional temperament traits compared to healthy-weight controls. Plasma concentrations of 2-arachidonoylglyceryl (2-AG) were greater in obese groups. Path-analysis identified a direct effect between greater MVPA and low BMI (b = -0.13, p = .039) and high MVPA levels were associated with elevated anandamide (AEA) levels (b = 0.16, p = .049) and N-oleylethanolamide (OEA) levels (b = 0.22, p = .004), as well as high Novelty seeking (b = 0.18, p<.001) and low Harm avoidance (b = -0.16, p<.001)., Conclusions: Obese individuals showed a distinct temperament profile and circulating endocannabinoids compared to controls. Temperament and endocannabinoids may act as moderators of the low MVPA in obesity.

Objective To analyze pelvic floor muscle strength (PFMS), urinary continence and quality of life related to urinary incontinence (UI) of women in the first trimester of pregnancy. Method Cross-sectional study with a sample of 500 women who started prenatal care in a complementary healthcare facility in Guarulhos, state of São Paulo, from 2012 and 2013. Pelvic floor muscle strength was evaluated through perineometry. The pregnant women who presented UI answered the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF). Results It was found that maternal age (OR=1.06; CI95% 1.02-1.11) and prior UI (OR=15.12; 95%CI 8.19-27.92) are the variables that, in tandem, best explain the occurrence of UI at the beginning of pregnancy. The mean score on the ICIQ-SF was 8.2 (SD=3.9), considered a moderate impact on quality of life. Conclusion Older pregnant women with prior UI are more likely to have UI in the first trimester of pregnancy.

Many of the interesting physics processes to be measured at the LHC have a signature involving one or more isolated electrons. The electron reconstruction and identification efficiencies of the ATLAS detector at the LHC have been evaluated using proton-proton collision data collected in 2011 at [Formula: see text] TeV and corresponding to an integrated luminosity of 4.7 fb[Formula: see text]. Tag-and-probe methods using events with leptonic decays of [Formula: see text] and [Formula: see text] bosons and [Formula: see text] mesons are employed to benchmark these performance parameters. The combination of all measurements results in identification efficiencies determined with an accuracy at the few per mil level for electron transverse energy greater than 30 GeV.

The mouse model of laser-induced choroidal neovascularization (CNV) has been used extensively in studies of the exudative form of age-related macular degeneration (AMD). This experimental in vivo model relies on laser injury to perforate Bruch's membrane, resulting in subretinal blood vessel recruitment from the choroid. By recapitulating the main features of the exudative form of human AMD, this assay has served as the backbone for testing antiangiogenic therapies. This standardized protocol can be applied to transgenic mice and can include treatments with drugs, recombinant proteins, antibodies, adenoviruses and pre-microRNAs to aid in the search for new molecular regulators and the identification of novel targets for innovative treatments. This robust assay requires 7-14 d to complete, depending on the treatment applied and whether immunostaining is performed. This protocol includes details of how to induce CNV, including laser induction, lesion excision, processing and different approaches to quantify neoformed vasculature.

Purpose: The objective of this study was to elucidate the signaling pathway through which cationic antimicrobial protein of 37 kDa (CAP37) mediates human corneal epithelial cell (HCEC) chemotaxis., Methods: Immortalized HCECs were treated with pertussis toxin (10 and 1000 ng/mL), protein kinase C (PKC) inhibitors (calphostin c, 50 nM and Ro-31-8220, 100 nM), phorbol esters (phorbol 12,13-dibutyrate, 200 nM and phorbol 12-myristate 13-acetate, 1 μM) known to deplete PKC isoforms, and siRNAs (400 nM) before a modified Boyden chamber assay was used to determine the effect of these inhibitors and siRNAs on CAP37-directed HCEC migration. PKCδ protein levels, PKCδ-Thr(505) phosphorylation, and PKCδ kinase activity was assessed in CAP37-treated HCECs using immunohistochemistry, Western blotting, and a kinase activity assay, respectively., Results: Chemotaxis studies revealed that treatment with pertussis toxin, PKC inhibitors, phorbol esters, and siRNAs significantly inhibited CAP37-mediated chemotaxis compared with untreated controls. CAP37 treatment increased PKCδ protein levels and led to PKCδ phosphorylation on residue Thr(505). Direct activation of PKCδ by CAP37 was demonstrated using a kinase activity assay., Conclusions: These findings lead us to conclude that CAP37 is an important regulator of corneal epithelial cell migration and mediates its effects through PKCδ.

Birth centers are maternal care models that use appropriate technology when providing care to birthing women. This descriptive study aimed to characterize intrapartum care in a freestanding birth center, in light of the practices recommended by the World Health Organization (WHO), with 1,079 assisted births from 2006 to 2009 in the Sapopemba Birth Center, São Paulo, Brazil. Results included the use of intermittent auscultation (mean=7 controls); maternal positions during delivery: semi-sitting (82.3%), side-lying (16.0%), other positions (1.7%), oral intake (95.6%); companionship (93.3%); exposure to up to three vaginal examinations (85.4%), shower bathing (84.0%), walking (68.0%), massage (60.1%), exercising with a Swiss ball (51.7%); amniotomy (53.4%), oxytocin use during the first (31.0%) and second stages of labor (25.8%), bath immersion (29.3%) and episiotomy (14.1%). In this birth center, care providers used practices recommended by the WHO, although some practices might have been applied less frequently.

Background: Recently, much interest has been generated in the use of intense pulsed light (IPL) sources in the treatment of various skin conditions. However, the underlying mechanism for its therapeutic action has not been elucidated., Objective: To investigate the effect of IPL on the in vivo expression of transforming growth factor beta1 (TGF-β1) and on the immunolocalization of Smad3 in biopsies obtained from perilesional skin in patients with mild-to-moderate inflammatory acne vulgaris., Methods: Biopsies obtained from 20 patients with inflammatory acne vulgaris at baseline (B1) and post-IPL treatment (B2 = 48 h after first treatment and B3 = 1 week after final treatment) were immunohistochemically analyzed to determine the expression of TGF-β1 and the immunolocalization of Smad3. Digital images were semiquantitatively assessed using image analysis software., Results: Intense pulsed light elicited a consistent increase in epidermal TGF-β1 expression (B2 vs. B1: P = 0.004 and B3 vs. B1: P = 0.007). Furthermore, it resulted in enhanced nuclear immunolocalization of Smad3 (B2 vs. B1: epidermis, P = 0.000055 and dermis, P = 0.014; B3 vs. B1: epidermis, P = 0.00024 and dermis, P = 0.008)., Conclusion: Intense pulsed light upregulates TGF-β1/Smad3 signaling in perilesional skin obtained from patients with mild-to-moderate inflammatory acne vulgaris. Further experiments on lesional skin and downstream effects are warranted to determine whether it may play a role in IPL-induced resolution of acne vulgaris., (© 2013 Wiley Periodicals, Inc.)