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Heat stress can disrupt the balance between the heat poultry release into the environment and the heat they generate. Pequi oil has antioxidant properties, which may mitigate the heat stress effects. This study aimed to investigate the response of laying hens to pequi oil supplementation under heat stress using a proteomic approach. A total of 96 Lohmann White laying hens with 26 weeks old were housed in a completely randomized design with a 2 × 2 factorial arrangement. They were housed in two climate chambers, thermal comfort temperature ± 24.04 °C with the relative humidity ± 66.35 and heat stress (HS) ± 31.26 °C with the relative humidity ± 60.62. They were fed two diets: a control diet (CON), basal diet (BD) without additives, and with Pequi oil (PO), BD + 0.6% PO. After 84 days, plasma samples were analyzed using Shotgun and LC-MS/MS. Proteins related to anti-inflammation, transport, and the immune system were differentially expressed in hens fed PO and CON under heat stress compared to those in thermoneutral environments. This helps protect against oxidative stress and may support the body's ability to manage heat-induced damage, stabilizing protein expression under stress conditions. The ovotransferrin proteins, fibrinogen isoforms, apolipoprotein A-I, Proteasome activator subunit 4, Transthyretin, and the enzyme serine Peptidase Inhibitor_Kazal Type 5, which presented Upregulated (Up) equal to 1, present characteristics that may be crucial for enhancing the adaptive responses of hens to thermal stress, thereby increasing their tolerance and minimizing the negative effects of heat on egg production. The data presented in this manuscript provides new insights into the plasma proteome alterations of laying hens fed a diet supplemented with pequi oil during heat stress challenges.

Objective: Coordination to get everyone in the room at the same time for family-centered rounds (FCR) is challenging. The objective of this study was to determine if using a virtual queue that notifies nurses and families in real time when to expect the rounding team could impact their presence on rounds., Methods: We observed rounds on two neonatal intensive care unit (NICU) teams for 6 weeks before and after implementation of a novel rounding software, Q-rounds, that shares real-time updates on when the team will arrive and allows families to répondez s'il vous plaît (RSVP) to join remotely when they cannot be there in person. Observers collected metrics pertinent to FCR including nurse and family presence (in-person or remotely) and duration of rounds and used Chi-square and two group t-tests for analysis., Results: Rounds were observed for 165 patient encounters pre-implementation and 179 patient encounters post-implementation, with an average rounding duration of 10.3 minutes (SD 6.5) and 10.4 minutes (SD 6.3) per patient respectively (P = 0.91). The proportion of nurses who were present for the entirety of the rounding discussion increased from 18.8% to 58.2% (P < 0.001). Family presence on rounds increased from 20.0% (95% CI, 13.9-26.1) to 43.0% (95% CI, 35.8-50.3; P < 0.001). The percentage of families that participated in rounds remotely increased from 15.2% to 55.8% (P < 0.001)., Conclusions: This observational study showed that the use of a novel rounding software was associated with a significant increase in family presence for rounds and nurse presence for the entirety of rounds without increasing rounding duration., Competing Interests: Declaration of Competing Interest Two authors, Dr Pitt and Sartori are co-founders with an ownership stake in Q-rounds Inc. which holds an exclusive license to the intellectual property evaluated in this project. This interest has been reviewed and managed by the University of Minnesota in accordance with its Conflict of Interest policies. Drs. Pitt and Sartori were not allowed access to the raw data collected in this study. No other authors have conflicts of interest to report., (Copyright © 2024 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.)

Context There is mounting evidence implicating kisspeptin signalling in placental development and function. Aims This study aimed to elucidate kisspeptin's role in trophoblast invasion and migration using three experimental models. Methods First, we examined the mouse fetus and placenta in a kisspeptin receptor (Kiss1r) knockout (KO) model. Fetal/placental weights and gene expression (quantitative polymerase chain reaction) were assessed. Second, we determined kisspeptin effects on a human trophoblast (BeWo) cell line in vitro . Third, we examined KISS1 and KISS1R gene expression in human placenta from term and pre-term pregnancies. Key results No difference was found in fetal or placental weight between Kiss1r KO and wildtype mice. However, expression of the trophoblast invasion marker, Mmp2 mRNA, was greater in the placental labyrinth zone of Kiss1r KO mice. BeWo cell models of villus cytotrophoblast and syncytiotrophoblast cells exhibited kisspeptin protein expression, with greater expression in syncytiotrophoblast, consistent with KISS1 mRNA. Kisspeptin treatment inhibited the migratory potential of cytotrophoblast-like cells. Finally, while no difference was seen in KISS1 and KISS1R mRNA between term and pre-term placentas, we saw a difference in the relative expression of each gene pre-term. We also observed a positive correlation between KISS1 expression and maternal body mass index. Conclusions Our results indicate that kisspeptin may inhibit trophoblast invasion. Implications Further investigation is required to clarify specific regulatory mechanisms.

Introduction: Autologous blood products like Platelet Rich Plasma (PRP) and Leukocyte and Platelets Rich Fibrin (L-PRF) have been used for many years across many types of skin ulcers. However, the effectiveness of autologous blood products on wound healing is not well established., Methods: We evaluated the 'second generation' autologous product- Leukocyte and Platelet- Rich Fibrin (L-PRF). Our trial was undertaken on patients suffering from neuropathic leprosy ulcers at the Anandaban hospital which serves the entire country of Nepal. We conducted a 1:1 (n = 130) individually randomised trial of L-PRF (intervention) vs. normal saline dressing (control) to compare rate of healing and time to complete healing. Rate of healing was estimated using blind assessments of ulcer areas based on three different measurement methods. Time to complete healing was measured by the local unblinded clinicians and by blind assessment of ulcer images., Results: The point estimates for both outcomes were favourable to L-PRF but the effect sizes were small. Unadjusted mean differences (intervention vs control) in mean daily healing rates (cm2) were respectively 0.012 (95% confidence interval 0.001 to 0.023, p = 0.027); 0.016 (0.004 to 0.027, p = 0.008) and 0.005 (-0.005 to 0.016, p = 0.313) across the three measurement methods. Time to complete healing at 42 days yielded Hazard Ratios (unadjusted) of 1.3 (0.8 to 2.1, p = 0.300) assessed by unblinded local clinicians and 1.2 (0.7 to 2.0, p = 0.462) on blind assessment., Conclusion: Any benefit from L-PRF appears insufficient to justify routine use in care of neuropathic ulcers in leprosy., Trial Registration: ISRCTN14933421. Date of trial registration: 16 June 2020., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Napit et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Leprosy leads to nerve damage and slow-healing ulcers, which are treatable with routine therapy. There has been a recent resurgence of interest in the use of honey for the treatment of different kinds of wounds., Objective: The aim of this study, Honey Experiment on Leprosy Ulcer (HELP), is to evaluate the healing properties of raw, unadulterated African honey in comparison with normal saline dressing for the treatment leprosy ulcers., Methods: This is a multicenter, comparative, prospective, single-blinded, parallel-group, and 1:1 individually randomized controlled trial to be conducted at The Leprosy Referral Hospital, Chanchaga in Minna, Niger State, North Central Nigeria, and St. Benedict Tuberculosis and Leprosy Rehabilitation Hospital in Ogoja, Cross River State, South-South Nigeria. Raw, unadulterated honey will be used in the ulcer dressing of eligible, consenting participants in the intervention group, whereas those in the control group will be treated by dressing with normal saline. The main outcomes will be the proportion of complete healing and the rate of healing up to 84 days after randomization. Follow-up will be conducted 6 months after randomization. We aim to enroll 90-130 participants into the study. Blinded observers will examine photographs of ulcers to determine the outcomes., Results: The recruitment of trial participants began on March 14, 2022, and has been continuing for approximately 24 months., Conclusions: Our study will provide an unbiased estimate of the effect of honey on the healing of neuropathic ulcers., (© Sunday Udo, Pius Ogbu Sunday, Paul Alumbugu Tsaku, Israel Olaoluwa Oladejo, Anthony Meka, Linda Chinonso Ugwu, Motunrayo Ajisola, Joshua Akinyemi, Abiola Oladejo, Akinyinka Omigbodun, Sopna Mannan Choudhury, Jo Sartori, Onaedo Ilozumba, Sam Watson, Richard Lilford. Originally published in JMIRx Med (https://med.jmirx.org).)

Supplementing minerals beyond dietary requirements can increase the risk of toxicity and mineral excretion, making the selection of more bioavailable sources crucial. Thus, this work aimed to use metalloproteomics tools to investigate possible alterations in the hepatic proteome of broilers fed with diets containing two sources (sulfate and hydroxychloride) and two levels of copper (15 and 150 ppm) and manganese (80 and 120 ppm), totaling four treatments: low Cu/Mn SO 4 , high Cu/Mn SO 4 , low Cu/Mn (OH)Cl and high Cu/Mn (OH)Cl. The difference in abundance of protein spots and copper and manganese concentrations in liver and protein pellets were analyzed by analysis of variance with significance level of 5%. The Cu and Mn concentrations determined in liver and protein pellets suggested greater bioavailability of hydroxychloride sources. We identified 19 Cu-associated proteins spots, 10 Mn-associated protein spots, and 5 Cu and/or Mn-associated protein spots simultaneously. The analysis also indicated the induction of heat shock proteins and detoxification proteins in broilers fed with high levels of copper and manganese, suggesting the involvement of these proteins in metal tolerance and stress., (© 2024. The Author(s).)

Introduction: People affected by leprosy are at increased risk of impairments and deformities from peripheral nerve damage. This mostly occurs if diagnosis and treatment is delayed and contributes to continued transmission within the community. Champa district of Chhattisgarh state in India is an endemic area with the highest national annual case detection and disability rates for leprosy. The Replicability Model is a system strengthening intervention implemented by the Leprosy Mission Trust India in Champa that aims to promote early diagnosis and treatment of leprosy, improve on-going management of the effects of leprosy and improve welfare for the people affected by leprosy. This protocol presents a plan to describe the overall implementation of the Replicability Model and describe the barriers and facilitators encountered in the process. We will also quantify the effect of the program on one of its key aims- early leprosy diagnosis., Methods: The replicability model will be implemented over four years, and the work described in this protocol will be conducted in the same timeframe. We have two Work Packages (WPs). In WP1, we will conduct a process evaluation. This will include three methods i) observations of replicability model implementation teams' monthly meetings ii) key informant interviews (n = 10) and interviews with stakeholders (n = 30) iii) observations of key actors (n = 15). Our purpose is to describe the implementation process and identify barriers and facilitators to successful implementation. WP2 will be a quantitative study to track existing and new cases of leprosy using routinely collected data. If the intervention is successful, we expect to see an increase in cases (with a higher proportion detected at an early clinical stage) followed by a decrease in total cases., Conclusion: This study will enable us to improve and disseminate the Replicability Model by identifying factors that promote success. It will also identify its effectiveness in fulfilling one of its aims: reducing the incidence of leprosy by finding and tracking cases at an earlier stage in the disease., Competing Interests: I have read the journal’s policy and three authors (Joydeepa Darlong, Karthikeyan Govindasamy and Anjali Shrivastva),of this manuscript have the following competing interests: They work for the implementing organization TLMTI, (Copyright: © 2023 Darlong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: Leprosy occurs among very poor people who may be stigmatised and pushed further to the margins of society. Programmes to improve social integration and stimulate economic development have been implemented to help break the vicious cycle of poverty, reduced quality of life and ulcer recurrence. These involve forming groups of people, with a common concern, to provide mutual support and form saving syndicates-hence the term 'self-help groups' (SHGs). While there is literature on the existence and effectiveness of SHGs during the funded periods, little is known about their sustainability. We aim to explore the extent to which SHG programme activities have continued beyond the funding period and record evidence of sustained benefits., Methods and Analysis: In India, Nepal and Nigeria, we identified programmes funded by international non-governmental organisations, primarily aimed at people affected by leprosy. In each case, financial and technical support was allocated for a predetermined period (up to 5 years).We will review documents, including project reports and meeting minutes, and conduct semistructured interviews with people involved in delivery of the SHG programme, potential beneficiaries and people in the wider environment who may have been familiar with the programme. These interviews will gauge participant and community perceptions of the programmes and barriers and facilitators to sustainability. Data will be analysed thematically and compared across four study sites., Ethics and Dissemination: Approval was obtained from the University of Birmingham Biomedical and Scientific Research Ethics Committee. Local approval was obtained from: The Leprosy Mission Trust India Ethics Committee; Federal Capital Territory Health Research Ethics Committee in Nigeria and the Health Research Ethics Committee of Niger State Ministry of Health; University of Nigeria Teaching Hospital and the Nepal Health and Research Council. Results will be disseminated via peer-reviewed journals, conference presentations and community engagement events through the leprosy missions., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The aim of this study was to characterize the proteins differentially expressed in the pectoralis major muscle of broilers supplemented with passion fruit seed oil (PFSO) under cyclic heat stress conditions. Ninety one-day-old male chicks were housed in cages arranged in a climatic chamber, where they were kept under cyclic heat stress for eight hours a day from the beginning to the end of the experiment. The birds were divided into two experimental groups, one group supplemented with 0.9% PFSO and a control group (CON) without PFSO supplementation. At 36 days of age, 18 birds were slaughtered to collect muscle samples. From pools of breast fillet samples from each group, proteolytic cleavage of the protein extracts was performed, and later, the peptides were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The 0.9% PFSO supplementation revealed the modulation of 57 proteins in the pectoralis major muscle of broilers exposed to cyclic heat stress. Among them, four proteins were upregulated, and 46 proteins were downregulated. In addition, seven proteins were expressed only in the CON group. These results suggest that PFSO may increase heat tolerance, with a possible reduction in oxidative stress, activation of neuroprotective mechanisms, protection against apoptosis, decrease in inflammatory responses, and regulation of energy metabolism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Burn injuries have decreased markedly in high-income countries while the incidence of burns remains high in Low- and Middle-Income Countries (LMICs) where more than 90% of burns are thought to occur. However, the cause of burns in LMIC is poorly documented. The aim was to document the causes of severe burns and the changes over time. A cross-sectional survey was completed for 2014 and 2019 in eight burn centers across Africa, Asia, and Latin America: Cairo, Nairobi, Ibadan, Johannesburg, Dhaka, Kathmandu, Sao Paulo, and Guadalajara. The information summarised included demographics of burn patients, location, cause, and outcomes of burns. In total, 15,344 patients were admitted across all centers, 37% of burns were women and 36% of burns were children. Burns occurred mostly in household settings (43-79%). In Dhaka and Kathmandu, occupational burns were also common (32 and 43%, respectively). Hot liquid and flame burns were most common while electric burns were also common in Dhaka and Sao Paulo. The type of flame burns varies by center and year, in Dhaka, 77% resulted from solid fuel in 2014 while 74% of burns resulted from Liquefied Petroleum Gas in 2019. In Nairobi, a large proportion (32%) of burns were intentional self-harm or assault. The average length of stay in hospitals decreased from 2014 to 2019. The percentage of deaths ranged from 5% to 24%. Our data provide important information on the causes of severe burns which can provide guidance in how to approach the development of burn injury prevention programs in LMIC., (© The Author(s) 2022. Published by Oxford University Press on behalf of the American Burn Association.)

When a person chooses a healthcare provider, they are trading off cost, convenience, and a latent third factor: "perceived quality". In urban areas of lower- and middle-income countries (LMICs), including slums, individuals have a wide range of choice in healthcare provider, and we hypothesised that people do not choose the nearest and cheapest provider. This would mean that people are willing to incur additional cost to visit a provider they would perceive to be offering better healthcare. In this article, we aim to develop a method towards quantifying this notion of "perceived quality" by using a generalised access cost calculation to combine monetary and time costs relating to a visit, and then using this calculated access cost to observe facilities that have been bypassed. The data to support this analysis comes from detailed survey data in four slums, where residents were questioned on their interactions with healthcare services, and providers were surveyed by our team. We find that people tend to bypass more informal local services to access more formal providers, especially public hospitals. This implies that public hospitals, which tend to incur higher access costs, have the highest perceived quality (i.e., people are more willing to trade cost and convenience to visit these services). Our findings therefore provide evidence that can support the 'crowding out' hypothesis first suggested in a 2016 Lancet Series on healthcare provision in LMICs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Conlan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objective: First, to obtain regional estimates of prevalence of hypertension and type 2 diabetes in urban slums; and second, to compare these with those in urban and rural areas., Design: Systematic review and meta-analysis., Eligibility Criteria: Studies that reported hypertension prevalence using the definition of blood pressure ≥140/90 mm Hg and/or prevalence of type 2 diabetes., Information Sources: Ovid MEDLINE, Cochrane CENTRAL and EMBASE from inception to December 2020., Risk of Bias: Two authors extracted relevant data and assessed risk of bias independently using the Strengthening the Reporting of Observational Studies in Epidemiology guideline., Synthesis of Results: We used random-effects meta-analyses to pool prevalence estimates. We examined time trends in the prevalence estimates using meta-regression regression models with the prevalence estimates as the outcome variable and the calendar year of the publication as the predictor., Results: A total of 62 studies involving 108 110 participants met the inclusion criteria. Prevalence of hypertension and type 2 diabetes in slum populations ranged from 4.2% to 52.5% and 0.9% to 25.0%, respectively. In six studies presenting comparator data, all from the Indian subcontinent, slum residents were 35% more likely to be hypertensive than those living in comparator rural areas and 30% less likely to be hypertensive than those from comparator non-slum urban areas., Limitations of Evidence: Of the included studies, only few studies from India compared the slum prevalence estimates with those living in non-slum urban and rural areas; this limits the generalisability of the finding., Interpretation: The burden of hypertension and type 2 diabetes varied widely between countries and regions and, to some degree, also within countries., Prospero Registration Number: CRD42017077381., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Background: Periorbital fractional CO2 laser resurfacing has been employed for facial rejuvenation purposes. However, to the best of our knowledge, no study has objectively assessed periorbital neoformation and remodeling of local cutaneous collagen, in a split-face model, from skin samples obtained during upper blepharoplasty., Objectives: The authors sought to objectively evaluate neoformation and remodeling of local cutaneous collagen after periorbital skin fractional CO2 laser resurfacing., Methods: Sixteen female patients presenting with dermatochalasis and periorbital rhytids were evaluated in a prospective and comparative study. All patients underwent unilateral periorbital fractional CO2 laser resurfacing 30 days before upper blepharoplasty. Quantification of types I and III collagen from laser-treated and untreated eyelid skin samples obtained during upper blepharoplasty was assessed with histochemical analysis (Picrosirius Red staining). Laser resurfacing treatment was applied to the untreated side immediately after the upper blepharoplasty. Two blinded, independent physicians evaluated clinical improvement in pretreatment and 1- and 6-month posttreatment digital images., Results: Histochemical analysis showed significantly higher intensity in collagen types I (treated: 158.7 ± 5.3, untreated: 139.2 ± 5.0; P < 0.0001) and III (treated: 105.1 ± 7.7, untreated: 104.1 ± 7.1; P < 0.0001) in the fractional CO2 laser treatment samples; a greater difference was detected in collagen type I. A significant improvement in periorbital rhytidosis was observed 1 month after laser resurfacing (23%); a greater improvement in the periorbital region was observed 6 months after laser resurfacing and upper blepharoplasty (43.67%)., Conclusions: Periorbital fractional CO2 laser resurfacing was an effective method to improve palpebral skin, with histochemical evidence of increase in collagen types I and III., (© 2021 The Aesthetic Society. Reprints and permission: journals.permissions@oup.com.)

Objective: With COVID-19, there was a need for a rapidly scalable annotation system that facilitated real-time integration with clinical decision support systems (CDS). Current annotation systems suffer from a high-resource utilization and poor scalability limiting real-world integration with CDS. A potential solution to mitigate these issues is to use the rule-based gazetteer developed at our institution., Materials and Methods: Performance, resource utilization, and runtime of the rule-based gazetteer were compared with five annotation systems: BioMedICUS, cTAKES, MetaMap, CLAMP, and MedTagger., Results: This rule-based gazetteer was the fastest, had a low resource footprint, and similar performance for weighted microaverage and macroaverage measures of precision, recall, and f1-score compared to other annotation systems., Discussion: Opportunities to increase its performance include fine-tuning lexical rules for symptom identification. Additionally, it could run on multiple compute nodes for faster runtime., Conclusion: This rule-based gazetteer overcame key technical limitations facilitating real-time symptomatology identification for COVID-19 and integration of unstructured data elements into our CDS. It is ideal for large-scale deployment across a wide variety of healthcare settings for surveillance of acute COVID-19 symptoms for integration into prognostic modeling. Such a system is currently being leveraged for monitoring of postacute sequelae of COVID-19 (PASC) progression in COVID-19 survivors. This study conducted the first in-depth analysis and developed a rule-based gazetteer for COVID-19 symptom extraction with the following key features: low processor and memory utilization, faster runtime, and similar weighted microaverage and macroaverage measures for precision, recall, and f1-score compared to industry-standard annotation systems., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Medical Informatics Association.)

1. This study investigated the effects of hydroxy trace minerals (HTM) compared to sulphate trace minerals (STM) supplementation on growth performance, carcase parameters and mineral retention in broilers.2. A total of 1792 male Cobb 500 d-old were allocated in a completely randomised trial design to one of eight dietary treatments with eight replicates per treatment. The HTM sources used were two levels of Cu hydroxychloride (CHC) (low and high), combined with three levels of Zn hydroxychloride (ZHC) (low, med and high) and two additional treatments STM; Cu sulphate monohydrate (CSM) (low and high) combined with high Zn sulphate monohydrate (ZSM). At 21 and 42 d-old growth performance was evaluated. Additionally, at 42 d-old the carcase traits, meat quality, apparent ileal absorption and activity of antioxidant enzymes were accessed.3. A data showed that broilers receiving high-CHC had higher body weight, weight gain and better feed conversion ratio as compared to low-CHC at 21 d-old. On day 42, the feed conversion ratio was improved for birds supplemented with high-CHC in diets containing med-ZHC, as compared to low-CHC.4. Dietary Cu increased the redness of breast colour at the level of high-CHC compared to low-CHC. Greater results were observed on carcase traits for the med-ZHC group as compared to low- or high-ZHC. The ceruloplasmin activity in serum increased in the high-CSM diets containing high-ZSM as compared to low-CSM. The AIA of Cu was higher in broilers supplemented with high-CHC containing med-ZHC as compared to low-CHC. Otherwise, the AIA of Zn increased in broilers fed low-CHC containing low- or med-ZHC as compared to high-CHC.5. The trial showed that mineral trace supplementation of broilers diets with high-CHC (150 mg/kg) and low-ZHC (80 mg/kg) was a good alternative to replace sulphate mineral sources in diets.

Background: Leprosy is curable with multidrug therapy and treatment in the early stages can prevent disability. However, local nerve damage can lead to injury and consequently recurring and disfiguring ulcers. The aim of this study is to evaluate the treatment of leprosy ulcers using an autologous blood product; leukocyte and platelet-rich fibrin (L-PRF) to promote healing., Methods: This is a single-centre study in the Anandaban Hospital, The Leprosy Mission Nepal, Kathmandu, Nepal. Consenting patients (n=130) will be individually randomised in a single-blinded, controlled trial. Participants will be 18 years of age or older, admitted to the hospital with a clean, dry and infection-free chronic foot ulcer between 2 and 20 cm 2 in size. If the ulcer is infected, it will be treated before enrolment into the study. The intervention involves the application of leukocyte and platelet-rich fibrin (L-PRF) matrix on the ulcer beds during twice-weekly dressing changes. Controls receive usual care in the form of saline dressings only during their twice-weekly dressing changes. Primary outcomes are the rate of healing assessed using standardised photographs by observers blind to allocated treatment, and time to complete re-epithelialization. Follow-up is at 6 months from randomisation., Discussion: This research will provide valuable information on the clinical and cost-effectiveness of L-PRF in the treatment of leprosy ulcers. An additional benefit is the evaluation of the effects of treatment on quality of life for people living with leprosy ulcers. The results will improve our understanding of the scalability of this treatment across low-income countries for ulcer healing in leprosy and potentially other conditions such as diabetic ulcers., Trial Registration: ClinicalTrials.gov ISRCTN14933421 . Registered on 16 June 2020., (© 2021. The Author(s).)

Background: People affected by leprosy are at increased risk of ulcers from peripheral nerve damage. This in turn can lead to visible impairments, stigmatisation and economic marginalisation. Health care providers suggest that patients should be empowered to self-manage their condition to improve outcomes and reduce reliance on services. Self-care involves carrying out personal care tasks with the aim of preventing disabilities or preventing further deterioration. Self-help, on the other hand, addresses the wider psychological, social and economic implications of leprosy and incorporates, for example, skills training and microfinance schemes. The aim of this study, known as SHERPA (Self-Help Evaluation for lepRosy and other conditions in NePAl) is to evaluate a service intervention called Integrated Mobilization of People for Active Community Transformation (IMPACT) designed to encourage both self-care and self-help in marginalised people including those affected by leprosy., Methods: A mixed-method evaluation study in Province 5, Nepal comprising two parts. First, a prospective, cluster-based, non-randomised controlled study to evaluate the effectiveness of self-help groups on ulcer metrics (people affected by leprosy only) and on four generic outcome measures (all participants) - generic health status, wellbeing, social integration and household economic performance. Second, a qualitative study to examine the implementation and fidelity of the intervention., Impact: This research will provide information on the effectiveness of combined self-help and self-care groups, on quality of life, social integration and economic wellbeing for people living with leprosy, disability or who are socially and economically marginalised in low- and middle- income countries.

Clinical records in primary healthcare settings in low- and middle-income countries (LMIC) are often lacking or of too poor quality to accurately assess what happens during the patient consultation. We examined the most common methods for assessing healthcare workers' clinical behaviour: direct observation, standardized patients and patient/healthcare worker exit interview. The comparative feasibility, acceptability, reliability, validity and practicalities of using these methods in this setting are unclear. We systematically review and synthesize the evidence to compare and contrast the advantages and disadvantages of each method. We include studies in LMICs where methods have been directly compared and systematic and narrative reviews of each method. We searched several electronic databases and focused on real-life (not educational) primary healthcare encounters. The most recent update to the search for direct comparison studies was November 2019. We updated the search for systematic and narrative reviews on the standardized patient method in March 2020 and expanded it to all methods. Search strategies combined indexed terms and keywords. We searched reference lists of eligible articles and sourced additional references from relevant review articles. Titles and abstracts were independently screened by two reviewers and discrepancies resolved through discussion. Data were iteratively coded according to pre-defined categories and synthesized. We included 12 direct comparison studies and eight systematic and narrative reviews. We found that no method was clearly superior to the others-each has pros and cons and may assess different aspects of quality of care provision by healthcare workers. All methods require careful preparation, though the exact domain of quality assessed and ethics and selection and training of personnel are nuanced and the methods were subject to different biases. The differential strengths suggest that individual methods should be used strategically based on the research question or in combination for comprehensive global assessments of quality., (© The Author(s) 2020. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.)

Tendon insertions to bone are heavily loaded transitions between soft and hard tissues. The fiber courses in the tendon have profound effects on the distribution of stress along and across the insertion. We tracked fibers of the Achilles tendon in mice in micro-computed tomographies and extracted virtual transversal sections. The fiber tracks and shapes were analyzed from a position in the free tendon to the insertion. Mechanically relevant parameters were extracted. The fiber number was found to stay about constant along the tendon. But the fiber cross-sectional areas decrease towards the insertion. The fibers mainly interact due to tendon twist, while branching only creates small branching clusters with low levels of divergence along the tendon. The highest fiber curvatures were found within the unmineralized entheseal fibrocartilage. The fibers inserting at a protrusion of the insertion area form a distinct portion within the tendon. Tendon twist is expected to contribute to a homogeneous distribution of stress among the fibers. According to the low cross-sectional areas and the high fiber curvatures, tensile and compressive stress are expected to peak at the insertion. These findings raise the question whether the insertion is reinforced in terms of fiber strength or by other load-bearing components besides the fibers. STATEMENT OF SIGNIFICANCE: The presented study is the first analysis of the 3D fiber tracks in macroscopic tendon samples as determined by a combination of cell-maceration, phase-contrast µCT and template-based tracking. The structural findings change the understanding of the tendon-bone insertion and its biomechanics: (1) The insertion is not reinforced in terms of fiber numbers or sizes. Its robustness remains unexplained. (2) The orientation of fibers in the tendon center is higher than in the margins. This arrangement could inspire material development. (3) Fibers inserting at a protrusion of the insertion area stem from a distinct portion within the tendon. The results show that fibrous structure analysis can link macro- to micromechanics and that it is ready for the application to complete muscle-tendon units., (Copyright © 2020 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: With COVID-19, there is urgency for policymakers to understand and respond to the health needs of slum communities. Lockdowns for pandemic control have health, social and economic consequences. We consider access to healthcare before and during COVID-19 with those working and living in slum communities., Methods: In seven slums in Bangladesh, Kenya, Nigeria and Pakistan, we explored stakeholder perspectives and experiences of healthcare access for non-COVID-19 conditions in two periods: pre-COVID-19 and during COVID-19 lockdowns., Results: Between March 2018 and May 2020, we engaged with 860 community leaders, residents, health workers and local authority representatives. Perceived common illnesses in all sites included respiratory, gastric, waterborne and mosquitoborne illnesses and hypertension. Pre-COVID, stakeholders described various preventive, diagnostic and treatment services, including well-used antenatal and immunisation programmes and some screening for hypertension, tuberculosis, HIV and vectorborne disease. In all sites, pharmacists and patent medicine vendors were key providers of treatment and advice for minor illnesses. Mental health services and those addressing gender-based violence were perceived to be limited or unavailable. With COVID-19, a reduction in access to healthcare services was reported in all sites, including preventive services. Cost of healthcare increased while household income reduced. Residents had difficulty reaching healthcare facilities. Fear of being diagnosed with COVID-19 discouraged healthcare seeking. Alleviators included provision of healthcare by phone, pharmacists/drug vendors extending credit and residents receiving philanthropic or government support; these were inconsistent and inadequate., Conclusion: Slum residents' ability to seek healthcare for non-COVID-19 conditions has been reduced during lockdowns. To encourage healthcare seeking, clear communication is needed about what is available and whether infection control is in place. Policymakers need to ensure that costs do not escalate and unfairly disadvantage slum communities. Remote consulting to reduce face-to-face contact and provision of mental health and gender-based violence services should be considered., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The poorest populations of the world lack access to quality healthcare. We defined the key components of consulting via mobile technology (mConsulting), explored whether mConsulting can fill gaps in access to quality healthcare for poor and spatially marginalised populations (specifically rural and slum populations) of low- and middle-income countries, and considered the implications of its take-up., Methods: We utilised realist methodology. First, we undertook a scoping review of mobile health literature and searched for examples of mConsulting. Second, we formed our programme theories and identified potential benefits and hazards for deployment of mConsulting for poor and spatially marginalised populations. Finally, we tested our programme theories against existing frameworks and identified published evidence on how and why these benefits/hazards are likely to accrue., Results: We identified the components of mConsulting, including their characteristics and range. We discuss the implications of mConsulting for poor and spatially marginalised populations in terms of competent care, user experience, cost, workforce, technology, and the wider health system., Conclusions: For the many dimensions of mConsulting, how it is structured and deployed will make a difference to the benefits and hazards of its use. There is a lack of evidence of the impact of mConsulting in populations that are poor and spatially marginalised, as most research on mConsulting has been undertaken where quality healthcare exists. We suggest that mConsulting could improve access to quality healthcare for these populations and, with attention to how it is deployed, potential hazards for the populations and wider health system could be mitigated., (© The Author(s) 2020.)

The activation of nicotinic acetylcholine receptor α7 subunit (α7nAChR) has been associated to anti-inflammatory response in macrophages. High-fat diet (HFD) consumption during pregnancy and lactation impairs the cholinergic anti-inflammatory pathway in liver and white adipose tissue of offspring. In order to evaluate the relationship between damage in the cholinergic anti-inflammatory pathway and insulin resistance (IR) development, the liver of offspring of obese dams was investigated. Additionally, the capacity of α7nAChR activation to reduce IR induced by saturated fatty acid was investigated in hepatoma cell line. Initially, female mice were subjected to either standard chow (SC) or HFD during pregnancy and lactation period. After weaning, only male offspring from HFD dams (HFD-O) and SC dams (SC-O) were fed with the SC diet. Hepatic α7nAChR expression was downregulated, and hepatic TNF-α, IL-1β, and pIKK level, but not pJNK, were elevated in the HFD-O compared to SC-O mice. Besides, hepatic expression of TNF-α in response to lipopolysaccharide (LPS) was higher in HFD-O than SC-O mice. Insulin-stimulated phosphorylation of the AKT was lower in HFD-O compared to SC-O. Additionally, insulin-stimulated phosphorylation of the AKT in KOα7 Alb-Cre mice fed HFD was lower than WT mice fed HFD. In hepatoma cell line, palmitate increased IL-6 and TNF-α expressions and pJNK level. These effects were accompanied by reduced capacity of insulin to stimulate AKT phosphorylation. PNU or nicotine reduced cytokine expression and JNK activation, but improved insulin resistance induced by palmitate. Our results suggest that maternal obesity impairs hepatic α7nAChR expression and AKT phosphorylation in the offspring. In vitro studies suggest that α7nAChR activation has potential to reduce deleterious effect of saturated fatty acids on insulin signalling.

Despite an estimated one billion people around the world living in slums, most surveys of health and well-being do not distinguish between slum and non-slum urban residents. Identifying people who live in slums is important for research purposes and also to enable policymakers, programme managers, donors and non-governmental organisations to better target investments and services to areas of greatest deprivation. However, there is no consensus on what a slum is let alone how slums can be distinguished from non-slum urban precincts. Nor has attention been given to a more fine-grained classification of urban spaces that might go beyond a simple slum/non-slum dichotomy. The purpose of this paper is to provide a conceptual framework to help tackle the related issues of slum definition and classification of the urban landscape. We discuss:The concept of space as an epidemiological variable that results in 'neighbourhood effects'.The problems of slum area definition when there is no 'gold standard'.A long-list of variables from which a selection must be made in defining or classifying urban slum spaces.Methods to combine any set of identified variables in an operational slum area definition.Two basic approaches to spatial slum area definitions-top-down (starting with a predefined area which is then classified according to features present in that area) and bottom-up (defining the areal unit based on its features).Different requirements of a slum area definition according to its intended use.Implications for research and future development., Competing Interests: Competing interests: None declared.

Introduction: Nausea and vomiting in pregnancy (NVP) are common. Whilst the impact on pregnant women has been well documented, there is less data on the impact on partners. This study evaluated awareness and impact of maternal NVP on expectant fathers., Methods: Observational study of 300 expectant fathers. Institutional ethics approval and consent were obtained. Fathers were recruited from antenatal clinics and community settings. Researchers administered demographic, attitudinal and the Hospital Anxiety and Depression scale questionnaires during the third trimester. Expectant fathers were asked if their partner experienced NVP. If aware, they were asked to comment upon the impact on their lives., Results: Participants were similar in demographics to those of the wider Australian community of expectant fathers. Most fathers were aware whether their partner experienced NVP (82%). Of these fathers, 20% reported no NVP, and 30%, 37% and 13% men reported maternal NVP was mild, moderate and severe, respectively. There was no correlation between paternal depression and maternal NVP, but a significant association was found between moderate and severe maternal NVP and paternal anxiety. In qualitative comments, five themes emerged: disruption on work, feelings of frustration and helplessness, concern over depression in their partner, concern for the developing baby and a sense of being manipulated in the third trimester of pregnancy., Discussion: Most expectant fathers are aware of NVP in their partner. Moderate and severe maternal NVP are associated with significantly higher symptoms of paternal anxiety.

Background: Community Health Workers (CHWs) have a crucial role in improving health in their communities and their role is being expanded in many parts of the world. However, the effectiveness of CHWs is limited by poor training and the education of CHWs has received little scientific attention., Methods: Our study was carried out in two districts of KwaZulu-Natal, South Africa. We developed and piloted an inexpensive (two day) training intervention covering national government priorities: HIV/AIDS, sexually transmitted disease and Tuberculosis; and Women's Sexual and Reproductive Health and Rights. Sixty-four CHWs consented to participate in the main study which measured knowledge gains using a modified Solomon design of four different testing schedules to distinguish between the effects of the intervention, testing and any interaction between intervention and testing. We also measured confidence, satisfaction and costs., Results: Following the training intervention, improvements in knowledge scores were seen across topics and across districts. These changes in knowledge were statistically significant (p<0.001) and of large magnitude (over 45 percentage points or four standard deviations). However, the CHWs assigned to the test-test-train schedule in one district showed high gains in knowledge prior to receiving the training. All CHWs reported high levels of satisfaction with the training and marked improvements in their confidence in advising clients. The training cost around US$48 per CHW per day and has the potential to be cost-effective if the large gains in knowledge are translated into improved field-based performance and thus health outcomes., Conclusion: Training CHWs can result in large improvements in knowledge with a short intervention. However, improvements seen in other studies could be due to test 'reactivity'. Further work is needed to measure the generalisability of our results, retention of knowledge and the extent to which improved knowledge is translated into improved practice., Competing Interests: AP is a trustee of Sizabantu, the local partner organisation based in South Africa. Sizabantu is a South African registered NPO (129-199). She declares no other competing interest. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The remaining authors have declared that no competing interests exist.

The whole-organ, three-dimensional microstructure of murine Achilles tendon entheses was visualized with micro-computed tomography (microCT). Contrast-enhancement was achieved either by staining with phosphotungstic acid (PTA) or by a combination of cell-maceration, demineralization and critical-point drying with low tube voltages and propagation-based phase-contrast (fibrous structure scan). By PTA-staining, X-ray absorption of the enthesial soft tissues became sufficiently high to segment the tendon and measure cross-sectional areas along its course. With the fibrous structure scans, three-dimensional visualizations of the collagen fiber networks of complete entheses were obtained. The characteristic tissues of entheses were identified in the volume data. The tendon proper was marked as a segment manually. The fibers within the tendon were marked by thresholding. Tendon and fiber cross-sectional areas were measured. The measurements were compared between individuals and protocols for contrast-enhancement, using a spatial reference system within the three-dimensional enthesis. The usefulness of the method for investigations of the fibrous structure of collagenous tissues is demonstrated., (© 2018 Anatomical Society.)

We aimed to study the behaviour of tissue renewal in blood, pectoral muscle and keel of fattening quails during their growth and adulthood through carbon-13 turnover using the stable isotope technique. Three hundred male European quails were randomly subjected to six treatments. Diets fed to animals were initially based on corn and soybean meal and were replaced at 0, 7, 14, 21, 28 and 35 days of age with diets of rice grits and soybean meal. These diets have distinct isotopic signals and over time it changes; the tissue will incorporate dietary signal, and then, we can measure the return time for each tissue in each age. Treatments were T1 (0 to 21 days), T2 (7 to 35 days), T3 (14 to 42 days), T4 (21 to 56 days), T5 (28 to 63 days) and T6 (35 to 70 days). Carbon-13 turnover in tissues of the birds at the above-mentioned time periods was calculated using the first-order exponential function. The values of half-lives were 2.6, 3.6, 5.4, 6.3, 9.0 and 9.8 days for blood and 2.0, 1.7, 4.8, 6.7, 6.9 and 6.6 days for pectoral muscle in treatments T1, T2, T3, T4, T5 and T6 respectively. The half-lives for the keel in treatments T2, T3, T4, T5 and T6 were 2.0, 5.4, 7.7, 8.9 and 15 days respectively. Thus, half-life in sampled tissues generally increased with age of birds. Initially, the tissue half-lives are influenced by growth, and at the end of the growth cycle, the breast muscle tissue was the most metabolically active in either periods, followed by blood and the keel. All tissues showed a sigmoidal growth curve, which can be confirmed by half-life as a function of age., (Journal of Animal Physiology and Animal Nutrition © 2017 Blackwell Verlag GmbH.)

Background: Growing evidence supports the existence of neurobiological trait abnormalities in individuals at genetic risk for bipolar disorder. The aim of this study was to examine potential differences in brain-derived neurotrophic factor, cytokines, oxidative stress, and telomere length markers between patients with bipolar disorder, their siblings, and healthy controls., Methods: Thirty-six patients with bipolar disorder type I, 39 siblings, and 44 healthy controls were assessed. Serum levels of brain-derived neurotrophic factor, interleukin-6, interleukin-10, tumor necrosis factor-α, C-C motif chemokine 11, C-C motif chemokine 24, and 3-nitrotyrosine were measured, as were the activities of glutathione peroxidase, glutathione reductase, and glutathione S-transferase. Telomere length (T/S ratio) was measured using quantitative polymerase chain reaction., Results: Telomere length was different between the 3 groups (P = .041) with both patients and siblings showing a shorter T/S ratio compared with healthy controls. Patients showed increased levels of interleukin-6 (P = .005) and interleukin-10 (P = .002) compared with controls as well as increased levels of interleukin-6 (p = 0.014) and CCL24 (P = .016) compared with their siblings. C-C motif chemokine 11 levels were increased in siblings compared with controls (P = .015), and a similar tendency was found in patients compared with controls (P = .045). Glutathione peroxidase activity was decreased in patients compared with controls (P = .006) and siblings (P = .025). No differences were found for the other markers., Conclusions: The present results suggest that unaffected siblings may present accelerated aging features. These neurobiological findings may be considered as endophenotypic traits. Further prospective studies are warranted., (© The Author 2017. Published by Oxford University Press on behalf of CINP.)

In the first paper in this Series we assessed theoretical and empirical evidence and concluded that the health of people living in slums is a function not only of poverty but of intimately shared physical and social environments. In this paper we extend the theory of so-called neighbourhood effects. Slums offer high returns on investment because beneficial effects are shared across many people in densely populated neighbourhoods. Neighbourhood effects also help explain how and why the benefits of interventions vary between slum and non-slum spaces and between slums. We build on this spatial concept of slums to argue that, in all low-income and-middle-income countries, census tracts should henceforth be designated slum or non-slum both to inform local policy and as the basis for research surveys that build on censuses. We argue that slum health should be promoted as a topic of enquiry alongside poverty and health., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Massive slums have become major features of cities in many low-income and middle-income countries. Here, in the first in a Series of two papers, we discuss why slums are unhealthy places with especially high risks of infection and injury. We show that children are especially vulnerable, and that the combination of malnutrition and recurrent diarrhoea leads to stunted growth and longer-term effects on cognitive development. We find that the scientific literature on slum health is underdeveloped in comparison to urban health, and poverty and health. This shortcoming is important because health is affected by factors arising from the shared physical and social environment, which have effects beyond those of poverty alone. In the second paper we will consider what can be done to improve health and make recommendations for the development of slum health as a field of study., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Recent evidence points to the involvement of the purinergic signaling in the pathophysiology of bipolar disorder. The aim of this study was to assess the serum levels of adenosine and to evaluate its relation to functioning in 24 euthymic patients with bipolar disorder type I and in 25 matched healthy controls. Subjects were evaluated using the functioning assessment short test. Serum purine levels were measured by high pressure liquid chromatography. Our results show a decrease in serum adenosine levels in bipolar disorder patients compared with controls (t= -4.8, df= 43.96, p<0.001). Moreover, a significant negative correlation was found between patient adenosine levels and depression scale scores (r= -0.642, p= 0.001). Higher functional impairment was linked to lower levels of adenosine in patients (rho= -0.551, p= 0.008). Taken together, our results provide evidence for a purinergic imbalance in bipolar disorder, specifically an adenosinergic dysfunction. Our results also indicate a relation between adenosine levels and the functional impairment caused by the disorder, which could demonstrate a potential relation of adenosine levels in worsening of symptoms., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The objective of this study was to determine if a diet supplemented simultaneously with vitamins C and E would alleviate the negative effects of heat stress, applied between 28 and 42 days of age, on performance, carcass and meat quality traits of broiler chickens. A total of 384 male broiler chickens were assigned to a completely randomized design, with a 2×3 factorial arrangement (diet with or without vitamin supplementation and two ambient temperatures plus a pair-feeding group) and 16 replicates. Chickens were kept in thermoneutral conditions up to 28 days of age. They were then housed in groups of four per cage, in three environmentally controlled chambers: two thermoneutral (22.5 and 22.6°C) and one for heat stress (32°C). Half the chickens were fed a diet supplemented with vitamins C (257 to 288 mg/kg) and E (93 to 109 mg/kg). In the thermoneutral chambers, half of the chickens were pair-fed to heat stressed chickens, receiving each day the average feed intake recorded in the heat stress chamber in the previous day. Meat physical quality analyses were performed on the pectoralis major muscle. No ambient temperature×diet supplementation interaction effects were detected on performance, carcass, or meat quality traits. The supplemented diet resulted in lower growth performance, attributed either to a carry-over effect of the lower initial BW, or to a possible catabolic effect of vitamins C and E when supplemented simultaneously at high levels. Heat stress reduced slaughter and carcass weights, average daily gain and feed intake, and increased feed conversion. Growth performance of pair-fed chickens was similar to that of heat stressed chickens. Exposure to heat stress increased carcass and abdominal fat percentages, but reduced breast, liver and heart percentages. Pair-fed chickens showed the lowest fat percentage and their breast percentage was similar to controls. Heat stress increased meat pH and negatively affected meat color and cooking loss. In pair-fed chickens, meat color was similar to the heat stressed group. Shear force was not influenced by heat stress, but pair-fed chickens showed the tenderest meat. In conclusion, reduction in growth performance and negative changes in meat color in heat stressed chickens were attributed to depression in feed intake, whereas negative changes in body composition, higher meat pH and cooking loss were credited to high ambient temperature per se. Diet supplementation with vitamins C and E as antioxidants did not mitigate any of these negative effects.

Introduction: Parents feel fear and anxiety before surgery is performed on their child, and those feelings could obstruct their preparation for the surgery. Preoperative information could relieve those feelings., Objective: To determine the preoperative information needs of parents of children undergoing elective surgery., Patients and Method: A study was conducted on the parents of children who underwent elective surgery. Demographic data of parents were recorded. Preoperative information received or would like to have received was assessed in terms of contents, methods, opportunity, place and informant. Descriptive statistics were used., Results: Thirteen hundred parents were surveyed. More than 80% of them want preoperative information about anaesthesia, surgery, preoperative fasting, drugs and anaesthetic complications, monitoring, intravenous line management, pain treatment, postoperative feeding, anxiety control, hospitalisation room, recovery room, and entertainment in recovery room. Most want to be informed verbally, one to two weeks in advance and not on the same day of surgery. The informant should be the surgeon and in his office. In addition, they want information through leaflets, videos and simulation workshops, or guided tours., Conclusions: Parents need complete preoperative information about anesthesia, surgery and postoperative care, received verbally and in advance., (Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.)

Nevoid basal cell carcinoma syndrome (NBCCS) is a rare, autosomal dominant disorder characterized by multiple basal cell carcinomas (BCCs), odontogenic keratocysts, palmar and/or plantar pits, and ectopic calcifications of the falx cerebri. Myriad ophthalmologic findings are associated with NBCCS, including periocular BCCs, hypertelorism, strabismus, myelinated nerve fibers, and disorders of the retina and retinal pigment epithelium. We performed a literature search in PubMed for articles on the ophthalmologic manifestations of Gorlin syndrome, published between 1984 and 2014. Of 33 papers, 31 were included. Although Gorlin syndrome is due to mutations in a single gene, it displays variable phenotypic expressivity. Therefore, familiarity with this disorder across clinical specialties is necessary to avoid misdiagnosis. The ophthalmologist should be included in the multidisciplinary team for the management of Gorlin syndrome in order to prevent visual loss and improve the quality of life of these patients.

Purpose: To report a series of patients with fungal orbital cellulitis who underwent exenteration surgery and describe presenting features, management and outcomes at a referral center., Methods: Retrospective case series., Results: From November 2011 to March 2014, four patients underwent orbital exenteration for fungal orbital cellulitis at the University of Illinois. Three patients had mucormycosis and one had aspergillosis. All patients were treated with intravenous antifungals and underwent orbital exenteration. Two patients were successfully treated with supplemental intra-orbital catheter delivery of amphotericin B. Presenting visual acuity in the affected eye ranged from 20/25 to no light perception. Some level of ophthalmoplegia was present in three patients. Significantly elevated intraocular pressure was found in two patients. All patients with mucormycosis were found to have uncontrolled diabetes mellitus. One patient had a history of myelodysplastic syndrome, chronic hepatitis C infection, polysubstance abuse and Crohn's disease. Another patient had a history of alcoholic liver cirrhosis, Crohn's disease treated with systemic immunosuppression and renal cell carcinoma. The patient with aspergillosis had myelodysplastic syndrome and portal hypertension, and the initial presentation resembled giant cell arteritis. Two of four patients died during their hospitalization., Conclusions: Fungal orbital cellulitis has a high mortality rate despite aggressive antifungal treatment and orbital exenteration performed soon after the diagnosis is confirmed. Patients often have a history of immunosuppression and the onset may be insidious. There must be a high rate of suspicion for fungal orbital cellulitis given the appropriate signs and medical history in order to avoid treatment delay.

Purpose: To determine if adjusting the resection amount within a small range has a significant effect in the amount of lift achieved when performing the Muller's muscle and conjunctiva resection procedure (MMCR)., Methods: A retrospective chart review was performed analyzing 102 eyelids of 68 patients with involutional blepharoptosis that had a MMCR resection amount ranging from 8.0-9.5 mm performed by a single surgeon (P.S.), Results: The average lift for all resections was 2.30 mm. When comparing amongst all resection groups, there was no significant difference in the amount of lift obtained (p = 0.2454)., Conclusion: When performing the MMCR procedure, adjusting the resection amount within a small range of 8.0-9.5 mm does not affect the amount of lift achieved.

Background: Impaired stress resilience and a dysfunctional hypothalamic-pituitary-adrenal (HPA) axis are suggested to play key roles in the pathophysiology of illness progression in bipolar disorder (BD), but the mechanisms leading to this dysfunction have never been elucidated. This study aimed to examine HPA axis activity and underlying molecular mechanisms in patients with BD and unaffected siblings of BD patients., Methods: Twenty-four euthymic patients with BD, 18 siblings of BD patients, and 26 healthy controls were recruited for this study. All subjects underwent a dexamethasone suppression test followed by analyses associated with the HPA axis and the glucocorticoid receptor (GR)., Results: Patients with BD, particularly those at a late stage of illness, presented increased salivary post-dexamethasone cortisol levels when compared to controls (p = 0.015). Accordingly, these patients presented reduced ex vivo GR responsiveness (p = 0.008) and increased basal protein levels of FK506-binding protein 51 (FKBP51, p = 0.012), a co-chaperone known to desensitize GR, in peripheral blood mononuclear cells. Moreover, BD patients presented increased methylation at the FK506-binding protein 5 (FKBP5) gene. BD siblings presented significantly lower FKBP51 protein levels than BD patients, even though no differences were found in FKBP5 basal mRNA levels., Conclusions: Our data suggest that the epigenetic modulation of the FKBP5 gene, along with increased FKBP51 levels, is associated with the GR hyporesponsiveness seen in BD patients. Our findings are consistent with the notion that unaffected first-degree relatives of BD patients share biological factors that influence the disorder, and that such changes are more pronounced in the late stages of the illness., (© The Author 2014. Published by Oxford University Press on behalf of CINP.)

Background: The pathophysiology of bipolar disorder (BD) includes several systemic alterations, such as inflammatory markers, oxidative stress, and DNA damage. Most of these parameters may be related to dysfunctions in cellular resilience mechanisms reported in patients, such as endoplasmic reticulum stress and mitochondrial damage. As a consequence, these impairments can ultimately lead to cell death. Therefore, the aim of this study was to assess cell death and viability in peripheral blood mononuclear cells (PBMCs) from patients with BD and controls., Methods: Ten euthymic patients with BD type I and seven age- and sex-matched healthy controls were recruited and had peripheral blood collected by venipuncture in heparine tubes. PBMCs were isolated from total blood, followed by measurement of cell viability by trypan blue exclusion, and apoptosis and necrosis by anexin V/propidium iodide (PI) staining., Results: Cell viability did not significantly differ between groups, as well as the percentage of cells in necrosis or in late apoptosis/necrosis. However, the percentage of cells in early apoptosis was higher in patients when compared with controls (p=0.002)., Limitations: This is a preliminary study with relatively small sample size., Conclusions: The systemic toxicity along with dysfunctional cell resilience mechanisms reported in patients with BD may be inducing apoptosis in PBMCs. A deeper look into the clinical relevance of such findings is warranted., (© 2013 Elsevier B.V. All rights reserved.)

Aflatoxins (AF) and fumonisins (FU) are a major problem faced by poultry farmers, leading to huge economic losses. This experiment was conducted to determine the effects of AF (1 mg/kg of feed) and FU (25 mg/kg of feed), singly or in combination, on the lipid metabolism in commercial layers and investigate the efficacy of a commercial binder (2 kg/t of feed) on reducing the toxic effects of these mycotoxins. A total of 168 Hisex Brown layer hens, 37 wk of age, were randomized into a 3 × 2 + 1 factorial arrangement (3 diets with no binder containing AF, FU, and AF+FU; 3 diets with binder containing AF, FU, and AF+FU; and a control diet with no mycotoxins and binders), totaling 7 treatments. The hens contaminated with AF showed the characteristic effects of aflatoxicosis, such as a yellow liver, resulting from the accumulation of liver fat, lower values of plasma very low-density lipoprotein and triglycerides, and higher relative weight of the kidneys and liver. Hepatotoxic and nephrotoxic effects of FU were not observed in this study. On the other hand, the FU caused a reduction in small intestine length and an increase in abdominal fat deposition. The glucan-based binder prevented some of the deleterious effects of these mycotoxins, particularly the effects of AF on hepatic lipid metabolism, kidney relative weight, and FU in the small intestine.

Objective: To test the hypothesis that successful implementation of a care bundle designed to prevent nosocomial airway infection will be associated with decreased incidence of ventilator-associated tracheobronchitis., Design: Prospective pre- and post interventional., Setting: PICU at an academic medical center, Patients: : All patients admitted to the PICU who received invasive mechanical ventilation for greater than or equal to 48 hours between March 1, 2009, and December 31, 2011., Intervention: Multidisciplinary, unit wide implementation of an evidence-based care bundle to prevent ventilator-associated airway infection., Measurements and Main Results: There were 725 patients included in the analysis (338 patients preintervention and 387 patients postintervention). Baseline ventilator-associated tracheobronchitis rate in the preintervention period was 3.9 cases per 1,000 ventilator days compared with 1.8 cases per 1,000 ventilator days postintervention (p = 0.04, Fisher exact test). Compared with patients without ventilator-associated tracheobronchitis or ventilator-associated pneumonia, patients with ventilator-associated tracheobronchitis had fewer ventilator-free days in 28 days (4.9 vs 22; p < 0.0001, Mann-Whitney U test) and fewer ICU-free days in 28 days (0.5 vs 19; p < 0.0001, Mann-Whitney U test). These relationships remained significant after adjusting for covariates by multivariable linear regression., Conclusions: Successful implementation of a care bundle to prevent ventilator-associated infection was associated with decreased incidence of ventilator-associated tracheobronchitis. Development of ventilator-associated tracheobronchitis was independently associated with adverse outcomes in our cohort of pediatric ICU patients.

Unlabelled: We describe a recently developed chopper, the retrochopper, and a technique for managing black and brunescent cataracts. The technique enables the surgeon to effectively disassemble the nucleus and perform a safe procedure with a short learning curve., Financial Disclosure: No author has a financial or proprietary interest in any material or method mentioned., (Copyright © 2013 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Objective: To identify risk factors for the development of hospital-acquired pneumonia (HAP) caused by multidrug-resistant (MDR) bacteria in non-ventilated patients., Methods: This was a retrospective observational cohort study conducted over a three-year period at a tertiary-care teaching hospital. We included only non-ventilated patients diagnosed with HAP and presenting with positive bacterial cultures. Categorical variables were compared with chi-square test. Logistic regression analysis was used to determine risk factors for HAP caused by MDR bacteria., Results: Of the 140 patients diagnosed with HAP, 59 (42.1%) were infected with MDR strains. Among the patients infected with methicillin-resistant Staphylococcus aureus and those infected with methicillin-susceptible S. aureus, mortality was 45.9% and 50.0%, respectively (p = 0.763). Among the patients infected with MDR and those infected with non-MDR gram-negative bacilli, mortality was 45.8% and 38.3%, respectively (p = 0.527). Univariate analysis identified the following risk factors for infection with MDR bacteria: COPD; congestive heart failure; chronic renal failure; dialysis; urinary catheterization; extrapulmonary infection; and use of antimicrobial therapy within the last 10 days before the diagnosis of HAP. Multivariate analysis showed that the use of antibiotics within the last 10 days before the diagnosis of HAP was the only independent predictor of infection with MDR bacteria (OR = 3.45; 95% CI: 1.56-7.61; p = 0.002)., Conclusions: In this single-center study, the use of broad-spectrum antibiotics within the last 10 days before the diagnosis of HAP was the only independent predictor of infection with MDR bacteria in non-ventilated patients with HAP.

Rabbits are very sensitive to heat stress because they have difficulty eliminating excess body heat. The objective of the current study was to evaluate the effects of heat stress on slaughter weight, dressing percentage and carcass and meat quality traits of rabbits from two genetic groups. Ninety-six weaned rabbits were used: half were from the Botucatu genetic group and half were crossbreds between New Zealand White sires and Botucatu does. They were assigned to a completely randomized design in a 2 × 3 factorial arrangement (two genetic groups and three ambient temperatures: 18°C, 25°C and 30°C) and kept under controlled conditions in three environmental chambers from 5 to 10 weeks of age. Slaughter took place at 10 weeks, on 2 consecutive days. Meat quality measurements were made in the longissimus muscle. Actual average ambient temperature and relative humidity in the three chambers were 18.4°C and 63.9%, 24.4°C and 80.2% and 29.6°C and 75.9%, respectively. Purebred rabbits were heavier at slaughter and had heavier commercial and reference carcasses than crossbreds at 30°C; however, no differences between genetic groups for these traits were found at lower temperatures. No genetic group × ambient temperature interaction was detected for any other carcass or meat quality traits. The percentages of distal parts of legs, skin and carcass forepart were higher in crossbred rabbits, indicating a lower degree of maturity at slaughter in this group. The percentage of thoracic viscera was higher in the purebreds. Lightness of the longissimus muscle was higher in the purebreds, whereas redness was higher in the crossbreds. Slaughter, commercial and reference carcass weights and the percentages of thoracic viscera, liver and kidneys were negatively related with ambient temperature. Commercial and reference carcass yields, and the percentage of distal parts of legs, on the other hand, had a positive linear relationship with ambient temperature. Meat redness and yellowness diminished as ambient temperature increased, whereas cooking loss was linearly elevated with ambient temperature. Meat color traits revealed paler meat in the purebreds, but no differences in instrumental texture properties and water-holding capacity between genetic groups. Purebred rabbits were less susceptible to heat stress than the crossbreds. Heat stress resulted in lower slaughter and carcass weights and proportional reductions of organ weights, which contributed to a higher carcass yield. Moreover, it exerted a small, but negative, effect on meat quality traits.

Background: The purpose of this paper is to describe clinical characteristics and determine correlations between clinical outcomes and antifungal susceptibility among molecularly characterized ocular Fusarium isolates in Brazil., Methods: Forty-one Fusarium isolates obtained from 41 eyes of 41 patients were retrieved from the ophthalmic microbiology laboratory at São Paulo Federal University and grown in pure culture. These isolates were genotyped and antifungal susceptibilities determined for each isolate using a broth microdilution method. The corresponding medical records were reviewed to determine clinical outcomes., Results: The 41 isolates were genotypically classified as Fusarium solani species complex (36 isolates, 88%), Fusarium oxysporum species complex (two isolates, 5%), Fusarium dimerum species complex (one isolate, 2%) and two isolates that did not group into any of the species complexes. Final best corrected visual acuity varied from 20/20 to light perception and was on average 20/800 (logarithm of the minimum angle of resolution (LogMAR) 1.6). A history of trauma was the most common risk factor, being present in 21 patients (51%). Therapeutic penetrating keratoplasty was necessary in 22 patients (54%). Amphotericin B had the lowest minimum inhibitory concentration for 90% of isolates (MIC90) value (2 μg/mL) and voriconazole had the highest (16 μg/mL). There was an association between a higher natamycin MIC and need for therapeutic penetrating keratoplasty (Mann-Whitney test, P < 0.005)., Conclusion: Trauma was the main risk factor, and therapeutic penetrating keratoplasty was necessary in 54% of patients. Amphotericin B had the lowest MIC90 (2 μg/mL) of the three antifungal agents tested. There was an association between higher natamycin MIC levels and corneal perforation, emphasizing the need for antifungal susceptibility testing and tailoring of antifungal strategies.

Studies on the detection of animal by-products in poultry meat are rare and practically nonexistent in chicken meat. With the development of the technique of stable isotopes for traceability purposes and the certification of broiler diet patterns, it has been necessary to know the behavior of the isotopic signature of different tissues in birds, in case of a potential replacement of a diet containing animal ingredients with a strictly vegetable one and vice versa. Thus, this study, carried out at the São Paulo State University, Botucatu Campus, Brazil, aimed to evaluate meat from the breast, thigh, drumstick, and wings to trace the presence of poultry offal meal (OM) in broiler feed using the analysis of stable isotopes of carbon ((13)C/(12)C) and nitrogen ((15)N/(14)N) by mass spectrometry. In total, 720 one-d-old chicks were distributed into 6 groups: vegetable diet (VD) from 1 to 42 d; 8% poultry offal meal (OM) diet from 1 to 42 d; VD from 1 to 21 d and 8% OM diet from 22 to 42 d; VD from 1 to 35 d and 8% OM diet from 36 to 42 d; 8% OM diet from 1 to 21 d and VD from 22 to 42 d; and 8% OM diet from 1 to 35 d and VD from 36 to 42 d. Through the analysis of C and N, it is possible to trace the use of OM in broiler feeding when this ingredient is part of the feeding throughout the breeding phase or when it substitutes a strictly VD even up to 35 d. When an OM diet is substituted by a VD, the animal ingredient has to be part of the feeding for 21 d or longer to be detected by this method.

The pharmacokinetics of enrofloxacin (ENRO), a fluoroquinolone antimicrobial agent, was studied in male broiler chickens (Cobb) after single oral administration of 10 mg of ENRO/kg b.w. A high-performance liquid chromatography-photodiode array detector (DAD) (HPLC-DAD) method was developed and validated and used for quantitation of ENRO and its major metabolite ciprofloxacin in plasma. The HPLC analyses were carried out using a cationic-octadecyl mixed column and 0.05 mol/L phosphate buffer (pH 2.5)/acetonitrile as mobile phase. The sample preparation of plasma consisted of the precipitation of proteins followed by solid phase extraction on cationic-octadecyl mixed cartridges. The method was validated considering linear range, linearity, selectivity, sensitivity, limit of detection (LOD), limit of quantitation (LOQ), intra- and inter-day precisions and accuracy. The LOD and LOQ for both fluoroquinolones were 60 and 200 ng/mL for plasma. The plasma concentration vs. time graph was characteristic of a two-compartment open model. The maximal plasma concentration of 1.5 +/- 0.2 mg/mL was achieved at 9 +/- 2 h. The elimination half-life and the mean residence time of ENRO were 1.5 +/- 0.2 and 15.64 h, respectively. The area under the concentration-time curve was calculated as 35 +/- 4 mgxh/mL.

The 13C turnover rates of the liver and thoracic pectoral muscle of growing broilers were determined by feeding diets with varying 13C content. Male chicks (1-d-old) were subjected to treatments based on free choice of 5 different mixes of energy and protein sources from plants with C3 and C4 photosynthetic pathways that had differing 13C content. Rice bran (R) and soybean meal (S) were the C3 sources, while maize (C) and maize gluten meal (G) were the C4 sources. Choices were R + S, C + G, R + G, C + S or R + C + G + S. The 6th treatment was a complete feed (CF) that was similar to a commercial broiler feed. The isotopic composition of the birds' tissues was representative of the isotopic composition of the diets. The assimilation was faster for C3, in both liver and muscle, than for C4 diets, and give the delta per mil difference between the diet and tissues. The liver is the most active metabolic tissue and gave more rapid isotope turnover than in muscle.