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Abstract Background Electrotherapy effectiveness at different doses has been demonstrated in preclinical and clinical studies; however, several aspects that occur in the tumor growth kinetics before and after treatment have not yet been revealed. Mathematical modeling is a useful instrument that can reveal some of these aspects. The aim of this paper is to describe the complete growth kinetics of unperturbed and perturbed tumors through use of the modified Gompertz equation in order to generate useful insight into the mechanisms that underpin this devastating disease. Methods The complete tumor growth kinetics for control and treated groups are obtained by interpolation and extrapolation methods with different time steps, using experimental data of fibrosarcoma Sa-37. In the modified Gompertz equation, a delay time is introduced to describe the tumor's natural history before treatment. Different graphical strategies are used in order to reveal new information in the complete kinetics of this tumor type. Results The first stage of complete tumor growth kinetics is highly non linear. The model, at this stage, shows different aspects that agree with those reported theoretically and experimentally. Tumor reversibility and the proportionality between regions before and after electrotherapy are demonstrated. In tumors that reach partial remission, two antagonistic post-treatment processes are induced, whereas in complete remission, two unknown antitumor mechanisms are induced. Conclusion The modified Gompertz equation is likely to lead to insights within cancer research. Such insights hold promise for increasing our understanding of tumors as self-organizing systems and, the possible existence of phase transitions in tumor growth kinetics, which, in turn, may have significant impacts both on cancer research and on clinical practice.

Incontinentia pigmenti (IP) is a genodermatosis with an X-linked dominant mode of inheritance, characterized by ectodermal, mesodermal, neurological, ocular, and dental manifestations. The purpose of this case study was to report the oral and dental manifestations of an IP case in a Venezuelan pediatric patient. A 9 year-old Venezuelan girl was evaluated. She showed macular pigmented lesions in her face, trunk, back, legs, and fingers as well as abnormal hair distribution, alopecia on the vertex, and hypoplasia of eyebrows. During the dental examination, conical shaped-teeth and delayed dental eruption was evidenced. The microanalytical examination showed dentin without significant alterations in the mineralization except for hypermineralization in focal areas. In addition, a decrease in the enamel mineralization was observed. [ABSTRACT FROM AUTHOR]

Stingless bee honey is a natural product consisting of sugars, organic acids, proteins, minerals, vitamins, phenolic compounds, and flavonoids. Due to its healing properties, honey is often used in phytotherapy and for homemade syrups. The search for natural therapeutic alternatives has been an increasing trend in recent years, mainly due to the side effects of artificial drugs and increasing antibiotic resistance. Therefore, the aim of this study was to characterize physicochemical properties and the antimicrobial activity of honey from different species of stingless bees against the pathogenicity of the bacteria Escherichia coli and Staphylococcus aureus and to determine the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs). Honey samples from 15 different species of stingless bees from different regions of Brazil were used, and the analysis was performed by the broth microdilution method. We found a large variation in the physicochemical features among all the samples and no correlation to the MIC or MBC. It was also found that honey produced by Melipona rufiventris and Scaptotrigona tubiba were the most effective in combating pathogenic microorganisms due to its high antimicrobial activity, comparable to the results found for propolis. These data are important for the development of new strategies for the prevention and control of diseases caused by pathogenic microorganisms.

Alzheimer's disease (AD) is the leading cause of dementia, characterized by progressive cognitive decline. Cholinesterase inhibitors are commonly used to manage symptoms but have limited efficacy as the disease progresses. Aducanumab, a monoclonal antibody targeting amyloid-β (Aβ) plaques, has emerged as a novel therapeutic approach. Despite its Food and Drug Administration (FDA) approval, its efficacy and safety remain contentious, particularly following the European Medicines Agency's (EMA's) rejection. This systematic review aims to evaluate the efficacy, safety, and clinical outcomes of aducanumab in treating mild AD. Adhering to Preferred Reporting Items for Systematic Reviews (PRISMA) 2020 guidelines, we conducted a comprehensive search of PubMed and Science Direct databases, including randomized controlled trials (RCTs), cohort studies, and case-control studies focusing on aducanumab versus placebo in mild AD. Studies were screened based on predefined inclusion and exclusion criteria, and data were extracted on clinical outcomes, biomarkers, and neuroimaging markers. The risk of bias was assessed using the Cochrane Handbook and Newcastle-Ottawa Scale. Out of 967 identified records, seven studies met the inclusion criteria. Findings indicated a dose-dependent reduction in Aβ plaques with aducanumab, but clinical outcomes varied. High-dose aducanumab (10 mg/kg) demonstrated significant improvements in some studies but not others. Adverse events, notably amyloid-related imaging abnormalities (ARIA), were frequent, especially at higher doses. The studies exhibited heterogeneous treatment effects and underscored the potential of cerebrospinal fluid biomarkers as an alternative to amyloid positron emission tomography (PET) scans. Aducanumab shows promise in reducing Aβ plaques and has potential clinical benefits at high doses; however, its safety profile, particularly concerning ARIA, remains a significant concern. The variability in clinical efficacy highlights the need for further research to optimize dosing regimens and identify patient populations most likely to benefit from treatment. Future studies should focus on refining treatment protocols and exploring alternative biomarkers to improve therapeutic outcomes for AD., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Medel Sánchez et al.)

Livestock predation constitutes the primary source of conflict between humans and large carnivores. Moreover, human factors, such as attitudes and emotions, can affect people's tolerance towards carnivores, exacerbating the conflict. Such conflicts often lead to retaliatory killing of carnivores, which not only poses significant threats to species conservation but also to ecosystem functioning and services. Therefore, mitigating human-carnivore conflicts is essential to promote both species conservation and human well-being. Here, we studied the conflict between extensive cattle ranching and the conservation of jaguars (Panthera onca) and pumas (Puma concolor) in 129 ranches located in the Amazon arc of deforestation. We interviewed ranchers about livestock management procedures, livestock mortality, approaches to reduce predation in the area, and attitudes regarding carnivores and conservation. Our results revealed that ranchers did not perceive carnivore attacks as the primary cause of cattle mortality. However, they exhibited a significant lack of tolerance towards these incidents, partially explained by economic reasons. They also showed negative attitudes towards big cats, which were mainly associated with social factors, such as low educational background. As a consequence, jaguar and puma were frequently killed in retaliation. Ranches showed different vulnerability to attacks depending on cattle management (cattle density, calves) and landscape (forest cover inside the ranch, distance to national parks). Our findings suggest that the conflict between cattle ranching and big cats conservation in the Amazon deforestation frontier is trigger by livestock predation, but perpetuated by limited knowledge about carnivores, the lack of support from the government to mitigate livestock losses, and the perception that conservation laws conditioned the viability of cattle ranching. Forthcoming mitigation strategies should focus on interventions designed to increase people's tolerance towards jaguars and pumas (e.g. improving knowledge about ecosystem services provided by large carnivores)., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Díaz-Vaquero 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.)

Transcription of antisense long noncoding RNAs (lncRNAs) occurs pervasively across eukaryotic genomes. Only a few antisense lncRNAs have been characterized and shown to control biological processes, albeit with idiosyncratic regulatory mechanisms. Thus, we largely lack knowledge about the general role of antisense transcription in eukaryotic organisms. Here, we characterized genes with antisense transcription initiating close to the poly(A) signal of genes (PAS genes) in Arabidopsis (Arabidopsis thaliana). We compared plant native elongation transcript sequencing (plaNET-seq) with RNA sequencing during short-term cold exposure and detected massive differences between the response in active transcription and steady-state levels of PAS gene-derived mRNAs. The cold-induced expression of transcription factors B-BOX DOMAIN PROTEIN28 (BBX28) and C2H2-TYPE ZINC FINGER FAMILY PROTEIN5 (ZAT5) was detected by plaNET-seq, while their steady-state level was only slightly altered due to high mRNA turnover. Knockdown of BBX28 and ZAT5 or of their respective antisense transcripts severely compromised plant freezing tolerance. Decreased antisense transcript expression levels resulted in a reduced cold response of BBX28 and ZAT5, revealing a positive regulatory role of both antisense transcripts. This study expands the known repertoire of noncoding transcripts. It highlights that native transcription approaches can complement steady-state RNA techniques to identify biologically relevant players in stress responses., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death among women worldwide. Surgical treatments, including mastectomy and subsequent breast reconstruction, are critical components of breast cancer management. This systematic review compares the outcomes of flap versus implant reconstruction post-mastectomy, focusing on aesthetic differences, pain, recovery, and psychological adaptation. Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, we conducted a comprehensive literature search across PubMed, Cochrane, and ScienceDirect databases. Inclusion criteria targeted studies comparing aesthetic outcomes, pain, recovery costs, duration, and psychological adaptation between flap and implant breast reconstructions. We excluded non-English and non-Spanish studies, case reports, and those without full-text availability. The risk of bias was assessed using the Newcastle-Ottawa Scale (NOS). From an initial pool of 25,881 articles, 16 high-quality studies involving 14,196 participants were selected for synthesis. Flap reconstruction was associated with higher patient satisfaction regarding aesthetic outcomes and psychological well-being but also had higher complication rates, including infections and wound dehiscence. Implant reconstruction showed fewer complications but did not achieve the same level of patient satisfaction. Flap reconstruction, despite its higher complication rates, tends to provide superior aesthetic and psychological outcomes compared to implant reconstruction. These findings highlight the importance of personalized treatment plans considering individual patient needs and preferences. Future research should focus on long-term randomized controlled trials (RCTs) and standardized outcome measures to further delineate the comparative effectiveness of these reconstruction techniques. Personalized care and ongoing research are essential to improving the quality of life for breast cancer survivors undergoing reconstruction., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Aleman Paredes et al.)

Stomata govern the gaseous exchange between the leaf and the external atmosphere, and their function is essential for photosynthesis and the global carbon and oxygen cycles. Rhythmic stomata movements in daily dark/light cycles prevent water loss at night and allow CO 2 uptake during the day. How the actors involved are transcriptionally regulated and how this might contribute to rhythmicity is largely unknown. Here, we show that morning stomata opening depends on the previous night period. The transcription factors PHYTOCHROME-INTERACTING FACTORS (PIFs) accumulate at the end of the night and directly induce the guard cell-specific K + channel KAT1. Remarkably, PIFs and KAT1 are required for blue light-induced stomata opening. Together, our data establish a molecular framework for daily rhythmic stomatal movements under well-watered conditions, whereby PIFs are required for accumulation of KAT1 at night, which upon activation by blue light in the morning leads to the K + intake driving stomata opening., (© 2024. The Author(s).)

This case report aims to delineate the challenges and management strategies for a patient with bilateral mutilated hands within a secondary care level in Mexico, contributing to medical literature and potentially guiding future patient care. Mutilated hands represent a significant surgical and rehabilitative challenge due to the profound structural damage they cause, leading to considerable functional impairment and psychological distress. The complexity of these injuries necessitates a multidisciplinary approach, particularly in resource-constrained settings. We present a case of a 45-year-old male with no prior significant medical history who sustained bilateral mutilated hands from an industrial accident involving hot rollers. The patient underwent extensive surgical reconstruction and postoperative care, facing complications such as skin graft integration issues and infections, which required a multidisciplinary treatment approach., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Aleman Paredes et al.)

Burn injuries, a major global health concern, result in an estimated 180,000 fatalities annually. Despite tremendous progress in treatment methods over the years, the morbidity and mortality associated with burns remain significant. Autologous skin grafting, particularly split-thickness skin grafting (STSG), has been a cornerstone in burn reconstruction, and it has facilitated survival and functional recovery for total body surface area (TBSA) significantly. However, the requirement for primary closure at the donor site due to the constraints of full-thickness donor harvesting continues to pose challenges. The introduction of dermal regenerative templates (DRT) in the late 1970s marked a substantial step forward in tissue engineering, addressing the inadequacy of dermal replacement with STSGs. This systematic review aimed to compare the outcomes of different graft types - bioengineered, autografts, allografts, and xenografts - in burn reconstruction over the last 24 years. The review focused on the pros and cons of each graft type, offering clinical insights grounded in experience and evidence. The approach involved a systematic review of studies published in English from January 2000 to January 2024, covering randomized controlled trials (RCTs), cohort studies, case-control studies, and case series. The participants comprised individuals of all ages who underwent burn reconstruction with skin grafts, specifically split-thickness grafts, full-thickness grafts, composite grafts, and epidermal grafts (autografts, allografts, and xenografts) and bioengineered grafts. The primary outcomes were functional and cosmetic results, patient satisfaction, graft survival, and complications. The risk of bias was evaluated using the Cochrane risk-of-bias tool for randomized trials version 2 (RoB 2), the Newcastle-Ottawa Scale (NOS) for non-randomized studies, and the Canada Institute for Health Economics (IHE) quality appraisal tool for case series. Our initial search yielded a total of 1,995 articles, out of which 10 studies were selected for final analysis. Among the four clinical trials assessed, 75% showed a high risk of bias. The studies reviewed involved various graft types, with six studies (60%) concentrating on allografts, three (30%) on autografts, and one (10%) on bioengineered skin grafts. The outcomes were varied, underlining the intricate nature of burn wound management. Our evaluation revealed promising results for autologous-engineered skin substitutes and allografts but also highlighted methodological disparities among the studies included. The dominance of observational studies and the diversity of outcome measures present obstacles to direct comparisons. Future research should address these limitations, employing well-structured RCTs, standardized outcome measures, and exploring long-term outcomes and patient-specific factors. The rapidly evolving field of regenerative medicine offers great potential for novel grafting methods. This systematic review provides valuable insights into the diverse outcomes of burn reconstruction using different graft types. Autologous-engineered skin substitutes and allografts seem to hold significant promise, suggesting a possible shift in grafting techniques. However, methodological inconsistencies and the lack of high-quality evidence underscore the necessity for further research to fine-tune burn care approaches., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Aleman Paredes et al.)

Purpose: Even though transjugular intrahepatic portosystemic shunt (TIPS) using Fluency Stent-grafts provides good shunt patency rates, shunt dysfunction is a great concern after TIPS creation, occurring in up to 20% of cases within one year. The objective of this study was to describe shunt dysfunction patterns after TIPS creation using a combination of generic stent-grafts/bare-stents., Materials and Methods: Single-center retrospective study of all TIPS revisions between January 2005 and December 2020. TIPS revision angiograms were analyzed for stents' positions, stenoses' diameters, and stenoses' locations., Results: Out of 99 TIPS, a total of 33 TIPS revisions were included. The median time to TIPS revision was 10.4 months. Angiograms showed four patterns of TIPS dysfunction-associated features (DAF), defined as follows: Type 1 was defined as stenosis located after the stent end in the hepatic vein (HV), type 2 as intra-stent stenosis located in the hepatic vein, type 3 as intra-stent stenosis or a kink in the parenchymal tract or the portal vein end of the TIPS, and type 4 as a complete TIPS occlusion. Types 1, 2, 3, and 4 were seen in 23 (69.7%), 5 (15.2%), 2 (6.1%), and 3 (9.1%) TIPS respectively. TIPS revision was successful in 30 (90.1%) patients with median pre- and post-TIPS revision PSG of 18.5 mmHg and 8 mmHg respectively (p < .001)., Conclusion: Our results illustrate the four angiographic patterns of TIPS DAF after TIPS creation using a combination of generic stent-grafts/bare-stents and emphasize the need for appropriate stent length extending to the HV/inferior vena cava junction., (© 2024. The Author(s).)

A wide range of nuclear proteins are involved in the spatio-temporal organization of the genome through diverse biological processes such as gene transcription and DNA replication. Upon stimulation by testosterone and translocation to the nucleus, multiple androgen receptors (ARs) accumulate in microscopically discernable foci which are irregularly distributed in the nucleus. Here, we investigated the formation and physical nature of these foci, by combining novel fluorescent labeling techniques to visualize a defined chromatin locus of AR-regulated genes-PTPRN2 or BANP-simultaneously with either AR foci or individual AR molecules. Quantitative colocalization analysis showed evidence of AR foci formation induced by R1881 at both PTPRN2 and BANP loci. Furthermore, single-particle tracking (SPT) revealed three distinct subdiffusive fractional Brownian motion (fBm) states: immobilized ARs were observed near the labeled genes likely as a consequence of DNA-binding, while the intermediate confined state showed a similar spatial behavior but with larger displacements, suggesting compartmentalization by liquid-liquid phase separation (LLPS), while freely mobile ARs were diffusing in the nuclear environment. All together, we show for the first time in living cells the presence of AR-regulated genes in AR foci., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

TBR1 is a neuron-specific transcription factor involved in brain development and implicated in a neurodevelopmental disorder (NDD) combining features of autism spectrum disorder (ASD), intellectual disability (ID) and speech delay. TBR1 has been previously shown to interact with a small number of transcription factors and co-factors also involved in NDDs (including CASK, FOXP1/2/4 and BCL11A), suggesting that the wider TBR1 interactome may have a significant bearing on normal and abnormal brain development. Here, we have identified approximately 250 putative TBR1-interaction partners by affinity purification coupled to mass spectrometry. As well as known TBR1-interactors such as CASK, the identified partners include transcription factors and chromatin modifiers, along with ASD- and ID-related proteins. Five interaction candidates were independently validated using bioluminescence resonance energy transfer assays. We went on to test the interaction of these candidates with TBR1 protein variants implicated in cases of NDD. The assays uncovered disturbed interactions for NDD-associated variants and identified two distinct protein-binding domains of TBR1 that have essential roles in protein-protein interaction., (© The Author(s) 2022. Published by Oxford University Press.)

Non-governmental organizations (NGOs) in dentistry seek to promote the improvement on oral health in the most disadvantaged regions. The objective of this study is to identify the level of knowledge, expectations, and motivations that dental school students have about volunteering in dentistry, as well as to evaluate possible differences in these variables depending on their level of dental training. During the month of September 2022, a voluntary and anonymous online survey was carried out among all the students at the Dentistry School of Oviedo University. There were 5 questions to judge knowledge about global oral health course. 12 additional questions were included to assess the willingness to volunteer in international setting, the volunteer profile, as well as the most effective means to improve oral health in host communities. None of the students from our center had participated as a volunteer in dental NGOs, but up to 64.4% of them had considered their collaboration. The level of knowledge about global oral health obtained was low, with the percentage of correct answers ranging between 14.4% (in the question about the ideal patient/dentist ratio) and 57.8% (in the question about the fluoride concentration in drinking water). Majority of dental students (98.9%) were not aware that basic package of oral care was created by WHO. Significantly, the students of the clinical courses showed a greater motivation to volunteer.

The coronavirus 19 (COVID-19) pandemic has been one of the most significant challenges to public health in recent decades. The heterogeneity of government responses and the varying preparedness of health systems has determined that the pandemic's impact differs from country to country. Chile is no stranger to the challenges posed by rehabilitation in a developing country. We aimed to describe the approach to rehabilitation during the pandemic in Chile in the public health system since rehabilitation is considered a relevant health strategy from the prevention to management of complications, mitigation of sequelae, or new complications associated with COVID-19. For this, a descriptive study was conducted on the rehabilitation strategies implemented by Chile to respond to the COVID-19 pandemic. The analysis includes the context of the Chilean health system and the matrix of access to rehabilitation services in COVID-19. The Health Ministry (MINSAL) rehabilitation strategy includes five central axes: approaches, specific lines, transversal lines, intervention, and funding. Additionally, the policies were based and supported by the WHO recommendations. Intensive care unit beds were increased approximately 68%, and the primary care response was the reconversion of function depending on the epidemiological context. During the 2021-2022 period, the estimated number of people diagnosed with a post-COVID-19 condition was 80,528. With this, we can conclude that a developing country has managed to coordinate a rehabilitation policy for people with COVID-19 by generating a structure of the different health system levels. However, the effectiveness of this policy will need to be evaluated in the future., Competing Interests: XN-Z, KH-M, RV-S, CC-A, MR-Q, and CÁ-V are workers of the Ministry of Health of Chile, however, they did not work directly in the analysis and interpretation of the data. The remaining 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 © 2022 Torres-Castro, Neculhueque-Zapata, Hrzic-Miranda, Gutiérrez-Arias, Valenzuela-Suazo, Castro-Acuña, Ríos-Quevedo, Águila-Villanueva and Seron.)

Dispersal is a key demographic process involving three stages: emigration, transience and settlement; each of which is influenced by individual, social and environmental determinants. An integrated understanding of species dispersal is essential for demographic modelling and conservation planning. Here, we review the dispersal patterns and determinants documented in the scientific literature for the grey wolf (Canis lupus) across its distribution range. We showed a surprisingly high variability within and among study areas on all dispersal parameters - dispersal rate, direction, distance, duration and success. We found that such large variability is due to multiple individual, social and environmental determinants, but also due to previously overlooked methodological research issues. We revealed a potential non-linear relationship between dispersal rate and population density, with dispersal rate higher at both ends of the gradient of population density. We found that human-caused mortality reduces distance, duration and success of dispersal events. Furthermore, dispersers avoid interaction with humans, and highly exposed areas like agricultural lands hamper population connectivity in many cases. We identified numerous methodological research problems that make it difficult to obtain robust estimates of dispersal parameters and robust inferences on dispersal patterns and their determinants. In particular, analyses where confounding factors were not accounted for led to substantial knowledge gaps on all aspects of dispersal in an otherwise much-studied species. Our understanding of wolf biology and management would significantly benefit if wolf dispersal studies reported the results and possible factors affecting wolf dispersal more transparently., (© 2021 The Authors. Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

Biomaterials and their surfaces regulate the biological response and ultimately the quality of healing at a possible site of implantation. The physical, chemical and topographical properties of implants' surfaces play a decisive role in the biological integration process for their immediate loading and long-term success. Since at this level of biological interaction nano-dimensionality is basically entailed, bio-functional nanostructured composites either as filling/cement or coating to metallic implants are required. This study shows the possibility of synthesizing two phases of nanostructured titanium phosphate (π and ρ polymorphs) and enriching them with silver nanoparticles and strontium. More importantly, Ag-Sr-enriched nanostructured π‑titanium phosphate is induced to grow on a commercially available titanium alloy (Ti-6Al-4V), widely used in orthopedic and dental implants, under highly controlled conditions. Structural and microscopic studies, using XRD, HRTEM and SEM altogether confirm the resultant phases and their enrichment with strontium and silver nanoparticles with an average particle size around 6 nm. Using confocal laser scanning microscopy, the surface roughness was measured and is found to lay at the interface between the nanosized and microsized topologies. Ion release assessments showed that the presence of strontium controlled the release rate of silver ions and this could be beneficial in terms of decreasing the accompanied cytotoxicity that is usually encountered at high concentrations of silver release. Antimicrobial and cell proliferation assays have proved that enriching titanium phosphate with strontium and silver nanoparticles has improved their antimicrobial properties, while the cytotoxicity could be controlled., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Tuberculosis (TB) misdiagnosis remains a public health concern, especially among people living with HIV (PLHIV), given the high mortality associated with missed TB diagnoses. The main objective of this study was to describe the all-cause mortality, TB incidence rates and their associated risk factors in a cohort of PLHIV with presumptive TB in whom TB was initially ruled out. We retrospectively followed a cohort of PLHIV with presumptive TB over a 2 year-period in a rural district in Southern Mozambique. During the study period 382 PLHIV were followed-up. Mortality rate was 6.8/100 person-years (PYs) (95% CI 5.2-9.2) and TB incidence rate was 5.4/100 PYs (95% CI 3.9-7.5). Thirty-six percent of deaths and 43% of TB incident cases occurred in the first 12 months of the follow up. Mortality and TB incidence rates in the 2-year period after TB was initially ruled out was very high. The TB diagnostic work-up and linkage to HIV care should be strengthened to decrease TB burden and all-cause mortality among PLHIV with presumptive TB.

In this study, the influence of defined extrusion-like treatment conditions on the denaturation behavior and kinetics of single- and multi-component protein model systems at a protein concentration of 70% ( w/w ) was investigated. α-Lactalbumin (αLA) and β-Lactoglobulin (βLG), and whey protein isolate (WPI) were selected as single- and multi-component protein model systems, respectively. To apply defined extrusion-like conditions, treatment temperatures in the range of 60 and 100 °C, shear rates from 0.06 to 50 s⁻ 1 , and treatment times up to 90 s were chosen. While an aggregation onset temperature was determined at approximately 73 °C for WPI systems at a shear rate of 0.06 s⁻ 1 , two significantly different onset temperatures were determined when the shear rate was increased to 25 and 50 s⁻ 1 . These two different onset temperatures could be related to the main fractions present in whey protein (βLG and αLA), suggesting shear-induced phase separation. Application of additional mechanical treatment resulted in an increase in reaction rates for all the investigated systems. Denaturation was found to follow 2.262 and 1.865 order kinetics for αLA and WPI, respectively. The reaction order of WPI might have resulted from a combination of a lower reaction order in the unsheared system (i.e., fractional first order) and higher reaction order for sheared systems, probably due to phase separation, leading to isolated behavior of each fraction at the local level (i.e., fractional second order).

The influence of thermomechanical treatment (temperature 60 °C-100 °C and shear rate 0.06 s -1 -50 s -1 ) and mixing ratio of β-lactoglobulin (βLG) and α-lactalbumin (αLA) (5:2 and 1:1) on the denaturation and aggregation of whey protein model systems with a protein concentration of 60% and 70% ( w/w ) was investigated. An aggregation onset temperature was determined at approx. 80 °C for both systems (5:2 and 1:1 mixing ratio) with a protein concentration of 70% at a shear rate of 0.06 s -1 . Increasing the shear rate up to 50 s -1 led to a decrease in the aggregation onset temperature independent of the mixing ratio. By decreasing the protein concentration to 60% in unsheared systems, the aggregation onset temperature decreased compared to that at a protein concentration of 70%. Furthermore, two significantly different onset temperatures were determined when the shear rate was increased to 25 s -1 and 50 s -1 , which might result from a shear-induced phase separation. Application of combined thermal and mechanical treatment resulted in overall higher degrees of denaturation independent of the mixing ratio and protein concentration. At the conditions applied, the aggregation of the βLG and αLA mixtures was mainly due to the formation of non-covalent bonds. Although the proportion of disulfide bond aggregation increased with treatment temperature and shear rate, it was higher at a mixing ratio of 5:2 compared to that at 1:1.

Background: There is scarce information detailing clinical and physiological effects of reversible injectable protocols of chemical restraint on Neotropical primates., Methods: Nineteen captive Spix´s Owl monkeys (Aotus vociferans) were assessed in a double-blind randomized crossover study using the following: ketamine/xylazine [KX], ketamine/midazolam [KM] and ketamine/xylazine/midazolam [KXM]. During immobilization, respiratory and pulse rates, rectal temperature, haemoglobin oxygen saturation and arterial blood pressure were recorded at 5-minute intervals during a 20-minute period; afterwards, antagonist drugs (yohimbine for xylazine and flumazenil for midazolam) were, respectively, administered. Quality and duration of induction, immobilization and recovery periods were recorded., Results: Ketamine/xylazine increased manipulation sensitivity and produced poor muscle relaxation. KM maintained all assessed parameters within physiological ranges. KXM produced depressant cardiorespiratory effects and hypotension. All protocols produced hypothermia., Conclusions: Based on its adequate anaesthetic depth and minimum effects on physiological parameters, KM is suitable for immobilizing A vociferans and performing short-term procedures lasting around 20 minutes., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The use of fiberglass in dentistry has increased due to the improvements in the development of adhesive techniques reducing the cost of treatment and avoiding abutment tooth craving. The present study aims to evaluate the clinical usefulness of the new technique to fabricate a direct fiber-reinforced composite bridge (FRCB) over a long period of time. Twenty-one FRCB were performed with the new direct technique on 21 patients with a mean age of 58.85 years and female predominance in the Faculty of Dentistry of Oviedo (Spain). The framework design releases the embrasures allowing adequate interproximal brushing, avoidance of periodontal disease and interproximal caries. A baseline examination was performed and the patients were examined regularly at six-month intervals (nine years' follow-up). The restorations were also evaluated by an examiner using parameters to check their stability, longevity and the lack of periodontal disease. The most frequent location was the maxillary premolar region and the purpose of the restorations was to give a definitive bridge in 100% of the patients. Only one total debonding of the prostheses was detected during the observation period at 24 months and three partial adhesive-cohesive veneering composite fractures at the pontic after 60, 72 and 84 months, respectively. Kaplan-Meier was performed to detect the overall survival rate of the restorations at the end of the follow-up. Nine-year survival rates for the FRCB was 95.2%. All the cases had a clinically acceptable periodontal condition and an interproximal absence of caries in the abutment teeth. Currently, this type of restoration allows a minimally invasive aesthetic and is an affordable procedure, being a good alternative to other types of treatments.

The aim of this study is to establish the falsifiability of the "osteoporotic hypothesis" for hip fracture, according to which the bone density and mineral composition of bone tissue in patients with hip fracture is poorer than when no such fracture is present, and that this circumstance is relevant to the occurrence of a fracture. The study population consisted of forty patients treated with arthroplasty. Twenty patients with femoral neck fracture and another twenty with hip osteoarthritis received the same diagnostic protocol and the same antibiotic, anaesthetic, surgical and antithrombotic prophylaxis. Levels of calcium (Ca), phosphorus (P) and vitamin D in blood, amongst other values, were determined, and five samples of bone tissue from the proximal femoral metaphysis were obtained and characterised by optical microscopy and microanalytical analysis. No statistically significant differences were observed between the two groups with respect to the trabecular number, area or thickness, or inter-trabecular distance. However, there were differences in the length of the trabeculae, which was greater in the patients with hip osteoarthritis (p = 0.002), but not when the groups were compared by gender. When compared by age, a greater inter-trabecular distance was observed in the patients aged over 75 years (p = 0.036) but there were no differences in the remaining parameters. Serum levels of Ca (p = 0.03), P (p < 0.01) and vitamin D (p < 0.01) were lower in the fracture group. In the quantitative microanalytical analysis, no significant differences were observed in bone levels of Ca or P or in the Ca/P index, nor was there any correlation between serum and levels of bone Ca or P (Ca-0.197:p = 0.314;P-0.274:p = 0.158).Multiple linear regression revealed no correlation between the diagnoses, vitamin D and bone levels of Ca or P. Despite the reduced serum levels of Ca and P in the patients with hip fracture, no correlation was observed with bone levels of Ca and P,which were similar in both groups. There were differences in the organic bone structure, in terms of length and inter-trabecular distance. For patients with osteoporosis, treatment should be aimed at increasing the synthesis of bone trabeculae to reinforce their structure. Nevertheless, no such treatment can prevent falls, and therefore no reduction in hip fractures amongst this population can be assured., Competing Interests: Declaration of Competing Interests None of the authors has received any economic consideration from third parties. There is no conflict of interest., (Copyright © 2020. Published by Elsevier Ltd.)

This ethnography was conducted in Barcelona, a city that provides different gay leisure resources, such as gay saunas. We aimed to analyze from studies on gender and masculinities, how sexuality, perception of HIV infection and other sexually transmitted infections (STIs), and preventive measures are articulated in gay sauna male sex workers (MSW). Ten in-depth interviews and observation were conducted between 2012 and 2016. Safe sex practices are more frequent with clients, while risk practices are carried out more with non-commercial partners. Sexual orientation plays an important role. Homosexuals assume riskier practices in sex work than heterosexuals. Drug use or lack of support networks were associated with higher social vulnerability and risk behaviors. Contracting HIV still creates fear, while having other STIs is perceived as part of a man's sexual life. The MSW affirms masculinity with concurrent sexual partners, breadwinner, and on the other hand, questions a heteronormative model. Interventions for the prevention of HIV and STIs in this group should consider social determinants such as inferior work alternatives and the provision of more significant social support.

This study using the Catalan PISCIS cohort explores risk factors of migrants' late presentation and the impact of late presentation on their health outcomes. We analyse 9590 new HIV diagnoses enrolled in the cohort between 2004 and 2016. Univariate and multivariate logistic regression models are used to identify risk factors associated with late presentation among migrants, giving crude and adjusted odds ratios and their 95% confidence intervals. Cox regression models are estimated to identify risk factors associated with AIDS/death, and crude and adjusted hazard ratios and 95% confidence intervals are reported. Late presentation is higher in migrants than non-migrants. Among migrants, region of origin is associated with late presentation and AIDS/death during follow-up. The results highlight persisting inequalities in HIV diagnosis and care among migrants in Catalonia. Targeted interventions addressed to specific subgroups in the migrant population are needed.

Objective: We analyse how reproductive health strategies have been incorporated into the everyday activities of the services and the resulting transformation of professional and user practices., Method: Cartographic research taking a multi-sited ethnographic approach that seeks to reveal the processes of transformation. Data generation techniques featuring participant observation and situated interviews. Discourse analysis of the text corpus using three analytical axes based on three main lines of action promoted by the strategies., Results: We identified transformations in: 1) demedicalisation: an increase in midwives' know-how and autonomy, changes in episiotomy practice and the facilitation of bonding practices; 2) warmth of care: incorporation of women's needs and expectations and improvements in the comfortableness of birth settings, especially in assistance at physiological birth; and 3) participation: actions that foster shared decision-making and the involvement of the persons accompanying women in labour., Conclusions: Above all, transformation is visible in the incorporation of new attitudes, sensibilities and practices that have developed around the old structures, especially during physiological childbirth. The more technological areas have been less permeable to change. Risk management in decision-making and addressing diversity are identified as areas where transformation is less evident., (Copyright © 2018 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.)

The Mediator complex regulates transcription by connecting enhancers to promoters. High Mediator binding density defines super enhancers, which regulate cell-identity genes and oncogenes. Protein interactions of Mediator may explain its role in these processes but have not been identified comprehensively. Here, we purify Mediator from neural stem cells (NSCs) and identify 75 protein-protein interaction partners. We identify super enhancers in NSCs and show that Mediator-interacting chromatin modifiers colocalize with Mediator at enhancers and super enhancers. Transcription factor families with high affinity for Mediator dominate enhancers and super enhancers and can explain genome-wide Mediator localization. We identify E-box transcription factor Tcf4 as a key regulator of NSCs. Tcf4 interacts with Mediator, colocalizes with Mediator at super enhancers and regulates neurogenic transcription factor genes with super enhancers and broad H3K4me3 domains. Our data suggest that high binding-affinity for Mediator is an important organizing feature in the transcriptional network that determines NSC identity.

The transversal screw was introduced in order to overcome some disadvantages of the transocclusal screw. However, its mechanical risk has not been studied sufficiently. The main purpose of this research was to assess and compare stress distribution in the screws and abutment of a single-crown implant with transversal and transocclusal screw models. Two 3D models were assembled to analyse a single-implant-supported prosthesis with transversal and transocclusal screws embedded in the jawbone. The crown was subjected to a static load of value 300 N with different levels of inclination. The transversal screw model, with an axial load of 15°, was the one with lowest stress values in all its components. However, the stress was greater with more inclined loads when compared with the transocclusal model. The prosthetic transversal screw showed much less stress than the rest of the components for any load inclination. The transversal screw design is the option with the lowest risk of mechanical complications, both in the prosthetic screw and in the abutment screw, when applying forces of lower inclination. The more oblique forces favoured a better biomechanical environment in the abutment and its screw in the transocclusal screw model., (© 2019 John Wiley & Sons, Ltd.)

This study aimed to describe the methodological characteristics of publications on HIV and masculinity, to identify possible information gaps and determine the main thematic areas. A systematic review was conducted of gender, masculinity, HIV infection and other sexually-transmitted infections in original articles published between 1992 and 2015. Original studies published from Pubmed and Scopus were included. A total of 303 articles were identified, of which 187 were selected. Most of the studies were qualitative and the most widely used technique was the interview. Twenty-nine-point five percent of studies were performed in South Africa, 20.8% in the USA, and 3.2% in Europe. Fifteen percent of the studies were performed in heterosexuals, 12.8% in men who have sex with men, and 60% did not specify the sexual orientation of the population. Eight thematic areas were defined, the most frequent being sexuality and risk behaviours, defined by men's need to demonstrate they were sexually active and a breadwinner. Most studies on HIV and masculinity show a gender bias by not specifying the sexual identity of the population. Studies should consider diversity in sexual and cultural identity in different contexts, including in Europe, to carry out more effective HIV interventions from a masculinity perspective.

Mesenchymal stem cells (MSCs) can differentiate toward epithelial cells and may be used as an alternative source for generation of heterotypical artificial human skin substitutes, thus, enhancing their development and translation potential to the clinic. The present study aimed at comparing four types of heterotypical human bioengineered skin generated using MSCs as an alternative epithelial cell source. Adipose-tissue-derived stem cells (ADSCs), dental pulp stem cells (DPSCs), Wharton's jelly stem cells (WJSCs) and bone marrow stem cells (BMSCs) were used for epidermal regeneration on top of dermal skin substitutes. Heterotypic human skin substitutes were evaluated before and after implantation in immune-deficient athymic mice for 30 d. Histological and genetic studies were performed to evaluate extracellular matrix synthesis, epidermal differentiation and human leukocyte antigen (HLA) molecule expression. The four cell types differentiated into keratinocytes, as shown by the expression of cytokeratin 10 and filaggrin 30 d post-grafting; also, they induced dermal fibroblasts responsible for the synthesis of extracellular fibrillar and non-fibrillar components, in a similar way among each other. WJSCs and BMSCs showed higher expression of cytokeratin 10 and filaggrin, suggesting these cells were more prone to epidermal regeneration. The absence of HLA molecules, even when the epithelial layer was differentiated, supports the future clinical use of these substitutes - especially ADSCs, DPSCs and WJSCs - with low rejection risk. MSCs allowed the generation of bioengineered human skin substitutes with potential clinical usefulness. According to their epidermal differentiation potential and lack of HLA antigens, WJSCs should preferentially be used.