Etiology of major limb amputations at a tertiary care centre in Malawi

Introduction Amputations in low-and middle-income countries (LMICs) represent an important cause of disability and economic hardship. LMIC patients are young and suffer from preventable causes, such as trauma and trauma-related infections. We herein studied the etiology in amputations in a Malawian tertiary care hospital over a 9-year period. Methods Operative and anaesthesia logs at Kamuzu Central Hospital (KCH) in Lilongwe, Malawi, were reviewed for 2008–2016. Baseline demographic and clinical variables and type of amputation performed were collected. Only major limb amputations, defined as above or below the knee, above or below the elbow, and above the wrist, were included in this study. Results A total of 610 patients underwent 630 major amputations during the study period. Of these, 170 (27%) patients were female, and the median age of the cohort was 39 (interquartile range [IQR] 25–55). Of these patients, 345 (54.8%) had infection or gangrene recorded among the indications for amputation, 203 (32.2%) had trauma, 94 (14.9%) had cancer and 67 (10.6%) had documented diabetes. Women underwent diabetes-related amputations more often than men (37 out of 67, or 56.1%), and were significantly younger when their amputations were due to diabetes (median age 48 vs 53 years old, P=0.004) or trauma (median age 21 vs 30 years old, P=0.02). The commonest operative procedures were below the knee amputations, at 271 (43%), and above the knee amputations, at 213 (33.8%). Conclusion Amputations in Malawi affect primarily the young, in the most economically productive time of their lives, in contrast to amputees in high-income countries. Preventable causes, such as infection and trauma, lead to the majority of amputations. These etiologies represent an important primary prevention target for public health efforts in LMICs

‘Bordering’ Life: denying the right to live before being born

This study pushes the boundaries of the border thinking discourse to examine grassroots perceptions of foeticide together with how women are valued in a society that is underpinned by preference for a male child. Using a bordering conceptual framework, the paper re-visits the female positionality within epistemic locations of culture and societal values in both colonial and the modern Indian context. Grounded in primary research in the state of Haryana that exhibits lowest female to male ratio at birth in the country, the analyses indicate rigid or at best sluggish movements in social norms as the key driver for India’s declining sex ratio. The border thinking discourse further enables to situate the different aspects of female positionality and gender perceptions in the society into the specific domains of the bordering conceptual framework. This offers a novel approach to engage with social norms that border life and opportunities for females in the society

BIM aplicado ao projeto de fôrmas de madeira em estrutura de concreto armado

ResumoO Projeto Construtivo de Fôrmas de Madeira (PCFM) faz uso tradicionalmente de ferramentas CAD na representação bidimensional, limitando sua inserção no contexto de Building Information Modeling (BIM). Considerando que BIM se encontra em grande expansão no mercado nacional esta pesquisa visa apontar um caminho para se vencer esta limitação. Propõe-se uma biblioteca de componentes para o projeto de fôrmas de madeira, incluindo usos de BIM tais como a Modelagem, a Quantificação, a Simulação 4D e procedimentos associados. O método de pesquisa utilizado foi a Constructive Research. Os componentes para a biblioteca foram desenvolvidos na ferramenta BIM Revit Structure. A proposta foi validada: em ambiente de ensino, escritório de projeto e na prática. Verifica-se que a pesquisa é consonante com os poucos estudos internacionais pioneiros e semelhantes, sendo contextualizada para o cenário nacional. Observa-se também que todas as pesquisas que tratam de BIM associado a fôrmas requerem um modelo de informação que inclua a modelagem de fôrmas no mesmo. Desta forma, este estudo é também fundamental, pois amplia desdobramentos da incorporação de BIM na cadeia produtiva da construção civil

SOX9 Governs Differentiation Stage-Specific Gene Expression in Growth Plate Chondrocytes via Direct Concomitant Transactivation and Repression

Cartilage and endochondral bone development require SOX9 activity to regulate chondrogenesis, chondrocyte proliferation, and transition to a non-mitotic hypertrophic state. The restricted and reciprocal expression of the collagen X gene, Col10a1, in hypertrophic chondrocytes and Sox9 in immature chondrocytes epitomise the precise spatiotemporal control of gene expression as chondrocytes progress through phases of differentiation, but how this is achieved is not clear. Here, we have identified a regulatory element upstream of Col10a1 that enhances its expression in hypertrophic chondrocytes in vivo. In immature chondrocytes, where Col10a1 is not expressed, SOX9 interacts with a conserved sequence within this element that is analogous to that within the intronic enhancer of the collagen II gene Col2a1, the known transactivation target of SOX9. By analysing a series of Col10a1 reporter genes in transgenic mice, we show that the SOX9 binding consensus in this element is required to repress expression of the transgene in non-hypertrophic chondrocytes. Forced ectopic Sox9 expression in hypertrophic chondrocytes in vitro and in mice resulted in down-regulation of Col10a1. Mutation of a binding consensus motif for GLI transcription factors, which are the effectors of Indian hedgehog signaling, close to the SOX9 site in the Col10a1 regulatory element, also derepressed transgene expression in non-hypertrophic chondrocytes. GLI2 and GLI3 bound to the Col10a1 regulatory element but not to the enhancer of Col2a1. In addition to Col10a1, paired SOX9–GLI binding motifs are present in the conserved non-coding regions of several genes that are preferentially expressed in hypertrophic chondrocytes and the occurrence of pairing is unlikely to be by chance. We propose a regulatory paradigm whereby direct concomitant positive and negative transcriptional control by SOX9 ensures differentiation phase-specific gene expression in chondrocytes. Discrimination between these opposing modes of transcriptional control by SOX9 may be mediated by cooperation with different partners such as GLI factors

Surviving Endoplasmic Reticulum Stress Is Coupled to Altered Chondrocyte Differentiation and Function

In protein folding and secretion disorders, activation of endoplasmic reticulum (ER) stress signaling (ERSS) protects cells, alleviating stress that would otherwise trigger apoptosis. Whether the stress-surviving cells resume normal function is not known. We studied the in vivo impact of ER stress in terminally differentiating hypertrophic chondrocytes (HCs) during endochondral bone formation. In transgenic mice expressing mutant collagen X as a consequence of a 13-base pair deletion in Col10a1 (13del), misfolded α1(X) chains accumulate in HCs and elicit ERSS. Histological and gene expression analyses showed that these chondrocytes survived ER stress, but terminal differentiation is interrupted, and endochondral bone formation is delayed, producing a chondrodysplasia phenotype. This altered differentiation involves cell-cycle re-entry, the re-expression of genes characteristic of a prehypertrophic-like state, and is cell-autonomous. Concomitantly, expression of Col10a1 and 13del mRNAs are reduced, and ER stress is alleviated. ERSS, abnormal chondrocyte differentiation, and altered growth plate architecture also occur in mice expressing mutant collagen II and aggrecan. Alteration of the differentiation program in chondrocytes expressing unfolded or misfolded proteins may be part of an adaptive response that facilitates survival and recovery from the ensuing ER stress. However, the altered differentiation disrupts the highly coordinated events of endochondral ossification culminating in chondrodysplasia

Postoperative outcomes in oesophagectomy with trainee involvement

BACKGROUND: The complexity of oesophageal surgery and the significant risk of morbidity necessitates that oesophagectomy is predominantly performed by a consultant surgeon, or a senior trainee under their supervision. The aim of this study was to determine the impact of trainee involvement in oesophagectomy on postoperative outcomes in an international multicentre setting. METHODS: Data from the multicentre Oesophago-Gastric Anastomosis Study Group (OGAA) cohort study were analysed, which comprised prospectively collected data from patients undergoing oesophagectomy for oesophageal cancer between April 2018 and December 2018. Procedures were grouped by the level of trainee involvement, and univariable and multivariable analyses were performed to compare patient outcomes across groups. RESULTS: Of 2232 oesophagectomies from 137 centres in 41 countries, trainees were involved in 29.1 per cent of them (n = 650), performing only the abdominal phase in 230, only the chest and/or neck phases in 130, and all phases in 315 procedures. For procedures with a chest anastomosis, those with trainee involvement had similar 90-day mortality, complication and reoperation rates to consultant-performed oesophagectomies (P = 0.451, P = 0.318, and P = 0.382, respectively), while anastomotic leak rates were significantly lower in the trainee groups (P = 0.030). Procedures with a neck anastomosis had equivalent complication, anastomotic leak, and reoperation rates (P = 0.150, P = 0.430, and P = 0.632, respectively) in trainee-involved versus consultant-performed oesophagectomies, with significantly lower 90-day mortality in the trainee groups (P = 0.005). CONCLUSION: Trainee involvement was not found to be associated with significantly inferior postoperative outcomes for selected patients undergoing oesophagectomy. The results support continued supervised trainee involvement in oesophageal cancer surgery

Migraine in women: the role of hormones and their impact on vascular diseases

Migraine is a predominantly female disorder. Menarche, menstruation, pregnancy, and menopause, and also the use of hormonal contraceptives and hormone replacement treatment may influence migraine occurrence. Migraine usually starts after menarche, occurs more frequently in the days just before or during menstruation, and ameliorates during pregnancy and menopause. Those variations are mediated by fluctuation of estrogen levels through their influence on cellular excitability or cerebral vasculature. Moreover, administration of exogenous hormones may cause worsening of migraine as may expose migrainous women to an increased risk of vascular disease. In fact, migraine with aura represents a risk factor for stroke, cardiac disease, and vascular mortality. Studies have shown that administration of combined oral contraceptives to migraineurs may further increase the risk for ischemic stroke. Consequently, in women suffering from migraine with aura caution should be deserved when prescribing combined oral contraceptives