Multiplex cytokine analysis of dermal interstitial blister fluid defines local disease mechanisms in systemic sclerosis.

Clinical diversity in systemic sclerosis (SSc) reflects multifaceted pathogenesis and the effect of key growth factors or cytokines operating within a disease-specific microenvironment. Dermal interstitial fluid sampling offers the potential to examine local mechanisms and identify proteins expressed within lesional tissue. We used multiplex cytokine analysis to profile the inflammatory and immune activity in the lesions of SSc patients

Vesicular sorting controls the polarity of expanding membranes in the C. elegans intestine

Biological tubes consist of polarized epithelial cells with apical membranes building the central lumen and basolateral membranes contacting adjacent cells or the extracellular matrix. Cellular polarity requires distinct inputs from outside the cell, e.g., the matrix, inside the cell, e.g., vesicular trafficking and the plasma membrane and its junctions.1 Many highly conserved polarity cues have been identified, but their integration during the complex process of polarized tissue and organ morphogenesis is not well understood. It is assumed that plasma-membrane-associated polarity determinants, such as the partitioning-defective (PAR) complex, define plasma membrane domain identities, whereas vesicular trafficking delivers membrane components to these domains, but lacks the ability to define them. In vitro studies on lumenal membrane biogenesis in mammalian cell lines now indicate that trafficking could contribute to defining membrane domains by targeting the polarity determinants, e.g., the PARs, themselves.2 This possibility suggests a mechanism for PARs’ asymmetric distribution on membranes and places vesicle-associated polarity cues upstream of membrane-associated polarity determinants. In such an upstream position, trafficking might even direct multiple membrane components, not only polarity determinants, an original concept of polarized plasma membrane biogenesis3,4that was largely abandoned due to the failure to identify a molecularly defined intrinsic vesicular sorting mechanism. Our two recent studies on C. elegans intestinal tubulogenesis reveal that glycosphingolipids (GSLs) and the well-recognized vesicle components clathrin and its AP-1 adaptor are required for targeting multiple apical molecules, including polarity regulators, to the expanding apical/lumenal membrane.5,6 These findings support GSLs’ long-proposed role in in vivo polarized epithelial membrane biogenesis and development and identify a novel function in apical polarity for classical post-Golgi vesicle components. They are also compatible with a vesicle-intrinsic sorting mechanism during membrane biogenesis and suggest a model for how vesicles could acquire apical directionality during the assembly of the functionally critical polarized lumenal surfaces of epithelial tubes

Burden and resilience in caregivers of patients on maintenance haemodialysis

Background: Chronic renal failure is one among the chronic illness which due to persistence of the disease has various effects on the physiological, psychological and functional ability of the patient and his family. Although haemodialysis has become a highly safe medical procedure that significantly extended life of such patients, it is nevertheless a stressful and lengthy treatment process. The task of personal life care for such patients falls primarily on the family members. The caregiver is expected to aid in patient’s daily life activities resulting in increased physical and emotional burden. With the considerable level of burden involved the concept of resilience thus become crucial as they could function as protective factors. The current study aims to assess the level of caregiver burden and resilience in caregivers of haemodialysis patients.Methods: A cross sectional observational study was done in 120 caregivers of patients diagnosed as having ESRD on maintenance hemodialysis. Zarit Burden Interview was used for assessing caregiver’s burden. Brief Resilience Scale was used to assess caregiver’s resilience.Results: 35.8% of caregivers had severe caregiver burden while looking after dialysis patients while 45% of caregivers had moderate burden. Caregivers showed low resilience about 72.5% which displays poor problem solving and emotion-focused coping strategies.Conclusions: The study shows that more than 80% of caregivers suffered from moderate to severe burden and poor resilience among them would be a contributing factor. The study also shows that female caregivers were most affected. The burden was significantly higher in caregivers as the years spent on caregiving increased and more hours spent per day looking after the patients. Health-care providers need to address these concerns based on both patient- and caregiver-focused approaches, rather than only patient focused

Heterotopic ossification of the hip post reamed intramedullary femoral nail: a case report

Hetorotopic Ossification (HO) is abnormal formation of bone in the soft tissue. Heterotopic ossification of the hip following reamed interlocking medullary nail is uncommon and it has received little attention from the clinician. We take this opportunity to report a young man who presented with symptomatic heterotopic ossification of the hip eight months post antegrade reamed interlocking medullary nail which failed conservative treatment. Reamed intramedullary nailing and delayed mobilization are the contributing factors in this patient. The pathophysiology of this condition is not fully understood. As a result, there is no consensus in the prevention of heterotopic ossification in such patients. Similarly, the management of this condition also is lacking but resection is the treatment of choice for symptomatic patient