The Enabling Effect of Food Assistance in Improving Adherence and/or Treatment Completion for Antiretroviral Therapy and Tuberculosis Treatment: A Literature Review

Socioeconomic costs of HIV and TB and the difficulty of maintaining optimal treatment are well documented. Social protection measures such as food assistance may be required to offset some of the treatment related costs as well as to ensure food security and maintain good health of the affected individual and household. Programmes have started placing greater emphasis on treatment adherence and are looking for proven interventions that can optimize it. This paper looks at the effect of food assistance for enabling treatment adherence and reviews studies that used food assistance to promote adherence. Eight of ten studies found that provision of food can improve adherence and/or treatment completion for HIV care and treatment, ART and TB-DOTS. This indicates that food provision is not only a biological, but also a behavioural intervention, and underscores that unresolved food insecurity can be an impediment to treatment adherence and consequently to good treatment outcomes.     

Predictability of pharyngeal airway space dimension changes after orthognathic surgery in class II patients: A mathematical approach

IntroductionAngle Class II malocclusion due to mandibular retrognathia is a common dentofacial deformity. It is well known that mandibular advancement increases pharyngeal airway dimensions. The aim of this study was to evolve a mathematical method for predicting posterior pharyngeal airway space (PAS) changes based on 2D lateral cephalographic radiographs (LCRs) and expected extent of mandibular advancement prior to BSSO.Materials and methodsLinear regression analyses were performed in order to investigate the relation between the posterior airway space and mandibular advancement. LCRs where carried out to assess skeletal landmarks and pharyngeal airway space pre- (T0) and postoperatively (T1). To detect changes postoperatively, the posterior airway space was divided into three units: nasopharyngeal airway space (superior airway space — SPAS), oropharyngeal airway space (mid airway space — MAS) and hypopharyngeal airway space (inferior airway space — IAS). The differences between the distances of distinct measurement points (DIFF) were measured pre- and postoperatively. DOA referred to the distance of mandibular advancement and DP to the distance between the measurement points preoperatively. The parameters a, b₁ and b₂ were the regression coefficients that were determined separately for each unit (SPAS, MAS, and IAS).Results49 patients (16 male and 33 female) with a mean age of 27.2 years (SD: 10.09), ranging from 18 to 51 years, who underwent mandibular advancement surgery (BSSO) were enrolled in this study. The mean distance of mandibular advancement was 5.05 mm (SD: 1.63). Regarding SPAS and IAS, mandibular advancement did not affect dimensions significantly: SPAS DIFF, 0.33 mm ± 1.13 mm (b₁, p = 0.0881; b₂, p = 0.087); IAS DIFF, 0.66 mm ± 2.45 mm (b₁, p = 0.342; b₂, p = 0.765). DOA and DP did not influence DIFF significantly in both sections. Regarding MAS, the mean effect of mandibular advancement was an expansion of 2.47 mm ± 2.24. The linear regression model showed a statistically significant (b₁, p = 0.0064; b₂, p = 0.0240) influence of DOA and DP on DIFF in posterior airway dimensions pre- and postoperatively.DiscussionBased on preoperative LCR imaging data, a linear regression model was developed as a mathematical approach to allow prediction of PAS development in patients with Angle Class II malocclusions of different degrees. Increasing mandibular advancement was shown to be linked to increasing PAS, while a greater distance between the measuring points preoperatively led to smaller predicted PAS increases postoperatively.ConclusionPredicting pharyngeal airway space (PAS) development after mandibular advancement by analysing lateral cephalometric radiographs (LCR) may be useful in the screening and treatment of obstructive sleep apnea syndrome (OSAS) patients. Our mathematical approach is a simple and sustainable prediction tool based on LTR data for patients with Class II malocclusions.     

ATP-regulated potassium channels and voltage-gated calcium channels in pancreatic alpha and beta cells: similar functions but reciprocal effects on secretion

Closure of ATP-regulated K⁺ channels (K_ATP channels) plays a central role in glucose-stimulated insulin secretion in beta cells. K_ATP channels are also highly expressed in glucagon-producing alpha cells, where their function remains unresolved. Under hypoglycaemic conditions, K_ATP channels are open in alpha cells but their activity is low and only ~1% of that in beta cells. Like beta cells, alpha cells respond to hyperglycaemia with K_ATP channel closure, membrane depolarisation and stimulation of action potential firing. Yet, hyperglycaemia reciprocally regulates glucagon (inhibition) and insulin secretion (stimulation). Here we discuss how this conundrum can be resolved and how reduced K_ATP channel activity, via membrane depolarisation, paradoxically reduces alpha cell Ca²⁺ entry and glucagon exocytosis. Finally, we consider whether the glucagon secretory defects associated with diabetes can be attributed to impaired K_ATP channel regulation and discuss the potential for remedial pharmacological intervention using sulfonylureas.     

Chemokine-mediated redirection of T cells constitutes a critical mechanism of glucocorticoid therapy in autoimmune CNS responses

Glucocorticoids (GCs) are the standard therapy for treating multiple sclerosis (MS) patients suffering from an acute relapse. One of the main mechanisms of GC action is held to be the induction of T cell apoptosis leading to reduced lymphocyte infiltration into the CNS, yet our analysis of experimental autoimmune encephalomyelitis (EAE) in three different strains of genetically manipulated mice has revealed that the induction of T cell apoptosis is not essential for the therapeutic efficacy of GCs. Instead, we identified the redirection of T cell migration in response to chemokines as a new therapeutic principle of GC action. GCs inhibited the migration of T cells towards CCL19 while they enhanced their responsiveness towards CXCL12. Importantly, blocking CXCR4 signaling in vivo by applying Plerixafor^® strongly impaired the capacity of GCs to interfere with EAE, as revealed by an aggravated disease course, more pronounced CNS infiltration and a more dispersed distribution of the infiltrating T cells throughout the parenchyma. Our observation that T cells lacking the GC receptor were refractory to CXCL12 further underscores the importance of this pathway for the treatment of EAE by GCs. Importantly, methylprednisolone pulse therapy strongly increased the capacity of peripheral blood T cells from MS patients of different subtypes to migrate towards CXCL12. This indicates that modulation of T cell migration is an important mechanistic principle responsible for the efficacy of high-dose GC therapy not only of EAE but also of MS.     

Cell crawling mediates collective cell migration to close undamaged epithelial gaps

Fundamental biological processes such as morphogenesis and wound healing involve the closure of epithelial gaps. Epithelial gap closure is commonly attributed either to the purse-string contraction of an intercellular actomyosin cable or to active cell migration, but the relative contribution of these two mechanisms remains unknown. Here we present a model experiment to systematically study epithelial closure in the absence of cell injury. We developed a pillar stencil approach to create well-defined gaps in terms of size and shape within an epithelial cell monolayer. Upon pillar removal, cells actively respond to the newly accessible free space by extending lamellipodia and migrating into the gap. The decrease of gap area over time is strikingly linear and shows two different regimes depending on the size of the gap. In large gaps, closure is dominated by lamellipodium-mediated cell migration. By contrast, closure of gaps smaller than 20 μm was affected by cell density and progressed independently of Rac, myosin light chain kinase, and Rho kinase, suggesting a passive physical mechanism. By changing the shape of the gap, we observed that low-curvature areas favored the appearance of lamellipodia, promoting faster closure. Altogether, our results reveal that the closure of epithelial gaps in the absence of cell injury is governed by the collective migration of cells through the activation of lamellipodium protrusion.