Allelic exclusion of {alpha} chains in TCRs

Although the ß chains of ß⁺ T cells exhibitallelic exclusion it has recently been shown that 20–30%of such cells express both chain alleles on their surface.Potentially these cells have dual specificity, and it has beensuggested that they may play a role in autoimmunity and alloreactlvtty.The analysis presented in this paper examines critically thepossibility that the observed violation of allelic exclusionof chain expression arises as a natural consequence of a chainrearrangement and intrathymlc positive selection. It is concludedthat, subject to certain identified conditions being satisfied,the observed frequency of T cells expressing two chains iscompatible with such a mechanism. However, It is an essentialassumption of the theory that, of the two ß chaincomplexes on these cells, only one mediates positive selection.It follows that to what extent both receptors are actually functionaldepends on whether an ß chain complex that has failedto satisfy the criterion of positive selection can mediate antigenrecognition in the periphery. In principle the answer to thisquestion may be different if one is considering autoreactlvltyor alloreactlvlty. Finally, attention is drawn to the apparentdiscrepancy between the frequency of peripheral T cells expressingtwo chains and the failure to find T cell clones of this phenotype.Possible explanations are discussed.     

Disease-specific electrophysiological findings in adult ceroid-lipofuscinosis (Kufs disease)

Two adults with mild dementia and a history of memory loss and disequilibrium were seen in the eye clinic following complaints of acuity loss in the 20/30–20/70 (Snellen) range. Results from the fundus examination of one patient were entirely normal; the other showed minimal vascular attenuation and optic atrophy. Electrophysiology was remarkable: (1) Photopic ERG b-waves were reduced, delayed, and showed pronounced oscillations. (2) EOG light-rise potentials were absent or very small. (3) Binocular pattern-VER signals showed addition of the monocular signal. Scotopic ERG signals were normal. Brain biopsy and microscopy showed intercellular, autofluorescent ceroid deposits which provided a clear diagnosis of Kufs disease. Histology of model animal retinal cells show ceroid deposits in cell classes implicated by the human retinal signals. The cluster of electrophysiological results point toward early changes in the pigment epithelium and inner plexiform layer cells as a means of non-invasive diagnosis.     

Mechanisms of central conduction time prolongation in brain-stem auditory evoked potentials

The wave I-wave V delay in the auditory brain-stem response is commonly used as a diagnostic tool in otoneurology. Normative values have been established for different populations and different types of stimuli. This I-V delay has been known for some time as "central conduction time" or "central transmission time." This implies that the measure reflects in normal and in pathologic cases delays due to nerve conduction, synaptic transmission, and neural integration and is not caused by cochlear processes. By virtue of the traveling wave delay in the cochlea, amounting to some 4 ms from the base to the "500-Hz place," it is conceivable that this delay contributes to the I-V delay. From a series of 69 pontine angle tumors in which the auditory brain-stem response was recorded, we selected cases with an apparent peripheral origin of a prolonged I-V delay by comparing the whole-click response to responses derived from high-pass noise masking. It seems that cases with an increased I-V delay in the whole-click response but (almost) normal I-V delays in the narrow-band response are indicative of small intracanalicular acoustic neuroma.     

Pharmacokinetics of vindesine bolus and infusion

Summary The pharmacokinetics of vindesine were investigated during treatment of 15 patients with progressive malignancies refractory to conventional treatment. Patients were administered one of three IV dose schedules: 3.0 mg/m² bolus injection, 1.2 mg/m²/day infusion for 5 days, or 2.0 mg/m²/day infusion for 2 days. Concentrations of the drug in the serum and urine were determined by radioimmunoassay. Serum concentrations were highest (5×10^-7 M) in patients receiving a bolus injection, but fell to nondetectable levels by 48 h in four of five patients (terminal t_1/2 15.0±9.4 h). Compared with bolus injection, 1.2-to 1.4-fold greater areas under the blood concentration curve were observed during infusions of 2.0 mg/m² and 1.2 mg/m². Whereas steady-state concentrations (1×10^-8 M) were maintained throughout the infusion of 1.2 mg/m²/day progressively increasing serum levels were observed during the infusion of 2.0 mg/m²/day. Serum concentrations fell rapidly following discontinuation of the 2.0-mg/m² infusion, but were somewhat more sustained in the 1.2-mg/m² infusion group. The average urinary excretion was similar for each dose-schedule (8%–11% of the total dose). The pharmacokinetics of vindesine are influenced by variations in dose schedule.     

Jan Hendrik Louw and intestinal atresia – a personal quest in pediatric surgery

Jan Hendrik Louw (1915–1992), considered the father of pediatric surgery in South Africa, gained prominence for his work on congenital intestinal atresia, a condition that had a mortality as high as 75 percent. His hypothesis, that jejunoileal atresia arose from mesenteric circulatory accidents in utero, was the dominant view until recent research uncovered the involvement of genetic and embryological mechanisms. In the mid-1950s he was one of a number of surgeons to resect the enlarged bulbous segment proximal to the site of the atresia, a crucial step in the surgical approach to intestinal atresia that brought mortality below 10 percent. A world leader in surgery as chair of surgery at the Groote Schur Hospital in Cape Town for more than a quarter century, his work in surgical research took root from his private tragedy early in his career of the death of his own infant son of intestinal atresia, a condition to which he would contribute so much.     

Remote intervention engagement and outcomes in the Clinical Trials in Organ Transplantation in Children consortium multisite trial

Remote interventions are increasingly used in transplant medicine but have rarely been rigorously evaluated. We investigated a remote intervention targeting immunosuppressant management in pediatric lung transplant recipients. Patients were recruited from a larger multisite trial if they had a Medication Level Variability Index (MLVI) ≥2.0, indicating worrisome tacrolimus level fluctuation. The manualized intervention included three weekly phone calls and regular follow-up calls. A comparison group included patients who met enrollment criteria after the subprotocol ended. Outcomes were defined before the intent-to-treat analysis. Feasibility was defined as ≥50% of participants completing the weekly calls. MLVI was compared pre- and 180 days postenrollment and between intervention and comparison groups. Of 18 eligible patients, 15 enrolled. Seven additional patients served as the comparison. Seventy-five percent of participants completed ≥3 weekly calls; average time on protocol was 257.7 days. Average intervention group MLVI was significantly lower (indicating improved blood level stability) at 180 days postenrollment (2.9 ± 1.29) compared with pre-enrollment (4.6 ± 2.10), p = .02. At 180 days, MLVI decreased by 1.6 points in the intervention group but increased by 0.6 in the comparison group (p = .054). Participants successfully engaged in a long-term remote intervention, and their medication blood levels stabilized. NCT02266888.     

Feeding inequality: food insecurity,social status and college student health

A growing but limited body of research has identified the college student population as one that is particularly vulnerable to food insecurity. Early estimates of food insecurity prevalence among college students range from 14 to 60 per cent. The present study utilises original survey data collected from a random sample (n = 300) of college students enrolled at an urban university in the Midwest region of the United States of America (USA). This study examines the impact of food insecurity on health outcomes and the mediation of this relationship by subjective social status among college students. Ordinary least squares (OLS) and logistic regression analyses find that food insecurity is related to worse self-rated, physical and mental health among college students, and Sobel-Goodman tests find that subjective social status plays a significant mediating role in the relationship between food insecurity and health among college students. The implications of these findings in a university context are discussed using a psychosocial framework and insights from the stress process model. In doing so, I discuss food insecurity among college students with an emphasis on the social significance of food and food insecurity.     

Impact of COVID‐19 on access to healthcare in low‐ and middle‐income countries: Current evidence and future recommendations

The COVID‐19 pandemic continues to be a major public health threat globally and low‐ and middle‐income countries (LMICs) are not an exception. The impact of the COVID‐19 pandemic is far‐reaching on many areas including but not limited to global health security, economic and healthcare delivery with a potential impact on access to healthcare in LMICs. We evaluate the impact of the COVID‐19 pandemic on access to healthcare in LMICs, as well as plausible strategies that can be put in place to ensure that the delivery of healthcare is not halted. In order to mitigate the devastating effect of the COVID‐19 pandemic on the already weak health systems in LMICs, it is much necessary to reinforce and scale up interventions and proactive measures that will ensure that access to healthcare is not disrupted even in course of the pandemic.     

EMG Biofeedback as a Tool for Simulating the Effects of Specific Leg Muscle Weakness on a Lifting Task

This study investigated the use of EMG biofeedback to simulate weakened rectus femorii and gastrocnemii muscles during the performance of a lifting task. Eight healthy women performed 15 kg free-style lifts from floor level. Three conditions were tested: unconstrained lifting, lifting with rectus femorii activity volitionally limited bilaterally through EMG biofeedback to less than 45% of maximal EMG activity, and lifting with the gastrocnemii limited to a similar level. Limiting leg muscle activity through biofeedback led to an alteration of lifting strategy, with resulting performance variables (joint angles and torques, angular velocities, center of pressure excursion, and segment coordination) comparing favorably with those from lifting trials performed by six women with moderate leg muscle weaknesses. The data indicate that EMG biofeedback can be used to simulate the effects of leg muscle weakness during these lifts, providing a new tool to study the biomechanics of muscle weakness.