HLA- and genotype-based risk assessment model to identify infantile onset pompe disease patients at high-risk of developing significant anti-drug antibodies (ADA).

In Pompe disease, anti-drug antibodies (ADA) to acid alpha-glucosidase (GAA) enzyme replacement therapy contribute to early mortality. Assessing individual risk for ADA development is notoriously difficult in (CRIM-positive) patients expressing endogenous GAA. The individualized T cell epitope measure (iTEM) scoring method predicts patient-specific risk of developing ADA against therapeutic recombinant human GAA (rhGAA) using individualized HLA-binding predictions and GAA genotype. CRIM-negative patients were six times more likely to develop high ADA titers than CRIM-positive patients in this retrospective study, whereas patients with high GAA-iTEM scores were 50 times more likely to develop high ADA titers than patients with low GAA-iTEM scores. This approach identifies high-risk IOPD patients requiring immune tolerance induction therapy to prevent significant ADA response to rhGAA leading to a poor clinical outcome and can assess ADA risk in patients receiving replacement therapy for other enzyme or blood factor deficiency disorders.

A lifestyle intervention programme for the prevention of Type 2 diabetes mellitus among South Asian women with gestational diabetes mellitus [LIVING study]: protocol for a randomized trial.

AIM: This study aims to determine whether a resource- and culturally appropriate lifestyle intervention programme in South Asian countries, provided to women with gestational diabetes (GDM) after childbirth, will reduce the incidence of worsening of glycaemic status in a manner that is affordable, acceptable and scalable. METHODS: Women with GDM (diagnosed by oral glucose tolerance test using the International Association of the Diabetes and Pregnancy Study Groups criteria) will be recruited from 16 hospitals in India, Sri Lanka and Bangladesh. Participants will undergo a repeat oral glucose tolerance test at 6 ± 3 months postpartum and those without Type 2 diabetes, a total sample size of 1414, will be randomly allocated to the intervention or usual care. The intervention will consist of four group sessions, 84 SMS or voice messages and review phone calls over the first year. Participants requiring intensification of the intervention will receive two additional individual sessions over the latter half of the first year. Median follow-up will be 2 years. The primary outcome is the proportion of women with a change in glycaemic category, using the American Diabetes Association criteria: (i) normal glucose tolerance to impaired fasting glucose, or impaired glucose tolerance, or Type 2 diabetes; or (ii) impaired fasting glucose or impaired glucose tolerance to Type 2 diabetes. Process evaluation will explore barriers and facilitators of implementation of the intervention in each local context, while trial-based and modelled economic evaluations will assess cost-effectiveness. DISCUSSION: The study will generate important new evidence about a potential strategy to address the long-term sequelae of GDM, a major and growing problem among women in South Asia. (Clinical Trials Registry of India No: CTRI/2017/06/008744; Sri Lanka Clinical Trials Registry No: SLCTR/2017/001; and ClinicalTrials.gov Identifier No: NCT03305939).

Utility of third trimester sonographic measurements for predicting SGA in cases of fetal gastroschisis.

OBJECTIVE: To assess the accuracy of different sonographic estimated fetal weight (EFW) cutoffs, and combinations of EFW and biometric measurements for predicting small for gestational age (SGA) in fetal gastroschisis. STUDY DESIGN: Gastroschisis cases from two centers were included. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated for different EFW cutoffs, as well as EFW and biometric measurement combinations. RESULTS: Seventy gastroschisis cases were analyzed. An EFW<10% had 94% sensitivity, 43% specificity, 33% PPV and 96% NPV for SGA at delivery. Using an EFW cutoff of <5% improved the specificity to 63% and PPV to 41%, but decreased the sensitivity to 88%. Combining an abdominal circumference (AC) or femur length (FL) z-score less than -2 with the total EFW improved the specificity and PPV but decreased the sensitivity. CONCLUSION: A combination of a small AC or FL along with EFW increases the specificity and PPV, but decreases the sensitivity of predicting SGA.

A survey of the value of routine intimate examination and related practices in subfertile couples.

The practice of undertaking routine intimate examinations in the management of subfertile couples varies among clinicians. An anonymous self-administered mailed questionnaire survey was carried out to determine the current practices followed by clinicians and the rationale supporting their practice. In the absence of large comparative studies, this survey provides expert opinion regarding this practice. The questionnaire was mailed to the Fellows and members of the Royal College of Obstetricians and Gynaecologists in the Northern, Yorkshire, West Midlands and Wales regions in the UK. A total of 802 questionnaires were posted, of which 516 were returned, giving an overall response rate of 64%. The responses and comments varied. Some 62% of respondents would routinely perform a pelvic examination on all women presenting with subfertility; 23% would do so only in selected cases and 63% of the clinicians would perform a routine transvaginal ultrasound. The male partners are examined by only 19% of the clinicians. A total of 83% of the respondents were of the opinion that the survey made them think about the role and justification of intimate examinations in greater detail. The practice of intimate examination of subfertile couples varies among clinicians in the survey group. There is a need for large prospective comparative studies to study the value of this examination and related practices in the management of subfertile couples. In the absence of comparative trials, this survey provides expert opinion. It may be suggested that an intimate examination should not be carried out routinely in all subfertile couples. It could be done when it has potential to add value to the management of the patient. A pragmatic approach should be adopted in every clinical situation.

Agenesis of corpus callosum - a rare case.

A case of corpus callosum agenesis associated with a chromosomal structural defect is described.

Hypokalemic paralysis.

A case of Hypokalemic paralysis is reported which had an atypical onset and clinical features. The paralysis totally recovered on replacement of potassium.

Biochemical changes in the liver of fish, Tilapia mossambica (Peters), during continuous exposure to monocrotophos.

The purpose of the present investigation was to determine the effect of continuous exposure to the organophosphate monocrotophos at 2.5 ppm for over a period of 2 through 45 days on protein, RNA, and DNA contents and on 5'-nucleotidase activity in the liver of Tilapia mossambica. Protein content was decreased by 45% after 5 days, returned to control levels at 10-30 days, and again decreased by 45 days. DNA content was decreased by 2 days, returned to control values by 5 days, and remained constant throughout the exposure. In contrast, RNA content was significantly lower starting from 2 through 45 days of exposure. 5'-Nucleotidase activity showed a transient increase at 5 and 30 days of monocrotophos exposure. These results indicate that monocrotophos altered the protein, DNA, and RNA contents and the 5'-nucleotidase activity levels as early as 2 and 5 days. However, these changes were reversed by 10 days and after a short period of recovery, the alterations reappeared. This supports our earlier histological observations of hepatic pathology during monocrotophos exposure.

Histological observations on the liver of Tilapia mossambica after exposure to monocrotophos, an organophosphorus insecticide.

The histological changes in the liver of Tilapia mossambica were observed after exposure to a sublethal level (2.5 ppm) of monocrotophos. The changes observed after 2 days of exposure were characterized by necrosis and vacuolation of hepatocytes. Fatty degeneration was observed after 10 days of exposure. However, normalization of histological picture was evident after 15 days of treatment, though some patches of degenerating zones were also found to exist concomitantly. A wave of secondary intensively degenerative changes was observed from 30 days up to 45 days of experimentation. The possible significance of histological lesions and adaptation to exposure after sublethal doses as well as continuous exposure are discussed.