Outcomes of 28+1 to 32+0 Weeks Gestation Babies in the State of Qatar: Finding Facility-Based Cost Effective Options for Improving the Survival of Preterm Neonates in Low Income Countries

In this retrospective study we did a comparative analysis of the outcome of 28+1 to 32+0 weeks gestation babies between the State of Qatar and some high income countries with an objective of providing an evidence base for improving the survival of preterm neonates in low income countries. Data covering a five year period (2002–2006) was ascertained on a pre-designed Performa. A comparative analysis with the most recent data from VON, NICHD, UK, France and Europe was undertaken. Qatar’s 28+1 to 32+0 weeks Prematurity Rate (9.23 per 1,000 births) was less than the UK’s (p < 0.0001). Of the 597 babies born at 28+1 to 32+0 weeks of gestation, 37.5% did not require any respiratory support, while 31.1% required only CPAP therapy. 80.12% of the MV and 96.28% of CPAP therapy was required for <96 hours. 86.1% of the mothers had received antenatal steroids. The 28+1 to 32+0 weeks mortality rate was 65.3/1,000 births with 30.77% deaths attributable to a range of lethal congenital and chromosomal anomalies. The survival rate increased with increasing gestational age (p < 0.001) and was comparable to some high income countries. The incidence of in hospital pre discharge morbidities in Qatar (CLD 2.68%, IVH Grade III 0.84%, IVH Grade IV 0.5%, Cystic PVL 0.5%) was less as compared to some high income countries except ROP ≥ Stage 3 (5.69%), which was higher in Qatar. The incidence of symptomatic PDA, NEC and severe ROP decreased with increasing gestational age (p < 0.05). We conclude that the mortality and in hospital pre discharge morbidity outcome of 28+1 to 32+0 weeks babies in Qatar are comparable with some high income countries. In two thirds of this group of preterm babies, the immediate postnatal respiratory distress can be effectively managed by using two facility based cost effective interventions; antenatal steroids and postnatal CPAP. This finding is very supportive to the efforts of international perinatal health care planners in designing facility-based cost effective options for low income countries

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Global variations in diabetes mellitus based on fasting glucose and haemogloblin A1c

Fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) are both used to diagnose diabetes, but may identify different people as having diabetes. We used data from 117 population-based studies and quantified, in different world regions, the prevalence of diagnosed diabetes, and whether those who were previously undiagnosed and detected as having diabetes in survey screening had elevated FPG, HbA1c, or both. We developed prediction equations for estimating the probability that a person without previously diagnosed diabetes, and at a specific level of FPG, had elevated HbA1c, and vice versa. The age-standardised proportion of diabetes that was previously undiagnosed, and detected in survey screening, ranged from 30% in the high-income western region to 66% in south Asia. Among those with screen-detected diabetes with either test, the agestandardised proportion who had elevated levels of both FPG and HbA1c was 29-39% across regions; the remainder had discordant elevation of FPG or HbA1c. In most low- and middle-income regions, isolated elevated HbA1c more common than isolated elevated FPG. In these regions, the use of FPG alone may delay diabetes diagnosis and underestimate diabetes prevalence. Our prediction equations help allocate finite resources for measuring HbA1c to reduce the global gap in diabetes diagnosis and surveillance.peer-reviewe

Cyclophilin A Peptidyl-Prolyl Isomerase Activity Promotes Zpr1 Nuclear Export

The peptidyl-prolyl isomerase (PPIase) cyclophilin A (Cpr1p) is conserved from eubacteria to mammals, yet its biological function has resisted elucidation. Unable to identify a phenotype that is suggestive of Cpr1p's function in a cpr1Δ Saccharomyces cerevisiae strain, we screened for CPR1-dependent strains. In all cases, dependence was conferred by mutations in ZPR1, a gene encoding an essential zinc finger protein. CPR1 dependence was suppressed by overexpression of EF1α (a translation factor that binds Zpr1p), Cpr6p (another cyclophilin), or Fpr1p (a structurally unrelated PPIase). Suppression by a panel of cyclophilin A mutants correlated with PPIase activity, confirming the relevance of this activity in CPR1-dependent strains. In CPR1(+) cells, wild-type Zpr1p was distributed equally between the nucleus and cytoplasm. In contrast, proteins encoded by CPR1-dependent alleles of ZPR1 accumulated in the nucleus, as did wild-type Zpr1p in cpr1Δ cells. Transport kinetic studies indicated that nuclear export of Zpr1p was defective in cpr1Δ cells, and rescue of this defect correlated with PPIase activity. Our results demonstrate a functional interaction between Cpr1p, Zpr1p, and EF1α, a role for Cpr1p in Zpr1p nuclear export, and a biological function for Cpr1p PPIase activity

Risk of Elevated Intraocular Pressure and Glaucoma in Patients with Uveitis

OBJECTIVE: To report the two-year incidence of raised intraocular pressure (IOP) and glaucomatous optic nerve damage in patients with uveitis randomized to either fluocinolone acetonide (FA) implants or systemic therapy. Secondarily, to explore patient and eye characteristics associated with IOP elevation or nerve damage. DESIGN: A randomized, partially masked trial in which patients were randomized to either FA implants or systemic therapy. PARTICIPANTS: Patients age 13 years or older with non-infectious intermediate, posterior or panuveitis active within the prior 60 days for which systemic corticosteroids were indicated were eligible. METHODS: Visual fields were obtained at baseline and every 12 months using the Humphrey 24-2 SITA-fast protocol. Stereoscopic optic nerve photos were taken at baseline and at 3, 6, 12 and 24-month follow-up visits. IOP was measured by masked examiners at every study visit. MAIN OUTCOME MEASURES: Glaucoma was diagnosed based on an increase in optic nerve cup-to-disc ratio with visual field worsening or increased cup-to-disc ratio alone, when visual fields were not available for cases where visual field change was not evaluable, due to missing data or severe visual field loss at baseline. RESULTS: Most patients were treated as assigned, among those evaluated for glaucoma 97% and 10% of patients assigned to implant and systemic treatment, respectively, received implants. More patients (65%) assigned to implants experienced an IOP elevation of at least 10 mmHg versus 24% assigned to systemic treatment (P<0.001). Similarly, 69% of patients assigned to the implant required IOP lowering therapy versus 26% in the systemic group (P<0.001). Glaucomatous optic nerve damage developed in 23% versus 6% (P<0.001) of implant and systemic patients, respectively. In addition to treatment assignment, black race, use of IOP-lowering medications and uveitis activity at baseline were associated with incident glaucoma (P < 0.05). CONCLUSION: Implant-assigned eyes had about a four-fold risk of developing IOP elevation ≥ 10 mmHg and of incident glaucomatous optic neuropathy over the first two years compared to those assigned to systemic therapy. Central visual acuity was unaffected. Aggressive IOP monitoring with early treatment (often including early filtration surgery) are needed to avoid glaucoma when vision-threatening inflammation requires implant therapy