The early activation of microglia that induces retinal inflammation in DR may serve as a target for therapeutic intervention of DR. Our demonstration that retinal inflammation is attenuated via adenosine receptor A2AAR supports the hypothesis that a mechanism to maintain extracellular concentrations of adenosine important in normal physiology is impaired in DR. Extracellular concentrations of adenosine are regulated by the interplay of equiliberative nucleoside transporter (ENT)s with enzymes of adenosine metabolism including adenosine deaminase-1 (ADA1), adenosine kinase (AK) and CD73. In the vertebrates but not rodents, a macrophage-associated ADA2 is identified. The role of ADA2 is, therefore, understudied as the sequencing probes or antibodies to mouse ADA2 are not available. We identified increased ADA2 expression and activity in human and porcine retinas with diabetes, and in Amadori glycated albumin (AGA)- or hyperglycemia-treated porcine and human microglia. In rodent as well as porcine cells, modulation of TNF-α release is mediated by A2AAR. Quantitative analysis of normal and diabetic porcine retinas reveals that while the expression levels of ADA2, A2AAR, ENT1, TNF-α and MMP9 are increased, the levels of AK are reduced during inflammation as an endogenous protective mechanism. To determine the role of ADA2, we found that AGA induces ADA2 expression, ADA2 activity and TNF-α release, and that TNF-α release is blocked by ADA2-neutralizing antibody or ADA2 siRNA, but not by scrambled siRNA. These results suggest that retinal inflammation in DR is mediated by ADA2, and that the anti-inflammatory activity of A2AAR signaling is impaired in diabetes due to increased ADA2 activity.

Globally, Pakistan has the third highest burden of maternal, fetal, and child mortality. It has made slow progress in achieving the Millennium Development Goals (MDGs) 4 and 5 and in addressing common social determinants of health. The country also has huge challenges of political fragility, complex security issues, and natural disasters. We undertook an in-depth analysis of Pakistan's progress towards MDGs 4 and 5 and the principal determinants of health in relation to reproductive, maternal, newborn, and child health and nutrition. We reviewed progress in relation to new and existing public sector programmes and the challenges posed by devolution in Pakistan. Notwithstanding the urgent need to tackle social determinants such as girls' education, empowerment, and nutrition in Pakistan, we assessed the effect of systematically increasing coverage of various evidence-based interventions on populations at risk (by residence or poverty indices). We specifically focused on scaling up interventions using delivery platforms to reach poor and rural populations through community-based strategies. Our model indicates that with successful implementation of these strategies, 58% of an estimated 367 900 deaths (15 900 maternal, 169 000 newborn, 183 000 child deaths) and 49% of an estimated 180 000 stillbirths could be prevented in 2015.

Non-communicable diseases, including cardiovascular diseases, cancers, respiratory diseases, diabetes, and mental disorders, and injuries have become the major causes of morbidity and mortality in Pakistan. Tobacco use and hypertension are the leading attributable risk factors for deaths due to cardiovascular diseases, cancers, and respiratory diseases. Pakistan has the sixth highest number of people in the world with diabetes; every fourth adult is overweight or obese; cigarettes are cheap; antismoking and road safety laws are poorly enforced; and a mixed public-private health-care system provides suboptimum care. Furthermore, almost three decades of exposure to sociopolitical instability, economic uncertainty, violence, regional conflict, and dislocation have contributed to a high prevalence of mental health disorders. Projection models based on the Global Burden of Disease 2010 data suggest that there will be about 3·87 million premature deaths by 2025 from cardiovascular diseases, cancers, and chronic respiratory diseases in people aged 30-69 years in Pakistan, with serious economic consequences. Modelling of risk factor reductions also indicate that Pakistan could achieve at least a 20% reduction in the number of these deaths by 2025 by targeting of the major risk factors. We call for policy and legislative changes, and health-system interventions to target readily preventable non-communicable diseases in Pakistan.

Please cite this paper as: Carvalho M, Vinayak S, Ochieng R, Choksey V, Musee N, Stones W, Knight H, Cheikh Ismail L, for the International Fetal and Newborn Growth Consortium for the 21(st) Century (INTERGROWTH-21(st) ). Implementation of the INTERGROWTH-21(st) Project in Kenya. BJOG 2013; DOI: 10.1111/1471-0528.12045. The African site in the INTERGROWTH-21(st) Project was Parklands, a wealthy suburb of Nairobi, Kenya, with a largely middle-to-high socio-economic status population. There are three hospitals with obstetric units in Parklands, with approximately 4300 births per year. The Newborn Cross-Sectional Study (NCSS) sample was drawn from all three hospitals, covering 100% of births in this target population. The Fetal Growth Longitudinal Study (FGLS) sample was recruited from antenatal clinics serving these hospitals, using the eligibility criteria in the INTERGROWTH-21(st) protocol. Special activities to raise awareness of the study included securing media coverage and distributing leaflets in antenatal clinic waiting rooms. FGLS required women to be recruited in the first trimester; therefore, a major challenge at this study site was the high background frequency of first antenatal consultations in the second trimester. The problem was overcome by the study awareness campaign, as a result of which more women started attending antenatal care earlier in pregnancy.

Please cite this paper as: Villar J, Altman D, Purwar M, Noble J, Knight H, Ruyan P, Cheikh Ismail L, Barros F, Lambert A, Papageorghiou A, Carvalho M, Jaffer Y, Bertino E, Gravett M, Bhutta Z, Kennedy S, for the International Fetal and Newborn Growth Consortium for the 21(st) Century (INTERGROWTH-21(st) ). The objectives, design and implementation of the INTERGROWTH-21(st) Project. BJOG 2013; DOI: 10.1111/1471-0528.12047. INTERGROWTH-21(st) is a multicentre, multiethnic, population-based project, being conducted in eight geographical areas (Brazil, China, India, Italy, Kenya, Oman, UK and USA), with technical support from four global specialised units, to study growth, health and nutrition from early pregnancy to infancy. It aims to produce prescriptive growth standards, which conceptually extend the World Health Organization (WHO) Multicentre Growth Reference Study (MGRS) to cover fetal and newborn life. The new international standards will describe: (1) fetal growth assessed by clinical and ultrasound measures; (2) postnatal growth of term and preterm infants up to 2 years of age; and (3) the relationship between birthweight, length and head circumference, gestational age and perinatal outcomes. As the project has selected healthy cohorts with no obvious risk factors for intrauterine growth restriction, these standards will describe how all fetuses and newborns should grow, as opposed to traditional charts that describe how some have grown at a given place and time. These growth patterns will be related to morbidity and mortality to identify levels of perinatal risk. Additional aims include phenotypic characterisation of the preterm and impaired fetal growth syndromes and development of a prediction model, based on multiple ultrasound measurements, to estimate gestational age for use in pregnant women without access to early/frequent antenatal care.

IMPORTANCE Identifying predictors of mortality from diabetes mellitus (DM) and heart disease can help shape treatment strategies. Presence of androgenetic alopecia (AGA) might be such a predictor.

OBJECTIVE

To determine whether the presence of AGA is associated with an elevated rate of mortality from DM and heart disease in both sexes after adjustment for potential confounders. DESIGN A population-based prospective cohort study. SETTING Community-based integrated screening in Taiwan. PARTICIPANTS A total of 7252 subjects aged 30 to 95 years participated in the baseline AGA survey using the Norwood and Ludwig classifications between April and June 2005. Baseline information on metabolic syndrome (MetS) and other possible risk factors was also collected. We then followed this cohort over time to ascertain death and cause of death until December 2010. INTERVENTIONS OR EXPOSURES Application of Norwood and Ludwig ALA classifications to study population. MAIN OUTCOMES AND MEASURES Deaths from DM and heart disease.

RESULTS

Among the 7126 subjects (2429 men and 4697 women) who provided complete data, there were 70 deaths from DM and heart disease during the 57-month follow-up period. Subjects with moderate to severe AGA vs normal or mild AGA had a significantly higher risk of mortality from DM (adjusted hazard ratio [HR], 2.97; 95% CI, 1.26-7.01) (P = .01) and heart disease (adjusted HR, 2.28; 95% CI, 1.00-5.23) (P = .05) after adjusting for age, family history of DM or heart disease, and MetS.

CONCLUSIONS

AND RELEVANCE AGA is an independent predictor of mortality from DM and heart disease in both sexes. This finding may have significant implications for the identification of risk factors for DM and heart disease in patients with moderate or severe AGA, regardless of whether MetS is present.

Congenital adrenal hyperplasia (CAH) refers to autosomal recessive diseases resulting from deficiency of enzymes involved in the production of cortisol by the adrenal glands. This study was designed to determine the frequency of suspected congenital adrenal hyperplasia patients by evaluating the laboratory data of blood 17-OHP. The study was conducted at Chemical Pathology Section of Department of Pathology at the Aga Khan University, Karachi. The basic demographic data of 2282 subjects was recorded, screened for blood 17-OHP levels from January 2007 to December 2010. A cutoff of ³ 4 ng/ml was considered as suggestive of CAH. The results showed 17-OHP levels ³ 4 ng/ml were found predominantly among infants (14.4%) and in females (18.2%).

Melanotic neuroectodermal tumour of infancy is a rare, mostly benign but locally aggressive tumour of neural crest cell origin occurring in infants. The most commonly affected anatomic site is the maxilla. Such tumours of the brain and skull are very rare. We present the case of an 8 months old baby girl whose presenting complaint was a swelling in the scalp for 6 months. She was otherwise asymptomatic. CT imaging confirmed the presence of an osteolytic tumour in the anterior parasagittal skull with dural involvement. The tumour was surgically excised enbloc. The patient has been well at 2 years follow-up without any evidence of recurrence.

Primary breast sarcomas, except for phyllodes tumour, are very rare entities, accounting for < 0.1% of all malignant neoplasms. Angiosarcoma of breast is infrequent malignancy and differential diagnosis from other sarcomatous and angiomatous breast tumours holds importance. Two cases of primary angiosarcoma of breast were encountered. One involved a 32 years lady who was treated by wide local excision and six cycles of chemotherapy. The other occurred in a 54 years old lady who was treated with mastectomy, did not receive any radiation or chemotherapy and was later lost to follow-up. Neither of the patient had history of previous breast surgery, chemotherapy or radiotherapy.