Ethnically diverse causes of Walker-Warburg syndrome (WWS): FCMD mutations are a more common cause of WWS outside of the Middle East

Walker-Warburg syndrome (WWS) is a genetically heterogeneous autosomal recessive disease characterized by congenital muscular dystrophy, cobblestone lissencephaly, and ocular malformations. Mutations in six genes involved in the glycosylation of á-dystroglycan (POMT1, POMT2, POMGNT1, FCMD, FKRP and LARGE) have been identified in WWS patients, but account for only a portion of WWS cases. To better understand the genetics of WWS and establish the frequency and distribution of mutations across WWS genes, we genotyped all known loci in a cohort of 43 WWS patients of varying geographical and ethnic origin. Surprisingly, we reached a molecular diagnosis for 40% of our patients and found mutations in POMT1, POMT2, FCMD and FKRP, many of which were novel alleles, but no mutations in POMGNT1 or LARGE. Notably, the FCMD gene was a more common cause of WWS than previously expected in the European/American subset of our cohort, including all Ashkenazi Jewish cases, who carried the same founder mutation.     

Out of Pocket Expenditure for Sick Newborn Care in Referral Hospitals of Nepal

Background

Almost all preventable neonatal deaths take place in low- and middle-income countries and affect the poorest who have the least access to high quality health services. Cost of health care is one of the factors preventing access to quality health services and universal health coverage. In Nepal, the majority of expenses related to newborn care are borne by the caregiver, regardless of socioeconomic status. We conducted a study to assess the out of pocket expenditure (OOPE) for sick newborn care in hospitals in Nepal.

Methods

This cross-sectional study of hospital care for newborns was conducted in 11 hospitals in Nepal and explored OOPE incurred by caregivers for sick newborn care. Data were collected from the caregivers of the sick newborn on the topics of cost of travel, accommodation, treatment (drugs, diagnosis) and documented on a sick newborn case record form.

Results

Data were collected from 814 caregivers. Cost of caregivers’ stay accounted for more than 40% of the OOPE for sick newborn care, followed by cost of travel, and the baby’s stay and treatment. The overall OOPE ranged from 13.6 to 226.1 US dollars (USD). The median OOPE was highest for preterm complications ($33.2 USD; CI 14.0–226.1), followed by hyperbilirubinemia ($31.9 USD; CI 14.0–60.7), respiratory distress syndrome ($26.9 USD; 15.3–121.5), neonatal sepsis ($ 25.8 USD; CI 13.6–139.8) and hypoxic ischemic encephalopathy ($23.4 USD; CI 13.6–97.7).

Discussion for practice

In Nepal, OOPE for sick newborn care in hospitals varied by neonatal morbidity and duration of stay. The largest proportion of OOPE were for accommodation and travel. Affordable and accessible health care will substantially reduce the OOPE for sick newborn care in hospitals.

     

青蒿琥酯皮肤擦剂在小鼠和兔体内的药代动力学研究

将青蒿琥酯溶于苯二甲酸二甲酯,加适量氨酮制成皮肤擦剂。给兔脱毛后,皮肤涂抹此擦剂25mg/kg后,血药浓度达峰时间平均为2 h,峰浓度平均为1.80μg/ml。药物在兔体内平均驻留时间为3.54 h,清除半衰期约为2.46 h。给小鼠脱毛皮肤涂抹擦剂6.7,31.3和71.4 mg/kg,血药浓度在给药后0.5～4 h达高峰,峰浓度分别为0.82,2.05和7.11μg/ml,体内药物平均驻留时间为3.39,2.79及3.54 h,清除半衰期为2.35,1.93及2.45 h。可见,给兔及小鼠皮肤擦剂后,青蒿琥酯吸收良好,血药浓度维持时间较长。     

乳酸中毒和pH对狗肺血管张力和气体交换功能影响的实验研究

急性代谢性酸中毒对狗血管张力和气体交换功能的影响进行了研究。当滴入乳酸或盐酸造成急性代谢性酸中毒（ｐＨ７．００）时，可引起肺血管收缩，肺动脉压力明显升高，血氧饱和度下降，并且乳酸和盐酸引起的酸中毒对肺动脉平均压影响程度相似，提示肺血管收缩和肺动脉压升高的程度与血中ｐＨ值下降关系密切，而与此时血中乳酸水平的高低无关。     

Continuous wave Doppler echocardiography after surgical repair of coarctation of the aorta

Objective—To find how closely pressure gradients across the aortic arch derived from Doppler echocardiography reflect gradients measured by catheter after surgical repair of coarctation of the aorta.Design—Pressure drop across the aortic arch was measured simultaneously by continuous wave Doppler and double lumen catheter in 20 patients with repaired coarctation of the aorta.Results—The peak pressure drop estimated by Doppler was almost invariably higher than the peak to peak gradient measured by catheter, as might be expected. Wide variation was seen between the Doppler measured pressure drop and instantaneous peak gradient measured by catheter, ranging from +22 to −17 mm Hg. The reasons for these differences are unclear but are probably related to a combination of complex flow dynamics in the aortic arch, difficulty in closely aligning the Doppler beam with flow, and inability to measure flow velocity immediately proximal to the site of the surgical repair with continuous wave Doppler.Conclusions—Continuous wave Doppler echocardiography may significantly overestimate or underestimate the pressure drop after repair of coarctation and it should be interpreted with caution in individual patients. Catheterisation with angiography remains the reference standard for assessment of surgical repair of the aortic arch.     

A histologically visible representation of the fingers and palm in primate area 3b and its immutability following long-term deafferentations

An isomorph of the glabrous hand is visible in primary somato-sensory cortex (area 3b) of owl monkeys in brain sections cut parallel to the surface and stained for myelin. A mediolateral row of five ovals, separated by myelin-light septa, represents digits and corresponds precisely with cortical sites activated by light touch on individual digits in microelectrode recordings. A number of caudal ovals relate to pads of the palm. A more distinct septum separates the hand from the more lateral face representation. Within the face representation, two large myelin-dense ovals can be identified that are activated by the upper or lower face in a caudo-rostral sequence. Accidental finger loss or dorsal column section, deafferentations that result in reorganization of the physiological map in area 3b, do not alter the morphological map. The proportions for each digit and palm in the morphological map do not vary across normal and deafferented animals. Similar isomorphs were also seen in area 3b of squirrel and macaque monkeys. We conclude that the anatomical isomorph for the body surface representation in area 3b is a reliable reflection of normal cortical organization and may be a common feature of the primate area 3b. The isomorph can provide a reference in studies of somatotopic reorganization.