A new photoreactive antagonist cross-links to the N-terminal domain of the gonadotropin-releasing hormone receptor

A new photoreactive gonadotropin-releasing hormone (GnRH) antagonist [Ac-(4-azidobenzoyl)-D-Lys1, D-4-Cl-Phe2, D-Trp3, D-Arg6, D-Ala10]GnRH (PAnt-1) was synthesized and shown to bind covalently to mouse and human GnRH receptors after ultraviolet irradiation. PAnt-1 exhibited high binding affinity (Ki = 3.1 +/- 0.8 nM), and high crosslinking efficiency as shown by loss of 78% of binding sites following crosslinking at saturating concentration. Crosslinking resulted in irreversible receptor blockade as shown by inhibition of GnRH-stimulated inositol phosphate production. PAnt-1 has a photoreactive group at residue 1 of the peptide, a region believed to be critical in determining antagonist versus agonist properties of GnRH analogues. The attachment site of PAnt- to the receptor was localized between residues 11 and 19 of the extracellular N-terminal domain of the receptor by peptide mapping studies using natural sequence differences between human, mouse and sheep GnRH receptors, as well as a panel of GnRH receptor constructs with a series of engineered protease cleavage sites. A disulphide bridge between Cys14 and Cys200 was cleaved during crosslinking, suggesting that Cys14 is the crosslinked residue. These results suggest that peptide GnRH antagonists bind to the receptor with the N-terminal end of the peptide positioned in a site comprising the constrained regions of the N-terminal domain and second extracellular loop in the vicinity of the Cys14-Cys200 disulphide bridge.     

Partograph utilization and associated factors among obstetric care providers in North Shoa Zone,Central Ethiopia: a cross sectional study

Background

Globally, prolonged and obstructed labor contributed to 8% of maternal deaths which can be reduced by proper utilization of partograph during labor.

Methods

An Institution based cross-sectional study was conducted in June, 2013 on 403 obstetric care providers. A pre-tested and structured questionnaire was used to collect data. Data was entered to EpiInfo version 3.5.1 statistical package and exported to SPSS version 20.0 for further analysis. Logistic regression analyses were used to see the association of different variables.

Results

Out of 403 obstetric care providers, 40.2% utilized partograph during labor.Those who were midwives by profession were about 8 times more likely to have a consistent utilization of the partograph than general practitioners (AOR=8. 13, 95% CI: 2.67, 24.78). Similarly, getting on job training (AOR=2. 86, 95% CI: 1.69, 4.86), being knowledgeable on partograph (AOR=3. 79, 95% CI: 2.05, 7.03) and having favorable attitude towards partograph (AOR=2. 35, 95% CI: 1.14, 4.87) were positively associated with partograph utilization.

Conclusion

Partograph utilization in labor monitoring was found to be low. Being a midwife by profession, on job training, knowledge and attitude of obstetric care providers were factors affecting partograph utilization. Providing on job training for providers would improve partograph utilization.     

Tuberous sclerosis complex (TSC) and Klippel-Trenaunay-Weber (KTW) syndromes association of two complete phakomatoses in a single individual

Tuberous sclerosis or tuberous sclerosis complex (TSC) and Klippel-Trenaunay-Weber (KTW) syndromes are phakomatoses which are believed to be inherited separately were associated in a 21 years old female, with no family history of similar illness presented with facial rash of reddish spots or bumps, facial angiofibroma (adenoma cebaceum), which appeared on the nose and cheeks in a butterfly distribution, and sub ependymal calcific nodules on brain CT, and multiple liver, pancreas hamartomas and multiple angiomyolipomas and cysts of both kidney on ultrasound, which is consistent with a sporadic TSC, in addition, the diagnostic triad of KTW involved the left upper limb : cutaneous naevi a vascular anomaly, soft tissue and osteohypertrophy. This is the second reported association of the fully developed symptomatology of TSC and KTW in one person in Ethiopian setting.     

HIV and intestinal parasites in adult TB patients in a teaching hospital in Northwest Ethiopia

The level of HIV infection and intestinal parasitoses among TB patients was assessed in a hospital-based cross-sectional study involving 257 patients in Gondar, Ethiopia. In TB patients, our study reported co-infection with HIV (52.1%) and intestinal parasites (40.9%) The high prevalence of HIV and intestinal parasites indicates an increased morbidity inTB patients and emphasized the importance of continued HIV sero-surveillance, stool analysis and treatment.     

Magnitude and determinants of nonadherence and nonreadiness to highly active antiretroviral therapy among people living with HIV/AIDS in Northwest Ethiopia: a cross - sectional study

Background  

Adequate antiretroviral drug potency is essential for obtaining therapeutic benefit, however, the behavioral aspects of proper adherence and readiness to medication, often determine therapeutic outcome. Therefore, this study aimed to assess the level and determinants of nonadherence and nonreadiness to highly active antiretroviral therapy (HAART) among people living with HIV/AIDS (PLWHA) at Gondar University Teaching Hospital and Felege Hiwot Hospital in Northwest Ethiopia.     

A case of medulloepithelioma of the left eye

The case of a 12 year old male patient with a diagnosis of medulloepithelioma of the ciliary body is reported. The difficulties in reaching diagnosis and management are discussed. The importance of keeping such a rare disease in mind is stressed.     

Malnutrition and mortality in Kohistan District, Afghanistan, April 2001.

CONTEXT: The humanitarian situation in Afghanistan has been deteriorating for more than 3 years because of civil war and severe drought. Because of recent events, the international community is predicting a severe worsening of the country's current situation. OBJECTIVE: To assess the magnitude and causes of mortality and prevalence of malnutrition in Kohistan district, Faryab province, Afghanistan. DESIGN: Two-stage, 30-cluster household survey conducted April 4 through 10, 2001, which included anthropometric measurements, assessment of food coping mechanisms, and retrospective mortality data collection for November 26, 2000, through April 4, 2001. SETTING AND PARTICIPANTS: A total of 378 households comprising 3165 people living in Kohistan district, Faryab province, Afghanistan. MAIN OUTCOME MEASURES: Crude mortality rate, mortality rate among children younger than 5 years, causes of death, prevalence of wasting and stunting among children aged 6 to 59 months (weight-for-height and height-for-age z scores <-2, respectively), and food coping mechanisms. RESULTS: The crude mortality rate among the 3165 persons surveyed during the period of interest was 2.6 (95% confidence interval [CI], 1.7-3.5) per 10 000 per day and the mortality rate among 763 children younger than 5 years was 5.9 (95% CI, 2.0-8.8) per 10 000 per day. Diarrhea (25.0%), respiratory tract infections (19.4%), measles (15.7%), and scurvy (6.5%) caused most of the 108 deaths. The prevalences of wasting and stunting among 708 children aged 6 to 59 months were 7.0% (95% CI, 5.9%-9.0%) and 63.7% (95% CI, 58.6%-68.8%), respectively. Evidence of late-stage food coping mechanisms and prefamine indicators existed among the population. CONCLUSIONS: These data indicate that, by April 2001, a humanitarian crisis already existed in Kohistan. Essential humanitarian services, including food aid and public health programs, are urgently required in such regions of Afghanistan and will be crucial if a worsening humanitarian crisis is to be avoided. For these services and programs to be implemented, the international community needs to create adequate humanitarian space (ie, a secure and accessible location where humanitarian organizations can provide services to emergency-affected populations) to ensure that humanitarian organizations have access to populations within Afghanistan as well as to refugees who flee to surrounding countries.     

Evaluation of the modified Baermann's method in the laboratory diagnosis of Strongyloides stercoralis

This study compares the modified Baermann's method with the formol-ether concentration and the direct/saline techniques in the diagnosis of Strongyloides stercoralis larvae in stool specimens. This study was conducted at Wonji-Shewa Sugar Estate located at about 110 kms. south east of Addis Abeba. Of the 718 randomly selected and examined stool specimens, 125 were found positive for Strongyloides stercoralis. Of these 98% were recovered by the modified Baermann's method, 23% by the formol-ether, and 22% by the direct saline techniques. The rate of recovery by the modified Baermann's method was significantly different (p less than 0.001) compared with those of the direct and the formol-ether concentration techniques. There was no difference (p greater than 0.1) between the direct saline and the formol-ether methods. The modified Baermann's method accounted for over 60% of the total positive findings. Furthermore, the sensitivity of the method excelled the other two techniques by four fold. Thus, the modified Baermann's method by the Merck and Sharp Dohme Company is effective, cheap and simple to use and hence recommended for routine use and epidemiological surveys.