Serological Assessment for <Emphasis Type="Italic">Leishmania donovani</Emphasis> Infection in Blood Donors of Sunsari District,Dharan, Nepal

Visceral leishmaniasis (VL) is a major vector-borne disease caused by Leishmania donovani, after replication of the parasites in macrophages, mononuclear phagocytic system. VL is endemic in 12 districts of central and eastern Terai lowlands of Nepal bordering North Bihar, India with an estimated 8 million population at risk. In addition, VL endemicity is also extending to new endemic regions like Dharan from its classical rural foci. Hence, we aimed to detect the evidence of Leishmania donovani infection in the blood samples received from blood donors of Sunsari district, Dharan, (eastern Nepal), a region endemic for human VL. Sera from 507 asymptomatic blood donors were subjected to serological screening for anti-Leishmania donovani antibodies. Direct agglutination test (DAT) was performed on the sera. Out of 507 donors, majority (78.50 %) were male. Among the donors, 472 (93.10 %) belonged to age group 18–45 years where as 35 (6.90 %) to age group >45 years. Circulating anti-Leishmania antibodies were detected in 5 (1 %) out of 507 healthy, Human Immunodeficiency Virus types 1 and 2 (HIV 1and 2), Hepatitis B Surface Antigen (HBsAg), anti- Hepatitis C Virus (anti-HCV)-negative, and Syphillis non-reactive donors. All the seropositive cases were male and belonged to the age group 18–45 years. The result suggests that there is an immediate need of screening asymptomatic blood donors for leishmania seropositivity especially in endemic areas.     

Piloting a Telephone Based Health Coaching Program for Pregnant Women: A Mixed Methods Study

Maternal and Child Health Journal - Objectives Get Healthy in Pregnancy (GHiP) is a telephone based lifestyle coaching service for pregnant women, in New South Wales, Australia. GHiP had two...     

Serological markers for leishmania donovani infection in Nepal: Agreement between direct agglutination test and rK39 ELISA

Visceral leishmaniasis (VL) is an important vector-borne disease caused by Leishmania donovani in the Indian subcontinent. The actual incidence and role of asymptomatic infections in the region are not wellknown. We used the direct agglutination test (DAT) and the rK39 ELISA as L. donovani infection markers in 10 VL endemic villages in Nepal. DAT titre distribution showed two subgroups in the population (infected and non-infected individuals), while rK39 did not. The agreement between both tests was moderate (j = 0.53; 95% CI 0.49–0.57). More research is needed to develop validated markers for Leishmania infection.     

Brain abscess due to Scedosporium apiospermum in a non immunocompromised child

Scedosporium apiospermum is a filamentous fungi that commonly causes cutaneous infection. In certain circumstances, S. apiospermum can also cause invasive disease, which can involve the central nervous system (CNS). When the CNS becomes involved, treatment is difficult, therapeutic options are limited and the prognosis is poor. Early identification and treatment can decrease the mortality rate. Here we present a case of brain abscess with chronic suppurative otitis media, caused by S. apiospermum. This is the first such case report from Nepal. We could identify the organism only post mortem. We could not save the patient, probably due to delay in diagnosis.     

A simple method for bone positioning of mandibular segments

A simple bone-positioning technique is reported, using a combination of bone plates and a flexible tube filled with acrylic polymer. The flexible tube is solidified by injection of acrylic monomer. This technique is applicable for bone positioning after mandibular resection as well as positioning of the proximal segment after sagittal split ramus osteotomy. This technique has the advantages of greater simplicity and flexibility compared to previously reported methods of bone positioning.     

Proyl isomerase Pin1 facilitates ubiquitin-mediated degradation of cyclin-dependent kinase 10 to induce tamoxifen resistance in breast cancer cells

Endocrine therapies that inhibit estrogen receptor (ER)-α signaling are the most common and effective treatment for ER-α-positive breast cancer. However, the use of these agents is limited by the frequent development of resistance. The aim of this study was to elucidate the mechanisms by which downregulation of CDK10 expression confers resistance to tamoxifen in breast cancer. Here, we show that peptidyl-prolyl isomerase Pin1 downregulates CDK10 protein as a result of its interaction with and ubiquitination of CDK10, thereby affecting CDK10-dependent Raf-1 phosphorylation (S338). Pin1(-/-) mouse embryonic fibroblasts (MEFs) show higher CDK10 expression than Pin1(+/+) MEFs, whereas CDK10 protein was downregulated in the rescued Pin1(-/-) MEFs after reexpression of Pin1. Pin1 silencing in SKBR-3 and MCF7 cells increased the CDK10 expression. In human tamoxifen-resistant breast cancer and tamoxifen-resistant MCF7 cells, immunohistochemical staining and immunoblotting analysis shows an inverse correlation between the expression of CDK10 and the degree of tamoxifen resistance. There was also a positive correlation between the high level of P-Raf-1 (Ser338) and Pin1 in human tamoxifen-resistant breast cancer and tamoxifen-resistant MCF7 (TAMR-MCF7) cells. Importantly, 4-OH tamoxifen (4-OHT), when used in combination with overexpressed CDK10 or Raf-1 inhibitor, increased cleaved PARP and DNA fragmentation to inhibit cologenic growth of MCF7 cells and Tamoxifen-resistant MCF7 cells, respectively. On the basis of these findings, we suggest that the Pin1-mediated CDK10 ubiquitination is a major regulator of tamoxifen-resistant breast cancer cell growth and survival.     

Prolongation of the QTc interval is seen uniformly during early transmural ischemia.

OBJECTIVES: In order to more clearly understand the electrocardiographic manifestations of early transmural ischemia, we studied electrocardiograms (ECGs) in patients undergoing balloon angioplasty. BACKGROUND: Decisions regarding reperfusion strategies in patients with acute myocardial infarction rely largely on the presence of ST-segment elevation (STE) in the ECG, consequently with significant limitations. Studies of the "ischemic cascade" show that ST-segment changes occur well after the onset of wall motion abnormalities. METHODS: We prospectively analyzed ECGs obtained at 20-s intervals in 74 patients undergoing elective balloon angioplasty. The ECGs were analyzed using 3 methodologies. In 74 patients, the ST-segment, the T-wave, and the QT-interval were analyzed using the MUSE (General Electric HC, Menomonee Falls, Wisconsin) automated system (MUSE). Fifty patients were also analyzed using the Interval Editor automated system (IE; General Electric HC). In 20 patients, measurements were made manually. RESULTS: Transmural ischemia prolonged the QTc interval (using the Bazett's formula) in 100% of patients. In all 74 patients analyzed with MUSE, QTc interval prolonged from 423 +/- 25 ms to 455 +/- 34 ms (p < 0.001). In the 50 patients analyzed with IE, QTc interval prolonged in 50 of 50 (100%) patients (from 424 +/- 27 ms to 458 +/- 33 ms [p < 0.001]). Mean time to maximal QTc interval prolongation, changes in T-wave polarity, > or =1 mm STE, and ST-segment depression (STD) were 22, 24, 29, and 35 s, respectively. Although QTc interval prolonged in 100% of patients, T-wave changes, STE, and STD (> or =1 mm) occurred in 7%, 15%, and 7%, respectively. CONCLUSIONS: The QTc interval prolongs in 100% of patients with early transmural ischemia. When compared with clinically accepted indexes of transmural ischemia (i.e., STD and STE [> or =1 mm]) it is the earliest ECG abnormality.     

Left atrial reverse remodeling in dogs with moderate and advanced heart failure treated with a passive mechanical containment device: an echocardiographic study

BackgroundAssessment of global left ventricular (LV) remodeling is important in evaluating the efficacy of pharmacologic and device therapies for the treatment of chronic heart failure (HF). The effects of pharmacologic or device therapies on global left atrial (LA) remodeling in HF, although also important, are not often examined. We showed that long-term therapy with the Acorn Cardiac Support Device (CSD), a passive mechanical ventricular containment device, prevents or reverses LV remodeling in dogs with HF. This study examined the effects of the CSD on global LA remodeling in dogs with moderate and advanced HF.Methods and ResultsStudies were performed in 24 dogs with coronary microembolization-induced HF. Of these, 12 had moderate HF (ejection fraction, EF 30% to 40%) and 12 advanced HF (EF ≤25%). In each group, the CSD was implanted in 6 dogs and the other 6 served as controls. Dogs were followed for 3 months in the moderate group and 6 months in the advanced HF group. LA maximal volume (LAVmax), LA volume at the onset of the p-wave (LAVp), LA minimal volume (LAVmin), LA active emptying volume (LAAEV), and LA active emptying fraction (LAAEF) were measured from 2-dimensional echocardiograms obtained before CSD implantation and at the end of the treatment period. Treatment effect (Δ) comparisons between CSD-treated dogs and controls showed that CSD therapy significantly decreased LA volumes (ΔLAVmax: 3.33 ± 0.70 vs. –2.87 ± 1.31 mL, P = .002; 7.77 ± 1.76 versus –0.37 ± 0.87 mL, P = .002) and improved LA function (ΔLAAEF: –6.00 ± 1.53 versus 1.85 ± 1.32%, P = .003; –2.39 ± 1.10 versus 3.13 ± 1.66%, P = .02) in the moderate HF and advanced HF groups, respectively.ConclusionsProgressive LA enlargement and LA functional deterioration occurs in untreated dogs with HF. Monotherapy with the CSD prevents LA enlargement and improves LA mechanical function in dogs with moderate and advanced HF indicating prevention or reversal of adverse LA remodeling.