xlgv7: a maternal gene product localized in nuclei of the central nervous system in Xenopus laevis

The Xenopus oocyte nucleus (GV) is a storehouse for a large number of proteins that are used during early development. We have cloned and characterized a cDNA coding for a maternal gene product that is localized in the GV and then becomes highly enriched in the nuclei of the central nervous system (CNS) of tadpoles and adult frogs. This cDNA (xlgv7) is 2.1 kb and hybridizes to a 2.4-kb RNA species on Northern blots. Southern blots of genomic DNA suggest that this gene is a member of a multigene family. The cDNA sequence reveals a long open reading frame (ORF) of 1773 nucleotides, with a putative nuclear targeting signal (Glu Arg Arg Lys Lys Lys Thr) at the extreme carboxyl terminus and an internal histidine (His)-rich region with a repeated conserved amino acid sequence between His pairs. The significance of this region is unclear, but the protein is a DNA-binding protein, and it is possible that this region is involved in this function. The xlgv7 protein also possesses a putative nucleotide-binding consensus sequence that is similar to the bacterial RecA and RecB and yeast RAD proteins. Protein xlgv7 exists as several isotypes that exhibit developmental and cell-specific changes during development. Northern blot analysis of the abundance of the xlgv7 mRNA shows an accumulation following neural induction at stages 15-16. There is a transient expression of the mRNA in the gut of tadpoles. In the adult, the mRNA is highly enriched in the brain and is absent or in very low abundance in other tissues. Immunohistochemical analysis of the protein shows that the protein is localized in the nuclei of the brain cells. We conclude that the xlgv7 gene product is a maternal protein that may serve several important functions, one of which may be in the development and maintanance of the CNS.     

Intracellular potentials of microperfused human sweat duct cells

Intracellular potentials of cells from isolated segments of microperfused human sweat ducts were measured in order to determine the electrical profiles of these cells under resting, transporting, and inhibited conditions. Even though the cells are relatively small (ca. 6–8 m), continuous recordings of intracellular potentials from the same impalement were stable for up to 2 h. In the resting condition in normal Ringer's solution when the lumen of the duct was collapsed and not perfused, the intracellular potential measured across the basal membrane was 34.6±1.5 mV (n=31; mean±SE). In the same bathing medium, when the duct lumen was also perfused with normal Ringer's solution, the basolateral membrane potential (V _b), the apical membrane potential (V _a) and transepithelial potential (V _t) was –33.8±0.47 mV, –23.7±0.48 mV and –9.6±0.9 mV (n=73), respectively. The average input impedence (R _i) of these cells was 19.6±0.4 M (n=36). The frequency distribution ofV _b was unimodal suggesting that only one functional cell type exists in this tissue. Amiloride (0.1 mM) in the lumen hyperpolarized bothV _a andV _b by –40.5±3.6 mV and –33.2±3.7 mV (n=15), respectively, with a slight but significant increase inR _i (15%), while abolishingV _t. Removing luminal Cl^– depolarizedV _a by +37.0±4.2 mV and hyperpolarizedV _b by –19.0±4.2 mV (n=11). Removing Cl^– from the bath hyperpolarizedV _a by –3.3±2.3 mV and depolarizedV _b by +24.3±2.7 mV (n=15). Ouabain caused an initial fast depolarization (+8 mV) followed by a prolonged slow depolarization ofV _b, and an increase inR _i of about 84%. These results not only provide the first electrical profile of the human sweat duct tissue, but they also show that its cell membrane potentials are unusually low. This unusual property of this epithelium appears to be due to the combination of a significant Na⁺ conductance at the apical membrane and a remarkably high tissue Cl^– conductance.     

Prostate cancer: results of external irradiation.

From 1975 to 1982, 205 patients with local prostate cancer were treated at the radiation oncology department, the University of Kansas Medical Center, Kansas City, Kansas. Patients'' median age was 73 years. All of the patients were staged according to American Urologic staging criteria. Twenty-eight patients had stage A2 cancer, 91 patients had stage B cancer, and 86 patients had stage C cancer. All patients were treated using megavoltage radiation (dosage range: 6000 cGy to 7100 cGy). The follow-up period ranged from a minimum of 8 years to a maximum of 15 years (median: 9.4 years). The clinical local control was 96% for stage A2, 94% for stage B, and 90% for stage C disease. The overall and disease-free survival rates were 71% and 60%, respectively. Fourteen patients developed moderate complications with one patient (0.5%) requiring surgical intervention. The local control and survival rates reported in this study are comparable with surgical results, suggesting that external beam irradiation in prostate cancer is safe and effective.     

Surgical management of synchronous coronary artery disease and multiple aortic stenosis: a case report with brief review of the literature

One-stage surgery was successfully performed in a 44-year-old hypertensive man with uncontrolled angina, multiple coarctations of the thoracic and abdominal aorta, and a previous subtotal gastrectomy. There was a gradient of 120 mm Hg between the thoracic and abdominal aorta. A graft was placed retroperitoneally from the infrarenal aorta to the ascending aorta and was followed by a coronary artery bypass graft. Twenty-four months postoperatively, the patient was free of angina, and his hypertension was easily controlled.     

Temporal trends in correlates of HIV testing uptake in South Africa: evaluation and population-level impacts of socio-economic factors and information sources

Aim

The primary objective of this study was to investigate temporal changes in HIV testing rates and quantify the degree to which these trends can be attributed to certain socio-economic characteristics, as well as exposure to information sources.

Subjects and methods

Data from a nationally representative sample of 30,020 sexually active black Africans who participated in the first, second, third and fourth South African National HIV, Behaviour and Health Surveys conducted in 2002, 2005, 2008 and 2012, respectively. Multivariable logistic regression models and population-attributable risks were calculated for the socio-economic characteristics and the information sources.

Results

The socio-economic characteristics of the survey participants remained stable over time, while HIV testing rates increased substantially from 20% in 2002 to 70% in 2012. However, there was little improvement in condom use rates. Combined impact of education, employment and geographical locations were associated with increased levels of HIV testing rates. Most of the survey participants (> 80%) were exposed to several mass-media and interpersonal information sources. The combined impact of mass-media tools on HIV testing rates ranged between 48 and 60%, while 40–50% of the HIV tests were collectively attributed to the interpersonal information sources.

Conclusion

We observed significant temporal changes in population-level impacts of several key socio-economic characteristics and information sources on HIV testing rates. Widespread nationwide HIV awareness efforts led to significant increases in access to testing facilities and substantial increases in HIV testing rates over time. However, this increase was not mirrored in condom use behaviour.

     

Success of Maternal and Child Health Pipeline Training Programs: Alumni Survey Results

Maternal and Child Health Journal - The Maternal and Child Health (MCH) Pipeline Training Program, promotes development of a diverse health workforce by training undergraduate students from...     

Estimate of Burden and Direct Healthcare Cost of Infectious Waterborne Disease in the United States

Provision of safe drinking water in the United States is a great public health achievement. However, new waterborne disease challenges have emerged (e.g., aging infrastructure, chlorine-tolerant and biofilm-related pathogens, increased recreational water use). Comprehensive estimates of the health burden for all water exposure routes (ingestion, contact, inhalation) and sources (drinking, recreational, environmental) are needed. We estimated total illnesses, emergency department (ED) visits, hospitalizations, deaths, and direct healthcare costs for 17 waterborne infectious diseases. About 7.15 million waterborne illnesses occur annually (95% credible interval [CrI] 3.88 million–12.0 million), results in 601,000 ED visits (95% CrI 364,000–866,000), 118,000 hospitalizations (95% CrI 86,800–150,000), and 6,630 deaths (95% CrI 4,520–8,870) and incurring US $3.33 billion (95% CrI 1.37 billion–8.77 billion) in direct healthcare costs. Otitis externa and norovirus infection were the most common illnesses. Most hospitalizations and deaths were caused by biofilm-associated pathogens (nontuberculous mycobacteria, Pseudomonas, Legionella), costing US $2.39 billion annually.     

Does Early Debridement,Antibiotic Therapy and Implant Retention (DAIR) have a Role in Managing Periprosthetic Joint Infection of the Knee in Indian Scenario: A Retrospective Analysis of Outcomes

PurposeTo report outcomes of Debridement, Antibiotic therapy and Implant Retention (DAIR) for periprosthetic knee joint infections (PJI) in the Indian population and to study factors influencing outcomes.MethodsThis was a Retrospective study of 80 cases of acute PJI after total knee arthroplasty who were treated by DAIR, within 2 weeks of onset of infection. A standardised institutional management protocol was applied to all cases. Patients were followed up for a minimum 1 year. Outcomes of DAIR were classified as successful or unsuccessful based on resolution or persistence of infection, and subsequent requirement of revision surgery. Influence of factors, like comorbidities, culture status and microbiological characteristics of causative organism, on outcomes was assessed.ResultsOverall 55 patients (68.75%) had successful eradication of infection after DAIR. 27 (33.7%) patients were culture negative and 53 (66.2%) patients grew organisms on culture. There was no statistically significant difference in outcomes (p = 0.082) between culture-positive cases (69.8% success rate) and (66.7% success rate) in culture negative cases. Furthermore, no difference in outcomes was observed in culture-positive patients between those who grew Gram-positive organisms versus Gram-negative organisms (p = 0.398) Similarly, patient comorbidities did not significantly alter the outcomes after DAIR (p = 0.732).ConclusionOur study demonstrates that early DAIR within 2 weeks of onset of infection using a standard protocol during surgery and postoperatively can result in good outcomes. Patient comorbidities, culture status (positive versus negative), Gram staining characteristics of organisms and the identity of pathogenic bacteria did not influence outcomes of DAIR for acute PJI.     

Pro-inflammatory cytokines and chemokines initiate multiple prostate cancer biologic pathways of cellular proliferation,heterogeneity and metastasis in a racially diverse population and underlie the genetic/biologic mechanism of racial disparity: Update

Pro-inflammatory cytokine and chemokines genes drive prostate cancer progression and metastasis: molecular mechanism update and the science that underlies racial disparity. comprehensive review article.Isaac J. Powell, S. Chinni, S.S. Reddy, Alexander Zaslavsky, Navnath Gavande Introduction: In 2013 we reported that with the use of bioinformatics and ingenuity pathway network analysis we were able to identify functional driver genes that were differentially expressed among a large population of African American men (AAM) and European American men (EAM). Pro-inflammatory cytokine genes were found to be more interactive and more expressed among AAM and have been found to be functional drivers of aggressive prostate cancer (CaP) and aggressiveness in other solid tumors. We examined these genes and biological pathways initiated by these cytokines in primary CaP tissue.Method We unravel the gene network and identified biologic pathways that impacted activation of the androgen receptor, mesenchymal epithelial transition (invasion) and chemokines associated with metastasis in the CaP tissue from 639 radical prostatectomy specimens.Results Biologic pathways identified by unraveling pro-inflammatory genes from our network, more expressed among AAM compared to EAM, were tumor necrosis factor (TNF), IL1b, IL6, and IL8. IL6 and IL8 are downstream of TNF activity and are known activators of androgen receptor and through mediators promote CaP cell proliferation. TNF and IL1b mediate tumor cell invasiveness through the activation of MMP (matrix metalloproteinase) which down regulates E-Cadherin to initiate epithelial mesenchymal transition which allows cells to become invasive in the microenvironment. Ultimately our network analysis indicates that TNF and IL1b activate CXCR4 receptor on CaP cells, which facilitates metastatic progression reportedly by binding to CXCL12 on lipid rafts and tumor implantation in the bone marrow.Conclusion Our retrospective biologic mechanistic model reveals a set of pro-inflammatory cytokines and chemokines that drive CaP aggressiveness, tumor heterogeneity, progression and metastasis. A prospective multi-institutional study needs to be conducted for clinical validation as well consideration of targeted therapy.