Cyclooxygenase-2 is Upregulated in Copper-Deficient Rats

Copper deficiency inactivates Cu/Zn-SOD and promotes accumulation of reactive oxygen species. This process likely impairs nitric oxide (NO)-mediated relaxation as well as triggers vascular inflammation. The current study was designed to determine whether COX-2, a proinflammatory protein, expression and activity are upregulated in the oxidative environment associated with inadequate Cu. Weanling male Sprague Dawley rats were fed purified diets which were either Cu-adequate (Cu-A); Cu-marginal (Cu-M), Cu-deficient (Cu-D), or the Cu-D diet combined with the SOD mimetic Tempol (Cu-D/T; 1 mM in drinking water) for 4 weeks. COX-2 protein, PGE₂ (COX-2 metabolite) and isoprostanes (index of oxidative stress) were all higher in the Cu-D group vs Cu-A group, but no significant differences occurred between the Cu-M and Cu-A groups. Tempol protected against an attenuation of NO-mediated vasodilation in the Cu-D rats but did not prevent the elevation of PGE₂ or isoprostanes. Our data suggest a role for copper as a modulator of oxidative stress and inflammation independent of SOD activity or NO-derived oxidants.     

Intratesticular angioleiomyoma

Angioleiomyomas are common benign smooth muscle tumors that occur in the subcutis of the extremities and to a lesser extent, of the head and trunk. Rarely, these tumors have been reported in other deeper tissues, but never within the testis. We present what we believe to be the first report of intratesticular angioleiomyoma, occurring in a 58-year-old man with a painless testicular swelling. Orchidectomy was the treatment of choice in this patient, as there was no reliable imaging technique to clinically distinguish this benign lesion from the more common malignant intratesticular tumors.     

Extended family and friendship support and suicidality among African Americans

Purpose

This study examined the relationship between informal social support from extended family and friends and suicidality among African Americans.

Methods

Logistic regression analysis was based on a nationally representative sample of African Americans from the National Survey of American Life (N = 3263). Subjective closeness and frequency of contact with extended family and friends and negative family interaction were examined in relation to lifetime suicide ideation and attempts.

Results

Subjective closeness to family and frequency of contact with friends were negatively associated with suicide ideation and attempts. Subjective closeness to friends and negative family interaction were positively associated with suicide ideation and attempts. Significant interactions between social support and negative interaction showed that social support buffers against the harmful effects of negative interaction on suicidality.

Conclusions

Findings are discussed in relation to the functions of positive and negative social ties in suicidality.

     

Prioritizing the sexual and reproductive health and rights of adolescent girls and young women within HIV treatment and care services in emergency settings: a girl-centered agenda

Background

The integration of family planning (FP) and HIV-related services is common in sub-Saharan Africa. Little research has examined how FP quality of care differs between integrated and non-integrated facilities. Using nationally representative data from Malawi and Tanzania, we examined how HIV integration was associated with FP quality of care.

Methods

Data were drawn from Service Provision Assessments (SPAs) from Malawi (2013–2014) and Tanzania (2014–2015). The analytic sample was restricted to lower-level facilities in Malawi (n = 305) and Tanzania (n = 750) that offered FP services. We matched SPA measures to FP quality of care indicators in the Quick Investigation of Quality (QIQ). We conducted bivariate and multivariate analyses of 22 QIQ indicators to examine how integration status was related to individual QIQ indicators and overall FP quality of care at the facility- and client-level.

Results

The prevalence of HIV integration in Malawi (39%) and Tanzania (38%) was similar. Integration of HIV services was significantly associated (p < 0.05) with QIQ indicators in Malawi (n = 3) and Tanzania (n = 4). Except for one negative association in Tanzania, all other associations were positive. At the facility-level, HIV integration was associated with increased odds of being at or above the median in FP quality of care in Malawi (adjusted odd ratio (OR) = 2.24; 95% confidence interval (CI) = 1.32, 3.79) and Tanzania (adjusted OR = 2.10; 95% CI = 1.37, 3.22). At the client-level, HIV integration was not associated with FP quality of care in either country.

Conclusion

Based on samples in Malawi and Tanzania, HIV integration appears to be beneficially associated with FP quality of care. Using a spectrum of FP quality of care indicators, we found little evidence to support concerns that HIV integration may strain facilities and providers, and adversely impact quality outcomes. Rather, it appears to strengthen FP service delivery by increasing the likelihood of stocked FP commodities and achievement of other facility-level quality indicators, potentially through HIV-related supply chains. Further research is needed to assess FP quality of care outcomes across the various platforms of FP integration found in sub-Saharan Africa.

     

Pectus Excavatum: A Case Study

This case study presents the diagnosis and treatment of a child with pectus excavatum (PE), a common congenital abnormality of the anterior chest wall characterized by depression of the lower sternum. This depression ranges in severity from a minor dent to a deep, concave hollow capable of displacing the heart and intrathoracic structures. PE could present as a mild, asymptomatic condition, primarily with cosmetic implications. PE may progress to become a severe pathology that induces both serious physical symptoms and psychosocial problems. Nurse practitioners must implement adequate assessment and care strategies for PE patients to achieve optimal health outcomes.     

Variation in Institutional Review Board Responses to a Standard, Observational, Pediatric Research Protocol

Background: Multicenter studies are becoming more common, and variability in local institutional review board (IRB) assessments can be problematic.
Objective: To investigate the variability of IRB responses to a multicenter observational study of children presenting to emergency departments.
Methods: The authors collected the original IRB applications, subsequent correspondence, and a survey assessing submission timing and response and the nature of IRB queries. The study was conducted as part of the Emergency Medicine Network http://www.emnet-usa.org
Results: Of 37 sites initiating the IRB process, 34 (92%) participated in this IRB-approved study. Institutional review boards returned initial applications in a median of 19 days (IQR, 11–34 d), and 91% considered the protocol to be minimal risk. Of 34 submissions, 13 required no changes, 18 received conditional approvals, and 3 were deferred. The median time from initial submission to final approval was 42 days (IQR, 27–61 d). Seven sites did not participate in patient recruitment: two had institutional issues, one obtained IRB approval too late for participation, and four sites (12%) reported that IRB hurdles contributed to their lack of participation. Nonetheless, 68% of sites that recruited patients reported that the overall experience made them more likely to participate in future multicenter research.
Conclusions: There was substantial variation in IRB assessment of a standard protocol in this study. The burden of the application process contributed to some investigators not participating, but the majority of investigators remain enthusiastic about multicenter research. A national IRB may streamline the review process and facilitate multicenter clinical research.     

A phase I study of hepatic arterial infusion of nab-paclitaxel in combination with intravenous gemcitabine and bevacizumab for patients with advanced cancers and predominant liver metastases

Purpose

We conducted a phase I clinical trial for patients with advanced cancer and predominant liver disease.

Methods

Patients were treated with HAI nab-paclitaxel (120–210 mg/m²; day 1); intravenous bevacizumab (10 mg/kg; day 1); and intravenous gemcitabine (600–800 mg/m²; days 1 and 8). A conventional “3 + 3” study design was used.

Results

Fifty patients with advanced cancer and predominant liver metastases were treated (median age, 58 years; 27 women, 23 men; median number of prior therapies, 3 [range 0–12]). The most common cancers were breast (n = 9) and pancreatic (n = 9). Overall, 264 cycles were administered (median/patient, 4; range 1–17). No dose-limiting toxicities were noted during the escalation phase. On dose level 4, 3 patients were unable to receive gemcitabine on day 8 because of severe thrombocytopenia. Dose level 3 was selected as the maximum-tolerated dose (HAI nab-paclitaxel 180 mg/m² and intravenous gemcitabine 800 mg/m² and bevacizumab 10 mg/kg); 32 patients were treated in the expansion phase. The most common treatment-related toxicities were thrombocytopenia (n = 17), neutropenia (n = 10), and fatigue (n = 12). Of 46 patients evaluable for response, 9 (20 %) had a partial response (PR) and 9 (20 %) had stable disease for ≥6 months. The median overall survival duration was 7.0 months (95 % CI: 4, 22 months), and the median progression-free survival duration was 4.2 months (95 % CI: 2.7, 8.6 months).

Conclusions

HAI nab-paclitaxel in combination with gemcitabine and bevacizumab was well tolerated and had antitumor activity in selected patients with advanced cancer and liver metastases.     

Vaccine development for bacterial pathogens: Advances,challenges and prospects

The advent and use of antimicrobials have played a key role in treating potentially life-threatening infectious diseases, improving health, and saving the lives of millions of people worldwide. However, the emergence of multidrug resistant (MDR) pathogens has been a significant health challenge that has compromised the ability to prevent and treat a wide range of infectious diseases that were once treatable. Vaccines offer potential as a promising alternative to fight against antimicrobial resistance (AMR) infectious diseases. Vaccine technologies include reverse vaccinology, structural biology methods, nucleic acid (DNA and mRNA) vaccines, generalised modules for membrane antigens, bioconjugates/glycoconjugates, nanomaterials and several other emerging technological advances that are offering a potential breakthrough in the development of efficient vaccines against pathogens. This review covers the opportunities and advancements in vaccine discovery and development targeting bacterial pathogens. We reflect on the impact of the already-developed vaccines targeting bacterial pathogens and the potential of those currently under different stages of preclinical and clinical trials. More importantly, we critically and comprehensively analyse the challenges while highlighting the key indices for future vaccine prospects. Finally, the issues and concerns of AMR for low-income countries (sub-Saharan Africa) and the challenges with vaccine integration, discovery and development in this region are critically evaluated.