Is there a role played by HLA-E,if any,in HPV immune evasion?

Cervical cancer incidence worldwide exceeds half a million new cases per year. The human papillomavirus (HPV) being the major causative agent of CC uses a variety of strategies to evade immune surveillance, where the immune status varies amongst individuals. This immune evasion altered by HPV is reflected in persistent infections, causing the evolution of cervical neoplasia. The role of the immune system in viral recognition and elimination is of extreme relevance in the development of CC. The interactions of the HLA-E ligand in the target cell along with CD94/NKG2 receptors, which are expressed predominantly, but not exclusively, on NK cells’ surface, are responsible for activating or inhibiting cytotoxic activity according to their function. The engagement between HLA-E and CD94/NKG2 molecules is one of the fundamental surveillance mechanisms in patients with CIN I, II and III, where HLA-E expression increases significantly, especially in HPV 16 and 18 infections. Higher HLA-E expression was observed in most histopathological types of CC, and at the same time was correlated to best survival of the patient. This review aims to summarize and discuss the immunological role of HLA-E in the context of HPV infection and immune system evasion, and the oncogenic process of cervical cancer.     

Non-Obstetric Surgical Care at Three Rural District Hospitals in Rwanda: More Human Capacity and Surgical Equipment May Increase Operative Care

Background

Most mortality attributable to surgical emergencies occurs in low- and middle-income countries. District hospitals, which serve as the first-level surgical facility in rural sub-Saharan Africa, are often challenged with limited surgical capacity. This study describes the presentation, management, and outcomes of non-obstetric surgical patients at district hospitals in Rwanda.

Methods

This study included patients seeking non-obstetric surgical care at three district hospitals in rural Rwanda in 2013. Demographics, surgical conditions, patient care, and outcomes are described; operative and non-operative management were stratified by hospitals and differences assessed using Fisher’s exact test.

Results

Of the 2660 patients who sought surgical care at the three hospitals, most were males (60.7 %). Many (42.6 %) were injured and 34.7 % of injuries were through road traffic crashes. Of presenting patients, 25.3 % had an operation, with patients presenting to Butaro District Hospital significantly more likely to receive surgery (57.0 %, p < 0.001). General practitioners performed nearly all operations at Kirehe and Rwinkwavu District Hospitals (98.0 and 100.0 %, respectively), but surgeons performed 90.6 % of the operations at Butaro District Hospital. For outcomes, 39.5 % of all patients were discharged without an operation, 21.1 % received surgery and were discharged, and 21.1 % were referred to tertiary facilities for surgical care.

Conclusion

Significantly more patients in Butaro, the only site with a surgeon on staff and stronger surgical infrastructure, received surgery. Availing more surgeons who can address the most common surgical needs and improving supplies and equipment may improve outcomes at other districts. Surgical task sharing is recommended as a temporary solution.

     

Pericardiectomy causing abdominal hernia incarceration

A 26-year-old Rwandan male presented with constrictive pericarditis, massive ascites and a giant umbilical hernia that had been asymptomatic for over a decade. Successful pericardiectomy was complicated by prompt incarceration of the abdominal hernia. This unexpected complication was caused by rapid resolution of the ascites due to autodiuresis and subsequent collapse of the hernial orifice. Patients with constrictive pericarditis and massive ascites who are evaluated for pericardiectomy should be carefully examined for the presence of abdominal hernias. If any such hernias are found, perioperative hernia repair should be considered and postoperative diuresis should be undertaken under close observation.     

Signaling defects in iPSC-derived fragile X premutation neurons

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a leading monogenic neurodegenerative disorder affecting premutation carriers of the fragile X (FMR1) gene. To investigate the underlying cellular neuropathology, we produced induced pluripotent stem cell-derived neurons from isogenic subclones of primary fibroblasts of a female premutation carrier, with each subclone bearing exclusively either the normal or the expanded (premutation) form of the FMR1 gene as the active allele. We show that neurons harboring the stably-active, expanded allele (EX-Xa) have reduced postsynaptic density protein 95 protein expression, reduced synaptic puncta density and reduced neurite length. Importantly, such neurons are also functionally abnormal, with calcium transients of higher amplitude and increased frequency than for neurons harboring the normal-active allele. Moreover, a sustained calcium elevation was found in the EX-Xa neurons after glutamate application. By excluding the individual genetic background variation, we have demonstrated neuronal phenotypes directly linked to the FMR1 premutation. Our approach represents a unique isogenic, X-chromosomal epigenetic model to aid the development of targeted therapeutics for FXTAS, and more broadly as a model for the study of common neurodevelopmental (e.g. autism) and neurodegenerative (e.g. Parkinsonism, dementias) disorders.     

Effects of introducing routinely ultrasound scanning during Ante Natal Care (ANC) clinics on number of visits of ANC and facility delivery: a cohort study

Background

Many countries have integrated antenatal care as an essential part of routine maternal health services. The importance of this service cannot be overemphasized as many women’s lives are usually saved particularly through early detection of pregnancy related complications. However, while many women would attend at least one visit for ante natal care (ANC), completion of recommended number of visits (4+) has been a challenge of many health systems particularly in developing countries like Tanzania.

Methods

We conducted a cohort study to include ultrasound scanning using a portable hand-held Vscan to test whether by integrating it in routine ANC clinics at dispensary and health centre levels would promote number of ANC visits by women.Health providers rendering ANC services in selected facilities were trained on how to use the simple technology of ultrasound scanning. Women living in catchment areas of the respective selected facilities were eligible to inclusion to the study when consented. A baseline status of the ANC attendance in the study area was established through baseline household and facility surveys. A total of 257 women consented and received the study treatment.

Results

Our results showed that, there was no a slight change between baseline (97.2 %) and endline (97.4 %) results among women attending ANC clinics at least once. However, there was a significant change in percentage of women attending ANC clinic four times or more (27.2 % during baseline and 60.3 %; p = 0001).

Conclusions

We conclude that, introduction of the simplified ultrasound scanning technology at lowest levels of care has an effect to improving ANC attendance in terms of number of visits and motivate facility delivery.     

Incidence of Malaria among Mosquito Collectors Conducting Human Landing Catches in Western Kenya

The human landing catch (HLC) has long been the gold standard for estimating malaria transmission by mosquitoes, but has come under scrutiny because of ethical concerns of exposing collectors to infectious bites. We estimated the incidence of Plasmodium falciparum malaria infection in a cohort of 152 persons conducting HLCs and compared it with that of 147 non-collectors in western Kenya. Participants were presumptively cleared of malaria with Coartem™ (artemether-lumefantrine) and tested for malaria every 2 weeks for 12 weeks. The HLC collections were conducted four nights per week for six weeks. Collectors were provided chemoprophylaxis with Malarone™ (atovaquone-proguanil) during the six weeks of HLC activities and one week after HLC activities were completed. The incidence of malaria was 96.6% lower in collectors than in non-collectors (hazard ratio = 0.034, P < 0.0001). Therefore, with proper prophylaxis, concern about increased risk of malaria among collectors should not be an impediment to conducting HLC studies.