Aortic dissection and bicuspid aortic valve: an autopsy study

Medico-legal post-mortems referred to the Department of Pathology, for the histopathological examination, revealed six cases of acute aortic dissection--two in isolation, three in combination with congenital bicuspid aortic valve; and one isolated case of congenital bicuspid aortic valve. One case of isolated aortic dissection was associated with Marfan's syndrome; and one case of aortic dissection with bicuspid aortic valve was associated with polycystic kidneys. History of hypertension could be elicited in two cases. Cystic medial degeneration of aorta was seen in three cases; one of which was associated with Marfan's syndrome. All five cases of aortic dissection belonged to type II of DeBakey classification.     

A temporal gene delivery system based on fibrin microspheres

Combining complementary nonviral gene delivery vehicles such as tissue engineering scaffolds and liposomes not only is a promising avenue for development of safe and effective gene delivery system but also provides an opportunity to design dynamic extended release systems with spatiotemporal control. However, the DNA loading capacity of scaffolds such as fibrin is limited. Fibrin microspheres carrying DNA complexes can be utilized to extend the capacity of fibrin scaffold. Here, in a proof of concept study, the feasibility of fibrin microspheres for extending gene delivery capacity is described. Toward this goal, fibrin microspheres encapsulating lipoplexes were fabricated. The structural and functional integrity of DNA was assessed respectively by gel electrophoresis and an in vivo pilot study, using endothelial nitric oxide synthase (eNOS) as a model therapeutic gene in a rabbit ear ulcer model of compromised wound healing. The results confirmed structural integrity and successful delivery and functional integrity, assessed qualitatively by angiogenic effect of eNOS. Finally, as a step toward development of a "fibrin in fibrin" temporal release system, fibrin microspheres were shown to degrade and release DNA differentially compared to fibrin scaffold. It can thus be concluded that fibrin microspheres can be utilized for gene delivery to extend the capacity of a fibrin scaffold and can form a component of a "fibrin in fibrin" temporal release system.     

The effects of oncotype DX recurrence scores on chemotherapy utilization in a multi-institutional breast cancer cohort

The use of clinicopathologic features in decision-making in early stage estrogen receptor (ER)-positive breast cancer (BC) may lead to over or under treatment. We investigated the effect of the Oncotype Dx? (ODX) on chemotherapy (CTX) utilization in two cancer centers. 276 cases of node-negative ER-positive BC had ODX between 2005 and 2009. Age at diagnosis, tumor size, grade, and progesterone receptor (PR) status were abstracted from records and provided to two medical oncologists blinded to the ODX score. A recommendation for or against CTX was made based on clinicopathologic characteristics. Median age was 55 years. Mean tumor size was 1.6 cm. The median 10-year Adjuvant! Online (AO) mortality risk was 8. The median Nottingham Prognostic Index (NPI) was 3.3. The median ODX recurrence score was 17. Without knowledge of the ODX, oncologists were more likely to recommend CTX to younger women (P < 0.0001), women with negative PR status (P < 0.0001), higher NPI (P < 0.012), and tumors > 1 cm (P = 0.033). On average, CTX recommended patients had larger tumors (2.0 vs. 1.2 cm) and higher AO 10-year mortality (11.4 vs. 4.4%). ODX resulted in a change in management for 38% of women. Of 188 total patients who did not receive CTX, 71 had a recommendation favoring CTX by an oncologist blinded to the ODX score. In our multi-institutional cohort, the ODX score had a significant impact on the receipt of adjuvant CTX and altered management for 38% of women.     

Situational analysis to inform development of primary care and community-based mental health services for severe mental disorders in Nepal

Background

Nepal is representative of Low and Middle Income Countries (LMIC) with limited availability of mental health services in rural areas, in which the majority of the population resides.

Methods

This formative qualitative study explores resources, challenges, and potential barriers to the development and implementation of evidence-based Comprehensive Community-based Mental Health Services (CCMHS) in accordance with the mental health Gap Action Programme (mhGAP) for persons with severe mental health disorders and epilepsy. Focus Group Discussions (FGDs, n = 9) and Key-Informant Interviews (KIIs, n = 26) were conducted in a rural district in western Nepal. Qualitative data were coded using the Framework Analysis Method employing QSR NVIVO software.

Results

Health workers, general community members, and persons living with mental illness typically attributed mental illness to witchcraft, curses, and punishment for sinful acts. Persons with mental illness are often physically bound or locked in structures near their homes. Mental health services in medical settings are not available. Traditional healers are often the first treatment of choice. Primary care workers are limited both by lack of knowledge about mental illness and the inability to prescribe psychotropic medication. Health workers supported upgrading their existing knowledge and skills through mhGAP resources. Health workers lacked familiarity with basic computing and mobile technology, but they supported the introduction of mobile technology for delivering effective mental health services. Persons with mental illness and their family members supported the development of patient support groups for collective organization and advocacy. Stakeholders also supported development of focal community resource persons to aid in mental health service delivery and education.

Conclusion

Health workers, persons living with mental illness and their families, and other stakeholders identified current gaps and barriers related to mental health services. However, respondents were generally supportive in developing community-based care in rural Nepal.