Brief strengths-based case management promotes entry into HIV medical care: results of the antiretroviral treatment access study-II

OBJECTIVE: The Antiretroviral Treatment Access Study-II (ARTAS-II) evaluated a brief case management intervention delivered in health departments and community-based organizations (CBOs) to link recently diagnosed HIV-infected persons to medical care rapidly. METHODS: Recently diagnosed HIV-infected persons were recruited from 10 study sites across the United States during 2005 to 2006. The intervention consisted of up to 5 sessions with an ARTAS linkage case manager over a 90-day period. The outcome measure was whether or not the participant had seen an HIV medical care provider at least once within 6 months of enrollment. Multivariate logistic regression was used to identify significant predictors of receiving HIV medical care. RESULTS: Seventy-nine percent (497 of 626) of participants visited an HIV clinician at least once within the first 6 months. Participants who were older than 25 years of age, Hispanic, and stably housed; had not recently used noninjection drugs; had attended 2 or more sessions with the case manager; and were recruited at a study site that had HIV medical care colocated on its premises were all significantly more likely to have received HIV care. CONCLUSIONS: The ARTAS linkage case management intervention provides a model that health departments and CBOs can use to ensure that recently diagnosed HIV-infected persons attend an initial HIV care encounter.     

Defensins and the convergent evolution of platypus and reptile venom genes

When the platypus (Ornithorhynchus anatinus) was first discovered, it was thought to be a taxidermist's hoax, as it has a blend of mammalian and reptilian features. It is a most remarkable mammal, not only because it lays eggs but also because it is venomous. Rather than delivering venom through a bite, as do snakes and shrews, male platypuses have venomous spurs on each hind leg. The platypus genome sequence provides a unique opportunity to unravel the evolutionary history of many of these interesting features. While searching the platypus genome for the sequences of antimicrobial defensin genes, we identified three Ornithorhynchus venom defensin-like peptide (OvDLP) genes, which produce the major components of platypus venom. We show that gene duplication and subsequent functional diversification of beta-defensins gave rise to these platypus OvDLPs. The OvDLP genes are located adjacent to the beta-defensins and share similar gene organization and peptide structures. Intriguingly, some species of snakes and lizards also produce venoms containing similar molecules called crotamines and crotamine-like peptides. This led us to trace the evolutionary origins of other components of platypus and reptile venom. Here we show that several venom components have evolved separately in the platypus and reptiles. Convergent evolution has repeatedly selected genes coding for proteins containing specific structural motifs as templates for venom molecules.     

Filariasis: diagnosis and treatment

Filariasis is an infectious disease of the lymphatics and subcutaneous tissues caused by nematodes or filariae. Carried by mosquito vectors, this disease causes millions of people to suffer from lymphedema and elephantiasis, characteristics of filariasis infection. This disease can be diagnosed through the identification of microfilariae in blood or skin samples, antigen detection, radiographic imaging, or polymerase chain reaction. Mass drug administration by the World Health Organization has helped to diminish the incidence of filariasis. However, continued research on new drugs and vaccinations will be needed to control and reduce the microfilarial levels in the human population.     

Dietary and stored iron as predictors of breast cancer risk: A nested case–control study in Shanghai

Increases in risk of breast cancer in successive generations of migrants to the United States from China and rapid temporal changes in incidence rates in China following social and economic changes clearly implicate environmental factors in the etiology of this disease. Case–control and cohort studies have provided evidence that at least some of these factors may be dietary. Iron, an essential element necessary for cell function, has also been demonstrated to have potential carcinogenic and co‐carcinogenic activities. Iron overload, which was previously uncommon, has become more common in the United States than iron deficiency and may be increasing in China concurrently with dramatic increases in meat consumption. A case–control study nested in a cohort of women in Shanghai, China, was conducted to evaluate possible associations between risk of proliferative and nonproliferative fibrocystic changes as well as breast cancer and dietary iron intake and plasma ferritin levels. Plasma ferritin levels and reported dietary iron intake were compared in 346 women with fibrocystic changes, 248 breast cancer cases and 1,040 controls. Increasing ferritin levels were significantly associated with increasing risk of nonproliferative fibrocystic changes (OR: 2.51, 95% CI: 1.16–5.45, p trend = 0.04). Similar, but weaker, trends were observed for proliferative changes and for breast cancer. Risk of breast cancer relative to the risk of fibrocystic changes was associated with dietary iron intake in women with nonproliferative fibrocystic changes (OR: 2.63, 95% CI: 1.04–6.68, p = 0.02). In conclusion, this study finds significant associations between iron (stored and dietary) and fibrocystic disease and breast cancer. © 2009 UICC     

Exposure to the Amino Acids Histidine,Lysine, and Threonine Reduces mTOR Activity and Affects Neurodevelopment in a Human Cerebral Organoid Model

Evidence of the impact of nutrition on human brain development is compelling. Previous in vitro and in vivo results show that three specific amino acids, histidine, lysine, and threonine, synergistically inhibit mTOR activity and behavior. Therefore, the prenatal availability of these amino acids could be important for human neurodevelopment. However, methods to study the underlying mechanisms in a human model of neurodevelopment are limited. Here, we pioneer the use of human cerebral organoids to investigate the impact of amino acid supplementation on neurodevelopment. In this study, cerebral organoids were exposed to 10 mM and 50 mM of the amino acids threonine, histidine, and lysine. The impact was determined by measuring mTOR activity using Western blots, general cerebral organoid size, and gene expression by RNA sequencing. Exposure to threonine, histidine, and lysine led to decreased mTOR activity and markedly reduced organoid size, supporting findings in rodent studies. RNA sequencing identified comprehensive changes in gene expression, with enrichment in genes related to specific biological processes (among which are mTOR signaling and immune function) and to specific cell types, including proliferative precursor cells, microglia, and astrocytes. Altogether, cerebral organoids are responsive to nutritional exposure by increasing specific amino acid concentrations and reflect findings from previous rodent studies. Threonine, histidine, and lysine exposure impacts the early development of human cerebral organoids, illustrated by the inhibition of mTOR activity, reduced size, and altered gene expression.     

Resource maximization during COVID-19 crunch – A novel graft marking technique to use one cornea for two recipients for either Descemet membrane endothelial keratoplasty or deep anterior lamellar keratoplasty

During pandemic, eye banks worldwide faced drastic reduction of corneal retrieval. Since precut tissues are uncommon in India, the onus is on corneal surgeons to maximize the donor corneal usage. The stumbling block making the stromal part unusable in the graft preparation of the Descemet membrane endothelial Keratoplasty is the stromal window creation to place the orientation mark on the stromal side of the folded graft. To overcome this, we simply marked directly on the folded Descemet graft, after partly stripping it from the donor cornea. Then, we unfolded, punched, and created two grafts after completely stripping it, retaining the Descemet part for the endothelial Keratoplasty and the stromal part for lamellar Keratoplasty. Initially, we used a special F marker, and later we marked an L using just a spatula. This simple technique needing no extra donor tissue or instrumentation maximizes the tissue utility with proper patient selection.     

Nipple‐sparing Mastectomy and Sub‐areolar Biopsy: To Freeze or not to Freeze? Evaluating the Role of Sub‐areolar Intraoperative Frozen Section

Use of nipple‐sparing mastectomy (NSM) for risk‐reduction and therapeutic breast cancer resection is growing. The role for intraoperative frozen section of the nipple‐areolar complex remains controversial. Records of patients undergoing NSM at our institution from 2006 to 2013 were reviewed. Records from 501 nipple‐sparing mastectomies were reviewed (216 therapeutic, 285 prophylactic). Of the 480 breasts with sub‐areolar biopsies, 307 had intraoperative frozen sections and 173 were evaluated with permanent paraffin section only. Among the 307 intraoperative frozen sections, 12 biopsies were positive on permanent paraffin section (3.9% or 12/307). Of the 12 positive permanent biopsies, five were false negative and the remaining seven concordant intraoperatively. Sensitivity and specificity of sub‐areolar frozen section were 0.58 and 1, respectively. Positive sub‐areolar biopsies consisted primarily of ductal carcinoma in situ (62% or 13/21). The nipples or nipple‐areolar complex were resected in a separate procedure following mastectomy (10/21), intraoperatively following frozen section results (7/21) or during second‐stage breast reconstruction (3/21; 1 additional scheduled). Only 30% (6/20) of resected specimens had abnormal residual pathology. Intraoperative frozen section is highly specific and moderately sensitive for the detection of positive sub‐areolar biopsies in NSM. Its use can help guide intraoperative reconstructive planning. The presence of positive sub‐areolar biopsies in both contralateral and high‐risk prophylactic mastectomy specimens emphasizes the need to perform sub‐areolar biopsies in all nipple‐sparing mastectomies.