Swietemicrolides A-D, mexicanolide-type limonoids from the bark of Swietenia macrophylla with in vitro cytotoxic and α-glucosidase inhibitory activities.

Four new mexicanolide-type limonoids, swietemicrolides A-D (1-4), together with three known compounds (5-7) were isolated from an ethyl acetate extract of the bark of Swietenia microphylla. 1 and 2 had 1,8-hemiacetal systems whilst 3 and 4 shared hexacyclic skeletons consisting of three fused five-membered rings. The structures of the isolated compounds were determined using spectroscopic methods. The five limonoids (1-5) were tested in vitro for their cytotoxic effects against two human cancer cell lines (KB carcinoma and A549 lung cancer cells) and α-glucosidase inhibitory activity. None of them showed significant cytotoxic activity, however, swietemicrolide C (3) exhibited strong effect towards α-glucosidase. Moreover, a possible biosynthetic pathway for compounds 1-4 was proposed to support a comprehensive understanding of the configurations of the new limonoids.

Assessing the therapeutic potential of Graptopetalum paraguayense on Alzheimer's disease using patient iPSC-derived neurons.

Alzheimer's disease (AD) is the most common type of dementia and also one of the leading causes of death worldwide. However, the underlying mechanisms remain unclear, and currently there is no drug treatment that can prevent or cure AD. Here, we have applied the advantages of using induced pluripotent stem cell (iPSC)-derived neurons (iNs) from AD patients, which are able to offer human-specific drug responsiveness, in order to evaluate therapeutic candidates for AD. Using approach involving an inducible neurogenin-2 transgene, we have established a robust and reproducible protocol for differentiating human iPSCs into glutamatergic neurons. The AD-iN cultures that result have mature phenotypic and physiological properties, together with AD-like biochemical features that include extracellular ß-amyloid (Aß) accumulation and Tau protein phosphorylation. By screening using a gene set enrichment analysis (GSEA) approach, Graptopetalum paraguayense (GP) has been identified as a potential therapeutic agent for AD from among a range of Chinese herbal medicines. We found that administration of a GP extract caused a significantly reduction in the AD-associated phenotypes of the iNs, including decreased levels of extracellular Aß40 and Aß42, as well as reduced Tau protein phosphorylation at positions Ser214 and Ser396. Additionally, the effect of GP was more prominent in AD-iNs compared to non-diseased controls. These findings provide valuable information that suggests moving extracts of GP toward drug development, either for treating AD or as a health supplement to prevent AD. Furthermore, our human iN-based platform promises to be a useful strategy when it is used for AD drug discovery.

Estimation of Surgery Capacity in Haiti: Nationwide Survey of Hospitals.

BACKGROUND: Haiti's surgical capacity was significantly strained by the 2010 earthquake. As the government and its partners rebuild the health system, emergency and essential surgical care must be a priority. METHODS: A validated, facility-based assessment tool developed by WHO was completed by 45 hospitals nationwide. The hospitals were assessed for (1) infrastructure, (2) human resources, (3) surgical interventions and emergency care, and (4) material resources for resuscitation. Fisher's exact test was used to compare hospitals by sectors: public compared to private and mixed (public-private partnerships). RESULTS: The 45 hospitals included first-referral level to the national referral hospital: 20 were public sector and 25 were private or mixed sector. Blood banks (33% availability) and oxygen concentrators (58%) were notable infrastructural deficits. For human resources, 69% and 33% of hospitals employed at least one full-time surgeon and anaesthesiologist, respectively. Ninety-eight percent of hospitals reported capacity to perform resuscitation. General and obstetrical surgical interventions were relatively more available, for example 93% provided hernia repairs and 98% provided cesarean sections. More specialized interventions were at a deficit: cataract surgery (27%), cleft repairs (31%), clubfoot (42%), and open treatment of fractures (51%). CONCLUSION: Deficiencies in infrastructure and material resources were widespread and should be urgently addressed. Physician providers were mal-distributed relative to non-physician providers. Formal task-sharing to midlevel and general physician providers should be considered. The parity between public and private or mixed sector hospitals in availability of Ob/Gyn surgical interventions is evidence of concerted efforts to reduce maternal mortality. This ought to provide a roadmap for strengthening of surgical care capacity.