Saroclazines A–C,thio-diketopiperazines from mangrove-derived fungi <Emphasis Type="Italic">Sarocladium kiliense</Emphasis> HDN11-84

Three new diketopiperazine derivatives (DKPs), saroclazines A–C (1–3) along with three known DKPs (4–6) were isolated from mangrove-derived fungi Sarocladium kiliense HDN11-84. Saroclazines A–B (1 and 2) possessed a free amide structure, which was first found in sulfur-containing aromatic DKPs. Their structures were elucidated by NMR, HRESIMS and X-ray. The cytotoxic activity of new compounds (1–3) was tested against HeLa cell lines, among which compound 2 showed an IC₅₀ value of 4.2 µM.     

Association between sperm mitochondrial ND2 gene variants and total fertilization failure

The objective of this study was to explore the association of sperm mitochondrial ND2 (MT-ND2) gene variants with total fertilization failure (TFF). A retrospective comparative study of 246 cases of fresh in vitro fertilization (IVF) cycles or half-intracytoplasmic sperm injection cycles in the Han Chinese population was performed from July 2011 to May 2017. A total of 59 cases undergoing TFF, and 187 control cases with normal fertilization (fertilization rates >50%) were included. The sperm mitochondrial genovariation was determined using nested sequencing. A total of 32 homoplasmic variants and 47 heteroplasmic variants of MT-ND2 gene were observed in this study. There were no significant differences in the frequencies of the 32 homoplasmic variants of MT-ND2 gene between the TFF and control groups. A total of 53 pair-wise comparisons were performed, and the general characteristics of the IVF failure and control subjects were adjusted in logistic models. Data suggested that there were no significant differences in the frequencies of point 4914, 5320, and 5426 heteroplasmic variants of MT-ND2 gene between the TFF and control groups. In addition, no significant difference was observed in the frequency of mtDNA haplogroup D or haplogroup G between the IVF failure group and the normal fertilization group. This study suggests that the MT-ND2 gene variants might not be associated with TFF.

Abbreviations: ATP: adenosine triphosphate; dNTP: deoxy-ribonucleoside triphosphate; FADH2: flavin adenine dinucleotide; FDR: false discovery rate; FSH: follicle-stimulating hormone; IVF: in vitro fertilization; LH: luteinizing hormone; MTATP6: mitochondrially encoded ATP synthase 6; MTCYB: mitochondrially encoded cytochrome b; mtDNA: mitochondrial DNA; MT-ND2: mitochondrial ND2; NADH: nicotinamide adenine dinucleotide; ND2: NADH dehydrogenase subunit 2; OXPHOS: oxidative phosphorylation; PCR: single nucleotide polymorphisms; SNPs: single nucleotide polymorphisms; TFF: total fertilization failure     

Clinical and other specialty services offered by pharmacists in the community: the international arena and Israel

The community pharmacy setting is a venue that is readily accessible to the public. In addition, it is staffed by a pharmacist, who is a healthcare provider, trained and capable of delivering comprehensive pharmaceutical care. As such, community pharmacists have a colossal opportunity to serve as key contributors to patients’ health by ensuring appropriate use of medications, preventing medication misadventures, identifying drug-therapy needs, as well as by being involved in disease management, screening, and prevention programs. This unique position gives the pharmacist the privilege and duty to serve patients in roles other than solely that of the stereotypical drug dispenser.Worldwide, as well as in Israel, pharmacists already offer a variety of pharmaceutical services and tend to patients’ and the healthcare system’s needs. This article provides examples of professional, clinical or other specialty services offered by community pharmacists around the world and in Israel and describes these interventions as well as the evidence for their efficacy. Examples of such activities which were recently introduced to the Israeli pharmacy landscape due to legislative changes which expanded the pharmacist’s scope of practice include emergency supply of medications, pharmacists prescribing, and influenza vaccination. Despite the progress already made, further expansion of these opportunities is warranted but challenging. Independent prescribing, as practiced in the United Kingdom or collaborative drug therapy management programs, as practiced in the United States, expansion of vaccination programs, or wide-spread recognition and reimbursement for medication therapy management (MTM) programs are unrealized opportunities. Obstacles such as time constraints, lack of financial incentives, inadequate facilities and technology, and lack of professional buy-in, and suggested means for overcoming these challenges are also discussed.     

Improving research and policy interactions requires a better understanding of what works in different contexts

There is keen interest in many jurisdictions in finding ways to improve the way that research evidence informs policy. One possible mechanism for this is to embed academics within government agencies either as advisers or full staff members. Our commentary argues that, in addition to considering the role of academics in government as proposed by Glied and colleagues, we need to understand better how research and policy interactions function across policy sectors. We believe more comparative research is needed to understand if and why academics from certain disciplines are more likely to be recruited to work in some policy sectors rather than others. We caution against treating government as monolithic by advocating the same model for collaborative interaction between academics and government. Lastly, we contend that contextualized research is needed to illuminate important drivers of research and policy interactions before we can recommend what is likely to be more and less effective in different policy sectors.     

A neo-institutional analysis of the hidden interaction between the Israeli Supreme Court and the Ministry of Finance: the right to healthcare services

Background

Under structural conditions of non-governability, most players in the policy arena in Israel turn to two main channels that have proven effective in promoting the policies they seek: the submission of petitions to the High Court of Justice and making legislative amendments through the Economic Arrangements Law initiated by the Ministry of Finance. Nevertheless, an analysis of the principal trends emerging from the High Court of Justice rulings and legislative amendments through the Economic Arrangements Law indicates that these channels are open to influence, primarily by forces that are essentially neo-liberal. Little is known about the effects of these trends on the right to healthcare services, which in Israel has not been legislated as an independent constitutional law in Basic Laws.

Methods

We use four major legal cases decided by the Supreme Court of Israel in the past 10 years where the Court reviewed new legislative initiatives proposed by the Economic Arrangements Law in the area of healthcare. We utilize an institutional approach in our analysis.

Results

A neo-institutional analysis of the legal cases demonstrates that petitions against the Economic Arrangements Law in the area of healthcare services have been denied, even though the Court uses strong rhetoric against that law and the government more generally in addressing issues that concern access to healthcare services and reforms in the healthcare system. This move strengthens the trend toward a neo-liberal public policy and significantly weakens the legal protection of the right to healthcare services.

Conclusion

In deciding petitions against the Economic Arrangements Law in the area of healthcare, the Supreme Court allows the Ministry of Finance to be a dominant player in the formation of public policy. In doing so, it may be promoting a goal of strengthening its position as a political institution that aspires to increase the public’s trust in the judiciary and especially in the Supreme Court itself, in addition to exercising judicial restraint and allowing more leeway to the executive and legislative branches more generally.

     

Evaluation of Transdermal Drug Permeation as Modulated by Lipoderm and Pluronic Lecithin Organogel

The transdermal delivery of 2 fluorescent probes with similar molecular weight but different lipophilicity, into and through the skin from 2 commercially available transdermal bases, pluronic lecithin organogel, and Lipoderm^® has been evaluated. First, in vitro penetration of fluorescein sodium and fluorescein (free acid) through porcine skin was evaluated. Retention and depth distribution profiles in skin were obtained by tape stripping and then followed by optical sectioning using multiphoton microscopy. The results showed that Lipoderm^® led to an enhanced penetration of the hydrophilic compound, fluorescein sodium. For the lipophilic compound fluorescein (free acid), Lipoderm^® performed similar to pluronic lecithin organogel base, where minimal drug was detected in either receptor phase. The skin retention and depth distribution results also showed that the hydrophilic fluorescein sodium had high skin retention with Lipoderm^®, whereas fluorescein (free acid) had very low penetration and retention with increasing skin depth. Moreover, optical sectioning by multiphoton microscopy revealed an uneven distribution of probes across the skin in the x-y plane for both transdermal bases. This work showed that a hydrophilic compound has significantly increased skin penetration and retention when formulated with Lipoderm^®, and the skin retention of the probe was the main determinant of its skin flux.     

Effect of correcting for gestational age at birth on population prevalence of early childhood undernutrition

Background

Postmenstrual and/or gestational age-corrected age (CA) is required to apply child growth standards to children born preterm (< 37 weeks gestational age). Yet, CA is rarely used in epidemiologic studies in low- and middle-income countries (LMICs), which may bias population estimates of childhood undernutrition. To evaluate the effect of accounting for GA in the application of growth standards, we used GA-specific standards at birth (INTERGROWTH-21st newborn size standards) in conjunction with CA for preterm-born children in the application of World Health Organization Child Growth Standards postnatally (referred to as ‘CA’ strategy) versus postnatal age for all children, to estimate mean length-for-age (LAZ) and weight-for-age (WAZ) z scores at 0, 3, 12, 24, and 48-months of age in the 2004 Pelotas (Brazil) Birth Cohort.

Results

At birth (n = 4066), mean LAZ was higher and the prevalence of stunting (LAZ < ?2) was lower using CA versus postnatal age (mean ± SD): ? 0.36 ± 1.19 versus ? 0.67 ± 1.32; and 8.3 versus 11.6%, respectively. Odds ratio (OR) and population attributable risk (PAR) of stunting due to preterm birth were attenuated and changed inferences using CA versus postnatal age at birth [OR, 95% confidence interval (CI): 1.32 (95% CI 0.95, 1.82) vs 14.7 (95% CI 11.7, 18.4); PAR 3.1 vs 42.9%]; differences in inferences persisted at 3-months. At 12, 24, and 48-months, preterm birth was associated with stunting, but ORs/PARs remained attenuated using CA compared to postnatal age. Findings were similar for weight-for-age z scores.

Conclusions

Population-based epidemiologic studies in LMICs in which GA is unused or unavailable may overestimate the prevalence of early childhood undernutrition and inflate the fraction of undernutrition attributable to preterm birth.

     

Evaluation and learning in complex,rapidly changing health systems: China’s management of health sector reform

Healthcare systems are increasingly recognised as complex, in which a range of non-linear and emergent behaviours occur. China’s healthcare system is no exception. The hugeness of China, and the variation in conditions in different jurisdictions present very substantial challenges to reformers, and militate against adopting one-size-fits-all policy solutions. As a consequence, approaches to change management in China have frequently emphasised the importance of sub-national experimentation, innovation, and learning. Multiple mechanisms exist within the government structure to allow and encourage flexible implementation of policies, and tailoring of reforms to context. These limit the risk of large-scale policy failures and play a role in exploring new reform directions and potentially systemically-useful practices. They have helped in managing the huge transition that China has undergone from the 1970s onwards. China has historically made use of a number of mechanisms to encourage learning from innovative and emergent policy practices. Policy evaluation is increasingly becoming a tool used to probe emergent practices and inform iterative policy making/refining. This paper examines the case of a central policy research institute whose mandate includes evaluating reforms and providing feedback to the health ministry. Evaluation approaches being used are evolving as Chinese research agencies become increasingly professionalised, and in response to the increasing complexity of reforms. The paper argues that learning from widespread innovation and experimentation is challenging, but necessary for stewardship of large, and rapidly-changing systems.