A review of JAK and IL-23 inhibitors to treat vitiligo.

Vitiligo is an autoimmune skin disorder resulting in the depigmentation of skin characterised by patches of varying sizes and shapes. A common disorder of pigmentation that affects 0.5%-2% of the global population. Despite its well-understood autoimmune pathogenesis, the targets for effective cytokine intervention remain unclear. Current first-line treatments include oral or topical corticosteroids, calcineurin inhibitors and phototherapy. These treatments are limited, have varying efficacies, and are associated with significant adverse events or can be time-consuming. Therefore, biologics should be explored as a potential treatment for vitiligo. There are currently limited data for the use of JAK and IL-23 inhibitors for vitiligo. A total of 25 studies were identified in the review. There is promising evidence regarding the use of JAK and IL-23 inhibitors for the treatment of vitiligo.

On the interdependence of ketone body oxidation, glycogen content, glycolysis and energy metabolism in the heart.

In heart, glucose and glycolysis are important for anaplerosis and potentially therefore for d-ß-hydroxybutyrate (ßHB) oxidation. As a glucose store, glycogen may also furnish anaplerosis. We determined the effects of glycogen content on ßHB oxidation and glycolytic rates, and their downstream effects on energetics, in the isolated rat heart. High glycogen (HG) and low glycogen (LG) containing hearts were perfused with 11 mM [5-3 H]glucose and/or 4 mM [14 C]ßHB to measure glycolytic rates or ßHB oxidation, respectively, then freeze-clamped for glycogen and metabolomic analyses. Free cytosolic [NAD+ ]/[NADH] and mitochondrial [Q+ ]/[QH2 ] ratios were estimated using the lactate dehydrogenase and succinate dehydrogenase reaction, respectively. Phosphocreatine (PCr) and inorganic phosphate (Pi ) concentrations were measured using 31 P-nuclear magnetic resonance spectroscopy. Rates of ßHB oxidation in LG hearts were half that in HG hearts, with ßHB oxidation directly proportional to glycogen content. ßHB oxidation decreased glycolysis in all hearts. Glycogenolysis in glycogen-replete hearts perfused with ßHB alone was twice that of hearts perfused with ßHB and glucose, which had significantly higher levels of the glycolytic intermediates fructose 1,6-bisphosphate and 3-phosphoglycerate, and higher free cytosolic [NAD+ ]/[NADH]. ßHB oxidation increased the Krebs cycle intermediates citrate, 2-oxoglutarate and succinate, the total NADP/H pool, reduced mitochondrial [Q+ ]/[QH2 ], and increased the calculated free energy of ATP hydrolysis (∆GATP ). Although ßHB oxidation inhibited glycolysis, glycolytic intermediates were not depleted, and cytosolic free NAD remained oxidised. ßHB oxidation alone increased Krebs cycle intermediates, reduced mitochondrial Q and increased ∆GATP . We conclude that glycogen facilitates cardiac ßHB oxidation by anaplerosis. KEY POINTS: Ketone bodies (d-ß-hydroxybutyrate, acetoacetate) are increasingly recognised as important cardiac energetic substrates, in both healthy and diseased hearts. As 2-carbon equivalents they are cataplerotic, causing depletion of Krebs cycle intermediates; therefore their utilisation requires anaplerotic supplementation, and intra-myocardial glycogen has been suggested as a potential anaplerotic source during ketone oxidation. It is demonstrated here that cardiac glycogen does indeed provide anaplerotic substrate to facilitate ß-hydroxybutyrate oxidation in isolated perfused rat heart, and this contribution was quantified using a novel pulse-chase metabolic approach. Further, using metabolomics and 31 P-MR, it was shown that glycolytic flux from myocardial glycogen increased the heart's ability to oxidise ßHB, and ßHB oxidation increased the mitochondrial redox potential, ultimately increasing the free energy of ATP hydrolysis.

Admission and Care Practices in United States Well Newborn Nurseries.

OBJECTIVES: Late preterm and term infants comprise 97.3% of annual births in the United States. Admission criteria and the availability of medical interventions in well newborn nurseries are key determinants of these infants remaining within a mother-infant dyad or requiring a NICU admission and resultant separation of the dyad. The objective of this study was to identify national patterns for well newborn nursery care practices. METHODS: We surveyed a physician representative from each nursery in the Better Outcomes through Research for Newborns Network. We described the admission criteria and clinical management of common newborn morbidities and analyzed associations with nursery demographics. RESULTS: Of 96 eligible nursery representatives, 69 (72%) completed surveys. Among respondents, 59 (86%) used a minimal birth weight criterion for admission to their well newborn nursery. The most commonly used criteria were 2000 g (n = 29, 49%) and 1800 g (n = 19, 32%), with a range between 1750 and 2500 g. All nurseries used a minimal gestational age criterion for admission; the most commonly used criterion was 35 weeks (n = 55, 80%). Eleven percent of sites required transfer to the NICU for phototherapy. Common interventions in the mother's room included dextrose gel (n = 56, 81%), intravenous antibiotics (n = 35, 51%), opiates for neonatal abstinence syndrome (n = 15, 22%), and an incubator for thermoregulation (n = 14, 20%). CONCLUSIONS: Wide variation in admission criteria and medical interventions exists in well newborn nurseries. Further studies may help identify evidence-based optimal admission criteria to maximize care within the mother-infant dyad.

Towards practical and robust DNA-based data archiving using the yin-yang codec system.

DNA is a promising data storage medium due to its remarkable durability and space-efficient storage. Early bit-to-base transcoding schemes have primarily pursued information density, at the expense of introducing biocompatibility challenges or decoding failure. Here we propose a robust transcoding algorithm named the yin-yang codec, using two rules to encode two binary bits into one nucleotide, to generate DNA sequences that are highly compatible with synthesis and sequencing technologies. We encoded two representative file formats and stored them in vitro as 200 nt oligo pools and in vivo as a ~54 kbps DNA fragment in yeast cells. Sequencing results show that the yin-yang codec exhibits high robustness and reliability for a wide variety of data types, with an average recovery rate of 99.9% above 104 molecule copies and an achieved recovery rate of 87.53% at ≤102 copies. Additionally, the in vivo storage demonstration achieved an experimentally measured physical density close to the theoretical maximum.

Low-Interventional Approaches to Intrapartum Care: Hospital Variation in Practice and Associated Factors.

INTRODUCTION: Despite evidence supporting the safety of low-interventional approaches to intrapartum care, defined by the American College of Obstetricians and Gynecologists as "practices that facilitate a physiologic labor process and minimize intervention," little is known about how frequently such practices are utilized. We examined hospital use of low-interventional practices, as well as variation in utilization across hospitals. METHODS: Data came from 185 California hospitals completing a survey of intrapartum care, including 9 questions indicating use of low- versus high-interventional practices (eg, use of intermittent auscultation, nonpharmacologic pain relief, and admission of women in latent labor). We performed a group-based latent class analysis to identify distinct groups of hospitals exhibiting different levels of utilization on these 9 measures. Multivariable logistic regression identified institutional characteristics associated with a hospital's likelihood of using low-interventional practices. Procedure rates and patient outcomes were compared between the hospital groups using bivariate analysis. RESULTS: We identified 2 distinct groups of hospitals that tended to use low-interventional (n = 44, 23.8%) and high-interventional (n = 141, 76.2%) practices, respectively. Hospitals more likely to use low-interventional practices included those with midwife-led or physician-midwife collaborative labor management (adjusted odds ratio [aOR], 7.52; 95% CI, 2.53-22.37; P < .001) and those in rural locations (aOR, 3.73; 95% CI, 1.03-13.60; P = .04). Hospitals with a higher proportion of women covered by Medicaid or other safety-net programs were less likely to use low-interventional practices (aOR, 0.96; 95% CI, 0.93-0.99; P = .004), as were hospitals in counties with higher medical liability insurance premiums (aOR, 0.53; 95% CI, 0.33-0.85; P = .008). Hospitals in the low-intervention group had comparable rates of severe maternal and newborn morbidities but lower rates of cesarean birth and episiotomy compared with hospitals in the high-intervention group. DISCUSSION: Only one-quarter of hospitals used low-interventional practices. Attention to hospital culture of care, incorporating the midwifery model of care, and addressing medical-legal concerns may help promote utilization of low-interventional intrapartum practices.

A prospective clinical study of Primo-Lacto: A closed system for colostrum collection.

BACKGROUND: Colostrum is the first nutritional liquid that comes out of the breast during lactation. Colostrum collection can be challenging due to the small volume produced, and because breast pumps are not designed for colostrum collection. Besides pumping colostrum, the generally accepted practice is to use any available container to hand-express colostrum. Transfer between containers may lead to contamination, higher chance of infection and loss of colostrum. Our aim was to understand if a dedicated colostrum collection system (Primo-Lacto, Maternal Life, LLC, Palo Alto, CA) is more effective than standard hospital practice. METHODS: Mothers who delivered preterm infants < 34 weeks gestation and mothers with non-latching infants were approached within 24 hours of delivery. Surveys were distributed to participating patients (n = 67), and nurses or lactation consultants (n = 89). Mothers compared ease of use, their confidence level and satisfaction with the amount collected during standard practice vs. the colostrum collection system. Nurses or lactation consultants compared ease of use, differences in colostrum loss and time invested collecting. Quantitative data were analyzed using the Wilcoxon signed rank test and qualitative data were analyzed with grounded theory methods. RESULTS: For mothers, ease of use and confidence were significantly better when they used the colostrum collection system than when they used the standard collection procedure, and this difference was true for both hand and pump expression (p<0.01). Nurses and lactation consultants perceived that ease of use was better, and percent of colostrum lost was significantly less with the colostrum collection system for both hand and pump expression. The collection times were not significantly different between the colostrum collection system and standard practice. CONCLUSION: The colostrum collection system is a tool to help facilitate successful colostrum collection and improve the experience both for clinicians and patients.

Transcutaneous bilirubinometer use and practices surrounding jaundice in 150 California newborn intensive care units.

OBJECTIVES: Transcutaneous bilirubin measurements (TcBs) provide a noninvasive method for screening infants for hyperbilirubinemia and have been used extensively in term and late preterm newborns in well baby nurseries, offices, and outpatient clinics. Several studies have also demonstrated the utility of TcBs as a screening tool for infants > 28 weeks' gestation and their ability to reduce the need for blood sampling. The objectives of this study are to identify how often TcBs are used among California Newborn Intensive Care Units (NICUs) in preterm, late preterm and term infants, and other aspects of jaundice management. METHODS: We conducted a survey on TcB use and practices relating to jaundice management in 150 California NICUs between April and October 2016. RESULTS: TcB screening is routinely used in 28% (42/150) of NICUs. Only 7% (11/150) of NICUs use TcB in preterm infants < 28 weeks. Practice varied similarly across NICU levels of care. Among the subset of NICUs that responded to questions related to phototherapy and screening practices, prophylactic phototherapy was used in 38% (23/59) and 90% (55/61) screened for glucose-6-phosphate dehydrogenase deficiency based on race, ethnicity, and/or family history. CONCLUSION(S): Despite studies validating the accuracy of TcB in preterm infants > 28 weeks, only 28% of California NICUs routinely use TcB devices. TcB screening in infants < 28 weeks gestation is not widely used and no recommendation can be made in this regard until there is more experience with its application using a standardized protocol in these infants and on a large scale.

Antibiotic treatment expands the resistance reservoir and ecological network of the phage metagenome.

The mammalian gut ecosystem has considerable influence on host physiology, but the mechanisms that sustain this complex environment in the face of different stresses remain obscure. Perturbations to the gut ecosystem, such as through antibiotic treatment or diet, are at present interpreted at the level of bacterial phylogeny. Less is known about the contributions of the abundant population of phages to this ecological network. Here we explore the phageome as a potential genetic reservoir for bacterial adaptation by sequencing murine faecal phage populations following antibiotic perturbation. We show that antibiotic treatment leads to the enrichment of phage-encoded genes that confer resistance via disparate mechanisms to the administered drug, as well as genes that confer resistance to antibiotics unrelated to the administered drug, and we demonstrate experimentally that phages from treated mice provide aerobically cultured naive microbiota with increased resistance. Systems-wide analyses uncovered post-treatment phage-encoded processes related to host colonization and growth adaptation, indicating that the phageome becomes broadly enriched for functionally beneficial genes under stress-related conditions. We also show that antibiotic treatment expands the interactions between phage and bacterial species, leading to a more highly connected phage-bacterial network for gene exchange. Our work implicates the phageome in the emergence of multidrug resistance, and indicates that the adaptive capacity of the phageome may represent a community-based mechanism for protecting the gut microflora, preserving its functional robustness during antibiotic stress.

The beneficial effect of ST-36 (Zusanli) acupressure on postoperative gastrointestinal function in patients with colorectal cancer.

PURPOSE/OBJECTIVES: To evaluate the effectiveness of ST-36 (Zusanli) acupressure on recovery of postoperative gastrointestinal function in patients with colorectal cancer. DESIGN: A longitudinal, randomized, controlled trial design. SETTING: An urban medical center in Taiwan. SAMPLE: 60 patients with colorectal cancer who had undergone abdominal surgery. METHODS: Patients were randomly assigned to two groups, the ST-36 acupressure group (n = 30) and a sham acupressure group (n = 30). Patients in the ST-36 group received an acupressure procedure in a three-minute cycle performed three times per day during the five days after surgery. Patients in the control group received routine postoperative care and sham acupressure. Generalized estimating equations (GEEs) were used to gauge longitudinal effects of the two groups of patients. MAIN RESEARCH VARIABLES: Frequency of bowel sounds, the time to first flatus passage, first liquid intake, solid intake, and defecation. FINDINGS: Patients who received acupressure had significantly earlier flatus passage and time to liquid intake as compared to patients in the control group. Other main variables, including the first time to solid intake and defecation, did not show significant difference between the two groups. The GEE method revealed that all patients had increasing bowel sounds over time, and the experimental group had greater improvement of bowel motility than the control group within the period of 2-3 days postoperatively. CONCLUSIONS: ST-36 acupressure was able to shorten the time to first flatus passage, oral liquid intake, and improve gastrointestinal function in patients after abdominal surgery. IMPLICATIONS FOR NURSING: ST-36 acupressure can be integrated into postoperative adjunct nursing care to assist patients' postoperative gastrointestinal function. KNOWLEDGE TRANSLATION: Few studies have explored the effectiveness of acupressure techniques on promoting bowel sounds. Evidence from this study suggests stimulation of the ST-36 acupressure point can increase bowel sound frequency for patients with colorectal cancer in the first three days after surgery. Application of this technique may improve a patient's comfort after surgery.

Losing sight of the wood for the trees: some issues in describing and valuing health, and another possible approach.

BACKGROUND AND OBJECTIVE: The ability to value health in a way that allows the comparison of different conditions across a range of population groups is central to determining priorities in healthcare. This paper considers some of the concerns with the 'received wisdom' in valuing health--to describe it using a generic descriptive system and to value it using the hypothetical preferences of the general public. METHODS: The literature on the dimensions of health that matter most to people was reviewed and this paper discusses the use of global measures of subjective well-being (SWB) as a possible alternative. New analysis of the British Household Panel Survey was conducted to explore the relationship between life satisfaction and the preference-based quality-of-life measure the SF-6D. The impact on life satisfaction of each level for each dimension of the SF-6D is estimated through a linear model predicting life satisfaction with the SF-6D levels as determinants. RESULTS: Valuing changes in the health of the general population via changes in life satisfaction would lead to different weights being attached to the different dimensions of health, as compared to a well used utility score in which weights are taken from general population preferences. If preferences elicited via standard gamble exercises are based only on a prediction of what it would be like to live in a particular health state, then these results suggest that reductions in physical functioning matter less than people imagine and reductions in mental health impact upon our lives more than preferences would suggest. CONCLUSIONS: Using data from the British Household Panel Survey, it is shown that a focus on SWB would place greater emphasis on mental health conditions. The implications for health policy are considered.

Seizing the moment: California's opportunity to prevent nutrition-related health disparities in low-income Asian American population.

Asian Americans and Pacific Islanders (AAPI) have the fastest growing rate of overweight and obese children. Aggressive programs are urgently needed to prevent unhealthy acculturation-related changes in diet and physical activity and to promote the healthier aspects of traditional lifestyle habits. We conducted focus groups and key informant interviews to explore knowledge, attitudes, dietary practices, and physical activity levels among three low-income Asian American ethnic groups, Chinese, Vietnamese, and Hmong, in California. Content analysis was used to identify similarities and differences among the groups. Several common health beliefs clearly emerged. Participants noted the importance of fresh (not frozen) fruit and vegetable consumption and physical activity for general health. The concept of good health included having a harmonious family, balance, and mental and emotional stability. All groups also expressed the general belief that specific foods have hot or cold properties and are part of the Yin/Yang belief system common to Asian cultures. The lure of fast food, children's adoption of American eating habits, and long work hours were identified as barriers to a healthy, more traditional lifestyle. A California campaign for Asian Americans using multilevel strategies is recommended to counter the alarming rise of obesity among AAPI youth. Strategies directed to individual, community, and policy levels should emphasize maintenance of healthy traditional diets, informed selection of mainstream U.S. foods, and promotion of active lifestyles to prevent an impending burden from cancer and nutrition-related chronic diseases in AAPI populations.

Muscle induces neuronal expression of acetylcholinesterase in neuron-muscle co-culture: transcriptional regulation mediated by cAMP-dependent signaling.

Presynaptic motor neuron synthesizes and secretes acetylcholinesterase (AChE) at vertebrate neuromuscular junctions. In order to determine the retrograde role of muscle in regulating the expression of AChE in motor neuron, a chimeric co-culture of NG108-15 cell, a cholinergic cell line that resembles motor neuron, with chick myotube was established to mimic the neuromuscular contact in vitro. A DNA construct of human AChE promoter tagged with luciferase (pAChE-Luc) was stably transfected into NG108-15 cells. The co-culture with myotubes robustly stimulated the promoter activity as well as the endogenous expression of AChE in pAChE-Luc stably transfected NG108-15 cells. Muscle extract derived from chick embryos when applied onto pAChE-Luc-expressing NG108-15 cells induced expressions of AChE promoter and endogenous AChE. The cAMP-responsive element mutation on human AChE promoter blocked the muscle-induced AChE transcriptional activity in cultured NG108-15 cells either in co-culturing with myotube or in applying muscle extract. The accumulation of intracellular cAMP and the phosphorylation of cAMP-responsive element-binding protein in cultured NG108-15 cells were stimulated by applied muscle extract. Part of the muscle-induced signaling was mimicked by application of calcitonin gene-related peptide in cultured NG108-15 cells. These results suggest the muscle-induced neuronal AChE expression in the co-culture is mediated by a cAMP-dependent signaling.

New steroidal antiinflammatory antedrugs: Methyl 3,20-dioxo-9 alpha-fluoro-11 beta,17 alpha,21-trihydroxy-1,4-pregnadiene-16 alpha-carboxylate and its 21-O-acyl derivatives.

In a continuing effort to increase local to systemic activity ratios of potent steroidal antiinflammatory antedrugs, a series of 21-O-acyl derivatives of methyl 3,20-dioxo-9 alpha-fluoro-11 beta,17 alpha,21-trihydroxy-1,4-pregnadiene-16 alpha-carboxylate, FP16CM, were synthesized. These derivatives were evaluated for antiinflammatory activity and their adverse effects in an acute and semi-chronic croton oil-induced ear edema bioassay. Following a single topical application in the croton oil-induced ear edema bioassay, treatment with all the compounds resulted in dose-dependent inhibition of edema. From these dose-response profiles, the following ID(50) values (nmol/ear resulting in a 50% reduction of edema) were calculated: prednisolone (Pred); 454, FP16CM; 255, 21-acetate (FP16CM-acetyl); 402, 21-propionate (FP16CM-propionyl); 474, 21-valerate (FP16CM-valeryl); 446 and 21-pivalate (FP16CM-pivalyl); 219 nmol. In a 5-day semi-chronic study at the equipotent doses, the novel steroidal antedrugs did not significantly alter body weight gain, thymus weights or plasma corticosterone levels unlike the parent compound Pred. The compounds were assessed for high-affinity glucocorticoid receptor binding and glucocorticoid-mediated inhibition of nitric oxide (NO) generation in an in vitro RAW 264.7 macrophage cell culture system. Binding affinities for cytosolic glucocorticoid receptors were Pred; 85, FP16CM-acetyl; 86, FP16CM-propionyl; 169, FP16CM-valeryl; 149, FP16CM-pivalyl; 126 nM, respectively. Concomitant potencies for inhibition of NO generation by macrophages stimulated with lipopolysaccharide were Pred; 159, FP16CM-acetyl; 377, FP16CM-propionyl; 405, FP16CM-valeryl; 344, FP16CM-pivalyl; 311 nM, respectively. Collectively, results of these investigations suggest that esterification of 21-OH with various anhydrides did not improve receptor binding, inhibition of NO generation and ear edema inhibition, however, serum corticosterone level and local over systemic activities (L/S) were markedly improved.