Assessing and documenting dark skin tones in stoma care.

The stoma care nurse (SCN) assesses peristomal skin during each patient intervention. Living in a diverse multicultural society, the SCN needs to consider dark skin tones and how these are documented. This article looks at how the literature on peristomal skin assessment and available tools discuss skin colour, and compare this with the tissue viability literature. Stoma care and peristomal skin literature features very little about skin colour. Registered nurses are often unaware of the differences when assessing light skin tones versus dark skin tones. The article discusses how to assess for, identify and document problems around peristomal skin with patients who have dark skin tones. The differences in skin breakdown between light skin tones and dark skin tones are highlighted. There needs to be further research and development of tools to assist clinicians in identification and documentation relating to skin tone, thus providing consistency in assessment.

An anatomical appraisal of dynamic muscle transfer of the orbicularis oculi muscle.

Facial nerve palsy can cause significant distress for patients. We investigated the innervation of the orbicularis oculi muscle (OOM) and assessed the viability of unipedicle contralateral muscle transfer to restore symmetrical and spontaneous blinking. Cadaveric dissection and measurements were performed on lite fixed cadavers (n = 15). Medial innervation of the OOM was identified prior to raising and transposing a flap to the contralateral eyelid. Measurements were performed in-situ and following transposition. A medial ascending branch of the buccal nerve innervating the OOM was identified bilaterally in all cadavers. The average length of flap raised was 59.85 mm (± 4.69 mm) with no difference between the left and right. Flaps with pedicles not dissected off the bone covered 48% of the ciliary margin length (CM) and 62% of the palpebral length (PL). Flaps dissected off the bone covered 72% of the CM and 92% of the PL. The results demonstrate that a flap can theoretically transpose to >50% of the contralateral eyelid length. Increased coverage of the eyelid was achieved by releasing the pedicle from the underlying bone. Little attention was focused on buccal innervation of the eyelids, and this consistent medial pattern may allow an innervated flap transfer to restore symmetrical blinking, something that eludes modern paralysis surgery in a single-stage procedure.

The Development of a Daily Comprehensive and Multidisciplinary Health Care Leadership Huddle.

INTRODUCTION: Consistent and concise communication in a large health care organization that is geographically dispersed is a challenge. Issues often are not addressed with the appropriate individuals in the most timely and effective manner, which results in patient flow disruptions, service gaps, and provider and administrator frustration. CASE PRESENTATION: This report describes the development of a daily leadership huddle with regional leadership and middle management to inform of daily operations, safety, quality, and service concerns, in order to allow for quicker action and issue resolution. DISCUSSION: Huddles have proven effective in organizations of similar size, but few organizations have attempted a multisite daily huddle. CONCLUSION: To ensure their success, key steps must be taken during the formation of daily leadership huddles, including buy-in from leaders and stakeholders at multiple levels. In our organization, the huddles have proven to be a forum for effective communication, quicker issue resolution, and an increased sense of camaraderie.

Selecting convexity to improve and maintain peristomal skin integrity.

Each person with a stoma is an individual who may react differently when faced with similar situations and, as such, each patient needs to be considered on a person-by-person basis to address their needs, support their acceptance of living with a stoma, as well as to encourage their rehabilitation. This article discusses the benefits that a convex flange can offer ostomates to reduce and minimise leakage episodes and in doing so support peristomal skin integrity and, in particular, the benefits of a convex pouch with a hydrocolloid flange containing medical grade Manuka honey. It reports on the findings of an independent nurse study, which included discussions about the varying types of convexity offered to ostomates, following an assessment of patients' needs.

Treating the locoregional lymph nodes with radiation and/or surgery significantly improves outcome in dogs with high-grade mast cell tumours.

High-grade canine mast cell tumours (HG-MCT) have a high rate of locoregional relapse. In this study, dogs with HG-MCT treated with radiation therapy (RT) were retrospectively evaluated to determine the benefit associated with treating the locoregional lymph nodes (LNs). Forty-two dogs were included. Variables assessed for association with overall survival (OS) and progression-free survival (PFS) included WHO stage, tumour location and size, LN irradiation (prophylactic, therapeutic or none), LN treatment (yes or no), LN status at RT (metastatic or nonmetastatic) and RT intent (definitive vs palliative). Lower-stage disease at irradiation was significantly associated with prolonged median PFS (425 vs 125 days for stage 0 vs 1-4), and OS (615 vs 314 days for stage 0 vs 1-4). Having any LN treatment and definitive RT were both significantly associated with prolonged OS. In order to evaluate the role of LN irradiation, dogs were divided into subgroups: (a) stage 0 at irradiation with no LN treatment (n = 14), (b) stage 0 at irradiation with prophylactic LN irradiation (n = 6), (c) stage 0 at irradiation but previously stage 2 (n = 5) and (d) stage >0 at irradiation (n = 17). Prophylactic LN irradiation significantly prolonged PFS (>2381 vs 197 days; group B vs A). Interestingly, dogs that were stage 2 and had LN treatment (C) had prolonged OS vs dogs with negative LNs and no LN treatment (A) (1908 vs 284 days; P = .012). This study confirms that prophylactic and therapeutic LN irradiation in dogs with HG-MCT is beneficial and improves outcome.

Clinical governance for ostomates at risk of peristomal skin complications.

This clinical study focuses on peristomal skin complications (PSCs). For many patients, the causative factor behind peristomal moisture-associated skin damage was contact dermatitis caused by effluent leakage, resulting in sore and excoriated skin. PSCs are costly to the patient in relation to pain, time and worry and also impact nursing activity levels and healthcare costs. The study identifies the number of patients presenting with PSC, the causative factors and their resolution using medical grade Manuka honey flanges.

Discovery of short-course antiwolbachial quinazolines for elimination of filarial worm infections.

Parasitic filarial nematodes cause debilitating infections in people in resource-limited countries. A clinically validated approach to eliminating worms uses a 4- to 6-week course of doxycycline that targets Wolbachia, a bacterial endosymbiont required for worm viability and reproduction. However, the prolonged length of therapy and contraindication in children and pregnant women have slowed adoption of this treatment. Here, we describe discovery and optimization of quinazolines CBR417 and CBR490 that, with a single dose, achieve >99% elimination of Wolbachia in the in vivo Litomosoides sigmodontis filarial infection model. The efficacious quinazoline series was identified by pairing a primary cell-based high-content imaging screen with an orthogonal ex vivo validation assay to rapidly quantify Wolbachia elimination in Brugia pahangi filarial ovaries. We screened 300,368 small molecules in the primary assay and identified 288 potent and selective hits. Of 134 primary hits tested, only 23.9% were active in the worm-based validation assay, 8 of which contained a quinazoline heterocycle core. Medicinal chemistry optimization generated quinazolines with excellent pharmacokinetic profiles in mice. Potent antiwolbachial activity was confirmed in L. sigmodontis, Brugia malayi, and Onchocerca ochengi in vivo preclinical models of filarial disease and in vitro selectivity against Loa loa (a safety concern in endemic areas). The favorable efficacy and in vitro safety profiles of CBR490 and CBR417 further support these as clinical candidates for treatment of filarial infections.

Wolbachia and host germline components compete for kinesin-mediated transport to the posterior pole of the Drosophila oocyte.

Widespread success of the intracellular bacterium Wolbachia across insects and nematodes is due to efficient vertical transmission and reproductive manipulations. Many strains, including wMel from Drosophila melanogaster, exhibit a specific concentration to the germplasm at the posterior pole of the mature oocyte, thereby ensuring high fidelity of parent-offspring transmission. Transport of Wolbachia to the pole relies on microtubules and the plus-end directed motor kinesin heavy chain (KHC). However, the mechanisms mediating Wolbachia's association with KHC remain unknown. Here we show that reduced levels of the host canonical linker protein KLC results in dramatically increased levels of Wolbachia at the oocyte's posterior, suggesting that KLC and some key associated host cargos outcompete Wolbachia for association with a limited amount of KHC motor proteins. Consistent with this interpretation, over-expression of KHC causes similarly increased levels of posteriorly localized Wolbachia. However, excess KHC has no effect on levels of Vasa, a germplasm component that also requires KHC for posterior localization. Thus, Wolbachia transport is uniquely KHC-limited because these bacteria are likely outcompeted for binding to KHC by some host cargo/linker complexes. These results reveal a novel host-symbiont interaction that underscores the precise regulation required for an intracellular bacterium to co-opt, but not disrupt, vital host processes.

Commercialization, Altruism, Clinical Practice: Seeking Explanation for Similarities and Differences in Californian and Canadian Gestational Surrogacy Outcomes.

BACKGROUND: Surrogacy is growing worldwide. Although recently some countries have sought to ban it, between 2010 and 2014 the number of babies born to gestational surrogates having in vitro fertilization treatment in California doubled, and in Canada it grew by 35%. This work seeks to fill identified knowledge gaps about the similarities and differences in the practices and outcomes of gestational surrogacy, which in California operates on a commercial basis, whereas in Canada it is illegal to pay a surrogate. The paper focusses on the period from 2010 to 2014, for which comparable American and Canadian national assisted reproduction technology information exist. STUDY DESIGN: A retrospective data analysis was performed using information on gestational surrogate multiple births obtained from the Centers for Disease Control and Prevention National Assisted Reproductive Technology Surveillance System (NASS) and Canada's Assisted Reproduction Registry-Better Outcomes Registry and Network (CARTR-BORN). Multiple birth rates and transfers of multiple embryos were compared using relative risk analysis. Adherence to voluntary American Society for Reproductive Medicine-Society for Assisted Reproductive Technology and Canadian Fertility and Andrology Society embryo transfer guidelines was modelled. FINDINGS: Among gestational surrogates, when donor ova embryos obtained from women aged less than 35 years were used, embryo transfer guideline adherence was 42% in California and 48% in Canada. CONCLUSIONS: Regardless of where on the commercial/noncommercial boundary North American surrogates reside, they are more likely to receive more donor ova embryos per in vitro fertilization transfer than other in vitro fertilization patients. An altruistic desire to assist childless couples and individuals create families along with clinic practices seem to play major roles in treatment decisions privileging the transfer two or more embryos.

Platelets from pulmonary hypertension patients show increased mitochondrial reserve capacity.

Accumulating evidence suggests that altered cellular metabolism is systemic in pulmonary hypertension (PH) and central to disease pathogenesis. However, bioenergetic changes in PH patients and their association with disease severity remain unclear. Here, we hypothesize that alteration in bioenergetic function is present in platelets from PH patients and correlates with clinical parameters of PH. Platelets isolated from controls and PH patients (n = 28) were subjected to extracellular flux analysis to determine oxygen consumption and glycolytic rates. Platelets from PH patients showed greater glycolytic rates than controls. Surprisingly, this was accompanied by significant increases in the maximal capacity for oxygen consumption, leading to enhanced respiratory reserve capacity in PH platelets. This increased platelet reserve capacity correlated with mean pulmonary artery pressure, pulmonary vascular resistance, and right ventricular stroke work index in PH patients and was abolished by the inhibition of fatty acid oxidation (FAO). Consistent with a shift to FAO, PH platelets showed augmented enzymatic activity of carnitine palmitoyltransferase-1 and electron transport chain complex II. These data extend the observation of a metabolic alteration in PH from the pulmonary vascular axis to the hematologic compartment and suggest that measurement of platelet bioenergetics is potentially useful in assessment of disease progression and severity.

Reliance of Wolbachia on High Rates of Host Proteolysis Revealed by a Genome-Wide RNAi Screen of Drosophila Cells.

Wolbachia are gram-negative, obligate, intracellular bacteria carried by a majority of insect species worldwide. Here we use a Wolbachia-infected Drosophila cell line and genome-wide RNA interference (RNAi) screening to identify host factors that influence Wolbachia titer. By screening an RNAi library targeting 15,699 transcribed host genes, we identified 36 candidate genes that dramatically reduced Wolbachia titer and 41 that increased Wolbachia titer. Host gene knockdowns that reduced Wolbachia titer spanned a broad array of biological pathways including genes that influenced mitochondrial function and lipid metabolism. In addition, knockdown of seven genes in the host ubiquitin and proteolysis pathways significantly reduced Wolbachia titer. To test the in vivo relevance of these results, we found that drug and mutant inhibition of proteolysis reduced levels of Wolbachia in the Drosophila oocyte. The presence of Wolbachia in either cell lines or oocytes dramatically alters the distribution and abundance of ubiquitinated proteins. Functional studies revealed that maintenance of Wolbachia titer relies on an intact host Endoplasmic Reticulum (ER)-associated protein degradation pathway (ERAD). Accordingly, electron microscopy studies demonstrated that Wolbachia is intimately associated with the host ER and dramatically alters the morphology of this organelle. Given Wolbachia lack essential amino acid biosynthetic pathways, the reliance of Wolbachia on high rates of host proteolysis via ubiquitination and the ERAD pathways may be a key mechanism for provisioning Wolbachia with amino acids. In addition, the reliance of Wolbachia on the ERAD pathway and disruption of ER morphology suggests a previously unsuspected mechanism for Wolbachia's potent ability to prevent RNA virus replication.

"One for Sorrow, Two for Joy?": American embryo transfer guideline recommendations, practices, and outcomes for gestational surrogate patients.

In January 2016, Melissa Cook, a California gestational surrogate experiencing a multiple-birth pregnancy following the in vitro fertilization (IVF) transfer of three embryos comprised of donor eggs and sperm provided by the intended father, went to the media when the intended father requested that she undergo a fetal reduction because twins were less expensive to raise than triplets. Much of the legal interest in this case to date has centered on the enforceability of surrogacy contracts. However, the Cook case also raises troubling issues about fertility treatment practices involving gestational surrogates, twin preference, and third-party reproduction medical decision-making. This paper focuses on multiple-embryo transfers in the context of US surrogacy arrangements. Offering an original analysis of data obtained from the US national-assisted reproduction registry, it examines single- and multiple-embryo transfer trends over a 12-year period (2003 to 2014). Findings reveal that recommended guidelines were followed in fewer than 42% of the cases in 2014. The paper argues that ensuring equitable medical treatment for all recipients of IVF requires the adoption of treatment guidelines tailored to, and offering protections for, specific patient groups, and that, once in place, guidelines must be robustly implemented.

Mechanisms of Horizontal Cell-to-Cell Transfer of Wolbachia spp. in Drosophila melanogaster.

Wolbachia is an intracellular endosymbiont present in most arthropod and filarial nematode species. Transmission between hosts is primarily vertical, taking place exclusively through the female germ line, although horizontal transmission has also been documented. The results of several studies indicate that Wolbachia spp. can undergo transfer between somatic and germ line cells during nematode development and in adult flies. However, the mechanisms underlying horizontal cell-to-cell transfer remain largely unexplored. Here, we establish a tractable system for probing horizontal transfer of Wolbachia cells between Drosophila melanogaster cells in culture using fluorescence in situ hybridization (FISH). First, we show that horizontal transfer is independent of cell-to-cell contact and can efficiently take place through the culture medium within hours. Further, we demonstrate that efficient transfer utilizes host cell phagocytic and clathrin/dynamin-dependent endocytic machinery. Lastly, we provide evidence that this process is conserved between species, showing that horizontal transfer from mosquito to Drosophila cells takes place in a similar fashion. Altogether, our results indicate that Wolbachia utilizes host internalization machinery during infection, and this mechanism is conserved across insect species.IMPORTANCE Our work has broad implications for the control and treatment of tropical diseases. Wolbachia can confer resistance against a variety of human pathogens in mosquito vectors. Elucidating the mechanisms of horizontal transfer will be useful for efforts to more efficiently infect nonnatural insect hosts with Wolbachia as a biological control agent. Further, as Wolbachia is essential for the survival of filarial nematodes, understanding horizontal transfer might provide new approaches to treating human infections by targeting Wolbachia Finally, this work provides a key first step toward the genetic manipulation of Wolbachia.

Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction.

BACKGROUND: Pulmonary hypertension (PH) is associated with poor outcomes, yet specific treatments only exist for a small subset of patients. The most common form of PH is that associated with left heart disease (Group 2), for which there is no approved therapy. Nitrite has shown efficacy in preclinical animal models of Group 1 and 2 PH, as well as in patients with left heart failure with preserved ejection fraction (HFpEF). We evaluated the safety and efficacy of a potentially novel inhaled formulation of nitrite in PH-HFpEF patients as compared with Group 1 and 3 PH. METHODS: Cardiopulmonary hemodynamics were recorded after acute administration of inhaled nitrite at 2 doses, 45 and 90 mg. Safety endpoints included change in systemic blood pressure and methemoglobin levels. Responses were also compared with those administered inhaled nitric oxide. RESULTS: Thirty-six patients were enrolled (10 PH-HFpEF, 20 Group 1 pulmonary arterial hypertension patients on background PH-specific therapy, and 6 Group 3 PH). Drug administration was well tolerated. Nitrite inhalation significantly lowered pulmonary, right atrial, and pulmonary capillary wedge pressures, most pronounced in patients with PH-HFpEF. There was a modest decrease in cardiac output and systemic blood pressure. Pulmonary vascular resistance decreased only in Group 3 PH patients. There was substantial increase in pulmonary artery compliance, most pronounced in patients with PH-HFpEF. CONCLUSIONS: Inhaled nitrite is safe in PH patients and may be efficacious in PH-HFpEF and Group 3 PH primarily via improvements in left and right ventricular filling pressures and pulmonary artery compliance. The lack of change in pulmonary vascular resistance likely may limit efficacy for Group 1 patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT01431313 FUNDING. This work was supported in part by the NIH grants P01HL103455 (to MAS and MTG), R01HL098032 (to MTG), and R01HL096973 (to MTG), and Mast Therapeutics, Inc.

Hidden from view: Canadian gestational surrogacy practices and outcomes, 2001-2012.

This paper raises some troubling questions about the fertility treatments provided to Canadian gestational surrogates, women not genetically related to the child that they carry. Using information published between 2003 and 2012 by Canada's Assisted Reproduction Registry, the paper traces the growing incidence of births to gestational surrogates. The transfer of more than one embryo increases the chance of pregnancy and the incidence of multiple births, and while the incidence of multiple births has declined overall since 2010, gestational surrogates consistently experience a higher proportion of multiple births and experienced higher levels of multiple embryo transfers. In 2012, just 26% of gestational surrogates received a single embryo transfer compared to 47% of other in vitro fertilisation (IVF) patients. The paper suggests that renewed attention needs to be paid to the counselling provided to gestational surrogates and treatment consenting mechanisms used by IVF clinics and that review of the 2007 Canadian Medical Association surrogate treatment guidelines is warranted. Finally, the paper describes the difficulties in obtaining accurate data about Canadian assisted reproductive medicine. Without good data, it becomes far more difficult to identify the possibility of potentially harmful practices.

SINGLE INSTITUTION VARIABILITY IN INTENSITY MODULATED RADIATION TARGET DELINEATION FOR CANINE NASAL NEOPLASIA.

Contouring variability is a significant barrier to the accurate delivery and reporting of radiation therapy. The aim of this descriptive study was to determine the variation in contouring radiation targets and organs at risk by participants within our institution. Further, we also aimed to determine if all individuals contoured the same normal tissues. Two canine nasal tumor datasets were selected and contoured by two ACVR-certified radiation oncologists and two radiation oncology residents from the same institution. Eight structures were consistently contoured including the right and left eye, the right and left lens, brain, the gross tumor volume (GTV), clinical target volume (CTV), and planning target volume (PTV). Spinal cord, hard and soft palate, and bulla were contoured on 50% of datasets. Variation in contouring occurred in both targets and normal tissues at risk and was particularly significant for the GTV, CTV, and PTV. The mean metric score and dice similarity coefficient were below the threshold criteria in 37.5-50% and 12.5-50% of structures, respectively, quantitatively indicating contouring variation. This study refutes our hypothesis that minimal variation in target and normal tissue delineation occurs. The variation in contouring may contribute to different tumor response and toxicity for any given patient. Our results also highlight the difficulty associated with replication of published radiation protocols or treatments, as even with replete contouring description the outcome of treatment is still fundamentally influenced by the individual contouring the patient.

Preference for language of instruction of an English language learner with autism.

OBJECTIVE: To use a preference assessment to identify the preferred language of instruction (English or Spanish) for a child with autism living in a Spanish-speaking home and receiving school services in English only. METHODS: We used a concurrent chains method to evaluate the participant's preference for English or Spanish instruction. Colored microswitches represented English instruction, Spanish instruction and no instruction (control). Switch presses resulted in instruction and reinforcement in either English or Spanish, or no instruction and no reinforcement. After session 10, switches were reprogrammed to control for color bias. RESULTS: The participant chose Spanish instruction most frequently. CONCLUSIONS: The participant preferred to receive instruction in Spanish. These data support previous research indicating the importance of child preference when individualizing educational programs for children with autism and that language of instruction is an important variable when working with children with autism who experience multiple languages across home and school.

Increased Butyrate Production During Long-Term Fermentation of In Vitro-Digested High Amylose Cornstarch Residues with Human Feces.

An in vitro semi-continuous long-term (3 wk) anaerobic incubation system simulating lower gut fermentation was used to determine variability in gut microbial metabolism between 4 predigested high amylose-resistant starch residues (SR): SRV, SRVI, SRVII, and SRGEMS in human fecal samples. Subjects participated twice, 5 mo apart: 30 in Phase I (15 lean, 9 overweight and 6 obese), 29 in Phase II (15 lean, 9 overweight, 5 obese); 13 of 15 lean subjects participated in both phases. Of the 4 SRs, SRV displayed the highest gelatinization temperature, peak temperature, enthalpy changes, and the least digestibility compared with the other SRs. In both phases, compared with blank controls, all SRs increased butyrate ∼2-fold which stabilized at week 2 and only SRV caused greater propionate concentration (∼30%) after 3 wk which might have been partly mediated by its lesser digestibility. Fecal samples from lean and overweight/obese subjects incubated with SRs showed similar short-chain fatty acid production across both time points, which suggests that resistant starch may benefit individuals across BMIs.