Metabolite profiling of foslevodopa/foscarbidopa in plasma of healthy human participants by LC-HRMS indicates no major differences compared to administration of levodopa/carbidopa intestinal gel.

Analysis was conducted to compare levodopa/carbidopa pharmacokinetics and drug-related material in plasma of healthy participants after receiving a continuous infusion of Levodopa/Carbidopa Intestinal Gel (LCIG) to a continuous subcutaneous infusion of foslevodopa/foscarbidopa. Study samples were from a randomized, open-label, 2-period crossover study in 20 healthy participants. Participants received either 24-h foslevodopa/foscarbidopa SC infusion to the abdomen or LCIG delivered for 24 h to the jejunum through a nasogastric tube with jejunal extension. Serial blood samples were collected for PK. Comparability of the LD PK parameters between the two treatment regimens was determined. Selected plasma samples were pooled per treatment group and per time point for metabolite profiling. LC-MSn was performed using high-resolution mass spectrometry to identify drug-related material across the dosing regimens and time points. The LD PK parameter central values and 90% confidence intervals following the foslevodopa/foscarbidopa subcutaneous infusion were between 0.8 and 1.25 relative to the LCIG infusion. With LCIG administration, LD, CD, 3-OMD, DHPA, DOPAC, and vanillacetic acid were identified in plasma at early and late time points (0.75 and 24 h); the metabolic profile after administration of foslevodopa/foscarbidopa demonstrated the same drug-related compounds with the exception of the administered foslevodopa. 3-OMD and vanillacetic acid levels increased over time in both treatment regimens. Relative quantification of LC-MS peak areas showed no major differences in the metabolite profiles. These results indicate that neither the addition of monophosphate prodrug moieties nor SC administration affects the circulating metabolite profile of foslevodopa/foscarbidopa compared to LCIG.

Nursing Students Perceptions of Using YouTube to Teach Psychomotor Skills: A Comparative Pilot Study.

Introduction: Current techniques to teach psychomotor skills to nursing students involve the traditional modeled performance by an instructor followed by rote memorization and practice. This outdated model presents many issues including no reference to refer back to, lacks technology integration, and only meets a few learning styles. A developmental study utilizing the social media platform YouTube was examined to gain student's perspective on this as a teaching tool to assist in skill acquisition. Objective: Do nursing students, who are enrolled in a Bachelor of Science Nursing (BSN) program and who are taught psychomotor nursing skills via demonstration on the social media platform YouTube, prefer this technology to traditional demonstration, and to evaluate their overall perceptions of YouTube? Methods: Data collection was done utilizing a nursing cohort enrolled in a BSN program. Participants were split into two groups. The control group was taught intravenous (IV) skills in the traditional teacher demonstration followed by practice. Experimental group was given access to a YouTube video series consisting of the identified IV skills. After testing for competency was concluded, control group was given access to the videos. A questionnaire was developed and sent out for evaluation. Results: Participants reported that their preferred learning style when learning new nursing skills was visual (41.7%) followed by a combination of visual, tactile, and auditory (41.7%). All respondents (100%) reported YouTube videos increased their learning. Respondents (100%) also noted that having access to the videos better prepared them. In experimental group, all participants (100%) watched the videos, and in the control group, only (16.7%) of students watched the videos after the skill had been learned. Conclusion: Results demonstrated that students prefer YouTube videos when learning new skills. They reported feeling better prepared to learn. YouTube is a potential way to increase skill acquisition and integrate technology into the nursing curriculum.

Cleft Lip and Palate: LeFort I Distraction with Halo and Hybrid Internal Maxillary Distractors.

Distraction osteogenesis is a viable treatment option for patients with a cleft associated with severe maxillary retrusion. A rigid external distraction device and a hybrid internal maxillary distractor have been used to advance the maxilla allowing for predictable and stable results. These techniques can be applied by itself or as an adjunct to traditional orthognathic procedures. The technical aspects are presented. These procedures tend to be simpler and demonstrate great stability compared to traditional surgical methods. The reasons for stability are discussed.

When is sitting height a better measure of adult body size than total height, and why? The contrasting examples of body mass, waist circumference, and lung volume.

OBJECTIVES: We aimed to establish which of sitting height (SH) and total height (Ht) is most appropriately used in the scaling of adult body mass (BM), waist circumference (WC), and forced vital capacity (FVC), considering likely explanations and proposing a suitable index for each. METHODS: Data were from the US Third National Health and Nutrition Survey for white and black American women and men aged 20 to 50 years. Statistical analysis involved mainly correlation coefficients, the multiple regression of BM, WC, or FVC on SH and leg length (LL), and fitting of allometric regression equations relating each of BM, WC, and FVC to SH or Ht. RESULTS: BM and WC correlated more strongly with SH than with Ht, and FVC correlated more strongly with Ht. Associations with LL were negative for WC, negative or nonsignificant for BM, and positive for FVC. Using round-number exponents for Ht and SH, the allometric relationships indicated that appropriate indices are BM/SH3 , WC/SH, and FVC/Ht2 . CONCLUSIONS: Contrary to usual practice, BM and WC are better scaled in relation to SH than to Ht. FVC is slightly better scaled in relation to Ht, as is conventional. Interpretations involve the small influence of LL on BM and the influence both of gluteo-femoral fatness on measured SH and of childhood health and nutrition on adult LL, WC, and FVC. It is evident that SH should be measured more often for research purposes.

The waist-hip ratio: a flawed index.

The waist-hip ratio, namely waist circumference (WC) divided by hip circumference (HC), has been referred to in thousands of articles, generally as a correlate and predictor either of health conditions such as cardiovascular disease and diabetes, or of amounts of visceral and subcutaneous abdominal fat. It has been argued that combining WC and HC as a ratio is inappropriate, and yet their individual roles can only be fully elucidated if considered jointly. Whereas WC is positively associated with cardiovascular disease, diabetes and premature mortality, the opposite is true of HC. With health-related measures taken as dependent variables, the present novel approach establishes that WC and HC are far better treated as separate independent variables in multiple regression equations than as their ratio. This necessarily produces closer fits to data. One should then allow for variations in height, or some other such measure of general body size, by including this in the regression equations. The widespread concern with the ratio seems to have distracted attention from HC, for this is discussed notably less often than WC. Given that other body parts, such as the thighs, may share relevant properties with the hips, measurements of these could perhaps replace HC.

Multidisciplinary care for a patient with syndromic craniosynostosis: A case report with 20 years of special care.

AIM: The functional and structural complexities accompanying syndromic craniosynostosis make dental care for these patients particularly challenging. We report a case of long-term care for a syndromic craniosynostosis patient. The objective of this report is to introduce special care guidance and clinical recommendation, so that oral health care providers, as key members of a multidisciplinary care team, can provide optimal diagnosis, treatment, and management for the patient with syndromic craniosynostosis. CASE REPORT: The patient of this case report had a medical history of syndromic craniosynostosis involving multiple comorbidities. Over the past 20 years, a multidisciplinary care team has successfully treated the patient. Dental and medical procedures that the patient has received include cranial surgeries, prophylactic dental care, caries control, growth hormone therapy, comprehensive orthodontic treatment in conjunction with orthognathic surgeries, and plastic surgery. CONCLUSION: Oral health care providers can play essential roles in multidisciplinary care for patients with craniosynostosis by understanding the patients' unique oral health conditions and dentofacial deformities. To provide optimal oral health care in a multidisciplinary team, clear communication between the members of the care team is crucial.

Assessment of the Biotransformation of Low-Turnover Drugs in the HµREL Human Hepatocyte Coculture Model.

Metabolic profiles of four drugs possessing diverse metabolic pathways (timolol, meloxicam, linezolid, and XK469) were compared following incubations in both suspended cryopreserved human hepatocytes and the HµREL hepatocyte coculture model. In general, minimal metabolism was observed following 4-hour incubations in both suspended hepatocytes and the HµREL model, whereas incubations conducted up to 7 days in the HµREL coculture model resulted in more robust metabolic turnover. In the case of timolol, in vivo human data suggest that 22% of the dose is transformed via multistep oxidative opening of the morpholine moiety. Only the first-step oxidation was detected in suspended hepatocytes, whereas the relevant downstream metabolites were produced in the HµREL model. For meloxicam, both the hydroxymethyl and subsequent carboxylic acid metabolites were abundant following incubation in the HµREL model, while only a trace amount of the hydroxymethyl metabolite was observed in suspension. Similar to timolol, linezolid generated substantially higher levels of morpholine ring-opened carboxylic acid metabolites in the HµREL model. Finally, while the major aldehyde oxidase-mediated mono-oxidative metabolite of XK469 was minimally produced in hepatocyte suspension, the HµREL model robustly produced this metabolite, consistent with a pathway reported to account for 54% of the total urinary excretion in human. In addition, low-level taurine and glycine conjugates were identified in the HµREL model. In summary, continuous metabolite production was observed for up to 7 days of incubation in the HµREL model, covering cytochrome P450, aldehyde oxidase, and numerous conjugative pathways, while predominant metabolites correlated with relevant metabolites reported in human in vivo studies.

The Sitting-Height Index of Build, (Body Mass)/(Sitting Height)³, as an Improvement on the Body Mass Index for Children, Adolescents and Young Adults.

The body mass index (BMI) is unsatisfactory in being affected by both relative leg length and height, and, for use with children and adolescents, therefore needs to be interpreted in relation to age. The sitting-height index of build (body mass)/(sitting height)³, is largely free of these disadvantages. Furthermore, because that index is independent of relative leg length, the latter can be treated as a separate indicator of nutritional history and health risks. Past studies on white children and adults have shown body mass to be approximately proportional to (sitting height)³. Moreover, multiple regression of (body mass)1/3 on sitting height and leg length, using year-by-year averages, has indicated that leg length is an insignificant predictor of body mass. The present study used data for individuals, namely 2-20 years old males and females, black as well as white. Regression analysis as above again showed leg length to be an insignificant predictor of body mass, but only above the age of about nine years. However, sitting height is still a stronger predictor of body mass than leg length at all ages. The advantages of the sitting-height index of build for use with young people are confirmed.

Relationships among fat mass, fat-free mass and height in adults: A new method of statistical analysis applied to NHANES data.

OBJECTIVES: The positive influence of fat mass (FM) on fat-free mass (FFM) has been quantified previously by various methods involving regression analysis of population data, but some are fundamentally flawed through neglect of the tendency of taller individuals to carry more fat. Differences in FFM due to differences in FM-and not directly related to differences in height-are expressed as ΔFFM/ΔFM, denoted KF . The main aims were to find a sounder regression-based method of quantifying KF and simultaneously of estimating mean BMI0 , the BMI of hypothetical fat-free individuals. Other, related, objectives were to check the linearity of FFM-FM relationships and to quantify the correlation between FM and height. METHODS: New statistical methods, explored and verified by Monte Carlo simulation, were applied to NHANES data. Regression of height2 on FFM and FM produced estimates of mean KF and indirectly of BMI0 . Both were then adjusted to allow for variability in KF around its mean. Its standard deviation was estimated by a novel method. RESULTS: Relationships between FFM and FM were linear, not semilogarithmic as is sometimes assumed. Mean KF is similar in Mexican American men and women, but higher in men than women in non-Hispanic European Americans and African Americans. Mean BMI0 is higher in men than in women. FM correlates more strongly with height than has been found previously. CONCLUSIONS: A more accurate way of quantifying mean BMI0 and the dependence of FFM on FM is established that may be easily applied to new and existing population data.

On Cooperative Behavior in Distributed Teams: The Influence of Organizational Design, Media Richness, Social Interaction, and Interaction Adaptation.

Self-interest vs. cooperation is a fundamental dilemma in animal behavior as well as in human and organizational behavior. In organizations, how to get people to cooperate despite or in conjunction with their self-interest is fundamental to the achievement of a common goal. While both organizational designs and social interactions have been found to further cooperation in organizations, some of the literature has received contradictory support, just as very little research, if any, has examined their joint effects in distributed organizations, where communication is usually achieved via different communication media. This paper reviews the extant literature and offers a set of hypotheses to integrate current theories and explanations. Further, it discusses how future research should examine the joint effects of media, incentives, and social interactions.

Metabolism and disposition of the DOT1L inhibitor, pinometostat (EPZ-5676), in rat, dog and human.

PURPOSE: The metabolism and disposition of the first-in-class DOT1L inhibitor, EPZ-5676 (pinometostat), was investigated in rat and dog. Metabolite profiles were compared with those from adult patients in the first-in-man phase 1 study as well as the cross-species metabolism observed in vitro. METHODS: EPZ-5676 was administered to rat and dog as a 24-h IV infusion of [(14)C]-EPZ-5676 for determination of pharmacokinetics, mass balance, metabolite profiling and biodistribution by quantitative whole-body autoradiography (QWBA). Metabolite profiling and identification was performed by radiometric and LC-MS/MS analysis. RESULTS: Fecal excretion was the major route of elimination, representing 79 and 81% of the total dose in and rat and dog, respectively. QWBA in rats showed that the radioactivity was well distributed in the body, except for the central nervous system, and the majority of radioactivity was eliminated from most tissues by 168 h. Fecal recovery of dose-related material in bile duct-cannulated animals as well as higher radioactivity concentrations in the wall of the large intestine relative to liver implicated intestinal secretion as well as biliary elimination. EPZ-5676 underwent extensive oxidative metabolism with the major metabolic pathways being hydroxylation of the t-butyl group (EPZ007769) and N-dealkylation of the central nitrogen. Loss of adenine from parent EPZ-5676 (M7) was observed only in rat and dog feces, suggesting the involvement of gut microbiota. In rat and dog, steady-state plasma levels of total radioactivity and parent EPZ-5676 were attained rapidly and maintained through the infusion period before declining rapidly on cessation of dosing. Unchanged EPZ-5676 was the predominant circulating species in rat, dog and man. CONCLUSIONS: The excretory and metabolic pathways for EPZ-5676 were very similar across species. Renal excretion of both parent EPZ-5676 and EPZ-5676-related material was low, and in preclinical species fecal excretion of parent EPZ-5676 and EPZ007769 accounted for the majority of drug-related elimination.

Sitting height as a better predictor of body mass than total height and (body mass)/(sitting height)(3) as an index of build.

BACKGROUND: The Rohrer Index and the ratio of sitting height (SH) to height fall similarly with growth in early childhood, then level off and rise slightly towards adulthood. In adults the BMI correlates with SH/height. The mean cross-sectional areas of the legs of adults are correlated positively with upper body masses and negatively with leg lengths. AIM: To find an index of body build that is less dependent on relative leg length and age in children and adults than are the BMI and the Rohrer Index. SUBJECTS AND METHODS: Published data are analysed to establish the relative importance of SH and leg length as predictors of body mass and to investigate the age dependence of the ratio (body mass)/SH(3). RESULTS: SH is a much better predictor of body mass than height, with leg length being barely relevant. Average values of (body mass)/SH(3) vary very little over the age range of 1-25 years, despite small non-random fluctuations. CONCLUSION: The ratio (body mass)/SH(3) is proposed as a useful "sitting-height index of build" that is superior to the Rohrer Index and could prove better than the BMI as a predictor of adiposity. Further studies are needed, notably using individual data and fat-free masses.

Adult fat content: reinterpreting and modelling the Benn Index and related sex differences.

BACKGROUND: In women, the height exponent, p, of the Benn Index, (body mass)/height(p), is typically lower than in men, body masses are more weakly correlated with height and fat masses tend to be higher. In both sexes fat masses correlate only weakly with height. Changes in fat mass are typically accompanied by changes in fat-free mass. AIMS: To integrate these facts, together with other published findings relating to fat content and to explain why p is lower in women. METHODS: Data and statistics are taken from the literature. The differences in p are explored by Monte Carlo and algebraic modelling. Mean transverse areas of the body (MTAs), calculated as (body mass)/height, are related to height. RESULTS AND CONCLUSIONS: The body can be modelled as consisting of a component, M1, varying roughly with the cube of height and another, M2, varying little with height. The low correlation between total body mass and height is due both to M2 and to data scatter. The low p values in women relate especially to M2. Relationships amongst height, fatness, MTAs and girths of body parts generally conform to this interpretation. Questions are raised as to how health risks are best related to fat mass.

Coordinated reconstruction with bilateral condylar replacement and dental implant rehabilitation: a clinical report.

The evaluation of complex facial-cranial trauma and subsequent restoration requires multidisciplinary treatment planning for optimal success and patient satisfaction. Patients with bilateral subcondylar fractures and facial-dental trauma are invariably challenging. Consideration of total joint replacement, along with the comprehensive evaluation of facial-dental esthetics and occlusion is critical for an optimal long-term outcome and for patient comfort. This patient treatment illustrates team cooperation and an optimal patient treatment outcome with long-term follow-up in the reconstruction of a complex cranial-facial injury from an unrestrained motor vehicle accident. The treatment included bilateral temporomandibular joint replacement with computer-aided design and computer-aided manufacturing fitted total temporomandibular joint reconstruction, grafting of a deficient anterior maxillary alveolar ridge, and dental implant placement and subsequent restoration with a partial fixed dental prosthesis.