The Schizosaccharomyces pombe Cdc42p GTPase signals through Pak2p and the Mkh1p-Pek1p-Spm1p MAP kinase pathway

The Cdc42p GTPase is involved in many aspects of growth and cell-cycle regulation, including actin cytoskeletal rearrangements and activation of signal transduction pathways. To further investigate these functions, genetic interactions were examined between Schizosaccharomyces pombe Cdc42p, its effectors Pak1p and Pak2p, and the Mkh1p-Pek1p-Spm1p signal transduction pathway, which functions in cytokinesis and cell division. Expression of a truncated version of Pak2p lacking its N-terminal autoinhibitory domain led to a growth defect that was suppressed by deltamkh1 and deltaspm1 null mutations and an elongated cell phenotype indicative of a cell division defect that was suppressed by the deltamkh1 mutation. In addition, expression of the constitutively activated cdc42G12V mutant allele led to a growth defect that was rescued by the deltapak2 and deltamkh1 mutations. The deltapak2 mutation did not suppress the growth defect conferred by plasmid expression of Mkh1p, suggesting that Pak2p functions upstream of Mkh1p in this pathway. A two-hybrid protein interaction was observed between Pak2p and Mkh1p, but not between Pak1p and Mkh1p. These results are consistent with Cdc42p interacting with Pak2p to signal through the Mkh1p-Pek1p-Spm1p pathway.     

TAS1R3 and TAS2R38 Polymorphisms Affect Sweet Taste Perception: An Observational Study on Healthy and Obese Subjects

Background: The inter-individual differences in taste perception find a possible rationale in genetic variations. We verified whether the presence of four different single nucleotide polymorphisms (SNPs) in genes encoding for bitter (TAS2R38; 145G > C; 785T > C) and sweet (TAS1R3; −1572C > T; −1266C > T) taste receptors influenced the recognition of the basic tastes. Furthermore, we tested if the allelic distribution of such SNPs varied according to BMI and whether the associations between SNPs and taste recognition were influenced by the presence of overweight/obesity. Methods: DNA of 85 overweight/obese patients and 57 normal weight volunteers was used to investigate the SNPs. For the taste test, filter paper strips were applied. Each of the basic tastes (sweet, sour, salty, bitter) plus pure rapeseed oil, and water were tested. Results: Individuals carrying the AV/AV diplotype of the TAS2R38 gene (A49P G/G and V262 T/T) were less sensitive to sweet taste recognition. These alterations remained significant after adjustment for gender and BMI. Moreover, a significant decrease in overall taste recognition associated with BMI and age was found. There was no significant difference in allelic distribution for the investigated polymorphisms between normal and overweight/obese patients. Conclusions: Our findings suggest that overall taste recognition depends on age and BMI. In the total population, the inter-individual ability to identify the sweet taste at different concentrations was related to the presence of at least one genetic variant for the bitter receptor gene but not to the BMI.     

Whole exome sequencing identified a novel single base pair insertion mutation in the EYS gene in a six generation family with retinitis pigmentosa

Retinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies (RD) and is characterized by photoreceptor degeneration. RP is clinically and genetically heterogeneous disorder. More than 70 genes are known and, thus, identification of causative genes and mutations in known genes is challenging. This study was designed to identify the underlying genetic defect in a large extended Saudi family with multiple RP affected members. Fundus photography, Optical Coherence Tomography (OCT) and visual field perimetry were performed for affected individuals. Whole exome sequencing was used to detect the underlying genetic defect in a large family with 12 affected individuals showing autosomal recessive isolated RP. WES data analysis identified a novel insertion mutation in the EYS (eyes shut homolog) gene (c.910_911insT; p.Trp304LeufsTer8). Sanger sequencing validates the variant discovered through exome in all 12 affected individuals and showed that this mutation is segregating with RP phenotype in an autosomal recessive manner in 51 individuals of the family tested here. Our study expands the mutation spectrum of EYS gene in RP patients and extends the body of evidence that supports the importance of EYS gene in eye development.     

White patients’ physical responses to healthcare treatments are influenced by provider race and gender

The healthcare workforce in the United States is becoming increasingly diverse, gradually shifting society away from the historical overrepresentation of White men among physicians. However, given the long-standing underrepresentation of people of color and women in the medical field, patients may still associate the concept of doctors with White men and may be physiologically less responsive to treatment administered by providers from other backgrounds. To investigate this, we varied the race and gender of the provider from which White patients received identical treatment for allergic reactions and measured patients’ improvement in response to this treatment, thus isolating how a provider’s demographic characteristics shape physical responses to healthcare. A total of 187 White patients experiencing a laboratory-induced allergic reaction interacted with a healthcare provider who applied a treatment cream and told them it would relieve their allergic reaction. Unbeknownst to the patients, the cream was inert (an unscented lotion) and interactions were completely standardized except for the provider’s race and gender. Patients were randomly assigned to interact with a provider who was a man or a woman and Asian, Black, or White. A fully blinded research assistant measured the change in the size of patients’ allergic reaction after cream administration. Results indicated that White patients showed a weaker response to the standardized treatment over time when it was administered by women or Black providers. We explore several potential explanations for these varied physiological treatment responses and discuss the implications of problematic race and gender dynamics that can endure “under the skin,” even for those who aim to be bias free.

The face of medicine is changing. Women and people of color make up an increasing percentage of health care providers (1–3). In 2017, for the first time in history, women were the majority of accepted medical school applicants in the United States and the number of non-White accepted applicants rose to above 50%. Here, we ask whether this recent demographic shift in the race and gender of doctors is also shifting long-held, societally pervasive notions of what a doctor “looks like.”Despite the increasing diversity of the medical field, for most people in most contexts, the association between “doctor” and “White man” is still likely strong and pervasive. This is hardly surprising. For most of medical history in North America, the majority of physicians fit this profile (see Fig. 1 A and B), and even now the majority of practicing physicians are still men and nearly half are White (see Fig. 1 C and D). Consequently, the emerging links between “Doctor and Woman” and between “Doctor and Black person,” for example, are likely weak. Moreover, to the extent that those associations exist, they are likely to have to compete for attention with an array of strong, frequent, and negative associations that undermine the links between women and competence and African Americans and competence (4–6).Open in a separate windowFig. 1.The change in the representation of women (A) and people color (B) in the number of accepted applicants to US medical schools, as well as the current representation of professionally active women physicians (C) and physicians of color (D). (A and B) From the Association of American Medical Colleges (AAMC). (C) From the Henry J. Kaiser Family Foundation. (D) From 2013 from the Association of American Medical Colleges (AAMC). AAMC data on race/ethnicity were not available for 2013 or 2014, hence explaining the gaps in the graph around these years in B.In patient–provider interactions, as in every social encounter, people bring with them a set of learned associations about social groups that have been formed by their various life experiences (e.g., personal interactions, media exposure) (6–12). Mirroring the historical representation of doctors in actual medical practice, representations of doctors in popular media have overwhelmingly been as White men (13–15). Patients who have learned this societally pervasive “Doctor = White man” association through their actual encounters with physicians as well as through movies, television, books, and advertising may respond less positively to care from Black and women providers. These associations may exist at an implicit level even in the context of positive explicit attitudes toward Black doctors and women doctors (16, 17), and they are potentially powerful, influencing the course of medical care. Also, while it is clear from past research that being a target of bias can be harmful to health (e.g., people who face race-based discrimination face adverse physical and mental health consequences) (18), it is unclear whether viewing another social group in light of societally pervasive associations (e.g., about doctors on the basis of gender and race) can be harmful to the health of the perceiver.Here, we focus on how the race and gender of doctors may impact patients’ responses to the expectations doctors set about medical treatment. Previous research shows that a provider’s expressed expectations for a medical treatment (i.e., that it will benefit patients) can improve patient engagement, adherence, and physiological responses to treatment (19–25). Based on these findings, we anticipate that patients who interact with a doctor whose personal characteristics (e.g., race, gender) do not conform to dominant societal representations of what a doctor looks like may be less responsive to such expectations. We hypothesize that patients may be less responsive to the exact same medical treatment when the doctor who sets expectations that this treatment will be beneficial is not a White man.This hypothesis draws on a large and growing body of research suggesting that the total effect of a healthcare treatment depends on the social context in which that treatment takes place (25–29). The realization that the social context can influence treatment and medical outcomes is bolstered by a large body of research on the placebo effect (26). Although people may sometimes assume that actual pharmaceutical properties of a medication or treatment are solely responsible for its total benefit, placebo paradigms show that the total effect of treatment is in fact a combined product of the drug and their medical properties (e.g., acetaminophen, antihistamines), the body’s natural healing abilities (e.g., endogenous opioids and antihistamines), and the psychological and social context (e.g., what a patient believes about treatment and the qualities of the person who administers the treatment) (SI Appendix, Fig. S1). For example, past research suggests that a physician’s characteristics, such as their projected warmth and competence, influences how much a patient improves in response to treatment. In one recent study (22), the researchers independently manipulated whether a provider acted more or less warm, and more or less competent, toward a patient during an allergy skin prick test that induced a mild allergic reaction. The provider set positive expectations about a placebo cream (i.e., unscented hand lotion) placed on the reaction, informing patients that this cream was an antihistamine that would reduce the reaction. When the provider was both warm and competent, patients showed a stronger physiological response to the placebo treatment over time; their allergic reaction decreased the most rapidly in size, in response to the positive expectations that the provider had set. Thus, aspects of social interactions with providers can influence the degree to which the positive expectations that a provider sets about treatment ultimately influence physiological treatment response.As in most social interactions in the United States, race and gender are likely salient aspects of the social context in patient–provider interactions (30, 31, 32). Previous research has found, for example, that patient race can influence the quality of care received from doctors in myriad ways (33–36). Here, we focus on provider race and provider gender as features of the social context that can influence patients’ response to treatment. Specifically, we ask the following: will White patients exhibit a weaker physiological response to the expectations set about treatment by doctors who are not White and men?     

Instagram Posts Related to Backwoods Cigarillo Blunts: Content Analysis

BackgroundInstagram, one of the most popular social media platforms among youth, offers a unique opportunity to examine blunts—partially or fully hollowed-out large cigars, little cigars, and cigarillos that are filled with marijuana. Cigarillo brands like Backwoods (Imperial Tobacco Group Brands LLC) have product features that facilitate blunt making, including a variety of brand-specific flavors that enhance the smoking experience (eg, honey, dark stout). Backwoods has an active online presence with a user-friendly website.ObjectiveThis study examined the extent to which Backwoods cigarillo–related posts on Instagram showed blunt making. Instagram offers a unique opportunity to examine blunt making as Instagram accounts will contain images reflective of behavior occurring without the prime of a researcher.MethodsData consisted of publicly available Instagram posts with the hashtag #backwoods collected from August 30 to September 12, 2018. Inclusion criteria for this study included an Instagram post with the hashtag “#backwoods”. Rules were established to content analyze posts. Categories included Type of post (ie, photo, video, or both); Blunt-related hashtags (ie, the corresponding post caption contained one or more hashtags like #blunts, #cannabis, and #weed that were identified in previous social media research); Rolling blunts (ie, the post contained an image of one or more individuals rolling a Backwoods cigarillo visibly containing marijuana); and Smoking blunts (ie, the post contained an image of one or more individuals blowing smoke or holding a lit blunt). We coded images for Product flavor reference, where a code of 1 showed a Backwoods cigarillo pack with a brand-specific flavor (eg, honey, dark stout, Russian crème) visible in the blunt-related image, and a code of 0 indicated that it was not visible anywhere in the image.ResultsAmong all posts (N=1206), 871 (72.2%) were coded as Blunt-related hashtags. A total of 125 (10.4%) images were coded as Smoking blunts, and 25 (2.1%) were coded as Rolling blunts (ie, Backwoods cigarillo explicitly used to roll blunts). Among blunt images, 434 of 836 (51.9%) were coded as Product flavor (ie, a Backwoods pack with a brand-specific flavor was visible).ConclusionsMost Backwoods cigarillo–related Instagram images were blunt-related, and these blunt-related images showed Backwoods packages indicating flavor preference. Continued monitoring and surveillance of blunt-related posts on Instagram is needed to inform policies and interventions that reduce the risk that youth may experiment with blunts. Specific policies could include restrictions on product features (eg, flavors, perforated lines, attractive resealable foil pouches, sale as singles) that facilitate blunt making.     

Impact of maternal age on preterm delivery and low birthweight: a hospital-based collaborative study of nulliparous Lebanese women in Greater Beirut.

OBJECTIVES: To analyze the impact of maternal age at first childbirth on the incidence of preterm delivery and low birthweight among single live births delivered to nulliparous Lebanese women in Greater Beirut. STUDY DESIGN: Eligible subjects were selected from a consecutive sample of neonatal admissions to nine National Collaborative Perinatal Network participating hospitals over a three-year period (April 1, 1999 to March 31, 2002). Chi-square tests and logistic regression analyses were applied. RESULTS: Out of 5556 nulliparous mothers, 5.4% had a preterm delivery and 5.2% a low-birthweight infant. In the multivariate analysis, preterm delivery was not significantly affected by old maternal age. Mothers aged 25 years or more remained a high-risk group for low birthweight even after controlling for potentially confounding characteristics. CONCLUSIONS: Maternal age at first childbirth above 25 years is an independent risk factor for low birthweight, but not for preterm delivery, an outcome influenced mainly by obstetric complications.     

A Computational Model for Simulation of Shallow Water Waves by Elastic Deformations in the Topography

We propose a coupled model to simulate shallow water waves induced by elastic deformations in the bed topography. The governing equations consist of the depth-averaged shallow water equations including friction terms for the water free-surface and the well-known second-order elastostatics formulation for the bed deformation. The perturbation on the free-surface is assumed to be caused by a sudden change in the bottom beds. At the interface between the water flow and the bed topography, transfer conditions are implemented. Here, the hydrostatic pressure and friction forces are considered for the elastostatic equations whereas bathymetric forces are accounted for in the shallow water equations. The focus in the present study is on the development of a simple and accurate representation of the interaction between water waves and bed deformations in order to simulate practical shallow water flows without relying on complex partial differential equations with free boundary conditions. The effects of location and magnitude of the deformation on the flow fields and free-surface waves are investigated in details. Numerical simulations are carried out for several test examples on shallow water waves induced by sudden changes in the bed. The proposed computational model has been found to be feasible and satisfactory.     

Increased risk organ transplantation in the pediatric population

IRD organs are classified by the Public Health Service to be at above‐average risk for harboring human immunodeficiency virus, hepatitis C, and hepatitis B. Traditionally underutilized, there exists even greater reluctance for their use in pediatric patients. We performed a retrospective analysis via the United Network for Organ Sharing database of all pediatric renal and hepatic transplants performed from 2004 to 2008 in the United States. Primary outcomes were patient and graft survival. Proportional hazards regression was performed to control for potentially confounding factors. Waitlist time, organ acceptance rates, and infectious transmissions were analyzed. There were 1830 SRD renal, 92 IRD renal, 1695 SRD hepatic, and 59 IRD hepatic transplants. There were no statistically significant differences in allograft or patient survival in either group. Acceptance rates of IRD organs were lower for kidney (1.5% IRD vs 4.82% SRD) and liver (1.99% IRD vs 4.51% SRD). One transmission of a bloodborne pathogen involving a pediatric recipient out of 7797 unique transplants was reported from 2008 to 2015. IRD organs appear to have equivalent outcomes. Increasing their utilization may improve access to transplant while decreasing wait times and circumventing waitlist morbidity and mortality.