Tumor protein Tctp regulates axon development in the embryonic visual system.

The transcript encoding translationally controlled tumor protein (Tctp), a molecule associated with aggressive breast cancers, was identified among the most abundant in genome-wide screens of axons, suggesting that Tctp is important in neurons. Here, we tested the role of Tctp in retinal axon development in Xenopus laevis We report that Tctp deficiency results in stunted and splayed retinotectal projections that fail to innervate the optic tectum at the normal developmental time owing to impaired axon extension. Tctp-deficient axons exhibit defects associated with mitochondrial dysfunction and we show that Tctp interacts in the axonal compartment with myeloid cell leukemia 1 (Mcl1), a pro-survival member of the Bcl2 family. Mcl1 knockdown gives rise to similar axon misprojection phenotypes, and we provide evidence that the anti-apoptotic activity of Tctp is necessary for the normal development of the retinotectal projection. These findings suggest that Tctp supports the development of the retinotectal projection via its regulation of pro-survival signalling and axonal mitochondrial homeostasis, and establish a novel and fundamental role for Tctp in vertebrate neural circuitry assembly.This work was supported by Fundação para a Ciência e Tecnologia (C.G.R.; fellowship SFRH/BD/33891/2009), Sir Edward Youde Memorial Fund, Croucher Foundation, Cambridge Commonwealth–European & International Trust (H.W.), Gates Cambridge Scholarship (J.Q.L.), and a Wellcome Trust Programme Grant (C.E.H.; grant 085314/Z/08/Z).This is the final version of the article. It first appeared from The Company of Biologists via http://dx.doi.org/10.1242/dev.13106

Precise B, B_s and B_c meson spectroscopy from full lattice QCD

We give the first accurate results for $B$ and $B_s$ meson masses from lattice QCD including the effect of $u$, $d$ and $s$ sea quarks, and we improve an earlier value for the $B_c$ meson mass. By using the Highly Improved Staggered Quark action for $u/d$, $s$ and $c$ quarks and NRQCD for the $b$ quarks, we are able to achieve an accuracy in the masses of around 10 MeV. Our results are: $m_B$ = 5.291(18) GeV, $m_{B_s}$ = 5.363(11) GeV and $m_{B_c}$ = 6.280(10) GeV. Note that all QCD parameters here are tuned from other calculations, so these are parameter free tests of QCD against experiment. We also give scalar, $B_{s0}^*$, and axial vector, $B_{s1}$, meson masses. We find these to be slightly below threshold for decay to $BK$ and $B^*K$ respectively.Comment: 22 pages, 19 figure

A Protocol for Single-Molecule Translation Imaging in Xenopus Retinal Ganglion Cells

Single-molecule translation imaging (SMTI) is a straightforward technique for the direct quantification of local protein synthesis. The protein of interest is fused to a fast-folding and fast-bleaching fluorescent protein, allowing one to monitor the appearance of individual fluorescence events after photobleaching of pre-existing proteins in the cell under investigation. The translation of individual molecules is then indicated by photon bursts of sub-second length that appear over a dark background. The method thus shares attributes with fluorescence recovery after photobleaching (FRAP) microscopy. Resulting datasets are similar to those generated by localization-based super-resolution microscopy techniques and can be used both to generate density maps of local protein production and to quantify the kinetics of local synthesis. The detailed protocol described in this chapter uses a Venus-β-actin fusion construct to visualize and measure the β-actin mRNA translational activity in Xenopus retinal ganglion cell growth cones upon Netrin-1 stimulation, which can be readily adapted for detecting translation events of other mRNAs in various cell types

Stage-Specific Generation of Human Pluripotent Stem Cell Derived Lung Models to Measure CFTR Function

Human embryonic stem cells (ES) and induced pluripotent stem cells (iPSC) are powerful tools that have the potential to generate in vitro human lung epithelial cells. However, challenges in efficiency and reproducibility remain in utilizing the cells for therapy discovery platforms. Here, we optimize our previously published protocols to efficiently generate three developmental stages of the lung model (fetal lung epithelial progenitors, fLEP; immature airway epithelial spheroid, AES; air-liquid interface culture, ALI), and demonstrate its potential for cystic fibrosis (CF) drug discovery platforms. The stepwise approach directs differentiation from hPSC to definitive endoderm, anterior ventral foregut endoderm, and fetal lung progenitor cells. The article also describes the generation of immature airway epithelial spheroids in Matrigel with epithelial cells sorted by a magnetic-activated cell sorting system, and the generation of adult-like airway epithelia through air-liquid interface conditions. We demonstrate that this optimized procedure generates remarkably higher cystic fibrosis transmembrane conductance regulator (CFTR) expression and function than our previous method, and thus is uniquely suitable for CF research applications. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: hESC/hiPSC differentiation to fetal lung progenitors Basic Protocol 2: Formation of airway epithelial spheroids Alternate Protocol 1: Cryopreservation of airway epithelial spheroids Basic Protocol 3: Differentiation and maturation in air-liquid interface culture Alternate Protocol 2: Differentiation and maturation of epithelial progenitors from airway epithelial spheroids in ALI culture

Outcomes of primary care delivery by nurse practitioners: Utilization, cost, and quality of care

ObjectiveTo examine whether nurse practitioner (NP)- assigned patients exhibited differences in utilization, costs, and clinical outcomes compared to medical doctor (MD)- assigned patients.Data SourcesVeterans Affairs (VA) administrative data capturing characteristics, outcomes, and provider assignments of 806 434 VA patients assigned to an MD primary care provider (PCP) who left VA practice between 2010 and 2012.Study DesignWe applied a difference- in- difference approach comparing outcomes between patients reassigned to MD and NP PCPs, respectively. We examined measures of outpatient (primary care, specialty care, and mental health) and inpatient (total and ambulatory care sensitive hospitalizations) utilization, costs (outpatient, inpatient and total), and clinical outcomes (control of hemoglobin A1c, LDL, and blood pressure) in the year following reassignment.Principal FindingsCompared to MD- assigned patients, NP- assigned patients were less likely to use primary care and specialty care services and incurred fewer total and ambulatory care sensitive hospitalizations. Differences in costs, clinical outcomes, and receipt of diagnostic tests between groups were not statistically significant.ConclusionsPatients reassigned to NPs experienced similar outcomes and incurred less utilization at comparable cost relative to MD patients. NPs may offer a cost- effective approach to addressing anticipated shortages of primary care physicians.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154625/1/hesr13246_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154625/2/hesr13246-sup-0001-Authormatrix.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154625/3/hesr13246.pd

Deeper Seated Than Skin Deep: Report of a Rare Case of Follicular Occlusion Tetrad and a Literature Review

Follicular occlusion tetrad (FOT) is a clinical syndrome consisting of hidradenitis suppurativa (HS), acne conglobata (AC), dissecting cellulitis of the scalp (DCS), and pilonidal cyst (PC). These entities typically occur independently, but occasionally present simultaneously comprising FOT. The four components share similar pathophysiology affecting the apocrine glands, follicular hyperkeratinization being the hallmark of each entity.Understanding shared similarities of each disease is paramount for the treatment approach as the relapsing and chronic nature of this syndrome can be burdening to patients. We present the case of a 22- year-old obese Hispanic man with a history of tobacco use who presented with worsening skin lesions. The patient developed extensive facial cystic acne 5 years before presentation, followed by left axillary hidradenitis suppurativa lesions two years before the presentation and right axillary involvement one year after. Skin manifestations then expanded to include the lower back, gluteal and perineal areas. The patient was diagnosed with FOT and despite conservative medical management, his lesions failed to improve. He ultimately underwent multiple staged excisional debridement surgeries and skin grafts. Our case underlines the presence of a syndromic association of cutaneous lesions that share a common pathogenesis and emphasizes that this entity requires a multidisciplinary approach. New biologic therapies continue to emerge and may potentially prevent the need for surgical intervention and the burden associated with it

Comparable, but distinct: Perceptions of primary care provided by physicians and nurse practitioners in full and restricted practice authority states

AimsTo understand patients- and providers- perceptions of primary care delivered by nurse practitioners (NPs) in the Veterans Affairs Healthcare System.DesignQualitative exploratory study (in convergent mixed- methods design).MethodsSemi- structured interviews in 2016 with primary care providers and patients from facilities in states with full and restricted practice authority for NPs. Patient sample based on reassignment to: (a) a NP; or (b) a different physician following an established physician relationship. Data were analysed using content analysis.ResultsWe interviewed 28 patients, 17 physicians and 14 NPs. We found: (a) NPs provided more holistic care than physicians; (b) patients were satisfied with NPs; and (c) providers- professional experience outweighed provider type.ConclusionsPatients- preferences for NPs (compared with prior physicians) contributed to perceptions of patient centredness. Similarities in providers- perceptions suggest NPs and physicians are both viable providers for primary care.ImpactNurse Practitioners (NPs): practice authorityVeterans Affairs Health care: nurse practitioners will continue to be a viable resource for primary care deliveryUnited States Health care: challenges notions patients may not be satisfied with care provided by NPs and supports expanding their use to provide much- needed access to primary care services; expanding Full Practice Authority would allow states to provide acceptable primary care without diminishing patient or provider experiencesæ è¦ ç ®æ  äº è§£æ £è å å »ç æ ºæ 对é ä¼ å äººå »ç ä¿ å ¥ç³»ç» ä¸­æ ¤ç å¸ æ ä¾ å çº§æ ¤ç ç ç æ³ ã è®¾è®¡æ ¢ç´¢æ §ç å® æ §ç  ç©¶(æ ¶æ æ··å æ ¹æ³ è®¾è®¡)ã æ ¹æ³ 2016å¹´è¿ è¡ ç å ç» æ å è®¿è° ,é è®¿äº å· å æ ¥æ æ ¤ç å¸ ç å ¨ç§ å é å ¨ç§ æ §ä¸ æ ºæ ç å çº§æ ¤ç æ ä¾ è å æ £è ã é æ °å é æ £è æ ·æ ¬:(a) ä¸ å æ ¤ç å¸ ;æ (b)ç¡®ç« å »ç å ³ç³»ç å ¦ä¸ å å »ç ã é ç ¨å 容å æ æ³ å¯¹æ °æ ®è¿ è¡ å æ ã ç» æ æ 们é è®¿äº 28å æ £è ,17å å »ç å 14å æ ¤ç å¸ ã æ 们å ç °:(a)æ ¤ç å¸ æ¯ å »ç æ ä¾ ç æ ¤ç æ ´å ¨é ¢;(b)æ £è å¯¹æ ¤ç å¸ æ å °æ»¡æ ;(c)å »ç æ ºæ ç ä¸ ä¸ ç» éª ç æ é æ¯ å »ç æ ºæ ç±»å ç æ é æ ´å¤§ã ç» è®ºæ £è å¯¹æ ¤ç å¸ ç å 好(ä¸ ä»¥å ç å »ç ç ¸æ¯ )æ å ©äº å»ºç« ä»¥æ £è ä¸ºä¸­å¿ ç è®¤ç ¥ã æ ä¾ è ç è§ å¿µç±»ä¼¼,表æ æ ¤ç å¸ å å »ç é ½æ ¯å ¯è¡ ç å çº§æ ¤ç æ ä¾ è ã å½±å - ¢æ ¤ç å¸ :æ §ä¸ æ ºæ - ¢é ä¼ å äººå »ç ä¿ å ¥ç³»ç» :æ ¤ç å¸ å° ç»§ç»­ä½ ä¸ºæ ä¾ å çº§æ ¤ç æ å ¡ç å ¯ç ¨èµ æº ã - ¢ç¾ å ½å «ç ä¿ å ¥:æ æ è§ å¿µ æ £è å ¯è ½ä¸ æ»¡æ ç ±æ ¤ç å¸ æ ä¾ ç æ ¤ç ,å ¶ä¼ æ ¯æ æ ©å¤§ä½¿ç ¨è å ´,以æ ä¾ æ ¥é ç å çº§ä¿ å ¥æ å ¡;æ ©å¤§å ¨ç§ æ §ä¸ æ ºæ å° ä½¿å å· è ½å¤ æ ä¾ å ¯æ ¥å ç å çº§ä¿ å ¥æ å ¡,è ä¸ ä¼ å å¼±æ £è æ æ ä¾ è ç ä½ éª ãPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163369/2/jan14501.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163369/1/jan14501_am.pd

Evaluation of Messages to Promote Intake of Calcium-Rich Foods in Early Adolescents

Parental practices influence intake of calcium-rich foods and beverages (CRFB) in adolescents. This study aimed to test two posters promoting such parental practices for comprehension, cultural and personal relevance, and ability to motivate parents to encourage CRFB intake. Interviews were conducted with 14 Hispanic and 6 Asian parents to evaluate two posters entitled “Good play starts with calcium” and “Strong families start with good nutrition.” Responses were reviewed for themes. For “Good play,” both racial/ethnic groups of parents understood the message to provide CRFB. Only Hispanics, however, recognized the connection between calcium and strong bones. For “Strong families,” both groups had difficulty understanding that foods pictured were calcium rich. Both posters were considered culturally and personally relevant; however, not all respondents indicated motivation to provide CRFB. Modifications are needed to emphasize the connection between images and taglines and calcium intake for use in a future intervention to improve CRFB-promoting practices

Predictors and trajectories of chronic postoperative pain following hip preservation surgery

Abstract Factors contributing to chronic postoperative pain (CPOP) are poorly defined in young people and developmental considerations are poorly understood. With over 5 million children undergoing surgery yearly and 25% of adults referred to chronic pain clinics identifying surgery as the antecedent, there is a need to elucidate factors that contribute to CPOP in surgical patients. The present study includes patients undergoing hip preservation surgery at a children’s hospital. The HOOS and SF-12 Health Survey were administered to 614 pre-surgical patients with 421 patients completing follow-up (6-months, 1-year and 2-years post-surgery). Pain, quality of life, and functioning across time were examined for each group within the population. A three trajectory model (low pain, pain improvement and high pain) emerged indicating three categories of treatment responders. Pain trajectory groups did not differ significantly on gender, pre-surgical age, BMI, prior hip surgery, surgical type, joint congruence or Tönnis grade. The groups differed significantly from each other on pre-surgical pain, pain chronicity, quality of life and functioning. Those in the high pain and pain improvement groups endorsed having pre-surgical depression at significantly higher rates and lower pre-surgical quality of life compared to those in the low pain group (P < 0.01). Those in the high pain group reported significantly worse pre-surgical functioning compared to those in the pain improvement (P < 0.0001) and low pain groups (P < 0.0001).The results demonstrate the need for preoperative screening prior to hip preservation surgery, as there may be a subset of patients who are predisposed to chronic pain independent of hip health