Being on top versus not dangling at the bottom: Popularity motivation and aggression in youth.

Whereas research on aggression and status motivation in youth has predominantly looked at a promotion focus (striving for popularity), a prevention focus (wanting to avoid low popularity) could also be an important determinant of aggression, as youth who fear low popularity may use strategic aggression to secure their position. The aim of the current study was to develop reliable measures for both popularity motivations, and examine how both motivations are uniquely and jointly related to aggression. Participants were 1123 Dutch secondary school students (M age = 14.4 years, 48% girls), who completed a 3-item measure of striving for high popularity based on existing questionnaires (Li & Wright, 2014; Ojanen et al., 2005), and a 3-item measure of avoiding low popularity consisting of an adapted version of the high popularity items. Aggressive behavior was measured through peer nominations. Motivations were moderately correlated (r = .51), but did not always co-occur within the same person, as 17% of the sample belonged to a cluster that scored low on striving for popularity, but moderately high on avoiding low popularity. When considered simultaneously, striving for high popularity was not related to any type of aggression, whereas avoiding affiliation with unpopular peers was related to strategic aggression. For physical and verbal aggression, gossiping, excluding and bullying, the association of avoiding low popularity with aggression was strongest when youth also strived for high popularity. Future work should take both popularity motivations into account to better understand, predict and intervene on youth's aggression toward peers.

Clinical and genetic features of dominant Essential Tremor in Tuscany, Italy: FUS, CAMTA1, ATXN1 and beyond.

OBJECTIVE: Essential Tremor (ET) is one of the most common neurological disorders. In most instances ET is inherited as an autosomal dominant trait with age-related penetrance (virtually complete in advanced age); however, ET genetics remains elusive. The current study aims to identify possibly pathogenic genetic variants in a group of well-characterized ET families. METHODS: 34 individuals from 14 families with dominant ET were clinically evaluated and studied by whole exome sequencing studies (after excluding trinucleotide expansion disorders). RESULTS: Most patients had pure ET. In 4 families, exome studies could identify a genetic variant potentially able to significantly alter the protein structure (CADD >20, REVEL score > 0.25), shared by all the affected individuals (in CAMTA1, FUS, MYH14, SGCE genes). In another family there were two variants in dominant genes (PCDH9 and SQSTM1). Moreover, an interrupted "intermediate" trinucleotide expansion in ATXN1 ("SCA1") was identified in a further family with pure ET. CONCLUSION: Combining our observations together with earlier reports, we can conclude that ET genes confirmed in at least two families to date include CAMTA1 and FUS (reported here), as well as CACNA1G, NOTCH2NLC and TENM4. Most cases of familial ET, inherited with an autosomal dominant inheritance, may result from "mild" variants of many different genes that, when affected by more harmful genetic variants, lead to more severe neurological syndromes (still autosomal dominant). Thus, ET phenotype may be the "mild", incomplete manifestation of many other dominant neurogenetic diseases. These findings further support evidence of genetic heterogeneity for such disease(s). Author's keywords: cerebellar ataxias, movement disorders, neurogenetics, rare neurological disorders, tremor.

WNK kinase is a vasoactive chloride sensor in endothelial cells.

Endothelial cells (ECs) line the wall of blood vessels and regulate arterial contractility to tune regional organ blood flow and systemic pressure. Chloride (Cl-) is the most abundant anion in ECs and the Cl- sensitive With-No-Lysine (WNK) kinase is expressed in this cell type. Whether intracellular Cl- signaling and WNK kinase regulate EC function to alter arterial contractility is unclear. Here, we tested the hypothesis that intracellular Cl- signaling in ECs regulates arterial contractility and examined the signaling mechanisms involved, including the participation of WNK kinase. Our data obtained using two-photon microscopy and cell-specific inducible knockout mice indicated that acetylcholine, a prototypical vasodilator, stimulated a rapid reduction in intracellular Cl- concentration ([Cl-]i) due to the activation of TMEM16A, a Cl- channel, in ECs of resistance-size arteries. TMEM16A channel-mediated Cl- signaling activated WNK kinase, which phosphorylated its substrate proteins SPAK and OSR1 in ECs. OSR1 potentiated transient receptor potential vanilloid 4 (TRPV4) currents in a kinase-dependent manner and required a conserved binding motif located in the channel C terminus. Intracellular Ca2+ signaling was measured in four dimensions in ECs using a high-speed lightsheet microscope. WNK kinase-dependent activation of TRPV4 channels increased local intracellular Ca2+ signaling in ECs and produced vasodilation. In summary, we show that TMEM16A channel activation reduces [Cl-]i, which activates WNK kinase in ECs. WNK kinase phosphorylates OSR1 which then stimulates TRPV4 channels to produce vasodilation. Thus, TMEM16A channels regulate intracellular Cl- signaling and WNK kinase activity in ECs to control arterial contractility.

Erg251 has complex and pleiotropic effects on azole susceptibility, filamentation, and stress response phenotypes.

Ergosterol is essential for fungal cell membrane integrity and growth, and numerous antifungal drugs target ergosterol. Inactivation or modification of ergosterol biosynthetic genes can lead to changes in antifungal drug susceptibility, filamentation and stress response. Here, we found that the ergosterol biosynthesis gene ERG251 is a hotspot for point mutations during adaptation to antifungal drug stress within two distinct genetic backgrounds of Candida albicans. Heterozygous point mutations led to single allele dysfunction of ERG251 and resulted in azole tolerance in both genetic backgrounds. This is the first known example of point mutations causing azole tolerance in C. albicans. Importantly, single allele dysfunction of ERG251 in combination with recurrent chromosome aneuploidies resulted in bona fide azole resistance. Homozygous deletions of ERG251 caused increased fitness in low concentrations of fluconazole and decreased fitness in rich medium, especially at low initial cell density. Dysfunction of ERG251 resulted in transcriptional upregulation of the alternate sterol biosynthesis pathway and ZRT2, a Zinc transporter. Notably, we determined that overexpression of ZRT2 is sufficient to increase azole tolerance in C. albicans. Our combined transcriptional and phenotypic analyses revealed the pleiotropic effects of ERG251 on stress responses including cell wall, osmotic and oxidative stress. Interestingly, while loss of either allele of ERG251 resulted in similar antifungal drug responses, we observed functional divergence in filamentation regulation between the two alleles of ERG251 (ERG251-A and ERG251-B) with ERG251-A exhibiting a dominant role in the SC5314 genetic background. Finally, in a murine model of systemic infection, homozygous deletion of ERG251 resulted in decreased virulence while the heterozygous deletion mutants maintain their pathogenicity. Overall, this study provides extensive genetic, transcriptional and phenotypic analysis for the effects of ERG251 on drug susceptibility, fitness, filamentation and stress responses.

CFTR function is impaired in a subset of patients with pancreatitis carrying rare CFTR variants.

BACKGROUND: Many affected by pancreatitis harbor rare variants of the cystic fibrosis (CF) gene, CFTR, which encodes an epithelial chloride/bicarbonate channel. We investigated CFTR function and the effect of CFTR modulator drugs in pancreatitis patients carrying CFTR variants. METHODS: Next-generation sequencing was performed to identify CFTR variants. Sweat tests and nasal potential difference (NPD) assays were performed to assess CFTR function in vivo. Intestinal current measurement (ICM) was performed on rectal biopsies. Patient-derived intestinal epithelial monolayers were used to evaluate chloride and bicarbonate transport and the effects of a CFTR modulator combination: elexacaftor, tezacaftor and ivacaftor (ETI). RESULTS: Of 32 pancreatitis patients carrying CFTR variants, three had CF-causing mutations on both alleles and yielded CF-typical sweat test, NPD and ICM results. Fourteen subjects showed a more modest elevation in sweat chloride levels, including three that were provisionally diagnosed with CF. ICM indicated impaired CFTR function in nine out of 17 non-CF subjects tested. This group of nine included five carrying a wild type CFTR allele. In epithelial monolayers, a reduction in CFTR-dependent chloride transport was found in six out of 14 subjects tested, whereas bicarbonate secretion was reduced in only one individual. In epithelial monolayers of four of these six subjects, ETI improved CFTR function. CONCLUSIONS: CFTR function is impaired in a subset of pancreatitis patients carrying CFTR variants. Mutations outside the CFTR locus may contribute to the anion transport defect. Bioassays on patient-derived intestinal tissue and organoids can be used to detect such defects and to assess the effect of CFTR modulators.

Prospective evaluation of the surgical stabilization and outcome of canine tibial plateau fractures in three cases.

OBJECTIVE: To report the surgical approaches and stabilization of lateral and medial tibial plateau fractures (TPF), as well as the long-term outcome following repair. STUDY DESIGN: Prospective series of three client-owned dogs. ANIMALS: Three dogs. METHODS: For the two lateral TPF cases (Unger type 41-B1), the surgical approach included separation of the lateral collateral ligament and long digital extensor tendon. The lateral meniscus was elevated to allow visualization of the tibial surface and assess fracture reduction. The first case was repaired using two 2.0 mm lag screws (with washers). The second case sustained a lateral TPF, fibular fracture and concurrent tubercle of Gerdy fracture. Both tibial fractures were stabilized using two 2.0 mm lag screws with washers and two 0.9 mm Kirschner wires (K-wires). A third case, diagnosed with an Unger type 41-B2 medial TPF, was treated using 0.9 mm K-wires and 22-gauge tension band. RESULTS: There were no major complications noted. One minor complication occurred (screw yield two weeks postoperatively). By 8 weeks, all patients reached clinical union with good limb function. Owners were contacted 9-36 months postoperatively. LOAD scores and examinations were performed for two of three patients; the third patient was not contactable after relocating out of state. Both cases with completed questionnaires had a LOAD score of 5/52. CONCLUSION: Tibial plateau fractures are rare in canine patients. While challenging, they can be successfully managed using a combination of lag screws, K-wires, and tension band. CLINICAL SIGNIFICANCE: Surgical stabilization of TPF is feasible and may reduce the risk of meniscal injury.

Addressing misinformation about the Dietary Guidelines for Americans.

The Dietary Guidelines for Americans (DGA) provides science-based advice on dietary intake to promote health, reduce risk of chronic disease, and meet nutrient needs. It is jointly published by the United States Departments of Health and Human Services and Agriculture (USDA) every 5 y. As chronic diseases continue to rise to pervasive levels, helping the United States population follow the DGA is especially important for improving the health of our nation. The DGA is developed using a rigorous and transparent scientific process, and with the advice of an independent, external committee of leading scientists. Career federal nutrition scientists who manage the process ensure that the methods used to develop the DGA remain state of the art. Unfortunately, misinformation about the scientific basis, transparency, and relevance of the DGA for the United States population threatens its credibility. The main objective of this article is to correct this misinformation with factual information about the process used to develop the DGA. The DGA provides guidelines for the general public, and its primary audience includes policymakers and nutrition and health professionals who help individuals and families consume a healthy dietary pattern. Providing accurate information may bolster trust in the recommendations among these audiences while improving implementation across sectors to promote better adherence to the DGA, thereby improving diet quality among the United States population.

Impact of a pharmacy technician on an interprofessional antithrombotic stewardship program at an academic medical center.

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. PURPOSE: The need for monitoring and standardization of anticoagulation management has garnered the attention of national organizations, driving the implementation of antithrombotic stewardship programs (ASPs). Established ASPs have highlighted interdisciplinary collaboration between physicians, nurses, and pharmacists and demonstrated financial benefits and positive patient care outcomes. While pharmacy technicians are key members of the pharmacy profession, they are rarely utilized to expand clinical programs. The aim of this report is to describe the impact of adding a pharmacy technician to an ASP at an academic medical center. SUMMARY: The departments of pharmacy and quality at West Virginia University Hospitals (WVUH) developed a business plan and financially justified an ASP. The ASP was implemented in January 2022 and consisted of 2 full-time clinical pharmacist specialists, 1 full-time clinical pharmacy technician, 2 full-time clinical nurse specialists, and 1 part-time physician medical director. The clinical pharmacy technician's primary role was to review patients' sequential compression device (SCD) compliance and newly started oral anticoagulants prior to discharge. The clinical nurse specialists educated patients newly started on oral anticoagulants within 24 hours of discharge and triaged any postdischarge medication access issues. The medical director provided high-level program oversight and acted as a clinical consultant on complex patient cases. In the first 6 months after the program's implementation, the clinical pharmacy technician made 174 recommendations to the clinical pharmacist specialists regarding discharge transitions of care and assessed SCD compliance in 246 patients. Of the 246 patients assessed, 217 patients (88%) were deemed to be noncompliant. CONCLUSION: The pharmacy department at WVUH successfully justified and implemented an interprofessional ASP at an academic medical center, which is the first ASP to date to incorporate a clinical pharmacy technician.

Continuous glucose monitoring in adults with type 2 diabetes: a systematic review and meta-analysis.

AIMS/HYPOTHESIS: Continuous glucose monitoring (CGM) is increasingly used in the treatment of type 2 diabetes, but the effects on glycaemic control are unclear. The aim of this systematic review and meta-analysis is to provide a comprehensive overview of the effect of CGM on glycaemic control in adults with type 2 diabetes. METHODS: We performed a systematic review using Embase, MEDLINE, Web of Science, Scopus and ClinicalTrials.gov from inception until 2 May 2023. We included RCTs investigating real-time CGM (rtCGM) or intermittently scanned CGM (isCGM) compared with self-monitoring of blood glucose (SMBG) in adults with type 2 diabetes. Studies with an intervention duration <6 weeks or investigating professional CGM, a combination of CGM and additional glucose-lowering treatment strategies or GlucoWatch were not eligible. Change in HbA1c and the CGM metrics time in range (TIR), time below range (TBR), time above range (TAR) and glycaemic variability were extracted. We evaluated the risk of bias using the Cochrane risk-of-bias tool version 2. Data were synthesised by performing a meta-analysis. We also explored the effects of CGM on severe hypoglycaemia and micro- and macrovascular complications. RESULTS: We found 12 RCTs comprising 1248 participants, with eight investigating rtCGM and four isCGM. Compared with SMBG, CGM use (rtCGM or isCGM) led to a mean difference (MD) in HbA1c of -3.43 mmol/mol (-0.31%; 95% CI -4.75, -2.11, p<0.00001, I2=15%; moderate certainty). This effect was comparable in studies that included individuals using insulin with or without oral agents (MD -3.27 mmol/mol [-0.30%]; 95% CI -6.22, -0.31, p=0.03, I2=55%), and individuals using oral agents only (MD -3.22 mmol/mol [-0.29%]; 95% CI -5.39, -1.05, p=0.004, I2=0%). Use of rtCGM showed a trend towards a larger effect (MD -3.95 mmol/mol [-0.36%]; 95% CI -5.46 to -2.44, p<0.00001, I2=0%) than use of isCGM (MD -1.79 mmol/mol [-0.16%]; 95% CI -5.28, 1.69, p=0.31, I2=64%). CGM was also associated with an increase in TIR (+6.36%; 95% CI +2.48, +10.24, p=0.001, I2=9%) and a decrease in TBR (-0.66%; 95% CI -1.21, -0.12, p=0.02, I2=45%), TAR (-5.86%; 95% CI -10.88, -0.84, p=0.02, I2=37%) and glycaemic variability (-1.47%; 95% CI -2.94, -0.01, p=0.05, I2=0%). Three studies reported one or more events of severe hypoglycaemia and macrovascular complications. In comparison with SMBG, CGM use led to a non-statistically significant difference in the incidence of severe hypoglycaemia (RR 0.66, 95% CI 0.15, 3.00, p=0.57, I2=0%) and macrovascular complications (RR 1.54, 95% CI 0.42, 5.72, p=0.52, I2=29%). No trials reported data on microvascular complications. CONCLUSIONS/INTERPRETATION: CGM use compared with SMBG is associated with improvements in glycaemic control in adults with type 2 diabetes. However, all studies were open label. In addition, outcome data on incident severe hypoglycaemia and incident microvascular and macrovascular complications were scarce. REGISTRATION: This systematic review was registered on PROSPERO (ID CRD42023418005).

Pro-inflammatory cytokines stimulate CFTR-dependent anion secretion in pancreatic ductal epithelium.

BACKGROUND: Loss of CFTR-dependent anion and fluid secretion in the ducts of the exocrine pancreas is thought to contribute to the development of pancreatitis, but little is known about the impact of inflammation on ductal CFTR function. Here we used adult stem cell-derived cell cultures (organoids) obtained from porcine pancreas to evaluate the effects of pro-inflammatory cytokines on CFTR function. METHODS: Organoids were cultured from porcine pancreas and used to prepare ductal epithelial monolayers. Monolayers were characterized by immunocytochemistry. Epithelial bicarbonate and chloride secretion, and the effect of IL-1ß, IL-6, IFN-γ, and TNF-α on CFTR function was assessed by electrophysiology. RESULTS: Immunolocalization of ductal markers, including CFTR, keratin 7, and zonula occludens 1, demonstrated that organoid-derived cells formed a highly polarized epithelium. Stimulation by secretin or VIP triggered CFTR-dependent anion secretion across epithelial monolayers, whereas purinergic receptor stimulation by UTP, elicited CFTR-independent anion secretion. Most of the anion secretory response was attributable to bicarbonate transport. The combination of IL-1ß, IL-6, IFN-γ, and TNF-α markedly enhanced CFTR expression and anion secretion across ductal epithelial monolayers, whereas these cytokines had little effect when tested separately. Although TNF-α triggered apoptotic signaling, epithelial barrier function was not significantly affected by cytokine exposure. CONCLUSIONS: Pro-inflammatory cytokines enhance CFTR-dependent anion secretion across pancreatic ductal epithelium. We propose that up-regulation of CFTR in the early stages of the inflammatory response, may serve to promote the removal of pathogenic stimuli from the ductal tree, and limit tissue injury.

Deep neurological phenotyping in oculo-dento-digital syndrome.

OBJECTIVES: Oculodentodigital dysplasia (ODDD) is a rare autosomal dominant congenital malformation syndrome characterized by high penetrance and great phenotypic heterogeneity. Neurological manifestations are thought to occur in about one third of cases, but systematic studies are not available. We performed deep neurological phenotyping of 10 patients in one ODDD pedigree. METHODS: Retrospective case series. We analyzed in depth the neurological phenotype of a three-generation family segregating the heterozygous c.416 T > C, p.(Ile139Thr) in GJA1. Clinical and neuroradiological features were retrospectively evaluated. Brain MRI and visual evoked potentials were performed in 8 and 6 cases, respectively. RESULTS: Central nervous system manifestations occurred in 5 patients, the most common being isolated ataxia either in isolation or combined with spasticity. Furthermore, sphincteric disturbances (neurogenic bladder and fecal incontinence) were recognized as the first manifestation in most of the patients. Subclinical electrophysiological alteration of the optic pathway occurred in all the examined patients. Neuroimaging was significant for supratentorial hypomyelination pattern and hyperintense superior cerebellar peduncle in all examined patients. CONCLUSION: The neurological involvement in ODDD carriers is often missed but peculiar clinical and radiological patterns can be recognized. Deep neurological phenotyping is needed to help untangle ODDD syndrome complexity and find genotype-phenotype correlations.

Predictors of Skip Laminotomy for Placement of Paddle Leads for Spinal Cord Stimulation.

OBJECTIVES: Placement of a standard paddle lead for spinal cord stimulation (SCS) requires a laminotomy for positioning of the lead within the epidural space. During initial placement, an additional laminotomy or laminectomy, termed a "skip" laminotomy, may be necessary at a higher level to pass the lead to the appropriate midline position. Patient and radiographic factors that predict the need for a skip laminotomy have yet to be identified. MATERIALS AND METHODS: Participants who underwent SCS paddle placement at Albany Medical Center between 2016 and 2017 were identified. Operative reports were reviewed to identify the paddle type, level of initial laminotomy, target level, and skip laminotomy level. Preoperative thoracic magnetic resonance images (MRIs) were reviewed, and spinal canal diameter, interpedicular distance, and dorsal cerebral spinal fluid thickness were measured for each participant when available. RESULTS: A total of 106 participants underwent thoracic SCS placement. Of these, 97 had thoracic MRIs available for review. Thirty-eight participants required a skip laminotomy for placement of the paddle compared with 68 participants who did not. There was no significant difference in demographic features including age, sex, body mass index, and surgical history. Univariate analyses that suggested trends were selected for further analysis using binary logistic regression. Level of initial laminotomy (odds ratio [OR] = 1.51, p = 0.028), spinal canal diameter (OR = 0.71, p = 0.015), and dorsal cerebrospinal fluid thickness (OR = 0.61, p = 0.011) were correlated with skip laminotomy. Target level (OR = 1.27, p = 0.138) and time from trial (1.01, p = 0.117) suggested potential association. The multivariate regression was statistically significant, X2(10) = 28.02, p = 0.002. The model explained 38.3% of the variance (Nagelkerke R2) and predicted skip laminectomy correctly in 73.3% of cases. However, for the multivariate regression, only a decrease in spinal canal diameter (OR = 0.59, p = 0.041) was associated with a greater odds of skip laminotomy. CONCLUSIONS: This study aims to characterize the patient and radiographic factors that may predict the need to perform a skip laminotomy during the initial placement of SCS paddles. Here, we show that radiographic and anatomic variables, primarily spinal canal diameter, play an important role in predicting the need for a skip laminotomy. Furthermore, we suggest that target level for placement and level of initial laminotomy also may contribute. Further investigation of the predictive factors for performing a skip laminotomy would help optimize surgical planning and preoperative patient selection and counseling.

Understanding the Relationship Between Facial Nerve Branch Sacrifice and Selective Neurectomy Outcome.

Introduction: While there is great interest in selective neurectomy (SN) for patients with synkinesis, outcomes can be inconsistent. Objective: To examine the relationships between intraoperative facial nerve branch transection and both postoperative outcome and functional deficits. Methods: SN cases, with minimal follow-up of 4 months, were retrospectively identified between 2019 and 2021; outcome was assessed using FaCE instrument, eFACE and Emotrics. Correlations between intraoperative facial nerve branch preservation or transection, and functional outcome and new functional deficits were examined. Results: Fifty-six cases were performed: 88% were females, and median age was 53 years (range 11-81). Mean follow-up was 19.5 months (range 4-42). Oral commissure excursion improved in patients where all smile branches were preserved, no vertical vector smile branches were transected, and more than three smile antagonist branches were transected. A linear trend between smile antagonist branch sacrifice and favorable smile outcome was found. Lower lip movement was improved in patients in whom more than half of the identified lower lip branches were transected. Thirty percent of patients experienced untoward postoperative functional deficits, from which 47% recovered with interventions. Conclusions: Several correlations between SN intra-operative decisions and outcome were identified; new or worsening functional deficit rate can be high. However, chemodenervation or fillers can help diminish these deficits.

Favorable Outcome Perception in Facial Selective Neurectomy.

OBJECTIVE: Facial selective neurectomy (SN) improves facial function by denervation of muscles antagonistic to the smile in nonflaccid facial paralysis (NFFP) patients. This study aims to assess whether and which objective facial function metrics affect favorable SN outcome in NFFP patients, as perceived by facial nerve (FN) practitioners. STUDY DESIGN: Retrospective cohort study. SETTING: NFFP patients who underwent SN at the facial nerve center. METHODS: Standardized preoperative and postoperative facial photographs of patients undergoing SN were analyzed using clinician-graded measures (eFACE) and automated facial measurement (Emotrics). Favorable outcome was ranked subjectively by 3 independent FN practitioners. Correlations between objective metrics and favorable subjective outcome were examined. RESULTS: Fifty-eight SN cases were included. Oral commissure excursion with smile, interlabial distance, and lower lip movement were all considered statistically significantly important for favorable outcome perception. Each +1 mm of smile excursion increases the odds of a favorable outcome by 75.4% (odds ratio [OR]: 1.754). Each +1 mm of interlabial distance asymmetry decreases the odds of a favorable outcome by 24.7% (OR: 0.753). Each +1-point change in lower lip movement eFACE score increases the odds of a favorable outcome by 2.7% (OR: 1.027). CONCLUSION: Several smile metrics contribute to favorable SN outcome perception among FN practitioners. Smile excursion, interlabial distance, and lower lip movement were significant predictors of success. These observations may be extrapolated to other facial reanimation interventions and serve surgeons and patients during counseling and expectation management, and during surgery.

Effects of Inclusion of Food Purchase Restrictions and Incentives in a Food Benefit Program on Diet Quality and Food Purchasing: Results From a Randomized Trial.

BACKGROUND: There is interest in reshaping the Supplemental Nutrition Assistance Program (SNAP) to better support family nutrition. OBJECTIVE: The Grocery Assistance Program Study (GAPS) for Families evaluated the effects of prohibiting using program funds for the purchase of certain sugary foods on the nutritional quality of foods purchased and consumed by program participants. DESIGN: A randomized experimental trial was carried out with participants randomized to one of three food benefit conditions. Baseline and follow-up measures collected included interviewer-administered 24-hour dietary recalls, food purchase receipts, food security, height, and weight. PARTICIPANT/SETTING: Adult-child dyads in households eligible for SNAP but currently not enrolled were recruited from the Minneapolis/St Paul MN metropolitan area from May of 2018 through May of 2019. A total of 293 adult-child dyads received the intervention as allocated. Of these dyads, 233 adults completed follow-up measures and met criteria for inclusion in the analytic sample, resulting in an attrition rate of 20.5%. A total of 224 children completed follow-up measures and met criteria for inclusion in the analytic sample, resulting in an attrition rate of 23.5%. INTERVENTION: Participants were randomized to 1 of 3 conditions: restriction (not allowed to buy sugar-sweetened beverages [SSB], sweet baked goods, or candy with program funds); restriction paired with incentive (30% incentive for fruits and vegetables [FV] purchased with funds); and control (funds provided with no restrictions or incentives). Funds were provided on a 4-week cycle for 20 weeks via a study-provided debit card. MAIN OUTCOME MEASURES: The primary outcome was the Healthy Eating Index (HEI)-2015 total score. Additional outcomes included selected HEI-2015 component scores; energy intake; food security; body weight; and purchasing of SSB, sweet baked goods, candies, fruits, and vegetables. STATISTICAL ANALYSIS: Linear regression analyses were conducted with change in the outcome regressed on treatment condition for the primary outcome analyses. RESULTS: No differences were observed between conditions in change in the nutrition and food security measures examined. Purchases of SSB and sweet baked goods and candies significantly differed by experimental condition. Purchase of restricted foods was lower at follow-up in the restriction and restriction paired with incentive conditions compared with the control condition. For example, spending on SSB at follow-up was significantly lower in the restriction ($2.66/week) and restriction paired with incentive ($2.06/week) conditions in comparison with control condition ($4.44/week) (P < 0.0003 and P < 0.0001, respectively). CONCLUSIONS: This study failed to find evidence in support of prohibiting the purchase of sugary foods with food program funds as a strategy to improve program participant nutrition, even when paired with an FV incentive. Research carried out in the context of the SNAP program is needed for a more robust evidence base.

Pre-Operative Factors May Predict Outcome in Selective Neurectomy for Synkinesis.

Background: While there has been great interest in offering selective neurectomy (SN) to patients with nonflaccid facial palsy (NFFP), postoperative outcomes are inconsistent. Objective: To assess overall SN outcome in NFFP patients and to examine correlation between preoperative factors and SN outcome. Methods: SN cases were retrospectively identified between 2019 and 2021. Patient factors and facial function were assessed using chart review, the Facial Clinimetric Evaluation (FaCE), the electronic clinician-graded facial function tool (eFACE), and an automated computer-aided facial assessment tool (Emotrics). Correlations between preoperative factors and patients outcome were established. Results: Fifty-eight SN cases were performed; 88% were females, and median age was 53 years (range 11-81). Outcome assessment was 8 months on average (1-24 months). Postoperatively, multiple eFACE and Emotrics parameters improved significantly, including ocular, perioral, and synkinesis metrics. In preoperative factors assessment, age >50, facial palsy (FP) duration >2 years, poor preoperative facial function, and nontrauma etiology all correlated with greater improvements compared with younger patients, those with shorter duration facial palsy, trauma etiology, and better preoperative facial function. Conclusions: SN can significantly improve facial function; we have identified several preoperative factors that correlated to outcome.

Effectiveness of systemic treatments on pruritus associated with atopic dermatitis: A systematic review in pediatric patients.

BACKGROUND/OBJECTIVES: Itch is one of the hallmarks of atopic dermatitis (AD), which has a significant impact on the quality of life of pediatric patients with AD and their caregivers. We aimed to conduct a systematic review and meta-analysis to evaluate the antipruritic effects of systemic AD treatments in pediatric patients with AD. METHODS: PubMed, EMBASE, Cochrane, and Web of Science databases were searched, including studies providing original data on the effects of systemic treatment on pruritus in pediatric patients (<18 years) with AD. Placebo-controlled trials reporting a Peak Pruritus Numerical Rating Scale 4 (PP-NRS4) response were included in a meta-analysis. RESULTS: A total of 30 studies were included, with most evidence available for dupilumab. Overall, marked improvements of pruritus (50% or greater reduction in pruritus outcome measurements) were found for treatment with cyclosporin A (2-16 years), dupilumab (6 months-17 years), abrocitinib, and upadacitinib (both 12 and 17 years). Nemolizumab (12-17 years) may be promising in reducing pruritus in pediatric patients; however, data are limited. Only five randomized controlled trials could be included in our meta-analysis, in which dupilumab, abrocitinib, and upadacitinib showed a significantly higher probability of achieving a PP-NRS4 response compared with placebo. Our study was limited by a lack of homogeneity of included studies. CONCLUSIONS: Cyclosporin A, dupilumab, abrocitinib, and upadacitinib are all effective in decreasing pruritus and, therefore, in improving the quality of life in children with AD. As more systemic treatments for AD become available, it will be imperative to incorporate patient-oriented treatment goals such as reduction of pruritus into therapeutic decision-making.

Does supercharging with cross-face nerve graft enhance smile in non-flaccid facial paralysis patients undergoing selective neurectomy?

BACKGROUND: Cross face nerve grafting (CFNG) is a well-established nerve transfer technique in facial reanimation; however, no study has assessed outcome of supercharging the smile with CFNG in patients with synkinesis. The goal of this study was to examine the smile outcome in non-flaccid facial paralysis (NFFP) patients after supercharging with CFNG during selective neurectomy. METHODS: NFFP patients who underwent CFNG with end-to-side coaptation to a smile branch on the paralyzed side during selective neurectomy were retrospectively identified and their charts were reviewed. Pre-operative and post-operative facial function was assessed with the electronic clinician-graded facial function tool (eFACE), and an automated computer-aided facial assessment tool (Emotrics). Smile metrics were compared pre-operatively, in early post-operative time (EPO, <6 months), and late post-operative time (LPO, >9 months) when CFNG contribution would be expected. RESULTS: Thirteen cases were performed between June 2019 and December 2021. No objective smile metrics improved following supercharging with CFNG. Oral commissure excursion improved by 1.23 points in eFACE (p = .812), and by 0.84 in Emotrtics (p = .187) from EPO to LPO. EFACE dynamic score was improved by 0.08 points from EPO to LPO (p = .969). CONCLUSIONS: Using CFNG for supercharging the smile during selective neurectomy in NFFP patients may not enhance smile. Longer term results following supercharging and long term natural history of selective neurectomy should be assessed.

Vasodilators activate the anion channel TMEM16A in endothelial cells to reduce blood pressure.

Systemic blood pressure is acutely controlled by total peripheral resistance as determined by the diameter of small arteries and arterioles, the contractility of which is regulated by endothelial cells lining the lumen of blood vessels. We investigated the physiological functions of the chloride (Cl-) channel TMEM16A in endothelial cells. TMEM16A channels generated calcium (Ca2+)-activated Cl- currents in endothelial cells from control (TMEM16Afl/fl) mice that were absent in those from mice with tamoxifen-inducible, endothelial cell-specific knockout of TMEM16A (TMEM16A ecKO). TMEM16A currents in endothelial cells were activated by the muscarinic receptor agonist acetylcholine and an agonist of the Ca2+ channel TRPV4, which localized in nanoscale proximity with TMEM16A as assessed by single-molecule localization imaging of endothelial cells. Acetylcholine stimulated TMEM16A currents by activating Ca2+ influx through surface TRPV4 channels without altering the nanoscale properties of TMEM16A and TRPV4 surface clusters or their colocalization. In pressurized arteries, activation of TMEM16A channels in endothelial cells induced by acetylcholine; TRPV4 channel stimulation; or intraluminal ATP, another vasodilator, produced hyperpolarization and dilation. Furthermore, deficiency of TMEM16A channels in endothelial cells resulted in increased systemic blood pressure in conscious mice. These data indicate that vasodilators stimulate TRPV4 channels, leading to Ca2+-dependent activation of nearby TMEM16A channels in endothelial cells to produce arterial hyperpolarization, vasodilation, and reduced blood pressure. Thus, TMEM16A is an anion channel in endothelial cells that regulates arterial contractility and blood pressure.

Perinatal Outcomes at Rural Hospitals That Participated in the Rural Surgical and Obstetrical Networks (RSON) of British Columbia (2016-2021).

BACKGROUND: The goal of the Rural Surgical and Obstetrical Networks (RSON) of British Columbia was to support safe and appropriate surgery, operative birth, and perinatal care closer to home for rural communities. Family physicians with enhanced obstetrical and/or surgical skills provide cesarean delivery and family practice anesthetists manage anesthesia for labour pain and operative births at RSON-supported hospitals, with the involvement of a local specialist at one site. OBJECTIVES: The objectives of the study were to: (1) compare perinatal outcomes at hospitals participating in the RSON initiative with outcomes at referral hospitals and (2) examine temporal changes in the proportion of childbearing people who resided in RSON communities and gave birth locally. METHODS: Poisson regression analysis was used to model the effect of hospital type (RSON vs. referral) on perinatal outcomes. We restricted the analysis to singleton births and controlled for differences in maternal characteristics, obstetric history, and pregnancy complications. RESULTS: Childbearing people who gave birth at RSON-supported hospitals (n = 3498) had a 10% lower incidence of adverse maternal-newborn outcomes compared to those who gave birth at referral hospitals (n = 14 772), after controlling for referral bias. We found a small increase (3.2 %) in the proportion of local births over the study period. CONCLUSION: Findings provide evidence that childbearing people can safely give birth at smaller rural hospitals in British Columbia and that investments in rural hospitals contribute to service stability. Stabilizing local birth services in rural communities benefits the whole region because it reduces surgical overload in regional referral centres.