HDAC6 inhibition as a mechanism to prevent neurodegeneration in the mSOD1G93A mouse model of ALS.

The loss of upper and lower motor neurons, and their axons is central to the loss of motor function and death in amyotrophic lateral sclerosis (ALS). Due to the diverse range of genetic and environmental factors that contribute to the pathogenesis of ALS, there have been difficulties in developing effective therapies for ALS. One emerging dichotomy is that protection of the neuronal cell soma does not prevent axonal vulnerability and degeneration, suggesting the need for targeted therapeutics to prevent axon degeneration. Post-translational modifications of protein acetylation can alter the function, stability and half-life of individual proteins, and can be enzymatically modified by histone acetyltransferases (HATs) and histone deacetyltransferases (HDACs), which add, or remove acetyl groups, respectively. Maintenance of post-translational microtubule acetylation has been suggested as a mechanism to stabilize axons, prevent axonal loss and neurodegeneration in ALS. This study used an orally dosed potent HDAC6 inhibitor, ACY-738, prevent deacetylation and stabilize microtubules in the mSOD1G93A mouse model of ALS. Co-treatment with riluzole was performed to determine any effects or drug interactions and potentially enhance preclinical research translation. This study shows ACY-738 treatment increased acetylation of microtubules in the spinal cord of mSOD1G93A mice, reduced lower motor neuron degeneration in female mice, ameliorated reduction in peripheral nerve axon puncta size, but did not prevent overt motor function decline. The current study also shows peripheral nerve axon puncta size to be partially restored after treatment with riluzole and highlights the importance of co-treatment to measure the potential effects of therapeutics in ALS.

Comparing the efficacy and safety of endovascular therapy versus surgical revascularization for critical limb-threatening ischemia: A systematic review and Meta-analysis.

INTRODUCTION: Critical limb-threatening ischemia (CLTI) is a severe manifestation of peripheral artery disease (PAD) that can lead to limb amputation and significantly reduce quality of life. In addition to guideline-directed medical therapy (GDMT), endovascular therapy and surgical revascularization are the two revascularization options for CLTI. In recent years, there has been an ongoing debate about the best approach for CLTI patients. The purpose of this meta-analysis is to examine the current evidence and compare the clinical outcomes of endovascular therapy and surgical revascularization for CLTI. METHODS: We conducted a systematic search of electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) for studies comparing the outcomes of endovascular therapy versus surgery in patients with CLTI. The primary outcomes were major adverse limb events (MALE) and major adverse cardiovascular events (MACE), while secondary outcomes included risk of bleeding, wound complications, readmission, unplanned reoperation, acute renal failure, and length of hospital stay. Pooled data was analyzed using the fixed-effect model or the random-effect model in Review Manager 5.3. The Newcastle-Ottawa Scale and Cochrane risk of bias assessment tool were used to assess the bias of included studies. RESULTS: A total of 16 studies (47,609 patients) were included in this meta-analysis. The overall effect favors surgery over endovascular intervention in terms of MALE [odds ratio (OR) 1.13, 95% CI (1.01-1.28), P = 0.04]. Endovascular therapy is associated with lower MACE rates compared to surgery [OR 0.62, 95% CI (0.51-0.76), P < 0.00001]. Furthermore, the risk of bleeding, wound complications, readmission, unplanned reoperation, acute renal failure as well as the length of hospital stay was lower for endovascular intervention. Finally, there was no statistically significant difference in 30-day mortality between the two groups [OR 0.94, 95% CI 0.79-1.12, P = 0.52; Fig. 3i], and the pooled studies were homogeneous [P = 0.39; I2 = 5%]. CONCLUSION: Surgery may be the preferred treatment option for CLTI patients, as it is associated with a lower risk of MALE than endovascular therapy. However, endovascular therapy may be associated with a lower risk of MACE and lower rates of bleeding, wound complications, readmission, unplanned reoperation, acute renal failure, and shorter hospital stays. There was no statistically significant difference in 30-day mortality between the two groups. Ultimately, the decision to use endovascular therapy or surgery as the primary treatment strategy should be based on a multi-disciplinary team approach with careful consideration of patient characteristics and anatomy.

Acute Effect of E-Cigarette Inhalation on Mucociliary Clearance in E-Cigarette Users.

Background: Recent studies show e-cigarette (EC) users have increased rates of chronic bronchitic symptoms that may be associated with depressed mucociliary clearance (MCC). Little is known about the acute or chronic effects of EC inhalation on in vivo MCC. Methods: In vivo MCC was measured in young adult vapers (n = 5 males, mean age = 21) after controlled inhalation of a radiolabeled (Tc99m sulfur colloid) aerosol. Whole-lung clearance of radiolabeled deposited particles was measured over a 90-minute period for baseline MCC and associated with controlled periodic vaping over the first 60 minutes of MCC measurements. The vaping challenge was administered from a fourth generation box mod EC containing unflavored e-liquid (65% propylene glycol/35% vegetable glycerin, 3 mg/mL freebase nicotine). The challenge was administered at the start of each 10-minute interval of MCC measurements and consisted of 1 puff every 30 seconds for 5 minutes (i.e., 10 puffs for each 10-minute period for a total of 60 puffs during the initial 60 minutes of MCC measurements). Results: Compared with baseline, peripheral lung average clearance (%) over the 90 minutes of MCC measures was enhanced, associated with EC challenge, 12 (±6) versus 24 (±6), respectively (p < 0.05 by Wilcoxon signed-rank test). Conclusions: Acute enhancement of in vivo MCC during EC challenge is contrary to recent studies showing nicotine-associated slowing of ciliary beat and mucus transport at higher nicotine levels than those used here. However, our findings are consistent with an acute increase in fluid volume and mucin secretion to the bronchial airway surface that is likely short lived. Research reported in this publication was supported by the National Institutes of Health R01HL139369 and registered with ClinicalTrials.gov (NCT03700892).

Satellite-based estimation of total suspended solids and chlorophyll-a concentrations for the Gold Coast Broadwater, Australia.

Satellite retrieval of total suspended solids (TSS) and chlorophyll-a (chl-a) was performed for the Gold Coast Broadwater, a micro-tidal estuarine lagoon draining a highly developed urban catchment area with complex and competing land uses. Due to the different water quality properties of the rivers and creeks draining into the Broadwater, sampling sites were grouped in clusters, with cluster-specific empirical/semi-empirical prediction models developed and validated with a leave-one-out cross validation approach for robustness. For unsampled locations, a weighted-average approach, based on their proximity to sampled sites, was developed. Confidence intervals were also generated, with a bootstrapping approach and visualised through maps. Models yielded varying accuracies (R2 = 0.40-0.75). Results show that, for the most significant poor water quality event in the dataset, caused by summer rainfall events, elevated TSS concentrations originated in the northern rivers, slowly spreading southward. Conversely, high chl-a concentrations were first recorded in the southernmost regions of the Broadwater.

The effect of discontinuing hypertonic saline or dornase alfa on mucociliary clearance in elexacaftor/tezacaftor/ivacaftor treated people with cystic fibrosis: The SIMPLIFY-MCC Study.

Many people with CF (pwCF) desire a reduction in inhaled treatment burden after initiation of elexacaftor/tezacaftor/ivacaftor. The randomized, open-label SIMPLIFY study showed that discontinuing hypertonic saline (HS) or dornase alfa (DA) was non-inferior to continuation of each treatment with respect to change in lung function over a 6-week period. In this SIMPLIFY substudy, we used gamma scintigraphy to determine whether discontinuation of either HS or DA was associated with deterioration in the rate of in vivo mucociliary clearance (MCC) in participants ≥12 years of age. While no significant differences in MCC endpoints were associated with HS discontinuation, significant improvement in whole and peripheral lung MCC was observed after discontinuing DA. These results suggest that pwCF on ETI with mild lung disease do not experience a subclinical deterioration in MCC that could later impact health outcomes after discontinuing HS, and in fact may benefit from improved MCC after stopping DA treatment.

Effect of elexacaftor/tezacaftor/ivacaftor on mucus and mucociliary clearance in cystic fibrosis.

BACKGROUND: The cystic fibrosis transmembrane conductance regulator (CFTR) modulator elexacaftor/tezacaftor/ivacaftor (E/T/I) is highly effective clinically for those with at least one F508del-CFTR allele. The effects of E/T/I on mucociliary clearance (MCC) and sputum properties are unknown. We, therefore, sought to characterize the effects of E/T/I on in vivo MCC and sputum characteristics hypothesized to impact mucus transport. METHODS: Forty-four participants ≥12 years of age were enrolled into this prospective, observational trial prior to initiation of E/T/I and had baseline measurement of MCC and characterization of induced sputum and exhaled breath condensate (EBC) samples. Study procedures were repeated after 1 month of E/T/I treatment. RESULTS: Average age was 27.7 years with baseline forced expiratory volume in 1 second (FEV1) of 78.2 % predicted. 52 % of subjects had previously been treated with a 2-drug CFTR modulator combination. The average whole lung MCC rate measured over 60 min (WLAveClr60) significantly improved from baseline to post-E/T/I (14.8 vs. 22.8 %; p = 0.0002), as did other MCC indices. Sputum% solids also improved (modeled mean 3.4 vs. 2.2 %; p<0.0001), whereas non-significant reductions in sputum macrorheology (G', G") were observed. No meaningful changes in exhaled breath condensate endpoints (sialic acid:urea ratio, pH) were observed. CONCLUSIONS: E/T/I improved the hydration of respiratory secretions (% solids) and markedly accelerated MCC. These data confirm the link between CFTR function, mucus solid content, and MCC and help to define the utility of MCC and mucus-related bioassays in future efforts to restore CFTR function in all people with CF.

Which should you choose for post operative atrial fibrillation, carvedilol or metoprolol? A systemic review and meta-analysis.

BACKGROUND: Postoperative atrial fibrillation (POAF) is the most common arrhythmic complication following cardiac surgery. Current guidelines suggest beta-blockers for the prevention of POAF. In comparing metoprolol succinate with carvedilol, the later has sparked interest in its usage as an important medication for POAF prevention. METHODS: We considered randomized controlled studies (RCTs) and retrospective studies that evaluated the efficacy of carvedilol versus metoprolol for the prevention of POAF. After literature search, data extraction, and quality evaluation, pooled data were analyzed using either the fixed-effect or random-effect model using Review Manager 5.3. The Cochrane risk of bias tool was used to assess the bias of included studies. The incidence of POAF was the primary endpoint, while mortality rate and bradycardia were secondary outcomes. RESULTS: In meta-analysis 5 RCTs and 2 retrospective studies with a total of 1000 patients were included. The overall effect did not favor the carvedilol over metoprolol groups in terms of mortality rate [risk ratio 0.45, 95 % CI (0.1-1.97), P=0.29] or incidence of bradycardia [risk ratio 0.63, 95 % CI (0.32-1.23), P=0.17]. However, the incidence of POAF was lower in patients who received carvedilol compared to metoprolol [risk ratio 0.54, 95 % CI (0.42-0.71), P < 0.00001]. CONCLUSION: In patients undergoing cardiac surgery, carvedilol may minimize the occurrence of POAF more effectively than metoprolol. To definitively establish the efficacy of carvedilol compared to metoprolol and other beta-blockers in the prevention of POAF, a large-scale, well-designed randomized controlled trials are required.

Effect of Remotely Supervised Weight Loss and Exercise Training Versus Lifestyle Counseling on Cardiovascular Risk and Clinical Outcomes in Older Adults With Rheumatoid Arthritis: A Randomized Controlled Trial.

OBJECTIVE: To compare a remotely supervised weight loss and exercise intervention to lifestyle counseling for effects on cardiovascular disease risk, disease activity, and patient-reported outcomes in older patients with rheumatoid arthritis (RA) and overweight/obesity. METHODS: Twenty older (60-80 years), previously sedentary participants with seropositive RA and overweight/obesity were randomized to 16 weeks of either Supervised Weight loss and Exercise Training (SWET) or Counseling Health As Treatment (CHAT). The SWET group completed aerobic training (150 minutes/week moderate-to-vigorous intensity), resistance training (two days/week), and a hypocaloric diet (7% weight loss goal). The CHAT control group completed two lifestyle counseling sessions followed by monthly check-ins. The primary outcome was a composite metabolic syndrome z-score (MSSc) derived from fasting glucose, triglycerides, high density lipoprotein-cholesterol, minimal waist circumference, and mean arterial pressure. Secondary outcomes included RA disease activity and patient-reported outcomes. RESULTS: Both groups improved MSSc (absolute change -1.67 ± 0.64 in SWET; -1.34 ± 1.30 in CHAT; P < 0.01 for both groups) with no between-group difference. Compared with CHAT, SWET significantly improved body weight, fat mass, Disease Activity Score-28 C-reactive protein, and patient-reported physical health, physical function, mental health, and fatigue (P < 0.04 for all between-group comparisons). Based on canonical correlations for fat mass, cardiorespiratory fitness, and leg strength, component-specific effects were strongest for (1) weight loss improving MSSc, physical health, and mental health; (2) aerobic training improving physical function and fatigue; and (3) resistance training improving Disease Activity Score-28 C-reactive protein. CONCLUSION: In older patients with RA and overweight/obesity, 16 weeks of remotely supervised weight loss, aerobic training, and resistance training improve cardiometabolic health, patient-reported outcomes, and disease activity. Less intensive lifestyle counseling similarly improves cardiovascular disease risk profiles, suggesting an important role for integrative interventions in the routine clinical care of this at-risk RA population.

Exercise Therapy in the Management of Peripheral Arterial Disease.

The incidence and prevalence of peripheral artery disease (PAD) are increasing globally and have a marked economic burden in the United States. The American Heart Association/American College of Cardiology guidelines recommend exercise therapy as a Class 1A, but its utilization remains suboptimal. This state-of-the-art review aims to provide a comprehensive review of the most updated information available on PAD, along with its risk factors, management options, outcomes, economic burden, and the role of exercise therapy in managing PAD.

Evolving microbial patterns of acute mastoiditis in pediatric patients undergoing mastoidectomy.

OBJECTIVE: To investigate the microbial patterns and clinical outcomes of pediatric patients undergoing mastoidectomy for acute coalescent mastoiditis and to identify factors associated with poor outcomes and/or prolonged treatment. STUDY DESIGN: Monocentric retrospective cohort study. SETTING: Tertiary referral pediatric hospital in Indiana. METHODS: By cross-referencing database data from the Pediatric Health Information System (PHIS) querying for all inpatient stays (patients younger than eighteen) with a diagnostic code of mastoiditis between January 1st, 2010 and August 31, 2019, and the electronic health record (Cerner) for Riley Hospital for Children, 46 patients with mastoidectomy were included. A two-tailed T-test was used to evaluate continuous parametric data. Statistical significance was determined as P < 0.05. For continuous variables, data was analyzed using continuous logistic regression. A criteria of p > 0.1 was used for inclusion in the multivariate regression. RESULTS: Inclusion criteria was met by 46 patients. From 2010 to 2019, S. pyogenes and S. pneumoniae were the most common bacteria, each isolated in 11 of 42 bacterial isolates (26.2%). There was no growth in 35.4% (17/48) of intra-operative wound cultures. On univariate analysis, patients with negative cultures had longer length of hospital stay (LOS) (7.7 days [6.5] vs. 4.3 [2.8]; p = 0.018) as well as higher rates of PICC (peripherally inserted central catheter) placement (53.3% vs. 19.4%; p = 0.021). There was a statistically significant difference in terms of gender (p = 0.021), with 15 males and 16 females in the positive culture cohort and 13 males and 2 females in the negative culture cohort. On multivariate analysis, which included gender, PICC placement, both intracranial and extracranial complications, duration of antibiotics, and LOS, female gender was the only significant predictor of positive culture status (p = 0.039). CONCLUSION: S. pyogenes and S. pneumoniae were the predominant etiologic agents in acute coalescent mastoiditis between 2010 and 2019, and negative wound cultures were associated with worse clinical outcomes.

Enterobacter cloacae infection characteristics and outcomes in battlefield trauma patients.

Enterobacter cloacae is a Gram-negative rod with multidrug-resistant potential due to chromosomally-induced AmpC ß-lactamase. We evaluated characteristics, antibiotic utilization, and outcomes associated with battlefield-related E. cloacae infections (2009-2014). Single initial and serial E. cloacae isolates (≥24 hours from initial isolate from any site) associated with a clinical infection were examined. Susceptibility profiles of initial isolates in the serial isolation group were contrasted against last isolate recovered. Characteristics of 112 patients with E. cloacae infections (63 [56%] with single initial isolation; 49 [44%] with serial isolation) were compared to 509 patients with bacterial infections not attributed to E. cloacae. E. cloacae patients sustained more blast trauma (78%) compared to non-E. cloacae infections patients (75%; p<0.001); however, injury severity scores were comparable (median of 34.5 and 33, respectively; p = 0.334). Patients with E. cloacae infections had greater shock indices (median 1.07 vs 0.92; p = 0.005) and required more initial blood products (15 vs. 14 units; p = 0.032) compared to patients with non-E. cloacae infections. Although E. cloacae patients had less intensive care unit admissions (80% vs. 90% with non-E. cloacae infection patients; p = 0.007), they did have more operating room visits (5 vs. 4; p = 0.001), longer duration of antibiotic therapy (43.5 vs. 34 days; p<0.001), and lengthier hospitalizations (57 vs. 44 days; p<0.001). Patients with serial E. cloacae had isolation of infecting isolates sooner than patients with single initial E. cloacae (median of 5 vs. 8 days post-injury; p = 0.046); however, outcomes were not significantly different between the groups. Statistically significant resistance to individual antibiotics did not develop between initial and last isolates in the serial isolation group. Despite current combat care and surgical prophylaxis guidelines recommending upfront provision of AmpC-inducing antibiotics, clinical outcomes did not differ nor did significant antibiotic resistance develop in patients who experienced serial isolation of E. cloacae versus single initial isolation.

Updated consensus guidelines on the management of Phelan-McDermid syndrome.

Phelan-McDermid syndrome (PMS) is a genetic condition caused by SHANK3 haploinsufficiency and characterized by a wide range of neurodevelopmental and systemic manifestations. The first practice parameters for assessment and monitoring in individuals with PMS were published in 2014; recently, knowledge about PMS has grown significantly based on data from longitudinal phenotyping studies and large-scale genotype-phenotype investigations. The objective of these updated clinical management guidelines was to: (1) reflect the latest in knowledge in PMS and (2) provide guidance for clinicians, researchers, and the general community. A taskforce was established with clinical experts in PMS and representatives from the parent community. Experts joined subgroups based on their areas of specialty, including genetics, neurology, neurodevelopment, gastroenterology, primary care, physiatry, nephrology, endocrinology, cardiology, gynecology, and dentistry. Taskforce members convened regularly between 2021 and 2022 and produced specialty-specific guidelines based on iterative feedback and discussion. Taskforce leaders then established consensus within their respective specialty group and harmonized the guidelines. The knowledge gained over the past decade allows for improved guidelines to assess and monitor individuals with PMS. Since there is limited evidence specific to PMS, intervention mostly follows general guidelines for treating individuals with developmental disorders. Significant evidence has been amassed to guide the management of comorbid neuropsychiatric conditions in PMS, albeit mainly from caregiver report and the experience of clinical experts. These updated consensus guidelines on the management of PMS represent an advance for the field and will improve care in the community. Several areas for future research are also highlighted and will contribute to subsequent updates with more refined and specific recommendations as new knowledge accumulates.

Penile Livedoid Vasculopathy: First Reported Case.

Livedoid vasculopathy is a thromboocclusive cutaneous vasculopathy manifested by livedoid changes, atrophie blanche, and ulceration. The pathogenesis is speculated to involve increasing coagulation or impaired thrombolysis leading to the occlusion of dermal blood vessels with fibrin thrombi. Livedoid vasculopathy is known to primarily affect the lower extremities. We report the first case of livedoid vasculopathy affecting the penis. A 60-year-old male was evaluated for a split urine stream with associated irritation and peeling of the skin of the glans penis. His penile ulcer continued to enlarge despite steroids and antibiotics. Due to diagnostic uncertainty, a biopsy was performed which revealed hyaline thrombi within the lumens of small vessels within the upper to mid dermis, fibrinoid material in the walls of these blood vessels and within the perivascular stroma with overlying and adjacent epidermal spongiosis, and mild perivascular lymphocytic infiltrate with a few scattered neutrophils most consistent with livedoid vasculitis. He was started on aspirin and pentoxifylline with limited improvement and was later started on apixaban with near-complete resolution in 6 months. Penile livedoid vasculopathy has not been previously reported in the English literature. Early diagnosis and treatment are imperative to limit morbidity.

Effects of exercise amount and intensity versus a combined exercise and lifestyle intervention on metabolic syndrome in adults with prediabetes: a STRRIDE-PD randomized trial.

The purpose of this secondary analysis was to determine what portion of the effects of a Diabetes Prevention Program-like intervention on metabolic syndrome (MetS) could be achieved with exercise alone, as well as to determine the relative importance of exercise intensity and amount to the total exercise effect on MetS. Sedentary, overweight adults with prediabetes were randomly assigned to one of four 6-month interventions: 1) low-amount/moderate-intensity (10 kcal/kg/week at 50% peak V˙O2); 2) high-amount/moderate-intensity (16 kcal/kg/week at 50% peak V˙O2); 3) high-amount/vigorous-intensity (16 kcal/kg/week at 75% peak V˙O2); or 4) diet (7% weight loss) plus low-amount/moderate-intensity (10 kcal/kg/week at 50% peak V˙O2). The primary outcome of this secondary analysis was change in the MetS z-score. A total of 130 participants had complete data for all five Adult Treatment Panel (ATP) III MetS criteria. The diet-and-exercise group statistically outperformed the MetS z-score and the ATP III score compared to the exercise alone group. Aerobic exercise alone achieved 24%-50% of the total effect of the combined diet-and-exercise intervention on the MetS score. Low-amount moderate-intensity exercise quantitatively performed equal to or better than the interventions of high-amount moderate-intensity or high-amount vigorous-intensity exercise in improving the MetS score. The combined diet-and-exercise intervention remains more efficacious in improving the MetS z-score. However, all three exercise interventions alone showed improvements in the MetS z-score, suggesting that a modest amount of moderate-intensity exercise is all that is required to achieve approximately half the effect of a diet-and-exercise intervention on the MetS. Clinical Trial Registration: clinicaltrials.gov, identifier NCT00962962.

Development of a Family-Centered Communication Tool for Kidney Health in Premature Infants: Qualitative Focus Group Study Using Human-Centered Design Methodology.

BACKGROUND: Premature infants are at increased risk of kidney-related complications, including acute kidney injury (AKI) and chronic kidney disease (CKD). The risk of CKD in prematurely born infants is underrecognized by health care teams and caregivers. Understanding how to communicate the risk of CKD to caregivers is essential for longitudinal clinical follow-up and adherence. OBJECTIVE: This study aimed to determine family caregiver attitudes toward kidney health and risk communication during a neonatal intensive care admission. We also sought to understand caregiver preferences for the communication of information surrounding the risk of CKD in premature infants. METHODS: We augmented standard qualitative group sessions with human-centered design methods to assess parent preferences and clinician perspectives. Caregivers recruited had a prematurely born child who spent time in the neonatal intensive care unit at Riley Hospital for Children in Indianapolis, Indiana, and experienced AKI or another kidney complication, which put them at risk for future CKD. We used a variety of specific design methods in these sessions, including card sorting, projective methods, experience mapping, and constructive methods. RESULTS: A total of 7 clinicians and 8 caregivers participated in 3 group sessions. Caregivers and clinicians readily acknowledged barriers to and drivers of long-term kidney monitoring as well as opportunities for communication of the risk of long-term kidney disease. Caregivers' primary concerns were for both the type and depth of information conveyed as well as the time at which it was communicated. Participants emphasized the importance of collaboration between the hospital care team and the primary care provider. Participant input was synthesized into several prototype concepts and, ultimately, into a rough prototype of a website and an informational flyer. CONCLUSIONS: Caregivers of premature infants are open to communication about kidney health during their neonatal admission. The next phase of this work will translate caregivers' preferences into family-centered communication tools and test their efficacy in the neonatal intensive care unit.

A novel method for the quantitative assessment of the fitted containment efficiency of face coverings.

BACKGROUND: Face masks reduce disease transmission by protecting the wearer from inhaled pathogens and reducing the emission of infectious aerosols. Although methods quantifying efficiency for wearer protection are established, current methods for assessing face mask containment efficiency rely on measurement of a low concentration of aerosols emitted from an infected or noninfected individual. METHODS: A small port enabled the introduction of 0.05 µm sodium chloride particles at a constant rate behind the mask worn by a study participant. A condensation particle counter monitored ambient particle numbers 60 cm in front of the participant over 3-minute periods of rest, speaking, and coughing. The containment efficiency (%) for each mask and procedure was calculated as follows: 100 × (1 - average ambient concentration with face covering worn/average ambient concentration with a sham face covering in place). The protection efficiency (%) was also measured using previously published methods. The probability of transmission (%) from infected to uninfected (a function of both the containment efficiency and the protection efficiency) was calculated as follows: {1 - (containment efficiency/100)}×{1 - (protection efficiency/100)}×100. RESULTS: The average containment efficiencies for each mask over all procedures and repeated measures were 94.6%, 60.9%, 38.8%, and 43.2%, respectively, for the N95 mask, the KN95 mask, the procedure face mask, and the gaiter. The corresponding protection efficiencies for each mask were 99.0%, 63.7%, 45.3%, and 24.2%, respectively. For example, the transmission probability for 1 infected and 1 uninfected individual in close proximity was ∼14.2% for KN95 masks, compared to 36%-39% when only 1 individual wore a KN95 mask. CONCLUSION: Overall, we detected a good correlation between the protection and containment that a face covering afforded to a wearer.

Cheilectomy Alone in Patients With Elevatus Yields Poor 5-Year Survival Rate.

This study was performed to evaluate the efficacy of the cheilectomy procedure for different degrees of elevatus. The study was Institutional Review Board approved and patients were evaluated retrospectively at Ascension St. John Hospital, St. John Surgery Center and St. John Macomb Township Surgery Center between 9/8/2012 and 1/8/2016. These were all performed by the same surgeon. The pre- and postoperative radiographs were analyzed and Seiberg's index was calculated. Charts were also reviewed, and demographic information was obtained. A telephone survey was performed, and Visual Analog Pain score and Foot and Ankle Ability Measure was obtained. Body mass index, age, calcaneal inclination angle, Seiberg's index, Foot and Ankle Ability Measure, and visual analog score were analyzed using chi-square test, bivariate regression analysis and independent t test. Seiberg's index had a statistically significant influence on 5-year survival rate for the cheilectomy procedure (p ≤ .05). For patients with Seiberg's index less than 0.20 cm demonstrated FAAM, and VAS p values .18 and .37 with 87.0% 5-year survival. Seiberg's index between 0.20 and 0.40 cm had FAAM and VAS scores with p values <.01 and .02 with 62.0% 5-year survival. Seiberg's index ≤0.40 cm p values <.01 and .55 with 5-year survival rate of 0.0%. Therefore, if Seiberg's index is greater than 0.20 cm based on this research a cheilectomy alone as a sole treatment is at greater risk of failure.

Utility of new image-derived biomarkers for autosomal dominant polycystic kidney disease prognosis using automated instance cyst segmentation.

New image-derived biomarkers for patients affected by autosomal dominant polycystic kidney disease are needed to improve current clinical management. The measurement of total kidney volume (TKV) provides critical information for clinicians to drive care decisions. However, patients with similar TKV may present with very different phenotypes, often requiring subjective decisions based on other factors (e.g., appearance of healthy kidney parenchyma, a few cysts contributing significantly to overall TKV, etc.). In this study, we describe a new technique to individually segment cysts and quantify biometric parameters including cyst volume, cyst number, parenchyma volume, and cyst parenchyma surface area. Using data from the Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) study the utility of these new parameters was explored, both quantitatively as well as visually. Total cyst number and cyst parenchyma surface area showed superior prediction of the slope of estimated glomerular filtration rate decline, kidney failure and chronic kidney disease stages 3A, 3B, and 4, compared to TKV. In addition, presentations such as a few large cysts contributing significantly to overall kidney volume were shown to be much better stratified in terms of outcome predictions. Thus, these new image biomarkers, which can be obtained automatically, will have great utility in future studies and clinical care for patients affected by autosomal dominant polycystic kidney disease.

Stratification of a Phelan-McDermid Syndrome Population Based on Their Response to Human Growth Hormone and Insulin-like Growth Factor.

Phelan-McDermid syndrome (PMS), caused by pathogenic variants in the SHANK3 gene or 22q13 deletions, is characterized by intellectual disability, autistic features, developmental delays, and neonatal hypotonia. Insulin-like growth factor 1 (IGF-1) and human growth hormone (hGH) have been shown to reverse neurobehavioral deficits in PMS. We assessed the metabolic profiling of 48 individuals with PMS and 50 controls and determined subpopulations by taking the top and bottom 25% of responders to hGH and IGF-1. A distinct metabolic profile for individuals with PMS showed a reduced ability to metabolize major energy sources and a higher metabolism of alternative energy sources. The analysis of the metabolic response to hGH or IGF-1 highlighted a major overlap between both high and low responders, validating the model and suggesting that the two growth factors share many target pathways. When we investigated the effect of hGH and IGF-1 on the metabolism of glucose, the correlation between the high-responder subgroups showed less similarity, whereas the low-responders were still relatively similar. Classification of individuals with PMS into subgroups based on responses to a compound can allow an investigation into pathogenic mechanisms, the identification of molecular biomarkers, an exploration of in vitro responses to candidate drugs, and eventually the selection of better candidates for clinical trials.

Multimodality annotated hepatocellular carcinoma data set including pre- and post-TACE with imaging segmentation.

Hepatocellular carcinoma (HCC) is the most common primary liver neoplasm, and its incidence has doubled over the past two decades owing to increasing risk factors. Despite surveillance, most HCC cases are diagnosed at advanced stages and can only be treated using transarterial chemo-embolization (TACE) or systemic therapy. TACE failure may occur with incidence reaching up to 60% of cases, leaving patients with a financial and emotional burden. Radiomics has emerged as a new tool capable of predicting tumor response to TACE from pre-procedural computed tomography (CT) studies. This data report defines the HCC-TACE data collection of confirmed HCC patients who underwent TACE and have pre- and post-procedure CT imaging studies and available treatment outcomes (time-to-progression and overall survival). Clinically curated segmentation of pre-procedural CT studies was done for the purpose of algorithm training for prediction and automatic liver tumor segmentation.