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Dr. Frederic E. Mohs significantly advanced the treatment of skin cancer with the development of Mohs micrographic surgery (MMS). His career was dedicated to improving patient outcomes through innovative surgical techniques. MMS involves the precise removal of skin cancer in a stepwise manner, with each layer examined microscopically to ensure the complete removal of cancerous cells. This method has become the preferred approach for treating complex and recurrent skin cancers, particularly in areas such as the face, ears, and hands, due to its tissue-sparing precision. The procedure's accuracy has led to high cure rates and low recurrence, solidifying its role in modern dermatologic oncology. This paper examines Mohs' life, the evolution of MMS, and its lasting influence on dermatologic surgery, addressing both the challenges and advancements within the field., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Brennan et al.)

We have made the compound 2O-BaPtO 3 by high-pressure, high-temperature synthesis, determined its structure, and tested its catalytic activity. Compounds of the same stoichiometry have been reported and tentatively identified as hexagonal perovskites, and although no structural model was ever established, 2O-BaPtO 3 is clearly different and, to the best of our knowledge, unique. It features continuous chains of face-sharing PtO 6 octahedra, like the well-known 2H hexagonal perovskite type, but with a staggered offset between the chains that breaks hexagonal symmetry and disrupts the close-packed array of A = Ba and X = O that is a defining characteristic of ABX 3 perovskites. We investigated this structure and its stability vs the conventional 2H form using X-ray and neutron diffraction, X-ray absorption spectroscopy, and ab initio calculations. Catalytic testing of 2O-BaPtO 3 showed that it is active for hydrogen evolution.

Objective: To correlate the surgical results of vocal fold mass excision with pre-operative existence of vocal fold paresis., Methods: Data were collected on 66 patients who underwent excision of benign vocal fold masses from 2015 to 2020. The pre- and post-operative strobovideolaryngoscopy (SVL) examinations for all patients included were evaluated blindly by three otolaryngologists using THE Voice-Vibratory Assessment with Laryngeal Imaging (VALI) Form for scar severity, mucosal wave, free edge contour, glottal closure, and phase closure. The success of mass excision surgery was determined based on the presence of the following criteria post-operatively: 1) improved mucosal wave motion 2) improved phase closure or glottic closure 3) improved free edge contour and 4) lack of worsening of vocal fold scar severity. Surgery was considered successful if 3 or 4 criteria were met, partially successful if 1 or 2 criteria were met, and unsuccessful if no criteria were met. The percent recruitment of the thyroarytenoid, posterior cricoarytenoid (PCA), and cricothyroid muscles were used evaluated the severity of paresis as mild (70-99% recruitment), moderate (40-60% recruitment), or severe (0-39% recruitment). VHI-10 scores were used as subjective measures of pre- and post-operative voice., Results: Sixty-six patients (26 male, 40 female) were included in this study, with a mean age of 37.25 ± 16.6 (range 18-78). Twelve patients had no evidence of VF paresis noted during the initial clinical evaluation; and 52 patients had paresis and had undergone laryngeal EMG. 81% of these patients had mild paresis, 12.8% had moderate paresis, and 5.8% had severe paresis. Based on pre- and post-operative strobovideolaryngoscopy, there was improvement in mucosal wave in 44.9% of cases, improvement of phase or glottic closure in 85.4% of cases, improved free edge contour in 95.5% of cases, and worsening of scar in 38.5% of cases. 39.6% of surgeries were fully successful, 33.3% of surgeries were partially successful, and 27.1% were not successful. There was a significant correlation between female gender and vocal fold paresis (P = 0.048). Paresis severity did not correlate with complete or partial surgical success (P = 0.956), pre-operative VHI-10 scores (P = 0.519), post-operative VHI-10 scores (P = 0.563), or strobovideolaryngoscopy parameters. Unilateral and bilateral paresis did not correlate with any other parameter of surgical success (P >0.05)., Conclusion: This study suggests that there is no correlation between pre-operative vocal fold paresis and voice outcomes after mass excision surgery, that the majority of mass excision surgeries (72.9%) are successful based on improvement in stroboscopic parameters, and that the proportion of patients with moderate and severe paresis is consistent across all laryngeal nerves., (Copyright © 2021 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Temporal bones in some patients with Ménière disease have demonstrated small vestibular aqueducts; however, the prevalence and clinical importance of small vestibular aqueducts remain unclear in patients without Ménière disease. This study correlates the presence of a small vestibular aqueduct with cochleovestibular symptoms., Materials and Methods: Consecutive temporal bone CTs in adults from January to December 2020 were reviewed. The midpoint vestibular aqueduct size in the 45°-oblique Pöschl view was measured by 2 reviewers independently in 684 patients (1346 ears). Retrospective chart review for the clinical diagnosis of Ménière disease, the presence of cochleovestibular symptoms, and indications for CT was performed., Results: Fifty-two of 684 patients (7.6% of patients, 62/1346 ears) had small vestibular aqueducts. Twelve patients (15/1346 ears) had Ménière disease. Five of 12 patients with Ménière disease (5 ears) had a small vestibular aqueduct. There was a significant correlation between a small vestibular aqueduct and Ménière disease ( P < .001). There was no statistical difference between the small vestibular aqueduct cohort and the cohort with normal vestibular aqueducts (0.3-0.7 mm) regarding tinnitus ( P = .06), hearing loss ( P = .88), vertigo ( P = .26), dizziness ( P = .83), and aural fullness ( P = .61)., Conclusions: While patients with Ménière disease were proportionately more likely to have a small vestibular aqueduct than patients without Ménière disease, the small vestibular aqueduct was more frequently seen in patients without Ménière disease and had no correlation with hearing loss, vertigo, dizziness, or aural fullness. We suggest that the finding of a small vestibular aqueduct on CT could be reported by radiologists as a possible finding in Ménière disease, but it remains of uncertain, and potentially unlikely, clinical importance in the absence of symptoms of Ménière disease., (© 2023 by American Journal of Neuroradiology.)

The α-helix is one of the most common protein surface recognition motifs found in nature, and its unique amide-cloaking properties also enable α-helical polypeptide motifs to exist in membranes. Together, these properties have inspired the development of α-helically constrained (Helicon) therapeutics that can enter cells and bind targets that have been considered "undruggable", such as protein-protein interactions. To date, no general method for discovering α-helical binders to proteins has been reported, limiting Helicon drug discovery to only those proteins with previously characterized α-helix recognition sites, and restricting the starting chemical matter to those known α-helical binders. Here, we report a general and rapid screening method to empirically map the α-helix binding sites on a broad range of target proteins in parallel using large, unbiased Helicon phage display libraries and next-generation sequencing. We apply this method to screen six structurally diverse protein domains, only one of which had been previously reported to bind isolated α-helical peptides, discovering 20 families that collectively comprise several hundred individual Helicons. Analysis of 14 X-ray cocrystal structures reveals at least nine distinct α-helix recognition sites across these six proteins, and biochemical and biophysical studies show that these Helicons can block protein-protein interactions, inhibit enzymatic activity, induce conformational rearrangements, and cause protein dimerization. We anticipate that this method will prove broadly useful for the study of protein recognition and for the development of both biochemical tools and therapeutics for traditionally challenging protein targets.

Objective: To examine referral pattern, the timing of diagnostic/staging processes, and treatment initiation for new head and neck cancer patients in a community setting., Methods: Patients with a newly diagnosed previously untreated diagnosis of head neck cancer managed at Asplundh Cancer Pavilion/Abington Memorial Hospital from October 2018 to March 2020. Source of referral and preceding workup were examined as well as intervals between initial head and neck consult and various timepoints of treatment initiation., Results: One hundred and five patients were included in the study. The primary referral sources were external general otolaryngology (56.3%). Oral surgery and dermatology obtained tissue biopsy approximately 80% of the time before referral. The average time from the ordering of initial staging positron emission tomography/computed tomography to finalized results was 14 days (range: 10-25 days). Patients referred from dermatology and oral surgery were more likely to require single modality care, namely definitive surgical management. Time to treatment initiation average was 37 days (range: 29-41 days). Patients with longer treatment times noted significantly higher times to both radiation and medical oncology consults (48.42 vs. 18.13 days; P  < 0.001)., Conclusions: No notable differences in treatment initiation times were identified based on referral source or extent of workup performed before head/neck surgery consult. It appears the largest opportunities for improvement in terms of reducing overall treatment length exist in the optimization of radiation initiation time., Competing Interests: The authors declare that there are no conflict of interests., (© 2022 The Authors. World Journal of Otorhinolaryngology‐Head and Neck Surgery published by John Wiley & Sons, Ltd on behalf of Chinese Medical Association.)

Background: We previously reported a trial using a DNA vaccine encoding prostatic acid phosphatase (MVI-816, pTVG-HP), given over 12 weeks concurrently or sequentially with pembrolizumab, in patients with mCRPC. We report the final analysis of this trial following two additional treatment arms in which patients with mCRPC continued concurrent treatment until progression., Materials and Methods: Patients with mCRPC were treated with MVI-816 and pembrolizumab every 3 weeks (arm 3, n=20) or MVI-816 every 2 weeks and pembrolizumab every 4 weeks (arm 4, n=20). The primary objectives were safety, 6-month progression-free survival (PFS), median time to radiographic progression, and objective response rates. Secondary objectives included immunological evaluations., Results: In 25 patients with measurable disease, there were no complete response and one confirmed partial response in a patient who subsequently found to have an MSI hi tumor. 4/40 patients (10%) had a prostate-specific antigen decline >50%. The estimated overall radiographic PFS rate at 6 months was 47.2% (44.4% arm 3, 61.5% arm 4). Accounting for all off-study events, overall median time on treatment was 5.6 months (95% CI: 5.4 to 10.8 months), 5.6 months for arm 3 and 8.1 months for arm 4 (p=0.64). Thirty-two per cent of patients remained on trial beyond 6 months without progression. Median overall survival was 22.9 (95% CI: 16.2 to 25.6) months. One grade 4 event (hyperglycemia) was observed. Immune-related adverse events (irAEs) >grade 1 were observed in 42% of patients overall. Interferon-γ and/or granzyme B immune response to prostatic acid phosphatase was detected in 2/20 patients in arm 3 and 6/20 patients in arm 4. Plasma cytokines associated with immune activation and CD8+ T-cell recruitment were augmented at weeks 6 and 12. The development of irAE was significantly associated with a prolonged time on treatment (HR=0.42, p=0.003). Baseline DNA homologous recombination repair mutations were not associated with longer time to progression., Conclusions: Findings here demonstrate that combining programmed cell death 1 blockade with MVI-816 is safe, can augment tumor-specific T cells, and can result in a favorable 6-month disease control rate. Correlative studies suggest T-cell activation by vaccination is critical to the mechanism of action of this combination. Future randomized clinical trials are needed to validate these findings., Trial Registration Number: NCT02499835., Competing Interests: Competing interests: DGM has ownership interest, has received research support, and serves as consultant to Madison Vaccines, which has licensed material described in this manuscript and supported this trial., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

The impact force experienced by a runner when his/her foot makes contact with the ground has been the subject of much research. This force is called the ground reaction force (GRF), and has been measured by several groups. In parallel with this, mathematical models have been developed to simulate GRFs in order to investigate various effects on this, such as the parameters of the human body and types of running shoe soles. Lumped parameter models have been developed by several researchers with limited success, because they are either constrained to model translational motion, or become complicated if they include rotational motion. This paper proposes a new approach based on modes of vibration, which encompasses the simplicity of the lumped parameter approach, without the motion constraints. The GRF is decomposed into contributions due to the various vibration modes of the system. To achieve this, a linear system is required, so a Zener model, which is used to model viscoelastic materials, is employed as the ground reaction model. The modal modelling approach is described in detail using established lumped parameter models used to predict the GRF. It is then applied to four experimental data sets from the literature, where it is shown that at most three modes are required to model GRF data accurately. Two of these modes are oscillatory modes and one is a non-oscillatory exponentially decaying mode. In general, it is shown that the modal model can capture the dynamics of each measured GRF independently of speed and running style., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The benefit of chemotherapy (NAC) for patients with ER/PR positive, HER2 negative breast cancer is unclear. Our aim was to determine factors associated with histopathologic response and oncologic outcome following NAC in this group., Methods: Consecutive female patients undergoing neoadjuvant therapy and surgery for locally advanced Luminal A breast cancer between 2010 and 2015 were studied. Multivariable linear, logistic, and Cox regression analysis was undertaken., Results: 114 patients were studied. Pathological complete response (pCR) was achieved in 7.9% of patients, ypN0 in 25.5%, and downstaging in 33.6%. However, 43.9% exhibited a Sataloff C-D response. Tumor grade independently predicted pCR (P = 0.039), while PR score predicted ypN0 (P = 0.017) and downstaging (P=0.029). 5-year invasive disease-free (iDFS) and overall survival (OS) were 68.5 ± 4.7% and 77.7 ± 4.3%, respectively., Conclusion: After NAC for Luminal A breast cancer, pCR rates are low. Patients with high grade tumors with weak PR expression exhibit the most promising response rates., Competing Interests: Declaration of competing interest The authors declare no conflict of interest in the production of this manuscript or in the research associated with it., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Introduction: Despite its popularity, there have been no reports outlining adult craniofacial trauma in the setting of golf injuries. Our main objective was to identify and describe trends in head and neck injuries incurred while participating in golf including injury type, anatomic location, and patient disposition., Methods: A retrospective cohort analysis of the National Electronic Injury Surveillance System (NEISS) was conducted from 2009-2018. Population characteristics of golf-related injuries were recorded, including, age, sex, and race distributions. Distribution of injury anatomic location, injury type, distribution of fracture location, patient disposition was further analyzed. A one way ANOVA was utilized to obtain the mean ages for all injuries and compare them for any statistical difference. To identify statistical significance, a Fisher exact test with a Monte Carlo simulation was performed., Results: A total of 509 golf-related injuries (national estimate 24,425 cases) were recorded over the study period. Lacerations were the most common injury overall (54.2%), while contusions and abrasions were the next most common injuries (27.3%). The most common fracture subtype observed was midface (40.43%), followed by nasal bone (27.66%), mandible (12.77%), skull (12.77%), and cervical spine (6.38%). The highest proportion of patients admitted for further treatment were individuals >70 years of age. Fractures had the highest rate of admission (29.8%)., Conclusions: A better understanding of golf injuries can allow for rapid detection and appropriate treatment when encountered. This knowledge can also help to develop safety precautions by potentially reforming rules and regulations as well as protective equipment., Competing Interests: The authors report no disclosures or conflicts of interest., (Copyright © 2020 by Mutaz B. Habal, MD.)

Background: Frailty has important implications for the care of the elderly and how their needs are met., Objective: To assess clinicians' acknowledgement of frailty in the electronic medical records (EMR) and the impact of frailty recognition on advance care planning (ACP)., Methods: We performed a retrospective study on 119 patients 65 years or older with moderate or severe frailty assessed using a validated frailty scale. We reviewed notes to determine if primary team identified frailty and obtained data regarding ACP planning. We present the characteristics and outcomes of patients who were identified as frail and compared them with patients whose frailty was unrecognized in EMR., Results: Among the 119 frail patients, one third were ≥85 years and one-year mortality was 25.4%. Most patients were taking ≥5 medications and only 14.3% rated their health as excellent or good prior to hospitalization. Only 15 patients (12.6%) were identified as frail in the EMR. The only significant differences between those recognized versus unrecognized frail were body mass index (23.4 vs 28.6, p = 0.02) and reported weight loss in the 3 months prior to admission (93.3% vs 59.6%, p = 0.009). Geriatric or palliative care consults, and changes in code status to do-not resuscitate were more frequent among those recognized vs not. (33.3% vs 11.5%; 13.3% vs 1.9% respectively)., Conclusion: Documentation of frailty in the EMR was rare and it was associated with a lower likelihood of providing advance care planning. These findings suggest a need for consistent frailty assessment, which might promote patient-centered care.

Lightning flashes have been observed by a number of missions that visited or flew by Jupiter over the past several decades. Imagery led to a flash rate estimate of about 4 × 10 -3 flashes per square kilometre per year (refs. 1,2 ). The spatial extent of Voyager flashes was estimated to be about 30 kilometres (half-width at half-maximum intensity, HWHM), but the camera was unlikely to have detected the dim outer edges of the flashes, given its weak response to the brightest spectral line of Jovian lightning emission, the 656.3-nanometre Hα line of atomic hydrogen 1,3-6 . The spatial resolution of some cameras allowed investigators to confirm 22 flashes with HWHM greater than 42 kilometres, and to estimate one with an HWHM of 37 to 45 kilometres (refs. 1,7-9 ). These flashes, with optical energies comparable to terrestrial 'superbolts'-of (0.02-1.6) × 10 10  joules-have been interpreted as tracers of moist convection originating near the 5-bar level of Jupiter's atmosphere (assuming photon scattering from points beneath the clouds) 1-3,7,8,10-12 . Previous observations of lightning have been limited by camera sensitivity, distance from Jupiter and long exposures (about 680 milliseconds to 85 seconds), meaning that some measurements were probably superimposed flashes reported as one 1,2,7,9,10,13 . Here we report optical observations of lightning flashes by the Juno spacecraft with energies of approximately 10 5 -10 8  joules, flash durations as short as 5.4 milliseconds and inter-flash separations of tens of milliseconds, with typical terrestrial energies. The flash rate is about 6.1 × 10 -2 flashes per square kilometre per year, more than an order of magnitude greater than hitherto seen. Several flashes are of such small spatial extent that they must originate above the 2-bar level, where there is no liquid water 14,15 . This implies that multiple mechanisms for generating lightning on Jupiter need to be considered for a full understanding of the planet's atmospheric convection and composition.

The detection and location of pipeline leakage can be deduced from the time difference between the arrival leak signals measured by sensors placed at the pipe access points on either side of a suspected leak. Progress has been made in this area to offer a potential improvement over the conventional cross-correlation method for time delay estimation. This paper is concerned with identifying suitable sensors that can be easily deployed to monitor the pipe vibration due to the propagation of leak noise along the pipeline. In response to this, based on the low-frequency propagation characteristics of leak noise in our previous study, polyvinylidene fluoride (PVDF) wire sensors are proposed as a potential solution to detect the pipeline leak signals. Experimental investigations were carried out at a leak detection pipe rig built in the Chinese Academy of Sciences. Their performances for leak detection were shown in comparison with hydrophones. It is suggested that with special considerations given to aspects pertaining to non-intrusive deployment and low cost, the PVDF wire sensors are of particular interest and may lead to a promising replacement for commercial leak noise transducers.

Treating tuberculosis (TB) requires a multidrug course of treatment lasting 6 months, or longer for drug-resistant TB, which is difficult to complete and often not well tolerated. Treatment failure and recurrence after end-of-treatment can have devastating consequences, including progressive debilitation, death, the transmission of Mycobacterium tuberculosis - the infectious agent responsible for causing TB - to others, and may be associated with the development of drug-resistant TB. The burden on health systems is important, with severe economic consequences. Vaccines have the potential to serve as immunotherapeutic adjuncts to antibiotic treatment regimens for TB. A therapeutic vaccine for TB patients, administered towards completion of a prescribed course of drug therapy or at certain time(s) during treatment, could improve outcomes through immune-mediated control and even clearance of bacteria, potentially prevent re-infection, and provide an opportunity to shorten and simplify drug treatment regimens. The preferred product characteristics (PPC) for therapeutic TB vaccines described in this document are intended to provide guidance to scientists, funding agencies, public and private sector organizations developing such vaccine candidates. This document presents potential clinical end-points for evidence generation and discusses key considerations about potential clinical development strategies., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Health-care professionals are faced with a daunting task: balancing appropriate care for chronic pain with their responsibility to keep patients and others safe from treatment-related harm. Whereas opioids have historically been considered an effective tool in the analgesic armamentarium, the rise of opioid abuse has caused the pendulum to swing away from prescribing opioids to an emphasis on safety. This paradigm shift risks neglecting the very real consequences of untreated/undertreated pain. Using data from the medical literature, this review examines influences on the real and perceived benefit-to-risk ratio for opioids and provides clinicians with a practical approach to prescribing opioids that minimizes the risk for abuse/misuse. There is appreciable clinical trial and observational evidence of efficacy/effectiveness with opioids used for pain management over the short or long term when considered in the context of pharmacologic alternatives. Enhancing the relative safety and minimizing the risk for abuse/misuse may be achieved through proactive prescription practices that include careful patient selection, risk assessment, individualized and multimodal treatment plans with established goals, initiating opioid treatment cautiously with an exit plan in place, ongoing assessments of response to therapy, and routine patient monitoring. Additionally, prescribing opioids with a lower potential for abuse or misuse (e.g. abuse-deterrent formulations) may provide a benefit. Using a pragmatic approach to prescribing practices, we postulate that the balance between benefit and risk can be favorable for opioid therapy in select patients, even for long-term treatment of chronic pain.

Background: Acute Care for Elders (ACE) programs improve outcomes for older adults; however, little is known about whether impact varies with comorbidity severity., Objective: To describe differences in hospital-level outcomes between ACE and routine care across various levels of comorbidity burden., Design: Cross-sectional quality improvement study., Setting: A 716-bed teaching hospital., Participants: Medical inpatients aged ≥70 years hospitalized between September 2014 and August 2017., Intervention: ACE care, including interprofessional rounds, geriatric syndromes screening, and care protocols, in an environment prepared for elders MEASUREMENTS: Total cost, length of stay (LOS), and 30-day readmissions. We calculated median differences for cost and LOS between ACE and usual care and explored variations across the distribution of outcomes at the 25th, 50th, 75th and 90th percentiles. Results were also stratified across quartiles of the combined comorbidity score., Results: A total of 1,429 ACE and 10,159 non-ACE patients were included in this study. The mean age was 81 years, 57% were female, and 81% were white. ACE patients had lower costs associated with care ranging from $171 at the 25th percentile to $3,687 at the 90th percentile, as well as lower LOS ranging from 0 days at the 25th percentile to 1.9 days at the 90th percentile. After stratifying by comorbidity score, the greatest differences in outcomes were among those with higher scores. There was no difference in 30-day readmission between the groups., Conclusion: The greatest reductions in cost and LOS were in patients with greater comorbidity scores. Risk stratification may help hospitals prioritize admissions to ACE units to maximize the impact of the more intensive intervention., (© 2019 Society of Hospital Medicine.)

In January 2018, the Society of Cardiovascular and Angiography Interventions (SCAI) and Avalere Health ("Avalere") launched the development of the Heart Valve Initiative to advance the identification and management of patients with heart valve disease. To define the priority gap areas in identification and management of valve disease, a formal environmental scan was conducted to uncover current and planned initiatives that might inform the development of the initiative and bring to light stakeholder activities that seek to address the target patient population. This document summarizes the methodology and key findings from the scan, which will inform the development of interventions, research questions, and quality measure concepts to consider. Understanding that quality improvement initiatives and evidence in cardiovascular care may evolve rapidly, this synopsis represents a snapshot of information gathered from February 2018 to May 2019., (© 2019 Wiley Periodicals, Inc.)

Objectives: Our objective was to determine if there are differences in caregiver perception of speech for patients that undergo frenulectomy compared to patients that were not surgically treated., Introduction: Ankyloglossia is a controversial topic without standardized treatment guidelines. Although there have been several studies suggesting that breastfeeding does improve after frenulectomy, there is a paucity of literature that investigates the relationship between ankyloglossia and speech., Methods: A retrospective chart review was conducted to identify patients with ankyloglossia. Patients were categorized into surgical treatment (frenulectomy) and non-treatment groups. Caregivers of both groups were contacted by phone and surveyed on speech quality and tongue mobility using Likert scores. Mann Whitney-U testing was used to determine if there were significant differences in perceived speech quality between the surgical and non-surgical groups., Results: The caregivers of seventy-seven patients participated in the phone survey: 46 (60%) children in the surgical group and 31 (40%) children in the non-surgical group who participated in the phone survey. There were no differences in difficulty with speech (p = 0.484) and tongue mobility (p = 0.064) between the two groups. However, patients that underwent surgical intervention for ankyloglossia reported less difficulty with tongue tasks (p < 0.001) compared to those who were not surgically treated. Additionally, 50% of patients that underwent surgery had a documented family history of ankyloglossia which was significantly higher than 16.1% in the non-surgical group (p = 0.002)., Conclusions: It appears that children with ankyloglossia might have similar speech quality following frenulectomy in comparison to speech quality without treatment. Children who undergo frenulectomy may experience improvements in tongue tasks. This data should encourage further research on the management of speech concerns in children with ankyloglossia., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Ankyloglossia is a controversial topic with no standardized treatment guidelines. A retrospective chart review was conducted to identify children who underwent lingual frenulectomy for speech and language impairment. Impairment severity was recorded pre- and postoperatively as mild, mild to moderate, moderate, moderate to severe, or severe. Variables were tested with chi-square analysis for their statistical relationship to improvements in speech and language. Children with preoperative moderate and moderate-to-severe speech and language impairment attained better speech and language outcomes after frenulectomy as compared with children with mild and mild-to-moderate impairment (100% vs 82%, P = .015). Sutured closure after frenulectomy was associated with better speech and language improvements (100% vs 83%, P = .033). One could consider observation of patients with mild and mild-to-moderate speech and language impairments. Sutured closure might result in better improvements in speech and language impairments. This pilot study sheds light on the potential impact of a larger study currently underway.

In leak noise correlation surveys, time delay estimation (TDE) is of great importance in pinpointing a suspected leak. Conventional TDE methods involve pre-filtering processes prior to performing cross-correlation, based on a priori knowledge of the leak and background noise spectra, to achieve the desired performance. Despite advances in recent decades, they have not proven to be capable of tracking changes in sensor signals as yet. This paper presents an adaptive phase transform method based on least mean square (LMS) algorithms for the determination of the leak location to overcome this limitation. Simulation results on plastic water pipes show that, compared to the conventional LMS method, the proposed adaptive method is more robust to a low signal-to-noise ratio. To further verify the effectiveness of the proposed adaptive method, an analysis is carried out on field tests of real networks. Moreover, it has been shown that by using the actual measured data, improved performance of the proposed method for pipeline leakage detection is achieved. Hence, this paper presents a promising method, which has the advantages of simple implementation and ability to track changes in practice, as an alternative technique to the existing correlation-based leak detection methods.

Many protein-based materials, such as soy and mussel adhesive proteins, have been the subject of scientific and commercial interest. Recently, a variety of protein adhesives have been isolated from diverse sources such as insects, frogs and squid ring teeth. Many of these adhesives have similar amino acid compositions to elastomeric proteins such as elastin. Although elastin is widely investigated for a structural biomaterial, little work has been done to assess its adhesive potential. In this study, recombinant elastin-like polypeptides were created to probe the factors affecting adhesion strength. Lap shear adhesion was used to examine the effects of both extrinsic factors (pH, concentration, cross-linker, humidity, cure time and cure temperature) and intrinsic factors (protein sequence, structure and molecular weight). Of the extrinsic factors tested, only humidity, cure time and cure temperature had a significant effect on adhesion strength. As water content was reduced, adhesion strength increased. Of the intrinsic factors tested, amino acid sequence did not significantly affect adhesion strength, but less protein structure and higher molecular weights increased adhesion strength directly. The strengths of proteins in this study (greater than 2 MPa) were comparable to or higher than those of two commercially available protein-based adhesives, hide glue and a fibrin sealant. These results may provide general rules for the design of adhesives from elastomeric proteins., Competing Interests: The authors declare no competing interests, but a non-provisional patent application has been filed on one of the proteins in this work.

Objective: There is a need to identify safe and effective opioid-sparing multimodal alternative treatment strategies and approaches, including topical analgesics, for opioid-experienced chronic pain patients to mitigate the risk of addiction, misuse, and abuse of opioids., Methods: This subset analysis from a prospective, observational study evaluated changes in opioid use, other concurrent medication use, and pain severity and interference in opioid-experienced patients (OEP) treated with topical analgesics for chronic pain with measures obtained at baseline and 3- and 6- month follow-up., Results: The 3-month opioid-experienced patient (3-month OEP) group included 121 patients who completed baseline and 3-month follow-up assessments; 27 opioid-experienced patients completed baseline and 6-month follow-up assessments (6-month OEP). Demographic characteristics, and mean pain severity and interference scores were similar between groups at baseline. After treatment with topical analgesics, 49% of patients in the 3-month and 56% of patients in the 6-month group reported they had completely discontinued use of opioids. In addition, 31% of patients at the 3-month assessment and 30% at the 6-month assessment reported that they were no longer taking any pain medication. Other concurrent medications decreased by 65% after 3 months, and 74% after 6 months. There were statistically significant decreases from baseline in pain severity and interference scores within the 3- (CI:0.7-1.4, 1.4-2.2) and 6-month (CI:0.7-2.4 (severity); CI:1.2-3.5 (interference)) OEP groups., Conclusions: Opioid use and other concurrent medications decreased among opioid-experienced chronic pain patients after 3- and 6- months of treatment with topical analgesics. Pain severity and interference scores also decreased. The topical analgesics were reported to be effective and safe for the treatment of chronic pain, with randomized controlled trials needed to confirm these findings.

Aim: To further characterize the pharmacokinetics of Xtampza ® ER., Subjects & Methods: This was an open-label, randomized, active-controlled, five-treatment, five-period, naltrexone-blocked, cross-over study. Healthy subjects received five equivalent oxycodone doses: Xtampza ER (intact or crushed), OxyContin ® (intact or crushed) or immediate-release (IR) oxycodone (crushed). Blood samples were collected to assess oxycodone concentrations., Results: Crushed and intact Xtampza ER resulted in lower peak plasma concentrations compared with crushed oxycodone IR; crushed and intact Xtampza ER were bioequivalent. Crushed OxyContin exhibited a rapid increase in plasma oxycodone and was bioequivalent to crushed oxycodone IR., Conclusion: This second pharmacokinetic study demonstrated that Xtampza ER maintains its ER properties after crushing, unlike OxyContin, which failed to retain its ER properties after crushing. ANZCTR registration number: ACTRN12614000613606.

Background: Opioids and other controlled substances prescribed for chronic pain are associated with abuse, addiction, and death, prompting national initiatives to identify safe and effective pain management strategies including topical analgesics., Methods: This prospective, observational study evaluated changes from baseline in overall mean severity and interference scores on the Brief Pain Inventory scale and the use of concurrent pain medications at 3- and 6-month follow-up assessments in chronic pain patients treated with topical analgesics. Changes in pain severity and interference and medication usage were compared between treated patients and unmatched and matched controls., Results: The unmatched intervention group (unmatched-IG) included 631 patients who completed baseline and 3-month follow-up surveys (3-month unmatched-IG) and 158 who completed baseline and 6-month follow-up assessments (6-month unmatched-IG). Baseline and 3-month follow-up data were provided by 76 unmatched controls and 76 matched controls (3-month unmatched-CG and matched-CG), and 51 unmatched and 36 matched patients completed baseline and 6-month follow-up surveys (6-month unmatched-CG and matched-CG). Baseline demographic characteristics and mean pain severity and interference scores were similar between groups. There were statistically significant decreases from baseline in mean pain severity and interference scores within the 3- and 6-month unmatched-IG (all P <0.001). Significantly greater decreases in the mean change from baseline in pain severity and interference scores were evident for the 3- and 6-month unmatched-IG versus unmatched-CG (all P <0.001), with similar results when the 3- and 6-month matched-IG and matched-CG were compared. A higher percentage of the 3- and 6-month unmatched-IG and matched-IG de-escalated use of concurrent pain medications (all P <0.001), while significantly higher percentages of the unmatched-CG and matched-CG escalated medication use. Side effects were reported by <1% of the unmatched-IG., Conclusion: Topical analgesics appear to be effective and safe for the treatment of chronic pain, with randomized controlled trials needed to confirm these findings., Competing Interests: Disclosure Jeffrey A Gudin and Michael J Brennan have received compensation from Clarity Science for their roles as principal investigators and for providing protocol-required services for the study. E Dennis Harris and Peter L Hurwitz are employees of Clarity Science. James D Strader is the CEO of Safe Harbor Compliance and Clinical Services. Derek T Dietze received compensation for study statistical analyses. The authors report no other conflicts of interest in this work.

The determinants of immunological protection against Mycobacterium tuberculosis (M.tb) infection in humans are not known. Mycobacterial growth inhibition assays have potential utility as in vitro surrogates of in vivo immunological control of M.tb. We evaluated a whole blood growth inhibition assay in a setting with high burden of TB and aimed to identify immune responses that correlate with control of mycobacterial growth. We hypothesized that individuals with underlying M.tb infection will exhibit greater M.tb growth inhibition than uninfected individuals and that children aged 4 to 12 years, an age during which TB incidence is curiously low, will also exhibit greater M.tb growth inhibition than adolescents or adults. Neither M.tb infection status, age of the study participants, nor M.tb strain was associated with differential control of mycobacterial growth. Abundance and function of innate or T cell responses were also not associated with mycobacterial growth. Our data suggest that this assay does not provide a useful measure of age-associated differential host control of M.tb infection in a high TB burden setting. We propose that universally high levels of mycobacterial sensitization (through environmental non-tuberculous mycobacteria and/or universal BCG vaccination) in persons from high TB burden settings may impart broad inhibition of mycobacterial growth, irrespective of M.tb infection status. This sensitization may mask the augmentative effects of mycobacterial sensitization on M.tb growth inhibition that is typical in low burden settings.

The development of a functional biomarker assay in the tuberculosis (TB) field would be widely recognized as a major advance in efforts to develop and to test novel TB vaccine candidates efficiently. We present preliminary studies using mycobacterial growth inhibition assays (MGIAs) to detect Mycobacterium bovis BCG vaccine responses across species, and we extend this work to determine whether a standardized MGIA can be applied in characterizing new TB vaccines. The comparative MGIA studies reviewed here aimed to evaluate robustness, reproducibility, and ability to reflect in vivo responses. In doing so, they have laid the foundation for the development of a MGIA that can be standardized and potentially qualified. A major challenge ahead lies in better understanding the relationships between in vivo protection, in vitro growth inhibition, and the immune mechanisms involved. The final outcome would be a MGIA that could be used with confidence in TB vaccine trials. We summarize data arising from this project, present a strategy to meet the goals of developing a functional assay for TB vaccine testing, and describe some of the challenges encountered in performing and transferring such assays., (Copyright © 2017 Brennan et al.)

The genome of Mycobacterium tuberculosis , the bacterium responsible for the disease tuberculosis, contains an unusual family of abundant antigens (PE/PPEs). To date, certain members of this multigene family occur only in mycobacteria that cause disease. It is possible that the numerous proteins encoded by these mycobacterial genes dictate the immune pathogenesis of this bacterial pathogen. There is also evidence that some of these antigens are present at the cell surface and that they affect the pathology and immunology of the organism in many ways. Also, they elicit both antibodies and T cells, they may be involved in antigenic variation, and they may be good candidates for vaccines and drugs. However, since they are plentiful and extremely homologous, these PE/PPEs are very challenging to study, and it is difficult to be certain what role(s) they have in the pathogenesis of tuberculosis. Consequently, how to develop treatments like vaccines using these antigens as candidates is complex., (Copyright © 2017 Brennan.)

Introduction: Falls are the leading cause of injury in almost all age-strata in the U.S. However, fall-related injuries (FI) and their circumstances are under-studied at the population level, particularly among young and middle-aged adults. This study examined the circumstances of FI among community-dwelling U.S. adults, by age and gender., Methods: Narrative texts of FI from the National Health Interview Survey (1997-2010) were coded using a customized taxonomy to assess place, activity, initiating event, hazards, contributing factors, fall height, and work-relatedness of FI. Weighted proportions and incidence rates of FI were calculated across six age-gender groups (18-44, 45-64, 65+ years; women, men)., Results: The proportion of FI occurring indoors increased with age in both genders (22%, 30%, and 48% among men, and 40%, 49% and 62% among women for 18-44, 45-64, 65+ age-groups, respectively). In each age group the proportion of indoor FI was higher among women as compared to men. Among women, using the stairs was the second leading activity (after walking) at the time of FI (19%, 14% and 10% for women in 18-44, 45-64, 65+ age groups, respectively). FI associated with tripping increased with age among both genders, and women were more likely to trip than men in every age group. Of all age-gender groups, the rate of FI while using ladders was the highest among middle-aged men (3.3 per 1000 person-year, 95% CI 2.0, 4.5). Large objects, stairs and steps, and surface contamination were the three most common hazards noted for 15%, 14% and 13% of fall-related injuries, respectively., Conclusions: The rate and the circumstances of FI differ by age and gender. Understanding these differences and obtaining information about circumstances could be vital for developing effective interventions to prevent falls and FI.

The development of adhesives that can be applied and create strong bonds underwater is a significant challenge for materials engineering. When the adhesive is intended for biomedical applications, further criteria, such as biocompatibility, must be met. Current biomedical adhesive technologies do not meet these needs. In response, we designed a bioinspired protein system that shows promise to achieve biocompatible underwater adhesion coupled with environmentally responsive behavior that is "smart" - that is, it can be tuned to suit a specific application. The material, ELY 16 , is constructed from an elastin-like polypeptide (ELP) that can be produced in high yields from Escherichia coli and can coacervate in response to environmental factors such as temperature, pH, and salinity. To confer wet adhesion, we utilized design principles from marine organisms such as mussels and sandcastle worms. When expressed, ELY 16 is rich in tyrosine. Upon modification with the tyrosinase enzyme to form mELY 16 , the tyrosine residues are converted to 3,4-dihydroxyphenylalanine (DOPA). Both ELY 16 and mELY 16 exhibit cytocompatibility and significant dry adhesion strength (>2 MPa). Modification with DOPA increases protein adsorption to glass and provides moderate adhesion strength (∼240 kPa) in a highly humid environment. Furthermore, this ELP exhibits a tunable phase transition behavior that can be formulated to coacervate in physiological conditions and provides a convenient mechanism for application underwater. Finally, mELY 16 possesses significantly higher adhesion strength in dry, humid, and underwater environments compared with a commercially available fibrin sealant. To our knowledge, mELY 16 provides the strongest bonds of any rationally designed protein when used completely underwater, and its high yields make it more viable for commercial application compared to natural adhesive proteins. In conclusion, this ELP shows great potential to be a new "smart" underwater adhesive., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Opioid-induced constipation (OIC) is a common side effect of opioid use and can occur from the outset of opioid therapy (Online access: http://courses.elseviercme.com/aapmr2016/638e). OIC has been reported to interfere with pain management, increase health care costs, decrease work productivity and daily activities, and significantly affect patient quality of life. It can also lead to bowel obstruction. Assessing and managing OIC is important for establishing maximum function for patients. Several pharmacologic approaches, with different mechanisms of action, are available or in development., (Copyright © 2017. Published by Elsevier Inc.)

PE and PPE are two large families of proteins typical of mycobacteria whose structural genes in the Mycobacterium tuberculosis complex (MTBC) occupy about 7% of the total genome. The most ancestral PE and PPE proteins are expressed by genes that belong to the same operon and in most cases are found inserted in the esx clusters, encoding a type VII secretion system. Duplication and expansion of pe and ppe genes, coupled with intragenomic and intergenomic recombination events, led to the emergence of the polymorphic pe&#95;pgrs and ppe&#95;mptr genes in the MTBC genome. The role and function of these proteins, and particularly of the polymorphic subfamilies, remains elusive, although it is widely accepted that PE and PPE proteins may represent a specialized collection used by MTBC to interact with the complex host immune system of mammals. In this chapter, we summarize what has been discovered since the identification of these genes in 1998, focusing on M. tuberculosis genetic variability, host-pathogen interaction and TB pathogenesis.

Background: A common issue in descriptive injury epidemiology is that in order to calculate injury rates that account for the time spent in an activity, both injury cases and exposure time of specific activities need to be collected. In reality, few national surveys have this capacity. To address this issue, we combined statistics from two different national complex surveys as inputs for the numerator and denominator to estimate injury rate, accounting for the time spent in specific activities and included a procedure to estimate variance using the combined surveys., Methods: The 2010 National Health Interview Survey (NHIS) was used to quantify injuries, and the 2010 American Time Use Survey (ATUS) was used to quantify time of exposure to specific activities. The injury rate was estimated by dividing the average number of injuries (from NHIS) by average exposure hours (from ATUS), both measured for specific activities. The variance was calculated using the 'delta method', a general method for variance estimation with complex surveys., Results: Among the five types of injuries examined, 'sport and exercise' had the highest rate (12.64 injuries per 100 000 h), followed by 'working around house/yard' (6.14), driving/riding a motor vehicle (2.98), working (1.45) and sleeping/resting/eating/drinking (0.23). The results show a ranking of injury rate by activity quite different from estimates using population as the denominator., Conclusions: Our approach produces an estimate of injury risk which includes activity exposure time and may more reliably reflect the underlying injury risks, offering an alternative method for injury surveillance and research., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Despite limited evidence of efficacy, antipsychotics (APs) are commonly used to treat delirium. There has been little research on the long-term outcomes of patients who are started on APs in the hospital., Methods: Using a previously described retrospective cohort of 300 elders (≥65 years old) who were newly prescribed APs while hospitalized between October 1, 2012 and September 31, 2013, we examined the 1-year outcomes of patients alive at the time of discharge. We examined number of readmissions, reasons for readmission, duration of AP therapy, use of other sedating medications, and incidence of readmission. We used the National Death Index to describe 1-year mortality and then created a multivariable model to identify predictors of 1-year mortality., Results: The 260 patients discharged alive from their index admissions had a 1-year mortality rate of 29% (75/260). Of the 146/260 patients discharged on APs, 60 (41%) patients experienced at least 1 readmission. At the time of first readmission, 65% of patients were still taking the same APs on which they had been discharged. Eighteen patients received new APs during the readmission hospitalizations. Predictors of death at 1 year included discharge to postacute facilities after index admission (odds ratio [OR]: 2.28; 95% confidence interval [CI]: 1.10-4.73, P = 0.03) and QT interval prolongation >500 ms during index admission (OR: 3.41; 95% CI: 1.34-8.67, P = 0.01)., Conclusions: Initiating an AP in the hospital is likely to result in long-term use of these medications. Patients who received an AP during a hospitalization were at high risk of death in the following year. Journal of Hospital Medicine 2016;11:550-555. © 2016 Society of Hospital Medicine., (© 2016 Society of Hospital Medicine.)

Background: The relevance of antibodies (Abs) in the defense against Mycobacterium tuberculosis infection remains uncertain. We investigated the role of Abs to the mycobacterial capsular polysaccharide arabinomannan (AM) and its oligosaccharide (OS) fragments in humans., Methods: Sera obtained from 29 healthy adults before and after primary or secondary bacillus Calmette-Guerin (BCG) vaccination were assessed for Ab responses to AM via enzyme-linked immunosorbent assays, and to AM OS epitopes via novel glycan microarrays. Effects of prevaccination and postvaccination sera on BCG phagocytosis and intracellular survival were assessed in human macrophages., Results: Immunoglobulin G (IgG) responses to AM increased significantly 4-8 weeks after vaccination (P < .01), and sera were able to opsonize BCG and M. tuberculosis grown in both the absence and the presence of detergent. Phagocytosis and intracellular growth inhibition were significantly enhanced when BCG was opsonized with postvaccination sera (P < .01), and these enhancements correlated significantly with IgG titers to AM (P < .05), particularly with reactivity to 3 AM OS epitopes (P < .05). Furthermore, increased phagolysosomal fusion was observed with postvaccination sera., Conclusions: Our results provide further evidence for a role of Ab-mediated immunity to tuberculosis and suggest that IgG to AM, especially to some of its OS epitopes, could contribute to the defense against mycobacterial infection in humans., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.)

The development of adhesives suitable for biomedical applications has been challenging given that these materials must exhibit sufficient adhesion strengths and biocompatibility. Biomimetic materials inspired by mussel adhesive proteins appear to contain many of the necessary characteristics for biomedical adhesives. In particular, poly[(3,4-dihydroxystyrene)-co-styrene] has been shown to be a high strength adhesive material with bonding comparable to or even greater than several commercial glues. Herein, a thorough study on the cytocompatibility of this copolymer provides insights on the suitability of a mussel-mimicking adhesive for applications development. The cytotoxicity of poly[(3,4-dihydroxystyrene)-co-styrene] was evaluated through assessment of the viability, proliferation rate, and morphology of NIH/3T3 fibroblasts when cultured with copolymer extracts or directly in contact with the adhesive. After 1 and 3 days of culture, both the copolymer alone and copolymer cross-linked with periodate exhibited minimal effects on cell viability. Likewise, cells cultured on the copolymer displayed proliferation rates and morphologies similar to cells on the poly-L-lysine control. These results indicate that poly[(3,4-dihydroxystyrene)-co-styrene] is highly cytocompatible and therefore a promising material for use where biological contact is important., (© 2016 Wiley Periodicals, Inc.)

PE&#95;PGRS represent a large family of proteins typical of pathogenic mycobacteria whose members are characterized by an N-terminal PE domain followed by a large Gly-Ala repeat-rich C-terminal domain. Despite the abundance of PE&#95;PGRS-coding genes in the Mycobacterium tuberculosis (Mtb) genome their role and function in the biology and pathogenesis still remains elusive. In this study, we generated and characterized an Mtb H37Rv mutant (MtbΔ33) in which the structural gene of PE&#95;PGRS33, a prototypical member of the protein family, was inactivated. We showed that this mutant entered macrophages with an efficiency up to ten times lower than parental or complemented strains, while its efficiency in infecting pneumocytes remained unaffected. Interestingly, the lack of PE&#95;PGRS33 did not affect the intracellular growth of this mutant in macrophages. Using a series of functional deletion mutants of the PE&#95;PGRS33 gene to complement the MtbΔ33 strain, we demonstrated that the PGRS domain is required to mediate cell entry into macrophages, with the key domain encompassing position 140-260 amino acids of PE&#95;PGRS33. PE&#95;PGRS33-mediated entry into macrophages was abolished in TLR2-deficient mice, as well as following treatment with wortmannin or an antibody against the complement receptor 3 (CR3), indicating that PE&#95;PGRS33-mediated entry of Mtb in macrophages occurs through interaction with TLR2.

Opioid abuse is a healthcare and societal problem that burdens individuals, their families and the healthcare professionals who care for them. Restricting access to opioid analgesics is one option to deter abuse, but this may prevent pain patients in need from obtaining effective analgesics. Therefore, strategies that mitigate the risk of opioid abuse while maintaining access are being pursued by several stakeholders including federal agencies, state governments, payors, researchers, the pharmaceutical industry and clinicians. Federal agency efforts have included required licensure and documentation for prescribing opioids, implementation of risk evaluation and mitigation strategies, and guidance on assessment and labeling of opioid abuse-deterrent formulations. In addition, state governments and payors have enacted monitoring programs, and pharmaceutical companies continue to develop abuse-deterrent opioid formulations. Strategies for clinicians to mitigate opioid abuse include comprehensive patient assessment and universal precautions (e.g. use of multimodal analgesia and abuse-deterrent opioid formulations, urine toxicology screening, participation in prescription drug monitoring and risk evaluation and mitigation strategy programs).

Introduction: Although exercise and strength training have been shown to be protective against falls in older adults (aged 65 years and older), evidence for the role of leisure-time physical activity (LTPA) in the prevention of falls and resulting injuries in middle-aged adults (aged 45-64 years) is lacking. In the present study, we investigate the association between self-reported engagement in LTPA and the frequency of falls and fall-related injuries among middle-aged and older adults, while controlling for key sociodemographic and health characteristics., Methods: Nationally representative data from the 2010 U.S. Behavioral Risk Factor Surveillance Survey were analyzed in April 2014 to examine the number of adults aged ≥45 years who self-reported their fall experience in the previous 3 months and any injuries that resulted from those falls. We then evaluated the association between LTPA and self-reported falls and injuries across three age strata (45-54, 55-64, and ≥65 years). The two main self-reported outcome measures were (1) frequency of falls in the 3 months prior to the survey interview date and (2) the number of injuries resulting from these falls. Prevalence ratios (PRs) and 95% CIs were calculated using Poisson regression models with robust SEs., Results: Of 340,680 survey participants aged ≥45 years, 70.7% reported engaging in LTPA, and 17% reported one or more falls. Among those reporting a fall within 3 months, 25.6% experienced one injurious fall (fall resulting in an injury) and 8.4% reported two or more injurious falls. Controlling for sociodemographic and health characteristics, among adults aged 45-54 years, those who engaged in LTPA were significantly less likely to report one fall (PR=0.90, 95% CI=0.81, 0.99); two or more falls (PR=0.84, 95% CI=0.77, 0.93); one injurious fall (PR=0.88, 95% CI=0.78, 0.99); and two or more injurious falls (PR=0.69, 95% CI=0.58, 0.83) than those who did not exercise. A similar protective effect of LTPA on reporting falls and injuries was noted for adults aged 55-64 and ≥65 years., Conclusions: Similar to older adults, middle-aged adults who engage in LTPA report fewer falls and fall-related injuries. Upon further confirmation of the relationship between LTPA and falls among middle-aged adults, fall prevention interventions could be developed for this population., (Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: Aims of this consensus panel were to determine (1) an optimal symptom-based method for assessing opioid-induced constipation in clinical practice and (2) a threshold of symptom severity to prompt consideration of prescription therapy., Methods: A multidisciplinary panel of 10 experts with extensive knowledge/experience with opioid-associated adverse events convened to discuss the literature on assessment methods used for opioid-induced constipation and reach consensus on each objective using the nominal group technique., Results: Five validated assessment tools were evaluated: the Patient Assessment of Constipation-Symptoms (PAC-SYM), Patient Assessment of Constipation-Quality of Life (PAC-QOL), Stool Symptom Screener (SSS), Bowel Function Index (BFI), and Bowel Function Diary (BF-Diary). The 3-item BFI and 4-item SSS, both clinician administered, are the shortest tools. In published trials, the BFI and 12-item PAC-SYM are most commonly used. The 11-item BF-Diary is highly relevant in opioid-induced constipation and was developed and validated in accordance with US Food and Drug Administration guidelines. However, the panel believes that the complex scoring for this tool and the SSS, PAC-SYM, and 28-item PAC-QOL may be unfeasible for clinical practice. The BFI is psychometrically validated and responsive to changes in symptom severity; scores range from 0 to 100, with higher scores indicating greater severity and scores >28.8 points indicating constipation., Conclusions: The BFI is a simple assessment tool with a validated threshold of clinically significant constipation. Prescription treatments for opioid-induced constipation should be considered for patients who have a BFI score of ≥30 points and an inadequate response to first-line interventions., (Wiley Periodicals, Inc.)

Tryptophan was substituted for residues in all four transmembrane domains of connexin32. Function was assayed using dual cell two-electrode voltage clamp after expression in Xenopus oocytes. Tryptophan substitution was poorly tolerated in all domains, with the greatest impact in TM1 and TM4. For instance, in TM1, 15 substitutions were made, six abolished coupling and five others significantly reduced function. Only TM2 and TM3 included a distinct helical face that lacked sensitivity to tryptophan substitution. Results were visualized on a comparative model of Cx32 hemichannel. In this model, a region midway through the membrane appears highly sensitive to tryptophan substitution and includes residues Arg-32, Ile-33, Met-34, and Val-35. In the modeled channel, pore-facing regions of TM1 and TM2 were highly sensitive to tryptophan substitution, whereas the lipid-facing regions of TM3 and TM4 were variably tolerant. Residues facing a putative intracellular water pocket (the IC pocket) were also highly sensitive to tryptophan substitution. Although future studies will be required to separate trafficking-defective mutants from those that alter channel function, a subset of interactions important for voltage gating was identified. Interactions important for voltage gating occurred mainly in the mid-region of the channel and focused on TM1. To determine whether results could be extrapolated to other connexins, TM1 of Cx43 was scanned revealing similar but not identical sensitivity to TM1 of Cx32., (© 2015 by The American Society for Biochemistry and Molecular Biology, Inc.)

Background/objective: Physical activity has been shown to be beneficial at improving health in some medical conditions and in preventing injury. Epidemiologic studies suggest that physical activity is one factor associated with a decreased risk for slips and falls in the older (≥ 65 years) adult population. While the risk of slips and falls is generally lower in younger than in older adults; little is known of the relative contribution of physical activity in preventing slips and falls in younger adults. We examined whether engagement in leisure-time physical activity (LTPA) was protective of slips and falls among a younger/middle-aged (≤ 50 years old) working population., Methods: 475 workers from 36 limited-service restaurants in six states in the U.S. were recruited to participate in a prospective cohort study of workplace slipping. Information on LTPA was collected at the time of enrollment. Participants reported their slip experience and work hours weekly for up to 12 weeks. We investigated the association between the rate of slipping and the rate of major slipping (i.e., slips that resulted in a fall and/or injury) and LTPA for workers 50 years of age and younger (n = 433, range 18-50 years old) using a multivariable negative binomial generalized estimating equation model., Results: The rate of major slips among workers who engaged in moderate (Adjusted Rate Ratio (RR)  = 0.65; 95% Confidence Interval (CI)  =  [0.18-2.44]) and vigorous (RR = 0.64; 95%CI  =  [0.18-2.26]) LTPA, while non-significant, were approximately one-third lower than the rate of major slips among less active workers., Conclusion: While not statistically significant, the results suggest a potential association between engagement in moderate and vigorous LTPA and the rate of major slips in younger adults. Additional studies that examine the role of occupational and non-occupational physical activity on the risk of slips, trips and falls among younger and middle aged adults appear warranted.

Objectives: We compared work and lifestyle activities for workers who work in 1 job with those who work in multiple jobs during a 1-week period., Methods: We used information from the 2003-2011 American Time Use Survey to classify workers into 6 work groups based on whether they were a single (SJH) or multiple (MJH) job holder and whether they worked their primary, other, multiple, or no job on the diary day., Results: The MJHs often worked 2 part-time jobs (20%), long weekly hours (27% worked 60+ hours), and on weekends. The MJHs working multiple jobs on the diary day averaged more than 2 additional work hours (2.25 weekday, 2.75 weekend day; P < .05), odd hours (more often between 5 pm and 7 am), with more work travel time (10 minutes weekday, 9 minutes weekend day; P < .05) and less sleep (-45 minutes weekday, -62 minutes weekend day; P < .05) and time for other household (P < .05) and leisure (P < .05) activities than SJHs., Conclusions: Because of long work hours, long daily commutes, multiple shifts, and less sleep and leisure time, MJHs may be at heightened risk of fatigue and injury.

A new and improved vaccine against tuberculosis (TB) would provide a powerful tool to conquer one of the most insidious infectious diseases of mankind. Protection afforded by bacillus Calmette-Guérin (BCG) has been shown to be limited and inconsistent, especially in adults that are known to transmit TB disease. In the last two decades, several new vaccines have been developed and tested with the aim to elicit robust and long-lived T-cell responses against Mycobacterium tuberculosis antigens. Although much progress has been made in the TB vaccine field, there is an urgent need to address critical research questions about TB immunity with a special focus on designing vaccines aimed at preventing infection and transmission of TB. Here, we discuss the rationale behind the current immunization strategies being implemented for TB vaccines and provide some suggestions for hypothesis driven research to encourage the development of novel TB vaccines., (© 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.)