Plural molecular and cellular mechanisms of pore domain KCNQ2 encephalopathy.

KCNQ2 variants in children with neurodevelopmental impairment are difficult to assess due to their heterogeneity and unclear pathogenic mechanisms. We describe a child with neonatal-onset epilepsy, developmental impairment of intermediate severity, and KCNQ2 G256W heterozygosity. Analyzing prior KCNQ2 channel cryoelectron microscopy models revealed G256 as keystone of an arch-shaped non-covalent bond network linking S5, the pore turret, and the ion path. Co-expression with G256W dominantly suppressed conduction by wild-type subunits in heterologous cells. Ezogabine partly reversed this suppression. G256W/+ mice have epilepsy leading to premature deaths. Hippocampal CA1 pyramidal cells from G256W/+ brain slices showed hyperexcitability. G256W/+ pyramidal cell KCNQ2 and KCNQ3 immunolabeling was significantly shifted from axon initial segments to neuronal somata. Despite normal mRNA levels, G256W/+ mouse KCNQ2 protein levels were reduced by about 50%. Our findings indicate that G256W pathogenicity results from multiplicative effects, including reductions in intrinsic conduction, subcellular targeting, and protein stability. These studies reveal pore "turret arch" bonding as a KCNQ structural novelty and introduce a valid animal model of KCNQ2 encephalopathy. Our results, spanning structure to behavior, may be broadly applicable because the majority of KCNQ2 encephalopathy patients share variants near the selectivity filter.

Disparities in self-reported healthcare access for airways disease in British Columbia, Canada, during the COVID-19 pandemic. Insights from a survey co-developed with people living with asthma and chronic obstructive pulmonary disease.

Patients' perspectives on the impact of the COVID-19 pandemic on their access to asthma and COPD healthcare could inform better, more equitable care delivery. We demonstrate this topic using British Columbia (BC), Canada, where the impact of the pandemic has not been described. We co-designed a cross-sectional survey with patient partners and administered it to a convenience sample of people living with asthma and COPD in BC between September 2020 and March 2021. We aimed to understand how access to healthcare for these conditions was affected during the pandemic. The survey asked respondents to report their characteristics, access to healthcare for asthma and COPD, types of services they found disrupted and telehealth (telephone or video appointment) use during the pandemic. We analysed 433 responses and found that access to healthcare for asthma and COPD was lower during the pandemic than pre-pandemic (p < 0.001). Specialty care services were most frequently reported as disrupted, while primary care, home care and diagnostics were least disrupted. Multivariable logistic regression revealed that access during the pandemic was positively associated with self-assessed financial ability (OR = 22.0, 95% CI: 7.0 - 84.0, p < 0.001, reference is disagreeing with having financial ability) and living in medium-sized urban areas (OR = 2.3, 95% CI: 1.0 - 5.2, p = 0.04, reference is rural areas). These disparities in access should be validated post-pandemic to confirm whether they still persist. They also indicate the continued relevance of exploring approaches for more equitable healthcare.

Integrative Strategy with Ayurveda and Electro-Acupuncture in Hemifacial Spasm: a Case Report.

We report a primary hemifacial spasm that started four years ago with sudden twitching of the face towards the right side. It was diagnosed as a hemifacial spasm by a neurologist and prescribed with Zeptol 100 mg 0.5 tablet BID for two weeks, followed by two sittings of Botox injection in a gap of 1 year. A year later, it reappeared more severely, driving her towards an integrative treatment modality. Ayurveda treatments including Nasya, Ksheera dhooma, internal medications, and Rasona navaneetha prayoga were administered. GV20, GB14, EX-HN5, ST3, ST4, ST6, TE17, LI4, and GB34 were selected for electro-acupuncture. The scores of hemifacial spasm grading and quality of life scale were 9 and 20 (before), 6 and 16 (after treatment), and 4 and 10 (follow-up after six months), respectively. This integrative approach was safe and has shown an improvement in hemifacial spasm.

"An integrative approach with Ayurveda and Traditional Chinese Acupuncture in post covid parosmia - A case study".

This case is about a post viral olfactory dysfunction due to SARS-CoV-2 infection, since six months treated effectively by a unique integrative approach with Ayurveda and Traditional Chinese Acupuncture (TCA). It started as a sudden onset of anosmia in the month of August 2020 with fever history two weeks prior. After three months Parosmia commenced which gradually worsened. A month later she experienced dysgeusia and nausea leading to tremendous stress and sleep disturbances. Ayurveda treatment included Shadbindu taila marsha nasya for seven days followed by Shadbindu taila pratimarsha nasya (intra nasal oil instillation) for a period of four months. Naradiya laxmivilasa rasa orally for one month. GV.20, LI.20, Ex.1, H.7, LI.11, GB.8, GB.21 and GV.25 Points were selected for TCA. The Indian Smell identification test score on day one of treatment was zero, day seven was four, at the end of one month was eight and after four months it was ten. Parosmia was assessed by VAS which was ten on day one and zero on day seven. We could achieve complete normalcy in olfactory function within four months of this treatment. This integrative approach was found to be safe and effective in treating Post covid parosmia.

Responses of forest ecosystems in Europe to decreasing nitrogen deposition.

Average nitrogen (N) deposition across Europe has declined since the 1990s. This resulted in decreased N inputs to forest ecosystems especially in Central and Western Europe where deposition levels are highest. While the impact of atmospheric N deposition on forests has been receiving much attention for decades, ecosystem responses to the decline in N inputs received less attention. Here, we review observational studies reporting on trends in a number of indicators: soil acidification and eutrophication, understory vegetation, tree nutrition (foliar element concentrations) as well as tree vitality and growth in response to decreasing N deposition across Europe. Ecosystem responses varied with limited decrease in soil solution nitrate concentrations and potentially also foliar N concentrations. There was no large-scale response in understory vegetation, tree growth, or vitality. Experimental studies support the observation of a more distinct reaction of soil solution and foliar element concentrations to changes in N supply compared to the three other parameters. According to the most likely scenarios, further decrease of N deposition will be limited. We hypothesize that this expected decline will not cause major responses of the parameters analysed in this study. Instead, future changes might be more strongly controlled by the development of N pools accumulated within forest soils, affected by climate change and forest management.

Costs of Transmission Assessment Surveys to Provide Evidence for the Elimination of Lymphatic Filariasis.

BACKGROUND: To reach the global goal of elimination of lymphatic filariasis as a public health problem by 2020, national programs will have to implement a series of transmission assessment surveys (TAS) to determine prevalence of the disease by evaluation unit. It is expected that 4,671 surveys will be required by 2020. Planning in advance for the costs associated with these surveys is essential to ensure that the required resources are available for this essential program activity. METHODOLOGY AND FINDINGS: Retrospective cost data was collected from reports from 13 countries which implemented a total of 105 TAS surveys following a standardized World Health Organization (WHO) protocol between 2012 and 2014. The median cost per survey was $21,170 (including the costs for rapid diagnostic tests [RDTs]) and $9,540 excluding those costs. Median cost per cluster sampled (without RDT costs) was $101. Analysis of costs (excluding RDTs) by category showed that the main cost drivers were personnel and travel. CONCLUSION: Transmission assessment surveys are critical to collect evidence to validate elimination of LF as a public health problem. National programs and donors can use the costing results to adequately plan and forecast the resources required to undertake the necessary activities to conduct high-quality transmission assessment surveys.

Leptobasis linda sp. nov. from Ecuador (Odonata: Coenagrionidae).

Leptobasis linda is described from the Pacific lowlands of Ecuador. The coloration of mature individuals is superficially similar to the widespread L. vacillans, but structural and color characteristics differentiate L. linda from all congeneric species. The male caudal appendages and the female posterior margin of the prothorax are unique among Leptobasis.

A new probabilistic method for quantifying n-dimensional ecological niches and niche overlap.

Considerable progress has been made in the development of statistical tools to quantify trophic relationships using stable isotope ratios, including tools that address size and overlap of isotopic niches. We build upon recent progress and propose a new probabilistic method for determining niche region and pairwise niche overlap that can be extended beyond two dimensions, provides directional estimates of niche overlap, accounts for species-specific distributions in niche space, and, unlike geometric methods, produces consistent and unique bivariate projections of multivariate data. We define the niche region (NR) as a given 95% (or user-defined a) probability region in multivariate space. Overlap is calculated as the probability that an individual from species A is found in the N(R) of species B. Uncertainty is accounted for in a Bayesian framework, and is the only aspect of the methodology that depends on sample size. Application is illustrated with three-dimensional stable isotope data, but practitioners could use any continuous indicator of ecological niche in any number of dimensions. We suggest that this represents an advance in our ability to quantify and compare ecological niches in a way that is more consistent with Hutchinson's concept of an "n-dimensional hypervolume".

Capitellar excision and hemiarthroplasty affects elbow kinematics and stability.

INTRODUCTION: Capitellar hemiarthroplasty is proposed as a reconstructive option for isolated capitellar deficiency, but there is limited data on its effect on elbow biomechanics. This study assessed the effect of capitellar excision with and without replacement on elbow kinematics and stability, and evaluated 2 different implant surface shapes. MATERIALS AND METHODS: Ten cadaveric arms were tested with an upper extremity joint simulator. Each arm underwent computer tomography scanning for implant sizing and computer-assisted implantation. Kinematic data were obtained using an electromagnetic tracking system during elbow flexion, with the arm oriented in the valgus, varus, and vertical positions. Implants were placed through an extended lateral epicondylar osteotomy using computer-assisted techniques. A repeated-measures design compared 2 implants (anatomical and spherical) to the native capitellum control and capitellar excision states. Outcomes were maximum varus-valgus laxity and rotation of the ulna with respect to the humerus. RESULTS: Excision of the capitellum increased the varus-valgus laxity up to 3.1° in active elbow flexion, with the forearm in pronation but not in supination. Both capitellar implant designs maintained normal varus-valgus laxity in both active and passive elbow flexion. Excision of the capitellum increased external ulnar rotation during active flexion in the vertical and valgus positions up to 1.5°, while both implants restored normal ulnar rotation. The kinematics and stability of the elbows were similar for both implant designs. CONCLUSION: The capitellum appears to have a role as a valgus and external rotational stabilizer of the ulnohumeral joint. This instability was corrected by both designs of capitellar hemiarthroplasty.

A comparison of two headless compression screws for operative treatment of scaphoid fractures.

PURPOSE: The purpose of this study was to compare the interfragmentary compression force across a simulated scaphoid fracture by two commonly used compression screw systems; the Acutrak 2 Standard and the 3.0 mm Synthes headless compression screw. METHODS: Sixteen (8 pairs; 6 female, 2 male) cadaver scaphoids were randomly assigned to receive either the Acutrak 2 or Synthes screw with the contralateral scaphoid designated to receive the opposite. Guide wires were inserted under fluoroscopic control. Following transverse osteotomy, the distal and proximal fragments were placed on either side of a custom load cell, to measure interfragmentary compression. Screws were placed under fluoroscopic control using the manufacturer's recommended surgical technique. Compressive forces were measured during screw insertion. Recording continued for an additional 60s in order to measure any loss of compression after installation was complete. The peak and final interfragmentary compression were recorded and paired t-tests performed. RESULTS: The mean peak compression generated by the Acutrak 2 Standard was greater than that produced by the Synthes compression screw (103.9 ± 33.2 N vs. 88.7 ± 38.6 N respectively, p = 0.13). The mean final interfragmentary compression generated by the Acutrak 2 screw (68.6 ± 36.4 N) was significantly greater (p = 0.04) than the Synthes screw (37.2 ± 26.8 N). Specimens typically reached a steady state of compression by 120-150s after final tightening. CONCLUSION: Peak interfragmentary compression observed during screw installation was similar for both screw systems. However, the mean interfragmentary compression generated by the Acutrak 2 Standard was significantly greater. Our study demonstrates that the Synthes headless compression screw experienced a greater loss of interfragmentary compressive force from the time of installation to the final steady state compression level. The higher post-installation compression of the Acutrak 2 Standard may be attributable to the greater number of threads throughout the entire length of the screw. The clinical significance of these results, are, at this point uncertain. We do demonstrate that a fully threaded design offers a more reliable compression that may translate to more predictable bony union.

A morphological analysis of the humeral capitellum with an interest in prosthesis design.

INTRODUCTION: Although interest in capitellar arthroplasty is increasing, the morphology of the capitellum has not been fully characterized. Our purpose was to quantify the anthropometric features of the capitellum with an interest in arthroplasty design. We hypothesized that the shape is more complex than originally believed, and cannot be accurately modeled as a spherical structure. METHODS: Fifty cadaveric human elbows underwent helical computer tomography scans. After reconstruction and establishment of a coordinate system for the distal humerus, circle-fits were applied to each of the 1-mm-thick slices. Sagittal radii of curvature were calculated every 10° of flexion around each circle (0-130° of flexion). A single transverse radius was calculated at 60° of flexion. The surface of the capitellum was described by sagittal and transverse radii of curvature and the footprint by height and width. These pairs of parameters were correlated to determine their strength of association. RESULTS: The average height was 23.2 ± 2.9 mm (range, 18.3-29.5), while the average width was 13.9 ± 2.3 (range, 9-19). The sagittal radius of curvature was 11.6 ± 1.4 mm (range, 8.7-14.8), and the transverse radius was 14.0 ± 3.0 mm (range, 9.6-20.9). Correlations of height and width and sagittal and transverse radii were significant (R = .547, .705) (P < .01). Sagittal and transverse radii and height and width were significantly different (P < .001 for each pair). CONCLUSION: The capitellum does not have a spherical surface or a circular footprint. There is substantial variability in the relationship between the height and width, and between the surface radii, that may be difficult to replicate with an off-the-shelf implant.

Osteochondral lesions of the capitellum do not affect elbow kinematics and stability with intact collateral ligaments: an in vitro biomechanical study.

PURPOSE: Osteochondritis dissecans (OCD) of the capitellum most commonly affects adolescent pitchers and gymnasts, who present with pain and mechanical symptoms. Patients with larger lesions have poorer outcomes, possibly related to increased contact pressures on the surrounding articular surface with or without instability. The purpose of this in vitro study was to determine whether displaced OCD lesions of the capitellum lead to altered kinematics and stability of the elbow. METHODS: We mounted 9 fresh-frozen cadaveric arms in an upper extremity joint testing system, with cables attaching the tendons of the major muscles to motors and pneumatic actuators. An electromagnetic receiver on the ulna enabled quantification of the kinematics of the radius and ulna with respect to the humerus. We used 3-dimensional computed tomography scans and computer-assisted techniques to navigate sequential osteochondral defects ranging in size from 12.5% to 100% of the capitellum. The arms were subjected to active and passive flexion in both the vertical and valgus positions with the forearm in both pronation and supination. RESULTS: We found no significant differences in valgus angulation or ulnar rotation between any of the OCD lesions and the intact elbow during flexion, regardless of arm position or forearm rotation. CONCLUSIONS: Osteochondritis dissecans lesions of the capitellum, both small and large, did not alter the ulnohumeral kinematics and stability with intact collateral ligaments. Therefore, excision of unfixable osteochondral fragments of the capitellum in the setting of intact collateral ligaments can be considered without the risk of creating instability.

The effect of specific versus combined warm-up strategies on the voice.

Although actors and singers typically warm-up the voice before performing, little is known about the effects of vocal warm-up on the voice. This study was designed to determine the relative effectiveness of specific versus combined warm-up strategies on the voice by group comparison. Twenty participants, 10 male and 10 female actors, completed two warm-up protocols, at least 1 week apart, in a counter-balanced order. Measures of phonation threshold pressure (PTP), jitter, noise-to-harmonics-ratio (NHR), and self-perceived vocal effort were obtained. For the males, there was no significant difference in PTP difference values between vocal warm-up only (specific) and vocal plus aerobic warm-up (combined) conditions. For the females, however, a significant difference was found, with a greater reduction in PTP in the combined warm-up condition. A significant difference was also found in male jitter percent values, with significantly lower values in the specific condition than in the combined condition. There were no significant differences in the remaining comparisons. Females appeared to respond more to the vocal warm-up when it had an aerobic exercise component. It is possible that the males' greater level of physical fitness impacted this finding.

Enhanced laboratory reports: using health information exchange data to provide contextual information to laboratory results for practices without electronic records.

We created a system that integrates contextual data for selected test results to help providers make appropriate clinical decisions on particular results. The system adds clinical reminders, historical test results, medication dispensing events, and visit information from a regional health information exchange database to create 'Enhanced Laboratory Reports'. The reports are delivered to the provider who ordered the test securely via web-based inbox or facsimile through a clinical messaging system.

Management academy for public health: creating entrepreneurial managers.

The Management Academy for Public Health develops public health managers' management skills. Ultimately, the program aims to develop civic entrepreneurs who can improve the efficiency and the effectiveness of their organizations. With help from a coach, teams write public health business plans to meet needs in their communities. An external evaluation found that 119 teams trained during the first 3 years of the program generated more than $6 million in enhanced revenue-including grants, contracts, and fees through their business plans--from $2 million in program funding. Approximately 38% of the teams expected to generate revenue from an academy business plan or a spin-off plan. Action-learning methods can help midcareer managers transfer their training to the workplace and build entrepreneurial skills.