Transfer of Guided Emergence Profile Developed Using Customized Provisional Implant Restoration and Cementation Using an Abutment Replica Technique: A Case Report.

The long-term success of dental implants depends not only upon implant osseointegration, but also on the surrounding soft tissue health and profile. An ideal emergence profile contributes to the aesthetics of an implant restoration. It maintains long-term implant health by preventing potential food accumulation and forming a barrier against bacterial ingress. This article describes a method for obtaining an impression of implants that will capture the custom guided peri-implant soft tissue contours accurately, thus contributing to a final restoration with favorable aesthetics. We also describe a technique for reducing excess cement in a cement retained implant crown, thereby contributing to the health of the peri-implant tissues.

A Cadaveric Study on Perforator Anatomy of the Medial Sural Artery Perforator Flap.

Background The medial sural artery perforator (MSAP) flap was described by Cavadas et al in 2001. The aim of this study was to analyze the flap characteristics in the regional population and was planned as a cadaveric dissection study. Methods Thirty-three legs of fresh cadavers were studied for perforator characteristics, length, and origin of pedicle and skin paddle thickness. Observations were documented and analyzed. Results Seventeen right legs (51.5%) and sixteen left legs (48.5%) were studied. Twenty-five pedicles originated from popliteal artery (86.2%) and four (13.8%) from the common sural trunk. No perforators were seen in four legs. The mean number of perforators is 2 (0-6). The mean distance of perforator from midpoint of popliteal fossa was 10.7 cm (8-13 cm) and from posterior midline it was 3.2 cm. The mean size of the perforator was 1.1 ± 0.8 mm (0.8-1.5 mm). The mean pedicle length was 9.3 ± 1.3 cm. The mean flap thickness was 4.3 ± 0.7 mm (3.0-5.5 mm). There was no correlation for flap or perforator characteristics with side of leg. Conclusion This study concludes that MSAP is a good flap in terms of perforator characteristics, pedicle length, and flap thickness, when a medium sized thin flap with long pedicle is needed. The location of perforator on calf varies in different population. Being a perforator flap, anatomical variability is common and should be thought of while choosing this flap.

Population-level analysis of natural control of HIV infection in Zambia and South Africa: HPTN 071 (PopART).

INTRODUCTION: HIV controllers have low viral loads (VL) without antiretroviral treatment (ART). We evaluated viraemic control in a community-randomized trial conducted in Zambia and South Africa that evaluated the impact of a combination prevention intervention on HIV incidence (HPTN 071 [PopART]; 2013-2018). METHODS: VL and antiretroviral (ARV) drug testing were performed using plasma samples collected 2 years after enrolment for 4072 participants who were HIV positive at the start of the study intervention. ARV drug use was assessed using a qualitative laboratory assay that detects 22 ARV drugs in five drug classes. Participants were classified as non-controllers if they had a VL ≥2000 copies/ml with no ARV drugs detected at this visit. Additional VL and ARV drug testing was performed at a second annual study visit to confirm controller status. Participants were classified as controllers if they had VLs <2000 with no ARV drugs detected at both visits. Non-controllers who had ARV drugs detected at either visit were excluded from the analysis to minimize potential confounders associated with ARV drug access and uptake. RESULTS: The final cohort included 126 viraemic controllers and 766 non-controllers who had no ARV drugs detected. The prevalence of controllers among the 4072 persons assessed was 3.1% (95% confidence interval [CI]: 2.6%, 3.6%). This should be considered a minimum estimate, since high rates of ARV drug use in the parent study limited the ability to identify controllers. Among the 892 participants in the final cohort, controller status was associated with biological sex (female > male, p = 0.027). There was no significant association between controller status and age, study country or herpes simplex virus type 2 (HSV-2) status at study enrolment. CONCLUSIONS: To our knowledge, this report presents the first large-scale, population-level study evaluating the prevalence of viraemic control and associated factors in Africa. A key advantage of this study was that a biomedical assessment was used to assess ARV drug use (vs. self-reported data). This study identified a large cohort of HIV controllers and non-controllers not taking ARV drugs, providing a unique repository of longitudinal samples for additional research. This cohort may be useful for further studies investigating the mechanisms of virologic control.

Torsion angles to map and visualize the conformational space of a protein.

Present understanding of protein structure dynamics trails behind that of static structures. A torsion-angle-based approach, called the representation of protein entities, derives an interpretable conformational space that correlates with data collection temperature, resolution, and reaction coordinate. For more complex systems, atomic coordinates fail to separate functional conformational states, which are still preserved by torsion angle-derived space. This indicates that torsion angles are often a more sensitive and biologically relevant descriptor for protein conformational dynamics than atomic coordinates.

Induction Chemotherapy Response in Childhood Acute Lymphoblastic Leukaemia and its Correlation with Cytogenetic and Molecular Features.

OBJECTIVE: To study the correlation of cytogenetic and molecular abnormalities on induction chemotherapy in childhood acute lymphoblastic leukaemia (ALL). STUDY DESIGN: Analytical study. PLACE AND DURATION OF STUDY: Department of Haematology, Armed Forces Institute of Pathology (AFIP), from March 2021 to August 2021. METHODOLOGY: Patients aged 1-18 years with newly diagnosed acute lymphoblastic leukaemia were inducted. Patients aged less than 1 year and more than 18 years were excluded from the study. The diagnosis was based on morphology, cytochemistry, flow cytometry, and cytogenetic/molecular analysis. Risk stratification was done on the basis of age, TLC, and cytogenetic/molecular defects. The UKALL 2011 protocol was used for treatment with regimen-A for standard risk and regimen-B for high-risk patients. Bone marrow was repeated on day 29 of induction therapy and blast percentage was assessed to establish post-induction remission. Association between cytogenetic / molecular abnormalities and post-induction remission status was analysed using chi-square test. RESULTS: There were total 142 patients with mean age of 6.4 + 3.6 years and a male- to-female ratio of 2.7:1. Immunophenotyping revealed 85.9% cases as B-cell ALL and 14.1% as T-cell ALL. The most frequent cytogenetic and molecular abnormalities were hyperdiploidy (19%), t(9;22)/BCR-ABL1(p190) (10.6%), complex karyotype (5.6%), E2A-PBX1 (8.5%), and TEL-AML1 (4.9%). A total of 127/142 (89.4%) achieved haematological remission after induction therapy with two deaths during induction therapy (1.4%). Post-induction remission rate in patients with favorable cytogenetic/molecular defects was 100% and in children with bad prognostic changes, the rate of remission was 69.2%. Chi-square test showed a significant association between cytogenetic/molecular abnormalities and post-induction remission (p-value <0.001). CONCLUSION: Cytogenetic and molecular abnormalities have a significant association with post-induction remission in children with acute lymphoblastic leukaemia. KEY WORDS: Acute lymphoblastic leukaemia, Cytogenetics, Chemotherapy, Induction, Remission.

Laboratory Evaluation and Pathological Features of Bone Marrow Metastasis in Non-haematological Malignancies.

This study aimed to analyse the diagnostic accuracy of different laboratory parameters that can predict bone marrow metastasis. A cross-sectional analytical study was conducted at the Armed Forces Institute of Pathology (AFIP), Rawalpindi from March 2021 to August 2021. Bone marrow aspirates and biopsy procedures were done on 60 newly diagnosed cases of non-haematological malignancies as part of staging. Laboratory parameters noted for the study included peripheral blood smear findings, serum lactate dehydrogenase (LDH), radiological findings, and bone marrow aspirate/trephine biopsy results. Bone marrow metastasis was seen in 21/60 patients. The most common malignancies with bone marrow involvement were retinoblastoma and neuroblastoma. Laboratory findings showed no significant statistical difference in mean haemoglobin and total leukocyte count between cases and controls. Positive cases had a mean platelet count of 261.7 x 109/L and mean LDH of 750.1 U/L (p <0.05) for both parameters. ROC analysis showed the area under the curve (AUC) for LDH to be 0.969 (highly significant) showing a strong predictive value of LDH. Positive radiological findings were detected in only one case with bone marrow metastasis. The elevated level of serum LDH is not only cost-effective but also has high diagnostic accuracy to predict bone marrow metastasis. Key Words: Bone marrow, Biochemical, Lactate dehydrogenase, Metastasis, Non-haematological malignancies.

Seasonal calving UK dairy herds: A farmer survey of fertility and veterinary services.

BACKGROUND: There is a lack of literature concerning dairy farmers' use of veterinary services and how satisfied they are with them. This study aimed to fill this gap for seasonal calving UK herds, with a focus on fertility, and included farmer perceived barriers to veterinary involvement. METHODS: A cross-sectional questionnaire (convenience sample), with 166 useable responses. RESULTS: Opportunities exist for further veterinary involvement in seasonal herds. Areas vets are least involved in currently are nutrition, breeding and genetics, growth rate monitoring and infrastructure changes. Current veterinary input was rated neutral or poor value by 21% of respondents. Over 90% of farmers want vets to ask questions to elicit their needs. Frequently mentioned barriers were 'lack of veterinary knowledge of our system', 'not enough cost-benefit of veterinary involvement' and 'we get our fertility information elsewhere'. Along with clinical ability and being approachable, 'understanding our system' and being 'proactive' were qualities participants most valued in a vet. After cost, 'pushing sales and interventions' were the least liked. CONCLUSION: Findings highlight the critical importance of clearly demonstrating the full cost-benefit of veterinary services to farmers. The results contain many details concerning farmer perceptions and values that can help veterinary businesses to strengthen existing services and develop new services.

Understanding doctors' emergency department antibiotic prescribing decisions in children with respiratory symptoms in the UK: a qualitative study.

OBJECTIVE: Exploration of the factors that influence hospital doctors' antibiotic prescribing decisions when treating children with respiratory symptoms in UK emergency departments. METHODS: A qualitative study using semistructured interviews based on a critical incident technique with 21 physicians of different grades and specialties that treat children in the UK. Interviews were audio-recorded then transcribed verbatim and analysed using thematic analysis. RESULTS: Four themes were identified. These themes illustrate factors which influence clinician prescribing. The three principal themes were authorities, pressures and risk. The fourth transcending theme that ran through all themes was clinician awareness and complicity ('knowing but still doing'). CONCLUSIONS: Hospital doctors prescribe antibiotics even when they know they should not. This appears to be due to the influence of those in charge or external pressures experienced while weighing up the immediate and longer term risks but clinicians do this with full insight into their actions. These findings have implications for invested parties seeking to develop future antimicrobial stewardship programmes. It is recommended that stewardship interventions acknowledge and target these themes which may in turn facilitate behaviour change and antimicrobial prescribing practice in emergency departments.

Non-compliance with clinical guidelines increases the risk of complications after primary total hip and knee joint replacement surgery.

BACKGROUND: Total hip and total knee replacement (THR/TKR) are common and effective surgeries to reduce the pain and disability associated with arthritis but are associated with small but significant risks of preventable complications such as surgical site infection (SSI) and venous-thrombo-embolism (VTE). This study aims to determine the degree to which hospital care was compliant with clinical guidelines for the prevention of SSI and VTE after THR/TKR; and whether non-compliant prophylaxis is associated with increased risk of complications. METHODS AND FINDINGS: A prospective multi-centre cohort study was undertaken in consenting adults with osteoarthritis undergoing elective primary TKR/THR at one of 19 high-volume Australian public or private hospitals. Data were collected prior to surgery and for one-year post-surgery. Four adjusted logistic regression analyses were undertaken to explore associations between binary non-compliance and the risk of surgical complications: (1) composite (simultaneous) non-compliance with both (VTE and antibiotic) guidelines and composite complications [all-cause mortality, VTE, readmission/reoperation for joint-related reasons (one-year) and non-joint-related reasons (35-days)], (2) VTE non-compliance and VTE outcomes, (3) antibiotic non-compliance and any SSI, and (4) antibiotic non-compliance and deep SSI. Data were analysed for 1875 participants. Guideline non-compliance rates were high: 65% (VTE), 87% (antibiotics) and 95% (composite guideline). Composite non-compliance was not associated with composite complication (12.8% vs 8.3%, adjusted odds ratio [AOR] = 1.41, 95%CI 0.68-3.45, p = 0.40). Non-compliance with VTE guidelines was associated with VTE outcomes (5% vs 2.4%, AOR = 2.83, 95%CI 1.59-5.28,p < 0.001). Non-compliance with antibiotic guidelines was associated with any SSI (14.8% vs 6.1%, AOR = 1.98, 95%CI 1.17-3.62,p = 0.02) but not deep infection (3.7% vs 1.2%,AOR = 2.39, 95%CI 0.85-10.00, p = 0.15). CONCLUSIONS: We found high rates of clinical variation and statistically significant associations between non-compliance with VTE and antibiotic guidelines and increased risk of VTE and SSI, respectively. Complications after THR/TKR surgery may be decreased by improving compliance with clinical guidelines.

Motivations and Barriers for Veterinarians When Facilitating Fertility Management on UK Dairy Farms.

It is economically essential, but challenging, for dairy farmers to manage bovine fertility. Vets can help farmers to improve fertility, and this is cost-effective bringing benefits for production, animal health and welfare, and the environment. However, the extent to which vets are involved in fertility varies considerably between farms, for reasons that are unclear. This study investigated the motivators and barriers that vets perceive when trying to increase their involvement with fertility management on UK dairy farms. Interviews were conducted with 20 vets and four themes identified. The first, "clinical baggage," highlighted vets' disillusionment due to past experiences of low uptake of their advice by farmers. Consequently, some vets made assumptions about farmer needs and behaviours, and exhibited ageist stereotyping. These issues, along with concerns and fatigue associated with repeatedly offering the same advice which was not acted upon, negatively influenced vets' engagement with farmers. The second theme "stuck in the comfort zone" revealed a loss of enthusiasm by some senior vets, whilst others lacked confidence to engage due to perceived gaps in their knowledge. Vets also reported farmers not perceiving their problems and lack of farm data or facilities, as barriers. The "vet-farmer relationship" theme highlighted building trust and developing strong relationships which were key drivers for vets to proactively engage and to "go the extra mile" for their clients. The final theme "money matters" explored vets' motivations to improve their clients' profitability and included the future sustainability of their own businesses. Our themes provide useful insight into the challenges vets face and provide key areas that can be targeted in future interventions to improve veterinary involvement in fertility management. For example, post-graduate training and support for vets needs to consider factors such as reflection, mentorship, stereotyping, relationships, communication, and leadership skills. This type of postgraduate support is currently limited for vets and requires investment from stakeholders if improvements in production, animal health and welfare, and the environment are to be achieved. Our findings are informative for facilitating veterinary involvement in any disease context, and are relevant for stakeholders including governments, educators, charities, farmer representatives, environmentalists, and veterinary leaders.

Lameness in Beef Cattle: A Cross-Sectional Descriptive Survey of On-Farm Practices and Approaches.

Cattle lameness is a concern to the United Kingdom (UK) cattle industry, negatively impacting upon welfare and production. Previous work involving one small study (n = 21) has identified that some UK beef farmers underestimate lameness prevalence, but also that farmers vary in their perception of the impact of lameness. Knowledge and skills of farmers were identified as a potential concern, and farmer-reported barriers were identified. However, the extent to which these views can be extrapolated is unknown. Therefore, the aim of this study was to produce descriptive results of UK beef farmer lameness-related activities concerning lameness identification, examination, treatment, and prevention. Questionnaires were circulated online and via post. Postal questionnaires were sent to registered Approved Finishing Units (a specific cohort of beef fattening units subject to strict biosecurity measures as part of UK bovine tuberculosis control) and a stratified sample of all registered beef enterprises in England and Wales. Online questionnaires were circulated on social media and via targeted emails asking selected industry bodies and veterinary practices to distribute to farmers. Descriptive results were produced, and thematic analysis was performed on free text responses. There were 532 usable responses, with most farmers self-reporting their current lameness prevalence as zero (mean 1.2%, range 0-20%). Most respondents did not locomotion score cattle, and most reported that it was not safe to examine feet. Most farmers did not use a foot bath, but of those who did, formaldehyde was the most commonly used product. Some farmers reported use of antibiotic foot baths. Most farmers reported dealing with lame animals within 48 h, but some only dealt with severe cases, and some felt that lame animals would get better by themselves. To deal with animals that have an ongoing lameness problem, transportation to slaughter was considered an option by 35% of farmers. It is worth noting, however, that the majority of lame animals would be precluded from transport under UK legislation. Farmers reported staff shortages, as well as a lack of time, training, and knowledge as barriers to lameness prevention and control. Overall, these results suggest that farmers may be underestimating lameness. Diagnosis is likely to be challenging, with unsafe facilities for lifting feet. The reported high threshold by some farmers for attending to a lame animal is a cause for concern, negatively impacting upon animal welfare, but this is also likely to have negative consequences for animal performance and farm profitability. Many participants in this study expressed a desire for farmer training in several aspects relating to lameness prevention and control, and this represents an opportunity for further knowledge exchange regarding lameness in beef cattle.

"Here Comes the Junkies," Opioid Replacement Therapy in Rural Australia.

BACKGROUND: Opioid replacement therapy (ORT) offers a harm minimization approach and is the mainstay treatment option for opioid dependence in Australia. Recovery is known to be complicated because of service access, cost, workforce availability, privacy, stigma, and discrimination. Rural living is considered to magnify each complication of recovery, yet little is understood about how opioid dependence recovery is experienced in rural Australia. This study aimed to explore the lived experience of people receiving ORT in rural Australia and describe impediments to recovery. METHODS: In this qualitative study design, all outpatients enrolled in ORT at two rural Australian sites were invited to participate. Six volunteers from each site participated in a semistructured interview (eight men, four women; mean age = 44.8 years). RESULTS: The participants had completed 3 years of secondary school education on average. Four major themes emerged: reinvention, restriction, employment, and reconnection. Small communities increased the likelihood of ORT participants knowing people both directly and indirectly, affecting their ability to reconstruct an identity. Lived distance from prescribers and dosing points dictated daily activity, including opportunities to seek and maintain employment. Rural ORT treatment seekers indicated that geographical displacement and separation from family, the people they needed to reconnect with, were challenging. CONCLUSION: Rural people engaged in ORT require positive reinforcement from service providers, enabling identity reinvention and disconnection from the drug-seeking world. Acknowledging underlying trauma and supporting reconnection with loved ones may foster positive social connectedness.

Segmented flow generator for serial crystallography at the European X-ray free electron laser.

Serial femtosecond crystallography (SFX) with X-ray free electron lasers (XFELs) allows structure determination of membrane proteins and time-resolved crystallography. Common liquid sample delivery continuously jets the protein crystal suspension into the path of the XFEL, wasting a vast amount of sample due to the pulsed nature of all current XFEL sources. The European XFEL (EuXFEL) delivers femtosecond (fs) X-ray pulses in trains spaced 100 ms apart whereas pulses within trains are currently separated by 889 ns. Therefore, continuous sample delivery via fast jets wastes >99% of sample. Here, we introduce a microfluidic device delivering crystal laden droplets segmented with an immiscible oil reducing sample waste and demonstrate droplet injection at the EuXFEL compatible with high pressure liquid delivery of an SFX experiment. While achieving ~60% reduction in sample waste, we determine the structure of the enzyme 3-deoxy-D-manno-octulosonate-8-phosphate synthase from microcrystals delivered in droplets revealing distinct structural features not previously reported.

Reliability of a beef cattle locomotion scoring system for use in clinical practice.

BACKGROUND: Locomotion (lameness) scoring has been used and studied in the dairy industry; however, to the authors' knowledge, there are no studies assessing the reliability of locomotion scoring systems when used with beef cattle. METHODS: A four-point scoring system was developed and beef cattle filmed walking on a firm surface. Eight veterinary researchers, eight clinicians and eight veterinary students were shown written descriptors of the scoring system and four video clips for training purposes, before being asked to score 40 video clips in a random order. Participants repeated this task 4 days later. RESULTS: The intra-observer agreement (the same person scoring on different days) was acceptable with weighted mean Kappa values of 0.84, 0.81 and 0.84 respectively for researchers, clinicians and students. The inter-observer agreement (different people scoring the same animal) was acceptable with weighted Gwet's Agreement Coefficient values of 0.70, 0.69 and 0.64 for researchers, clinicians and students. Most disagreement occurred over scores one (not lame but imperfect locomotion) and two (lame, but not severe). CONCLUSION: This scoring system has the potential to reliably score lameness in beef cattle and help facilitate lameness treatment and control; however, some disagreements will occur especially over scores one and two.

Lameness in Beef Cattle: UK Farmers' Perceptions, Knowledge, Barriers, and Approaches to Treatment and Control.

Lameness in the beef industry has received little attention in the UK, despite the fact that it is a well-recognised problem in the dairy industry. The aims of this study were to (i) compare UK beef farmers' estimates of lameness prevalence to that of researchers, (ii) explore beef farmers' attitudes towards lameness, and (iii) help identify farmer reported barriers to lameness control and treatment. Beef farmers (11 finishing units and 10 suckler farms) were recruited from England and Wales. Farmers were asked to estimate their lameness prevalence, before a researcher conducted locomotion scoring using a five point scale, and a Bland Altman analysis performed. Face to face interviews were also conducted using a semi structured interview script aimed at capturing information such as current approaches and protocols as well as their views of lameness importance. Interviews were recorded and transcribed. An inductive thematic analysis was performed. All but two farmers underestimated lameness prevalence on their farms when compared to the researcher. Farmers initially underestimated lameness prevalence compared to the researchers estimates, with a mean underestimate of 7% (95% CI 5-9%). This is an important barrier to lameness detection and treatment. Thematic analysis identified four major themes: (1). Perception of lameness prevalence, (2). Technical knowledge and skills, (3). Perception of the impact of lameness, and (4). Barriers to the treatment and control of lameness. This study highlights that some approaches to lameness treatment are likely to be causing harm, despite being done with the intention to help the animal. There were four key areas of concern identified: recognition of lameness, treatment approaches, the training provided to farmers and confusion over transport and slaughter options available to farmers. This suggests an urgent need for future work to quantify and address the problem, and to provide evidence to justify the role of prevention and potentially start to break down barriers to control and treatment of lameness.

Megahertz serial crystallography.

The new European X-ray Free-Electron Laser is the first X-ray free-electron laser capable of delivering X-ray pulses with a megahertz inter-pulse spacing, more than four orders of magnitude higher than previously possible. However, to date, it has been unclear whether it would indeed be possible to measure high-quality diffraction data at megahertz pulse repetition rates. Here, we show that high-quality structures can indeed be obtained using currently available operating conditions at the European XFEL. We present two complete data sets, one from the well-known model system lysozyme and the other from a so far unknown complex of a ß-lactamase from K. pneumoniae involved in antibiotic resistance. This result opens up megahertz serial femtosecond crystallography (SFX) as a tool for reliable structure determination, substrate screening and the efficient measurement of the evolution and dynamics of molecular structures using megahertz repetition rate pulses available at this new class of X-ray laser source.

Preservation of female fertility in humans and animal species.

A detailed understanding of the cryobiology of gametes and complex tissues has led to the development of methods that facilitate the successful low temperature banking of isolated mature human oocytes, or immature oocytes in situ within fragments of human ovarian cortex. Although many outstanding research challenges remain to be addressed, the successful development of new treatments to preserve female fertility for a range of clinical indications has largely been underpinned by the conduct of extensive, fundamental research on oocytes and ovarian tissues from a number of laboratory and commercially important farm species. Indeed, the most recent evidence from large animals suggests that it is also possible to cryopreserve intact whole ovaries along with their supporting vasculature for later auto-transplantation and restoration of natural fertility. This review will explore how the methods developed to preserve human oocytes and ovarian tissues can now be used strategically to support the development of conservation strategies aimed at safeguarding the genetic diversity of commercially important domestic animals and also of preserving the female germplasm for wild animals and endangered species.

The slip-and-slide algorithm: a refinement protocol for detector geometry.

Geometry correction is traditionally plagued by mis-fitting of correlated parameters, leading to local minima which prevent further improvements. Segmented detectors pose an enhanced risk of mis-fitting: even a minor confusion of detector distance and panel separation can prevent improvement in data quality. The slip-and-slide algorithm breaks down effects of the correlated parameters and their associated target functions in a fundamental shift in the approach to the problem. Parameters are never refined against the components of the data to which they are insensitive, providing a dramatic boost in the exploitation of information from a very small number of diffraction patterns. This algorithm can be applied to exploit the adherence of the spot-finding results prior to indexing to a given lattice using unit-cell dimensions as a restraint. Alternatively, it can be applied to the predicted spot locations and the observed reflection positions after indexing from a smaller number of images. Thus, the indexing rate can be boosted by 5.8% using geometry refinement from only 125 indexed patterns or 500 unindexed patterns. In one example of cypovirus type 17 polyhedrin diffraction at the Linac Coherent Light Source, this geometry refinement reveals a detector tilt of 0.3° (resulting in a maximal Z-axis error of ∼0.5 mm from an average detector distance of ∼90 mm) whilst treating all panels independently. Re-indexing and integrating with updated detector geometry reduces systematic errors providing a boost in anomalous signal of sulfur atoms by 20%. Due to the refinement of decoupled parameters, this geometry method also reaches convergence.

Relationship Between Laryngeal Electromyography and Video Laryngostroboscopy in Vocal Fold Paralysis.

OBJECTIVES/HYPOTHESIS: The objective of this study was to better define the relationship of laryngeal electromyography and video laryngostroboscopy in the diagnosis of vocal fold paralysis. STUDY DESIGN: Retrospective diagnostic cohort study with cross-sectional data analysis METHODS: Data were obtained from 57 patients with unilateral vocal fold paralysis who attended a large tertiary voice referral center. Electromyographic findings were classified according to recurrent laryngeal nerve, superior laryngeal nerve, and high vagal/combined lesions. Video laryngostroboscopy recordings were classified according to the position of the immobile fold into median, paramedian, lateral, and a foreshortened/hooded vocal fold. The position of the paralyzed vocal fold was then analyzed according to the lesion as determined by electromyography. RESULTS: The recurrent laryngeal nerve was affected in the majority of cases with left-sided lesions more common than right. Vocal fold position differed between recurrent laryngeal and combined vagal lesions. Recurrent laryngeal nerve lesions were more commonly associated with a laterally displaced immobile fold. No fold position was suggestive of a combined vagal lesion. The inter-rater reliability for determining fold position was high. CONCLUSION: Laryngeal electromyography is useful in diagnosing neuromuscular dysfunction of the larynx and best practice recommends its continued implementation along with laryngostroboscopy. While recurrent laryngeal nerve lesions are more likely to present with a lateral vocal fold, this does not occur in all cases. Such findings indicate that further unknown mechanisms contribute to fold position in unilateral paralysis.

Nup358 binds to AGO proteins through its SUMO-interacting motifs and promotes the association of target mRNA with miRISC.

MicroRNA (miRNA)-guided mRNA repression, mediated by the miRNA-induced silencing complex (miRISC), is an important component of post-transcriptional gene silencing. However, how miRISC identifies the target mRNA in vivo is not well understood. Here, we show that the nucleoporin Nup358 plays an important role in this process. Nup358 localizes to the nuclear pore complex and to the cytoplasmic annulate lamellae (AL), and these structures dynamically associate with two mRNP granules: processing bodies (P bodies) and stress granules (SGs). Nup358 depletion disrupts P bodies and concomitantly impairs the miRNA pathway. Furthermore, Nup358 interacts with AGO and GW182 proteins and promotes the association of target mRNA with miRISC A well-characterized SUMO-interacting motif (SIM) in Nup358 is sufficient for Nup358 to directly bind to AGO proteins. Moreover, AGO and PIWI proteins interact with SIMs derived from other SUMO-binding proteins. Our study indicates that Nup358-AGO interaction is important for miRNA-mediated gene silencing and identifies SIM as a new interacting motif for the AGO family of proteins. The findings also support a model wherein the coupling of miRISC with the target mRNA could occur at AL, specialized domains within the ER, and at the nuclear envelope.