Impact of visual rotations on heading direction and center of mass control during steady state gait.

Visual information is essential to navigate the environment and maintain postural stability during gait. Visual field rotations alter the perceived heading direction and center of mass (CoM) trajectory. This interaction, referred to as visual coupling, is poorly characterized during steady-state gait. Moreover, it is unclear how visual field rotations affect CoM control relative to the continuously changing base of support (BoS). This study aimed to characterize the role of visual information in heading and mediolateral (ML) balance control during unperturbed, steady-state gait. Sixteen healthy participants walked on an instrumented treadmill, naïve to sinusoidal low-frequency (0.1 Hz) rotations of the virtual environment. Rotations had a 1) high (CMH) or 2) low amplitude (CML), or were 3) periodical left-right manipulations (PM) with 10 second intervals. Coupling between CoM trajectory and visual manipulations was in-phase and showed strong cross-correlations on group level (CML: 0.88, CMH: 0.91 and PM: 0.95) and moderate to strong on individual level (CML: 0.52 ± 0.15, CMH: 0.56 ± 0.17 and PM: 0.80 ± 0.07). Higher manipulation amplitudes induced stronger CoM trajectory deviations. The margin of stability (MoSML), characterizing ML balance control, decreased towards the deviation direction and increased at the opposite side. Furthermore, a pelvis and feet reorientation towards the manipulation direction was observed. We concluded that visual information is continuously used to determine and adjust heading direction during steady-state gait. To facilitate these adjustments, the body was reorientated and the CoM-ML shifted closer to the lateral BoS boundary towards the adjusted heading direction, while preserving CoM excursion.

Efficacy of Walking Adaptability Training on Walking Capacity in Ambulatory People With Motor Incomplete Spinal Cord Injury: A Multicenter Pragmatic Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: Balance and walking capacity are often impaired in people with motor incomplete spinal cord injury (iSCI), frequently resulting in reduced functional ambulation and participation. This study aimed to assess the efficacy of walking adaptability training compared to similarly dosed conventional locomotor and strength training for improving walking capacity, functional ambulation, balance confidence, and participation in ambulatory people with iSCI. METHODS: We conducted a 2-center, parallel-group, pragmatic randomized controlled trial. Forty-one people with iSCI were randomized to 6 weeks of (i) walking adaptability training (11 hours of Gait Real-time Analysis Interactive Lab (GRAIL) training-a treadmill in a virtual reality environment) or (ii) conventional locomotor and strength training (11 hours of treadmill training and lower-body strength exercises). The primary measure of walking capacity was maximal walking speed, measured with an overground 2-minute walk test. Secondary outcome measures included the Spinal Cord Injury Functional Ambulation Profile (SCI-FAP), the Activities-specific Balance Confidence (ABC) scale, and the Utrecht Scale for Evaluation of Rehabilitation-Participation (USER-P). RESULTS: No significant difference in maximal walking speed between the walking adaptability (n = 17) and conventional locomotor and strength (n = 18) training groups was found 6 weeks after training at follow-up (-0.05 m/s; 95% CI = -0.12-0.03). In addition, no significant group differences in secondary outcomes were found. However, independent of intervention, significant improvements over time were found for maximal walking speed, SCI-FAP, ABC, and USER-P restrictions scores. Conclusions. Our findings suggest that walking adaptability training may not be superior to conventional locomotor and strength training for improving walking capacity, functional ambulation, balance confidence, or participation in ambulatory people with iSCI. TRIAL REGISTRATION: Dutch Trial Register; Effect of GRAIL training in iSCI.

Exploiting long read sequencing to detect azole fungicide resistance mutations in Pyrenophora teres using unique molecular identifiers.

Resistance to fungicides is a global challenge as target proteins under selection can evolve rapidly, reducing fungicide efficacy. To manage resistance, detection technologies must be fast and flexible enough to cope with a rapidly increasing number of mutations. The most important agricultural fungicides are azoles that target the ergosterol biosynthetic enzyme sterol 14α-demethylase (CYP51). Mutations associated with azole resistance in the Cyp51 promoter and coding sequence can co-occur in the same allele at different positions and codons, increasing the complexity of resistance detection. Resistance mutations arise rapidly and cannot be detected using traditional amplification-based methods if they are not known. To capture the complexity of azole resistance in two net blotch pathogens of barley we used the Oxford Nanopore MinION to sequence the promoter and coding sequence of Cyp51A. This approach detected all currently known mutations from biologically complex samples increasing the simplicity of resistance detection as multiple alleles can be profiled in a single assay. With the mobility and decreasing cost of long read sequencing, we demonstrate this approach is broadly applicable for characterizing resistance within known agrochemical target sites.

Maternal ethnicity and socioeconomic deprivation: influence on adverse pregnancy outcomes.

OBJECTIVES: To evaluate the relative importance of ethnicity and socioeconomic deprivation in determining the likelihood and the percentage of composite adverse pregnancy outcomes (CAPO) and composite of severe adverse pregnancy outcomes (CAPO-S) METHODS: This is a single centre retrospective cohort study conducted in a tertiary maternity unit. Data regarding the ethnicity and socioeconomic deprivation were collected for 13,165 singleton pregnant women routinely screened in the first trimester for preeclampsia using the Fetal Medicine Foundation combined algorithm. RESULTS: The prevalence or risk of CAPO was 16.3% for White women, 29.3% for Black women and 29.3% for South Asian women. However, half of all CAPO cases (51.7%) occurred in White women. There is a strong interaction between ethnicity and socioeconomic deprivation (as measured with indices of multiple deprivation). Both influence the prevalence of CAPO and CAPO-S, with the contribution of ethnicity being strongest. CONCLUSIONS: Black and Asian ethnicity as well as socioeconomic deprivation influence the prevalence of placentally-mediated adverse pregnancy outcomes. Despite this, most adverse pregnancy outcomes occur in White women, who represent the majority of the population and are also affected by socioeconomic deprivation. For these reasons, inclusion of socioeconomic deprivation should be considered in early pregnancy risk assessment for placentally-mediated CAPO. This article is protected by copyright. All rights reserved.

SARS-Cov-2 small viral RNA suppresses gene expression via complementary binding to mRNA 3' UTR.

SARS-CoV-2 (SC2) has been intensely studied since its emergence. However, the mechanisms of host immune dysregulation triggered by SC2 remain poorly understood. That said, it is well established that many prominent viral families encode microRNAs (miRNAs) or related small viral RNAs (svRNAs) capable of regulating human genes involved in immune function. Importantly, recent reports have shown that SC2 encodes its own svRNAs. In this study, we have identified 12 svRNAs expressed during SC2 infection and show that one of these svRNAs can regulate target gene expression via complementary binding to mRNA 3' untranslated regions (3'UTRs) much like human microRNAs.

Assessment of Foot Strike Angle and Forward Propulsion with Wearable Sensors in People with Stroke.

Effective retraining of foot elevation and forward propulsion is a critical aspect of gait rehabilitation therapy after stroke, but valuable feedback to enhance these functions is often absent during home-based training. To enable feedback at home, this study assesses the validity of an inertial measurement unit (IMU) to measure the foot strike angle (FSA), and explores eight different kinematic parameters as potential indicators for forward propulsion. Twelve people with stroke performed walking trials while equipped with five IMUs and markers for optical motion analysis (the gold standard). The validity of the IMU-based FSA was assessed via Bland-Altman analysis, ICC, and the repeatability coefficient. Eight different kinematic parameters were compared to the forward propulsion via Pearson correlation. Analyses were performed on a stride-by-stride level and within-subject level. On a stride-by-stride level, the mean difference between the IMU-based FSA and OMCS-based FSA was 1.4 (95% confidence: -3.0; 5.9) degrees, with ICC = 0.97, and a repeatability coefficient of 5.3 degrees. The mean difference for the within-subject analysis was 1.5 (95% confidence: -1.0; 3.9) degrees, with a mean repeatability coefficient of 3.1 (SD: 2.0) degrees. Pearson's r value for all the studied parameters with forward propulsion were below 0.75 for the within-subject analysis, while on a stride-by-stride level the foot angle upon terminal contact and maximum foot angular velocity could be indicative for the peak forward propulsion. In conclusion, the FSA can accurately be assessed with an IMU on the foot in people with stroke during regular walking. However, no suitable kinematic indicator for forward propulsion was identified based on foot and shank movement that could be used for feedback in people with stroke.

Workflows for detecting fungicide resistance in net form and spot form net blotch pathogens.

BACKGROUND: Fungicide resistance in Pyrenophora teres f. maculata and P. teres f. teres has become an important disease management issue. Control of the associated barley foliar diseases, spot form and net form net blotch, respectively, relies on three major groups of fungicides, demethylation inhibitors (DMIs), succinate dehydrogenase inhibitors (SDHIs) and quinone outside inhibitors (QoIs). However, resistance has been reported for the DMI and SDHI fungicides in Australia. To enhance detection of different resistance levels, phenotyping and genotyping workflows were designed. RESULTS: The phenotyping workflow generated cultures directly from lesions and compared growth on discriminatory doses of tebuconazole (DMI) and fluxapyroxad (SDHI). Genotyping real-time polymerase chain reaction (PCR) assays were based on alleles associated with sensitivity or resistance to the DMI and SDHI fungicides. These workflows were applied to spot form and net form net blotch collections from 2019 consisting predominantly of P. teres f. teres from South Australia and P. teres f. maculata from Western Australia. For South Australia the Cyp51A L489-3 and SdhC-R134 alleles, associated with resistance to tebuconazole and fluxapyroxad, respectively, were the most prevalent. These alleles were frequently found in single isolates with dual resistance. This study also reports the first detection of a 134 base pair insertion located at position-66 (PtTi-6) in the Cyp51A promoter of P. teres f. maculata from South Australia. For Western Australia, the PtTi-1 insertion was the most common allele associated with resistance to tebuconazole. CONCLUSION: The workflow and PCR assays designed in this study have been demonstrated to efficiently screen P. teres collections for both phenotypic and genetic resistance to DMI and SDHI fungicides. The distribution of reduced sensitivity and resistance to DMI and SDHI fungicides varied between regions in south-western Australia, suggesting the emergence of resistance was impacted by both local pathogen populations and disease management programmes. The knowledge of fungicide resistance in regional P. teres collections will be important for informing appropriate management strategies. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Orthopedic footwear has a positive influence on gait adaptability in individuals with hereditary motor and sensory neuropathy.

BACKGROUND: Individuals with Hereditary Motor and Sensory Neuropathy (HMSN) are commonly provided with orthopedic footwear to improve gait. Although orthopedic footwear has shown to improve walking speed and spatiotemporal parameters, its effect on gait adaptability has not been established. RESEARCH QUESTION: What is the effect of orthopedic footwear on gait adaptability in individuals with HMSN? METHODS: Fifteen individuals with HMSN performed a precision stepping task on an instrumented treadmill projecting visual targets, while wearing either custom-made orthopedic or standardized footwear (i.e. minimally supportive, flexible sneakers). Primary measure of gait adaptability was the absolute Euclidean distance [mm] between the target center and the middle of the foot (absolute error). Secondary outcomes included the relative and variable error [mm] in both anterior-posterior (AP) and medial-lateral (ML) directions. Dynamic balance was assessed by the prediction of ML foot placement based on the ML center of mass position and velocity, using linear regression. Dynamic balance was primarily determined by foot placement deviation in terms of root mean square error. Another aspect of dynamic balance was foot placement adherence in terms of the coefficient of determination (R2). Differences between the footwear conditions were analyzed with a paired t-test or Wilcoxon signed-rank test (α = 0.05). RESULTS: The absolute error, relative error (AP) and variable error (AP and ML) decreased with orthopedic footwear, whereas the relative error in ML-direction slightly increased. As for dynamic balance, no effect on foot placement deviation or adherence was found. SIGNIFICANCE: Gait adaptability improved with orthopedic compared to standardized footwear in people with HMSN, as indicated by improved precision stepping. Dynamic balance, as a possible underlying mechanism, was not affected by orthopedic footwear.

Improved walking capacity after complementary ankle-foot surgery and gait training in a person with an incomplete tetraplegia; a case report.

INTRODUCTION: The population of people with a spinal cord injury (SCI) is changing to a diverse population with an increasing number of incomplete lesions. Often, these individuals have the capacity to walk, but experience disabling gait impairments. CASE PRESENTATION: The course of a 34-year-old male with a chronic incomplete traumatic cervical SCI who initially could walk no more than a few steps with supervision or a wheeled walker is described. He participated in a clinical trial with Targeted Epidural Spinal Stimulation (TESS). After this trial, he was able to walk with a wheeled walker and bilateral orthosis over a distance of 100 meters. Despite these improvements, his main complaints were (1) difficulty to correctly preposition the feet, and (2) pain in his toe and calf muscles. An interdisciplinary approach and the use of structured gait analysis formed the basis for shared decision-making with the team and the patient to perform ankle-foot surgery followed by 2-month gait training with a body weight support system. After this trajectory his walking distance increased to 250 meters, with a wheeled walker; but now without orthosis and with an increased walking speed compared to pre-surgery. Additionally, there was reduction of pain and he experienced no disturbances during sleeping, washing and clothing anymore. DISCUSSION: This case shows that surgical interventions can improve the gait capacity even in case of chronic incomplete SCI. Furthermore, training with a body weight support system after medical-technical interventions is useful to utilize the full potential of these interventions.

Quantitative assessment of plantar pressure patterns in relation to foot deformities in people with hereditary motor and sensory neuropathies.

BACKGROUND: Hereditary motor and sensory neuropathies (HMSN), also known as Charcot-Marie-Tooth disease, are characterized by affected peripheral nerves. This often results in foot deformities that can be classified into four categories: (1) plantar flexed first metatarsal, neutral hindfoot, (2) plantar flexed first metatarsal, correctable hindfoot varus, (3) plantar flexed first metatarsal, uncorrectable hindfoot varus, and (4) hindfoot valgus. To improve management and for the evaluation of surgical interventions, a quantitative evaluation of foot function is required. The first aim of this study was to provide insight into plantar pressure of people with HMSN in relation to foot deformities. The second aim was to propose a quantitative outcome measure for the evaluation of surgical interventions based on plantar pressure. METHODS: In this historic cohort study, plantar pressure measurements of 52 people with HMSN and 586 healthy controls were evaluated. In addition to the evaluation of complete plantar pressure patterns, root mean square deviations (RMSD) of plantar pressure patterns from the mean plantar pressure pattern of healthy controls were calculated as a measure of abnormality. Furthermore, center of pressure trajectories were calculated to investigate temporal characteristics. Additionally, plantar pressure ratios of the lateral foot, toes, first metatarsal head, second/third metatarsal heads, fifth metatarsal head, and midfoot were calculated to measure overloading of foot areas. RESULTS: Larger RMSD values were found for all foot deformity categories compared to healthy controls (p < 0.001). Evaluation of the complete plantar pressure patterns revealed differences in plantar pressure between people with HMSN and healthy controls underneath the rearfoot, lateral foot, and second/third metatarsal heads. Center of pressure trajectories differed between people with HMSN and healthy controls in the medio-lateral and anterior-posterior direction. The plantar pressure ratios, and especially the fifth metatarsal head pressure ratio, differed between healthy controls and people with HMSN (p < 0.05) and between the four foot deformity categories (p < 0.05). CONCLUSIONS: Spatially and temporally distinct plantar pressure patterns were found for the four foot deformity categories in people with HMSN. We suggest to consider the RMSD in combination with the fifth metatarsal head pressure ratio as outcome measures for the evaluation of surgical interventions in people with HMSN.

The Influence of Stride Selection on Gait Parameters Collected with Inertial Sensors.

Different methods exist to select strides that represent preferred, steady-state gait. The aim of this study was to identify the effect of different stride-selection methods on spatiotemporal gait parameters to analyze steady-state gait. A total of 191 patients with hip or knee osteoarthritis (aged 38-85) wearing inertial sensors walked back and forth over 10 m for two minutes. After the removal of strides in turns, five stride-selection methods were compared: (ALL) include all strides, others removed (REFERENCE) two strides around turns, (ONE) one stride around turns, (LENGTH) strides <63% of median stride length, and (SPEED) strides that fall outside the 95% confidence interval of gait speed over the strides included in REFERENCE. Means and SDs of gait parameters were compared for each trial against the most conservative definition (REFERENCE). ONE and SPEED definitions resulted in similar means and SDs compared to REFERENCE, while ALL and LENGTH definitions resulted in substantially higher SDs of all gait parameters. An in-depth analysis of individual strides showed that the first two strides after and last two strides before a turn were significantly different from steady-state walking. Therefore, it is suggested to exclude the first two strides around turns to assess steady-state gait.

Examining the role of intrinsic and reflexive contributions to ankle joint hyper-resistance treated with botulinum toxin-A.

BACKGROUND: Spasticity, i.e. stretch hyperreflexia, increases joint resistance similar to symptoms like hypertonia and contractures. Botulinum neurotoxin-A (BoNT-A) injections are a widely used intervention to reduce spasticity. BoNT-A effects on spasticity are poorly understood, because clinical measures, e.g. modified Ashworth scale (MAS), cannot differentiate between the symptoms affecting joint resistance. This paper distinguishes the contributions of the reflexive and intrinsic pathways to ankle joint hyper-resistance for participants treated with BoNT-A injections. We hypothesized that the overall joint resistance and reflexive contribution decrease 6 weeks after injection, while returning close to baseline after 12 weeks. METHODS: Nine participants with spasticity after spinal cord injury or after stroke were evaluated across three sessions: 0, 6 and 12 weeks after BoNT-A injection in the calf muscles. Evaluation included clinical measures (MAS, Tardieu Scale) and motorized instrumented assessment using the instrumented spasticity test (SPAT) and parallel-cascade (PC) system identification. Assessments included measures for: (1) overall resistance from MAS and fast velocity SPAT; (2) reflexive resistance contribution from Tardieu Scale, difference between fast and slow velocity SPAT and PC reflexive gain; and (3) intrinsic resistance contribution from slow velocity SPAT and PC intrinsic stiffness/damping. RESULTS: Individually, the hypothesized BoNT-A effect, the combination of a reduced resistance (week 6) and return towards baseline (week 12), was observed in the MAS (5 participants), fast velocity SPAT (2 participants), Tardieu Scale (2 participants), SPAT (1 participant) and reflexive gain (4 participants). On group-level, the hypothesis was only confirmed for the MAS, which showed a significant resistance reduction at week 6. All instrumented measures were strongly correlated when quantifying the same resistance contribution. CONCLUSION: At group-level, the expected joint resistance reduction due to BoNT-A injections was only observed in the MAS (overall resistance). This observed reduction could not be attributed to an unambiguous group-level reduction of the reflexive resistance contribution, as no instrumented measure confirmed the hypothesis. Validity of the instrumented measures was supported through a strong association between different assessment methods. Therefore, further quantification of the individual contributions to joint resistance changes using instrumented measures across a large sample size are essential to understand the heterogeneous response to BoNT-A injections.

Global Switch from DICER-dependent MicroRNA to DICER-independent SnoRNA-derived RNA Biogenesis in Malignancy.

SnoRNAs are frequently processed into snoRNA-derived RNAs (sdRNAs) that function much like traditional microRNAs (miRNAs). That said, our analyses suggest a global switch from DICER-dependent (predominately miRNA) to DICER-independent (predominately sdRNA) biogenesis/gene regulation in colon cancer. Whereas the expressions of 259 of 288 appreciably expressed miRNAs are significantly decreased (avg. 6.4% of WT) in human colon cancer DICER-KOs, 95 of 103 sdRNAs are conversely, significantly increased (avg. 679.3%) in DICER-KOs as compared to WT. As many diseases are characterized by DICER deficiency, this putative global switch to DICER-independent sdRNA regulations may contribute to an array of human diseases.

Characterisation of vaping liquids used in vaping devices across four countries: results from an analysis of selected vaping liquids reported by users in the 2016 ITC Four Country Smoking and Vaping Survey.

OBJECTIVES: This study presents an analysis of vaping products (VPs) purchased in the USA, Canada, England and Australia and assesses whether differences in regulations were associated with differences in the chemical composition of the VPs. METHODS: April-September 2017, a total of 234 VP refill liquids and prefilled cartridges were purchased in convenience samples of retail locations in each country. Products were chosen from brands and styles most commonly reported by current VP users in the 2016 ITC Four Country Smoking and Vaping Survey. All products were tested for nicotine, tobacco-specific nitrosamines (TSNAs), minor tobacco alkaloids, organic acids and flavouring chemicals. RESULTS: Consistent with the laws in Canada and Australia at the time of product purchase, nicotine was not detected in any of the VPs (n=10 in Canada; n=15 in Australia). US liquids (n=54) had a mean nicotine concentration of 16.2 mg/mL, (range=0.0-58.6) and English liquids (n=166) had a mean concentration of 11.9 mg/mL ((range=0.0-31.2) F(3244)=12.32, p<0.001). About 5% of English samples exceeded the UK's 20 mg/mL nicotine limit. Substantial country differences were observed in levels ofTSNAs, with the USA being higher than elsewhere. Of all products tested, 18.8% contained at least one organic acid. Liquids purchased in England contained far more identifiable flavouring chemicals than those in the other countries. CONCLUSIONS: VP composition, particularly with respect to nicotine and flavouring, varies by country, likely reflecting both marketplace preferences and country-specific regulations. There are differences between nicotine levels claimed on the package and actual levels, particularly in England.

Needs and wishes for the future lower limb exoskeleton: an interview study among people with spinal cord injury with community-based exoskeleton experience.

PURPOSE: Exoskeleton use by people with complete spinal cord injury (SCI) in daily life is challenging. To optimize daily exoskeleton use, a better understanding of the purpose of use and the accompanying improvements are needed. The perspective of experienced exoskeleton users could guide design improvements. METHODS: Face-to-face semi-structured interviews were held with 13 people with SCI with exoskeleton experience. Interviews were audio-taped, transcribed, and analysed thematically. RESULTS: Participants expressed three future purposes of exoskeleton use: for daily activities (e.g., stair climbing), exercise (e.g., staying healthy), and social interaction (e.g., standing at parties). Exoskeleton use during daily activities was the ultimate goal. Therefore, the future exoskeleton should be: easy to use, small and lightweight, tailor made, safe, comfortable, less distinctive, durable, and affordable. Improving the ease of use was relevant for all purposes, for all participants. The other suggestions for improvement varied depending on the purpose of use and the participant. CONCLUSION: Increasingly more advanced improvements are needed to transition from an exercise purpose to social interaction, and ultimately use during daily activities. In the current study, detailed suggestions for improvements have been made. Only when multiple of these suggestions are adjusted, can the exoskeleton be used to its full potential.IMPLICATIONS FOR REHABILITATIONThe use of an exoskeleton by people with a complete spinal cord injury in daily life is still in its infancy.To optimize daily exoskeleton use, a better understanding of the purpose of use and exoskeleton improvements is needed.More advanced improvements to future exoskeletons are needed to make a transition from use as an exercise device to use during social interaction and daily activities.Improving the ease of use of future exoskeletons is considered a priority by experienced users, followed by making the exoskeleton small, lightweight, and tailor made.

[Decision-making process and evaluation of public health interventions]. / Démarche décisionnelle et évaluation des interventions de santé publique.

OBJECTIVE: We have designed a methodological framework for experts involved in the support of decision-making in public health interventions. METHODS: The methodological framework consists of four elements: 1) A series of nine questions, formulated in non-technical terms, relevant to assessment of the usefulness of an intervention, at a given time in a given context; 2) Translation of these questions into concepts related to the evaluation of interventions (definition of the intervention, its target and objective, potential and actual effectiveness, safety, efficiency, and equity); 3) Logical organization of the information needed to address and answer the questions; and 4) An algorithm to translate the available information into recommendations on the real usefulness of the intervention in the context in which the questions were raised. RESULTS: Each step is illustrated by questions raised about road safety interventions, screening, blood transfusion and measures proposed during the COVID-19 pandemic. CONCLUSION: Decision-making can be facilitated if experts provide decision-makers with a formal summary of the strengths and weaknesses of existing knowledge, based on an analysis of all facets of an intervention's potential usefulness.

Precision nephrology identified tumor necrosis factor activation variability in minimal change disease and focal segmental glomerulosclerosis.

The diagnosis of nephrotic syndrome relies on clinical presentation and descriptive patterns of injury on kidney biopsies, but not specific to underlying pathobiology. Consequently, there are variable rates of progression and response to therapy within diagnoses. Here, an unbiased transcriptomic-driven approach was used to identify molecular pathways which are shared by subgroups of patients with either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). Kidney tissue transcriptomic profile-based clustering identified three patient subgroups with shared molecular signatures across independent, North American, European, and African cohorts. One subgroup had significantly greater disease progression (Hazard Ratio 5.2) which persisted after adjusting for diagnosis and clinical measures (Hazard Ratio 3.8). Inclusion in this subgroup was retained even when clustering was limited to those with less than 25% interstitial fibrosis. The molecular profile of this subgroup was largely consistent with tumor necrosis factor (TNF) pathway activation. Two TNF pathway urine markers were identified, tissue inhibitor of metalloproteinases-1 (TIMP-1) and monocyte chemoattractant protein-1 (MCP-1), that could be used to predict an individual's TNF pathway activation score. Kidney organoids and single-nucleus RNA-sequencing of participant kidney biopsies, validated TNF-dependent increases in pathway activation score, transcript and protein levels of TIMP-1 and MCP-1, in resident kidney cells. Thus, molecular profiling identified a subgroup of patients with either MCD or FSGS who shared kidney TNF pathway activation and poor outcomes. A clinical trial testing targeted therapies in patients selected using urinary markers of TNF pathway activation is ongoing.

Clinical utility of ozone therapy and hyperbaric oxygen therapy in degenerative disc disease.

Ozone can be medically useful concerning healing wounds and relieving pain in various conditions, such as disc disease. The aspects of human blood ozonation have been reviewed, as well as potential complications that may arise. The mechanisms of ozone therapy are discussed in detail. It is imperative to recognize ozone as a useful proxy in oxidative-stress related diseases, consolidating other medical gases recognized for their therapeutic importance. The utility of hyperbaric oxygen therapy is also discussed. Disc herniation is very common, as more than 3 million cases are treated per year. Herein we review the medical, surgical, and gene-based therapies that ozone therapy can provide regarding disc disease.

Clinical practice guidelines for the diagnosis and management of Dyspnea in primary care and outpatient setting

Background@#Dyspnea also referred to as shortness of breath or breathlessness is defined as “a subjective experience of breathing discomfort that consists of qualitatively distinct sensations that vary in intensity.” Dyspnea is a symptom of the disease, rather than a disease itself. Its etiology can be designated as arising from four primary categories: respiratory, cardiac, neuromuscular, psychogenic, systemic illness, or a combination of these.@*Objective@#The general objective in developing this guideline is to improve the quality and outcomes of care to adult patients with dyspnea or shortness of breath in primary care and outpatient setting.@*Methods@#The ADAPTE process was utilized in the development of the initial guideline recommendations where the following steps were followed: 1) definition of clinical questions, 2) searching, screening and appraisal of guidelines, 3) decision and selection of evidence and 4) iterative drafting of guideline recommendation was done. The retrieved guidelines were systematically evaluated for their quality and validity using the Appraisal of Guidelines for Research & Evaluation (AGREE) II Instrument, which is a tool developed to assess the methodological quality of practice guidelines. If the adopted guideline did not have recommendations for our clinical question, we developed the recommendations de novo using the GRADE approach. We prioritized retrieving systematic reviews and meta-analysis articles that are relevant to our clinical questions. In the development of recommendations, the guideline development team prioritized the interventions that address the following outcomes i.e., decrease in severity of dyspnea, resolution of dyspnea, improved quality of life and decrease mortality. Data from the articles were extracted and the evidence was then summarized and appraised based on the type of study. The recommendations were then developed by the team as the initial draft that was subjected to external review and consensus panel discussion for finalization.

Occupational health: COVID-19 pandemic and post-pandemic era

@#The COVID-19 pandemic has resulted into issues on occupational health, especially in health care services sector. Due to the nature of their work, this sector is at an increased risk of exposure to the virus. In this issue, we further discuss the importance of occupational health as our special theme. Occupational Health is an area of work in public health to promote the highest degree of physical, mental, and social well-being of workers in all occupations. Occupational health deals with all aspects of health and safety in the workplace and has a strong focus on primary prevention of hazards. The Philippine College of Occupational Medicine (PCOM), which is an affiliate specialty society of the PAFP, is responsible for promoting occupational health in the country. PCOM, formerly known as the Philippine Occupational and Industrial Medical Association (POIMA), was established in 1977 through the merger of three occupational health associations, namely the Industrial Medical Association of the Philippines (IMAP), the Philippine Association of Occupational Health (PAOH), and the Philippine Association of Compensation Medicine (PACOM). As a medical specialty society and a DOLE-accredited safety and health training organization, PCOM is a prime mover in the preservation, promotion, protection, and enhancement of health, safety and wellness of workers in all occupations through its active members nationwide and collaboration with various stakeholders both locally and internationally.