Patient Advocates for Clinical Research (PACER): A Step Toward Ethical, Relevant, and Truly Participatory Clinical Research in India.

Background Clinical research presents a promising path for improving healthcare in contemporary India. Yet, researchers identify gaps in trust, awareness, as well as misconceptions about being a '"guinea pig." We proposed building the capacity of training patient advocacy groups (PAGs) in patient-centered clinical research and through them creating aware patients as research partners. Methodology Patient Advocates for Clinical Research (PACER) is a tiered program to share information and education about clinical research with PAGs. Tier one is a self-paced online learning course, followed by workshops on clinical research, Good Clinical Practice, research consent, case studies, and group discussions. Results A total of 20 PAGs represented by 48 participants, active in areas of pediatric cancer, breast cancer, multiple myeloma, type I diabetes, spinal muscular atrophy, sickle cell disease, and inflammatory bowel diseases, participated. Among 48 participants 30 successfully completed the online course (multiple-choice question evaluation score cut-off >70%), attaining an average score of 23.9 ± 2.1 out of 30. Overall, 48 participants attended workshop 1 and 45 workshop 2, with 140 participants joining the focus group discussion (FGD). An overall improvement of 9.4% (𝜒2 = 46.173; p < 0.001) for workshop 1 and 8.2% (𝜒2 = 25.412; p < 0.001) for workshop 2 was seen in knowledge gain about clinical research. The FGD raised issues such as misleading information from research teams, unethical recruitment, incomprehensible information sheets, and limited trial-related knowledge fostering fear of participation in clinical research. Conclusions Multimodal and tiered learning of clinical research such as that used by PACER has a good participatory and learning response from PAGs and may be further explored.

Integrating Physio-Yogic Exercises for Rotator Cuff Tendinopathy in Indian Overhead Athletes: A Comprehensive Approach.

Background: Athletes affected by rotator cuff tendinopathy experience discomfort, stiffness, reduced range of motion, diminished athletic performance, and decreased quality of life. This study aimed to determine the efficacy of physio-yogic exercises in reducing pain and disability, increasing range of motion, and improving quality of life in Indian overhead athletes with rotator cuff tendinopathy. Methods: Sample from 45 athletes was divided into three groups scapular recruitment exercises, physio-yogic exercises, and yoga asanas. Pre-intervention readings of the Shoulder Pain and Disability Index (SPADI), Athlete Quality of Life Scale (ALQS), and Shoulder Active Range of Motion (AROM) were taken at day 1 and post-intervention readings were taken at the end of week 8. The paired Student's t-test was used to compare the values of the outcome measures for the preintervention and postintervention within the groups. Analysis of variance was used to compare the mean values of change in the outcome measures from preintervention to postintervention between the groups. Post hoc test was conducted to compare the postintervention values of the outcome measures between the groups. Results: Total scores of SPADI (p < 0.0001), ALQS (p < 0.0001), and Shoulder AROM (p < 0.0001) demonstrated statistically significant improvements in the physio-yogic exercise group. Conclusion: The physio-yogic exercise protocol for rotator cuff tendinopathy is a unique regimen that combines the positive effects of yoga asanas and the advantages of scapular recruitment exercises. Thus, the physio-yogic exercise protocol can further promote the rehabilitation program for rotator cuff tendinopathy.

Determination of optimum levels of binding antibody units (BAU) of new quantitative chemiluminescent immuno-assay (CLIA) in COVID-19 vaccinated volunteer blood donors.

BACKGROUND: For assessment of COVID-19 vaccine efficacy, neutralization activity of anti-SARS-CoV-2 antibody is measured. This study was undertaken to determine optimum levels of binding antibody units (BAU/ml) in new quantitative chemiluminescent assay (CLIA) that corresponded to neutralizing potential (30% inhibition) of sVNT assay. METHODS: Ninety-one blood samples were analyzed by CLIA and sVNT assays. Test samples (n = 75) were collected from blood donors post-2nd vaccination dose, while control samples (n = 16) were archived pre-COVID donor samples. Correlation between CLIA and sVNT was calculated and receiver operating characteristic (ROC) curve was drawn and analyzed. RESULTS: Results indicated excellent correlation between 57.5 BAU/ml on CLIA and 30%inhibition on sVNT assay. ROC curve analysis revealed that the area under the curve (AUC) was 0.971. DISCUSSION: The present study determined that 57.5 BAU/ml on CLIA corresponded to 30% inhibition on sVNT assay. Periodic quantitative analysis.

Role of infrastructure and operation in disease prevalence in dairy farms: groundwork for disease prevention-based antibiotic stewardship.

Attempts at regulating misuse of antibiotics in the dairy industry have been ineffective, especially in low- and middle-income countries, who also typically have high burden of preventable infectious disease, we propose a disease prevention-based approach to minimize the need and in turn consumption of antibiotics in dairy farms. Since the immediate environment of the animals is key to disease prevalence, we targeted the infrastructure- and operation-related factors in dairy farms and their link with prevalence of most common diseases and symptoms. We conducted four focused group discussions and a cross-sectional survey in 378 dairy farms to investigate disease prevalence and associated infrastructural (housing system, and manger shape), and operational (waste management, feed management, and type of cleaning agent) parameters. The most common diseases (Mastitis and secondary infections related to Foot-and-mouth disease) and symptoms (fever and diarrhoea) in the focus area were linked with the infrastructural and operational factors on the dairy farm with higher disease prevalence reported in dairy farms, where the animals were exposed to variations in diurnal temperatures or were hard to clean. We further used ML classifiers - Neural Network (NN), k-Nearest Neighbour (kNN), Support Vector Machine (SVM), Decision Tree (DT), and Random Forest (RF) - to corroborate the relationship between infrastructure and operations of the dairy farms and disease prevalence- The DT classifier on randomly sampled data could predict the prevalence of the two most common diseases (accuracy = 92%, F1-score = 0.919) Our results open new avenues for cost-effective interventions such as use of curve-edged mangers, use of rubber mats on floors, not reusing leftover feed etc. in dairy farms to prevent the most common diseases and symptoms in dairy farms and reduce the need and consumption of antibiotics.

I2-Cs2CO3 Mediated Intramolecular C2-Amination and Oxidative Rearrangement Cascade of C-3 Phenylthio Indoles: A Route to Synthesize Thiosulfonate-Embedded 2-Iminoindolin-3-ones.

An efficient, transition-metal-free protocol employing I2/Cs2CO3 for the synthesis of thiosulfonate containing 2-iminoindolin-3-ones motifs has been developed from C-3 phenylthio indoles. The reaction proceeded through intramolecular cyclization involving C-N bond formation, leading to the formation of indole-fused benzothiazines as a key intermediate. Remarkably, Cs2CO3 played a crucial role in the reaction as an oxygen source, enabling oxidative rearrangement with [1,4]-sulfonyl migration to furnish the final products with the formation of multiple functional groups such as C═O, C═N, and S-SO2.

Contrary effects of increasing temperatures on the spread of antimicrobial resistance in river biofilms.

River microbial communities regularly act as the first barrier of defense against the spread of antimicrobial resistance genes (ARGs) that enter environmental microbiomes through wastewater. However, how the invasion dynamics of wastewater-borne ARGs into river biofilm communities will shift due to climate change with increasing average and peak temperatures remains unknown. Here, we aimed to elucidate the effects of increasing temperatures on the naturally occurring river biofilm resistome, as well as the invasion success of foreign ARGs entering through wastewater. Natural biofilms were grown in a low-anthropogenic impact river and transferred to artificial laboratory recirculation flume systems operated at three different temperatures (20°C, 25°C, and 30°C). After 1 week of temperature acclimatization, significant increases in the abundance of the naturally occurring ARGs in biofilms were detected at higher temperatures. After this acclimatization period, biofilms were exposed to a single pulse of wastewater, and the invasion dynamics of wastewater-borne ARGs were analyzed over 2 weeks. After 1 day, wastewater-borne ARGs were able to invade the biofilms successfully with no observable effect of temperature on their relative abundance. However, thereafter, ARGs were lost at a far increased rate at 30°C, with ARG levels dropping to the initial natural levels after 14 days. Contrary to the lower temperatures, ARGs were either lost at slower rates or even able to establish themselves in biofilms with stable relative abundances above natural levels. Hence, higher temperatures come with contrary effects on river biofilm resistomes: naturally occurring ARGs increase in abundance, while foreign, invading ARGs are lost at elevated speeds.IMPORTANCEInfections with bacteria that gained resistance to antibiotics are taking millions of lives annually, with the death toll predicted to increase. River microbial communities act as a first defense barrier against the spread of antimicrobial resistance genes (ARGs) that enter the environment through wastewater after enrichment in human and animal microbiomes. The global increase in temperature due to climate change might disrupt this barrier effect by altering microbial community structure and functions. We consequently explored how increasing temperatures alter ARG spread in river microbial communities. At higher temperatures, naturally occurring ARGs increased in relative abundance. However, this coincided with a decreased success rate of invading foreign ARGs from wastewater to establish themselves in the communities. Therefore, to predict the effects of climate change on ARG spread in river microbiomes, it is imperative to consider if the river ecosystem and its resistome are dominated by naturally occurring or invading foreign ARGs.

Environmental stress increases the invasion success of antimicrobial resistant bacteria in river microbial communities.

Environmental microbiomes are constantly exposed to invasion events through foreign, antibiotic resistant bacteria that were enriched in the anthropic sphere. However, the biotic and abiotic factors, as well as the natural barriers that determine the invasion success of these invader bacteria into the environmental microbiomes are poorly understood. A great example of such invasion events are river microbial communities constantly exposed to resistant bacteria originating from wastewater effluents. Here, we aim at gaining comprehensive insights into the key factors that determine their invasion success with a particular focus on the effects of environmental stressors, regularly co-released in wastewater effluents. Understanding invasion dynamics of resistant bacteria is crucial for limiting the environmental spread of antibiotic resistance. To achieve this, we grew natural microbial biofilms on glass slides in rivers for one month. The biofilms were then transferred to laboratory, recirculating flume systems and exposed to a single pulse of a model resistant invader bacterium (Escherichia coli) either in presence or absence of stress induced by Cu2+. The invasion dynamics of E. coli into the biofilms were then monitored for 14 days. Despite an initially successful introduction of E. coli into the biofilms, independent of the imposed stress, over time the invader perished in absence of stress. However, under stress the invading strain successfully established and proliferated in the biofilms. Noteworthy, the increased establishment success of the invader coincided with a loss in microbial community diversity under stress conditions, likely due to additional niche space becoming available for the invader.

Iodine-Catalyzed Synthesis of Benzo-ß-carbolines through Desulfurative Cyclization of 2-(1H-Indol-3-ylsulfanyl)-phenylamines with Aryl Methyl Ketones.

A novel transition metal-free strategy for the synthesis of benzene-fused ß-carboline scaffolds has been developed. This protocol offers a rapid and direct pathway to access the benzene fused ß-carboline from 2-(1H-indol-3-ylsulfanyl)-phenylamines and aryl methyl ketones using an efficient catalytic system of I2/DMSO. The present mild protocol proceeds through the sequential reactions of Kornblum oxidation, Pictet-Spengler cyclization, and desulfurization to afford the desired products in excellent yields up to 99%. Moreover, this method has a wide range of substrate tolerance and is operationally simple and applicable in gram-scale synthesis.

Repurposing Artificial Intelligence Tools for Disease Modeling: Case Study of Face Recognition Deficits in Neurodegenerative Diseases.

Face recognition deficits occur in diseases such as prosopagnosia, autism, Alzheimer's disease, and dementias. The objective of this study was to evaluate whether degrading the architecture of artificial intelligence (AI) face recognition algorithms can model deficits in diseases. Two established face recognition models, convolutional-classification neural network (C-CNN) and Siamese network (SN), were trained on the FEI faces data set (~ 14 images/person for 200 persons). The trained networks were perturbed by reducing weights (weakening) and node count (lesioning) to emulate brain tissue dysfunction and lesions, respectively. Accuracy assessments were used as surrogates for face recognition deficits. The findings were compared with clinical outcomes from the Alzheimer's Disease Neuroimaging Initiative (ADNI) data set. Face recognition accuracy decreased gradually for weakening factors less than 0.55 for C-CNN, and 0.85 for SN. Rapid accuracy loss occurred at higher values. C-CNN accuracy was similarly affected by weakening any convolutional layer whereas SN accuracy was more sensitive to weakening of the first convolutional layer. SN accuracy declined gradually with a rapid drop when nearly all nodes were lesioned. C-CNN accuracy declined rapidly when as few as 10% of nodes were lesioned. CNN and SN were more sensitive to lesioning of the first convolutional layer. Overall, SN was more robust than C-CNN, and the findings from SN experiments were concordant with ADNI results. As predicted from modeling, brain network failure quotient was related to key clinical outcome measures for cognition and functioning. Perturbation of AI networks is a promising method for modeling disease progression effects on complex cognitive outcomes.

Safety and Outcomes of Midline and Peripherally Inserted Central Catheters in a Pediatric Intensive Care Unit.

OBJECTIVES: We describe our experience with use of midline catheters in PICU and compare the performance of midline catheters to peripherally inserted central catheters (PICC). METHODS: A review of hospital records was done to including all pediatric patients admitted in the pediatric intensive care unit of a tertiary care centre who underwent placement of midline catheters or PICC, over a period of 18 months (July, 2019 to January, 2021). Patient details, indication, type of catheter and number of attempts at insertion, type and number of infusions administered, dwell time and complications were retrieved from the records. Comparison was made between the midline and PICC groups. RESULTS: The median (IQR) age of children was 7 (3-12) years (75.5% males). 161 midline catheters and 104 PICC were inserted with first attempt success rates of 87.6% and 78.8%, respectively. Median cubital vein was used for majority of the insertions (52.8%). Common complications with midline catheters were pain (n=9, 5.6%), blockage (n=8, 5%) and thrombophlebitis (n=6, 3.7%). Median (interquartile range) dwell time in midline group was 7 (5-10) days. The duration of backflow and dwell time were higher in the PICC group compared to midline group (5.5 vs 3 days; P<0.001 and 9 vs 7 days; P<0.001, respectively). CONCLUSION: Retrospective data showed that midline catheters had good utility in PICU, especially in moderately sick children (PRISM score up to 12), and provide a secure intravenous access, which can last for a week.

Elevated levels of anthropogenic antibiotic resistance gene marker, sul1, linked with extreme fecal contamination and poor water quality in wastewater-receiving ponds.

In several low- and middle-income countries, such as India, the rapid construction of toilets to combat open defecation has not been matched with adequate wastewater treatment, resulting in extreme fecal contamination of the receiving environments. The sewage-receiving surface water bodies, typically close to the residences, are a potential hotspot for disease transmission and antibiotic resistance. Water, soil, and sediment samples from seven wastewater-receiving ponds (WRPs) were analyzed for water quality, chlorophyll-a, fecal contamination (yccT for Escherichia coli), 16S rRNA gene copies, and anthropogenic antibiotic resistance gene markers-sul1 and intI1. These WRPs were contrasted with two ponds that did not directly receive sewage. The water quality in the WRPs was comparable to raw sewage (BOD: 210-380 mg/L; COD: 350-630 mg/L; total-N: 100-190 mg/L; and total-P: 6-21 mg/L), and the relative levels of the DNA marker of E. coli were very high (yccT: 0.1% to ∼100% of total bacterial count) indicating extreme fecal contamination. The relative levels of sul1 and intI1 were 1-3 orders of magnitude higher in WRPs (sul1: 0.32%-10% of total bacterial count; and intI1: 0.2%-5% of total bacterial count) compared to the ponds that did not receive sewage directly. The relative levels of sul1 correlated with the DNA marker for the fecal indicator, E. coli (p-value < 0.05; r = 0.50; Spearman's rank correlation), and poor water quality.

Outcomes of expedited rotator cuff surgery in injured workers: Impact of pathology on readiness for return to work.

OBJECTIVES: The objectives of this study were to (1) examine the overall recovery and satisfaction following an expedited rotator cuff (RC) decompression or repair at 3-6 months and (2) explore group differences (repair vs. decompression) in demographics, clinical, disability, and psychosocial factors. METHODS: This was a prospective longitudinal study of injured workers whose surgery was expedited. The outcome measures were Quick disabilities of the arm, shoulder, and hand ( QuickDASH), the Hospital Anxiety and Depression Scale (HADS), the readiness for return to work (RRTW) scale, and satisfaction with surgery and overall recovery. RESULTS: Of 118 patients participated in the study, 106 patients, age: 51 (9), 71 males (67%) completed the study. Sixty-four (60%) patients underwent a RC repair and 42 (40%) had RC decompression. Patients improved on average in QuickDASH ( p = 0.004), anxiety ( p = 0.003), and depression scores ( p = 0.004). The majority of patients (75%) were satisfied with surgery. In the decompression group, the pre-contemplation (PC) stage of the RRTW which documents the absence of desire or planning for return to work in the non-working sample ( r = 0.81, p = 0.008) and the uncertain maintenance (UM) stage of the RRTW which explores the worker's struggle to stay at work in the working sample correlated with physical disability as measured by the QuickDASH scores ( r = 0.62, p = 0.0001). In the repair group, the above domains correlated with the depression HADS scores (PC: r = 0.64, p = 0.001 and UM: r = 0.57, p < 0.0001). CONCLUSION: Expedited RC surgery improved physical disability and mental well-being and was associated with a relatively high satisfaction at a maximum of 6 months. The poorer report of readiness for return to work was associated with higher physical disability in the decompression group and higher report of depression in the repair group. These differential associations may emphasize the importance of physical versus psychological management in patients with different levels of pathology.

Outcome of Expedited Rotator Cuff Surgery in Injured Workers: Determinants of Successful Recovery.

BACKGROUND: Work-related rotator cuff injuries are a common cause of disability and employee time loss. PURPOSE: To examine the effectiveness of expedited rotator cuff surgery in injured workers who underwent rotator cuff decompression or repair and to explore the impact of demographic, clinical, and psychosocial factors in predicting the outcome of surgery. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Injured workers who were seen at a shoulder specialty program and who underwent expedited arthroscopic rotator cuff decompression or repair were observed for a period of 6 to 12 months based on their type of surgery and recovery trajectory. The primary outcome measure was the American Shoulder and Elbow Surgeons (ASES) Standardized Shoulder Assessment Form. The impact of surgery was assessed by whether the change in the ASES score exceeded the minimal clinically important difference (MCID) of 17 points. Secondary outcomes were range of motion (ROM), medication consumption, and work status. RESULTS: One hundred forty-six patients (43 women [29%], 103 men [71%]; mean age, 52 years; SD, 8 years) completed the study. Sixty-seven (46%) patients underwent rotator cuff repair. The mean time between the date the patient consented to have surgery and the date of surgery was 82 (SD, 44) days. There was a statistically significant improvement in ASES score and ROM and work status (52 returned to regular duties and 59 to modified duties) (P < .0001). Eighty-four percent (n = 122) of patients exceeded the MCID of 17 points. Individual factors that affected patient overall disability were preoperative ASES, work status prior to surgery, access to care, and autonomy at work. Achieving a minimal clinically meaningful change was influenced by perceived access to care, autonomy and stress at work, and overall satisfaction with the job. CONCLUSION: Expedited rotator cuff surgery improved disability, ROM, and work status in injured workers. Successful recovery after work-related shoulder injuries may further be facilitated by improving the psychosocial work environment and increasing access to care.

MetaStorm: A Public Resource for Customizable Metagenomics Annotation.

Metagenomics is a trending research area, calling for the need to analyze large quantities of data generated from next generation DNA sequencing technologies. The need to store, retrieve, analyze, share, and visualize such data challenges current online computational systems. Interpretation and annotation of specific information is especially a challenge for metagenomic data sets derived from environmental samples, because current annotation systems only offer broad classification of microbial diversity and function. Moreover, existing resources are not configured to readily address common questions relevant to environmental systems. Here we developed a new online user-friendly metagenomic analysis server called MetaStorm (http://bench.cs.vt.edu/MetaStorm/), which facilitates customization of computational analysis for metagenomic data sets. Users can upload their own reference databases to tailor the metagenomics annotation to focus on various taxonomic and functional gene markers of interest. MetaStorm offers two major analysis pipelines: an assembly-based annotation pipeline and the standard read annotation pipeline used by existing web servers. These pipelines can be selected individually or together. Overall, MetaStorm provides enhanced interactive visualization to allow researchers to explore and manipulate taxonomy and functional annotation at various levels of resolution.

Biodegradation of nanocrystalline cellulose by two environmentally-relevant consortia.

Nanocellulose is growing in popularity due to its versatile properties and applications. However, there is a void of knowledge regarding the environmental fate of nanocellulose and the response of environmental microbial communities that are historically adapted to non-nano cellulose forms. Given its distinction in terms of size and chemical and physical properties, nanocellulose could potentially resist biodegradation and/or pose a xenobiotic influence on microbial communities during wastewater treatment or in receiving environments. In this study, biodegradation of H2SO4 hydrolyzed nanocrystalline cellulose (HNC) was compared with that of microcrystalline cellulose using two distinct anaerobic cellulose-degrading microbial consortia initially sourced from anaerobic digester (AD) and wetland (W) inocula. Equivalent cellulose masses were dosed and monitored with time by measurement of liberated glucose. HNC biodegraded at slightly faster rate than microcrystalline cellulose (1st order decay constants: 0.62 ± 0.08 wk-1 for HNC versus 0.39 ± 0.05 wk-1 for microcrystalline cellulose for the AD consortium; 0.69 ± 0.04 wk-1for HNCversus 0.58 ± 0.05 wk-1 for microcrystalline cellulose for the W consortium). 16S rRNA (total bacteria) and cel48 (glycoside hydrolase gene family 48, indicative of cellulose-degrading potential) genes were observed to be more enriched in the HNC condition for both consortia. According to Illumina amplicon sequencing of 16S rRNA genes, the composition of the consortia underwent distinct shifts in concert with HNC versus microcrystalline cellulose degradation. This study demonstrates that the biodegradation of cellulose is not inhibited in the nano-size range, particularly in the crystalline form, though the microbes and pathways involved likely differ.

Effect of drinking water treatment process parameters on biological removal of manganese from surface water.

Soluble manganese (Mn) presents a significant treatment challenge to many water utilities, causing aesthetic and operational concerns. While application of free chlorine to oxidize Mn prior to filtration can be effective, this is not feasible for surface water treatment plants using ozonation followed by biofiltration because it inhibits biological removal of organics. Manganese-oxidizing bacteria (MOB) readily oxidize Mn in groundwater treatment applications, which normally involve pH > 7.0. The purpose of this study was to evaluate the potential for biological Mn removal at the lower pH conditions (6.2-6.3) often employed in enhanced coagulation to optimize organics removal. Four laboratory-scale biofilters were operated over a pH range of 6.3-7.3. The biofilters were able to oxidize Mn at a pH as low as pH 6.3 with greater than 98% Mn removal. Removal of simulated organic ozonation by-products was also greater than 90% in all columns. Stress studies indicated that well-acclimated MOB can withstand variations in Mn concentration (e.g., 0.1-0.2 mg/L), hydraulic loading rate (e.g., 2-4 gpm/ft(2); 1.36 × 10(-3)-2.72 × 10(-3) m/s), and temperature (e.g., 7-22 °C) typically found at surface water treatment plants at least for relatively short (1-2 days) periods of time.

Influence of petroleum deposit geometry on local gradient of electron acceptors and microbial catabolic potential.

A field survey was conducted following the Deepwater Horizon blowout and it was noted that resulting coastal petroleum deposits possessed distinct geometries, ranging from small tar balls to expansive horizontal oil sheets. A subsequent laboratory study evaluated the effect of oil deposit geometry on localized gradients of electron acceptors and microbial community composition, factors that are critical to accurately estimating biodegradation rates. One-dimensional top-flow sand columns with 12-h simulated tidal cycles compared two contrasting geometries (isolated tar "balls" versus horizontal "sheets") relative to an oil-free control. Significant differences in the effluent dissolved oxygen and sulfate concentrations were noted among the columns, indicating presence of anaerobic zones in the oiled columns, particularly in the sheet condition. Furthermore, quantification of genetic markers of terminal electron acceptor and catabolic processes via quantitative polymerase chain reaction of dsrA (sulfate-reduction), mcrA (methanogenesis), and cat23 (oxygenation of aromatics) genes in column cores suggested more extensive anaerobic conditions induced by the sheet relative to the ball geometry. Denaturing gradient gel electrophoresis similarly revealed that distinct gradients of bacterial communities established in response to the different geometries. Thus, petroleum deposit geometry impacts local dominant electron acceptor conditions and may be a key factor for advancing attenuation models and prioritizing cleanup.