Prokinetic agents in adult intensive care unit patients (PATIENCE)-An international inception cohort study protocol.

BACKGROUND: Feeding intolerance is common in critically ill patients and can lead to malnutrition. Prokinetic agents may be used to enhance the uptake of nutrition. However, the evidence on the effectiveness and safety of prokinetic agents is sparse, and there is a lack of data on their use in intensive care units (ICU). METHODS: We will conduct an international 14-day inception cohort study of 1000 acutely admitted adult ICU patients. Data will be collected from ICU admission and daily during ICU stay for up to 90 days. The primary outcome will be the proportion of ICU patients who receive prokinetic agents. Secondary outcomes include mortality, days alive without life support, days alive out of ICU, days alive out of hospital (all within 90 days) and the number of patients with one or more serious adverse events. RESULTS: We will present data on the use of prokinetic agents descriptively and use Cox regressions with death and ICU discharge as competing events to evaluate the association between patient characteristics and the use of prokinetic agents. We will use extended Cox models with time-varying covariates and linear regression models to assess the associations between the use of prokinetic agents and the secondary outcomes. CONCLUSION: The outlined international cohort study will provide valuable epidemiological data on the use of prokinetic agents in adult, acutely admitted ICU patients.

Identification of Cercospora spp. on corn in North America and baseline flutriafol fungicide sensitivity.

Gray leaf spot (GLS) is an important corn disease reportedly caused by Cercospora zeae-maydis and C. zeina. Recently, flutriafol, a demethylation inhibitor (azole) fungicide received EPA registration as Xyway® LFR®, a product that is applied at planting for management of fungal diseases in corn, including suppression of GLS. In this study, 448 Cercospora spp. isolates were collected in 2020 and 2021 from symptomatic corn leaf samples submitted from the United States and Ontario, Canada. The Cercospora spp. were identified using multi-locus genotyping of the internal transcribe spacer (ITS), elongation factor 1-α (EF1), calmodulin (CAL), histone H3 (HIS), and actin (ACT) gene. Based on the multi-locus phylogenetic analyses, six species were identified; C. cf. flagellaris (n = 77), C. kikuchii (n = 4), C. zeae-maydis (n = 361), Cercospora sp. M (n = 2), Cercospora sp. Q (n = 1), and Cercospora sp. T (n = 3). In subsequent pathogenicity tests using selected isolates from each of these species, only C. zeae-maydis resulted in symptoms on corn with no disease symptoms observed after inoculation with C. cf. flagellaris, C. kikuchii, Cercospora sp. M, Cercospora sp. Q, and Cercospora sp. T. While disease symptoms were observed on soybean following inoculation with C. cf. flagellaris, C. kikuchii, and Cercospora sp. Q, but not the other three species. Fungicide sensitivity of Cercospora spp. to flutriafol was assessed using a subset of 340 isolates. The minimum inhibitory concentration (MIC) to inhibit the growth of Cercospora spp. completely was determined based on growth of each species on flutriafol-amended clarified V8 agar at nine concentrations. The EC50 was also calculated from the same trial by measuring relative growth as compared to the non-amended control. Cercospora zeae-maydis was sensitive to flutriafol with mean MIC values of 2.5 µg/mL and EC50 values ranging from 0.016 to 1.020 µg/mL with a mean of 0.346 µg/mL. Cercospora cf. flagellaris, C. kikuchii, Cercospora sp. M, Cercospora sp. Q, and Cercospora sp. T had mean EC50 values of 1.25 µg/mL, 7.14 µg/mL, 2.48 µg/mL, 1.81 µg/mL, and 2.24 µg/mL respectively. These findings will assist in monitoring the sensitivity to the flutriafol fungicide in Cercospora spp. populations.

Estimates of Potential Demand for Measles and Rubella Microarray Patches.

Global measles vaccine coverage has stagnated at approximately 85% for over a decade. By simplifying vaccine logistics and administration, the measles and rubella microarray patch (MR-MAP) may improve coverage. Clinical trials have demonstrated similar safety and immunogenicity in 9-month-old infants for MR-MAPs compared with syringe-and-needle vaccination. To aid commercialization, we present estimates of MR-MAP demand. We created a spreadsheet-based tool to estimate demand for MR-MAPs using data from 180 WHO countries during 2000-2016. Five immunization scenarios were analyzed: (1a) Supplementary Immunization Activities (SIAs) in Gavi, the Vaccine Alliance (Gavi)-eligible countries and (1b) WHO countries where preventive SIAs are routinely conducted; (2) SIAs and outbreak response immunization in all WHO countries; (3) routine immunization (RI) and SIAs in six high-burden measles countries (the Democratic Republic of the Congo, Ethiopia, India, Indonesia, Nigeria, and Pakistan); (4) RI and SIAs in six high-burden countries and Gavi-eligible countries; and (5) hard-to-reach populations. MR-MAP demand varied greatly across scenarios. Forecasts for 2025-2034 estimate from 137 million doses in hard-to-reach populations (scenario 5) to 2.587 billion doses for RI and SIAs in six high-burden countries and Gavi-eligible countries (scenario 4). When policymakers and manufacturers assess MR-MAP demand, they may consider multiple scenarios to allow for a complete consideration of potential markets and public health needs.

Emergence of antibiotic-specific Mycobacterium tuberculosis phenotypes during prolonged treatment of mice.

A major challenge in tuberculosis (TB) therapeutics is that antibiotic exposure leads to changes in the physiologic state of M. tuberculosis (Mtb) which may enable the pathogen to withstand treatment. While antibiotic-treated Mtb have been evaluated in short-term in vitro experiments, it is unclear if and how long-term in vivo treatment with diverse antibiotics with varying treatment-shortening activity (sterilizing activity) affect Mtb physiologic states differently. Here, we used SEARCH-TB, a pathogen-targeted RNA-sequencing platform, to characterize the Mtb transcriptome in the BALB/c high-dose aerosol infection mouse model following 4-week treatment with three sterilizing and three non-sterilizing antibiotics. Certain transcriptional changes were concordant among most antibiotics, including decreased expression of genes associated with protein synthesis and metabolism, and the induction of certain genes associated with stress responses. However, the magnitude of this concordant response differed between antibiotics. Sterilizing antibiotics rifampin, pyrazinamide, and bedaquiline generated a more quiescent Mtb state than did non-sterilizing antibiotics isoniazid, ethambutol, and streptomycin, as indicated by decreased expression of genes associated with translation, transcription, secretion of immunogenic proteins, metabolism, and cell wall synthesis. Additionally, we identified distinguishing transcriptional effects specific to each antibiotic, indicating that different mechanisms of action induce distinct patterns of cellular injury. In addition to elucidating Mtb physiologic changes associated with antibiotic stress, this study demonstrates the value of SEARCH-TB as a highly granular pharmacodynamic assay that reveals antibiotic effects that are not apparent based on culture alone.

Nitric oxide induces the distinct invisibility phenotype of Mycobacterium tuberculosis.

During infection Mycobacterium tuberculosis (Mtb) forms physiologically distinct subpopulations that are recalcitrant to treatment and undetectable using standard diagnostics. These difficult to culture or differentially culturable (DC) Mtb are revealed in liquid media, their revival is often stimulated by resuscitation-promoting factors (Rpf) and prevented by Rpf inhibitors. Here, we investigated the role of nitric oxide (NO) in promoting the DC phenotype. Rpf-dependent DC Mtb were detected following infection of interferon-γ-induced macrophages capable of producing NO, but not when inducible NO synthase was inactivated. After exposure of Mtb to a new donor for sustained NO release (named NOD), the majority of viable cells were Rpf-dependent and undetectable on solid media. Gene expression analyses revealed a broad transcriptional response to NOD, including down-regulation of all five rpf genes. The DC phenotype was partially reverted by over-expression of Rpfs which promoted peptidoglycan remodelling. Thus, NO plays a central role in the generation of Rpf-dependent Mtb, with implications for improving tuberculosis diagnostics and treatments.

Real-World Evidence of Adjuvant Immunotherapy in Resected Stage III and IV Melanoma Patients: CADIM Trial Final Results. Experience from 2 Tertiary Referral Centers. / Evidencia en la práctica clínica del tratamiento adyuvante con inmunoterapia en pacientes con melanoma en estadios III y IV resecados: resultados finales del estudio CADIM. Experiencia de 2centros de tercer nivel.

INTRODUCTION: Clinical trials have validated the use of nivolumab and pembrolizumab as adjuvant therapies regarding relapse-free survival in patients with resected stage III and IV melanoma. Evidence in real-world patients is currently limited. MATERIAL AND METHOD: The CADIM trial (Characterization of adjuvant immunotherapy in melanoma patients) recruited a total of 81 patients with resected stage III and IV melanoma on nivolumab or pembrolizumab as adjuvant therapy from February 2018 through December 2022. RESULTS: The stage distribution rate was 81.5% (n=71) for stage III, while 15 patients (18.5%) had resected stage IV. Among stage III patients, 38 were stage IIIC (46.9%). With a median follow-up of 22.8 months, the relapse-free survival in the intention-to-treat population was 84% at one year and 81.5% at 2 years. The overall survival rate was 99% at one year and 91.4% at 2 years. Grade 3-4 treatment-related adverse events were reported in 12.3% of the patients. CONCLUSIONS: This study shows the results of resected stage III and IV melanoma patients on adjuvant therapy with anti-PD-1, and eventually confirmed the safety and efficacy profile described by clinical trials. Comparing clinical trial data with real-world evidence is necessary for a more practical, reliable, and accessible use of these drugs.

Clinical application of the UroLift® prostatic urethral lift in Spain: consensus on the treatment of lower urinary tract symptoms associated with urinary flow obstruction and secondary to benign prostatic hyperplasia (BPH).

Benign prostatic hyperplasia (BPH) is an increasingly common pathology in the adult male. BPH increases after the age of 40-45 years, and its management consumes an enormous amount of resources. The UroLift® System is an approved technology designed to treat lower urinary tract symptoms (LUTS) secondary to BPH and is used to perform the prostatic urethral lift (PUL) procedure. Various urology specialists in Spain with experience in PUL have prepared this consensus document. Endorsed by the Spanish Urology Association, its information is based on the most recent findings. The main objective of this document is to disseminate the consensus recommendations among all professionals treating patients with LUTS/BPH. Both primary care physicians and urologists can assess and offer PUL as an effective, minimally invasive treatment.

Automated Insulin Delivery for Young People with Type 1 Diabetes and Elevated A1c.

BACKGROUND: Automated insulin delivery is the treatment of choice in adults with type 1 diabetes. Data are needed on the efficacy and safety of automated insulin delivery for children and youth with diabetes and elevated glycated hemoglobin levels. METHODS: In this multicenter, open-label randomized controlled trial, we assigned patients with type 1 diabetes in a 1:1 ratio either to use an automated insulin delivery system (MiniMed 780G) or to receive usual diabetes care of multiple daily injections or non--automated pump therapy (control). The patients were children and youth (defined as 7 to 25 years of age) with elevated glycemia (glycated hemoglobin ≥8.5% with no upper limit). The primary outcome was the baseline-adjusted between-group difference in glycated hemoglobin at 13 weeks. RESULTS: A total of 80 patients underwent randomization (37 to automated insulin delivery and 43 to control) and all patients completed the trial. At 13 weeks, the mean (±SD) glycated hemoglobin decreased from 10.5±1.9% to 8.1±1.8% in the automated insulin delivery group but remained relatively consistent in the control group, changing from 10.4±1.6% to 10.6±1.8% (baseline-adjusted between-group difference, -2.5 percentage points; 95% confidence interval [CI], -3.1 to -1.8; P<0.001). Patients in the automated insulin delivery group spent on average 8.4 hours more in the target glucose range of 70 to 180 mg/dl than those in the control group. One severe hypoglycemia event and two diabetic ketoacidosis events occurred in the control group, with no such events in the automated insulin delivery group. CONCLUSIONS: In this trial of 80 children and youth with elevated glycated hemoglobin, automated insulin delivery significantly reduced glycated hemoglobin compared with usual diabetes care, without resulting in severe hypoglycemia or diabetic ketoacidosis events. (Funded by Lions Clubs New Zealand District 202F and others; Australian New Zealand Clinical Trials Registry number, ACTRN12622001454763.).

A review of radiation doses and associated parameters in Western Australian mining operations (2020-23).

Government policies have stimulated the Western Australian (WA) mining industry to position itself as a significant global supplier of critical minerals, including lithium and rare earths. In WA the lithology that supports these minerals is often associated with elevated concentrations of naturally occurring radioactive materials (NORMs) and the increase in the number of mining operations pursuing the minerals has witnessed a commensurate increase in the number of workers potentially exposed to the radiation emitted from the NORMs. The regulatory framework for radiation protection in WA mining operations underwent significant change with the implementation of the Work Health and Safety Act 2020 and Work Health and Safety (Mines) Regulations 2022 which both came into effect on the 31 of March 2022. Under the new framework mining operations identified as having workers who were likely to receive annual effective doses (EDs) from NORMS above one mSvy-1are referenced asrelevant mines (RM). RMs are required to submit an annual report of the estimates of EDs)received by their workforce to the mining regulatory authority (WorkSafe WA: Mines Safety). This research provides an overview of the new legislative framework and updates the information in Ralph and Cattani (2022J. Radiol. Prot.42012501) to include data derived from annual occupational EDs submitted by RMs in the three-year period spanning 2020-21, 2021-22 and 2022-23. In 2022-23, 38 mining operations were identified as RMs, an increase of ten from 2021-22 which in turn had increased by six from the 2020-21 reporting period. The mean annual ED reported for the three-year period was 1.0 mSv, the level at which regulatory intervention should be considered. The maximum ED was 4.9 mSv, just below the threshold of 5 mSv above which exposed workers are considered Designated Workers and are subject to focused monitoring. The collective effective annual dose of the mine worker population reached an historical maximum of 2339 man mSv in 2022-23. Analysis of the three main exposure pathways confirms that inhalation of long-lived alpha emitting radionuclides in dust remains the most significant contributor to worker EDs. Inhalation of radon-222 and radon-220 and their short-lived progeny, once considered as a negligible contributor to worker annual EDs is the second most significant exposure pathway. A declining trend in the number of samples collected per worker is highlighted as requiring remediation to provide confidence in the reported annual EDs. The transition to the new legislative framework for radiation protection in mines has been supported by the publication of guidance materials which have been widely endorsed by the industry.

DNA methylation analysis reveals local changes in resistant and susceptible soybean lines in response to Phytophthora sansomeana.

Phytophthora sansomeana is an emerging oomycete pathogen causing root rot in many agricultural species including soybean. However, as of now, only one potential resistance gene has been identified in soybean, and our understanding of how genetic and epigenetic regulation in soybean contributes to responses against this pathogen remains largely unknown. In this study, we performed whole genome bisulfite sequencing (WGBS) on two soybean lines, Colfax (resistant) and Williams 82 (susceptible) in response to P. sansomeana at two time points: 4 and 16 hours post inoculation to compare their methylation changes. Our findings revealed that there were no significant changes in genome-wide CG, CHG (H = A, T, or C), and CHH methylation. However, we observed local methylation changes, specially an increase in CHH methylation around genes and transposable elements (TEs) after inoculation, which occurred earlier in the susceptible line and later in the resistant line. After inoculation, we identified differentially methylated regions (DMRs) in both Colfax and Williams 82, with a predominant presence in TEs. Notably, our data also indicated that more TEs exhibited changes in their methylomes in the susceptible line compared to the resistant line. Furthermore, we discovered 837 DMRs within or flanking 772 differentially expressed genes (DEGs) in Colfax and 166 DMRs within or flanking 138 DEGs in Williams 82. These DEGs had diverse functions, with Colfax primarily showing involvement in metabolic process, defense response, plant and pathogen interaction, anion and nucleotide binding, and catalytic activity, while Williams 82 exhibited a significant association with photosynthesis. These findings suggest distinct molecular responses to P. sansomeana infection in the resistant and susceptible soybean lines.

The public health impact of COVID-19 variants of concern on the effectiveness of contact tracing in Vermont, United States.

Case investigation and contact tracing (CICT) are public health measures that aim to break the chain of pathogen transmission. Changes in viral characteristics of COVID-19 variants have likely affected the effectiveness of CICT programs. We estimated and compared the cases averted in Vermont when the original COVID-19 strain circulated (Nov. 25, 2020-Jan. 19, 2021) with two periods when the Delta strain dominated (Aug. 1-Sept. 25, 2021, and Sept. 26-Nov. 20, 2021). When the original strain circulated, we estimated that CICT prevented 7180 cases (55% reduction in disease burden), compared to 1437 (15% reduction) and 9970 cases (40% reduction) when the Delta strain circulated. Despite the Delta variant being more infectious and having a shorter latency period, CICT remained an effective tool to slow spread of COVID-19; while these viral characteristics did diminish CICT effectiveness, non-viral characteristics had a much greater impact on CICT effectiveness.

Helicopter emergency medical services in Iceland between 2018 and 2022-A retrospective study.

BACKGROUND: Helicopter emergency services (HEMS) are widely used to bring medical assistance to individuals that cannot be reached by other means or individuals that have time-critical medical conditions, such as chest pain, stroke or severe trauma. It is a very expensive resource whose use and importance depends on local conditions. The aim of this study was to describe flight and patient characteristics in all HEMS flights done in Iceland, a geographically isolated, mountainous and sparsely populated country, over a 5-year course. METHODS: This retrospective study included all individuals requiring HEMS transportation in Iceland during 2018-2022. The electronic database of the Icelandic Coast Guard was used to identify the individuals and register flight data. Electronic databases from Landspitali and Akureyri hospitals were used to collect clinical variables. Descriptive statistics was applied. RESULTS: The average number of HEMS transports was 3.5/10,000 inhabitants and the median [IQR] activation time and flight times were 30 min [20-42] and 40 min [26-62] respectively. The vast majority of patients were transported to Landspitali Hospital in Reykjavik. More than half of the transports were due to trauma, the most common medical transports were due to chest pain or cardiac arrests. Advanced medical therapy was provided for 66 (10%) of individuals during primary transports, 157 (24%) of individuals were admitted to intensive care, 188 (28%) needed surgery and 53 (7.9%) needed a coronary angiography. CONCLUSION: In Iceland, the number of transports is lower but activation and flight times for HEMS flights are considerably longer than in other Nordic countries, likely due to geographical features and the structure of the service including utilizing helicopters both for HEMS and search and rescue operations. The transport times for some time-sensitive conditions are not within standards set by international studies and guidelines.

Observation of a core-excited dipole-bound state ∼1 eV above the electron detachment threshold in cryogenically cooled acetylacetonate.

Dipole-bound states in anions exist when a polar neutral core binds an electron in a diffuse orbital through charge-dipole interaction. Electronically excited polar neutral cores can also bind an electron in a diffuse orbital to form Core-Excited Dipole-Bound States (CE-DBSs), which are difficult to observe because they usually lie above the electron detachment threshold, leading to very short lifetimes and, thus, unstructured transitions. We report here the photodetachment spectroscopy of cryogenically cooled acetylacetonate anion (C5H7O2-) recorded by detecting the neutral radical produced upon photodetachment and the infrared spectroscopy in He-nanodroplets. Two DBSs were identified in this anion. One of them lies close to the electron detachment threshold (∼2.74 eV) and is associated with the ground state of the radical (D0-DBS). Surprisingly, the other DBS appears as resonant transitions at 3.69 eV and is assigned to the CE-DBS associated with the first excited state of the radical (D1-DBS). It is proposed that the resonant transitions of the D1-DBS are observed ∼1 eV above the detachment threshold because its lifetime is determined by the internal conversion to the D0-DBS, after which the fast electron detachment takes place.

Potentially Inappropriate Medication Use and Polypharmacy Before and After Admission to Internal Medicine for Older Patients.

BACKGROUND: With the aging of the population and the increase in chronic diseases, there is an inherent risk of polypharmacy and inappropriate medication use. This study aimed to determine the prevalence and incidence of potentially inappropriate medication use and its correlation with polypharmacy. METHODS: This was a retrospective, population-based cohort study among patients ≥ 65 years hospitalized at The National University Hospital of Iceland from 2010-2020. Data on medication usage were retrieved from the National Prescription Medicine Registry. Based on the number of medications filled in the year prior to admission and post-discharge, participants were categorized as non-polypharmacy (<5), polypharmacy (5-9), and hyper-polypharmacy (≥10). The prevalence and incidence of potentially inappropriate medication use was assessed based on the 2019 Beers criteria. Regression models were used to correlate sociodemographic, clinical, and pharmacoepidemiologic variables and the odds of new potentially inappropriate medication use. RESULTS: The cohort comprised 55,859 patients (48.5% male) with a median [interquartile range] age of 80 [73-86] years. The prevalence of inappropriate medication use in the year preceding admission was 34.0%, 77.7%, and 96.4% for patients with non-polypharmacy, polypharmacy, and hyper-polypharmacy, respectively. The incidence of new potentially inappropriate medication use was 46.7% (95% confidence interval 45.6%-47.6%) among those with no potentially inappropriate medication use pre-admission. Factors associated with higher odds of new potentially inappropriate medication use after discharge were the use of multi-dose dispensing services, dementia, polypharmacy, and hyper-polypharmacy. CONCLUSIONS: An increased emphasis is needed to review and reevaluate the appropriateness of medication use among the older population in internal medicine.

Transcriptomic and epigenetic responses shed light on soybean resistance to Phytophthora sansomeana.

Phytophthora root rot, caused by oomycete pathogens in the Phytophthora genus, poses a significant threat to soybean productivity. While resistance mechanisms against Phytophthora sojae have been extensively studied in soybean, the molecular basis underlying immune responses to Phytophthora sansomeana remains unclear. In this study, we investigated transcriptomic and epigenetic responses of two resistant (Colfax and NE2701) and two susceptible (Williams 82 and Senaki) soybean lines at four time points (2, 4, 8, and 16 h post inoculation [hpi]) after P. sansomeana inoculation. Comparative transcriptomic analyses revealed a greater number of differentially expressed genes (DEGs) upon pathogen inoculation in resistant lines, particularly at 8 and 16 hpi. These DEGs were predominantly associated with defense response, ethylene, and reactive oxygen species-mediated defense pathways. Moreover, DE transposons were predominantly upregulated after inoculation, and more of them were enriched near genes in Colfax than other soybean lines. Notably, we identified a long non-coding RNA (lncRNA) within the mapped region of the resistance gene that exhibited exclusive upregulation in the resistant lines after inoculation, potentially regulating two flanking LURP-one-related genes. Furthermore, DNA methylation analysis revealed increased CHH (where H = A, T, or C) methylation levels in lncRNAs after inoculation, with delayed responses in Colfax compared to Williams 82. Overall, our results provide comprehensive insights into soybean responses to P. sansomeana, highlighting potential roles of lncRNAs and epigenetic regulation in plant defense.

Behavioral interventions and behavior change techniques used to improve sleep outcomes in athlete populations: A scoping review.

BACKGROUND: Athletes display a high prevalence of undesired sleep characteristics that may affect both performance and wellbeing. OBJECTIVES: This scoping review aimed to identify and map the existing evidence of behavioral sleep interventions and their effects on sleep outcomes in athletes, and retrospectively code the behavior change techniques (BCTs) implemented using the Behavior Change Technique Taxonomy (BCTTv1). METHODS: Conducted following the JBI methodology for scoping reviews, four online databases were used to identify prospective interventions with at least one behavioral component in competitive athletes, and reporting a sleep outcome pre- and post-intervention. RESULTS: Thirty-three studies met the inclusion criteria, encompassing 892 participants with a median age of 23. Five intervention categories were identified (education, mind-body practices, direct, multi-component, and other), with each demonstrating mixed efficacy but the potential to improve sleep outcomes. The BCTs varied in type and frequency between each category, with only 18 unique BCTs identified across all studies. CONCLUSIONS: The varied efficacy of previous studies at improving sleep outcomes may be attributed to the lack of behavior change theory applied during intervention development. Designing interventions following a targeted specification of the behavioral problem, and the integration of corresponding BCTs should be considered in future research.

Sex-specific growth and lifespan effects of germline removal in the dioecious nematode Caenorhabditis remanei.

Germline regulates the expression of life-history traits and mediates the trade-off between reproduction and somatic maintenance. However, germline maintenance in itself can be costly, and the costs can vary between the sexes depending on the number of gametes produced across the lifetime. We tested this directly by germline ablation using glp-1 RNA interference (RNAi) in a dioecious nematode Caenorhabditis remanei. Germline removal strongly increased heat-shock resistance in both sexes, thus confirming the role of the germline in regulating somatic maintenance. However, germline removal resulted in increased lifespan only in males. High costs of mating strongly reduced lifespan in both sexes and obliterated the survival benefit of germline-less males even though neither sex produced any offspring. Furthermore, germline removal reduced male growth before maturation but not in adulthood, while female growth rate was reduced both before and especially after maturation. Thus, germline removal improves male lifespan without major growth costs, while germline-less females grow slower and do not live longer than reproductively functional counterparts in the absence of environmental stress. Overall, these results suggest that germline maintenance is costlier for males than for females in C. remanei.

Rv0100: An essential acyl carrier protein from M. tuberculosis important in dormancy.

We have identified an acyl-carrier protein, Rv0100, that is up-regulated in a dormancy model. This protein plays a critical role in the fatty acid biosynthesis pathway, which is important for energy storage and cell wall synthesis in Mycobacterium tuberculosis (MTB). Knocking out the Rv0100 gene resulted in a significant reduction of growth compared to wild-type MTB in the Wayne model of non-replicating persistence. We have also shown that Rv0100 is essential for the growth and survival of this pathogen during infection in mice and a macrophage model. Furthermore, knocking out Rv0100 disrupted the synthesis of phthiocerol dimycocerosates, the virulence-enhancing lipids produced by MTB and Mycobacterium bovis. We hypothesize that this essential gene contributes to MTB virulence in the state of latent infection. Therefore, inhibitors targeting this gene could prove to be potent antibacterial agents against this pathogen.

A Prospective Randomized Pilot Study: One-Year Outcomes of Ligament Reconstruction Tendon Interposition Versus Suture Tape Suspensionplasty for Thumb Carpometacarpal Joint Arthritis.

PURPOSE: We performed a randomized controlled trial assessing patient-reported outcome measures following trapeziectomy with ligament reconstruction and tendon interposition (LRTI) or suture tape suspensionplasty (STS) for treatment of thumb carpometacarpal joint osteoarthritis. METHODS: Patients undergoing surgery for thumb carpometacarpal joint osteoarthritis were prospectively randomized to LRTI or STS. Outcome measures were collected at 2 weeks, 4 weeks, 3 months, and 1 year and included visual analog scale pain, Patient-Reported Outcomes Measurement Information System (PROMIS) Upper Extremity, return to work/activity, range of motion, grip/pinch strength, and complications. RESULTS: Thirty-one patients (32 thumbs) were randomized from 51 patients offered participation over two years. One-year follow-up was 97%. Both groups had a decrease in visual analog scale pain scores at all postoperative time points. The trajectory of postoperative Patient-Reported Outcomes Measurement Information System Upper Extremity scores was similar, and both groups achieved the meaningful clinically important difference for improvement in PROMIS Upper Extremity by three months. Grip strength was substantially increased in both groups at one year. Return to work/activity and surgical complications favored the LRTI group. CONCLUSIONS: Our study did not suggest any clinically relevant differences in the postoperative patient-reported outcome measures or objective clinical measurements between LRTI and STS, although LRTI patients had a faster return to work/activity and lower complication rates. TYPE OF STUDY/LEVEL OF EVIDENCE: Prospective randomized clinical trial, level IIB clinical.

Acceptability and experiences of real-time continuous glucose monitoring in adults with type 2 diabetes using insulin: a qualitative study.

Aims: To explore the lived experiences of initiating real-time continuous glucose monitoring (rt-CGM) use in individuals with type 2 diabetes using insulin. Methods: Twelve semi-structured interviews were conducted amongst individuals with type 2 diabetes taking insulin who were enrolled in the 2GO-CGM randomised controlled trial and had completed 3 months of rtCGM. Interviews were transcribed verbatim and analysed to identify common themes regarding their experiences. Results: The interviews revealed three key themes: i) rtCGM as a facilitator of improved health behaviours; ii) the acceptability of rtCGM systems compared to capillary blood glucose testing; and iii) barriers to the continual usage of rtCGM technology - including: connection difficulties, longevity of the sensors, and local cutaneous reactions to the sensor adhesive. Conclusion: Adults on insulin with type 2 diabetes find rtCGM systems widely acceptable, and easier to engage with than traditional self-monitoring of capillary blood glucose. Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01403-9.