Guidelines for the description of rhizobial symbiovars.

Rhizobia are bacteria that form nitrogen-fixing nodules in legume plants. The sets of genes responsible for both nodulation and nitrogen fixation are carried in plasmids or genomic islands that are often mobile. Different strains within a species sometimes have different host specificities, while very similar symbiosis genes may be found in strains of different species. These specificity variants are known as symbiovars, and many of them have been given names, but there are no established guidelines for defining or naming them. Here, we discuss the requirements for guidelines to describe symbiovars, propose a set of guidelines, provide a list of all symbiovars for which descriptions have been published so far, and offer a mechanism to maintain a list in the future.

"Now I Am Walking Toward Health": A Qualitative Study About the Outcomes of Physical Activity Participation That Matter to Older Adults.

BACKGROUND/OBJECTIVES: Randomized controlled trials that deliver physical activity interventions have demonstrated benefits for older adults across numerous health outcomes. However, too little attention has been directed to ensuring that such trials are measuring patient-relevant outcomes. To support outcome selection for future trials, the objective of this study was to understand what outcomes related to their physical activity participation older adults find important. METHODS: We conducted 12 semistructured interviews with adults aged 65 years and older and analyzed interview transcripts with a reflexive thematic analysis. RESULTS: Older adults desired diverse outcomes from their physical activity participation, ranging from generic (e.g., quality of life) to specific (e.g., leg strength). Relevant outcomes were classified under five themes: physical, clinical, social, psychological, and overarching, each with respective subthemes. CONCLUSIONS: The outcomes that older adults found important were plentiful and rooted in a desire to improve their quality of life. Some of the outcome themes have been reported frequently in past trials (e.g., physical), but others have not (e.g., social). Future researchers should be aware of, and responsive to, the priorities of older adults when designing trials and defining outcomes. Significance/Implications: This study will help to improve outcome selection for future trials of physical activity with older adults. In alignment with a patient-oriented research philosophy, this study will also ground future outcome selection in the priorities of older adults.

Apilimod dimesylate in C9orf72 amyotrophic lateral sclerosis: a randomized phase 2a clinical trial.

Apilimod dimesylate is a first-in-class phosphoinositide kinase, FYVE-type zinc finger containing (PIKfyve) inhibitor with favourable clinical safety profile and has demonstrated activity in preclinical C9orf72 and TDP-43 amyotrophic lateral sclerosis models. In this amyotrophic lateral sclerosis clinical trial, the safety, tolerability, CNS penetrance, and modulation of pharmacodynamic target engagement biomarkers were evaluated. This Phase 2a, randomized, double-blind, placebo-controlled, biomarker-endpoint clinical trial was conducted in four USA centres (ClinicalTrials.gov NCT05163886). Participants with C9orf72 repeat expansion were randomly assigned (2:1) to receive twice-daily oral treatment of 125 mg apilimod dimesylate capsules or matching placebo for 12 weeks, followed by a 12-week open-label extension. Safety was measured as the occurrence of treatment-emergent adverse or serious adverse events attributable to study drug, and tolerability as trial completion on treatment over 12 weeks. Changes from baseline in plasma and CSF and concentrations of apilimod and its active metabolites and of pharmacodynamic biomarkers of PIKfyve inhibition (soluble glycoprotein nonmetastatic melanoma protein B [sGPNMB] upregulation) and disease-specific CNS target engagement (poly[GP]). Between Dec 16, 2021, and Jul 7, 2022, 15 eligible participants were enrolled. There were no drug-related serious adverse events reported in the trial. Fourteen (93%) participants completed the double-blind period with 99% dose compliance (N=9 [90%] apilimod dimesylate; N=5 [100%] placebo). At Week 12, apilimod dimesylate was measurable in CSF at 1.63 ng/mL (SD: 0.937). At Week 12, apilimod dimesylate increased plasma sGPNMB by > 2.5-fold (p < 0.001) indicating PIKfyve inhibition and lowered CSF poly(GP) protein levels by 73% (p < 0.001) indicating CNS tissue-level proof of mechanism. Apilimod dimesylate met prespecified key safety and biomarker endpoints in this Phase 2a trial and demonstrated CNS penetrance and pharmacodynamic target engagement. Apilimod dimesylate was observed to have the greatest reduction in CSF poly(GP) levels observed to date in C9orf72 clinical trials.

Implementation and Evaluation of a Pilot Narrative Medicine Curriculum for Internal Medicine Residents.

Background Narrative medicine has been integrated into medical training to enhance competencies such as observation, reflection, and self-care. However, few studies have assessed the impact of a single narrative medicine session using a pre- and post-test study design. The authors of this study sought to implement a pilot narrative medicine curriculum into a large internal medicine residency program and to evaluate its feasibility and impact. Methodology The curriculum consisted of a one-hour reading and writing workshop held during ambulatory academic half-days from 2021 to 2022. Resident participants completed a retrospective pre- and post-workshop survey evaluating their interest and confidence in practicing narrative medicine skills, as well as their beliefs about the impacts of narrative medicine on patient care and provider well-being. Descriptive statistics evaluated pre- and post-workshop differences using the Wilcoxon signed-rank test. Subgroup analyses were conducted based on postgraduate year, residency track, and workshop setting. Additionally, participants completed open-ended questions that were analyzed qualitatively. Results Of 218 resident participants, 152 (69.7%) completed the post-session survey. Participants noted significantly higher levels of confidence and interest in listening to patient stories, analyzing literary texts, and engaging in reflective writing after the workshop. They also expressed significantly higher levels of agreement that engaging in literary analysis and reflective writing could improve patient care, reduce provider burnout, and strengthen connectedness with colleagues. Qualitative analysis demonstrated that participants found the sessions to be worthwhile and appreciated how narrative medicine could enhance their medical practice. Conclusions Incorporating a brief narrative medicine curriculum into an internal medicine residency program is both feasible and valuable. A single narrative medicine session was practical and well-received by residents, as it promoted self-reflection, observational skills, and connection with colleagues. Future workshops should be customized for different training levels and residency tracks, and additional studies should evaluate whether the outcomes persist over time.

Nicolau Syndrome Following Glatiramer Injection in a Middle-Aged Woman.

Nicolau syndrome is a rare adverse reaction that can occur in the setting of intramuscular, intravenous, and subcutaneous injections. Proper diagnosis and management are critical to avoid complications including abscesses, muscular atrophy, and necrotizing fasciitis. Here, we report a 55-year-old female with multiple sclerosis who presented to our clinic following a subcutaneous injection of 40mg of glatiramer. She immediately noted a sharp pain and erythema, which developed into a purple discoloration, became purulent, and eventually necrosed. The patient's wound was debrided, and she was advised to clean the wound with soap and water, apply topical mupirocin, and change dressings twice daily. She continued to receive appropriate follow-up care with weekly to bi-weekly debridement with excellent resolution.

Inspiratory Muscle Dysfunction Mediates and Predicts a Disease Continuum of Hypercapnic Failure in Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Advanced chronic obstructive pulmonary disease (COPD) is associated with chronic hypercapnic failure. The present work aimed to comprehensively investigate inspiratory muscle function as a potential key determinant of hypercapnic respiratory failure in patients with COPD. METHODS: Prospective patient recruitment encompassed 61 stable subjects with COPD across different stages of respiratory failure, ranging from normocapnia to isolated nighttime hypercapnia and daytime hypercapnia. Arterialized blood gas analyses and overnight transcutaneous capnometry were used for patient stratification. Assessment of respiratory muscle function encompassed body plethysmography, maximum inspiratory pressure (MIP), diaphragm ultrasound, and transdiaphragmatic pressure recordings following cervical magnetic stimulation of the phrenic nerves (twPdi) and a maximum sniff manoeuvre (Sniff Pdi). RESULTS: Twenty patients showed no hypercapnia, 10 had isolated nocturnal hypercapnia, and 31 had daytime hypercapnia. Body plethysmography clearly distinguished patients with and without hypercapnia but did not discriminate patients with isolated nocturnal hypercapnia from those with daytime hypercapnia. In contrast to ultrasound parameters and transdiaphragmatic pressures, only MIP reflected the extent of hypercapnia across all three stages. MIP values below -48 cmH2O predicted nocturnal hypercapnia (area under the curve = 0.733, p = 0.052). CONCLUSION: In COPD, inspiratory muscle dysfunction contributes to progressive hypercapnic failure. In contrast to invasive tests of diaphragm strength only MIP fully reflects the pathophysiological continuum of hypercapnic failure and predicts isolated nocturnal hypercapnia.

Judicial Opinion 129.

Opinion 129 addresses the status of Firmicutes corrig. Gibbons and Murray 1978 (Approved Lists 1980). The name has the category 'division' and was included in the Approved Lists of Bacterial Names, although that category had previously been removed from the International Code of Nomenclature of Bacteria (1975 revision onwards). When the category 'phylum' was introduced into the International Code of Nomenclature of Prokaryotes (ICNP) in 2021, equivalence between 'phylum' and 'division' was not stipulated. Since the definition of the taxonomic categories and their relative order is one of the principal tasks of every code of nomenclature, the inclusion of Firmicutes corrig. Gibbons and Murray 1978 in the Approved Lists was an error. The name is either not validly published or illegitimate because its category is not covered by the ICNP. If Firmicutes corrig. Gibbons and Murray 1978 (Approved Lists 1980) was a validly published phylum name, it would be illegitimate because it would contravene Rule 8, which does not permit any deviation from the requirement to derive a phylum name from the name of the type genus. Since Firmicutes corrig. Gibbons and Murray 1978 is also part of a 'misfitting megaclassification' recognized in Opinion 128, the name is rejected, without any pre-emption regarding a hypothetically validly published name Firmicutes at the rank of phylum. Gracilicutes Gibbons and Murray 1978 (Approved Lists 1980) and Anoxyphotobacteriae Gibbons and Murray 1978 (Approved Lists 1980) are also rejected. The validly published phylum names have a variety of advantages over their not validly published counterparts and cannot be replaced with ad hoc names suggested in the literature. To ease the transition, it is recommended to mention the not validly published phylum names which strongly deviate in spelling from their validly published counterparts along with the latter in publications during the next years.

Positive airway pressure telehealth models and long-term therapy termination: a healthcare database analysis.

Background: Telemonitoring-guided interventions can improve short-term positive airway pressure (PAP) therapy adherence, but long-term effects are unknown. This study investigated long-term PAP therapy termination in patients with sleep apnoea managed with standard care, telemonitoring-guided proactive care or telemonitoring-guided proactive care + patient engagement tool. Methods: German healthcare provider data were analysed retrospectively. Individuals aged 18-100 years who started PAP from 2014 to 2019 and had device type/interface data were included. Time-to-termination periods were analysed using Kaplan-Meier plots and Cox proportional hazards regression, adjusted for age, sex, insurance type, and device and mask type. Results: The per-protocol population (valid telemonitoring data) included 104 612 individuals (71% male; 95% aged >40 years). Mean follow-up was 3.3±2.0 years. The overall therapy termination rate was significantly lower in the telemonitoring-guided proactive care group versus standard care (20% versus 27%; p<0.001), and even lower in the telemonitoring-guided care + patient engagement tool group (11%; p<0.001 versus other treatment groups). Adjusted risk of therapy termination was lower versus standard care (hazard ratio 0.76, 95% confidence interval 0.74-0.78; and 0.41 (0.38-0.44) for telemonitoring-guided proactive care alone + patient engagement). Age <50 or >59 years and use of a nasal pillows or full-face mask were significant predictors of therapy termination; male sex, use of telemonitoring-guided proactive care (± patient engagement) and private insurance were significantly associated with lower therapy termination rates. Conclusions: Use of telemonitoring-guided proactive care and a patient engagement tool was associated with lower rates of PAP therapy termination.

Getting rights right: implementing 'Martha's Rule'.

The UK government has recently committed to adopting a new policy-dubbed 'Martha's Rule'-which has been characterised as providing patients the right to rapidly access a second clinical opinion in urgent or contested cases. Support for the rule emerged following the death of Martha Mills in 2021, after doctors failed to admit her to intensive care despite concerns raised by her parents. We argue that framing this issue in terms of patient rights is not productive, and should be avoided. Insofar as the ultimate goal of Martha's Rule is the provision of a clinical service that protects patient safety, an approach that focuses on the obligations of the health system-rather than the individual rights of patients-will better serve this goal. We outline an alternative approach that situates rapid clinical review as part of a suite of services aimed at enhancing and protecting patient care. This approach would make greater progress towards addressing the difficult systemic issues that Martha's Rule does not, while also better engaging with the constraints of clinical practice.

Medical ethics education as translational bioethics.

We suggest that in the particular context of medical education, ethics can be considered in a similar way to other kinds of knowledge that are categorised and shaped by academics in the context of wider society. Moreover, the study of medical ethics education is translational in a manner loosely analogous to the study of medical education as adjunct to translational medicine. Some have suggested there is merit in the idea that much as translational research attempts to connect the laboratory scientist's work to its implications for patient care, translational ethics focuses on bringing ethics scholarship into the sphere of personal and public action. We distinguish the term 'translational ethics' (the study of ethics being translated between academy, classroom and clinic) from other prominent definitions in the bioethics literature. To do this, we build off a notion of knowledge translation that focuses on the nonlinear movement of information that comes to professionals through multiple competing sources. We suggest that this knowledge, and particularly knowledge about ethics, becomes embodied by the individual. It is through a reflective practice that internally embedded ethics knowledge might be modified, and this work might be best carried out with a moral community that maintains a sense of practical wisdom. Applying this translational approach to the study of medical ethics education can be both academically relevant and practically useful. This view of translation can help bridge the evident, multidirectional relationships between research, education and performance. It might also create further opportunities to develop medical ethics education theory.

Diversity of PA cohorts during the evolution to an entry-level master's degree.

OBJECTIVE: This study evaluated the racial and ethnic diversity of physician associate/assistant (PA) graduating cohorts during the profession's transition from a standard undergraduate degree to an entry-level master's degree. METHODS: Using all existing program reports from the Physician Assistant Education Association (1985-2019), we explored potential associations between changes in tuition, degree types offered, and racial/ethnic makeup of graduating cohorts. RESULTS: We observed a strong negative association between Black students and graduates versus increasing tuition and the rise of master's level programs. CONCLUSIONS: More equitable opportunities for joining the PA profession may be needed.

Impact of simulated reduced injected dose on the assessment of amyloid PET scans.

PURPOSE: To investigate the impact of reduced injected doses on the quantitative and qualitative assessment of the amyloid PET tracers [18F]flutemetamol and [18F]florbetaben. METHODS: Cognitively impaired and unimpaired individuals (N = 250, 36% Aß-positive) were included and injected with [18F]flutemetamol (N = 175) or [18F]florbetaben (N = 75). PET scans were acquired in list-mode (90-110 min post-injection) and reduced-dose images were simulated to generate images of 75, 50, 25, 12.5 and 5% of the original injected dose. Images were reconstructed using vendor-provided reconstruction tools and visually assessed for Aß-pathology. SUVRs were calculated for a global cortical and three smaller regions using a cerebellar cortex reference tissue, and Centiloid was computed. Absolute and percentage differences in SUVR and CL were calculated between dose levels, and the ability to discriminate between Aß- and Aß + scans was evaluated using ROC analyses. Finally, intra-reader agreement between the reduced dose and 100% images was evaluated. RESULTS: At 5% injected dose, change in SUVR was 3.72% and 3.12%, with absolute change in Centiloid 3.35CL and 4.62CL, for [18F]flutemetamol and [18F]florbetaben, respectively. At 12.5% injected dose, percentage change in SUVR and absolute change in Centiloid were < 1.5%. AUCs for discriminating Aß- from Aß + scans were high (AUC ≥ 0.94) across dose levels, and visual assessment showed intra-reader agreement of > 80% for both tracers. CONCLUSION: This proof-of-concept study showed that for both [18F]flutemetamol and [18F]florbetaben, adequate quantitative and qualitative assessments can be obtained at 12.5% of the original injected dose. However, decisions to reduce the injected dose should be made considering the specific clinical or research circumstances.

Rare Primary Malignant Melanoma of the Breast Presenting as a Solitary Breast Mass in a 43-Year-Old Male.

Primary malignant melanoma of the breast (PMMB) is an extremely rare lesion that carries a poor prognosis. Therefore, it is crucial to examine the patient's medical history, clinical presentation, and histopathology considering this diagnosis. The rarity of this lesion has made it difficult to identify classic presentations or specific treatment guidelines. Staining for specific biomarkers can be helpful for diagnosis in the absence of melanin pigment on histology. Additional molecular studies to determine gene status can also be useful for targeted immunotherapy and increased survival time for patients. In this paper, we introduce a rare case of PMMB without skin involvement presenting as a solitary breast mass in a male and explore the radiology, histology, evaluation, and treatment options.

Distinguishing Fibroepithelial Lesions Requires Clinical, Imaging, and Pathology Correlation.

Phyllodes tumor (PT) is a rare tumor that can present as benign, borderline, or malignant. These tumors arise from the breast stroma, similar to fibroadenomas. Phyllodes tumors and fibroadenomas often have overlapping features in both radiological imaging and pathologic analysis. As a result, these two lesions are often difficult to differentiate and require the correlation of multiple modalities, including clinical context, radiologic imaging, and histological evaluation. This article presents a case of a borderline phyllodes tumor in a 51-year-old female, with the inclusion of its radiologic and pathologic images and performed treatment. The goal of this article is to provide a review of the clinical presentation, diagnostic imaging and pathology features, treatment, and management of a phyllodes tumor and compare and contrast this against the more common fibroadenomas, in order to provide aid for differentiating these two breast lesions.

Cutaneous larva migrans in the northeastern US.

Cutaneous larva migrans (CLM) is a dermo-epidermal parasitic infection with a disproportionate incidence in developing countries, particularly in, and near tropical areas. It is characterized by erythematous, twisting, and linear plaques that can migrate to adjacent skin. Herein, we present an otherwise healthy 45-year-old woman who acquired a pruritic, erythematous, and serpiginous rash localized to her right medial ankle during a trip to New England. Oral ivermectin, the preferred first-line treatment for cutaneous larva migrans, was administered in combination with triamcinolone. This was followed by removal of the papular area via punch biopsy; treatment was successful with a one-week recovery. Although cutaneous larva migrans has traditionally been considered a tropical disease, clinicians should be cognizant of its expanding geographic spread.