bluuebunny/crossref_metadata_2025_split huggingface dataset:
Challenges in the distribution of antimicrobial medications in community dispensaries in Accra, Ghana
Authors: Greene Hannah Camille , Makovi Kinga , Abdul-Mumin Rafiatu , Bansal Akhil , Frimpong Jemima 
Published: February 2023

AbstractIntroductionCommunity distribution of medications in low- and middle-income countries has been shown to accelerate the emergence of antimicrobial resistance. The distribution of medications is often carried out by private vendors operating under constrained conditions. Yet patterns in medicine distribution—and their consequences—are not well understood. The aim of this study was to illuminate the challenges reported by employees of chemical shops and pharmacies throughout Accra. Our objectives are twofold: to 1) assess obstacles and challenges faced by medicine vendors during their sales of antibiotic and antimalarial medications, and 2) identify opportunities for improving community-level stewardship of antimicrobials.MethodsResponses to open-ended questions from a survey of 80 shopkeepers in pharmacies and chemical shops throughout Accra were analyzed using the socioecological model of public health.ResultsOverall, shopkeepers most often reported constraints at the interpersonal and community levels of the socioecological model of public health. These included the prohibitive costs of medicines, customer attitudes, and customers’ attempts at self-medication and uninformed antimicrobial use. Other challenges included a lack of diagnostic testing, supply chain issues, and the larger economic and healthcare situation of the community.DiscussionThe safe and effective distribution of medications was truncated by three main sources of obstacles: financial insecurity among customers, challenges directly in the treatment of illnesses, and broader issues with the fragmented healthcare infrastructure affecting shopkeepers’ roles as health educators and gatekeepers of medicines.ConclusionThese context-specific findings identify tractable challenges faced by medicine vendors in Ghana, with relevance to antimicrobial stewardship across resource-poor settings globally. Addressing barriers faced by shopkeepers would provide an opportunity for significantly improving the provision of medications, and ultimately healthcare, at the community level. Such efforts will likely expand access to populations who may otherwise be unable to access services in formal institutions of care.
Relationship between cognition and frailty-A cross-sectional study among elders in the tribal areas of Mysuru
Authors: Vanmathi A , Kulkarni Praveen , Chauhan Dennis , Kumar D Sunil , Periera Prathiba , Kishor M , basheer Sayana 
Published: February 2023

AbstractBackgroundCognition declines as age advances. Frailty is a pre-disability state. cognitive impairment and frailty lower the quality of life of elders. studies done in this background were mostly in urban or rural areas. Hence the current study was conducted among elders in the tribal areas to find the relationship between cognition and frailty.Materials and methodsIt was a cross-sectional study done for a period of one year among 316 elders >60 years. Based on the reported prevalence of cognitive dysfunction among the elderly to be 25% (Rakesh M Patel et al), with 5% absolute allowable error,5% of alpha error, and 10% non-response rate) residing in the tribal areas of Mysuru. WHO-30 cluster sampling was used. MOCA-B was used for assessing cognition scale and the TFI scale was used for assessing frailty.ResultsThe prevalence of cognitive impairment and frailty was 95.3 % and 61.4% respectively. Factors like Gender, education, type of family, physical, financial and emotional dependency, and preference of treatment were associated with cognition. There was also a significant association between cognition and frailty.ConclusionThere was a higher prevalence of cognitive impairment among frail elders. Thus, early diagnosis and appropriate management are necessary for healthy ageing
A patient-centered comparative effectiveness research study of culturally appropriate options for diabetes self-management
Authors: Page-Reeves Janet , Murray-Krezan Cristina , Burge Mark R. , Mishra Shiraz I. , Regino Lidia , Bleecker Molly , Perez Daniel , McGrew Hannah Cole , Bearer Elaine L. , Erhardt Erik 
Published: February 2023

AbstractThis project compared the effectiveness of two evidence-based models of culturally competent diabetes health promotion:The Diabetes Self-Management Support Empowerment Model(DSMS), andThe Chronic Care Model(CCM). Our primary outcome was improvement in patient capacity for diabetes self-management as measured by the Diabetes Knowledge Questionnaire (DKQ) and the Patient Activation Measure (PAM). Our secondary outcome was patient success at diabetes self-management as measured by improvement in A1c, depression sores using the PHQ-9, and Body Mass Index (BMI). We also gathered data on the cultural competence of the program using the Consumer Assessment of HealthcareProviders and Systems Cultural Competence Set(CAHPS-CC). We compared patient outcomes in two existing sites in Albuquerque, New Mexico that serve a large population of Latino diabetes patients from low-income households. Participants were enrolled as dyads—a patient participant (n=226) and a social support participant (n=226). Outcomes over time and by program were analyzed using longitudinal linear mixed modeling, adjusted for patient participant demographic characteristics and other potential confounding covariates. Secondary outcomes were also adjusted for potential confounders. Interactions with both time and program helped to assess outcomes. This study did not find a difference between the two sites with respect to the primary outcome measures and only one of the three secondary outcomes showed differential results. The main difference between programs was that depression decreased more for CCM than for DSMS. An exploratory, subgroup analysis revealed that at CCM, patient participants with a very high A1c (>10) demonstrated a clinically meaningful decrease. However, given the higher cultural competence rating for the CCM, statistically significant improvement in depression, and the importance of social support to the patients, results suggest that a culturally and contextually situated diabetes self-management and education program design may deliver benefit for patients, especially for patients with higher A1c levels.
Clinico-microbiological profile and treatment outcomes in patients with isoniazid monoresistant tuberculosis in South India
Authors: Prasanna M Venkata , Muthuraj R , Raj R Vimal , Govindarajan S , Pajanivel R 
Published: February 2023

ABSTRACTIsoniazid (INH) is an important first-line medication for the treatment of tuberculosis. The impact that tuberculosis drug resistance has on treatment outcomes is a topic that is receiving a lot of attention these days because of the rising incidence of INH-resistant cases. Study involves a single group of patients who have been diagnosed with Isoniazid monoresistant tuberculosis. Treatment history and demographic data of the patients were obtained after informed consent. The mutation patterns of isoniazid were observed after multiplex PCR and Line Probe Assay (LPA). A total of 101 patient (M,F) records at the IRL, Puducherry were analyzed. The predominant gene responsible for TB was KATG (67.3%). The KATG Mut1 was a prime mutation observed in the present study population (58.41%). Study showed positive association with males (74%), occupation as coolie (88%), diabetes as comorbidity (33%), pulmonary tuberculosis as the TB site (98.01%), history of previous ATT intake in 43 patients (42.6%), katG mutation (67.3%), katG Mut 1 was the prime mutation (58.4%).The cure rate was high inINH high concentration resistancepatients which was statistically significant (p=0.0167). INH monoresistance mutations seen in 64.3% of the patients with katG, compared to inhA (34.65%). Similar to katG mutations, inhA mutations also have MUT1 as their most frequent gene pattern. There is a significant association between males, diabetes, smoking and alcohol addictions were associated with high risk of developing high dose INH monoresistance (katG). High prevalence of recurrent tuberculosis was seen in high dose INH monoresistance tuberculosis. Patients who are microbiologically confirmed pulmonary tuberculosis and diabetes with rifampicin sensitive status needs to be checked for LPA for isoniazid sensitivity status to prevent treatment failure and relapse. It is crucial to understand the gene pattern in each of these patients since these mutations are closely associated to high or low-degree resistance to INH
Correlates of symptomatic remission among individuals with post-COVID-19 condition
Authors: Perlis Roy H. , Santillana Mauricio , Ognyanova Katherine , Lazer David 
Published: February 2023

AbstractImportancePost-COVID-19 condition (PCC), or long COVID, has become prevalent. The course of this syndrome, and likelihood of remission, has not been characterized.ObjectiveTo quantify the rates of remission of PCC, and the sociodemographic features associated with remission.Design16 waves of a 50-state U.S. non-probability internet survey conducted between August 2020 and November 2022SettingPopulation-basedParticipantsSurvey respondents age 18 and olderMain Outcome and MeasurePCC remission, defined as reporting full recovery from COVID-19 symptoms among individuals who on a prior survey wave reported experiencing continued COVID-19 symptoms beyond 2 months after the initial month of symptoms.ResultsAmong 423 survey respondents reporting continued symptoms more than 2 months after acute test-confirmed COVID-19 illness, who then completed at least 1 subsequent survey, mean age was 53.7 (SD 13.6) years; 293 (69%) identified as women, and 130 (31%) as men; 9 (2%) identified as Asian, 29 (7%) as Black, 13 (3%) as Hispanic, 15 (4%) as another category including Native American or Pacific Islander, and the remaining 357 (84%) as White. Overall, 131/423 (31%) of those who completed a subsequent survey reported no longer being symptomatic. In Cox regression models, male gender, younger age, lesser impact of PCC symptoms at initial visit, and infection when the Omicron strain predominated were all statistically significantly associated with greater likelihood of remission; presence of ‘brain fog’ or shortness of breath were associated with lesser likelihood of remission.Conclusions and RelevanceA minority of individuals reported remission of PCC symptoms, highlighting the importance of efforts to identify treatments for this syndrome or means of preventing it.Trial registrationN/AKey PointsQuestionHow often do individuals with post-COVID-19 condition, or long COVID, recover fully, and what predicts this recovery?FindingsAmong 423 individuals who initially reported post-COVID-19 condition and completed at least one subsequent survey, 131 (31%) later described symptomatic remission. Younger age, male gender, lesser symptom severity at initial survey, and infection during Omicron-predominance were associated with greater likelihood of reporting recovery.MeaningA minority of people with post-COVID-19 condition report spontaneous remission of symptoms, highlighting the importance of developing treatments for this syndrome.
Research priorities for improving menstrual health across the life-course in low- and middle-income countries
Authors: Plesons Marina , Torondel Belen , Caruso Bethany A. , Hennegan Julie , Sommer Marni , Haver Jacqueline , Keiser Danielle , van Eijk Anna M , Zulaika Garazi , Mason Linda , Phillips-Howard Penelope A. 
Published: February 2023

AbstractBackgroundResearch on menstrual health is required to understand the needs of girls, women, and others who menstruate; and to strengthen programmes with evidence-based interventions to improve health, wellbeing, and productivity. The identification of research priorities is an important process to help researchers, policymakers, programmers, and funding agencies decide where to invest their efforts and resources.MethodsA modified version of the Child Health and Nutrition Research Initiative (CHNRI) approach was utilized to reach consensus on a set of research priority questions. Multisector stakeholders with expertise in policy, programming, financial support, and/or research relating to menstrual health were identified through networks and the literature. Individuals were invited to submit priority questions through survey monkey online on i) understanding the problem; ii) designing and implementing interventions; iii) integrating and scaling up interventions. Responses were consolidated and individuals were then invited to rank these questions based on i) novelty; ii) potential for intervention; and iii) importance/impact. Research priority scores were calculated from these responses and analyzed to evaluate associations with social and occupational characteristics of participating respondents.ResultsEighty-two participants, of whom 89% were female and 39.0% from low- and middle-income countries (LMIC), proposed a total of 1135 research questions: 45.9% on understanding the problem, 39.7% on designing and implementing interventions, 12.7% on integrating and scale-up, plus 1.5% on other aspects. Questions were consolidated into a final list of 91 unique research questions. Sixty-six participants, of whom 80.3% were women and 39.4% from LMIC, ranked these questions. Top ten-ranked research priority questions comprised four questions on ‘understanding the problem’, four on ‘designing and implementing interventions’, one on ‘integrating and scaling up’, and one on ‘measurement and research’. Academics gave higher prioritization to ‘designing and implementing interventions,’ and lower prioritization to questions on ‘understanding the problem,’ ‘integrating and scaling up,’ and ‘measurement and research.ConclusionsUse of CHNRI generated unique research priority questions from expertise internationally. The top-ranking research priorities can be utilized by policymakers, programmers, researchers, and funders to guide future research in menstrual health.
Potentiated cholinergic and corticofugal inputs support reorganized sensory processing in the basolateral amygdala during auditory threat acquisition and retrieval
Authors: Asokan Meenakshi M. , Watanabe Yurika , Kimchi Eyal Y. , Polley Daniel B. 
Published: February 2023

SummaryReappraising neutral stimuli as environmental threats reflects rapid and discriminative changes in sensory processing within the basolateral amygdala (BLA). To understand how BLA inputs are also reorganized during discriminative threat learning, we performed multi-regional measurements of acetylcholine (ACh) release, single unit spiking, and functional coupling in the mouse BLA and higher-order auditory cortex (HO-AC). During threat memory recall, sounds paired with shock (CS+) elicited relatively higher firing rates in BLA units and optogenetically targeted corticoamygdalar (CAmy) units, though not in neighboring HO-AC units. Functional coupling was potentiated for descending CAmy projections prior to and during CS+ threat memory recall but ascending amygdalocortical coupling was unchanged. During threat acquisition, sound-evoked ACh release was selectively enhanced for the CS+ in BLA but not HO-AC. These findings suggest that phasic cholinergic inputs facilitate discriminative plasticity in the BLA during threat acquisition that is subsequently reinforced through potentiated auditory corticofugal inputs during memory recall.
Stable sound decoding despite modulated sound representation in the auditory cortex
Authors: Funamizu Akihiro , Marbach Fred , Zador Anthony M 
Published: February 2023

SummaryThe activity of neurons in the auditory cortex is driven by both sounds and non-sensory context. To investigate the neuronal correlates of non-sensory context, we trained head-fixed mice to perform a two-alternative choice auditory task in which either reward or stimulus expectation (prior) was manipulated in blocks. Using two-photon calcium imaging to record populations of single neurons in auditory cortex, we found that both stimulus and reward expectation modulated the activity of these neurons. A linear decoder trained on this population activity could decode stimuli as well or better than predicted by the animal’s performance. Interestingly, the optimal decoder was stable even in the face of variable sensory representations. Neither the context nor the mouse’s choice could be reliably decoded from the recorded neural activity. Our findings suggest that in spite of modulation of auditory cortical activity by task priors, auditory cortex does not represent sufficient information about these priors to exploit them optimally and that decisions in this task require that rapidly changing sensory information be combined with more slowly varying task information extracted and represented in brain regions other than auditory cortex.
Comprehensive mutagenesis maps the effect of all single codon mutations in the AAV2repgene on AAV production
Authors: Jain Nina K. , Ogden Pierce J. , Church George M. 
Published: February 2023

AbstractRecombinant adeno-associated viruses (rAAVs) are the predominant gene therapy vector. Several rAAV vectored therapies have achieved regulatory approval, but production of sufficient rAAV quantities remains difficult. The AAV Rep proteins, which are essential for genome replication and packaging, represent a promising engineering target for improvement of rAAV production but remain underexplored. To gain a comprehensive understanding of the Rep proteins and their mutational landscape, we assayed the effects of all 39,297 possible single codon mutations to the AAV2repgene on AAV2 production. Most beneficial variants are not observed in nature, indicating that improved production may require synthetic mutations. Additionally, the effects of AAV2repmutations were largely consistent across capsid serotypes, suggesting that production benefits are capsid independent. Our results provide a detailed sequence-to-function map that enhances our understanding of Rep protein function and lays the groundwork for Rep engineering and enhancement of large-scale gene therapy production.
The biocide triclosan induces (p)ppGpp dependent antibiotic tolerance and alters SarA dependent biofilm structures inStaphylococcus aureus
Authors: Walsh Dean , Salzer Andrea , Wolz Christiane , Aylott Jonathan , Hardie Kim R 
Published: February 2023

AbstractThe biocide triclosan is used extensively in both household and hospital settings. The chronic exposure to the biocide occurring in individuals that use triclosan-containing products results in low levels of triclosan present in the human body that has been linked to induction of antibiotic tolerance and altered biofilm formation. Here we aimed to unravel the molecular mechanisms involved in triclosan induced antibiotic tolerance and biofilm formation inStaphylococcus aureus. Triclosan treatment prior to planktonic exposure to bactericidal antibiotics resulted in 1,000 fold higher viable cell counts compared to non-pretreated cultures. Triclosan pretreatment also protectedS. aureusbiofilms against otherwise lethal doses of antibiotics as shown by live/dead cell staining and viable cell counting. Triclosan mediated antibiotic tolerance in planktonic and biofilm cultures required an active stringent response because a pppGpp0strain was not protected from antibiotic killing. Incubation ofS. aureuswith triclosan also altered biofilm structure due to SarA-mediated overproduction of the polysaccharide intercellular adhesin (PIA) in the biofilm matrix. Thus, physiologically relevant concentrations of triclosan can trigger (p)ppGpp dependent antibiotic tolerance as well as SarA dependent biofilm formation.ImportanceThe prevalent bacteriumStaphylococcus aureusinfects skin lesions and indwelling devices, and this can cause sepsis with 33% mortality. Intrinsic to this is the formation of co-ordinated communities (biofilms) protected by a polysaccharide coat.S. aureusis increasingly difficult to eradicate due to its antibiotic resistance. Protection against Methicillin ResistantS. aureus(MRSA) includes pre-hospital admission washing with products containing biocides. The biocide triclosan is the predominant antibacterial compound in sewage in Ontario due to its use in household and hospital settings. Levels of triclosan accumulate with exposure in humans. The significance of our research is in identifying the mechanisms triggered by exposure ofS. aureusto physiological levels of triclosan that go on to raise the tolerance ofS. aureusto antibiotics and promote the formation of biofilms. This understanding will inform future criteria used to determine effective antimicrobial treatments.
Imaging dendritic spines in the hippocampus of a living mouse by 3D-STED microscopy
Authors: Bancelin Stéphane , Mercier Luc , Roos Johannes , Belkadi Mohamed , Pfeiffer Thomas , Kim Sun Kwang , Nägerl U. Valentin 
Published: February 2023

AbstractSTED microscopy has been used to address a wide range of neurobiological questions in optically well-accessible samples like cell culture or brain slices. However, the application of STED to deeply embedded structures in the brain of living animals remains technically challenging. In previous work, we established chronic STED imaging in the hippocampusin vivobut the gain in spatial resolution was restricted to the lateral plane. In this study, we report on extending the gain in STED resolution into the optical axis to visualize dendritic spines in the hippocampusin vivo. The approach is based on a spatial light modulator to shape the focal STED light intensity in all three dimensions and a conically shaped window that is compatible with an objective that has a long working distance and a high numerical aperture. Moreover, we corrected distortions of the laser wavefront to optimize the shape of the bottle beam of the STED laser, which is required for 3D-STED microscopy. In summary, we present a methodology to improve the axial resolution for STED microscopy in the deeply embedded hippocampusin vivo, facilitating longitudinal studies of neuroanatomical plasticity at the nanoscale in a wide range of (patho-)physiological contexts.