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Functional magnetic resonance imaging (fMRI) has dramatically advanced non-invasive human brain mapping and decoding. Functional near-infrared spectroscopy (fNIRS) and high-density diffuse optical tomography (HD-DOT) non-invasively measure blood oxygen fluctuations related to brain activity, like fMRI, at the brain surface, using more-lightweight equipment that circumvents ergonomic and logistical limitations of fMRI. HD-DOT grids have smaller inter-optode spacing (~ 13 mm) than sparse fNIRS (~ 30 mm) and therefore provide higher image quality, with spatial resolution ~ 1/2 that of fMRI, when using the several source-detector distances (13-40 mm) afforded by the HD-DOT grid. Herein, simulations indicated reducing inter-optode spacing to 6.5 mm, creating a higher-density grid with more source-detector distances, would further improve image quality and noise-resolution tradeoff, with diminishing returns below 6.5 mm. We then constructed an ultra-high-density DOT system (6.5-mm spacing) with 140 dB dynamic range that imaged stimulus-evoked activations with 30-50% higher spatial resolution and repeatable multi-focal activity with excellent agreement with participant-matched fMRI. Further, this system decoded visual stimulus position with 19-35% lower error than previous HD-DOT, throughout occipital cortex., Competing Interests: Declarations. Competing interests: Drs. Culver and Trobaugh have financial ownership interests in EsperImage LLC and may financially benefit from products related to this research. The authors declare no other competing interests., (© 2025. The Author(s).)

Accurate sensor placement is vital for non-invasive brain imaging, particularly for functional near-infrared spectroscopy (fNIRS) and diffuse optical tomography (DOT), which lack standardized layouts such as those in electroencephalography (EEG). Custom, manually prepared probe layouts on textile caps are often imprecise and labor intensive. We introduce a method for creating personalized, 3D-printed headgear, enabling the accurate translation of 3D brain coordinates to 2D printable panels for custom fNIRS and EEG sensor layouts while reducing costs and manual labor. Our approach uses atlas-based or subject-specific head models and a spring-relaxation algorithm for flattening 3D coordinates onto 2D panels, using 10-5 EEG coordinates for reference. This process ensures geometrical fidelity, crucial for accurate probe placement. Probe geometries and holder types are customizable and printed directly on the cap, making the approach agnostic to instrument manufacturers and probe types. Our ninjaCap method offers 2.7 ± 1.8    mm probe placement accuracy. Over the last five years, we have developed and validated this approach with over 50 cap models and 500 participants. A cloud-based ninjaCap generation pipeline along with detailed instructions is now available at openfnirs.org. The ninjaCap marks a significant advancement in creating individualized neuroimaging caps, reducing costs and labor while improving probe placement accuracy, thereby reducing variability in research., (© 2024 The Authors.)

Background: Video-enabled directly observed therapy (video-DOT) has been proposed as an additional option for treatment provision besides in-person DOT for patients with drug-resistant TB (DRTB) disease. However, evidence and implementation experience mainly originate from well-resourced contexts. This study describes the operationalization of video-DOT in a low-resourced setting in Eswatini facing a high burden of HIV and TB amid the emergence of the COVID-19 pandemic., Methods: This is a retrospectively established cohort of patients receiving DRTB treatment during the implementation of video-DOT in Shiselweni from May 2020 to March 2022. We described intervention uptake (vs. in-person DOT) and assessed unfavorable DRTB treatment outcome (death, loss to care) using Kaplan-Meier statistics and multivariable Cox-regression models. Video-related statistics were described with frequencies and medians. We calculated the fraction of expected doses observed (FEDO) under video-DOT and assessed associations with missed video uploads using multivariable Poisson regression analysis., Results: Of 71 DRTB patients eligible for video-DOT, the median age was 39 (IQR 30-54) years, 31.0% (n = 22) were women, 67.1% (n = 47/70) were HIV-positive, and 42.3% (n = 30) were already receiving DRTB treatment when video-DOT became available. About half of the patients (n = 37; 52.1%) chose video-DOT, mostly during the time when COVID-19 appeared in Eswatini. Video-DOT initiations were lower in new DRTB patients (aHR 0.24, 95% CI 0.12-0.48) and those aged ≥ 60 years (aHR 0.27, 95% CI 0.08-0.89). Overall, 20,634 videos were uploaded with a median number of 553 (IQR 309-748) videos per patient and a median FEDO of 92% (IQR 84-97%). Patients aged ≥ 60 years were less likely to miss video uploads (aIRR 0.07, 95% CI 0.01-0.51). The cumulative Kaplan-Meier estimate of an unfavorable treatment outcome among all patients was 0.08 (95% CI 0.03-0.19), with no differences detected by DOT approach and other baseline factors in multivariable analysis., Conclusions: Implementing video-DOT for monitoring of DRTB care provision amid the intersection of the HIV and COVID-19 pandemics seemed feasible. Digital health technologies provide additional options for patients to choose their preferred way to support treatment taking, thus possibly increasing patient-centered health care while sustaining favorable treatment outcomes., (© 2024. The Author(s).)

Purpose: To evaluate the impact on the lag of accommodation (LOA) in emmetropic children after short-term wear of full-field Diffusion Optics Technology TM (DOT) spectacle lenses, designed to modulate retinal contrast to control myopia progression., Patients and Methods: This was a single-visit, prospective, randomized, subject-masked study of emmetropes (ametropes ±1.00D or less in each meridian) with no history of myopia control treatment. Unaided logMAR visual acuity was measured, and ocular dominance was determined using the sighting method. In a randomized order, participants wore plano full-field contrast management (DOT) spectacles (no clear central aperture) or control spectacles (standard single vision spectacle lenses). Each participant was given 5 minutes for adaptation to the respective lenses before open field autorefraction measurements were taken at 6 meters and 40 cm. Ten measurements were taken for each eye. Data were evaluated from the right eye and the dominant eye separately., Results: A total of 30 participants (20 females and 10 males) with a mean age of 10.4 ± 2.8 (7 to 17) years completed the study. There was no significant difference in right eye mean LOA with contrast management spectacles 0.57 ± 0.39D versus control spectacles 0.62 ± 0.34D; Wilcoxon test, p = 0.37. For dominant eyes, LOA values were 0.60 ± 0.40D and 0.68 ± 0.33D with contrast management spectacles and control spectacles, respectively (p = 0.14). Additionally, no significant difference was observed in mean LOA between males and females or between age groups (7-11 years vs 12-17 years) for either right or dominant eyes with contrast management or control spectacles (all p > 0.05)., Conclusion: Full-field contrast management spectacle lenses had no significant effect on LOA compared to standard single vision spectacle lenses, indicating no differential impact on accommodative response over the short period of lens wear tested., Competing Interests: Jennifer S Hill is an employee of SightGlass Vision. All other authors are members of CORE, who received partial funding from SightGlass Vision to conduct this work. Over the past 3 years, CORE has received research support from Alcon, Azura Ophthalmics, Bausch & Lomb Corp, CooperVision, Essilor, Hoya, iMed Pharma, Johnson & Johnson Vision, Menicon, Novartis, Ophtecs, Ote Pharma, Santen, SightGlass, SightSage, Topcon and Visioneering. Lyndon Jones reports grants from SightGlass, during the conduct of the study; grants, personal fees from Alcon, grants from Azura Ophthalmics, grants from Bausch + Lomb, grants, personal fees from CooperVision, grants from Essilor, grants from Hoya, grants from IMedPharma, personal fees from Johnson & Johnson, grants, personal fees from Menicon, grants, personal fees from Novartis, personal fees from Ophtecs, grants from Ote Pharma, grants from Santen, grants from SightGlass, grants from SightSage, grants from Topcon, grants, personal fees from Visioneering, outside the submitted work. Jill Woods reports personal fees from SightGlass Vision, outside the submitted work. The authors report no other conflicts of interest in this work., (© 2024 Jabeen et al.)

Functional near infrared spectroscopy (fNIRS) and functional magnetic resonance imaging (fMRI) both measure the hemodynamic response, and so both imaging modalities are expected to have a strong correspondence in regions of cortex adjacent to the scalp. To assess whether fNIRS can be used clinically in a manner similar to fMRI, 22 healthy adult participants underwent same-day fMRI and whole-head fNIRS testing while they performed separate motor (finger tapping) and visual (flashing checkerboard) tasks. Analyses were conducted within and across subjects for each imaging approach, and regions of significant task-related activity were compared on the cortical surface. The spatial correspondence between fNIRS and fMRI detection of task-related activity was good in terms of true positive rate, with fNIRS overlap of up to 68 % of the fMRI for analyses across subjects (group analysis) and an average overlap of up to 47.25 % for individual analyses within subject. At the group level, the positive predictive value of fNIRS was 51 % relative to fMRI. The positive predictive value for within subject analyses was lower (41.5 %), reflecting the presence of significant fNIRS activity in regions without significant fMRI activity. This could reflect task-correlated sources of physiologic noise and/or differences in the sensitivity of fNIRS and fMRI measures to changes in separate (vs. combined) measures of oxy and de-oxyhemoglobin. The results suggest whole-head fNIRS as a noninvasive imaging modality with promising clinical utility for the functional assessment of brain activity in superficial regions of cortex physically adjacent to the skull., Competing Interests: Declaration of competing interest There are no competing interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: In 2017, the WHO recommended the use of digital technologies, such as medication monitors and video observed treatment (VOT), for directly observed treatment (DOT) of drug-susceptible TB. The WHO's 2020 guidelines extended these recommendations to multidrug-resistant tuberculosis (MDR-TB), based on low evidence. The impact of COVID on health systems and patients underscored the need to use digital technologies in the management of MDR-TB., Methods: A decision-tree model was developed to explore the costs of several potential DOT alternatives: VOT, 99DOTS (Directly-observed Treatment, Short-course) and family-observed DOT. Assuming a 9-month, all-oral regimen (as evaluated within the STREAM trial), we constructed base-case cost models for the standard-of-care DOTs in Ethiopia, India, and Uganda, as well as for the three alternative DOT approaches. The models were populated with STREAM Stage 2 clinical trial outcome and cost data, supplemented with market prices data for the digital DOT strategies. Sensitivity analyses were conducted on key parameters., Results: Modelling suggested that the standard-of-care DOT approach is the most expensive DOT strategy from a societal perspective in all three countries evaluated (Ethiopia, India, Uganda), with considerable direct- and indirect-costs incurred by patients. The second most expensive DOT approach is VOT, with high health-system costs, largely caused by up-front technology expenditure. Each of VOT, 99DOTS and family-observed DOT would reduce by more than 90% patients' direct and indirect costs compared to standard of care DOT. Results were robust to the sensitivity analyses., Conclusions: While data on the costs and efficacy of alternative DOT approaches in the context of shorter MDR-TB treatment is limited, our modelling suggests alternative DOT approaches can significantly reduce patient costs in all three countries. Health system costs are higher for VOT and lower for 99DOTS and family-observed therapy when compared to standard of care DOT, as low smartphone penetration and internet availability requires the VOT health system to fund the cost of making them available to patients., (© 2023. The Author(s).)

Background: In tuberculosis (TB) control, nonadherence to treatment persists as a barrier. The traditional method of ensuring adherence, that is, directly observed therapy, faces significant challenges that hinder its widespread adoption. Digital adherence technologies such as video directly observed therapy (VDOT) are emerging as promising solutions. However, as these novel technologies gain momentum, a critical gap is the lack of comprehensive studies evaluating their efficacy and the unique experiences of patients in Africa., Objective: The aim of this study was to assess patients' experiences that affected acceptability, usefulness, and ease of use with an enhanced VDOT system during monitoring of TB treatment., Methods: We conducted individual open-ended interviews in a cross-sectional exit qualitative study in Kampala, Uganda. Thirty participants aged 18-65 years who had completed the VDOT randomized trial were purposively selected to represent variability in sex, adherence level, and HIV status. We used a hybrid process of deductive and inductive coding to identify content related to the experience of study participation with VDOT. Codes were organized into themes and subthemes, which were used to develop overarching categories guided by constructs adapted from the modified Technology Acceptance Model for Resource-Limited Settings. We explored participants' experiences regarding the ease of use and usefulness of VDOT, thereby identifying the facilitators and barriers to its acceptability. Perceived usefulness refers to the benefits users expect from the technology, while perceived ease of use refers to how easily users navigate its various features. We adapted by shifting from assessing perceived to experienced constructs., Results: The participants' mean age was 35.3 (SD 12) years. Of the 30 participants, 15 (50%) were females, 13 (43%) had low education levels, and 22 (73%) owned cellphones, of which 10 (45%) had smartphones. Nine (28%) were TB/HIV-coinfected, receiving antiretroviral therapy. Emergent subthemes for facilitators of experienced usefulness and ease of VDOT use were SMS text message reminders, technology training support to patients by health care providers, timely patient-provider communication, family social support, and financial incentives. TB/HIV-coinfected patients reported the added benefit of adherence support for their antiretroviral medication. The external barriers to VDOT's usefulness and ease of use were unstable electricity, technological malfunctions in the app, and lack of cellular network coverage in rural areas. Concerns about stigma, disease disclosure, and fear of breach in privacy and confidentiality affected the ease of VDOT use., Conclusions: Overall, participants had positive experiences with the enhanced VDOT. They found the enhanced VDOT system user-friendly, beneficial, and acceptable, particularly due to the supportive features such as SMS text message reminders, incentives, technology training by health care providers, and family support. However, it is crucial to address the barriers related to technological infrastructure as well as the privacy, confidentiality, and stigma concerns related to VDOT., (©Juliet Nabbuye Sekandi, Adenike McDonald, Damalie Nakkonde, Sarah Zalwango, Vicent Kasiita, Patrick Kaggwa, Robert Kakaire, Lynn Atuyambe, Esther Buregyeya. Originally published in JMIR Formative Research (https://formative.jmir.org), 10.11.2023.)

Introduction: Neurosurgical residency is a challenging journey demanding cognitive acuity and resilience, mirrored strikingly in the dynamics of video gaming. Gaming concepts of Down-But-Not-Out (DBNO), Heal-over-Time (HoT), and Damage-over-Time (DoT) can serve as compelling analogues to elements of neurosurgical training., Material and Methods: An innovative, cross-disciplinary methodology was implemented, blending elements of autoethnography, personal reflective narrative, and comprehensive literary review. The cornerstone of this approach was an experiential reflective analysis, where two neurosurgical residents critically examined the parallels between their residency experiences and video game mechanics, thereby applying a lens of heuristic introspection to their professional journey. Complementing this, a comprehensive narrative synthesis of existing literature on resilience, wellness, and stress in neurosurgical residency training was conducted., Results: The DBNO concept parallels the resilience demonstrated by neurosurgical residents, emphasizing the importance of a supportive network. The HoT concept, analogous to wellness practices, underscores the incremental restoration of energy necessary for maintaining stamina in neurosurgery training. The DoT concept symbolizes the need to manage the often insidious and deleterious effects of chronic stress on residents' wellbeing., Discussion and Conclusion: These gaming concepts provide an integrative framework for understanding the challenges faced and strategies employed in neurosurgical residency. The interplay between resilience, wellness practices, and effective stress management, represented by DBNO, HoT, and DoT respectively, is critical for maintaining health and fostering professional excellence. By embedding these metaphors within the training paradigm, the neurosurgical residency journey can be navigated more effectively, promoting not only professional success but also personal growth and wellbeing., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Background/purpose: Precise detection of respiratory pathogens by molecular method potentially may shorten the time to diagnose and reduce unnecessary antibiotic use., Methods: Medical records of hospitalized children from January 2020 to June 2021 with acute respiratory illness who received a FilmArray RP for respiratory pathogens were reviewed and compared with data from diagnosis-matched patients without receiving the test., Results: In total, 283 patients and 150 diagnosis-matched controls were included. Single pathogen was detected in 84.3% (193/229) of the patients. The most common pathogen was human rhinovirus/enterovirus (31.6%, 84/266), followed by respiratory syncytial virus (18.8%, 50/266) and adenovirus (15%, 40/266). Although antimicrobial days of therapy (DOT) was significantly longer in FilmArray group than the control [7.1 ± 4.9 days vs 5.7 ± 2.7 days, P = 0.002], the former showed a higher intensive care unit (ICU) admission rate (3.9% vs 0%; P = 0.010). All ICU admissions were in FilmArray RP-positive group. There was no difference in antimicrobial DOT between FilmArray RP-positive and the negative groups, in all admissions, even after excluding ICU admissions. Antimicrobial DOT was shorter in the positive than negative group in patients with lower respiratory tract infections without admission to ICU [median (IQR): 6 (4-9) days vs 9 (4-12) days, P = 0.047]., Conclusions: Shorter antimicrobial DOTs were identified in children with lower respiratory tract infection admitted to general pediatric ward and with an identifiable respiratory pathogen, indicating a role of the multiplex PCR in reducing antimicrobial use for children with respiratory tract infection., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

Days of therapy (DOT) currently serve as the standard antimicrobial utilization metric. However, by assigning the same weight to each agent rather than accounting for differences in spectrum of activity, DOT ignore key differences between agents that are fundamental to infectious diseases and critical to antimicrobial stewardship. Spectrum scoring assigns numeric values to individual antibiotic agents to quantify their spectrum of activity, allowing for the normalization of antibiotic utilization data. When used in conjunction with traditional metrics, spectrum scores may offer further clarity to antibiotic utilization; however, issues related to development, application, and standardization of spectrum scores remain. Despite these challenges, the potential applications of spectrum scores are vast. Here, we summarize existing data and explore the future of spectrum scoring, including application to both data analysis and routine patient care, use in inpatient and outpatient settings, integration within the electronic medical record, and opportunities for future research., Competing Interests: Potential conflicts of interest . All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The Domain Name System (DNS) is a fundamental component of the internet, responsible for resolving domain names into IP addresses. DNS servers are typically categorized into four types: recursive resolvers, root name servers, Top-Level Domain (TLD) name servers, and authoritative name servers. The latter three types of servers store actual records, while recursive resolvers do not store any real data and are only responsible for querying the other three types of servers and responding to clients. Recursive resolvers typically maintain a caching system to speed up response times, but these caching systems have the drawbacks of a low real-time performance, a poor accuracy, and many security and privacy issues. In this paper, we propose a caching system based on a consortium blockchain, namely DNS-BC, which uses the synchronization mechanism of the consortium blockchain to achieve a high real-time performance, uses the immutable mechanism of the consortium blockchain and our designed credibility management system to achieve up to a 100% accuracy, and has been combined with encrypted transmission protocols to solve common security and privacy issues. At the same time, this caching system can greatly reduce the traffic that name servers need to handle, thereby protecting them from Denial-of-Service (DoS) attacks. To further accelerate the data transmission speed, we have designed a new encrypted DNS protocol called DNS over KCP (DoK). The DoK protocol is based on the KCP protocol, which is a fast and reliable transmission protocol, and its latency can reach one-third of that of TCP when the network environment deteriorates. In our experiments, the transmission time of this protocol is about a quarter of that of the widely used encrypted protocols DNS over TLS (DoT) and DNS over HTTPS (DoH).

Setting: Papua New Guinea (PNG) has one of the world's highest TB incidence rates. It is difficult for patients to access TB care in remote provinces due to insufficient infrastructure and challenging terrain, making varied, targeted delivery models for treating TB necessary., Objective: To assess treatment outcomes using self-administered treatment (SAT), family-supported treatment and community-based directly observed therapy (DOT) via treatment supporter (TS) in the PNG context., Design: A retrospective, descriptive analysis of routinely collected data from 360 patients at two sites in 2019-2020. All patients were assigned a treatment model based on risk factors (adherence or default) and offered patient education and counselling (PEC), family counselling and transportation fees. End-of-treatment outcomes were assessed for each model., Results: Treatment success rates among drug-susceptible TB (DS-TB) were good overall: 91.1% for SAT, 81.4% for family-supported treatment and 77% for DOT patients. SAT was strongly associated with favourable outcomes (OR 5.7, 95% CI 1.7-19.3), as were PEC sessions (OR 4.3, 95% CI 2.5-7.2)., Conclusion: By considering risk factors when determining their treatment delivery model, strong outcomes were seen in all three groups. Multiple modes of treatment administration, tailored to individuals' needs and risk factors, is a feasible, effective, patient-centred care model for hard-to-reach, resource-limited settings., Competing Interests: Conflicts of interest: none declared., (© 2023 The Union.)

Background: WHO recommended multidrug-resistant tuberculosis (MDR-TB) should be treated mainly under ambulatory model, but outcome of ambulatory treatment of MDR-TB in China was little known., Methods: The clinical data of 261 MDR-TB patients treated as outpatients in Shenzhen, China during 2010-2015 were collected and analyzed retrospectively., Results: Of 261 MDR-TB patients receiving ambulatory treatment, 71.1% (186/261) achieved treatment success (cured or completed treatment), 0.4% (1/261) died during treatment, 11.5% (30/261) had treatment failure or relapse, 8.0% (21/261) were lost to follow-up, and 8.8% (23/261) were transferred out. The culture conversion rate at 6 months was 85.0%. Although 91.6% (239/261) of patients experienced at least one adverse event (AE), only 2% of AEs caused permanent discontinuation of one or more drugs. Multivariate analysis showed that previous TB treatment, regimens containing capreomycin and resistance to FQs were associated with poor outcomes, while experiencing three or more AEs was associated with good outcomes., Conclusion: Good treatment success rates and early culture conversions were achieved with entirely ambulatory treatment of MDR-TB patients in Shenzhen, supporting WHO recommendations. Advantageous aspects of the local TB control program, including accessible and affordable second-line drugs, patient support, active monitoring and proper management of AEs and well-implemented DOT likely contributed to treatment success rates., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lecai, Mijiti, Chuangyue, Qian, Weiguo and Jihong.)

Background: Successful tuberculosis (TB) treatment is necessary for disease control. The World Health Organization (WHO) has a target TB treatment success rate of ≥90%. We assessed whether the different types of unfavorable TB treatment outcome had different predictors., Methods: Using data from Regional Prospective Observational Research for Tuberculosis-Brazil, we evaluated biological and behavioral factors associated with each component of unsuccessful TB outcomes, recently updated by WHO (death, loss to follow-up [LTFU], and treatment failure). We included culture-confirmed, drug-susceptible, pulmonary TB participants receiving standard treatment in 2015-2019. Multinomial logistic regression models with inverse probability weighting were used to evaluate the distinct determinants of each unsuccessful outcome., Results: Of 915 participants included, 727 (79%) were successfully treated, 118 (13%) were LTFU, 44 (5%) had treatment failure, and 26 (3%) died. LTFU was associated with current drug-use (adjusted odds ratio [aOR] = 5.3; 95% confidence interval [CI], 3.0-9.4), current tobacco use (aOR = 2.9; 95% CI, 1.7-4.9), and being a person with HIV (PWH) (aOR = 2.0; 95% CI, 1.1-3.5). Treatment failure was associated with PWH (aOR = 2.7; 95% CI, 1.2-6.2) and having diabetes (aOR = 2.2; 95% CI, 1.1-4.4). Death was associated with anemia (aOR = 5.3; 95% CI, 1.4-19.7), diabetes (aOR = 3.1; 95% CI, 1.4-6.7), and PWH (aOR = 3.9; 95% CI, 1.3-11.4). Direct observed therapy was protective for treatment failure (aOR = 0.5; 95% CI, .3-.9) and death (aOR = 0.5; 95% CI, .2-1.0)., Conclusions: The treatment success rate was below the WHO target. Behavioral factors were most associated with LTFU, whereas clinical comorbidities were correlated with treatment failure and death. Because determinants of unsuccessful outcomes are distinct, different intervention strategies may be needed to improve TB outcomes., Competing Interests: Potential conflicts of interest. The authors do not have an association that might pose a conflict of interest. V. C. R. reports grants or contracts outside of the submitted work from TB Alliance for Drug Development (NC-008), Impacto da COVID-19 Nas Manifestações Clínicas, Diagnóstico, Desfecho Do Tratamento e Resposta Imune para Tuberculose Pulmonar (440933/2020-0 to CNPq account (not to self), Associative BRICS Research in COVID-19 and Tuberculosis (ABRICOT) (G-202105-67821 to Fiotec), RePORT International Data Harmonization (R-202108-68053 to Fiotec), Transcriptional Signature of TB in advanced HIV (DAA3-18-64313 to Fiotec), Predictors of Resistance Emergence Evaluation in Multidrug-resistant Tuberculosis patients on Treatment – PREEMPT (R01AI134430), Caribbean, Central, and South America network for HIV Epidemiology (CCASAnet) (U01AI069923 to Fiotec), and immunogenetic predictors of active and incipient TB in HIV-negative and -positive close TB contacts (R01AI147765 to Fiotec); consulting fees paid to self from ONU-OMS Country review for HIV response Myanmar; payment or honoraria paid to self from GLAXOSMITHKLINE BRASIL LTDA, Qiagen (Infecto Rio Conference), and virology education (Infecto Rio Conference); payment directly to the conference for registration for ViiV 18 European AIDS conference; and payment directly to self from NIH Data Safety Monitoring Board., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: A high level of community awareness and positive perception towards tuberculosis and its management is crucial for the successful outcome of any control measure. In India the Accredited Social Health Activist (ASHA) plays a key role in providing awareness and counselling on healthcare issues and management, particularly in remote areas. The tribal population is vulnerable to such infectious diseases due to resource limitations and remote locations. We assessed the knowledge, attitude, and practice (KAP) regarding directly observed therapy (DOT) among ASHA workers in the tribal belt of the Sirohi district of Rajasthan state., Material and Methods: This cross-sectional study was conducted among ASHA workers of Sirohi district from January 2021 to June 2021. A predesigned and structured questionnaire was used to gather information on knowledge, attitude, and practices regarding the management of tuberculosis and DOT., Results: A total of 95 ASHAs participated in the study with a mean age of 35.82 years. Good knowledge (Mean score = 6.2947 ± 1.08052) was observed regarding tuberculosis and DOT. 81% ( n = 74) have good knowledge regarding DOT whereas most have a poor attitude and only 47% have adequate practice. A 55% of ASHAs did not adhere even a single TB patient in the last three years., Conclusion: In our study, knowledge gaps were identified which may result in substandard patient care. The structured refresher training towards DOT and also training to work in tribal areas will further improve the KAP of ASHAs. It might be needed to provide a module or curriculum regarding awareness among ASHAs for strengthening follow-up system for tuberculosis patients among the tribal population., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Family Medicine and Primary Care.)

As a common food seasoning in China, Zanthoxylum schinifolium Sieb. et Zucc. is desired by consumers for its special aroma; however, its bitter taste has a negative economic impact on the food industry. In this study, untargeted metabolomics was used to perform full-coverage detection of metabolites in Z. schinifolium Sieb. et Zucc. A total of 53 potential bitter metabolites were screened. Additionally, key bitter compounds were concentrated using sensory-guided fractionation technique and subsequently characterized by UPLC-Q-TOF-MS, and a total of 13 bitter compounds were obtained. Then, dose over threshold values (DOT) of these 13 compounds were calculated, showing that 11 compounds significantly contribute to the bitterness of Z. schinifolium Sieb. et Zucc., with quercetin, isorhamnetin and kaempferol have particularly low thresholds and high contents. This study is the first to comprehensively define the bitter substances in Z. schinifolium Sieb. et Zucc., providing a reliable theoretical basis for future research on bitterness mechanisms., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Aim: To understand patients' perceptions and experiences of directly observed therapy (DOT) for tuberculosis treatment in the UK., Method: Patients receiving DOT as part of their TB treatment participated in semi-structured and audio-recorded interviews. Data were analysed using a framework approach., Results: Non-adherence was driven by socio-cultural, mental health, employment and discrimination factors. Patients valued DOT for its support and social connection but those in employment feared it could lead to disclosure and social discredit., Conclusion: TB patients experience social isolation and fear discrimination. DOT offers a degree of social connection and support for marginalised patients but fails to tackle fundamental barriers to adherence such as mental health issues, addictions, housing and discrimination. Practice implications: Flexible patient-centred methods of DOT should be offered throughout patients' treatment. Research into multi-agency responsibility for promoting adherence needs to be commissioned, implemented and evaluated. Telemedicine and nurse-led clinics may improve access to care and improve patient experience.

Surface nanopatterning induced by ion beam irradiation (IBI) has emerged as an effective nanostructuring technique since it induces patterns on large areas of a wide variety of materials, in short time, and at low cost. Nowadays, two main subfields can be distinguished within IBI nanopatterning depending on the irrelevant or relevant role played by the surface composition. In this review, we give an up-dated account of the progress reached when surface composition plays a relevant role, with a main focus on IBI surface patterning with simultaneous co-deposition of foreign atoms. In addition, we also review the advances in IBI of compound surfaces as well as IBI systems where the ion employed is not a noble gas species. In particular, for the IBI with concurrent metal co-deposition, we detail the chronological evolution of these studies because it helps us to clarify some contradictory early reports. We describe the main patterns obtained with this technique as a function of the foreign atom deposition pathway, also focusing in those systematic studies that have contributed to identify the main mechanisms leading to the surface pattern formation and development. Likewise, we explain the main theoretical models aimed at describing these nanopattern formation processes. Finally, we address two main special features of the patterns induced by this technique, namely, the enhanced pattern ordering and the possibility to produce both morphological and chemical patterns., (Creative Commons Attribution license.)

In magnetic resonance imaging, the application of a strong diffusion weighting suppresses the signal contributions from the less diffusion-restricted constituents of the brain's white matter, thus enabling the estimation of the transverse relaxation time T 2 that arises from the more diffusion-restricted constituents such as the axons. However, the presence of cell nuclei and vacuoles can confound the estimation of the axonal T 2 , as diffusion within those structures is also restricted, causing the corresponding signal to survive the strong diffusion weighting. We devise an estimator of the axonal T 2 based on the directional spherical variance of the strongly diffusion-weighted signal. The spherical variance T 2 estimates are insensitive to the presence of isotropic contributions to the signal like those provided by cell nuclei and vacuoles. We show that with a strong diffusion weighting these estimates differ from those obtained using the directional spherical mean of the signal which contains both axonal and isotropically-restricted contributions. Our findings hint at the presence of an MRI-visible isotropically-restricted contribution to the signal in the white matter ex vivo fixed tissue (monkey) at 7T, and do not allow us to discard such a possibility also for in vivo human data collected with a clinical 3T system., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The intracellular pathogen Legionella pneumophila, as well as other Legionella species, utilize the Icm/Dot type-IV secretion system to translocate an exceptionally large and diverse repertoire of effectors into their host cells. However, only nine core effectors were found to be present in all analyzed Legionella species. In this study, we investigated the core effectors, and used intracellular growth complementation to determine whether orthologs of core effectors perform the same function in different Legionella species. We found that three out of the nine L. pneumophila core effectors are required for maximal intracellular growth . Examination of orthologous core effectors from four Legionella species spread over the Legionella phylogenetic tree revealed that most of them perform the same function. Nevertheless, some of the orthologs of the core effector LegA3 did not complement the L. pneumophila legA3 deletion mutant for intracellular growth. LegA3 is encoded as part of an operon together with another gene, which we named legA3C, encoding a non-translocated protein. We found that LegA3 and LegA3C physically interact with each other, are both required for maximal intracellular growth, and the LegA3-LegA3C orthologous pairs from all the Legionella species examined fully complement the L. pneumophila legA3 deletion mutant for intracellular growth. Our results indicate that the Legionella core effectors orthologs generally perform the same function and establish that LegA3 requires LegA3C to fulfill its conserved function., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

This article summarizes the background, specific conditions, main measures, steps and effects of the implementation of Mass Drug Administration (MDA) to control the local P. vivax malaria epidemic in Anhui Province in central China. Distributing medicines to the designated population quickly controlled the local epidemic of P. vivax. Implementing MDA to control P. vivax ensured the correct selection of medicines, clarification of the targeted population for receipt of medicines, and assurance of a high rate of compliance through government support and health education. These results provide a reference for countries and regions experiencing similar events and planning to implement MDA in malaria control., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Purpose: Increase in the antimicrobial resistance causes a concern globally. To mitigate the rapidly rising antimicrobial resistance in the health system globally antimicrobial stewardship programs (AMSP) have been advocated. Therefore, we aim to measure aggregate antibiotic consumption by both Defined Daily Dosage (DDD) and Days of Therapy (DOT) methods., Methods: As a part of Indian Council of Medical Research initiative to develop local AMSP, this prospective study of six months was conducted at a level -1 Trauma Centre of AIIMS, New Delhi. In this, we have included all the patients of polytrauma and neurosurgical Intensive care units between April to October 2019. Consumption of antibiotics data were collected manually daily by infection control practitioners. Data were presented as Days of Therapy (DOT) and Defined Daily Dose (DDD)., Results: During the six months of study, antimicrobial consumption of ICU was compared with empirical therapy v/s culture-based therapy. Overall average antimicrobial consumption for the six months for both empirical therapy and culture-based therapy DDD/1000 patient days was 531.8 and 460.7 whereas DOT/1000 patient days 489.9 and 426.04 respectively., Conclusions: Antimicrobial Stewardship activities aim to ensure judicious consumption of antimicrobials. Such data will be of value in establishing, evaluating and monitoring the function of the AMSP in the healthcare settings., Competing Interests: Declaration of competing interest All authors report no conflict of interest relevant to this article., (Copyright © 2021 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Objective: To quantify antimicrobial use in inpatients setting as part of antimicrobial stewardship program surveillance., Method: Antimicrobial use was obtained using a pre-designed data collection form in this point prevalence study. Setting: The study was conducted in a tertiary academic hospital in the North of Jordan on 13 August 2018. Main outcome measures: antimicrobial use was determined using two methods: defined daily use (DDD) and days of therapy (DOT)., Results: This study identified antimicrobial use in 144 patients. Carbapenems, glycopeptides, and piperacillin-tazobactam were the most utilized antimicrobials in the inpatients' setting in both measures DDD and DOT. The highest prescription rate of antibiotics was in the internal medicine wards (49.8 DDD/100 admissions), followed by surgery wards (33.2 DDD/100 admissions) and intensive care unit (20.6 DDD/100 admissions)., Conclusion: This surveillance study addressed patterns of antimicrobial usage in inpatients settings in a tertiary care hospital in Jordan. This practice is feasible and could be adopted routinely by antimicrobial stewardship programs.

Background: According to the Centers for Disease Control and Prevention, patients admitted to the hospital are commonly discharged on antibiotic therapy with prolonged courses of therapy, which contributes to excessive antibiotic exposure and adverse events. The purpose of this study was to evaluate total antibiotic duration of therapy at hospital discharge at Indiana University Health Arnett, White Memorial, and Frankfort hospitals., Methods: A multicenter, retrospective electronic health record review was conducted from 1 January to 30 June 2019. Patients were included if they were at least 18 years of age, began antibiotic therapy while admitted, and continued antibiotic therapy at hospital discharge for 1 of the following indications: skin/soft tissue infection (SSTI), urinary tract infection (UTI), community-acquired pneumonia (CAP), or acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The number of days of therapy (DOT) of each inpatient and outpatient antibiotic prescribed was collected to calculate the total DOT, which was utilized to determine the appropriateness of the duration of therapy., Results: Of the 547 patients included, 233 patients (42.6%) had CAP, 120 (21.9%) had UTI, 101 (18.5%) had SSTI, and 93 (17%) had AECOPD. The median duration of antibiotic therapy across all indications was 9 days (interquartile range [IQR], 7-11). Median duration for CAP was 9 days (IQR, 7-10), AECOPD was 7 days (IQR, 5-9), UTI was 8 days (IQR, 6-10), and SSTI was 12 days (IQR, 10-14)., Conclusions: Excess antimicrobial duration at hospital discharge represents an unmet need of antimicrobial stewardship programs., (© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Red dot basal cell carcinoma is a distinctive clinical subtype of basal cell carcinoma. It has been reported in eight individuals with a male to female ratio of 1:1; and the patients' ages ranged from 50 to 74 years. All patients had prior history of actinic keratoses and basal cell carcinoma. In addition, some patients also had prior squamous cell carcinoma, malignant melanoma, and/or dysplastic nevus. The tumor was usually of recent onset, asymptomatic, and on sun-exposed skin. It was most commonly located on the nose (five patients); other sites were the upper lip, the mid back, or thigh-each in one patient. The red dot basal cell carcinoma was solitary and small-usually 4 mm or less in diameter. It typically presented as a red macule or papule; however, it sometimes appeared as a flesh-colored or pink to light-red papule with a bright-red central area. Microscopic features showed basaloid tumor cells (arranged as either nodular aggregates or superficial buds or both). In the central portion of the lesion, there was a proliferation of erythrocyte-containing vascular spaces between the epidermis and the neoplasm. The basal cell carcinoma pathology subtype was either nodular and superficial (three patients), nodular (two patients), or superficial (one patient). The clinical differential diagnosis of red dot basal cell carcinoma included not only benign vascular lesions (such as hemangioma and telangiectasia) but also inflammatory conditions and adnexal tumors. Other basaloid cell neoplasms were in the pathologic differential diagnosis. The pathogenesis of red dot basal cell carcinoma is similar to that of other basal cell carcinoma clinical subtypes. Mohs surgery is the treatment of choice for red dot basal cell carcinomas. Red dot basal cell carcinoma has two categories of biologic behavior based on the ratio of the postoperative wound size as compared with the size of the preoperative tumor: nonaggressive (for which the ratio was 5:1 or less for three patients) and aggressive (for which the ratio was greater than 12:1 for three patients). There was no recurrence of the red dot basal cell carcinoma after treatment. In conclusion, the incidence of red dot basal cell carcinoma-a unique morphologic variant of basal cell carcinoma-may be higher than suggested by the number of reported patients with this basal cell carcinoma subtype.

Background: Drug resistant tuberculosis (DR-TB) infringes substantial burden in terms of longer treatment duration, morbidity and mortality. Timely identification of patients at risks of DR-TB will aid individualized treatment. Current study was aimed to ascertain several factors associated with DR-TB among patients attending a tertiary care hospital., Methods: This retrospective study was conducted among patients with confirmed diagnosis of DR-TB and drug susceptible TB (DS-TB) seeking medical care from a tertiary care hospital during 2014-2019. The types of DR-TB included were rifampicin resistant tuberculosis (RR-TB), Multidrug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB). Appropriate statistical methods were implied to evaluate the factors associated with DR-TB., Results: Out of 580 patients, DS-TB was diagnosed in 198 (34.1%) patients while DR-TB was present in 382 patients. Of resistance cases, RR-TB, MDR-TB and XDR-TB were diagnosed in 176 (30.3%), 195 (33.6%) and 11 (1.9%) patients, respectively. Significant differences ( P < 0.05) in demographics and clinico-laboratory characteristics were observed between patients with DS-TB and DR-TB. Logistic regression analysis revealed age ≤38 years (OR: 2.5), single marital status (OR: 11.1), tobacco use (OR: 2.9), previous treatment (OR: 19.2), treatment failure (OR: 9.2) and cavity on chest X-ray (OR: 30.1) as independent risk factors for MDR-TB. However, XDR-TB was independently associated with age group of ≤38 years (OR: 13.6), students (OR: 13.0), previous treatment (OR: 12.5), cavity on chest X-ray (OR: 59.6). The independent risk factors associated with RR-TB are age ≤38 years (OR: 2.8), females (OR: 5.7), unemployed (OR: 41.5), treatment failure (OR: 4.9), previous treatment (OR: 38.2) and cavity on chest X-ray (OR: 4.3). ROC curve analysis accentuate the excellent predictive accuracy of all logistic regression models as shown by AUC (0.968, P < 0.001) for MDR-TB, AUC (0.941, P < 0.001) for XDR-TB and AUC (0.962, P < 0.001) for RR-TB., Conclusions: Current study demonstrates a sizeable extent of resistant cases among pulmonary TB patients. This study presaged significant risk of DR-TB among females, young adults, unemployed, smokers, patients with previous treatment failure and cavitation on chest X-ray. Timely identification of high risk patients will give pronounced advantages regarding appropriate choices of prevention, treatment and disease control., Competing Interests: The authors declare that they have no competing interests., (© 2021 Saifullah et al.)

Introduction: Updated international guidelines recommend the use of a two-step algorithm (glutamate dehydrogenase [GDH] or nucleic-acid amplification test [NAAT] plus toxin) rather than NAAT alone for the diagnosis of Clostridioides difficile (formerly Clostridium difficile ) infections. The goal of our project was to evaluate the impact of a new bundle on the rate of hospital-acquired C. difficile infections (CDIs), hospital-acquired CDI standardized infection ratio (SIR), antibiotic days of therapy (DOT), and financial cost., Materials and Methods: The new bundle was implemented in April 2018. This bundle was implemented across five hospitals in Catholic Health Initiatives (CHI) Texas Division. The bundle included a switch from NAAT to a two-step process (GDH and toxin). We placed the new test in an order panel which included enteric isolation and required indications for C. difficile testing. We used quarterly data pre- and post-intervention to calculate SIR and DOT., Results: In the pre-intervention period, 15.5% of the total 3513 C. difficile NAAT was positive. In the post-intervention period, 5.7% of a total of 2845 GDH and toxin assays was positive for both GDH and toxin ( P < 0.0001). SIR, which adjusts for denominator and change in testing methodology, also dropped from 1.02 to 0.43. The estimated cost associated with positive C. difficile cases dropped from 1,932,150 USD to 1,113,800 USD with an estimated yearly cost saving of 794,150 USD. Compliance with enteric isolation improved from 73.1% to 92.5% ( P = 0.008)., Conclusion: The new testing bundle led to a marked reduction in hospital-acquired CDI and unnecessary treatment, reduction in C. difficile testing, an increase in compliance with enteric isolation, and significant cost savings., Competing Interests: There are no conflicts of interest., (Copyright: © 2021 Avicenna Journal of Medicine.)

Purpose: To examine the structure of photoreceptors surrounding two subtypes of subretinal drusenoid deposits (SDD), namely, dot and ribbon SDD, using multimodal imaging including adaptive optics scanning laser ophthalmoscopy (AOSLO) and spectral-domain optical coherence tomography (SD-OCT)., Methods: Twenty-six eyes of 13 patients with age-related macular degeneration (AMD) and SDD and 16 eyes of 8 subjects in normal chorioretinal health were studied. SDD presence, stage, and subtype were determined using color fundus photographs, infrared reflectance, autofluorescence imaging, and SD-OCT. SDD and surrounding photoreceptors were imaged using AOSLO. The structure of cone photoreceptors and SDD was examined at the baseline and at 2-year follow-up studies in 6 patients., Results: Dot SDD were identified in 18 eyes of 9 patients and coexisting dot and ribbon SDD were observed in 8 eyes of 4 patients. While a characteristic photoreceptor mosaic was clearly revealed by AOSLO in the area unaffected by lesions in those eyes with dot-only SDD, in unaffected areas adjacent to retinal regions with predominantly ribbon SDD, photoreceptors could no longer be visualized., Conclusion: The invisibility of the photoreceptor mosaic in unaffected areas adjacent to retinal regions with predominantly ribbon SDD suggests degeneration in the outer segment and the interdigitation zone, which impairs the waveguiding ability of the photoreceptors. Our study implies possible differentiation of disease outcome and functional impact in different types of SDD.

Making decisions regarding return-to-play after sport-related concussion (SRC) based on resolution of symptoms alone can expose contact-sport athletes to further injury before their recovery is complete. Task-related functional near-infrared spectroscopy (fNIRS) could be used to scan for abnormalities in the brain activation patterns of SRC athletes and help clinicians to manage their return-to-play. This study aims to show a proof of concept of mapping brain activation, using tomographic task-related fNIRS, as part of the clinical assessment of acute SRC patients. A high-density frequency-domain optical device was used to scan 2 SRC patients, within 72 h from injury, during the execution of 3 neurocognitive tests used in clinical practice. The optical data were resolved into a tomographic reconstruction of the brain functional activation pattern, using diffuse optical tomography. Moreover, brain activity was inferred using single-subject statistical analyses. The advantages and limitations of the introduction of this optical technique into the clinical assessment of acute SRC patients are discussed., Competing Interests: The authors declare no conflict of interest.

Background: Mobile health (mHealth) interventions have the potential to improve health through patient education and provider engagement while increasing efficiency and lowering costs. This raises the question of whether disparities in access to mobile technology could accentuate disparities in mHealth mediated care. This study addresses whether programs planning to implement mHealth interventions risk creating or perpetuating health disparities based on inequalities in smartphone ownership., Methods: Video Directly Observed Therapy (VDOT) is an mHealth intervention for monitoring tuberculosis (TB) treatment adherence through videos sent by patients to their healthcare provider using smartphones. We conducted secondary analyses of data from a single-arm trial of VDOT for TB treatment monitoring by San Diego, San Francisco, and New York City health departments. Baseline and follow-up treatment interviews were used to assess participant smartphone ownership, sociodemographics and TB treatment perceptions. Univariate and multivariable logistic regression analyses were used to identify correlates of smartphone ownership., Results: Of the 151 participants enrolled, mean age was 41 years (range: 18-87 years) and 41.1% were female. Participants mostly identified as Asian (45.0%) or Hispanic/Latino (29.8%); 57.8% had at most a high school education. At baseline, 30.4% did not own a smartphone, which was similar across sites. Older participants (adjusted odds ratio [AOR] = 1.09 per year, 95% confidence interval [CI]: 1.05-1.12), males (AOR = 2.86, 95% CI: 1.04-7.86), participants having at most a high school education (AOR = 4.48, 95% CI: 1.57-12.80), and those with an annual income below $10,000 (AOR = 3.06, 95% CI: 1.19, 7.89) had higher odds of not owning a smartphone., Conclusions: Approximately one-third of TB patients in three large United States of America (USA) cities lacked smartphones prior to the study. Patients who were older, male, less educated, or had lower annual income were less likely to own smartphones and could be denied access to mHealth interventions if personal smartphone ownership is required.

Today, there are a lack of studies focusing on the relationship between occupational complexity and executive functioning. This is noteworthy since executive functions are core aspects of cognitive processing. The present study was aimed to investigate if three occupational complexity factors (with data, people, and things) of main lifetime occupation were related to performance in executive tasks (inhibition, switching, updating). We analyzed cross-sectional data that were available for 225 participants aged 50-75 years. Results from structural equation models showed that higher complexity levels of working with data were related to lower error rates in the updating component of cognitive control. In addition, higher rates of complexity working with people was associated with lower error rates in task-switching, which also persisted after adjustment of fluid intelligence. Complexity with things, however, was not related to performance in the executive tasks. Future studies would benefit from a longitudinal design to investigate if the results from this study also hold in the long term and to further investigate the directionality between factors.

Introduction: We assessed the influence of a result-based financing (RBF) model, which included incentives for Primary Healthcare facilities on TB treatment outcomes., Methodology: We compared TB patients > 17 years and their treatment outcomes among those who did and did not benefit from RBF-model in 14 districts of Odeska oblast, Ukraine in 2017. Log-binomial regression was used to examine factors associated with being included in RBF-model., Results: Of 2,269 reported TB patients, 308 (14%) were included in RBF-model. Most patients in the RBF-model were from rural areas 229 (74%), unemployed 218 (71%), and HIV-infected 131 (43%). Individuals from urban areas (Adjusted risk ratio, ARR =0.9, 95% Confidence Interval, CI:0.89-0.94), having drug-resistant TB (ARR = 0.3, 95% CI: 0.18-0.45), and relapse TB (ARR = 0.6, 95% CI:0.40-0.83) were less likely to be included in RBF-model. Favorable outcomes in new/relapse cases with RBF-model was 89% compared with 41% (p < 0.001) without RBF. Similarly, for other retreatment this was 83% versus 40% (p < 0.001). Failures in the no-RBF group was 29% for new and relapse cases while for other retreatment cases, it was 26% (significantly higher than in the RBF-model)., Conclusion: RBF-model is effective in achieving high levels of favorable TB treatment outcomes. Almost three-in-ten TB patients in non-RBF category failed TB treatment despite having drug-susceptible TB. Efforts are now needed to include it within ongoing public health reforms and assess the feasibility of scaling-up this intervention through implementation research and dedicated funding., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2019 Evgenia Geliukh, Dilyara Nabirova, Karapet Davtyan, Svetlana Yesypenko, Rony Zachariah.)

Background: With the availability of low-cost mobile devices and the ease of internet access, mobile health (mHealth) is digitally revolutionizing the health sector even in resource-constrained settings. It is however necessary to assess end-user perceptions before deploying potential interventions., Objective: This study aimed to assess the mobile phone usage patterns and the acceptability of mobile phone support during care and treatment in patients with tuberculosis (TB) in South India., Methods: This exploratory study was conducted at an urban private tertiary care teaching hospital and nearby public primary-level health care facilities in Bangalore, South India. We recruited 185 patients with TB through consecutive sampling. Subsequent to written informed consent, participants responded to an interviewer-administered pretested questionnaire. The questionnaire included questions on demographics, phone usage patterns, and the benefits of using of mobile phone technology to improve health outcomes and treatment adherence. Frequency, mean, median, and SD or interquartile range were used to describe the data. Bivariate associations were assessed between demographics, clinical details, phone usage, and mHealth communication preferences using the chi-square test and odds ratios. Associations with a P value ≤.20 were included in a logistic regression model. A P value of <.05 was considered significant., Results: Of the 185 participants, 151 (81.6%) used a mobile phone, and half of them owned a smartphone. The primary use of the mobile phone was to communicate over voice calls (147/151, 97.4%). The short message service (SMS) text messaging feature was used by only 66/151 (43.7%) mobile phone users. A total of 87 of the 151 mobile phone users (57.6%) knew how to use the camera. Only 41/151 (27.2%) mobile phone users had used their mobile phones to communicate with their health care providers. Although receiving medication reminders via mobile phones was acceptable to all participants, 2 participants considered repeated reminders as an intrusion of their privacy. A majority of the participants (137/185, 74.1%) preferred health communications via voice calls. Of the total participants, 123/185 (66.5%) requested reminders to be sent only at specific times during the day, 22/185 (11.9%) suggested reminders should synchronize with their prescribed medication schedule, whereas 40/185 (21.6%) did not have any time preferences. English literacy was associated with a preference for SMS in comparison with voice calls. Most participants (142/185, 76.8%) preferred video-based directly observed treatment when compared with in-person directly observed treatment., Conclusions: Although mobile phones for supporting health and treatment adherence were acceptable to patients with TB, mHealth interventions should consider language, mode of communication, and preferred timing for communication to improve uptake., (©Anil A Kumar, Ayesha De Costa, Arundathi Das, GA Srinivasa, George D'Souza, Rashmi Rodrigues. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 03.04.2019.)

Objective: Dynamic Optimal Timing (Dot) is a smartphone application (app) that estimates the menstrual cycle fertile window based on the user's menstrual period start dates. Dot uses machine learning to adapt to cycles over time and informs users of 'low' and 'high' fertility days. We investigated Dot's effectiveness, calculating perfect- and typical-use failure rates., Methods: This prospective, 13 cycle observational study (ClinicalTrials.gov NCT02833922) followed 718 women who were using Dot to prevent pregnancy. Participants contributed 6616 cycles between February 2017 and October 2018, providing data on menstrual period start dates, daily sexual activity and prospective intent to prevent pregnancy. We determined pregnancy through participant-administered urine pregnancy tests and/or written or verbal confirmation. We calculated perfect- and typical-use failure rates using multi-censoring, single-decrement life-table analysis, and conducted sensitivity, attrition and survival analyses., Results: The perfect-use failure rate was calculated to be 1.0% (95% confidence interval [CI]: 0.9%, 2.9%) and the typical-use failure rate was 5.0% (95% CI: 3.4%, 6.6%) for women aged 18-39 (n = 718). Survival analyses identified no significant differences among age or racial/ethnic groups or women in different types of relationships. Attrition analyses revealed no significant sociodemographic differences, except in age, between women completing 13 cycles and those exiting the study earlier., Conclusion: Dot's effectiveness is within the range of other user-initiated contraceptive methods.

Purpose: To determine the incidence of the 'dot sign' in patients with colloid cysts of the third ventricle and to characterise its MRI appearances., Materials and Methods: Single institution retrospective analysis between January 2007 and October 2016 of all patients with either an imaging or imaging and histology-confirmed diagnosis of colloid cysts of the 3rd ventricle was undertaken. For all cases, MRI signal intensities of the cyst fluid component were graded by two independent radiologists relative to brain parenchyma. Presence of a dot, and if present, its size and relative position within the cyst were recorded. Signal intensities of the dot were then similarly assessed., Results: 37 cases of colloid cyst were identified. Of these 37.8% (n = 14) demonstrated the dot sign. The majority (11 of 14) were observed inferiorly within the cyst; two cases were anteroinferior, and one other was posterior. All identified intracystic nodules displayed low signal intensity with respect to cyst fluid on T2 weighted sequences, and only two nodules were hypointense to fluid on T1-weighted imaging, with the remainder either iso- or hyperintense., Conclusions: An intracystic low T2 'dot' is a common MRI feature of colloid cysts of the third ventricle, and to our knowledge not previously systematically described. Presence of such a dot should not only not dissuade from a diagnosis of colloid cyst being made, but should in fact be used to strengthen the imaging diagnosis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Objective: To assess six-cycle perfect and typical use efficacy of Dynamic Optimal Timing (Dot), an algorithm-based fertility app that identifies the fertile window of the menstrual cycle using a woman's period start date and provides guidance on when to avoid unprotected sex to prevent pregnancy., Study Design: We are conducting a prospective efficacy study following a cohort of women using Dot for up to 13 cycles. Study enrollment and data collection are being conducted digitally within the app and include a daily coital diary, prospective pregnancy intentions and sociodemographic information. We used data from the first six cycles to calculate life-table failure rates., Results: We enrolled 718 women age 18-39 years. Of the 629 women 18-35 years old, 15 women became pregnant during the first six cycles for a typical use failure rate of 3.5% [95% CI 1.7-5.2]. All pregnancies occurred with incorrect use, so we did not calculate a perfect use failure rate., Conclusions: These findings are promising and suggest that the 13-cycle results will demonstrate high efficacy of Dot., Implications: While final 13-cycle efficacy results are forthcoming, 6-cycle results suggest that Dot's guidance provides women with useful information for preventing pregnancy., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Antimicrobial stewardship program aims to reduce antibiotic use. Periodic measurement and monitoring of antibiotic use and comparison within the institution as well as with other organizations are important indicators. We analyzed antibiotic usage in a general hospital in Saudi Arabia. Antibiotic data were collected retrospectively for 2011 and from 2013 to 2015, and only adult patients (>15year of age) were included in the study. Data were presented as days of therapy (DOT) and defined daily dose (DDD). DDD was adjusted per 100 bed-days and according to the case mix index (CMI). The total DDD was 37,557 in 2013, 36,550 in 2014 and 38,738 in 2015. The DDD per 100 patient-days was 90.7-94.5. There was a discordant findings of antibiotic measurements based on the DDD compared to DOT, and DDD/100 bed-days compared to DOT/100 bed-days. There was a negative correlation between CMI and DDD per 100 bed days (r -0.696), but a positive correlation of CMI with DOT (r +0.93). Adjusted DDD/100 bed-days showed decrease in the usage of antibiotics, reflecting activities of the antibiotic stewardship program. The increase in DOT/100 bed-days may indicate the favorable utilization of combination therapy. Antibiotic usage needs to be adjusted per 100 bed-days and correlated with CMI for better reflection of optimal antibiotic utilization, activities of the antibiotic stewardship program, and to allow benchmarking., (Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Smartphone apps that provide women with information about their daily fertility status during their menstrual cycles can contribute to the contraceptive method mix. However, if these apps claim to help a user prevent pregnancy, they must undergo similar rigorous research required for other contraceptive methods. Georgetown University's Institute for Reproductive Health is conducting a prospective longitudinal efficacy trial on Dot (Dynamic Optimal Timing), an algorithm-based fertility app designed to help women prevent pregnancy., Objective: The aim of this paper was to highlight decision points during the recruitment-enrollment process and the effect of modifications on enrollment numbers and demographics. Recruiting eligible research participants for a contraceptive efficacy study and enrolling an adequate number to statistically assess the effectiveness of Dot is critical. Recruiting and enrolling participants for the Dot study involved making decisions based on research and analytic data, constant process modification, and close monitoring and evaluation of the effect of these modifications., Methods: Originally, the only option for women to enroll in the study was to do so over the phone with a study representative. On noticing low enrollment numbers, we examined the 7 steps from the time a woman received the recruitment message until she completed enrollment and made modifications accordingly. In modification 1, we added call-back and voicemail procedures to increase the number of completed calls. Modification 2 involved using a chat and instant message (IM) features to facilitate study enrollment. In modification 3, the process was fully automated to allow participants to enroll in the study without the aid of study representatives., Results: After these modifications were implemented, 719 women were enrolled in the study over a 6-month period. The majority of participants (494/719, 68.7%) were enrolled during modification 3, in which they had the option to enroll via phone, chat, or the fully automated process. Overall, 29.2% (210/719) of the participants were enrolled via a phone call, 19.9% (143/719) via chat/IM, and 50.9% (366/719) directly through the fully automated process. With respect to the demographic profile of our study sample, we found a significant statistical difference in education level across all modifications (P<.05) but not in age or race or ethnicity (P>.05)., Conclusions: Our findings show that agile and consistent modifications to the recruitment and enrollment process were necessary to yield an appropriate sample size. An automated process resulted in significantly higher enrollment rates than one that required phone interaction with study representatives. Although there were some differences in demographic characteristics of enrollees as the process was modified, in general, our study population is diverse and reflects the overall United States population in terms of race/ethnicity, age, and education. Additional research is proposed to identify how differences in mode of enrollment and demographic characteristics may affect participants' performance in the study., Trial Registration: ClinicalTrials.gov NCT02833922; http://clinicaltrials.gov/ct2/show/NCT02833922 (Archived by WebCite at http://www.webcitation.org/6yj5FHrBh)., (©Dominick Shattuck, Liya T Haile, Rebecca G Simmons. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 20.04.2018.)

Background: In clinical trials, an extended therapy duration has been associated with better outcomes in patients with newly diagnosed multiple myeloma (NDMM). However, data on how the therapy duration affects the outcomes for patients with relapsed/refractory multiple myeloma (RRMM) are limited. We conducted a large, retrospective study in the United States to evaluate the effect of the duration of second-line therapy on overall survival., Patients and Methods: Adults with NDMM from January 2008 to June 2015 were followed up to identify their second-line therapy. The duration of therapy (DOT) and time to next therapy (TTNT), as a proxy for progression-free survival, were estimated using the Kaplan-Meier method. The relationship between the duration of second-line therapy and overall survival was evaluated with a logistic marginal structural model to mitigate the risk of treatment selection and survival bias., Results: A total of 628 NDMM patients developed a relapse after initial therapy. The median DOT for second-line therapy was 6.9 months (95% confidence interval [CI], 5.9-7.7 months), which was shorter than the corresponding TTNT (median, 15.1 months; 95% CI, 13.4-17.3 months). Each additional month of second-line therapy was associated with a reduced adjusted risk of death at 1 year (odds ratio, 0.78; 95% CI, 0.77-0.83; P < .001)., Conclusion: In a large database capturing a heterogeneous patient population and varied treatment patterns reflecting routine clinical care, we found a clinical benefit for continued longer DOT at first relapse. Despite the emerging paradigm favoring continuous therapy, second-line progression-free survival (utilizing TTNT as the proxy) was more than twofold longer than the DOT. Understanding the barriers to extended DOT could help to improve the outcomes for RRMM patients., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Aim: Many neurodegenerative diseases have a memory component. Brain structures related to memory are affected by environmental stimuli, and it is difficult to dissociate effects of all behavior of neurons., Materials & Methods: Here, visual cortex of mice was stimulated with gratings and dot, and an observation of neuronal activity before and after was made. Bandwidth, firing rate and orientation selectivity index were evaluated., Results: A primary communication between primary visual cortex and short-term memory appeared to show an interesting path to train cognitive circuitry and investigate the basics mechanisms of the neuronal learning. The findings also suggested the interplay between primary visual cortex and short-term plasticity., Conclusion: The properties inside a visual target shape the perception and affect the basic encoding. Using visual cortex, it may be possible to train the memory and improve the recovery of people with cognitive disabilities or memory deficit.

Background: The Direct Observation of Treatment (DOT) is an important component of the country's TB Control strategy. Standards of TB care in India and the End TB strategy emphasised the importance of a patient-centered approach to foster adherence. A qualitative study was conducted to explore the perception of people with Tuberculosis in Kerala regarding DOT, mechanisms to make the treatment of TB more patients centered and to identify the preferable mechanisms to ensure adherence., Methods: Six focus group discussions were conducted - two among people with TB from rural area, two among people with TB in urban area, one among multipurpose health workers of rural area and one among key field staff of TB control in urban area., Results: Patients who were on a strict DOT were unhappy about the issues of confidentiality, patient inconvenience and provider centered approach. A flexible, patient centered approach were a family member can act as the DOT provider with guidance from a trained health worker was evolved as the most acceptable and comfortable mode of treatment to majority of the TB patients. They felt that a strict external monitor as a DOT provider was not a necessity in majority of the cases. Only practical way to effectively incorporate ICT in monitoring patient compliance in current scenario was identified as daily phone call reminders. Patients also expressed their concerns in keeping the medicines for entire duration at home., Conclusion: A flexible patient wise individualized system based on patient's behavior, literacy and awareness along with attitude of family members is needed to ensure adherence to anti TB drugs., (Copyright © 2016 Tuberculosis Association of India. Published by Elsevier B.V. All rights reserved.)

Red dot basal cell carcinoma is a unique variant of basal cell carcinoma. Including the three patients described in this report, red dot basal cell carcinoma has only been described in seven individuals. This paper describes the features of two males and one female with red dot basal cell carcinoma and reviews the characteristics of other patients with this clinical subtype of basal cell carcinoma. A 70-year-old male developed a pearly-colored papule with a red dot in the center on his nasal tip. A 71-year-old male developed a red dot surrounded by a flesh-colored papule on his left nostril. Lastly, a 74-year-old female developed a red dot within an area of erythema on her left mid back. Biopsy of the lesions all showed nodular and/or superficial basal cell carcinoma. Correlation of the clinical presentation and pathology established the diagnosis of red dot basal cell carcinoma. The tumors were treated by excision using the Mohs surgical technique. Pubmed was searched with the keyword: basal, cell, cancer, carcinoma, dot, red, and skin. The papers generated by the search and their references were reviewed. Red dot basal cell carcinoma has been described in three females and two males; the gender was not reported in two patients. The tumor was located on the nose (five patients), back (one patient) and thigh (one patient). Cancer presented as a solitary small red macule or papule; often, the carcinoma was surrounded by erythema or a flesh-colored papule. Although basal cell carcinomas usually do not blanch after a glass microscope slide is pressed against them, the red dot basal cell carcinoma blanched after diascopy in two of the patients, resulting in a delay of diagnosis in one of these individuals. Dermoscopy may be a useful non-invasive modality for evaluating skin lesions when the diagnosis of red dot basal cell carcinoma is considered. Mohs surgery is the treatment of choice; in some of the patients, the ratio of the area of the postoperative wound to that of the preoperative cancer was greater than 12:1, demonstrating a significant lateral spread of the tumor beyond the observed clinical margins of the neoplasm. In conclusion, in a patient with a personal history of actinic keratosis or nonmelanoma skin cancer, the appearance of a new red dot in a sun-exposed site should prompt additional evaluation of the skin lesion to exclude or establish the diagnosis of red dot basal cell carcinoma., Competing Interests: The authors have declared that no competing interests exist.

Aim: Safer and shorter antituberculosis treatment (ATT) regimens represent the unmet medical need., Patients & Methods: The patients were randomly assigned into two arms: the first (n = 137) received once-daily sublingual honey lozenge formulated with botanical immunomodulator Immunoxel and the second (n = 132) received placebo lozenges along with conventional ATT. Immunoxel and placebo arms were demographically similar: 102 versus 106 had drug-susceptible TB; 28 versus 20 multidrug-resistant TB (MDR-TB); 7 versus 7 extensively drug-resistant TB (XDR-TB); and 22 versus 20 TB-HIV. The primary end point was sputum smear conversion., Results: After 1 month 87 out 132 (65.9%) of Immunoxel recipients became sputum smear negative, whereas 32 out of 127 (25.2%) in placebo group had converted (p < 0.0001). Sputum clearance produced by Immunoxel was equally effective across all forms of TB. In the immunotherapy arm the average weight gain was 2 kg, but placebo recipients gained only 0.6 kg. Immunoxel reduced TB-associated inflammation as evidenced by defervescence and normalization of elevated leukocyte counts and erythrocyte sedimentation rate. No adverse effects were seen at any time. The liver function tests indicate that ATT-caused hepatotoxicity was counteracted by Immunoxel. These results are in agreement with prior 20 trials of Immunoxel conducted over the past 17 years., Conclusion: Immunoxel is affordable, safe, effective, fast-acting, commercially available immunotherapeutic intervention to supplement conventional TB chemotherapy. Clinicaltrials.gov ID: NCT01061593.

dot-app is a Cytoscape 3 app that allows Cytoscape to import and export Graphviz (.dot, .gv) files, also known as DOT files due to the .dot extension and their conformance to the DOT language syntax. The DOT format was originally created in the early 2000s to represent graph topologies, layouts and formatting. DOT-encoded files are produced and consumed by a number of open-source graph applications, including Graphviz, Gephi, Tulip, and others. While DOT-based graph applications are popular, they emphasize general graph layout and styling over the topological and semantic analysis functions available in domain-focused applications such as Cytoscape. While domain-focused applications have easy access to large networks (10,000 to 100,000 nodes) and advanced analysis and formatting, they do not have as many styling options as the Graphviz software suite. dot-app enables the interchange of networks between Cytoscape and DOT-compatible applications so that users can benefit from the features of both. dot-app was first deployed to the Cytoscape App Store in August 2015, has since registered more than 1,200 downloads, and has been highly rated by more than 20 users., Competing Interests: Competing interests: No competing interests were disclosed.

dot-app is a Cytoscape 3 app that allows Cytoscape to import and export Graphviz (*.dot, *.gv) files, also known as DOT files due to the *.dot extension and their conformance to the DOT language syntax. The DOT format was originally created in the early 2000s to represent graph topologies, layouts and formatting. DOT-encoded files are produced and consumed by a number of open-source graph applications, including GraphViz, Gephi, neato, smyrna, and others. While DOT-based graph applications are popular, they emphasize general graph layout and styling over the topological and semantic analysis functions available in domain-focused applications such as Cytoscape. While domain-focused applications have easy access to large networks (10,000 to 100,000 nodes) and advanced analysis and formatting, they do not offer all of the styling options that DOT-based applications (particularly GraphViz) do. dot-app enables the interchange of networks between Cytoscape and DOT-based applications so that users can benefit from the features of both. dot-app was first deployed to the Cytoscape App Store in August 2015, has since registered more than 1,200 downloads, and has been highly rated by more than 20 users., Competing Interests: No competing interests were disclosed.

The incidence of tuberculosis decreases. However, clinical cases frequently raise questions, mainly in the context of contact tracing or when antimicrobial resistance is suspected. Empiric standard treatment consists of rifampin, isoniazid, ethambutol and pyrazinamide. This initial regimen aims to reduce the number of pathogenic germs while the consolidation therapy should eradicate the remaining pathogens. Treatment duration and adherence are crucial for cure. For the treatment of latent tuberculosis the traditional 6 to 9 months isoniazid regimen is still the treatment of choice. In complex cases such as tuberculosis in immunocompromised patients or if resistant tuberculosis is suspected, patients should be referred to a specialized center.

A recent innovation to help patients adhere to daily tuberculosis (TB) treatment over many months is video (or virtually) observed therapy (VOT). VOT is becoming increasingly feasible as mobile telephone applications and tablet computers become more widely available. Studies of the effectiveness of VOT in improving TB patient outcomes are being conducted.

Near-infrared spectroscopy (NIRS) was originally designed for clinical monitoring of tissue oxygenation, and it has also been developed into a useful tool in neuroimaging studies, with the so-called functional NIRS (fNIRS). With NIRS, cerebral activation is detected by measuring the cerebral hemoglobin (Hb), where however, the precise correlation between NIRS signal and neural activity remains to be fully understood. This can in part be attributed to the situation that NIRS signals are inherently subject to contamination by signals arising from extracerebral tissue. In recent years, several approaches have been investigated to distinguish between NIRS signals originating in cerebral tissue and signals originating in extracerebral tissue. Selective measurements of cerebral Hb will enable a further evolution of fNIRS. This chapter is divided into six sections: first a summary of the basic theory of NIRS, NIRS signals arising in the activated areas, correlations between NIRS signals and fMRI signals, correlations between NIRS signals and neural activities, and the influence of a variety of extracerebral tissue on NIRS signals and approaches to this issue are reviewed. Finally, future prospects of fNIRS are described., (© 2016 Elsevier B.V. All rights reserved.)