Exploring opportunities to strengthen rural tuberculosis health service delivery: a qualitative study with health workers in Tibet autonomous region, China.

OBJECTIVES: This qualitative study aimed to explore opportunities to strengthen tuberculosis (TB) health service delivery from the perspectives of health workers providing TB care in Shigatse prefecture of Tibet Autonomous Region, China. DESIGN: Qualitative research, semi-structured in-depth interviews. SETTING: The TB care ecosystem in Shigatse, including primary and community care. PARTICIPANTS: Participants: 37 semi-structured interviews were conducted with village doctors (14), township doctors and nurses (14), county hospital doctors (7) and Shigatse Centre for Disease Control staff (2). RESULTS: The three main themes reported include (1) the importance of training primary and community health workers to identify people with symptoms of TB, ensure TB is diagnosed and link people with TB to further care; (2) the need to engage community health workers to ensure retention in care and adherence to TB medications; and (3) the opportunity for innovative technologies to support coordinated care, retention in care and adherence to medication in Shigatse. CONCLUSIONS: The quality of TB care could be improved across the care cascade in Tibet and other high-burden, remote settings by strengthening primary care through ongoing training, greater support and inclusion of community health workers and by leveraging technology to create a circle of care. Future formative and implementation research should include the perspectives of health workers at all levels to improve care organisation and delivery.

Rapid and accurate quality evaluation of Angelicae Sinensis Radix based on near-infrared spectroscopy and Bayesian optimized LSTM network.

The authentic traditional Chinese medicines (TCMs) including Angelicae Sinensis Radix (ASR) are the representative of high-quality herbals in China. However, ASR from authentic region being adulterated or counterfeited is frequently occurring, and there is still a lack of rapid quality evaluation methods for identifying the authentic ASR. In this study, the color features of ASR were firstly characterized. The results showed that the authentic ASR cannot be fully identified by color characteristics. Then near-infrared (NIR) spectroscopy combined with Bayesian optimized long short-term memory (BO-LSTM) was used to evaluate the quality of ASR, and the performance of BO-LSTM with common classification and regression algorithms was compared. The results revealed that following the pretreatment of NIR spectra, the optimal NIR spectra combined with BO-LSTM not only successfully distinguished authentic, non-authentic, and adulterated ASR with 100 % accuracy, but also accurately predicted the adulteration concentration of authentic ASR (R2 > 0.99). Moreover, BO-LSTM demonstrated excellent performance in classification and regression compared with common algorithms (ANN, SVM, PLSR, etc.). Overall, the proposed strategy could quickly and accurately evaluate the quality of ASR, which provided a reference for other TCMs.

Effectiveness of a comprehensive package based on electronic medication monitors at improving treatment outcomes among tuberculosis patients in Tibet: a multicentre randomised controlled trial.

BACKGROUND: WHO recommends that electronic medication monitors, a form of digital adherence technology, be used as a complement to directly observed treatment (DOT) for tuberculosis, as DOT is inconvenient and costly. However, existing evidence about the effectiveness of these monitors is inconclusive. Therefore, we evaluated the effectiveness of a comprehensive package based on electronic medication monitors among patients with tuberculosis in Tibet Autonomous Region (hereafter Tibet), China. METHODS: This multicentre, randomised controlled trial recruited patients from six counties in Shigatse, Tibet. Eligible participants had drug-susceptible tuberculosis and were aged 15 years or older when starting standard tuberculosis treatment. Tuberculosis doctors recruited patients from the public tuberculosis dispensary in each county and the study statistician randomly assigned them to the intervention or control group based on the predetermined randomised allocation sequence. Intervention patients received an electronic medication monitor box. The box included audio medication-adherence reminders and recorded box-opening data, which were transmitted to a cloud-based server and were accessible to health-care providers to allow remote adherence monitoring. A linked smartphone app enabled text, audio, and video communication between patients and health-care providers. Patients were also provided with a free data plan. Patients selected a treatment supporter (often a family member) who was trained to support patients with using the electronic medication monitor and app. Patients in the control group received usual care plus a deactivated electronic medication monitor, which only recorded and transmitted box-opening data that was not made available to health-care providers. The control group also had no access to the app or trained treatment supporters. The primary outcome was a binary indicator of poor monthly adherence, defined as missing 20% or more of planned doses in the treatment month, measured using electronic medication monitor opening data, and verified by counting used medication blister packages during consultations. We recorded other secondary treatment outcomes based on national tuberculosis reporting data. We analysed the primary outcome based on the intention-to-treat population. This trial is registered at ISRCTN, 52132803. FINDINGS: Between Nov 17, 2018, and April 5, 2021, 278 patients were enrolled into the study. 143 patients were randomly assigned to the intervention group and 135 patients to the control group. Follow-up ended when the final patient completed treatment on Oct 4, 2021. In the intervention group, 87 (10%) of the 854 treatment months showed poor adherence compared with 290 (37%) of the 795 months in the control group. The corresponding adjusted risk difference for the intervention versus control was -29·2 percentage points (95% CI -35·3 to -22·2; p<0·0001). Five of the six secondary treatment outcomes also showed clear improvements, including treatment success, which was found for 133 (94%) of the 142 individuals in the intervention arm and 98 (73%) of the 134 individuals in the control arm, with an adjusted risk difference of 21 percentage points (95% CI 12·4-29·4); p<0·0001. INTERPRETATION: The interventions were effective at improving tuberculosis treatment adherence and outcomes, and the trial suggests that a comprehensive package involving electronic medication monitors might positively affect tuberculosis programmes in high-burden and low-resource settings. FUNDING: TB REACH.

Substrate-free dissolving microneedles with barbed shape to increase adhesion and drug-delivery efficiency to skin.

Microneedle drug delivery has recently emerged as a clinical method, and dissolving microneedles (DMNs) offer exclusive simplicity and efficiency, compared to the other kinds of microneedles. The tips of most currently available DMNs are cone/house-shaped to result in a lower penetration force. Penetration of the needle tips into the skin relies mainly on the back tape or external pressure, and their adhesion to the skin is relatively low. In addition, only the drug in the part of tips that are pierced into the dermis can be dissolved, resulting in drug waste. Inspired from the barbed structure of the honeybee stinger, we reported substrate-free DMNs with a barbed structure by a dual-molding process, which is suitable for mass production. Those DMNs showed 3-fold greater adhesion force between the needle tips and the skin, better dissolution and deeper penetration than house-shaped DMNs in vivo under the same conditions. For the in situ treatment of psoriasis in mice, the barbed DMNs required only the half dose of house-shaped DMNs to achieve similar efficacy.

Protective effects of Huang-Qi-Ge-Gen decoction against diabetic liver injury through regulating PI3K/AKT/Nrf2 pathway and metabolic profiling.

ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Qi-Ge-Gen decoction (HGD) is a traditional Chinese medicine prescription that has been used for centuries to treat "Xiaoke" (the name of diabetes mellitus in ancient China). However, the ameliorating effects of HGD on diabetic liver injury (DLI) and its mechanisms are not yet fully understood. AIM OF THE STUDY: To elucidate the ameliorative effect of HGD on DLI and explore its material basis and potential hepatoprotective mechanism. MATERIALS AND METHODS: A diabetic mice model was induced by feeding a high-fat diet and injecting intraperitoneally with streptozotocin (40 mg kg-1) for five days. After the animals were in confirmed diabetic condition, they were given HGD (3 or 12 g kg-1, i. g.) for 14 weeks. The effectiveness of HGD in treating DLI mice was evaluated by monitoring blood glucose and blood lipid levels, liver function, and pathological conditions. Furthermore, UPLC-MS/MS was used to identify the chemical component profile in HGD and absorption components in HGD-treated plasma. Network pharmacology and molecular docking were performed to predict the potential pathway of HGD intervention in DLI. Then, the results of network pharmacology were validated by examining biochemical parameters and using western blotting. Lastly, urine metabolites were analyzed by metabolomics strategy to explore the effect of HGD on the metabolic profile of DLI mice. RESULTS: HGD exerted therapeutic potential against the disorders of glucose metabolism and lipid metabolism, liver dysfunction, liver steatosis, and fibrosis in a DLI model mice induced by HFD/STZ. A total of 108 chemical components in HGD and 18 absorption components in HGD-treated plasma were preliminarily identified. Network pharmacology and molecular docking results of the absorbed components in plasma indicated PI3K/AKT as a potential pathway for HGD to intervene in DLI mice. Further experiments verified that HGD markedly reduced liver oxidative stress in DLI mice by modulating the PI3K/AKT/Nrf2 signaling pathway. Moreover, 19 differential metabolites between normal and DLI mice were detected in urine, and seven metabolites could be significantly modulated back by HGD. CONCLUSIONS: HGD could ameliorate diabetic liver injury by modulating the PI3K/AKT/Nrf2 signaling pathway and urinary metabolic profile.

Wireless facial biosensing system for monitoring facial palsy with flexible microneedle electrode arrays.

Facial palsy (FP) profoundly influences interpersonal communication and emotional expression, necessitating precise diagnostic and monitoring tools for optimal care. However, current electromyography (EMG) systems are limited by their bulky nature, complex setups, and dependence on skilled technicians. Here we report an innovative biosensing approach that utilizes a PEDOT:PSS-modified flexible microneedle electrode array (P-FMNEA) to overcome the limitations of existing EMG devices. Supple system-level mechanics ensure excellent conformality to the facial curvilinear regions, enabling the detection of targeted muscular ensemble movements for facial paralysis assessment. Moreover, our apparatus adeptly captures each electrical impulse in response to real-time direct nerve stimulation during neurosurgical procedures. The wireless conveyance of EMG signals to medical facilities via a server augments access to patient follow-up evaluation data, fostering prompt treatment suggestions and enabling the access of multiple facial EMG datasets during typical 6-month follow-ups. Furthermore, the device's soft mechanics alleviate issues of spatial intricacy, diminish pain, and minimize soft tissue hematomas associated with traditional needle electrode positioning. This groundbreaking biosensing strategy has the potential to transform FP management by providing an efficient, user-friendly, and less invasive alternative to the prevailing EMG devices. This pioneering technology enables more informed decision-making in FP-management and therapeutic intervention.

Comparative study on Angelica sinensis after different processing with yellow rice wine in color, aromas, chemical components, and antioxidant activities.

This study aimed to explore the differences in raw Angelica Sinensis (RAS), wine washing AS (WAS), and wine stir-frying AS (WSAS). The results showed there were differences among the three AS in color and aroma, and 34 aroma compounds were identified. The content determination results revealed the ferulic acid and Z-ligustilide levels of RAS decreased after processing, and those in WAS were higher than in WSAS. Furthermore, 85 representative common components and 37 unique components were tentatively identified in three AS. Finally, the free radical scavenging assay results indicated the antioxidant capacity of RAS was reduced after processing, and the antioxidant capacity of WAS was better than WSAS. Collectively, the RAS undergoes significant changes in color, aromas, components, and antioxidant ability after processing, and the different processing methods also result in significant differences between WAS and WSAS.

Factors Influencing Medication Adherence in Elderly Patients with Hypertension: A Single Center Study in Western China.

Purpose: To develop and empirically test a conceptual model that explains the factors influencing antihypertensive medication adherence behavior in elderly patients in a city in western China. Patients and Methods: The conceptual model was based on the Theory of Planned Behavior and the Health Belief Model and was empirically tested using cross-sectional survey data from Nanchong City, a city in western China, collected between October and December 2020. Data were analyzed using structural equation modeling. Results: Behavioral intentions were the main predictor of medication adherence behavior (path coefficient of 0.353). Perceived benefits and perceived barriers directly (path coefficient = 0.201 and -0.150, respectively), and indirectly (path coefficient = 0.118 and -0.060) through behavioral intentions, influenced medication adherence behavior. Perceived susceptibility (path coefficient = 0.390) and perceived severity (path coefficient = 0.408) influenced behavioral attitudes, which influenced behavioral intentions (path coefficient = 0.298). Conclusion: The conceptual model demonstrates a robust ability to predict and explain medication adherence behavior among elderly patients with hypertension, facilitating the adoption and maintenance of changes in adherence behavior and the potential for preventing disease progression and improving quality of life.

Combination of UHPLC-Q Exactive-Orbitrap MS, Bioinformatics and Molecular Docking to Reveal the Mechanism of Huan-Lian-Jie-Du Decoction in the Treatment of Diabetic Encephalopathy.

Diabetic encephalopathy (DE) is a serious complication of diabetes, which affects patients' quality of life. We aimed to explore HLJDD in the treatment of DE by LC/MS and bioinformatics. UPLC-Q Exactive-Orbitrap MS was employed to clarify the compounds. The modules and hub targets of DE were gained from WGCNA. Subsequently, an Herb-Compound-Target network was constructed and enrichment analysis was used. In addition, a protein-protein interaction (PPI) network was constructed and molecular docking was used to verify the above analysis. As result, 138 compounds and 10 prototypes in brain were identified. In network pharmacology, 8 modules and 5692 hub targets were obtained from WGCNA. An Herb-Compound-Target network was constructed by 4 herbs, 10 compounds and 56 targets. The enrichment analysis showed that the treatment of DE with HLJDD involve oxidative stress and neuroprotection. Beside, SRC, JUN, STAT3, MAPK1 and PIK3R1 were identified and as hub targets of HLJDD in treating DE. Moreover, Molecular docking showed that five hub targets had strong affinity with the corresponding alkaloids. Therefore, we explored the underlying mechanisms of HLJDD in the treatment of DE and to provide the theoretical and scientific basis for subsequent experimental studies and clinical applications.

Customized flexible hollow microneedles for psoriasis treatment with reduced-dose drug.

Microneedles, especially hollow microneedles (HMNs), play an important role in drug delivery, but most of the current HMNs are manufactured based on silicon microfabrication (lithography, etching, etc.), which are slightly conservative due to the lack of low-cost, batch-scale and customized preparation approach, especially for the HMNs with flexible substrate. For the first time, we propose the use of a high-precision 3D printed master mold followed by a dual-molding process for the preparation of HMNs with different shapes, heights, and inner and outer diameters to satisfy different drug delivery needs. The 3D printed master mold and negative mold can be reused, thereby significantly reducing the cost. HMNs are based on biocompatible materials, such as heat-curing polymers or light-curing resins. The thickness and rigidity/flexibility characteristics of the substrate can be customized for different applications. The drug delivery efficiency of the fabricated HMNs was verified by the in situ treatment of psoriasis on the backs of mice, which required only a 0.1-fold oral dose to achieve similar efficacy, and the associated side effects and drug toxicity were reduced. Thus, this dual-molding process can reinvigorate HMNs development.

Pterostilbene could alleviate diabetic cognitive impairment by suppressing TLR4/NF-кB pathway through microbiota-gut-brain axis.

Diabetic cognitive impairment (DCI) is a serious neurodegenerative disorder caused by diabetes, with chronic inflammation being a crucial factor in its pathogenesis. Pterostilbene is a well-known natural stilbene derivative that has excellent anti-inflammatory activity, suggesting its potential medicinal advantages for treating DCI. Therefore, this study is to explore the beneficial effects of pterostilbene for improving cognitive dysfunction in DCI mice. A diabetic model was induced by a high-fat diet plus streptozotocin (40 mg·kg-1 ) for consecutive 5 days. After the animals were confirmed to be in a diabetic state, they were treated with pterostilbene (20 or 60 mg·kg-1 , i.g.) for 10 weeks. Pharmacological evaluation showed pterostilbene could ameliorate cognitive dysfunction, regulate glycolipid metabolism disorders, improve neuronal damage, and reduce the accumulation of ß-amyloid in DCI mice. Pterostilbene alleviated neuroinflammation by suppressing oxidative stress and carbonyl stress damage, astrocyte and microglia activation, and dopaminergic neuronal loss. Further investigations showed that pterostilbene reduced the level of lipopolysaccharide, modulated colon and brain TLR4/NF-κB signaling pathways, and decreased the release of inflammatory factors, which in turn inhibited intestinal inflammation and neuroinflammation. Furthermore, pterostilbene could also improve the homeostasis of intestinal microbiota, increase the levels of short-chain fatty acids and their receptors, and suppress the loss of intestinal tight junction proteins. In addition, the results of plasma non-targeted metabolomics revealed that pterostilbene could modulate differential metabolites and metabolic pathways associated with inflammation, thereby suppressing systemic inflammation in DCI mice. Collectively, our study found for the first time that pterostilbene could alleviate diabetic cognitive dysfunction by inhibiting the TLR4/NF-κB pathway through the microbiota-gut-brain axis, which may be one of the potential mechanisms for its neuroprotective effects.

A Low-Cost Flexible Perforated Respiratory Sensor Based on Platinum for Continuous Respiratory Monitoring.

Monitoring sleep conditions is of importance for sleep quality evaluation and sleep disease diagnosis. Accurate respiration detection provides key information about sleep conditions. Here, we propose a perforated temperature sensor that can be worn below the nasal cavity to monitor breath. The sensing system consists of two perforated temperature sensors, signal conditioning circuits, a transmission module, and a supporting analysis algorithm. The perforated structure effectively enhances the sensitivity of the system and shortens the response time. The sensor's response time is 0.07 s in air and sensitivity is 1.4‱°C-1. The device can achieve a monitoring respiratory temperature range between normal room temperature and 40 °C. The simple and standard micromachining process ensures low cost and high reproducibility. We achieved the monitoring of different breathing patterns, such as normal breathing, panting, and apnea, which can be applied to sleep breath monitoring and exercise information recording.

Trilobatin alleviates non-alcoholic fatty liver disease in high-fat diet plus streptozotocin-induced diabetic mice by suppressing NLRP3 inflammasome activation.

Diabetes mellitus (DM) is a factor with great risk in the course of non-alcoholic fatty liver disease (NAFLD) due to its high glucotoxicity and lipotoxicity. Trilobatin, a glycosylated dihydrochalcone derived from the leaves of the Chinese sweet tea Lithocarpus polystachyus Rehd, is reported to possess various pharmacological activities. Nevertheless, it is still unclear regarding if trilobatin can alleviate liver injury in diabetic mice with NAFLD and its mechanism. Our aim was to investigative the protective effects of trilobatin against DM with NAFLD and its mechanism of action. A DM mice model was established by high-fat diet (HFD) feeding with streptozocin (STZ) injections, and treated with trilobatin for 10 weeks. The biochemical results showed that trilobatin restored glucose metabolic disorder and liver function in diabetic mice. The histopathological evaluation revealed that trilobatin improved liver injury by alleviating lipid accumulation and liver fibrosis. Mechanistically, trilobatin decreased expression of NLRP3, p65 NF-κB, cleaved-Caspase-1 and N-GSDMD, as well as the release of IL-18 and IL-1ß, leading to a alleviation of inflammation and pyroptosis. Taken together, we determined for the first time found that trilobatin could prevent liver injury in diabetic mice with NAFLD by suppressing NLRP3 inflammasome activation to reduce inflammation and pyroptosis.

High-Performance Flexible Microneedle Array as a Low-Impedance Surface Biopotential Dry Electrode for Wearable Electrophysiological Recording and Polysomnography.

HIGHLIGHTS: Polyimide-based flexible microneedle array (PI-MNA) electrodes realize high electrical/mechanical performance and are compatible with wearable wireless recording systems. The normalized electrode-skin interface impedance (EII) of the PI-MNA electrodes reaches 0.98 kΩ cm2 at 1 kHz and 1.50 kΩ cm2 at 10 Hz, approximately 1/250 of clinical standard electrodes. This is the first report on the clinical study of microneedle electrodes. The PI-MNA electrodes are applied to clinical long-term continuous monitoring for polysomnography. Microneedle array (MNA) electrodes are an effective solution to achieve high-quality surface biopotential recording without the coordination of conductive gel and are thus very suitable for long-term wearable applications. Existing schemes are limited by flexibility, biosafety, and manufacturing costs, which create large barriers for wider applications. Here, we present a novel flexible MNA electrode that can simultaneously achieve flexibility of the substrate to fit a curved body surface, robustness of microneedles to penetrate the skin without fracture, and a simplified process to allow mass production. The compatibility with wearable wireless systems and the short preparation time of the electrodes significantly improves the comfort and convenience of electrophysiological recording. The normalized electrode-skin contact impedance reaches 0.98 kΩ cm2 at 1 kHz and 1.50 kΩ cm2 at 10 Hz, a record low value compared to previous reports and approximately 1/250 of the standard electrodes. The morphology, biosafety, and electrical/mechanical properties are fully characterized, and wearable recordings with a high signal-to-noise ratio and low motion artifacts are realized. The first reported clinical study of microneedle electrodes for surface electrophysiological monitoring was conducted in tens of healthy and sleep-disordered subjects with 44 nights of recording (over 8 h per night), providing substantial evidence that the electrodes can be leveraged to substitute for clinical standard electrodes.

Exploring the translation process for multilingual implementation research studies: a collaborative autoethnography.

INTRODUCTION: In an increasingly globalised and interconnected world, evidence to evaluate complex interventions may be generated in multiple languages. However, despite its influence in shaping the evidence base, there is little literature explicitly connecting the translation process to the goals and processes of implementation research. This study aims to explore the processes and experience of an international implementation research team conducting a process evaluation of a complex intervention in Tibet Autonomous Region, China. METHODS: This study uses a collaborative autoethnographic approach to explore the translation process from Chinese or Tibetan to English of key stakeholder interview transcripts. In this approach, multiple researchers and translators contributed their reflections, and conducted joint analysis through dialogue, reflection and with consideration of multiple perspectives. Seven researchers involved with the translation process contributed their perspectives through in-depth interviews or written reflections and jointly analysed the resulting data. RESULTS: We describe the translation process, synthesise key challenges including developing a 'voice' and tone as a translator, conveying the depth of idioms across languages, and distance from the study context. We further offer lessons learnt including the importance of word banks with unified translations of words and phrases created iteratively during the translation process, the need to collaborate between translators and the introspective work necessary for translators to explore their positionality and reflexivity during the work. We then offer a summary of these learnings for other implementation research teams. CONCLUSION: Our findings emphasise that in order to ensure rigour in their work, implementation research teams using qualitative data should make concerted effort to consider both the translation process as well as its outcomes. Given the numerous multinational or multilingual implementation research studies using qualitative methods, there is a need for further consideration and reflection on the translation process.

Protective effects of Huang-Lian-Jie-Du Decoction on diabetic nephropathy through regulating AGEs/RAGE/Akt/Nrf2 pathway and metabolic profiling in db/db mice.

BACKGROUND: Diabetic nephropathy (DN) is a severe diabetic complication that is the principal cause of end-stage kidney disease worldwide. Huang-Lian-Jie-Du Decoction (HLJDD) is widely used to treat diabetes clinically. However, the nephroprotective effects and potential mechanism of action of HLJDD against DN have not yet been fully elucidated. PURPOSE: This study aimed to investigate the potential roles of HLJDD in DN and elucidate its mechanisms in db/db mice. METHODS: An integrated strategy of network pharmacology, pharmacodynamics, molecular biology, and metabolomics was used to reveal the mechanisms of HLJDD in the treatment of DN. First, network pharmacology was utilized to predict the possible pathways for DN using the absorbed ingredients of HLJDD in rat plasma in silico. Then, combined with histopathological examination, biochemical evaluation immunohistochemistry/immunofluorescence assay, western blot analysis, and UPLC-Q-Orbitrap HRMS/MS-based metabolomics approach were applied to evaluate the efficacy of HLJDD against DN and its underlying mechanisms in vivo. RESULTS: In silico, network pharmacology indicated that the AGEs/RAGE pathway was the most prominent pathway for HLJDD against DN. In vivo, HLJDD exerted protective effects against DN by ameliorating glycolipid metabolic disorders and kidney injury. Furthermore, we verified that HLJDD protected against DN by regulating the AGEs/RAGE/Akt/Nrf2 pathway for the first time. In addition, 22 potential biomarkers were identified in urine, including phenylalanine metabolism, tryptophan metabolism, glucose metabolism, and sphingolipid metabolism. CONCLUSION: These findings suggest that HLJDD ameliorates DN by regulating the AGEs/RAGE/Akt/Nrf2 pathway and metabolic profiling.

Adaptive estimation of continuous gait phase based on capacitive sensors.

Continuous gait phase plays an important role in robotic prosthesis control. In this paper, we have conducted the offline adaptive estimation (at different speeds and on different ramps) of continuous gait phase of robotic transtibial prosthesis based on the adaptive oscillators. We have used the capacitive sensing method to record the deformation of the muscles. Two transtibial amputees joined in this study. Based on the strain signals of the prosthetic foot and the capacitive signals of the residual limb, the maximum and minimum of estimation errors are 0.80 rad and 0.054 rad, respectively, and their corresponding ratios in one gait cycle are 1.27% and 0.86%, respectively. This paper proposes an effective method to estimate the continuous gait phase based on the capacitive signals of the residual muscles, which provides a basis for the continuous control of robotic transtibial prosthesis.

Metabolic Profiling of Carbonyl Compounds for Unveiling Protective Mechanisms of Pueraria lobata against Diabetic Nephropathy by UPLC-Q-Orbitrap HRMS/MS Analysis.

Carbonyl compounds play a critical role in the pathogenesis of diabetic nephropathy (DN). Pueraria lobata (PL), also known as "Kudzu", is a widely consumed functional food or nutraceutical and has shown promise in the prevention of diabetes and complications such as DN. To explore the beneficial effects and the underlying mechanisms of PL against DN, a new strategy for in-depth metabolic profiling of carbonyl compounds in DN mice plasma by chemical derivatization combined with UPLC-Q-Orbitrap high-resolution mass spectrometry (HRMS)/MS analysis was developed for the first time. Pharmacological evaluation revealed that PL extracts containing a total of 73 identified compounds could ameliorate kidney injury and regulate abnormal glycolipid metabolism. In metabolomics analysis, 19 carbonyl compounds with significant differences were identified between DN mice and normal mice. Moreover, 12 metabolites had a tendency to return to normal levels after PL treatment. Overall, PL exerts beneficial effects on DN by regulating abnormal glycolipid metabolism and carbonyl stress, and endogenous carbonyl compounds might serve as potential biomarkers for DN.

A qualitative study of perspectives on access to tuberculosis health services in Xigaze, China.

BACKGROUND: Tuberculosis (TB) is a major global health threat and the leading infectious disease cause of death worldwide. Access to and retention in TB care remains a challenge for patients, particularly those living in rural and remote settings. This qualitative study explored barriers and facilitators to accessing and maintaining contact with TB care services in communities in Xigaze (Shigatse) prefecture, Xizang Autonomous Region (Tibet Autonomous Region), China from the perspective of persons impacted by TB. METHODS: We conduced in-depth interviews with 23 participants impacted by TB in four rural districts in Xigaze prefecture, Xizang Autonomous Region, China between April 2019 and November 2020. Interviews were conducted in Tibetan and Mandarin, transcribed in Mandarin and translated into English. Transcripts were checked against recordings by native Tibetan and Mandarin speakers. QSR NVivo12 software was used for framework analysis guided by an access to care conceptual framework by Levesque et al. RESULTS: Overall patients reported low awareness of and an indifferent attitude towards TB, although all reported understanding the need to adhere to treatment. Participants reported complex pathways to care, often requiring visits to multiple healthcare facilities. Some participants reported visiting traditional Tibetan medicine (TTM) providers. Participants reported various barriers to accessing care including challenges physically reaching care, out-of-pocket payments for tests, diagnostics and transport. Barriers to maintaining care included medication side effects and worry about treatment effectiveness. Enablers to accessing care identified included knowledge or past experience with TB, integrated models of TTM and western care, supportive village doctors who conducted home visits, free TB treatment and other subsidies, as well as having family support with care and social support as barriers and facilitators to maintaining treatment. CONCLUSIONS: We identified barriers and facilitators to accessing services in rural communities in Xigaze from the perspective of persons impacted by TB. Challenges include complex pathways to care, travel distances, wait times and low awareness. Tuberculosis care in the region could be strengthened by ongoing culturally tailored educational campaigns to increase awareness, partnerships with TTM providers, providing comprehensive treatment subsidies and strengthening the role of family members in comprehensive TB care.

Codevelopment of COVID-19 infection prevention and control guidelines in lower-middle-income countries: the 'SPRINT' principles.

INTRODUCTION: The COVID-19 pandemic has required the rapid development of comprehensive guidelines to direct health service organisation and delivery. However, most guidelines are based on resources found in high-income settings, with fewer examples that can be implemented in resource-constrained settings. This study describes the process of adapting and developing role-specific guidelines for comprehensive COVID-19 infection prevention and control in low-income and middle-income countries (LMICs). METHODS: We used a collaborative autoethnographic approach to explore the process of developing COVID-19 guidelines. In this approach, multiple researchers contributed their reflections, conducted joint analysis through dialogue, reflection and with consideration of experiential knowledge and multidisciplinary perspectives to identify and synthesise enablers, challenges and key lessons learnt. RESULTS: We describe the guideline development process in the Philippines and the adaptation process in Sri Lanka. We offer key enablers identified through this work, including flexible leadership that aimed to empower the team to bring their expertise to the process; shared responsibility through equitable ownership; an interdisciplinary team; and collaboration with local experts. We then elaborate on challenges including interpreting other guidelines to the country context; tensions between the ideal compared with the feasible and user-friendly; adapting and updating with evolving information; and coping with pandemic-related challenges. Based on key lessons learnt, we synthesise a novel set of principles for developing guidelines during a public health emergency. The SPRINT principles are grounded in situational awareness, prioritisation and balance, which are responsive to change, created by an interdisciplinary team navigating shared responsibility and transparency. CONCLUSIONS: Guideline development during a pandemic requires a robust and time sensitive paradigm. We summarise the learning in the 'SPRINT principles' for adapting guidelines in an epidemic context in LMICs. We emphasise that these principles must be grounded in a collaborative or codesign process and add value to existing national responses.