Determination of intracellular tenofovir-diphosphate and emtricitabine-triphosphate concentrations in dried blood spots for pre-exposure prophylaxis adherence.

OBJECTIVES: We measured the intracellular concentrations of tenofovir-diphosphate (TFV-DP) and emtricitabine-triphosphate (FTC-TP) in dried blood spots (DBS) for pre-exposure prophylaxis (PrEP) adherence using sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS). METHODS: A total of 191 DBS were obtained from 85 participants who were receiving tenofovir disoproxil fumarate (TDF; 300 mg) and emtricitabine (FTC; 200 mg) as PrEP at the Sexual Health Clinic, National Center for Global Health and Medicine, Tokyo, Japan. DBS punch (3 mm) added to 25 µL of 50% methanol and 400 µL of internal standard solution was used for solid phase extraction. Chromatographic separation was achieved on an Atlantis Premier BEH C18 AX Column (50 mm × 2.1 mm i.d.; particle size 1.7 µm) using gradient elution (flow rate: 0.6 mL/min); injection volume: 7 µL and run time: 5.5 min. Calibration curves for the two drugs were linear in the range 0.05-12.5 ng/punch. RESULTS: We determined the intracellular TFV-DP and FTC-TP concentrations in 191 DBS obtained from 85 patients administered with TDF and FTC as PrEP. The analytical performance data (calibration curve and QC samples) for all the analytical runs met the acceptance criteria. Intracellular concentrations of TFV-DP and FTC-TP in the DBS remained stable for at least 24 h after oral administration. CONCLUSIONS: A multiplex LC-MS/MS method was successfully developed for DBS, which can be useful for monitoring the levels of TFV-DP and FTC-TP in individuals receiving PrEP.

Got milk? Maternal immune activation during the mid-lactational period affects nutritional milk quality and adolescent offspring sensory processing in male and female rats.

Previous studies have underscored the importance of breastfeeding and parental care on offspring development and behavior. However, their contribution as dynamic variables in animal models of early life stress are often overlooked. In the present study, we investigated how lipopolysaccharide (LPS)-induced maternal immune activation (MIA) on postnatal day (P)10 affects maternal care, milk, and offspring development. MIA was associated with elevated milk corticosterone concentrations on P10, which recovered by P11. In contrast, both milk triglyceride and percent creamatocrit values demonstrated a prolonged decrease following inflammatory challenge. Adolescent MIA offspring were heavier, which is often suggestive of poor early life nutrition. While MIA did not decrease maternal care quality, there was a significant compensatory increase in maternal licking and grooming the day following inflammatory challenge. However, this did not protect against disrupted neonatal huddling or later-life alterations in sensorimotor gating, conditioned fear, mechanical allodynia, or reductions in hippocampal parvalbumin expression in MIA offspring. MIA-associated changes in brain and behavior were likely driven by differences in milk nutritional values and not by direct exposure to LPS or inflammatory molecules as neither LPS binding protein nor interleukin-6 milk levels differed between groups. These findings reflected comparable microbiome and transcriptomic patterns at the genome-wide level. Animal models of early life stress can impact both parents and their offspring. One mechanism that can mediate the effects of such stressors is changes to maternal lactation quality which our data show can confer multifaceted and compounding effects on offspring physiology and behavior.

Synthesis of solar-driven Cu-doped graphitic carbon nitride photocatalyst for enhanced removal of caffeine in wastewater.

Caffeine (CaF), a widely consumed compound, has been associated with various harmful effects on human health, including metabolic, cardiovascular disease, and reproductive disorders. Moreover, it poses a signifincant threat to organisms and aquatic ecosystems, leading to water pollution concerns. Therefore, the removal of CaF from wastewater is crucial for mitigating water pollution and minimizing its detrimental impacts on both humans and the environment. In this study, a solar-driven Cu-doped graphitic carbon nitride (Cu/CN) photocatalyst was synthesized and evaluated for its effectiveness in oxidizing CaF in wastewater. The Cu/CN photocatalyst, with a low band gap energy of 2.58eV, exhibited superior performance in degrading CaF compared to pure graphitic carbon nitride (CN). Under solar light irradiation, CuCN achieved a remarkable CaF degradation efficiency of 98.7% CaF, surpassing CN's efficiency of 74.5% by 24.2%. The synthesized Cu/CN photocatalyst demonstrated excellent removal capability, achieving a removal rate of over 88% for CaF in wastewater. Moreover, the reusability test showed that Cu/CN could be successfully reused up to five cycles maintaining a high removal efficiency of 74% for CaF in the fifth cycle. Additionally, the study elucidated the oxidation mechanism of CaF using solar-driven Cu/CN photocatalyst and highlighted the environmental implications of the process.

Prevalence and risk factors of prehypertension/hypertension among freshman students from the Vietnam National University: a cross-sectional study.

BACKGROUND: Prehypertension (PHT) and hypertension (HTN) in young adults are essential risk factors for other cardiovascular diseases (CVD) in later years of life. However, there is a lack of knowledge about the burden and risk factors of PHT/HTN for Vietnamese youth. The aim of this study was to investigate the prevalence of PHT/HTN and risk factors among university students in Hanoi, Vietnam. METHODS: This study was designed as a cross-sectional investigation with 840 students (394 males and 446 females) randomly sampled from freshmen of Vietnam National University, Hanoi (VNU). Socio-demographic, anthropometric, and lifestyle data were collected using questionnaire forms and physical measurements. HTN was defined as blood pressure (BP) ≥ 140/90 mmHg and/or current treatment with antihypertensive medications. PHT was defined as a systolic BP from 120 to 139 mmHg and/or a diastolic BP from 80 to 89 mmHg. Body mass index (BMI) was classified according to the WHO diagnostic criteria for Asian adults: normal weight (BMI 18.5-22.9 kg/m2), underweight (BMI < 18.5 kg/m2), overweight (BMI 23-24.9 kg/m2), and obese (BMI ≥ 25 kg/m2). Bivariable and multivariable log-binomial regression analyses were conducted to explore the association of PHT/HTN with different risk factors. RESULTS: The overall prevalence of prehypertension and hypertension was 33.5% [95% CI: 30.3-36.8%] (54.1% in men and 15.3% in women) and 1.4% [95% CI: 0.7-2.5%] (2.5% in men and 0.5% in women), respectively. Regarding CVD major risk factors, 119 (14.2%) were identified as overweight/obese, 461 (54.9%) were physical inactivity, 29.4% of men and 8.1% of women reported consuming alcohol. The multivariable analysis indicated the male sex (adjusted prevalence ratio [aPR] = 3.07; 95% CI: 2.32-4.06), alcohol consumption (aPR = 1.28; 95% CI: 1.03-1.59) and obesity (aPR = 1.35; 95% CI: 1.08-1.68) as the independent risk factors for PHT/HTN. CONCLUSIONS: The results revealed the high burden of prehypertension and hypertension among university freshmen in VNU. Male sex, alcohol consumption, and obesity were identified as important risk factors for PHT/HTN. Our study suggests an early screening program for PHT/HTN and campaigns to promote a healthy lifestyle for young adults in Vietnam.

Modified hepaticocholecystoenterostomy technique for certain hepatobiliary and pancreatic diseases: Case series report by a single surgeon.

Prior to this research, very few reports of hepaticocholecystoenterostomy (HCE) and its modification have been published. Two anastomoses were used to establish a biliary bypass using the gallbladder as a conduit by a senior hepato-biliary surgeon. Between 2013 and 2019, 11 patients (five men and six women) with a mean age of 61.7±15.7 (range, 31-85) years were seen. Disease indications included periampullary malignant tumours of Vater (7 cases), chronic pancreatitis (1 patient), cystic pancreatic head tumours (2 patients), and choledochal cysts (1 patient). Pancreaticoduodenectomy, bypass, cholangiocarcinoma, and choledochal cystectomy were performed on 4, 4, 2, and 1 patients, respectively. Follow-up showed no jaundice at all with no recurrent biliary obstruction. HCE is both safe and effective in a subgroup of patients. This is a treatment of choice in some instances, such as a small common bile duct, a limited surgical field in the hilar area, or a difficult hepaticojejunostomy.

Poly (I:C)-induced maternal immune activation modifies ventral hippocampal regulation of stress reactivity: prevention by environmental enrichment.

Environmental enrichment (EE) has been successfully implemented in human rehabilitation settings. However, the mechanisms underlying its success are not understood. Incorporating components of EE protocols into our animal models allows for the exploration of these mechanisms and their role in mitigation. Using a mouse model of maternal immune activation (MIA), the present study explored disruptions in social behavior and associated hypothalamic pituitary adrenal (HPA) axis functioning, and whether a supportive environment could prevent these effects. We show that prenatal immune activation of toll-like receptor 3, by the viral mimetic polyinosinic-polycytidylic acid (poly(I:C)), led to disrupted maternal care in that dams built poorer quality nests, an effect corrected by EE housing. Standard housed male and female MIA mice engaged in higher rates of repetitive rearing and had lower levels of social interaction, alongside sex-specific expression of several ventral hippocampal neural stress markers. Moreover, MIA males had delayed recovery of plasma corticosterone in response to a novel social encounter. Enrichment housing, likely mediated by improved maternal care, protected against these MIA-induced effects. We also evaluated c-Fos immunoreactivity associated with the novel social experience and found MIA to decrease neural activation in the dentate gyrus. Activation in the hypothalamus was blunted in EE housed animals, suggesting that the putative circuits modulating social behaviors may be different between standard and complex housing environments. These data demonstrate that augmentation of the environment supports parental care and offspring safety/security, which can offset effects of early health adversity by buffering HPA axis dysregulation. Our findings provide further evidence for the viability of EE interventions in maternal and pediatric settings.

Active roles of dysfunctional vascular endothelium in fibrosis and cancer.

Chronic inflammation is the underlying pathological condition that results in fibrotic diseases. More recently, many forms of cancer have also been linked to chronic tissue inflammation. While stromal immune cells and myofibroblasts have been recognized as major contributors of cytokines and growth factors that foster the formation of fibrotic tissue, the endothelium has traditionally been regarded as a passive player in the pathogenic process, or even as a barrier since it provides a physical divide between the circulating immune cells and the inflamed tissues. Recent findings, however, have indicated that endothelial cells in fact play a crucial role in the inflammatory response. Endothelial cells can be activated by cytokine signaling and express inflammatory markers, which can sustain or exacerbate the inflammatory process. For example, the activated endothelium can recruit and activate leukocytes, thus perpetuating tissue inflammation, while sustained stimulation of endothelial cells may lead to endothelial-to-mesenchymal transition that contributes to fibrosis. Since chronic inflammation has now been recognized as a significant contributing factor to tumorigenesis, it has also emerged that activation of endothelium also occurs in the tumor microenvironment. This review summarizes recent findings characterizing the molecular and cellular changes in the vascular endothelium that contribute to tissue fibrosis, and potentially to cancer formation.

Effect of ceftriaxone and cefepime on high-dose methotrexate clearance.

Numerous drug interactions with methotrexate have been identified, which can lead to serious life-threatening effects. Up to 90% of methotrexate is excreted unchanged in the urine with primary excretion dependent on organic anion transport in the renal proximal tubule. The two pathways responsible for methotrexate secretion are organic anion transport 1 and primarily organic anion transport 3. Penicillins undergo tubular secretion via organic anion transport, and cephalosporins are believed to also possess a similar risk when administered with methotrexate; however, there are no human studies observing this interaction with cephalosporins and methotrexate. Ceftriaxone undergoes biliary clearance and has low affinity for the same organic anion transports as methotrexate; therefore, ceftriaxone has a low potential to interact with methotrexate. Cefepime is primarily secreted by organic cation transport N2, and also has a low potential to interact with methotrexate. This case report describes the pharmacokinetic effect of concomitant beta-lactam therapy in a patient receiving high-dose methotrexate.

Relative Host Resistance to Black Spot Disease in Field Pea (Pisum sativum) is Determined by Individual Pathogens.

Black spot, also known as Ascochyta blight, is the most important disease on field pea (Pisum sativum). It is caused by a complex of pathogens, the most important of which in Australia include Didymella pinodes, Phoma pinodella, and P. koolunga. The relative proportions of these and other component pathogens of the complex fluctuate widely across time and geographic locations in Australia, limiting the ability of breeders to develop varieties with effective resistance to black spot. To address this, 40 field pea genotypes were tested under controlled environment conditions for their individual stem and leaf responses against these three pathogens. Disease severity was calculated as area under disease progress curve (AUDPC), and subsequently converted to mean rank (MR). The overall rank (OR) for each pathogen was used to compare response of genotypes under inoculation with each pathogen. The expressions of host resistance across the field pea genotypes were largely dependent upon the individual test pathogen and whether the test was on stem or leaf. Overall, P. koolunga caused most severe stem disease; significantly more severe than either D. pinodes or P. pinodella. This is the first report of the host resistance identified in field pea to P. koolunga; the five genotypes showing highest resistance on stem, viz. 05P778-BSR-701, ATC 5338, ATC 5345, Dundale, and ATC 866, had AUDPC MR values <250.4, while the AUDPC MR values of the 19 genotypes showing the best resistance on leaf was less than 296.8. Two genotypes, ATC 866 and Dundale, showed resistance against P. koolunga on both stem and leaf. Against D. pinodes, the four and 16 most resistant genotypes on stem and leaf had AUDPC MR values <111.2 and <136.6, respectively, with four genotypes showing resistance on both stem and leaf including 05P770-BSR-705, Austrian Winter Pea, 06P822-(F5)-BSR-6, and 98107-62E. Against P. pinodella, four and eight genotypes showing the best resistance on stem and leaf had AUDPC MR values <81.3 and <221.9, respectively; three genotypes, viz. 98107-62E, Dundale, and Austrian Winter Pea showed combined resistance on stem and leaf. A few genotypes identified with resistance against two major pathogens of the complex will be of particular significance to breeding programs. These findings explain why field pea varieties arising from breeding programs in Australia fail to display the level or consistency of resistance required against black spot and why there needs to be a wider focus than D. pinodes in breeding programs.

Temporal and Spatial Changes in the Pea Black Spot Disease Complex in Western Australia.

Black spot (also referred to as Ascochyta blight, Ascochyta foot rot and black stem, and Ascochyta leaf and pod spot) is a devastating disease of pea (Pisum sativum) caused by one or more pathogenic fungi, including Didymella pinodes, Ascochyta pisi, and Phoma pinodella. Surveys were conducted across pea-growing regions of Western Australia in 1984, 1987, 1989, 1996, 2010, and 2012. In total, 1,872 fungal isolates were collected in association with pea black spot disease symptoms. Internal transcribed spacer regions from representative isolates, chosen based on morphology, were sequenced to aid in identification. In most years and locations, D. pinodes was the predominant pathogen in the black spot complex. From 1984 to 2012, four new pathogens associated with black spot symptoms on leaves or stems (P. koolunga, P. herbarum, Boeremia exigua var. exigua, and P. glomerata) were confirmed. This study is the first to confirm P. koolunga in association with pea black spot symptoms in field pea in Western Australia and show that, by 2012, it was widely present in new regions. In 2012, P. koolunga was more prevalent than D. pinodes in Northam and P. pinodella in Esperance. P. herbarum and B. exigua var. exigua were only recorded in 2010. Although A. pisi was reported in Western Australia in 1912 and again in 1968 and is commonly associated with pea black spot in other states of Australia and elsewhere, it was not recorded in Western Australia from 1984 to 2012. It is clear that the pathogen population associated with the pea black spot complex in Western Australia has been dynamic across time and geographic location. This poses a particular challenge to development of effective resistance against the black spot complex, because breeding programs are focused almost exclusively on resistance to D. pinodes, largely ignoring other major pathogens in the disease complex. Furthermore, development and deployment of effective host resistance or fungicides against just one or two of the pathogens in the disease complex could radically shift the make-up of the population toward pathogen species that are least challenged by the host resistance or fungicides, creating an evolving black spot complex that remains ahead of breeding and other management efforts.

BioInstruct: instruction tuning of large language models for biomedical natural language processing.

OBJECTIVES: To enhance the performance of large language models (LLMs) in biomedical natural language processing (BioNLP) by introducing a domain-specific instruction dataset and examining its impact when combined with multi-task learning principles. MATERIALS AND METHODS: We created the BioInstruct, comprising 25 005 instructions to instruction-tune LLMs (LLaMA 1 and 2, 7B and 13B version). The instructions were created by prompting the GPT-4 language model with 3-seed samples randomly drawn from an 80 human curated instructions. We employed Low-Rank Adaptation (LoRA) for parameter-efficient fine-tuning. We then evaluated these instruction-tuned LLMs on several BioNLP tasks, which can be grouped into 3 major categories: question answering (QA), information extraction (IE), and text generation (GEN). We also examined whether categories (eg, QA, IE, and generation) of instructions impact model performance. RESULTS AND DISCUSSION: Comparing with LLMs without instruction-tuned, our instruction-tuned LLMs demonstrated marked performance gains: 17.3% in QA on average accuracy metric, 5.7% in IE on average F1 metric, and 96% in Generation tasks on average GPT-4 score metric. Our 7B-parameter instruction-tuned LLaMA 1 model was competitive or even surpassed other LLMs in the biomedical domain that were also fine-tuned from LLaMA 1 with vast domain-specific data or a variety of tasks. Our results also show that the performance gain is significantly higher when instruction fine-tuning is conducted with closely related tasks. Our findings align with the observations of multi-task learning, suggesting the synergies between 2 tasks. CONCLUSION: The BioInstruct dataset serves as a valuable resource and instruction tuned LLMs lead to the best performing BioNLP applications.

Encapsulation of W/O/W Acerola Emulsion by Spray Drying: Optimization, Release Kinetics, and Storage Stability.

Acerola (Malpighia emarginata DC.) is a sub-tropical and tropical fruit renowned for its high levels of vitamin C and phenolic compounds, which offer health benefits. This study aimed to optimize the spray drying process by determining the inlet and outlet temperatures using response surface methodology (RSM) with the central composite design. Additionally, it aimed to evaluate the release kinetics in the hydrophilic food simulation environment and the stability of the resulting powder under various storage temperatures. The RSM method determined the optimal inlet and outlet temperatures as 157 °C and 91 °C, respectively. High-accuracy prediction equations (R2 ≥ 0.88) were developed for moisture content (3.02%), process yield (91.15%), and the encapsulation yield of total polyphenol content (61.44%), total flavonoid content (37.42%), and vitamin C (27.19%), with a predicted monolayer moisture content below 4.01%, according to the BET equation. The powder exhibited good dissolution characteristics in the acidic hydrophilic food simulation environment and showed greater stability when stored at 10 °C for 30 days, compared to storage at 35 °C and 45 °C.

Evolving pathways towards water security in the Vietnamese Mekong Delta: An adaptive management perspective.

The interplay of climate change, upstream hydropower development, and local water engineering interventions for agricultural production contributes substantially to the transformation of waterscapes and water scarcity in the Vietnamese Mekong Delta. This paper aims to examine how these dynamics are linked to the paradigm shift in water management in An Giang and Ben Tre, the two ecologically distinct provinces that face serious water scarcity in the delta. We used the adaptive management concept to examine how state-led policy directions from food security towards water security enable change in water management that gives priority to water retention. While policy learning is evident, questions remain about how this ad-hoc solution could help address the presently acute water scarcity and water security over the long term. The paper advocates achieving water security should focus not only on diplomatic interventions into upstream climate-development complexities but also local water-livelihood politics.

Health Care Challenges in the Management of Primary Aldosteronism in Southeast Asia.

CONTEXT: While guidelines have been formulated for the management of primary aldosteronism (PA), following these recommendations may be challenging in developing countries with limited health care access. OBJECTIVE: We aimed to assess the availability and affordability of health care resources for managing PA in the Association of Southeast Asian Nations (ASEAN) region, which includes low-middle-income countries. METHODS: We instituted a questionnaire-based survey to specialists managing PA, assessing the availability and affordability of investigations and treatment. Population and income status data were taken from the national census and registries. RESULTS: Nine ASEAN country members (48 respondents) participated. While screening with aldosterone-renin ratio is performed in all countries, confirmatory testing is routinely performed in only 6 countries due to lack of facilities and local assays, and cost constraint. Assays are locally available in only 4 countries, and some centers have a test turnaround time exceeding 3 weeks. In 7 countries (combined population of 442 million), adrenal vein sampling (AVS) is not routinely performed due to insufficient radiological facilities or trained personnel, and cost constraint. Most patients have access to adrenalectomy and medications. In 6 countries, the cost of AVS and adrenalectomy combined is more than 30% of its annual gross domestic product per capita. While most patients had access to spironolactone, it was not universally affordable. CONCLUSION: Large populations currently do not have access to the health care resources required for the optimal management of PA. Greater efforts are required to improve health care access and affordability. Future guideline revisions for PA may need to consider these limitations.

Organo-photocatalytic C-H bond oxidation: an operationally simple and scalable method to prepare ketones with ambient air.

Oxidative C-H functionalization with O2 is a sustainable strategy to convert feedstock-like chemicals into valuable products. Nevertheless, eco-friendly O2-utilizing chemical processes, which are scalable yet operationally simple, are challenging to develop. Here, we report our efforts, via organo-photocatalysis, in devising such protocols for catalytic C-H bond oxidation of alcohols and alkylbenzenes to ketones using ambient air as the oxidant. The protocols employed tetrabutylammonium anthraquinone-2-sulfonate as the organic photocatalyst which is readily available from a scalable ion exchange of inexpensive salts and is easy to separate from neutral organic products. Cobalt(ii) acetylacetonate was found to be greatly instrumental to oxidation of alcohols and therefore was included as an additive in evaluating the alcohol scope. The protocols employed a nontoxic solvent, could accommodate a variety of functional groups, and were readily scaled to 500 mmol scale in a simple batch setting using round-bottom flasks and ambient air. A preliminary mechanistic study of C-H bond oxidation of alcohols supported the validity of one possible mechanistic pathway, nested in a more complex network of potential pathways, in which the anthraquinone form - the oxidized form - of the photocatalyst activates alcohols and the anthrahydroquinone form - the relevant reduced form of the photocatalyst - activates O2. A detailed mechanism, which reflected such a pathway and was consistent with previously accepted mechanisms, was proposed to account for formation of ketones from aerobic C-H bond oxidation of both alcohols and alkylbenzenes.

Epileptic seizure clustering and accumulation at transition from activity to rest in GAERS rats.

Knowing when seizures occur may help patients and can also provide insight into epileptogenesis mechanisms. We recorded seizures over periods of several days in the Genetic Absence Epileptic Rat from Strasbourg (GAERS) model of absence epilepsy, while we monitored behavioral activity with a combined head accelerometer (ACCEL), neck electromyogram (EMG), and electrooculogram (EOG). The three markers consistently discriminated between states of behavioral activity and rest. Both GAERS and control Wistar rats spent more time in rest (55-66%) than in activity (34-45%), yet GAERS showed prolonged continuous episodes of activity (23 vs. 18 min) and rest (34 vs. 30 min). On average, seizures lasted 13 s and were separated by 3.2 min. Isolated seizures were associated with a decrease in the power of the activity markers from steep for ACCEL to moderate for EMG and weak for EOG, with ACCEL and EMG power changes starting before seizure onset. Seizures tended to occur in bursts, with the probability of seizing significantly increasing around a seizure in a window of ±4 min. Furthermore, the seizure rate was strongly increased for several minutes when transitioning from activity to rest. These results point to mechanisms that control behavioral states as determining factors of seizure occurrence.

An Undetected Pheochromocytoma Leading to Fulminant Adrenergic Myocarditis Complicated by Cardiogenic Shock.

Pheochromocytomas are rare catecholamine-secreting neuroendocrine tumors. Their episodic nature is correlated with abrupt catecholamine release and clinical manifestations that mimic other vascular conditions, leading to delayed diagnosis and potentially life-threatening complications, such as acute myocarditis and pheochromocytoma crises. In this report, we described the case of fulminant adrenergic myocarditis-induced cardiogenic shock requiring extracorporeal membrane oxygenation support in a Vietnamese middle-aged man with a 5-year history of Brugada syndrome, hypertension, and previously undiagnosed pheochromocytoma. After stabilization, the patient was medically treated with a combination of α- and ß-blockers before undergoing laparoscopic right adrenalectomy.

Steady-state pharmacokinetics of plasma tenofovir alafenamide (TAF), tenofovir (TFV) and emtricitabine (FTC), and intracellular TFV-diphosphate and FTC-triphosphate in HIV-1 infected old Japanese patients treated with bictegravir/FTC/TAF.

Emtricitabine (FTC) plus tenofovir alafenamide (TAF) has demonstrated efficacy and safety for pre-exposure prophylaxis (PrEP) to prevent HIV-1 infection. We measured the plasma PK of FTC, tenofovir (TFV), and TAF in a steady-state pharmacokinetic (PK) study of bictegravir/FTC/TAF in HIV-1-infected patients. Furthermore, validated liquid chromatography-tandem mass spectrometry was used to measure intracellular TFV-diphosphate (DP) and FTC-triphosphate (TP), the active metabolites of TFV and FTC, respectively. Plasma and dried blood spot samples were collected from 10 male patients aged ≥ 50 years at various time intervals: 0 (trough), 1, 2, 3, 4, 6, 8, 12, and 24 h after drug administration. The mean ± standard deviation of plasma PK parameters were as follows: The maximum concentrations of TAF, TFV, and FTC were 104.0 ± 72.5, 27.9 ± 5.2, and 3,976.0 ± 683.6 ng/mL, respectively. Additionally, their terminal elimination half-lives were 0.6 ± 0.5, 31.6 ± 10.4, and 6.9 ± 1.4 h, respectively. These results were consistent with previously reported data. The intracellular levels of TFV-DP and FTC-TP varied widely among individuals; however, they remained stable over 24 h in each individual at approximately 1,000-1,500 and 2,000-3,000 fmol/punch, respectively, indicating that plasma concentrations did not affect the intracellular concentrations of their active metabolites. These results demonstrated that measuring intracellular TFV-DP and FTC-TP could be useful for monitoring adherence to PrEP in clients on this regimen.

A review on the status and modeling of suitable habitats of the southern white-cheeked gibbon.

The southern white-cheeked gibbon Nomascus siki is endemic to Indochina and is classified as critically endangered on the International Union for Conservation of Nature (IUCN) Red List. The most updated information on the status of this species dates back to a decade ago. As hunting has tremendous impacts on wildlife in Southeast Asia, the population of N. siki might have changed a lot in the last decade. Updated information on the status and potential distribution of this species is critically important for conservation and prioritization, especially for N. siki because of its undefined distribution range. The goal of this study was to review the population status of N. siki in Vietnam and Lao People's Democratic Republic (PDR) and to model its potential distribution. In Vietnam, this species has been intensively surveyed in all major areas of occurrence from 2016 to 2021. The total number of N. siki groups recorded and estimated in Vietnam were 324 and 483, respectively. In Lao PDR, the occurrence of N. siki has been confirmed in Nam Kading, Nakai Nam Theun, Hin Nam No, and Phou Hinpoun national protected areas. However, population estimates are generally lacking. The suitable habitat of N. siki was predicted from about 105.00° to 106.80° E longitude and from about 16.60° to 17.90° N latitude located in Quang Binh and Quang Tri provinces (Vietnam), and Khammounan and Savannakhet provinces (Lao PDR). The area of the potential distribution range is about 9894.15 km2, both in Vietnam and Lao PDR. Particularly, the high, medium, and low suitable habitats were estimated at around 1229.58 km2, 3019.68 km2, and 5644.89 km2, respectively. The area of suitable habitat of N. siki in Vietnam was predicted to be 4151.25 km2, of which only 1257.93 km2 (30.30%) is in the protected area network. Dong Chau-Khe Nuoc Trong and Bac Huong Hoa Nature Reserves, and Phong Nha-Ke Bang National Park should receive priority for conservation of N. siki in Vietnam. Improving conservation beyond the protected areas' boundaries or transforming the forest enterprises and watershed protection forests into protected areas should also be considered as an alternative for the conservation of N. siki. In Lao PDR, surveys of the species in its entire distribution range should be the first priority.

Relationship between BMI and prognosis of chronic heart failure outpatients in Vietnam: a single-center study.

Background: Insufficient data exists regarding the relationship between body mass index (BMI) and the prognosis of chronic heart failure (CHF) specifically within low- and middle-income Asian countries. The objective of this study was to evaluate the impact of BMI on adverse outcomes of ambulatory patients with CHF in Vietnam. Methods: Between 2018 and 2020, we prospectively enrolled consecutive outpatients with clinically stable CHF in an observational cohort, single-center study. The participants were stratified according to Asian-specific BMI thresholds. The relationships between BMI and adverse outcomes (all-cause death and all-cause hospitalization) were analyzed by Kaplan-Meier survival curves and Cox proportional-hazards model. Results: Among 320 participants (age 63.5 ± 13.3 years, 57.9% male), the median BMI was 21.4 kg/m2 (IQR 19.5-23.6), and 10.9% were underweight (BMI <18.50 kg/m2). Over a median follow-up time of 32 months, the cumulative incidence of all-cause mortality and hospitalization were 5.6% and 19.1%, respectively. After multivariable adjustment, underweight patients had a significantly higher risk of all-cause mortality than patients with normal BMI (adjusted hazard ratios = 3.03 [95% CI: 1.07-8.55]). Lower BMI remained significantly associated with a worse prognosis when analyzed as a continuous variable (adjusted hazard ratios = 1.27 [95% CI: 1.03-1.55] per 1 kg/m2 decrease for all-cause mortality). However, BMI was not found to be significantly associated with the risk of all-cause hospitalization (p > 0.05). Conclusion: In ambulatory patients with CHF in Vietnam, lower BMI, especially underweight status (BMI < 18.5 kg/m2), was associated with a higher risk of all-cause mortality. These findings suggest that BMI should be considered for use in risk classification, and underweight patients should be managed by a team consisting of cardiologists, nutritionists, and geriatricians.