Visual function correlates of self-reported vision-related nighttime driving difficulties / La función visual se correlaciona con las dificultades de conducción nocturna relacionadas con la visión autoinformadas

Purpose: To investigate the visual function correlates of self-reported vision-related night driving difficulties among drivers. Methods: One hundred and seven drivers (age: 46.06 ± 8.24, visual acuity [VA] of 0.2logMAR or better) were included in the study. A standard vision and night driving questionnaire (VND-Q) was administered. VA and contrast sensitivity were measured under photopic and mesopic conditions. Mesopic VA was remeasured after introducing a peripheral glare source into the participants' field of view to enable computation of disability glare index. Regression analyses were used to assess the associations between VND-Q scores, and visual function measures. Results: The mean VND-Q score was -3.96±1.95 logit (interval scale score: 2.46±1.28). Simple linear regression models for photopic contrast sensitivity, mesopic VA, mesopic contrast sensitivity, and disability index significantly predicted VND-Q score (P<0.05), with mesopic VA and disability glare index accounting for the greatest variation (21 %) in VND-Q scores followed by photopic contrast sensitivity (19 %), and mesopic contrast sensitivity (15 %). A multiple regression model to determine the association between the predictors (photopic contrast sensitivity, mesopic VA, mesopic contrast sensitivity, and disability index) and VND-Q score yielded significant results, F (4, 102) = 8.58, P < 0.001, adj. R2 = 0.2224. Seeing dark-colored cars was the most challenging vision task. Conclusion: Changes in mesopic visual acuity, photopic and mesopic contrast sensitivity, as well as disability glare index are associated with and explain night driving-related visual difficulties. It is recommended to incorporate measurement of these visual functions into assessments related to driving performance.(AU)

Adaptación y validación del Voice Handicap Index y su versión abreviada al español rioplatense de Argentina

Objetivo: Este estudio tuvo como objetivo principal validar el Voice Handicap Index (VHI) y su versión abreviada (VHI-10) adaptados al español rioplatense de Argentina, con objetivos específicos centrados en evaluar su fiabilidad y validez. Metodología: La adaptación cultural incluyó técnicas de traducción directa, síntesis y retrotraducción, evaluación de la equivalencia semántica y aplicación a un grupo piloto. Para la validación se evaluó la fiabilidad de ambos índices adaptados mediante la consistencia interna (coeficiente alfa de Cronbach) y la estabilidad test-retest (prueba de Bland-Altman, CCI y r de Spearman). Además, se examinó la validez de criterio y de constructo. 213 sujetos participaron en la validación del índice adaptado de 30 ítems (123 disfónicos; 90 de control); 113, en la del índice abreviado (63 disfónicos; 50 de control). Resultados: Se constituyó el Índice de Desventaja Vocal (IDV) como la versión adaptada del VHI al español rioplatense de Argentina. Ambos índices demostraron excelente consistencia interna (IDV-30 α = 0,96; IDV-10 α = 0,92) y estabilidad y concordancia (IDV-30 CCI = 0,95; IDV-10 CCI = 0,96). Se halló alta correlación entre los puntajes de ambos índices y la autoevaluación de la severidad de la disfonía de los participantes (r = 0,85). Ambos índices demostraron capacidad de diferenciar entre individuos con disfonía y sujetos sanos (p< 0,001). El análisis factorial reveló tres factores para el IDV-30 y un factor para el IDV-10. Conclusiones: El IDV-30 e IDV-10 presentan grados adecuados de fiabilidad y validez. Ambos pueden ser incluidos en protocolos de valoración de la función vocal por profesionales de Argentina.

Aim: This study aimed to validate the Voice Handicap Index (VHI) and its abbreviated version (VHI-10) adapted into Rioplatense Spanish from Argentina, with specific goals centered on assessing their reliability and validity. Methods: Cultural adaptation involved direct translation, synthesis and back-translation techniques, followed by an assessment of semantic equivalence and application to a pilot group. For the validation process, the reliability of both adapted indices was assessed through measures of internal consistency (Cronbach's alpha coefficient) and test-retest stability (Bland-Altman test, ICC and Spearman's correlation coefficient). Additionally, we conducted analyses to asses criterion and construct validity. 213 subjects participated in the validation of the adapted 30-items index, (123 with dysphonia; 90 from control group); 113, in the abbreviated version (63 with dysphonia; 50 from control group). Results: The "Índice de Desventaja Vocal" (IDV) was established as the adapted version of the VHI into Rioplatense Spanish from Argentina. Both indeces exhibited excellent internal consistency (IDV-30 α = 0,96; IDV-10 α = 0,92) and satisfactory stability and agreement (IDV-30 CCI = 0,95; IDV-10 CCI = 0,96). Regarding validity, a strong correlation was observed between the scores of both indeces and the participant's self-assessment of dysphonia degree (r = 0,85). Both indices effectively differentiated between individuals with dysphonia and healthy subjects (p< 0,001). Factor analysis revealed three factors for the IDV-30 and one factor for the IDV-10. Conclusion: The IDV-30 and IDV-10 demonstrate satisfactory levels of reliability and validity. Both indices can be incorporated into the assessment protocols for evaluating the vocal function by professionals in Argentina.

Occurrence, distribution, and ecological risk assessment of heavy metals in Chao Phraya River, Thailand.

Understanding heavy metals in rivers is crucial, as their presence and distribution impact water quality, ecosystem health, and human well-being. This study examined the presence and levels of nine heavy metals (Cd, Cr, Cu, Fe, Hg, Mn, Ni, Pb, and Zn) in 16 surface water samples along the Chao Phraya River, identifying Fe, Mn, Zn, and Cr as predominant metals. Although average concentrations in both rainy and dry seasons generally adhered to WHO guidelines, Mn exceeded these limits yet remained within Thailand's acceptable standards. Seasonal variations were observed in the Chao Phraya River, and Spearman's correlation coefficient analysis established significant associations between season and concentrations of heavy metals. The water quality index (WQI) demonstrated varied water quality statuses at each sampling point along the Chao Phraya River, indicating poor conditions during the rainy season, further deteriorating to very poor conditions in the dry season. The hazard potential index (HPI) was employed to assess heavy metal contamination, revealing that during the dry season in the estuary area, the HPI value exceeded the critical threshold index, indicating the presence of heavy metal pollution in the water and unsuitable for consumption. Using the species sensitivity distribution model, an ecological risk assessment ranked the heavy metals' HC5 values as Pb > Zn > Cr > Cu > Hg > Cd > Ni, identifying nickel as the most detrimental and lead as the least toxic. Despite Cr and Zn showing a moderate risk, and Cu and Ni posing a high risk to aquatic organisms, the main contributors to ecological risk were identified as Cu, Ni, and Zn, suggesting a significant potential ecological risk in the Chao Phraya River's surface water. The results of this study provide fundamental insights that can direct future actions in preventing and managing heavy metal pollution in the river ecosystem.

Effects of a 10-Week Exercise and Nutritional Intervention with Variable Dietary Carbohydrates and Glycaemic Indices on Substrate Metabolism, Glycogen Storage, and Endurance Performance in Men: A Randomized Controlled Trial.

BACKGROUND: Daily nutrition plays an important role in supporting training adaptions and endurance performance. The objective of this 10-week study was to investigate the consequences of varying carbohydrate consumption and the glycaemic index (GI) together with an endurance training regimen on substrate oxidation, muscle energy storage and endurance performance under free-living conditions. Sixty-five moderately trained healthy men (29 ± 4 years; VO2 peak 55 ± 8 mL min-1 kg-1) were randomized to one of three different nutritional regimes (LOW-GI: 50-60% CHO with ≥ 65% of these CHO with GI < 50 per day, n = 24; HIGH-GI: 50-60% CHO with ≥ 65% CHO with GI > 70 per day, n = 20; LCHF: ≤ 50 g CHO daily, n = 21). Metabolic alterations and performance were assessed at baseline (T0) and after 10 weeks (T10) during a graded exercise treadmill test. Additionally, a 5 km time trial on a 400-m outdoor track was performed and muscle glycogen was measured by magnet resonance spectroscopy. RESULTS: Total fat oxidation expressed as area under the curve (AUC) during the graded exercise test increased in LCHF (1.3 ± 2.4 g min-1 × km h-1, p < 0.001), remained unchanged in LOW-GI (p > 0.05) and decreased in HIGH-GI (- 1.7 ± 1.5 g min-1 × km h-1, p < 0.001). After the intervention, LOW-GI (- 0.4 ± 0.5 mmol L-1 × km h-1, p < 0.001) and LCHF (- 0.8 ± 0.7 mmol L-1 × km h-1, p < 0.001) showed significantly lower AUC of blood lactate concentrations. Peak running speed increased in LOW-GI (T0: 4.3 ± 0.4 vs. T10: 4.5 ± 0.3 m s-1, p < 0.001) and HIGH-GI (T0: 4.4 ± 0.5 vs. T10: 4.6 ± 0.4 m s-1), while no improvement was observed in LCHF. Yet, time trial performance improved significantly in all groups. Muscle glycogen content increased for participants in HIGH-GI (T0: 97.3 ± 18.5 vs. T10: 144.5 ± 39.8 mmol L wet-tissue-1, p = 0.027) and remained unchanged in the LOW-GI and the LCHF group. At the last examination, muscle glycogen concentration was significantly higher in LOW-GI compared to LCHF (p = 0.014). CONCLUSION: Changes in fat oxidation were only present in LCHF, however, lower lactate concentrations in LOW-GI resulted in changes indicating an improved substrate metabolism. Compared to a LCHF diet, changes in peak running speed, and muscle glycogen stores were superior in LOW- and HIGH-GI diets. The low GI diet seems to have an influence on substrate metabolism without compromising performance at higher intensities, suggesting that a high-carbohydrate diet with a low GI is a viable alternative to a LCHF or a high GI diet. TRIAL REGISTRATION: Clinical Trials, NCT05241730. https://clinicaltrials.gov/study/NCT05241730 . Registered 25 January 2021.

Pfp-fm: an accelerated FM-index.

FM-indexes are crucial data structures in DNA alignment, but searching with them usually takes at least one random access per character in the query pattern. Ferragina and Fischer [1] observed in 2007 that word-based indexes often use fewer random accesses than character-based indexes, and thus support faster searches. Since DNA lacks natural word-boundaries, however, it is necessary to parse it somehow before applying word-based FM-indexing. In 2022, Deng et al. [2] proposed parsing genomic data by induced suffix sorting, and showed that the resulting word-based FM-indexes support faster counting queries than standard FM-indexes when patterns are a few thousand characters or longer. In this paper we show that using prefix-free parsing-which takes parameters that let us tune the average length of the phrases-instead of induced suffix sorting, gives a significant speedup for patterns of only a few hundred characters. We implement our method and demonstrate it is between 3 and 18 times faster than competing methods on queries to GRCh38, and is consistently faster on queries made to 25,000, 50,000 and 100,000 SARS-CoV-2 genomes. Hence, it seems our method accelerates the performance of count over all state-of-the-art methods with a moderate increase in the memory. The source code for PFP - FM is available at https://github.com/AaronHong1024/afm .

Association between obstructive sleep apnea and visceral adiposity index and lipid accumulation product: NHANES 2015-2018.

BACKGROUND: Obesity refers to a significant contributor to the development of obstructive sleep apnea (OSA). Early prediction of OSA usually leads to better treatment outcomes, and this study aims to employ novel metabolic markers, visceral adiposity index (VAI), and lipid accumulation product (LAP) to evaluate the relationship to OSA. METHODS: The data used in the current cross-sectional investigation are from the National Health and Nutrition Examination Survey (NHANES), which was carried out between 2015 and 2018. To examine the correlation between LAP and VAI levels and OSA, multivariate logistic regression analysis was adopted. In addition, various analytical methods were applied, including subgroup analysis, smooth curve fitting, and threshold effect analysis. RESULTS: Among totally 3932 participants, 1934 were included in the OSA group. The median (Q1-Q3) values of LAP and VAI for the participants were 40.25 (21.51-68.26) and 1.27 (0.75-2.21), respectively. Logistic regression studies indicated a positive correlation between LAP, VAI, and OSA risk after adjusting for potential confounding variables. Subgroup analysis revealed a stronger correlation between LAP, VAI levels, and OSA among individuals aged < 60 years. Through smooth curve fitting, specific saturation effects of LAP, VAI, and BMD were identified, with inflection points at 65.684 and 0.428, respectively. CONCLUSION: This study demonstrates that elevated levels of LAP and VAI increase the risk of OSA, suggesting their potential as predictive markers for OSA and advocating for dietary and exercise interventions to mitigate OSA risk in individuals with high LAP and VAI levels.

Association of lipid profile and obesity in patients with polycystic ovary syndrome.

Objective. Abnormal lipid profile and obesity increase the risk of polycystic ovary syndrome (PCOS). PCOS patients may have a greater risk of infertility, metabolic syndrome (MetS) and cardiovascular disease (CVD) due to abnormal lipid profile and obesity. The aim of the study was to find the association between abnormal lipid profile and obesity in patients with PCOS. Methods. In this case-control study, a total of 102 female subjects (51 diagnosed PCOS and 51 age-matched healthy controls) were enrolled, aged between 20-40 years. Biochemical parameters such as total cholesterol (TC), triglycerides (TG), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), very low-density lipoprotein-cholesterol (VLDL-C), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were estimated. Anthropometric parameters such as body mass index (BMI), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) were recorded. A p<0.05 was considered statistically significant. Results. Mean of BMI, WC, WHR, LH, FSH, TC, TG, LDL-C, and VLDL-C was found significantly elevated in patients with PCOS as compared to controls (p<0.01). However, the mean of HDL-C was found significantly reduced in patients with PCOS as compared to controls (p<0.01). BMI has shown a significant positive correlation with WC (r=0.562, p<0.01) and WHR (r=0.580, p<0.01) among PCOS patients. LH has shown a significant positive correlation with FSH (r=0.572, p<0.01) among PCOS patients. TC has shown a significant positive correlation with TG (r=0.687, p<0.01), LDL-C (r=0.917, p<0.01), and VLDL-C (r=0.726, p<0.01) among PCOS patients. Conclusion. The results showed that abnormal lipid profile and obesity have a significant association with PCOS patients. Regular monitoring and treatment of PCOS patients are required to reduce the risk of infertility, MetS, and CVD.

Predictive role of systemic immune-inflammation index and neutrophil/lymphocyte ratio values in infants with retinopathy of prematurity.

PURPOSE: To search the relationship between serum neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) values with the development of retinopathy of prematurity (ROP) and the requirement for laser treatment. METHODS: This retrospective cohort study was carried out with 195 preterm infants between 2012 and 2023. The NLR, PLR, LMR, and SII values were calculated on both the first day and at the end of the first month after birth. The association between development of ROP and other risk factors were analyzed using univariate analysis and multivariate logistic regression analysis. RESULTS: Of patients, 92 infants were diagnosed with ROP. Laser treatment was administered to 36 infants. The postnatal first-day NLR and SII values were higher in infants with ROP than in infants without ROP (p < 0.001 for both). Postnatal first-month NLR, LMR, and SII values were higher in infants with ROP (p < 0.001, p = 0.007, and p < 0.001, respectively). In multivariate analyses, postnatal first-day NLR and first-month LMR values were regarded as independent risk factors for the development of ROP (OR:8.867 and 1.286, p = 0.002 and p = 0.009, respectively). In multivariate analyses performed for laser treatment requirement, postnatal first-month PLR and SII values were determined as independent risk factors (OR:0.951 and 1.011, respectively, p = 0.004 for both). CONCLUSIONS: Postnatal first-day NLR and first-month LMR values were determined as independent risk factors for the development of ROP. For the requirement of laser treatment, the postnatal first-month PLR and SII values were determined as independent risk factors.

Soil organic carbon fractionation, carbon index, and microbial activity under different agroforestry systems in North Eastern Himalayas, India.

The potential of soil organic carbon fractions for agroforestry systems (AFSs) is not well understood. Five distinct AFSs were tested for its impact on soil organic carbon fractionation, carbon index, and microbial activity in North Eastern Himalayas, India. The mean labile carbon (LC) ranged from 4.55 to 5.43 kg soil-1 across the land use systems. Napier system observed the lowest very labile carbon (VLC) 12.36 kg soil-1 in 60-75-cm depth. The mean non labile carbon (NLC) ranged from 15.67 to 16.83 g kg soil-1 across the land use. Highest less labile carbon (LLC) was observed in agri-horti-silviculture (AHS) followed by agri-silvi-horticulture (ASH) land use system. The black gram + mandarin + Alnus nepalensis land use recorded higher lability index (1.66) followed by maize + Schima wallichii (1.65) in 0-15-cm depth. Among the different land use systems, carbon pool index increased in all the depths over buckwheat + mandarin. The mean carbon management index (CMI) value ranged from 167.02 to 210.12 among the land use system. The mean CMI was highest in black gram + mandarin + Alnus nepalensis (210.12) followed by soybean + Ficus hookerii + guava (191.56), maize + Schima wallichii (281.71), and lowest in buckwheat + mandarin (167.02). Among the AFSs, black gram + mandarin + Alnus nepalensis showed greater amount of carbon pool index, lability index, and carbon management index and, hence, considered the best sustainable agroforestry system to sequester more carbon in the Sikkim Himalaya. Such system also retained more different organic carbon fractions. The mean CMI value ranged from 167.02 to 210.12 among AFSs. Acid phosphatase activity was more during the rainy season followed by winter and summer season. Similar trends were followed by the urease activity in all the three seasons. Overall conclusion from this investigation is that SOC fractions, carbon index, and microbial activity levels are strongly influenced by the prevailing agroforestry systems.

Enhanced Spatial Fuzzy C-Means Algorithm for Brain Tissue Segmentation in T1 Images.

Magnetic Resonance Imaging (MRI) plays an important role in neurology, particularly in the precise segmentation of brain tissues. Accurate segmentation is crucial for diagnosing brain injuries and neurodegenerative conditions. We introduce an Enhanced Spatial Fuzzy C-means (esFCM) algorithm for 3D T1 MRI segmentation to three tissues, i.e. White Matter (WM), Gray Matter (GM), and Cerebrospinal Fluid (CSF). The esFCM employs a weighted least square algorithm utilizing the Structural Similarity Index (SSIM) for polynomial bias field correction. It also takes advantage of the information from the membership function of the last iteration to compute neighborhood impact. This strategic refinement enhances the algorithm's adaptability to complex image structures, effectively addressing challenges such as intensity irregularities and contributing to heightened segmentation accuracy. We compare the segmentation accuracy of esFCM against four variants of FCM, Gaussian Mixture Model (GMM) and FSL and ANTs algorithms using four various dataset, employing three measurement criteria. Comparative assessments underscore esFCM's superior performance, particularly in scenarios involving added noise and bias fields.The obtained results emphasize the significant potential of the proposed method in the segmentation of MRI images.

Role of triglyceride-glucose index in metabolic assessment of sarcoidosis patients.

Sarcoidosis is a rare granulomatous disease that can affect any organ. It leads to an increased risk of metabolic syndrome and insulin resistance, due to biochemical pathways involved in low-grade inflammation in both diseases. The aim of our retrospective case-control study was to evaluate the utility of triglyceride-glucose (TyG) index, a surrogate of insulin resistance, for metabolic assessment of sarcoidosis patients. A cohort of 90 sarcoidosis patients and a cohort of 90 control subjects were enrolled. Clinical, anamnestic, and biochemical data were collected. Results showed that TyG index values were higher in the sarcoidosis cohort than in the control group (p < 0.001), even after excluding the influence of diabetes and metabolic syndrome (p = 0.018). In the sarcoidosis cohort, TyG index was not correlated with clinical phenotyping (p = 0.358), gender (p = 0.139), radiological stage (p = 0.656), glucocorticoids cumulative dose (p = 0.682) or treatment regimen (p = 0.093), while significant positive correlations with waist circumference (p < 0.001), systolic and diastolic pressure (p = 0.041 and p = 0.029, respectively), Framingham score (p = 0.007) were found. Receiving operating characteristics curve analysis identified a TyG index optimal cut-off value of 8.64 (66.7% sensitivity, 77.8% specificity, area under the curve -AUC- 75%, 95% confidence interval -CI- 65-85, p < 0.001) to detect metabolic syndrome and a cut-off value of 8.69 (64.1% sensitivity, 70.6% specificity; AUC 67%, 95% CI 55-78, p = 0.007) to detect an intermediate cardiovascular risk according to Framingham risk score. Concluding, TyG index can be considered a useful tool for the metabolic assessment of sarcoidosis patients, given its capacity to predict metabolic syndrome and cardiovascular risk.

Maintenance of Normal Blood Pressure From Middle to Older Age: Results From the Atherosclerosis Risk in Communities Study.

BACKGROUND: It is unknown whether maintaining normal blood pressure (BP) from middle to older age is associated with improved health outcomes. METHODS: We estimated the proportion of Atherosclerosis Risk in Communities study participants who maintained normal BP from 1987 to 1989 (visit 1) through 1996 to 1998 and 2011 to 2013 (over 4 and 5 visits, respectively). Normal BP was defined as systolic BP <120 mm Hg and diastolic BP <80 mm Hg, without antihypertensive medication. We estimated the risk of cardiovascular disease, dementia, and poor physical functioning after visit 5. In exploratory analyses, we examined participant characteristics associated with maintaining normal BP. RESULTS: Among 2699 participants with normal BP at baseline (mean age 51.3 years), 47.1% and 15.0% maintained normal BP through visits 4 and 5, respectively. The hazard ratios comparing participants who maintained normal BP through visit 4 but not visit 5 and through visit 5 versus those who did not maintain normal BP through visit 4 were 0.80 (95% CI, 0.63-1.03) and 0.60 (95% CI, 0.42-0.86), respectively, for cardiovascular disease, and 0.85 (95% CI, 0.71-1.01) and 0.69 (95% CI, 0.54-0.90), respectively, for poor physical functioning. Maintaining normal BP through visit 5 was more common among participants with normal body mass index versus obesity at visit 1, those with normal body mass index at visits 1 and 5, and those with overweight at visit 1 and overweight or normal body mass index at visit 5, compared with those with obesity at visits 1 and 5. CONCLUSIONS: Maintaining normal BP was associated with a lower risk of cardiovascular disease and poor physical functioning.

Association Between Body Mass Index, Obesity, and Clinical Outcomes Following Coronary Artery Bypass Grafting in Brazil: An Analysis of One Year of Follow-up of BYPASS Registry Patients.

OBJECTIVE: To investigate the association between body mass index (BMI), obesity, clinical outcomes, and mortality following coronary artery bypass grafting (CABG) in Brazil using a large sample with one year of follow-up from the Brazilian Registry of Cardiovascular Surgeries in Adults (or BYPASS) Registry database. METHODS: A multicenter cohort-study enrolled 2,589 patients submitted to isolated CABG and divided them into normal weight (BMI 20.0-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2), and obesity (BMI > 30.0 kg/m2) groups. Inpatient postoperative outcomes included the most frequently described complications and events. Collected post-discharge outcomes included rehospitalization and mortality rates within 30 days, six months, and one year of follow-up. RESULTS: Sternal wound infections (SWI) rate was higher in obese compared to normal-weight patients (relative risk [RR]=5.89, 95% confidence interval [CI]=2.37-17.82; P=0.001). Rehospitalization rates in six months after discharge were higher in obesity and overweight groups than in normal weight group (χ=6.03, P=0.049); obese patients presented a 2.2-fold increase in the risk for rehospitalization within six months compared to normal-weight patients (RR=2.16, 95% CI=1.17-4.09; P=0.045). Postoperative complications and mortality rates did not differ among groups during time periods. CONCLUSION: Obesity increased the risk for SWI, leading to higher rehospitalization rates and need for surgical interventions within six months following CABG. Age, female sex, and diabetes were associated with a higher risk of mortality. The obesity paradox remains controversial since BMI may not be sufficient to assess postoperative risk in light of more complex and dynamic evaluations of body composition and physical fitness.

Quality by Design Considerations for Drop-on-Demand Point-of-Care Pharmaceutical Manufacturing of Precision Medicine.

Distributed and point-of-care (POC) manufacturing facilities enable an agile pharmaceutical production paradigm that can respond to localized needs, providing personalized and precision medicine. These capabilities are critical for narrow therapeutic index drugs and pediatric or geriatric dosing, among other specialized needs. Advanced additive manufacturing, three-dimensional (3D) printing, and drop-on-demand (DoD) dispensing technologies have begun to expand into pharmaceutical production. We employed a quality by design (QbD) approach to identify critical quality attributes (CQAs), critical material attributes (CMAs), and critical process parameters (CPPs) of a POC pharmaceutical manufacturing paradigm. This theoretical framework encompasses the production of active pharmaceutical ingredient (API) "inks" at a centralized facility, which are distributed to POC sites for DoD dispensing into/onto delivery vehicles (e.g., orodispersible films, capsules, single liquid dose vials). Focusing on the POC dispensing/dosing processes, QbD considerations and cause-and-effect analyses identified the dispensed API quantity and solid-state form (CQAs), as well as the nozzle diameter, system pressure channel, and number of drops dispensed (CPPs) for detailed investigation. Final assay quantification and content uniformity CQAs were measured from demonstrative levothyroxine sodium single-dose liquid vials of glycerin/water, meeting the standard acceptance values. Each POC facility is unlikely to maintain full quality control laboratory capabilities, requiring the development of appropriate atline or inline methods to ensure quality control. We developed control strategies, including atline ultraviolet-visible (UV-vis) verification of the API ink prior to dispensing, inline drop counting during dispensing, intermediate atline-dispensed volume checks, and offline batch confirmation by liquid chromatography-tandem mass spectrometry (LC-MS/MS) following production.

Validation study of age-independent fibrosis score (Fibrosis-3 index) in patients with metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Because the accuracy of the Fibrosis-4 (FIB-4) index for predicting liver fibrosis changes with age, the need for different cut-offs in various age groups has frequently been discussed. We developed the age-independent score, the Fibrosis-3 (FIB-3) index, and have shown its usefulness in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to validate the diagnostic ability of the FIB-3 index to predict fibrosis progression using a large new patient cohort. METHODS: The ability of the FIB-3 index to predict liver fibrosis was analyzed by comparing it with that of the FIB-4 index using data from 1398 patients with MASLD enrolled in the Asia-based clinical outcome NAFLD study. RESULTS: The areas under the receiver operating characteristic curves for predicting fibrosis stage F3 or higher were not different between the FIB-3 and FIB-4 indices in the entire cohort. Using the single ideal cut-offs of the indices (3.41 for FIB-3 index and 2.01 for FIB-4 index), the predictive accuracy of the FIB-3 index was not significantly different from that of the FIB-4 index among patients aged <60 years; however, the accuracy of the FIB-3 index was significantly higher than that of the FIB-4 index in those aged ≥60 years (0.645 and 0.529, respectively; p < 0.0001). CONCLUSION: The high ability of the FIB-3 index with a single cut-off to predict liver fibrosis in patients with MASLD was confirmed. The FIB-3 index could serve as a useful tool for assessing liver fibrosis regardless of age.

Impact of rice variety, cooking equipment and pretreatment method on the quality of lightly milled rice.

Lightly milled rice is a healthier choice compared to refined white rice. In this study, the effects of variety, cooking equipment and pretreatment method on the quality of six varieties of lightly milled rice from China after cooking was investigated through physics, chemistry and instrumental analysis method. Nanjing-No.5055 has the best eating quality, Xiadao-No.1 has higher appearance score, and Fengliangyouxiang-No.1 has the lowest glycemic index. Compared with microwave oven and electric cooker, steamer has a more significant positive impact on component retention, eating quality and sensory quality, but the former has lower cooking time and higher glycemic index. Soaking can effectively improve the water absorption rate, thus reducing hardness. Cleaning affects component retention but is beneficial for sensory quality. The most obvious variation in organizational structure can be observed in the steamer and soaking processes. These findings could serve as a valuable reference for the processing of lightly milled rice.

Bispectral index monitoring for sedation in scheduled adult colonoscopy: A randomized controlled trial.

BACKGROUND: Patients should be closely monitored during procedures under sedation outside the operating room, but it is unclear which type of monitoring is best. We investigated the efficacy and safety of BIS monitoring vs conventional monitoring for sedation during colonoscopy. METHODS: We performed a double-blind clinical trial in 180 patients undergoing elective colonoscopy. Patients were randomized to 1) the BIS group or 2) a control group, in which sedation was monitored with a BIS monitor or the Ramsay Sedation Score, respectively. The primary outcome was the rate of sedation-induced adverse events in both groups. Secondary outcomes were the characteristics of patients who developed adverse events, and duration of colonoscopy when these events occurred, propofol and remifentanil dosage, and patient satisfaction. RESULTS: Univariate analysis showed fewer cardiopulmonary complications in the BIS group (41.11% vs 57.78% in controls; p = 0.02). Multivariate analysis found a significantly higher risk of adverse events in older patients (95% CI, 1.013-1.091; p = 0.0087) and in men (95% CI, 1.129-7.668; p = 0.0272). These events were observed at the hepatic flexure. No significant differences between propofol or remifentanil dosage, use of rescue medication, and patient satisfaction were observed between groups. CONCLUSIONS: Our data suggest that BIS monitoring during sedation in scheduled colonoscopies reduces adverse respiratory events. Although its routine use in sedation does not appear to be warranted, clinicians should take steps to identify patients with a higher risk of complications who might benefit from this type of monitoring.

Categorization of Patients with Pulmonary Embolism by Charlson Comorbidity Index.

BACKGROUND: Short-term outcomes of pulmonary embolism are closely related to right ventricular dysfunction and patient's hemodynamic status, but also to individual comorbidity profile. However, the impact of patients' comorbidities on survival during pulmonary embolism might be underrated. Although the Charlson Comorbidity Index (CCI) is the most extensively studied comorbidity index for detecting comorbidity burden, studies analysing the impact of CCI on pulmonary embolism patients' survival are limited. METHODS: We used the German nationwide inpatient sample to analyse all hospitalised patients with pulmonary embolism in Germany 2005-2020 and calculated CCI for each patient, compared the CCI classes (very-low: CCI=0points, mild: CCI=1-2 points, moderate: CCI=3-4, high severity: CCI>4 points) and impact of CCI class on outcomes. RESULTS: Overall, 1,373,145 hospitalizations of patients with acute pulmonary embolism (53.0% females, 55.9% aged ≥70years) were recorded in Germany between 2005 and 2020; the CCI class stratified them. Among these, 100,156 (7.3%) were categorized as very-low, 221,545; (16.1%) as mild, 394,965 (28.8%) as moderate, and 656,479 (47.8%) as patients with a high comorbidity burden according to CCI class. In-hospital case-fatality increased depending on the CCI class: 3.6% in very-low, 6.5% in mild, 12.1% in moderate and 22.1% in high CCI class (P<0.001). CCI class was associated with increased in-hospital case-fatality (OR 2.014 [95%CI 2.000-2.027], P<0.001). CONCLUSION: Our study results may help to better understand and measure the association between an aggravated comorbidity profile and increased in-hospital case-fatality in patients with pulmonary embolism.

Predictability of noninvasive liver fibrosis score for cardiac events in patients with nonalcoholic fatty liver disease.

BACKGROUND AND AIMS: Patients with nonalcoholic fatty liver disease (NAFLD) have a higher risk of cardiac events. However, although the severity of liver fibrosis is related to worsening prognosis in patients with NAFLD, it is unclear whether the noninvasive liver fibrosis score has a predictive value for cardiac events. METHODS AND RESULTS: We evaluated 4071 patients with NAFLD diagnosed using ultrasonography. Liver fibrosis was assessed and divided into three groups based on the Fibrosis-4 (FIB4) index and NAFLD fibrosis score (NFS). The primary outcome of this study was major adverse cardiac events (MACE), including cardiac death, nonfatal myocardial infarction, and revascularization due to coronary artery disease. The median age of the evaluated patients was 61 (52-69) years, and 2201 (54.1%) were male. During the median follow-up period of 6.6 years, 179 (4.4%) patients experienced MACE. Kaplan-Meier survival analysis demonstrated that MACE increased progressively with the FIB4 index (log-rank, p < 0.001) and NFS (log-rank, p < 0.001). Multivariable analysis showed that the higher the FIB4 index, the higher the risk for MACE (low group as reference vs. intermediate group, hazard ratio [HR]: 1.860 [95% confidence interval (CI), 1.326-2.610; p < 0.001]; vs. high group, HR:3.325 [95% CI, 2.017-5.479; p < 0.001]), as well as NFS (low NFS group as reference vs. intermediate group, HR: 1.938 [95% CI, 1.391-2.699; p < 0.001]; vs. high group, HR: 3.492 [95% CI, 1.997-6.105; p < 0.001]). CONCLUSIONS: The FIB4 index and NFS are associated with the probability of MACE in patients with NAFLD. CLINICAL TRIALS: The study design was approved by the ethics review board of Ogaki Municipal Hospital (approval number: 20221124-12, registration date: November 28th, 2022). https://www.ogaki-mh.jp/chiken/kenkyu.html.