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JPMA. the Journal of the Pakistan... Jun 2024Organic acid disorders are rare inherited metabolic disorders of key metabolic pathways. For the identification of specific organic acids, investigation of urinary... (Review)
Review
Organic acid disorders are rare inherited metabolic disorders of key metabolic pathways. For the identification of specific organic acids, investigation of urinary metabolites and genetic testing are required through newborn screening programmes. Delayed diagnosis leads to complications, such as cardiac attacks, respiratory problems, neuro-developmental disorders, intellectual disability, and even premature death. The burden of such inherited disorders is quite high in developing countries of South Asia due to high rate of consanguinity in the region. Unfortunately, such disorders are left untreated due to the lack of screening facilities in such countries. The current narrative review was planned to highlight the urgent need for closing this gap and implementing effective newborn screening programmes for organic acid disorders in developing countries. The implementation of effective programmes is crucial for reducing morbidity and mortality, and for improving the quality of life for the affected children and of their families, thus promoting global health equity.
Topics: Humans; Neonatal Screening; Infant, Newborn; Developing Countries; Metabolism, Inborn Errors; Amino Acid Metabolism, Inborn Errors
PubMed: 38948986
DOI: 10.47391/JPMA.10223 -
JPMA. the Journal of the Pakistan... Jun 2024To evaluate the under-nutrition risk of children admitted to hospitals using a validated tool.
OBJECTIVES
To evaluate the under-nutrition risk of children admitted to hospitals using a validated tool.
METHODS
The cross-sectional study was conducted from September 2017 to June 2018 in the paediatrics wards of a tertiary referral paediatric government hospital, a tertiary teaching hospital and a government district hospital in Malaysia. The sample comprised paediatric patients aged 2-12 years within 24-72 hours of hospital admission. Data was collected using the 3-Minute Nutrition Screening-Paediatrics tool. Data was analysed using SPSS 20.
RESULTS
Of the 341 patients screened, 284(83.3%) were included; 170(59.9%) boys and 114(40.1%) girls. The overall median age was 4.85 years (interquartile range: 4.33 years). The median length of hospital stay was 3 days (interquartile range: 3 days). There were 72(25.4%) participants at high under-nutrition risk, with the highest proportion being at the district government hospital 31(33%). Among those with high risk, 5.4% subjects had severe acute malnutrition, 9.7% had severe chronic malnutrition, and 11.1% had severe thinness.
CONCLUSION
The 3-Minute Nutrition Screening-Paediatrics scale was found to be effective as a nutrition screening tool for hospitalised children in Malaysia.
Topics: Humans; Female; Male; Malaysia; Child, Preschool; Child; Cross-Sectional Studies; Nutrition Assessment; Hospitalization; Child Nutrition Disorders; Length of Stay; Nutritional Status; Malnutrition; Mass Screening; Thinness; Risk Assessment
PubMed: 38948974
DOI: 10.47391/JPMA.9616 -
HemaSphere Jul 2024Twenty percent of children with T-cell lymphoblastic lymphoma (T-LBL) will relapse and have an extremely poor outcome. Currently, we can identify a genetically low-risk...
Twenty percent of children with T-cell lymphoblastic lymphoma (T-LBL) will relapse and have an extremely poor outcome. Currently, we can identify a genetically low-risk subgroup in pediatric T-LBL, yet these high-risk patients who need intensified or alternative treatment options remain undetected. Therefore, there is an urgent need to recognize these high-risk T-LBL patients through identification of molecular characteristics and biomarkers. By using RNA sequencing which was performed in 29/49 T-LBL patients who were diagnosed in the Princess Maxima Center for Pediatric Oncology between 2018 and 2023, we discovered a previously unknown high-risk biological subgroup of children with T-LBL. This subgroup is characterized by gene fusions, found in 21% of our T-LBL cohort (6/29). All patients presented with a large mediastinal mass, pleural/pericardial effusions, and absence of blasts in the bone marrow, blood, and central nervous system. Blood CCL17 (C-C Motif Chemokine Ligand 17, TARC) levels were measured at diagnosis in 26/29 patients, and all six patients with gene fusions patients exclusively expressed highly elevated blood CCL17 levels, defining a novel and previously not known clinically relevant biomarker for T-cell lymphoblastic lymphoma. Four out of these six patients relapsed during therapy, a fifth developed a therapy-related acute myeloid leukemia during maintenance therapy. These data indicate that T-LBL patients with a fusion have a high risk of relapse which can be easily identified using a blood CCL17 screening at diagnosis. Further molecular characterization through gene fusion analysis offers these patients the opportunity for treatment intensification or new treatment strategies.
PubMed: 38948925
DOI: 10.1002/hem3.117 -
Frontiers in Endocrinology 2024Thyroid nodules, increasingly prevalent globally, pose a risk of malignant transformation. Early screening is crucial for management, yet current models focus mainly on...
BACKGROUND
Thyroid nodules, increasingly prevalent globally, pose a risk of malignant transformation. Early screening is crucial for management, yet current models focus mainly on ultrasound features. This study explores machine learning for screening using demographic and biochemical indicators.
METHODS
Analyzing data from 6,102 individuals and 61 variables, we identified 17 key variables to construct models using six machine learning classifiers: Logistic Regression, SVM, Multilayer Perceptron, Random Forest, XGBoost, and LightGBM. Performance was evaluated by accuracy, precision, recall, F1 score, specificity, kappa statistic, and AUC, with internal and external validations assessing generalizability. Shapley values determined feature importance, and Decision Curve Analysis evaluated clinical benefits.
RESULTS
Random Forest showed the highest internal validation accuracy (78.3%) and AUC (89.1%). LightGBM demonstrated robust external validation performance. Key factors included age, gender, and urinary iodine levels, with significant clinical benefits at various thresholds. Clinical benefits were observed across various risk thresholds, particularly in ensemble models.
CONCLUSION
Machine learning, particularly ensemble methods, accurately predicts thyroid nodule presence using demographic and biochemical data. This cost-effective strategy offers valuable insights for thyroid health management, aiding in early detection and potentially improving clinical outcomes. These findings enhance our understanding of the key predictors of thyroid nodules and underscore the potential of machine learning in public health applications for early disease screening and prevention.
Topics: Thyroid Nodule; Humans; Machine Learning; Female; Male; China; Cross-Sectional Studies; Middle Aged; Adult; Early Detection of Cancer; Aged; Mass Screening; Ultrasonography
PubMed: 38948526
DOI: 10.3389/fendo.2024.1385167 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Cantrell syndrome, a rare congenital disorder, is characterized by a unique collection of defects on the midline abdominal wall, the lower sternum, the anterior...
OBJECTIVE
Cantrell syndrome, a rare congenital disorder, is characterized by a unique collection of defects on the midline abdominal wall, the lower sternum, the anterior diaphragm, and the diaphragmatic pericardium in addition to some form of intracardiac defect. So far, most of the reports on fetuses with Cantrell syndrome worldwide are either case reports or literature reviews, and few comprehensive studies on fetuses with Cantrell syndrome have been reported, especially in domestic literature. This study aims to provide a detailed analysis of 15 cases of Cantrell syndrome fetuses, focusing on their prenatal ultrasound manifestations and postnatal examination outcomes.
METHODS
A retrospective analysis was conducted with 15 cases of fetuses diagnosed with Cantrell syndrome via prenatal ultrasound examinations between March 2018 and July 2023. Ultrasound examinations were performed in accordance with the Guidelines for Obstetric Ultrasound in China, including first-trimester fetal ultrasound scan and routine second-trimester fetal ultrasound scan. Gestational age was evaluated and nuchal translucency (NT) was measured during first-trimester fetal ultrasound scan at 11 to 13+6 weeks. The diagnostic criterion for NT thickening was NT≥3.0 mm and the screening of severe fetal structural malformations was performed, including the screening of the head, the neck, the thorax, the abdominal content, the abdominal wall, the limbs and other structures. During routine second-trimester fetal ultrasound scan, the fetal biometry was assessed and an anatomy survey was performed. Post-induction and postnatal outcomes of fetuses diagnosed with Cantrell syndrome by prenatal ultrasound were followed up by postnatal observation, inquiries with the electronic medical record system, or telephone follow-up. The prenatal ultrasound imaging manifestations and features of the fetuses with Cantrell syndrome, as well as their post-induction or postnatal examination results were comprehensively summarized and analyzed.
RESULTS
The study involved pregnant women of the average age of 30.1±3.5 years, with ultrasound diagnoses made between 11 to 26 weeks of gestation (mean: 13.4±4.0 weeks). Among the 15 cases, there were 10 singleton pregnancies and 5 cases of one twin in a pair of twins. These twins comprised 3 monochorionic diamniotic twins and 2 dichorionic diamniotic twins, with Cantrell syndrome present in one of the twins in all 5 cases. Thirteen cases were diagnosed by fetal ultrasound scan conducted in the first trimester, with 10 being singleton pregnancies and 3 being twin pregnancies (1 monochorionic diamniotic twins and 2 dichorionic diamniotic twins). One case was missed in the first-trimester ultrasound scan, resulting in a missed diagnosis rate of 7.1%. Two cases were diagnosed in second-trimester fetal ultrasound scan, both involving monochorionic diamniotic twins. One case was a referral from another hospital at 19 weeks, while the other was initially not diagnosed for Cantrell syndrome and was diagnosed at 26 weeks. Prenatal ultrasound examinations revealed a consistent pattern of abnormalities across all 15 fetuses, including manifestations of ectopic cordis combined with abdominal protrusion mass. Specifically, 4 cases were diagnosed with omphalocele, 4 with gastroschisis, and the remaining 7 had uncertain coverage of the membrane on the surface of the abdominal protrusion mass. Six fetuses had complete ectopic cordis, while nine had partial ectopic cordis. Fetal echocardiography was performed in 5 cases, revealing intracardiac malformations in 4 cases (80%). Notably, 2 cases were diagnosed in the second trimester, including one with right ventricular hypoplasia accompanied by interventricular septal defect and another with double outlet right ventricle accompanied by interventricular septal defect. Additionally, 2 cases were diagnosed in the first trimester, one with single atrium and single ventricle, and the other with complete transposition of the great arteries. Of the 15 cases of fetuses with Cantrell syndrome, 13 (86.7%) exhibited concomitant malformations in other systems. These included 7 cases of spinal malformations, 4 limb abnormalities, 3 umbilical cord abnormalities, 2 central nervous system malformations, 1 facial malformation, and 2 fetal hydrops. Spinal malformations were the most prevalent concomitant malformation, accounting for 46.7% of all cases. Among the 14 fetuses undergoing NT examination, 7 (50%) had increased NT, and 5 of them had cystic hygroma. All 10 singleton pregnancies underwent induced abortion, and the appearance of the induced fetuses was consistent with the prenatal ultrasound manifestations. In the twin pregnancies, 2 cases experienced intrauterine fetal death, while 2 underwent selective reduction. Notably, 3 of these cases exhibited postnatal appearances consistent with prenatal ultrasound manifestation, while 1 case showed an indistinct appearance after selective reduction during delivery. One case was lost to follow-up. Genetic testing was conducted for 4 induced fetuses, none of which yielded any relevant pathogenic or potentially pathogenic variants.
CONCLUSION
In conclusion, Cantrell syndrome manifests prenatally with ectopic cordis combined with abdominal protrusion mass, often accompanied by intracardiac malformations and other concomitant malformations. While most cases can be diagnosed in the first trimester, there remains the possibility of missed diagnoses, which underscores the importance of close follow-up in the second trimester.
Topics: Humans; Female; Pregnancy; Pentalogy of Cantrell; Ultrasonography, Prenatal; Retrospective Studies; Nuchal Translucency Measurement; Gestational Age; Adult
PubMed: 38948286
DOI: 10.12182/20240560208 -
Sichuan Da Xue Xue Bao. Yi Xue Ban =... May 2024Gallstone disease (GSD) is one of the common digestive tract diseases with a high worldwide prevalence. The effects of GSD on patients include but are not limited to the...
OBJECTIVE
Gallstone disease (GSD) is one of the common digestive tract diseases with a high worldwide prevalence. The effects of GSD on patients include but are not limited to the symptoms of nausea, vomiting, and biliary colic directly caused by GSD. In addition, there is mounting evidence from cohort studies connecting GSD to other conditions, such as cardiovascular diseases, biliary tract cancer, and colorectal cancer. Early identification of patients at a high risk of GSD may help improve the prevention and control of the disease. A series of studies have attempted to establish prediction models for GSD, but these models could not be fully applied in the general population due to incomplete prediction factors, small sample sizes, and limitations in external validation. It is crucial to design a universally applicable GSD risk prediction model for the general population and to take individualized intervention measures to prevent the occurrence of GSD. This study aims to conduct a multicenter investigation involving more than 90000 people to construct and validate a complete and simplified GSD risk prediction model.
METHODS
A total of 123634 participants were included in the study between January 2015 and December 2020, of whom 43929 were from the First Affiliated Hospital of Chongqing Medical University (Chongqing, China), 11907 were from the First People's Hospital of Jining City (Shandong, China), 1538 were from the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China), and 66260 were from the People's Hospital of Kaizhou District (Chongqing, China). After excluding patients with incomplete clinical medical data, 35976 patients from the First Affiliated Hospital of Chongqing Medical University were divided into a training data set (=28781, 80%) and a validation data set (=7195, 20%). Logistic regression analyses were performed to investigate the relevant risk factors of GSD, and a complete risk prediction model was constructed. Factors with high scores, mainly according to the nomograms of the complete model, were retained to simplify the model. In the validation data set, the diagnostic accuracy and clinical performance of these models were validated using the calibration curve, area under the curve (AUC) of the receiver operating characteristic curve, and decision curve analysis (DCA). Moreover, the diagnostic accuracy of these two models was validated in three other hospitals. Finally, we established an online website for using the prediction model (The complete model is accessible at https://wenqianyu.shinyapps.io/Completemodel/, while the simplified model is accessible at https://wenqianyu.shinyapps.io/Simplified/).
RESULTS
After excluding patients with incomplete clinical medical data, a total of 96426 participants were finally included in this study (35876 from the First Affiliated Hospital of the Chongqing Medical University, 9289 from the First People's Hospital of Jining City, 1522 from the Tianjin Medical University Cancer Institute, and 49639 from the People's Hospital of Kaizhou District). Female sex, advanced age, higher body mass index, fasting plasma glucose, uric acid, total bilirubin, gamma-glutamyl transpeptidase, and fatty liver disease were positively associated with risks for GSD. Furthermore, gallbladder polyps, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and aspartate aminotransferase were negatively correlated to risks for GSD. According to the nomograms of the complete model, a simplified model including sex, age, body mass index, gallbladder polyps, and fatty liver disease was constructed. All the calibration curves exhibited good consistency between the predicted and observed probabilities. In addition, DCA indicated that both the complete model and the simplified model showed better net benefits than treat-all and treat-none. Based on the calibration plots, DCA, and AUCs of the complete model (AUC in the internal validation data set=74.1% [95% CI: 72.9%-75.3%], AUC in Shandong=71.7% [95% CI: 70.6%-72.8%], AUC in Tianjin=75.3% [95% CI: 72.7%-77.9%], and AUC in Kaizhou=72.9% [95% CI: 72.5%-73.3%]) and the simplified model (AUC in the internal validation data set=73.7% [95% CI: 72.5%-75.0%], AUC in Shandong=71.5% [95% CI: 70.4%-72.5%], AUC in Tianjin=75.4% [95% CI: 72.9%-78.0%], and AUC in Kaizhou=72.4% [95% CI: 72.0%-72.8%]), we concluded that the complete and simplified risk prediction models for GSD exhibited excellent performance. Moreover, we detected no significant differences between the performance of the two models (>0.05). We also established two online websites based on the results of this study for GSD risk prediction.
CONCLUSIONS
This study innovatively used the data from 96426 patients from four hospitals to establish a GSD risk prediction model and to perform risk prediction analyses of internal and external validation data sets in four cohorts. A simplified model of GSD risk prediction, which included the variables of sex, age, body mass index, gallbladder polyps, and fatty liver disease, also exhibited good discrimination and clinical performance. Nonetheless, further studies are needed to explore the role of low-density lipoprotein cholesterol and aspartate aminotransferase in gallstone formation. Although the validation results of the complete model were better than those of the simplified model to a certain extent, the difference was not significant even in large samples. Compared with the complete model, the simplified model uses fewer variables and yields similar prediction and clinical impact. Hence, we recommend the application of the simplified model to improve the efficiency of screening high-risk groups in practice. The use of the simplified model is conducive to enhancing the self-awareness of prevention and control in the general population and early intervention for GSD.
Topics: Humans; Gallstones; Female; Male; Risk Factors; Middle Aged; Risk Assessment; China; Adult; Aged
PubMed: 38948266
DOI: 10.12182/20240560501 -
The Lancet Regional Health. Western... Jun 2024Type 2 diabetes (T2DM) remains a challenge to treat despite the expansion of various therapeutic classes. Visepegenatide (PB-119) is a once a week, subcutaneous,...
Efficacy and safety of visepegenatide, a long-acting weekly GLP-1 receptor agonist as monotherapy in type 2 diabetes mellitus: a randomised, double-blind, parallel, placebo-controlled phase 3 trial.
BACKGROUND
Type 2 diabetes (T2DM) remains a challenge to treat despite the expansion of various therapeutic classes. Visepegenatide (PB-119) is a once a week, subcutaneous, glucagon-like peptide-1 receptor agonist (GLP-1 RA) injection without the requirement of dose titration that has shown glycaemic control and safety profile in two phase 2 studies conducted in China and the United States, respectively. The aim of this study was to evaluate the efficacy and safety of visepegenatide as a monotherapy in treatment-naïve patients with T2DM.
METHODS
This was a multicentre, double-blind, parallel, placebo-controlled, phase 3 trial conducted in 30 centres in China. Adult participants (aged 18-75 years) with T2DM, glycated haemoglobin (HbA1c) of 7.5%-11.0% [58.47-96.73 mmol/mol], body mass index (BMI) of 18-40 kg/m, and who had been treated with diet and exercise alone for at least 8 weeks before the screening visit were eligible for enrolment. After a 4-week placebo injection run-in period, participants with HbA1c of 7.0%-10.5% [53.0-91.3 mmol/mol] and fasting plasma glucose (FPG) < 15 mmol/L were randomised in a ratio of 1:1 to receive visepegenatide (150 μg) or placebo subcutaneous injections once a week for 24 weeks. The treatment was extended to another 28 weeks during which all participants received visepegenatide. The primary outcome was a change in HbA1c from baseline to week 24. This study was registered with ClinicalTrials.gov, as NCT04504370.
FINDINGS
Between November 2, 2020, and November 2, 2022, we randomly assigned 273 adult participants to the visepegenatide (n = 137) and placebo (n = 136) groups. In total, 257 (94.12%) participants, 131 (95.6%) on visepegenatide, and 126 (92.6%) on placebo, completed the double-blinded treatment period. At baseline, the mean (SD) HbA1c was 8.47% (0.81) [69.07 [8.81] mmol/mol], which rapidly decreased to 7.63% (0.80) [59.94 [8.70] mmol/mol] with visepegenatide by week 4 of treatment, and the change from baseline was significantly greater than that in the placebo group (-0.82% [-0.90 to -0.74]; [-8.99 [-9.89 to -8.10] mmol/mol] -0.30% [-0.41 to -0.19]; [-3.30 [-4.50 to -2.09] mmol/mol]). At week 24, when evaluating the effects of treatment with treatment policy estimand, the least square mean (LSM change in HbA1c from baseline was -1.36 (95% confidence interval [CI] -1.52 to -1.20) [-14.84 [-16.60 to -13.08] mmol/mol] in the visepegenatide group -0.63 (-0.79 to -0.46) [-6.84 [-8.61 to -5.07] mmol/mol] in the placebo group. The reduction in HbA1c was significantly greater with visepegenatide than placebo (LSM difference -0.73, 95% CI -0.96 to -0.50; p < 0.001). When evaluating the treatment estimand with hypothetic policy, the LSM change in HbA1c from baseline in the visepegenatide group (-1.37 [-1.53 to -1.20]) [-14.95 [-16.76 to -13.14] mmol/mol] was significantly greater than the placebo group (-0.63 [-0.81 to -0.45]) [6.90 (-8.89 to -4.90) mmol/mol]. The LSM difference was (-0.74, 95% CI -0.98 to -0.49; [-8.00 [-10.50 to -5.50] mmol/mol]; p < 0.001]. A significantly greater proportion of the visepegenatide group achieved a target HbA1c level of <7% (<53 mmol/mol) than the placebo (50.4% 14.2%; p < 0.05) and stringent HbA1c level of ≤6.5% (≤48 mmol/mol) (26.7% 7.9%), respectively. There was also a significantly greater improvement in FPG, 2-h postprandial glucose, homeostasis model assessment (HOMA) of beta cell function, post-prandial insulin, fasting, and post-prandial C-peptide level (p < 0.05) with visepegenatide treatment. The number (3 [2.2%]) of participants who received rescue therapy in the visepegenatide group was remarkably lower compared with those (17 [12.5%]) in the placebo group (p < 0.05). During the extended treatment period, visepegenatide consistently maintained the efficacy till week 52 confirmed by all the above endpoints. The reduction in HbA1c at week 52 was -1.39% (-1.58 to -1.19) [-15.14 [-17.28 to -13.01] mmol/mol], which was even greater than that at week 24. There was also a significant improvement in HOMA-insulin resistance (p = 0.004) at week 52 compared with the baseline value. For the placebo→visepegenatide group, which received visepegenatide in the extended treatment period, a notable decrease in HbA1c at week 52 compared to baseline was observed. The change from baseline in HbA1c was -1.49% (-1.68 to -1.30) [-16.27 [-18.37 to -14.16] mmol/mol]. The outcome was in the same direction as the visepegenatide group from the double-blind treatment period. Comprehensive benefits of visepegenatide including weight loss, improvement in lipid profile, and reduction in blood pressure have been demonstrated in this study. Visepegenatide reduced the body weight in a BMI-dependent manner that was prominent in BMI ˃32 kg/m with a mean (SD) reduction of -4.77 (13.94) kg at week 52 (p < 0.05). Incidences of gastrointestinal adverse events were less common than other weekly GLP-1 RA in the market, and most of the adverse events were mild and moderate in nature, occurring in the first weeks of the treatment, and were transient. No serious hypoglycaemia or grade 2 hypoglycaemia (blood glucose: ≤3 mmol/L) was reported during the study.
INTERPRETATION
As a monotherapy, visepegenatide provided rapid without the risk of hypoglycaemia, significant, and sustainable glycaemic control by improving islet β-cell function and insulin resistance. Treatment with visepegenatide induced early treatment response in reducing HbA1c and maintaining glycaemic control for 52 weeks. Meanwhile, visepegenatide provided a comprehensive benefit in body weight loss, lipids, and blood pressure reduction. Visepegenatide had a better safety profile than other weekly GLP-1 RA in participants with T2DM even without the requirement of dose titration. Visepegenatide would provide an optimal treatment approach with its high benefit and low-risk balance.
FUNDING
PegBio Co., Ltd.
PubMed: 38948164
DOI: 10.1016/j.lanwpc.2024.101101 -
ACS Omega Jun 2024Microcystins are hepatotoxic cyclic heptapeptides produced by some cyanobacterial species and usually contain the unusual β-amino acid...
Microcystins are hepatotoxic cyclic heptapeptides produced by some cyanobacterial species and usually contain the unusual β-amino acid 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid (Adda) at position-5. The full microcystin gene cluster from PCC 7806 has been expressed in . In an earlier study, the engineered strain was shown to produce MC-LR and [d-Asp]MC-LR, the main microcystins reported in cultures of PCC 7806. However, analysis of the engineered strain of using semitargeted liquid chromatography with high-resolution tandem mass spectrometry (LC-HRMS/MS) and thiol derivatization revealed the presence of 15 additional microcystin analogues, including four linear peptide variants and, in total, 12 variants with modifications to the Adda moiety. Four of the Adda-variants lacked the phenyl group at the Adda-terminus, a modification that has not previously been reported in cyanobacteria. Their HRMS/MS spectra contained the product-ion from Adda at / 135.1168, but the commonly observed product-ion at / 135.0804 from Adda-containing microcystins was almost completely absent. In contrast, three of the variants were missing a methyl group between C-2 and C-8 of the Adda moiety, and their LC-HRMS/MS spectra displayed the product-ion from Adda at / 135.0804. However, instead of the product-ion at / 135.1168, these three variants gave product-ions at / 121.1011. These observations, together with spectra from microcystin standards using in-source fragmentation, showed that the product-ion at / 135.1168 found in the HRMS/MS spectra of most microcystins originated from the C-2 to C-8 region of the Adda moiety. Identification of the fragmentation pathways for the Adda side chain will facilitate the detection of microcystins containing modifications in their Adda moieties that could otherwise easily be overlooked with standard LC-MS screening methods. Microcystin variants containing Abu at position-1 were also prominent components of the microcystin profile of the engineered bacterium. Microcystin variants with Abu or without the phenyl group on the Adda side chain were not detected in the original host cyanobacterium. This suggests not only that the microcystin synthase complex may be affected by substrate availability within its host organism but also that it possesses an unexpected degree of biosynthetic flexibility.
PubMed: 38947807
DOI: 10.1021/acsomega.4c03332 -
Cureus May 2024Introduction Diabetes mellitus (DM) remains a primary cause of morbidity and mortality, leading to complications such as blindness, kidney failure, and lower limb...
Introduction Diabetes mellitus (DM) remains a primary cause of morbidity and mortality, leading to complications such as blindness, kidney failure, and lower limb amputations. Early detection of kidney damage, indicated by microalbuminuria (MA), is crucial for managing DM. Given the impact of these conditions, evaluating the prevalence of chronic kidney disease (CKD) in diabetic populations within primary healthcare is essential. Methodology This was a cross-sectional and observational study. Adults diagnosed with DM type 1 or 2 from five primary care units (PCUs) located in the North of Portugal, were included in this study. Descriptive and correlational statistics were performed using IBM SPSS Statistics for Windows, Version 28.0 (IBM Corp., Armonk, NY). Statistical significance was set to < 0,05. Logistic regression models were created to identify the factors associated with CKD and DM Results A sample of 357 diabetic patients was obtained, with 166 (46.5%) females. Of the sample, 250 (70.1%) were aged 65 or older, and the median known duration of DM was 9.36 years. Excess weight or obesity accounted for 79.8%, with a median body mass index of 28.73 kg/m and hypertension in 284 (79.6%). An estimated glomerular filtration rate (eGFR) less than 60 mL/min was present in 89 (24.9%) and an MA of 30 mg/dL or higher was present in 68 (19.0%). In total, 130 (36.4%) individuals exhibited eGFR and MA consistent with CKD. Among these, 25 (78.1%) had other identifiable causes of CKD besides DM, hypertension, overweight, or obesity. Binary logistic regression models were constructed to find a relationship between CKD with eGFR < 60 mL/min and MA. A statistically significant association was found between CKD with eGFR < 60 mL/minute and age (odds ratio [OR] = 1.150; < 0.001), kidney stones (OR = 5.112; = 0.003), absence of excess weight or obesity (OR = 0.267; < 0.001). The use of GLP1 agonists showed statistical significance as a predictor (OR = 4.653; = 0.042) of the presence of MA. Discussion The study investigates the impact of DM and its complications in the surveyed population. While most patients had controlled DM (284, 76.2%), prolonged disease duration correlated with poorer glycemic control, underscoring the need for more effective management strategies in advanced disease stages. Notably, a third of individuals with DM had CKD, with significant implications for therapeutic interventions and heightened risks of renal failure and cardiovascular morbidity. MA was a crucial marker for endothelial injury, with prevalence influenced by DM duration and medication type. However, in many cases, correct identification of CKD was lacking, suggesting under-recognition of renal deterioration in DM. While the study offers valuable insights, its limited sample size and geographic scope warrant cautious interpretation, emphasizing the need for broader, context-specific research to inform comprehensive healthcare strategies. Conclusions In conclusion, this study highlights the significant burden of CKD among diabetic patients, emphasizing the need for proactive screening, personalized management, and accurate diagnosis. Despite limitations, it underscores the importance of early detection and tailored interventions, advocating for improved diabetes care to mitigate renal complications on a broader scale.
PubMed: 38947587
DOI: 10.7759/cureus.61417 -
Frontiers in Public Health 2024Scalable PTSD screening strategies must be brief, accurate and capable of administration by a non-specialized workforce.
BACKGROUND
Scalable PTSD screening strategies must be brief, accurate and capable of administration by a non-specialized workforce.
METHODS
We used PTSD as determined by the structured clinical interview as our gold standard and considered predictors sets of (a) Posttraumatic Stress Checklist-5 (PCL-5), (b) Primary Care PTSD Screen for the DSM-5 (PC-PTSD) and, (c) PCL-5 and PC-PTSD questions to identify the optimal items for PTSD screening for public sector settings in Kenya. A logistic regression model using LASSO was fit by minimizing the average squared error in the validation data. Area under the receiver operating characteristic curve (AUROC) measured discrimination performance.
RESULTS
Penalized regression analysis suggested a screening tool that sums the Likert scale values of two PCL-5 questions-intrusive thoughts of the stressful experience (#1) and insomnia (#21). This had an AUROC of 0.85 (using hold-out test data) for predicting PTSD as evaluated by the MINI, which outperformed the PC-PTSD. The AUROC was similar in subgroups defined by age, sex, and number of categories of trauma experienced (all AUROCs>0.83) except those with no trauma history- AUROC was 0.78.
CONCLUSION
In some East African settings, a 2-item PTSD screening tool may outperform longer screeners and is easily scaled by a non-specialist workforce.
Topics: Humans; Stress Disorders, Post-Traumatic; Female; Male; Adult; Kenya; Mass Screening; Middle Aged; Regression Analysis; Young Adult; Adolescent; Surveys and Questionnaires
PubMed: 38947359
DOI: 10.3389/fpubh.2024.1383171