Tag: nevin manimala

J Biomol Struct Dyn. 2023 Jun 19:1-13. doi: 10.1080/07391102.2023.2225007. Online ahead of print.

ABSTRACT

The in silico evaluation of 27 p-aminosalicylic acid derivatives, also referred to as neuraminidase inhibitors was the focus of the current study. To search and predict new potential neuraminidase inhibitors, this study was based on the ligand-based pharmacophore modeling, 3D QSAR, molecular docking, ADMET and MD simulation studies. The data was generated from recently reported inhibitors and divided into two groups, one of these group has 17 compounds for training and the second group has 10 compounds for testing purpose. The generated pharmacophore has known as ADDPR_4 was found statistically significant 3D-QSAR model owing the high trust scores (R² = 0.974, Q² = 0.905, RMSE = 0.23). Morever external validation was also employed to evaluate the prediction capacity of the built pharmacophore model (R²_pred = 0.905). In addition, in silico ADMET, analyses were employed to evaluate the obtained hits for drug likeness properties. The stability of formed complexes was further evaluated using molecular dynamics. Top two hits showed stable complexes with Neuraminidase based on calculated total binding energy by MM-PBSA.Communicated by Ramaswamy H. Sarma.

PMID:37334701 | DOI:10.1080/07391102.2023.2225007

Ann Surg. 2023 Jun 19. doi: 10.1097/SLA.0000000000005942. Online ahead of print.

ABSTRACT

OBJECTIVE: This proof-of-concept explores the use of an episode grouper to more accurately identify the complete set of surgical services typically provided in a surgical episode of care and the corresponding range of prices, using colectomy for cancer as the example.

SUMMARY /BACKGROUND DATA: Price transparency is an important policy issue that will require surgeons to better understand the components and cost of care.

METHODS: This study uses the Episode Grouper for Medicare (EGM) business logic to construct colectomy surgical episodes of care for cancer using Medicare claims data for the Boston Hospital Referral Region (HRR) from 2012-2015. Descriptive statistics show the mean reimbursement based on patient severity and stage of surgery along with the number of unique clinicians billing for care and the mix of services provided.

RESULTS: The EGM episode grouper identified 3,182 colectomies in Boston between 2012 and 2015 with 1,607 done for cancer. The mean Medicare allowed amount per case is $29,954 and varies from $26,605 to $36,850 as you move from low to high severity cases. The intra-facility stage is the most expensive ($23,175 on average) compared to the pre ($780) and post ($6,479) facility stages. There is tremendous heterogeneity in service mix.

CONCLUSION: Episode groupers are a potentially valuable tool for identifying variation in service mix and teaming patterns that correlate with total price. By looking at patient care holistically, stakeholders can identify opportunities for price transparency and care redesign that have heretofore been hidden.

PMID:37334700 | DOI:10.1097/SLA.0000000000005942

Pigment Cell Melanoma Res. 2023 Jun 19. doi: 10.1111/pcmr.13103. Online ahead of print.

ABSTRACT

In the last decades, the concept of adipose organ has emerged, giving adipose tissue an active endocrine and immunologic function through the secretion of multiple cytokines and chemokines that seem to be implicated in the development and progression of several cancer, including cutaneous melanoma. In this pilot experimental study, we analyzed the expression in the peritumor subcutaneous adipose tissue of the most significant adipokines involved in the processes of carcinogenesis and metastasis in a population of melanoma patients and in two control groups composed of melanocytic nevi and epidermoid cysts, respectively. We correlated the results obtained with the main disease prognostic factors observing a statistically significant increase in the expression of PAI1, LEP, CXCL1, NAMPT, and TNF-α at the level of the peritumor tissue of the melanoma samples compared to the control groups and a correlation of the same with the histopathological prognostic factor of melanoma. Our preliminary study shows that the overexpression of PAI1, LEP, CXCL1, NAMPT, and TNF-α may contribute to the growth and to the local aggressiveness of cutaneous melanoma. It opens the hypothesis of a direct oncogenic role of subcutaneous adipose tissue and adipokines in the tumorigenesis of melanoma.

PMID:37334675 | DOI:10.1111/pcmr.13103

J Neuromuscul Dis. 2023 Jun 12. doi: 10.3233/JND-230025. Online ahead of print.

ABSTRACT

Open bite (OB) is a common malocclusion in individuals with orofacial dysfunction and syndromes, especially in neuromuscular diseases.

OBJECTIVES: The objectives were to explore the prevalence of OB in myotonic dystrophy type 1 (DM1) and Duchenne muscular dystrophy (DMD) and to create and compare orofacial dysfunction profiles.

METHODS: In this database study, 143 individuals with DM1 and 99 with DMD were included. The Mun-H-Center questionnaire and observation chart were used together with the Nordic Orofacial Test -Screening (NOT-S) to create orofacial dysfunction profiles. OB was categorised as: lateral (LOB); anterior (AOB); severe anterior (AOBS); or both types of anterior OB (AOBTot). Descriptive and multivariate statistics were used to compare the OB prevalence and to study associations with orofacial variables, respectively.

RESULTS: There was a statistically significant difference in OB prevalence between the DM1 (37%) and DMD (49%) groups (p = 0.048). LOB was seen in < 1% of DM1 and 18% of DMD. LOB was associated with macroglossia and closed mouth posture, AOB with hypotonic lips, and open mouth posture and AOBS with hypotonic jaw muscles. The orofacial dysfunction profiles showed similar patterns, although the mean NOT-S total scores for DM1 and DMD were 4.2±2.8 (median 4.0, min-max 1-8) and 2.3±2.0 (median 2.0, min-max 0-8), respectively.

LIMITATIONS: The two groups were not age- or gender-matched.

CONCLUSION: OB malocclusion is common in patients with DM1 and DMD and is associated with different types of orofacial dysfunction. This study highlights the need for multi-disciplinary assessments to support tailored treatment strategies that improve or sustain orofacial functions.

PMID:37334614 | DOI:10.3233/JND-230025

J Alzheimers Dis. 2023 Jun 10. doi: 10.3233/JAD-221116. Online ahead of print.

ABSTRACT

BACKGROUND: Herpesviruses have been proposed to be involved in Alzheimer’s disease development as potentially modifiable pathology triggers.

OBJECTIVE: To investigate associations of serum antibodies for herpes simplex virus (HSV)-1 and cytomegalovirus (CMV) and anti-herpesvirus treatment with cognitive outcomes in relation to interactions with APOE ɛ4.

METHODS: The study included 849 participants in the population-based Prospective Investigation of the Vasculature in Uppsala Seniors study. Cognitive performance at the ages of 75 and 80 years was assessed using the Mini-Mental State Examination (MMSE), trail-making test (TMT) A and B, and 7-minute screening test (7MS).

RESULTS: Anti- HSV-1 IgG positivity was associated cross-sectionally with worse performance on the MMSE, TMT-A, TMT-B, 7MS, enhanced free recall, and verbal fluency tests (p = 0.016, p = 0.016, p < 0.001, p = 0.001, p = 0.033, and p < 0.001, respectively), but not orientation or clock drawing. Cognitive scores did not decline over time and longitudinal changes did not differ according to HSV-1 positivity. Anti- CMV IgG positivity was not associated cross-sectionally with cognition, but TMT-B scores declined more in anti- CMV IgG carriers. Anti- HSV-1 IgG interacted with APOE ɛ4 in association with worse TMT-A and better enhanced cued recall. Anti- HSV IgM interacted with APOE ɛ4 and anti-herpesvirus treatment in association with worse TMT-A and clock drawing, respectively.

CONCLUSION: These findings indicate that HSV-1 is linked to poorer cognition in cognitively healthy elderly adults, including impairments in executive function, memory, and expressive language. Cognitive performance did not decline over time, nor was longitudinal decline associated with HSV-1.

PMID:37334589 | DOI:10.3233/JAD-221116

Rev Esp Salud Publica. 2023 Jun 19;97:e202306052.

ABSTRACT

OBJECTIVE: HIV Clinical Guidelines have positioned integrase inhibitors recently as first-line treatment. However, two of these drugs have also been associated with adverse side effects on the central nervous system, especially with sleep disturbances. The objective was to analyse the influence of bictegravir and dolutegravir on the sleep quality in HIV patients.

METHODS: An observational, cross-sectional study was carried out between December 2020 and January 2021 in HIV patients attended in a pharmacy care clinic. Demographic and adherence variables were collected. Sleep quality was measured using the Pittsburgh questionnaire or PSQI. We classified patients into two groups: patients with bictegravir or dolutegravir in their treatment (study group) and the rest (control group). The influence of the variables collected on the PSQI result was analysed using the Chi-Square test for categorical variables and the student t-test or Mann-Whitney U test for continuous variables.

RESULTS: One hundred and nineteen patients were included. 64% in the study group and 67% in the control group suffered from sleep disorders according to the PSQI questionnaire (p=0.788). Neither were statistical differences found when the different components of sleep were analysed between the two groups.

CONCLUSIONS: A high percentage of patients, regardless of whether their treatment includes bictegravir or dolutegravir, have problems with their sleep quality. We didn’t find a correlation between sleep quality and treatment with bictegravir or dolutegravir compared to the other treatments.

PMID:37334559

Nucl Med Commun. 2023 Jun 12. doi: 10.1097/MNM.0000000000001719. Online ahead of print.

ABSTRACT

OBJECTIVE: In this study, we aimed to compare the diagnostic value of [68Ga]Ga-Pentixafor and [18F]FDG PET/CT in the evaluation of non-small cell lung cancer (NSCLC) patients.

METHODS: Patients with pathology-proven NSCLC were prospectively included. Patients underwent [18F]FDG and [68Ga]Ga-Pentixafor PET/CT within 1 week. All suspicious lesions were interpreted as benign or malignant, and the corresponding PET/CT semi-quantitative parameters were recorded. A two-sided P-value <0.05 was considered significant.

RESULTS: Twelve consecutive NSCLC patients (mean age: 60 ± 7) were included. All patients underwent both [18F]FDG and [68Ga]Ga-Pentixafor PET/CT scans with a median interval of 2 days. Overall, 73 abnormal lesions were detected, from which 58 (79%) were concordant between [18F]FDG and [68Ga]Ga-Pentixafor PET/CT. All primary tumors were clearly detectable in both scans visually. Also, [68Ga]Ga-Pentixafor PET/CT demonstrated rather comparable results with [18F]FDG PET/CT scan in detecting metastatic lesions. However, malignant lesions demonstrated significantly higher SUVmax and SUVmean in [18F]FDG PET/CT (P-values <0.05). Regarding the advantages, [68Ga]Ga-Pentixafor depicted two brain metastases that were missed by [18F]FDG PET/CT. Also, a highly suspicious lesion for recurrence on [18F]FDG PET/CT scan was correctly classified as benign by subsequent [68Ga]Ga-Pentixafor PET/CT.

CONCLUSION: [68Ga]Ga-Pentixafor PET/CT was concordant with [18F]FDG PET/CT in detecting primary NSCLC tumors and could visualize the majority of metastatic lesions. Moreover, this modality was found to be potentially helpful in excluding tumoural lesions when the [18F]FDG PET/CT was equivocal, as well as in detecting brain metastasis where [18F]FDG PET/CT suffers from poor sensitivity. However, the count statistics were significantly lower.

PMID:37334548 | DOI:10.1097/MNM.0000000000001719

Blood Press Monit. 2023 Jun 19. doi: 10.1097/MBP.0000000000000660. Online ahead of print.

ABSTRACT

Accurate office blood pressure (BP) measurement remains crucial in diagnosing and managing hypertension. In this study, we aimed to compare BP measurements done over a bare arm versus a sleeved arm, while controlling all other possible sources of variance. We collected BP measurements of 100 hypertensive patients visiting a nephrology and hypertension clinic between January 2019 and December 2023. Measurements were taken by a single operator and according to the updated guidelines. BP measurements were performed first with one arm bare, and the other arm sleeved, with measurements taken simultaneously. Then, measurements were again taken simultaneously after exposing the arm which was first sleeved, and dressing the arm which was bare at first. a nonparametric Wilcoxon was performed to compare each patient’s measurements on each arm. No statistically significant differences were found between the sleeved and the bare arm measurements, with one exception of SBP measured on the left arm (slightly lower SBP on the bare arm). While looking at the absolute value of differences, the median difference was impressive with a 7-8 mmHg systolic difference and 5.5 mmHg diastolic difference. Our study revealed a robust and unpredicted effect of clothing on BP; in some patients, BP was increased while in others decreased. Therefore, we believe there is importance in measuring BP on bare skin, regardless of clothing or sleeve type.

PMID:37334547 | DOI:10.1097/MBP.0000000000000660

Nucl Med Commun. 2023 Jun 19. doi: 10.1097/MNM.0000000000001721. Online ahead of print.

ABSTRACT

BACKGROUND: Diabetic cardiomyopathy is defined as an independent entity with a specified pathological progression from diastolic dysfunction with preserved ejection fraction to overt heart failure. Myocardial perfusion imaging (MPI) with gated-single-photon emission computed tomography (G-SPECT) has been introduced as a feasible tool to evaluate left ventricular (LV) diastolic function. The aim of this study was to investigate the characteristics of diastolic parameters derived from G-SPECT MPI in diabetic patients compared to patients at very low risk of coronary artery disease (CAD) and with no other CAD risk factors.

METHODS: This cross-sectional study was performed on patients referred to the nuclear medicine department for G-SPECT MPI. Demographic and clinical data, as well as medical history, were extracted from a digital registry system including 4447 patients. Then, two matched groups of patients with only diabetes as cardiac risk factor (n = 126) and those without any identifiable CAD risk factors (n = 126) were selected. Diastolic parameters of MPI, including peak filling rate, time to peak filling rate, mean filling rate at the first third of diastole and second peak filling rate, were derived using quantitative software for eligible cases.

RESULTS: The mean age of the diabetic and nondiabetic groups was 57.1 ± 14.9 and 56.7 ± 10.6 years, respectively (P = 0.823). Comparison of quantitative SPECT MPI parameters between the two groups showed a statistically significant difference only in total perfusion deficit scores, whereas none of the functional parameters, including diastolic and dyssynchrony indices and the shape index, were significantly different. There were also no significant differences in diastolic function parameters between diabetes and nondiabetes patients in the age and gender subgroups.

CONCLUSION: Based on the G-SPECT MPI findings, there is a comparable prevalence of diastolic dysfunction in patients with only diabetes as a cardiovascular risk factor and low-risk patients with no cardiovascular risk factors in the setting of normal myocardial perfusion and systolic function.

PMID:37334545 | DOI:10.1097/MNM.0000000000001721

Diabetes Obes Metab. 2023 Jun 19. doi: 10.1111/dom.15177. Online ahead of print.

ABSTRACT

AIM: Early identification of incident chronic kidney disease (CKD) in individuals with diabetes may help improve patients’ clinical outcomes. This study aimed to develop a prediction equation for incident CKD among people with type 2 diabetes (T2D).

MATERIALS AND METHODS: A time-varying Cox model was applied to data from the ACCORD trial to predict the risk of incident CKD. A list of candidate variables was chosen based on literature reviews and experts’ consultations, including demographic characteristics, vitals, laboratory results, medical history, drug use and health care utilization. Model performance was evaluated. Decomposition analysis was conducted, and external validation was performed.

RESULTS: In total, 6006 patients with diabetes free of CKD were included, with a median follow-up of 3 years and 2257 events. The risk model included age at T2D diagnosed, smoking status, body mass index, high-density lipoprotein, very-low-density lipoprotein, alanine aminotransferase, estimated glomerular filtration rate, urine albumin-creatinine ratio, hypoglycaemia, retinopathy, congestive heart failure, coronary heart disease history, antihyperlipidaemic drug use, antihypertensive drug use and hospitalization. The urine albumin-creatinine ratio, estimated glomerular filtration rate and congestive heart failure were the top three factors that contributed most to the incident CKD prediction. The model showed acceptable discrimination [C-statistic: 0.772 (95% CI 0.767-0.805)] and calibration [Brier Score: 0.0504 (95% CI 0.0477-0.0531)] in the Harmony Outcomes Trial.

CONCLUSION: Incident CKD prediction among individuals with T2D was developed and validated for use in decision support of CKD prevention.

PMID:37334525 | DOI:10.1111/dom.15177