Category: Nevin Manimala

Mult Scler Relat Disord. 2021 Jul 24;55:103170. doi: 10.1016/j.msard.2021.103170. Online ahead of print.

ABSTRACT

BACKGROUND: Clinically stable multiple sclerosis (MS) patients often have negligible inflammatory MRI changes. Brain atrophy may provide insight into subclinical disease progression. The objective was to compare brain atrophy rates in stable patients on long term natalizumab treatment vs. age and gender matched healthy non-MS controls (HC) prospectively over two-years examining brain volume, cognition, and patient reported outcomes (PROs).

METHODS: MS patients treated with natalizumab for a minimum of 2 years, age 18-60 were recruited and compared with age- and gender-matched healthy controls (HC). Both groups were followed prospectively to obtain two years of consecutive magnetic resonance imaging, clinical and PRO data. Baseline normalized brain volume (NBV), yearly T2 lesion volume (T2LV), and percent brain volume change (PBVC) were measured using SIENAX, JIM 6.0, and SIENA respectively. Neuropsychological tests from the MACFIMS battery were selected to optimize assessments for impairments in the domains of information processing speed and memory. Patient reported outcomes (PROs) for domains of physical, mental and social quality of life were evaluated using the NeuroQol short forms.

RESULTS: Forty-eight natalizumab and 62 HC completed all study visits. At baseline, unadjusted mean NBV (natalizumab=1508.80cm (Popescu et al., 2013) vs. HC=1539.23cm (Popescu et al., 2013); p=0.033) and median baseline T2LV (natalizumab=1724.62mm (Popescu et al., 2013) vs. HC=44.20mm (Popescu et al., 2013); p=<0.0001) were different. The mean PBVC at year 2, adjusted for gender and baseline age was -0.57% (CI: 0.7620, -0.3716) for natalizumab and -0.50% (-0.7208, -0.2831) for HC, but the difference between groups was not statistically significant (0.073%; p=0.62). Over the 2-year period, HC demonstrated mild improvements in some cognitive tests vs. natalizumab subjects. However, PROs were similar between the two groups.

CONCLUSION: Stable MS patients on natalizumab have similar brain volume loss as people who do not have MS, suggesting normalization of brain atrophy.

PMID:34364034 | DOI:10.1016/j.msard.2021.103170

Spectrochim Acta A Mol Biomol Spectrosc. 2021 Jul 29;264:120241. doi: 10.1016/j.saa.2021.120241. Online ahead of print.

ABSTRACT

A new approach to determine the local anesthetic benoxinate spectrofluorimetrically was developed. It was found that benoxinate exhibits strong native fluorescence in ethanol at 371 nm after excitation at 297 nm. There was a linear response between the fluorescence intensity and the concentration of the studied drug over the range of 10.0-100.0 ng/ mL. The suggested spectrofluorimetric method was optimized and validated following the pharmacopoeial guidelines. The obtained results were fully discussed and statistically analyzed in relevance to a previous published spectroscopic method. The limit of quantification (LOQ) of the present method was 1.79 ng/mL. Inter-day and intra-day precision relative standard deviations were lower than 1.5%.Finally, the proposed methodology has been adopted for determination of benoxinate in aqueous humor with a mean percentage recovery 99.87 ± 1.66 as well as in the pharmaceutical eye drops with a mean percentage recovery 100.37 ± 1.32. The method is cost-effective and green as it depends in water and ethanol mainly.

PMID:34364038 | DOI:10.1016/j.saa.2021.120241

Biol Psychiatry Cogn Neurosci Neuroimaging. 2021 Aug 4:S2451-9022(21)00204-4. doi: 10.1016/j.bpsc.2021.07.010. Online ahead of print.

ABSTRACT

BACKGROUND: Antidepressant efficacy in people with major depressive disorder (MDD) remains modest, yet identifying treatment predictive neurobiological markers may improve outcomes. While disruptions in functional connectivity within and between large-scale brain networks predict poorer treatment outcome, it is unclear whether higher trait neuroticism – which has been associated with generally poorer outcome – contributes to these disruptions and to antidepressant-specific treatment outcomes. Here, we used whole-brain functional connectivity analysis to identify a neural connectomic signature of neuroticism and tested whether this signature predicted antidepressant treatment outcome.

METHOD: Participants were 229 adults with MDD and 68 healthy controls who underwent functional MRI and were assessed on clinical features at baseline. MDD participants were then randomized to one of three commonly prescribed antidepressants and after 8 weeks completed a second functional MRI and were reassessed for depressive symptom remission/response. Baseline intrinsic functional connectivity between each pair of 436 brain regions were analysed using network-based statistics to identify connectomic features associated with neuroticism. Features were then assessed on their ability to predict treatment outcome and whether they changed after 8 weeks of treatment.

RESULTS: Higher baseline neuroticism was associated with greater connectivity within and between the salience, executive control, and somatomotor brain networks. Greater connectivity across these networks predicted poorer treatment outcome that was not mediated by baseline neuroticism, and connectivity strength decreased after antidepressant treatment.

CONCLUSIONS: Our findings demonstrate that neuroticism is associated with organization of intrinsic neural networks that predict treatment outcome, elucidating its biological underpinnings and opportunity for better treatment personalization.

PMID:34363999 | DOI:10.1016/j.bpsc.2021.07.010

Clin Neurol Neurosurg. 2021 Jul 31;208:106857. doi: 10.1016/j.clineuro.2021.106857. Online ahead of print.

ABSTRACT

OBJECTIVE: Daytime sleepiness is known to be related to stroke, but whether daytime sleepiness is a risk factor for stroke remains unclear. We conducted a two-sample Mendelian randomization study to assess the relationship between daytime sleepiness and stroke, ischemic stroke (IS) and IS subtypes.

METHODS: Thirty-six single-nucleotide polymorphisms (SNPs) associated with daytime sleepiness were selected as instrumental variables, which were identified from a recent genome-wide association study(N = 452,071). Summary statistics of the SNPs on stroke, IS and IS subtypes were derived from the MEGASTROKE consortium with 40,585 stroke cases and 406,111 controls.

RESULTS: We found that daytime sleepiness was associated with large artery stroke (OR, 6.75; 95%CI, 1.49-30.57; p = 0.013), but not with all stroke (OR, 1.29; 95%CI, 0.81-2.05; p = 0.282), all ischemic stroke(OR, 1.46; 95%CI, 0.90-2.39; p = 0.136), cardioembolic stroke(OR, 1.0; 95%CI, 0.39-2.64; p = 0.984), or small artery stroke(OR, 1.52; 95%CI, 0.46-5.05; p = 0.485).

CONCLUSION: Our findings indicated that daytime sleepiness is causally associated with an increased risk of large artery stroke. Further studies are necessary to verify our results and explain the physiological mechanisms.

PMID:34364029 | DOI:10.1016/j.clineuro.2021.106857

Ocul Surf. 2021 Aug 4:S1542-0124(21)00083-5. doi: 10.1016/j.jtos.2021.08.001. Online ahead of print.

ABSTRACT

PURPOSE: To analyze and review the clinical features and main outcomes of laminar resorption from the UK osteo-odonto-keratoprosthesis (OOKP) cohort.

METHODS: A retrospective review of case records was undertaken for patients who underwent keratoprostheses between 1996-2014 at the Sussex Eye Hospital, Brighton, UK. The main clinical outcomes of resorption, including its clinical signs, complications, treatments, and laminar survival, were evaluated.

RESULTS: Sixty-four patients (25-females, 39-males) were included, and in total, 74 laminae (3-tibial, 11-allografts, 60-autografts) were implanted. The age of the patients ranged from 20 to 91 years. Focal laminar thinning was the first sign of detectable resorption in 50% of autografts and 27% of allografts. All the tibial grafts and 55% of allografts presented with complications of resorption like endophthalmitis and aqueous leakage as the first signs of resorption. The survival of first implanted autografts was 82.4%(±6.3%) at 18 years, which was enhanced to 91.5%(±5.0%) by prophylactic exchanges of critically resorbed laminae with new laminae. Visual acuity survival analysis did not reveal a statistically significant difference between grafts with and without resorption for all graft types (p = 0.825). Patients treated with Alendronic acid and acetazolamide demonstrated trends toward the slower progression of resorption, but this was not statistically significant.

CONCLUSIONS: Focal laminar thinning was the common presenting feature of resorption in autografts. Timely replacement of the resorbed laminae with new laminae should be considered to avoid complications. Alendronic acid supplementation may be considered in high-risk cases of resorption to reduce further progression.

PMID:34363977 | DOI:10.1016/j.jtos.2021.08.001

Reprod Toxicol. 2021 Aug 4:S0890-6238(21)00120-9. doi: 10.1016/j.reprotox.2021.07.012. Online ahead of print.

ABSTRACT

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a man-made chemical compound contaminating the environment. An exposure of organisms to TCDD results in numerous disorders. The main mechanism of TCDD action involves the induction of the aryl hydrocarbon receptor (AhR) pathway followed by the increase in the expression and activity of cytochrome P450 family 1 (CYP1) enzymes. The main aim of the present study was to identify, by means of RNA sequencing, transcripts involved in the mechanism of TCDD action in Chinese hamster ovary (CHO) cells, known to not express CYP1A1 enzyme. The CHO cells were treated with TCDD for 3, 12 or 24 h, and total RNA was isolated and sequenced. Thirty six (padjusted < 0.05) or six (padjusted < 0.05, log2FC ≥ 1.0/log2FC≤-1.0) differentially expressed genes (DEGs) were identified in TCDD-treated cells depending on the assumed statistical criteria. The dioxin up- and downregulated the expression of genes associated with ovarian follicle functions, development, cardiovascular system, signal transduction, inflammation and carcinogenesis. TCDD did not affect the expression of any of 522 miRNAs which were identified in the cells. The expression of CYP1A1, CYP1A2 and CYP1B1 was demonstrated neither in control nor in TCDD-treated CHO cells, although the respective genes were found in the cell genome. Twenty two other CYP enzymes were identified in CHO cells, however their expression was also not affected by TCDD.

PMID:34363982 | DOI:10.1016/j.reprotox.2021.07.012

J Cosmet Dermatol. 2021 Aug 7. doi: 10.1111/jocd.14369. Online ahead of print.

ABSTRACT

BACKGROUND: Photodynamic therapy had made great progress in the treatment of acne vulgaris. However, there is no meta-analysis on the effectiveness and safety of red light therapy for acne vulgaris.

OBJECTIVE: To assess the efficiency and safety of red light therapy for acne vulgaris.

METHODS: PubMed, Cochrane Library, EMBASE, and Web of Science were retrieved to identify related studies. The outcomes were expressed as improvement in the average percentages of inflammatory acne lesions (MPRI) and non-inflammatory acne lesions (NMPRI), as well as the improvement of acne lesions respectively after treatment.

RESULTS: 13 randomized controlled trials (RCTs) consisting of 422 participants were included. There was no significant difference in the average number of non-inflammatory lesions (weighted mean difference (WMD = -0.527; 95% CI,-3.055~2.001; p = 0.683). Moreover, there was no statistically significant difference in the average number of inflammatory lesions (WMD =0.701; 95% CI, -0.809~2.212; p =0.363). In the subgroup analysis of the outcome changes in comedones, pustules, papules, and total lesions, it was found that red light therapy elicited no significant superiority compared with other conventional treatment methods (WMD = -1.125; 95% CI, -3.122~0.873; p = 0.270). Adverse events of the red light group were generally mild or even completely non-existent.

CONCLUSION: There was no statistically significant difference between red light therapy and traditional therapies in terms of efficacy. However, due to the heterogeneity of the researches and the lack of large sample size, the result of this study needs to be interpreted with caution.

PMID:34363730 | DOI:10.1111/jocd.14369

ACR Open Rheumatol. 2021 Aug 7. doi: 10.1002/acr2.11320. Online ahead of print.

ABSTRACT

OBJECTIVE: Hydroxychloroquine (HCQ) is commonly prescribed for the treatment of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other rheumatic diseases. To limit retinal toxicity, the 2016 American Academy of Ophthalmology (AAO) guidelines recommended limiting the HCQ dose to 5 mg/kg/day or less. Our objective was to develop a quality improvement program to improve adherence to these guidelines.

METHODS: We performed a retrospective analysis of 801 adult patients receiving HCQ for SLE and RA in a single academic rheumatology practice. In 2018, we calculated weight-based doses of HCQ at two time points at least 6 months apart. We surveyed provider opinions regarding the 2016 AAO guidelines and implemented a quality improvement intervention during which dosing data were shared with all prescribers (individually and in aggregate) and nurse-aided decision support was provided for HCQ refill requests. One year after the initial analysis and intervention, we again assessed weight-based doses of HCQ for the 674 patients still taking HCQ.

RESULTS: At both measured time points during 2018, 22.8% of patients received doses greater than 5 mg/kg/day. For 60% of those patients, the dose of HCQ was reduced to 5 mg/kg/day or less by the study end. Between the second time point in 2018 and the postintervention time point in 2019, there was a statistically significant increase in the proportion of patients receiving of dose of 5 mg/kg/day or less (from 74% to 87%; P < 0.0001).

CONCLUSION: We observed a significant increase in adherence with current AAO guidelines for weight-based HCQ dosing after providing feedback to providers regarding their prescribing data and reviewing weight-based dosing prior to refilling prescriptions.

PMID:34363746 | DOI:10.1002/acr2.11320

Int J Dermatol. 2021 Aug 7. doi: 10.1111/ijd.15672. Online ahead of print.

ABSTRACT

BACKGROUND: Cutaneous myiasis in patients with malignant wounds or skin cancer is a rare and undesirable event with limited epidemiological data. A subregister of reports, lack of education in the population, inadequate empirical treatments, and medical underestimation are components of a public health problem that threatens patients’ lives.

METHODS: We conducted a systematic review of the literature of cutaneous myiasis associated with malignant wounds and skin cancer, characterizing sociodemographic variables, risk factors, clinical and histological features, and treatment. Additionally, we present a demonstrative case with the adequate taxonomic evaluation.

DISCUSSION: Cutaneous myiasis is an underestimated and poorly managed infestation, which can generate severe complications in oncological patients. This is the first systematic review in the literature about this clinical scenario, which provides information to the physician and clinical researcher about the epidemiological gaps and what has been published so far.

CONCLUSIONS: Findings from the current review have helped to display the sociodemographic, epidemiological, and clinical behavior of myiasis in skin cancer and malignant wounds. Its contribution to the greater tumor tissue destruction is clear; however, more studies are required. The therapeutic management in these patients is equally clarified.

PMID:34363696 | DOI:10.1111/ijd.15672

Aust Endod J. 2021 Aug 7. doi: 10.1111/aej.12554. Online ahead of print.

ABSTRACT

This study aimed to evaluate the prevalence of oval-shaped root canals at the apical, medial and coronal cross sections of all tooth groups using CBCT and image analysis software. Based on the diameter values, the long/short diameter ratio was calculated and each root canal was classified regarding its shape. Oval-shaped canals were present in 45% at the apical, 50% at the medial and 56% at the coronal level of all teeth. The mandibular central incisors presented oval canals in 24%, long oval in 28% and flat in 2% at the apical level. Mandibular molars showed a statistically significant difference (P < 0.05) in the distribution of oval-shaped canals between cross-sectional levels. Analysis of CBCT scans with an image analysis software could be a reliable and reproducible method and a valuable tool for objective determination of root canal shape in further research.

PMID:34363716 | DOI:10.1111/aej.12554