Nevin Manimala

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

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

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

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

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

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

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

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

J Neuropathol Exp Neurol. 2021 Aug 7:nlab075. doi: 10.1093/jnen/nlab075. Online ahead of print.

ABSTRACT

Polymorphous low-grade neuroepithelial tumor of the young (PLNTY) is a recently described epileptogenic tumor characterized by oligodendroglioma-like components, aberrant CD34 expression, and frequent mitogen-activated protein kinase (MAPK) pathway activation. We molecularly profiled 13 cases with diagnostic histopathological features of PLNTY (10 female; median age, 16 years; range, 5-52). Patients frequently presented with seizures (9 of 12 with available history) and temporal lobe tumors (9 of 13). MAPK pathway activating alterations were identified in all 13 cases. Fusions were present in the 7 youngest patients: FGFR2-CTNNA3 (n = 2), FGFR2-KIAA1598 (FGFR2-SHTN1) (n = 1), FGFR2-INA (n = 1), FGFR2-MPRIP (n = 1), QKI-NTRK2 (n = 1), and KIAA1549-BRAF (n = 1). BRAF V600E mutation was present in 6 patients (17 years or older). Two fusion-positive cases additionally harbored TP53/RB1 abnormalities suggesting biallelic inactivation. Copy number changes predominantly involving whole chromosomes were observed in all 10 evaluated cases, with losses of chromosome 10q occurring with FGFR2-KIAA1598 (SHTN1)/CTNNA3 fusions. The KIAA1549-BRAF and QKI-NTRK2 fusions were associated respectively with a 7q34 deletion and 9q21 duplication. This study shows that despite its name, PLNTY also occurs in older adults, who frequently show BRAF V600E mutation. It also expands the spectrum of the MAPK pathway activating alterations associated with PLNTY and demonstrates recurrent chromosomal copy number changes consistent with chromosomal instability.

PMID:34363682 | DOI:10.1093/jnen/nlab075

J Burn Care Res. 2021 Aug 7:irab141. doi: 10.1093/jbcr/irab141. Online ahead of print.

ABSTRACT

BACKGROUND: Topical silver sulfadiazine (SSD) is an effective antimicrobial therapy used to prevent burn wound infection and promote healing, but the frequency of application has not been previously examined. This study compares once versus twice daily dressing changes with SSD, focusing on development of wound infections, incidence of hospital acquired complications, patient pain scores, and length of stay.

OBJECTIVE: To evaluate whether a once-daily or twice-daily application of SSD impacts burn wound healing outcomes.

METHODS: Our institution maintained a twice-daily dressing change standard of care until 01/01/2019. Patients admitted after that date had their dressing changed once-daily. We performed a non-inferiority analysis which indicated that a sample size of 75 per group would be sufficient to detect a significant difference with a power of 0.80. Our goal is to review outcomes for 75 patients before the change-of-practice and 75 patients after. Our main outcomes recorded are wound infection, average pain scores, average daily narcotic requirements, and length-of-stay.

RESULTS: Results from 75 pre-change-of-practice and 75 post-change-of-practice patients showed slightly better outcomes in the post-change-of-practice group. The wound-infection rates were the same for both groups (pre=5.33%, post=5.33%), average daily pain-levels for the pre-change group were slightly higher but the difference was negligible and not statistically significant (pre=5.27, post=5.25), hospital-related complication rates (unrelated to wound care) were higher pre-change (pre=10.67%, post=6.67%), and length-of-stay, was longer in the pre-change group (pre=11.97, post=10.31). The amount average amount of SSD (g/day) used per patient per hospital stay was higher as well (pre=320.14, post=202.12). Further statistical analysis of the results, particularly in the distribution of burn type, age, and burn depth showed no discrepancy and a generalized decreased length-of-stay with once-daily SSD dressing change.

CONCLUSION: Our results show that once-daily dressing changes of SSD in burn wounds have no negative impact on wound outcomes. However, it is associated with a decreased length-of-stay, decreased pain levels, and less hospital-acquired complications. A decreased length-of-stay means reduced medical expenses for the patient and the hospital. In addition, less hospital-acquired complications result in better patient recovery. Since the difference in wound outcomes is negligible and statistically insignificant, changing the standard-of-care to once-daily could prove beneficial.

PMID:34363678 | DOI:10.1093/jbcr/irab141