Nevin Manimala

Arch Orthop Trauma Surg. 2021 Jun 14. doi: 10.1007/s00402-021-03991-0. Online ahead of print.

ABSTRACT

INTRODUCTION: The risk factors for a second nonsimultaneous hip fracture are unclear, and in general, it is empirically assumed that they are similar to those associated with the first hip fracture. We aimed to determine the incidence of a second hip fracture and define the characteristics of the patients sustaining the event in a prospective cohort study in a Spanish population.

MATERIALS AND METHODS: We conducted a multicentric, prospective cohort study in a representative sample of 45 hospitals from 15 autonomic regions in Spain. In total, the study included 994 patients. One hundred and one patients presented a nonsimultaneous contralateral hip fracture, constituting the intervention group. The remaining 893 patients presenting with a hip fracture formed the control group. The main outcome measures of this study were sociodemographic characteristics of the patient, comorbid conditions, and baseline and postfracture clinical outcomes (inpatient complications and acute mortality).

RESULTS: The key fracture risk factors were a history of fragility fractures, the need for assistance when walking outdoors and a history of falls. There were no associations between the groups in any of the common fragility risk factors, including rheumatoid arthritis, secondary osteoporosis, or steroid consumption. The results showed that patients suffering a nonsimultaneous hip fracture had an increased risk of mortality after discharge compared with the control group.

CONCLUSION: A nonsimultaneous second hip fracture leads to a near-significant increase in four-month mortality. In our study, this fracture was associated with a history of falls, prior fragility fractures, and the need for a walking aid.

PMID:34125250 | DOI:10.1007/s00402-021-03991-0

Acta Neuropathol. 2021 Jun 14. doi: 10.1007/s00401-021-02325-z. Online ahead of print.

ABSTRACT

Heterozygous gain-of-kinase function variants in LRRK2 (leucine-rich repeat kinase 2) cause 1-2% of all cases of Parkinson’s disease (PD) albeit with incomplete and age-dependent penetrance. All pathogenic LRRK2 mutations reside within the two catalytic domains of LRRK2-either in its kinase domain (e.g. G2019S) with modest effect or its ROC-COR GTPase domain (e.g. R1441G/H) with large effect on LRRK2 kinase activity. We have previously reported assays to interrogate LRRK2 kinase pathway activity in human bio-samples measuring phosphorylation of its endogenous substrate Rab10, that mirrors LRRK2 kinase activation status. Here, we isolated neutrophils from fresh peripheral blood from 101 participants including 42 LRRK2 mutation carriers (21 with the G2019S and 21 with the R1441G mutations), 27 patients with idiopathic PD, and 32 controls. Using a dual approach, LRRK2 dependent Rab10 phosphorylation at Threonine 73 (pRab10^Thr73) was measured by quantitative multiplexed immunoblotting for pRab10^Thr73/total Rab10 as well as targeted mass-spectrometry for absolute pRab10^Thr73 occupancy. We found a significant over fourfold increase in pRab10^Thr73 phosphorylation in carriers of the LRRK2 R1441G mutation irrespective of clinical disease status. The effect of the LRRK2 G2019S mutation did not reach statistical significance. Furthermore, we show that LRRK2 phosphorylation at Serine 935 is not a marker for LRRK2 kinase activity in human neutrophils. When analysing pRab10^Thr73 phosphorylation in post-mortem brain samples, we observed overall high variability irrespective of clinical and LRRK2 mutation status and attributed this mainly to the adverse effect of the peri- and post-mortem period on the stability of posttranslational modifications such as protein phosphorylation. Overall, in vivo LRRK2 dependent pRab10^Thr73 phosphorylation in human peripheral blood neutrophils is a specific, robust and promising biomarker for significant LRRK2 kinase hyperactivation, as with the LRRK2 R1441G mutation. Additional readouts and/or assays may be needed to increase sensitivity to detect modest LRRK2 kinase activation, as with the LRRK2 G2019S mutation. Our assays could be useful for patient stratification and target engagement studies for LRRK2 kinase inhibitors.

PMID:34125248 | DOI:10.1007/s00401-021-02325-z

HNO. 2021 Jun 14. doi: 10.1007/s00106-021-01066-5. Online ahead of print.

ABSTRACT

BACKGROUND: Endoscopic ear surgery (EES) is increasingly used internationally instead of microscopic ear surgery (MES), but has not yet become established as a routine procedure everywhere in Germany.

OBJECTIVE: The incision-suture time and practicability of EES in the setting of a German clinic were investigated.

MATERIALS AND METHODS: In a retrospective study, 60 consecutive MES patients from 2015 were compared with 60 consecutive EES patients from 2018. Hearing results, tympanic membrane findings after 3 weeks, and incision-suture times were compared.

RESULTS: In EES, access was mostly transmeatal and bone of the anterior auditory canal wall had to be removed less often than in MES. There was no statistically significant difference in surgery times between the two groups. Perforation closure was achieved in 57/60 and 59/60 ears in the MES and EES groups, respectively. Hearing was improved in both groups. There was no statistical difference in hearing improvement between the two groups.

CONCLUSION: EES is a time efficient and minimally invasive method which represents a viable alternative to MES with comparable results.

PMID:34125238 | DOI:10.1007/s00106-021-01066-5

HNO. 2021 Jun 14. doi: 10.1007/s00106-021-01063-8. Online ahead of print.

ABSTRACT

BACKGROUND: Perpendicular vascular changes (PVC) are markers of tumor-induced neoangiogenesis at the vocal folds. Contact endoscopy with narrow-band imaging (CE-NBI) allows a detailed analysis of such vascular changes.

OBJECTIVE: This work intends to evaluate the potential of CE-NBI for diagnosis of benign, dysplastic, and malignant lesions of the vocal folds. In addition, it should be determined whether CE-NBI offers an additional benefit in detecting PVC compared to white-light endoscopy (WLE) and NBI alone.

MATERIALS AND METHODS: Three examiners evaluated histologically verified cases of benign, dysplastic, and malignant lesions of the larynx in WLE, NBI, and CE-NBI (n = 60). In each mode, they examined the lesion for PVC and assessed the lesion’s dignity. The proportion of lesions with detected PVC, the statistical measures of performance in detecting high-grade dysplasia and carcinoma, and the interrater variability for each mode were calculated.

RESULTS: CE-NBI proved superior to the other investigated diagnostic methods in terms of detecting PVC and in terms of sensitivity and accuracy in the diagnosis of high-grade dysplasia and carcinoma. A clear association of such pathologies with PVC was seen.

CONCLUSION: CE-NBI detects PVC more frequently and reliably than the other methods investigated. The association of these vascular patterns to high-grade dysplasia and vocal fold carcinomas could be confirmed. Compared to WLE and NBI endoscopy, the diagnostic quality for detecting high-grade dysplasia and carcinoma is increased. Thus, CE-NBI can improve endoscopic differentiation between benign and malignant lesions of the vocal folds by enhancing the detection of PVC.

PMID:34125236 | DOI:10.1007/s00106-021-01063-8

Infect Agent Cancer. 2021 Jun 13;16(1):42. doi: 10.1186/s13027-021-00382-3.

ABSTRACT

BACKGROUND: Epigenetic mechanisms are hypothesized to contribute substantially to the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer, although empirical data are limited.

METHODS: Women (n = 419) were enrolled at colposcopic evaluation at Duke Medical Center in Durham, North Carolina. Human papillomavirus (HPV) was genotyped by HPV linear array and CIN grade was ascertained by biopsy pathologic review. DNA methylation was measured at differentially methylated regions (DMRs) regulating genomic imprinting of the IGF2/H19, IGF2AS, MESTIT1/MEST, MEG3, PLAGL1/HYMAI, KvDMR and PEG10, PEG3 imprinted domains, using Sequenom-EpiTYPER assays. Logistic regression models were used to evaluate the associations between HPV infection, DMR methylation and CIN risk overall and by race.

RESULTS: Of the 419 participants, 20 had CIN3+, 52 had CIN2, and 347 had ≤ CIN1 (CIN1 and negative histology). The median participant age was 28.6 (IQR:11.6) and 40% were African American. Overall, we found no statistically significant association between altered methylation in selected DMRs and CIN2+ compared to ≤CIN1. Similarly, there was no significant association between DMR methylation and CIN3+ compared to ≤CIN2. Restricting the outcome to CIN2+ cases that were HR-HPV positive and p16 staining positive, we found a significant association with PEG3 DMR methylation (OR: 1.56 95% CI: 1.03-2.36).

CONCLUSIONS: While the small number of high-grade CIN cases limit inferences, our findings suggest an association between altered DNA methylation at regulatory regions of PEG3 and high grade CIN in high-risk HPV positive cases.

PMID:34120615 | DOI:10.1186/s13027-021-00382-3

BMC Med Educ. 2021 Jun 13;21(1):342. doi: 10.1186/s12909-021-02759-9.

ABSTRACT

BACKGROUND: Assessment is a necessary part of training postgraduate medical residents. The implementation of methods located at the “shows how” level of Miller’s pyramid is believed to be more effective than previous conventional tools. In this study, we quantitatively compared electronic and conventional methods in assessing ophthalmology residents.

METHODS: In this retrospective study, eight different conventional methods of assessment including residents’ attendance, logbook, scholarship and research skills, journal club, outpatient department participation, Multiple Choice Question (MCQ), Objective Structured Clinical Examination (OSCE), and professionalism/360-degree (as one complex) were used to assess 24 ophthalmology residents of all grades. Electronic media consisting of an online Patient Management Problem (e-PMP), and modified electronic OSCE (me-OSCE) tests performed 3 weeks later were also evaluated for each of the 24 residents. Quantitative analysis was then performed comparing the conventional and electronic assessment tools, statistically assessing the correlation between the two approaches.

RESULTS: Twenty-four ophthalmology residents of different grades were included in this study. In the electronic assessment, average e-PMP scores (48.01 ± 12.40) were much lower than me-OSCE (65.34 ± 17.11). The total average electronic score was 56.67 ± 11.28, while the total average conventional score was 80.74 ± 5.99. Female and male residents’ average scores in the electronic and conventional method were (59.15 ± 12.32 versus 83.01 ± 4.95) and (55.19 ± 10.77 versus 79.38 ± 6.29), respectively. The correlation between modified electronic OSCE and all conventional methods was not statistically significant (P-value >0.05). Correlation between e-PMP and six conventional methods, consisting of professionalism/360-degree assessment tool, logbook, research skills, Multiple Choice Questions, Outpatient department participation, and Journal club active participation was statistically significant (P-value < 0.05). The overall correlation between conventional and electronic methods was significant (P-value = 0.017).

CONCLUSION: In this study, we conclude that electronic PMP can be used alongside all conventional tools, and overall, e-assessment methods could replace currently used conventional methods. Combined electronic PMP and me-OSCE can be used as a replacement for currently used gold-standard assessment methods, including 360-degree assessment.

PMID:34120607 | DOI:10.1186/s12909-021-02759-9

BMC Public Health. 2021 Jun 14;21(1):1135. doi: 10.1186/s12889-021-11154-4.

ABSTRACT

BACKGROUND: Antenatal care (ANC) played a crucial role in ensuring maternal and child safety and reducing the risk of complications, disability, and death in mothers and their infants. The objective of this study was to evaluate the current status of ANC emphasizing the number, timing, and content of examinations on a national scale.

METHODS: The data was collected from maternal and newborn’s health monitoring system at 8 provinces in China. After ethical approval, all pregnant women registered in the system at their first prenatal care visit, we included 49,084 pregnant women who had delivered between January 1, 2018 and December 31, 2018. Descriptive statistics of all study variables were calculated proportions and chi-square for categorical variables.

RESULTS: Of the 49,084 women included in this study, the mean number of ANC visits was 6.95 ± 3.45. By percentage, 78.79% women received ANC examinations at least five times, 39.93% of the women received ANC examinations at least eight times and 16.66% of the women received ANC examinations at least 11 times. The proportion of first ANC examination in first trimester was 61.87%. The percentage of normative ANC examinations and the percentage of qualified ANC examinations were 30.98 and 8.03% respectively. Only 49.40% of the total women received all six kinds of examination items in first ANC examination: 91.47% received a blood test, 91.62% received a urine test, 81.56% received a liver function examination, 80.52% received a renal function examination, 79.07% received a blood glucose test, and 86.66% received a HIV/HBV/syphilis tests. 50.85% women received the first ANC examination in maternal and child health care (MCH) institutions, 14.07% in a general hospital, 18.83% in a township hospital, 13.15% in a community health services center, and 3.08% in an unspecified place. The proportion of women who received each of the ANC examination items in community health services center was the highest, but that in the MCH institutions was the lowest.

CONCLUSIONS: There is a big difference between the results of this study and the data in official reports, this study found the current status of antenatal care is not optimal in China, findings from this study suggest that the systematization, continuity and quality of ANC examinations need to be improved.

PMID:34120600 | DOI:10.1186/s12889-021-11154-4

BMC Public Health. 2021 Jun 14;21(1):1136. doi: 10.1186/s12889-021-11155-3.

ABSTRACT

BACKGROUND: Nepal recorded 5754 suicides in 2018-19 – a high number for a relatively small country. Over 24% of these suicides were by poisoning, most by ingestion of highly concentrated agricultural pesticides. Nepal has actively regulated pesticides to reduce their health impacts since 2001. We aimed to analyse Nepal’s history of pesticide regulation, pesticides responsible for poisonings, and relate them to national suicide rates.

METHODS: Information on pesticide regulation was collected from the Plant Quarantine and Pesticide Management Centre of the Ministry of Agriculture and Livestock Development. National data on suicides from 1980 to 2019 were obtained from the National Statistical Bureau and Nepal Police. Data on the pesticides responsible for self-poisoning and pesticide suicides over time were obtained from a systematic literature review.

RESULTS: As of June 2020, 171 pesticides were registered for use in Nepal, of which one was extremely hazardous (WHO Class Ia), one other highly hazardous (WHO Class Ib), and 71 moderately hazardous (WHO Class II). Twenty-four pesticides have been banned since 2001, with eight (including five WHO Class I compounds) banned in 2019. Although the suicide rate has increased more than twelve-fold since 1980, particularly for hanging (15-fold increase from 1980 to 2018), fatal pesticide self-poisoning has increased by 13-fold. Methyl-parathion is reported to be the key pesticide responsible for pesticide self-poisoning in Nepal, despite being banned in 2006.

CONCLUSION: The full effect of the recent pesticide policy reform in Nepal remains to be seen. Our analysis shows a continuing increase in suicide numbers, despite bans of the most important pesticide in 2006. This may indicate smuggling across the border and the use of the brand name (Metacid) for pesticides in general making it difficult to identify the responsible pesticide. More information is required from forensic toxicology labs that identify the individual compounds found. The effect of recent bans of common suicide pesticides needs to be monitored over the coming years. Evidence from other Asian countries suggests that HHPs bans will lead to a marked reduction in suicides, as well as fewer cases of occupational poisoning.

PMID:34120596 | DOI:10.1186/s12889-021-11155-3

BMC Bioinformatics. 2021 Jun 13;22(1):322. doi: 10.1186/s12859-021-04240-2.

ABSTRACT

BACKGROUND: Assessing the nucleosome-forming potential of specific DNA sequences is important for understanding complex chromatin organization. Methods for predicting nucleosome positioning include bioinformatics and biophysical approaches. An advantage of bioinformatics methods, which are based on in vivo nucleosome maps, is the use of natural sequences that may contain previously unknown elements involved in nucleosome positioning in vivo. The accuracy of such prediction attempts reflects the genomic coordinate resolution of the nucleosome maps applied. Nucleosome maps are constructed using micrococcal nuclease digestion followed by high-throughput sequencing (MNase-seq). However, as MNase has a strong preference for A/T-rich sequences, MNase-seq may not be appropriate for this purpose. In addition to MNase-seq-based maps, base pair-resolution chemical maps of in vivo nucleosomes from three different species (budding and fission yeasts, and mice) are currently available. However, these chemical maps have yet to be integrated into publicly available computational methods.

RESULTS: We developed a Bioconductor package (named nuCpos) to demonstrate the superiority of chemical maps in predicting nucleosome positioning. The accuracy of chemical map-based prediction in rotational settings was higher than that of the previously developed MNase-seq-based approach. With our method, predicted nucleosome occupancy reasonably matched in vivo observations and was not affected by A/T nucleotide frequency. Effects of genetic alterations on nucleosome positioning that had been observed in living yeast cells could also be predicted. nuCpos calculates individual histone binding affinity (HBA) scores for given 147-bp sequences to examine their suitability for nucleosome formation. We also established local HBA as a new parameter to predict nucleosome formation, which was calculated for 13 overlapping nucleosomal DNA subsequences. HBA and local HBA scores for various sequences agreed well with previous in vitro and in vivo studies. Furthermore, our results suggest that nucleosomal subsegments that are disfavored in different rotational settings contribute to the defined positioning of nucleosomes.

CONCLUSIONS: Our results demonstrate that chemical map-based statistical models are beneficial for studying nucleosomal DNA features. Studies employing nuCpos software can enhance understanding of chromatin regulation and the interpretation of genetic alterations and facilitate the design of artificial sequences.

PMID:34120589 | DOI:10.1186/s12859-021-04240-2

Virulence. 2021 Dec;12(1):1527-1537. doi: 10.1080/21505594.2021.1936769.

ABSTRACT

We prospectively investigated the neurological development in infants born from mothers treated with telbivudine (LdT) in the third trimester for prevention of hepatitis B virus (HBV) mother-to-infant transmission. Mothers with high HBV load were assigned to either the LdT group (n = 81, 600 mg of LdT each day from gestational week 28 to delivery) or the Control group (n = 39, untreated). Their infants were followed for 36 months to assess physical and neurological developments with Gesell Developmental Schedule tools. At 12 months after birth, the mean scores in the LdT group for gross motor, fine motor, adaptive, linguistic, and personal social domains were similar to those in the Control group. At 36 months, infants in the LdT group had higher mean scores for gross motor than the Control group (98.42 ± 9.69 vs. 94.54 ± 7.48, P = 0.03). In the LdT group, the rates of normal development were higher for gross motor (96.30% vs. 82.05% P = 0.01) and lower for adaptive (74.07% vs. 92.31% P = 0.02). Multivariate regression analyses showed that exposure to LdT during pregnancy was independently associated with infant’s development in gross motor (OR 6.49, 95% CI 1.37-30.20, P = 0.02) and adaptive (OR 0.18, 95% CI 0.05-0.71, P = 0.01) at 36 months. These results suggest that prenatal LdT exposure might affect neurological development in long-term observation.Abbreviations: LdT: telbivudine; HBV: hepatitis B virus; HBsAg: hepatitis B surface antigen; HBeAg: hepatitis Be antigen; HbsAb: hepatitis B surface antibody; ALT: alanine aminotransferase; NA: nucleoside/nucleotide analog; LAM: lamivudine; MTCT: mother-to-child transmission; GDS: Gesell Developmental Schedule; OR: odds ratio; CI: confidence interval; DQ: developmental quotient; RMB: renminbi; BMI: body mass Index; HBIG: hepatitis B immunoglobulin.

PMID:34120564 | DOI:10.1080/21505594.2021.1936769