Category: Nevin Manimala

Genetics. 2023 Jun 22:iyad115. doi: 10.1093/genetics/iyad115. Online ahead of print.

ABSTRACT

Exonic variants present some of the strongest links between genotype and phenotype. However, these variants can have significant inter-individual pathogenicity differences, known as variable penetrance. In this study, we propose a model where genetically controlled mRNA splicing modulates the pathogenicity of exonic variants. By first cataloging exonic inclusion from RNA-seq data in GTEx v8, we find that pathogenic alleles are depleted on highly included exons. Using a large-scale phased WGS data from the TOPMed consortium, we observe that this effect may be driven by common splice-regulatory genetic variants, and that natural selection acts on haplotype configurations that reduce the transcript inclusion of putatively pathogenic variants, especially when limiting to haploinsufficient genes. Finally, we test if this effect may be relevant for autism risk using families from the Simons Simplex Collection, but find that splicing of pathogenic alleles has a penetrance reducing effect here as well. Overall, our results indicate that common splice-regulatory variants may play a role in reducing the damaging effects of rare exonic variants.

PMID:37348055 | DOI:10.1093/genetics/iyad115

Mod Rheumatol. 2023 Jun 22:road061. doi: 10.1093/mr/road061. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate the impact of obesity on the treatment response to secukinumab and drug survival rate in patients with ankylosing spondylitis (AS).

METHODS: We performed an observational cohort study that included AS patients based on the TURKBIO Registry between 2018 and 2021. The patients were divided into three groups normal (BMI<25 kg/m²), overweight (BMI:25-30 kg/m²), and obese (BMI≥30 kg/m²). Disease activity was evaluated at baseline, three, six, and 12 months. Drug retention rates at 12 months were also investigated.

RESULTS: There were 166 AS patients using secukinumab (56.6 % male, mean age: 44.9 ± 11.6 years). The median follow-up time was 17.2 (3-33.2) months. Forty-eight (28.9%) patients were obese. The mean age was higher in the obese group than in others (p=0.003). There was no statistically significant difference in BASDAI50, ASAS20, ASAS40, ASDAS low disease activity, and ASDAS-CII (clinically important improvement) responses between the three groups at three, six, and 12 months, although they were numerically lower in obese patients. Drug retention rates at 12 months were similar in all groups (p>0.05).

CONCLUSIONS: This study suggested that obesity did not affect secukinumab treatment response and drug retention in AS patients.

PMID:37348053 | DOI:10.1093/mr/road061

J Anim Sci. 2023 Jun 22:skad212. doi: 10.1093/jas/skad212. Online ahead of print.

ABSTRACT

Ocimum gratissimum (OG) was found to have immunity boosting effect on Taiwan country chickens and broiler chickens raised in moderate ambient temperature in previous studies, and the current study investigates its potential on the growth performance, blood traits, intestinal traits, and immune responses in Ross 308 broilers raised in high ambient temperature which can induce mild heat-stress (26-33˚C, average 30˚C). Two hundred one day-old male/female chicks were randomly assigned to a control group, three OG (1 g/kg, 3 g/kg, and 5 g/kg)/basal diet groups, and one Amoxicillin group. Data collected during the experiment indicated that the weight gain increase of 1742 g/bird to 1815 g/bird comparing control to 5 g/kg OG supplementation was statistically significant. In addition, the production efficiency factor (PEF) was also noticeably increased by OG, particularly in the 5 g/kg group, and the uric acid levels were decreased in the 3 g/kg and 5 g/kg OG groups (from 4.26 mg/dL to 2.91 mg/dL and 2.90 mg/dL, respectively), indicating heat-stress alleviation was observed. Several areas of the carcass saw desirable growth changes, including the increase of breast muscle ratio observed in the 5 g/kg OG group, an overall decrease in abdominal fat in all OG groups, as well as dimensional changes in several areas of the digestive system. Lastly, the hemaglutination, hemaglutination inhibition, and phytohemaglutinin tests indicated elevated immuno-response in all OG groups. In conclusion, OG has exhibited the ability to alleviate symptoms of mild heat-stress, leading to improvement of the digestive organ development and increase of carcass mass and mean weight gain for birds, and we find OG to be a potentially beneficial feed supplement for poultry raising in high-ambient temperature conditions.

PMID:37348050 | DOI:10.1093/jas/skad212

JCO Glob Oncol. 2023 Jun;9:e2200445. doi: 10.1200/GO.22.00445.

ABSTRACT

PURPOSE: The aim of this study was to document the available resources and needs for the detection, diagnosis, and treatment of retinoblastoma (RB) in Ethiopia.

METHODS: A health services needs assessment focused on RB care in Ethiopia was conducted. Information was obtained through a web-based survey and field visits. Facilities offering RB service delivery were categorized into three tiers, on the basis of the ability to detect (tier 1) and manage simple (tier 2) or complex (tier 3) patients with RB. Descriptive statistics were performed to quantify human and material resources available at each facility.

RESULTS: The web survey received 29 responses from ophthalmologists at 19 health care facilities. Of the 19 units surveyed, seven (36.8%) had an ophthalmologist dedicated to RB treatment, classifying them as either a tier 2 or 3 facility. All tier 3 facilities had an affiliated health facility offering access to off-site pediatric oncology and pathology services. Of the focal therapies offered at tier 3 facilities, none included local chemotherapy or brachytherapy. Enucleation was offered at all tier 2 facilities, but availability of orbital implants and ocular prostheses was variable. None of the health facilities offered genetics services.

CONCLUSION: This study demonstrated that the human and material resources needed for RB care in Ethiopia are constrained. Tier 3 RB facilities are rare and concentrated in urban areas, which could make it difficult for many patients to access. With focused capacity-building efforts, it is possible to increase the efficiency of RB therapy.

PMID:37348044 | DOI:10.1200/GO.22.00445

J Orthop Trauma. 2023 Jun 21. doi: 10.1097/BOT.0000000000002655. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine if there is a threshold of elevated HbA1c above which the complication risk is so high that fracture fixation should be avoided.

DESIGN: Retrospective cohort study.

SETTING: Academic, level I trauma center, 2008-2018.

PATIENTS/PARTICIPANTS: A cohort of 187 patients with Hgb A1c values >7 and operatively treated extremity fractures.

INTERVENTION: Surgical fixation of extremity fractures.

MAIN OUTCOME MEASUREMENTS: Rate of major orthopedic complication (loss of reduction, nonunion, infection, and need for salvage procedure).

RESULTS: 34.8% demonstrated HgA1c >9 and 12.3% with HgA1c>11. Major complications occurred in 31.4%; HgA1c values were not predictive. We found no evidence of a clinically or statistically significant relationship between HbA1c and risk of major complication. The odds ratio for a one-point increase in HbA1c was 1.006 (p=0.9439), and the area under the receiver operating characteristic curve (AUC), which reflects the average probability that someone with a major complication will have a higher HbA1c than someone without, was 0.51 (95% CI 0.42 – 0.61), equivalent to random chance.

CONCLUSION: Diabetic fracture patients demonstrated an extremely high overall rate of complications, with 30.5% experiencing a major complication. However, patients with extreme diabetic neglect did not have higher complication rates after extremity fracture fixation when compared to patients with controlled and uncontrolled diabetes. There was no correlation between rate of complication and level of HbA1c. In addition, there was no difference in complication rate between upper and lower extremity fractures, or between fractures treated with open or percutaneous fixation. This suggests that fracture treatment decision-making should not be altered for patients with poor diabetic control, and that surgery is not contraindicated in patients with an extremely high HbA1c.

LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

PMID:37348040 | DOI:10.1097/BOT.0000000000002655

J Neurosci Nurs. 2023 Jun 20. doi: 10.1097/JNN.0000000000000712. Online ahead of print.

ABSTRACT

BACKGROUND: Parkinson disease (PD), a neurodegenerative disease characterized by motor and nonmotor symptoms, can affect the daily activities of individuals. This study was conducted to determine nonmotor symptom burden in patients with PD and to reveal the relationship of nonmotor symptom burden with activities of daily living and fear of falling. METHODS: This cross-sectional and correlational study was carried out with 309 patients given a diagnosis of PD. The data were collected using a personal information form, the Non-Motor Symptoms Scale, the Katz Activities of Daily Living Scale, and the Fear of Falling Questionnaire. RESULTS: Whereas 70.2% of the patients had very high nonmotor symptom severity levels, 33.7% were semidependent or dependent in terms of performing their activities of daily living. The fear of falling was experienced by 32.7% of the patients. A statistically significant inverse relationship was found between the mean Non-Motor Symptoms Scale scores of the patients and their mean Katz Activities of Daily Living Scale and Fear of Falling Questionnaire scores (P < .05). Nonmotor symptom burden independently explained 66% of the total variance in the performance of activities of daily living and 69% of the total variance in fear of falling (P < .01). CONCLUSION: Nonmotor symptom burden in PD patients is a significant determinant for participation in activities of daily living and fear of falling. Nurses should approach patients with PD with a focus not only on assessing motor symptoms but also on assessing nonmotor symptoms.

PMID:37348005 | DOI:10.1097/JNN.0000000000000712

Int J Inj Contr Saf Promot. 2023 Jun 22:1-14. doi: 10.1080/17457300.2023.2225168. Online ahead of print.

ABSTRACT

The number of deaths due to road accident is increasing day by day and has become an alarming global problem over the decades. India, with her rising motorization is no stranger to this global catastrophe. In this paper two relatively simple yet powerful and versatile techniques for forecasting time series data, autoregressive integrated moving average method (ARIMA) and exponential smoothing method are used to forecast the number of deaths due to road accidents in India from the year 2022-2031. The results based on the two methods are compared and it is found that they are in sync with each other and pre-existing literature. Furthermore, this is a unique attempt to use two time series analysis techniques on the same data and carry out a comparative analysis. The data was collected from the annual report of Ministry of Road Transport and Highways, India (2020) and Accidental Deaths & Suicides in India (ADSI) Report of National Crime Record Bureau (2021). After examining all the probable models, it is observed that ARIMA (2, 2, 2) model and exponential smoothing (M, A, N) model are suitable for the given data. Amongst the two, ARIMA (2, 2, 2) model has a lower AIC and BIC value. Thus, this comes out to be the best model as per our model selection criterion. Further, the study also reveals an upward trend of number of road accidental deaths for the upcoming 10 years in India.

PMID:37348002 | DOI:10.1080/17457300.2023.2225168

Int J Periodontics Restorative Dent. 2023 Jun 22. doi: 10.11607/prd.6406. Online ahead of print.

ABSTRACT

This study aimed to clinically evaluate the efficacy of two different home whitening protocols and to determine which is more effective: applying the whitening gel every 24 hours or every 48 hours for 2 weeks. The differences in terms of tooth sensitivity are also analyzed. A sample of 60 patients was divided into three groups of 20 (N=20). Group A: 16% carbamide peroxide applied every 24h for 2 weeks. Group B: 16% carbamide peroxide applied every 48h for 2 weeks. Group C (control group): a placebo gel without peroxide (glycerin gel) was applied every 24h for 2 weeks. To compare the groups, color measurements were made using a spectrophotometer and Student’s t-test for independent samples was used. The confidence level was set at 95% (p ≤ 0.05) and no statistically significant differences between applying 16% carbamide peroxide every 24h or every 48h for 2 weeks (p> 0.05) were found. The study concluded that carbamide peroxide 16% is equally effective applied with both protocols, obtaining the same results, but the application of every other day protocol produces less sensitivity than the daily application protocol.

PMID:37347995 | DOI:10.11607/prd.6406

Science. 2023 Jun 23;380(6651):1222-1223. doi: 10.1126/science.adi0248. Epub 2023 Jun 22.

ABSTRACT

Models can convey biases and false information to users.

PMID:37347992 | DOI:10.1126/science.adi0248

Otolaryngol Pol. 2023 Jan 14;77(2):24-29. doi: 10.5604/01.3001.0016.2167.

ABSTRACT

&lt;br&gt;&lt;b&gt;Introduction:&lt;/b&gt; Injury of the external branch of the superior laryngeal nerve can cause a hoarse or weak voice due to the functional loss (dysergia) of the cricothyroid muscle. Defining the anatomical variations of the external branch of the superior laryngeal nerve and estimating their frequency are crucial for surgical interventions.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Aim:&lt;/b&gt; To reveal the topography of the external branch in the Anatolian population, to prevent injury of it during the surgical intervention in the anterior neck region.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Material and methods:&lt;/b&gt; 26 bilateral hemilarynges (4 females, 22 males) were dissected. The morphometric and morphological features of the external branch were examined. The obtained results were compared statistically, left and right.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Results:&lt;/b&gt; Landmarks such as the thyroid gland and laryngeal prominence were determined for the detection of the external branch. The variations of the course of the external branch and the points of piercing the cricothyroid muscle or inferior pharyngeal constrictor muscle were evaluated.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Discussion:&lt;/b&gt; Although safe approaches have been described for nerve protection during neck surgeries, injuries may occur during preliminary surgery as the mentioned nerve is thinner and more superficial than other branches of the vagus nerve. However, it can be detected more easily and safely by knowing the defined anatomical landmarks and morphological variations of the external branch.&lt;/br&gt; &lt;br&gt;&lt;b&gt;Conclusion:&lt;/b&gt; The anatomical variations described can be a safe and important guide in surgeries of the anterior neck region.&lt;/br&gt.

PMID:37347976 | DOI:10.5604/01.3001.0016.2167