Category: Nevin Manimala

JAMA Psychiatry. 2023 Apr 19. doi: 10.1001/jamapsychiatry.2023.0685. Online ahead of print.

ABSTRACT

IMPORTANCE: Metabolomics reflect the net effect of genetic and environmental influences and thus provide a comprehensive approach to evaluating the pathogenesis of complex diseases, such as depression.

OBJECTIVE: To identify the metabolic signatures of major depressive disorder (MDD), elucidate the direction of associations using mendelian randomization, and evaluate the interplay of the human gut microbiome and metabolome in the development of MDD.

DESIGN, SETTING AND PARTICIPANTS: This cohort study used data from participants in the UK Biobank cohort (n = 500 000; aged 37 to 73 years; recruited from 2006 to 2010) whose blood was profiled for metabolomics. Replication was sought in the PREDICT and BBMRI-NL studies. Publicly available summary statistics from a 2019 genome-wide association study of depression were used for the mendelian randomization (individuals with MDD = 59 851; control individuals = 113 154). Summary statistics for the metabolites were obtained from OpenGWAS in MRbase (n = 118 000). To evaluate the interplay of the metabolome and the gut microbiome in the pathogenesis of depression, metabolic signatures of the gut microbiome were obtained from a 2019 study performed in Dutch cohorts. Data were analyzed from March to December 2021.

MAIN OUTCOMES AND MEASURES: Outcomes were lifetime and recurrent MDD, with 249 metabolites profiled with nuclear magnetic resonance spectroscopy with the Nightingale platform.

RESULTS: The study included 6811 individuals with lifetime MDD compared with 51 446 control individuals and 4370 individuals with recurrent MDD compared with 62 508 control individuals. Individuals with lifetime MDD were younger (median [IQR] age, 56 [49-62] years vs 58 [51-64] years) and more often female (4447 [65%] vs 2364 [35%]) than control individuals. Metabolic signatures of MDD consisted of 124 metabolites spanning the energy and lipid metabolism pathways. Novel findings included 49 metabolites, including those involved in the tricarboxylic acid cycle (ie, citrate and pyruvate). Citrate was significantly decreased (β [SE], -0.07 [0.02]; FDR = 4 × 10-04) and pyruvate was significantly increased (β [SE], 0.04 [0.02]; FDR = 0.02) in individuals with MDD. Changes observed in these metabolites, particularly lipoproteins, were consistent with the differential composition of gut microbiota belonging to the order Clostridiales and the phyla Proteobacteria/Pseudomonadota and Bacteroidetes/Bacteroidota. Mendelian randomization suggested that fatty acids and intermediate and very large density lipoproteins changed in association with the disease process but high-density lipoproteins and the metabolites in the tricarboxylic acid cycle did not.

CONCLUSIONS AND RELEVANCE: The study findings showed that energy metabolism was disturbed in individuals with MDD and that the interplay of the gut microbiome and blood metabolome may play a role in lipid metabolism in individuals with MDD.

PMID:37074710 | DOI:10.1001/jamapsychiatry.2023.0685

JAMA Psychiatry. 2023 Apr 19. doi: 10.1001/jamapsychiatry.2023.0716. Online ahead of print.

ABSTRACT

IMPORTANCE: Cognitive impairment in depression is poorly understood. Family history of depression is a potentially useful risk marker for cognitive impairment, facilitating early identification and targeted intervention in those at highest risk, even if they do not themselves have depression. Several research cohorts have emerged recently that enable findings to be compared according to varying depths of family history phenotyping, in some cases also with genetic data, across the life span.

OBJECTIVE: To investigate associations between familial risk of depression and cognitive performance in 4 independent cohorts with varied depth of assessment, using both family history and genetic risk measures.

DESIGN, SETTING, AND PARTICIPANTS: This study used data from the Three Generations at High and Low Risk of Depression Followed Longitudinally (TGS) family study (data collected from 1982 to 2015) and 3 large population cohorts, including the Adolescent Brain Cognitive Development (ABCD) study (data collected from 2016 to 2021), National Longitudinal Study of Adolescent to Adult Health (Add Health; data collected from 1994 to 2018), and UK Biobank (data collected from 2006 to 2022). Children and adults with or without familial risk of depression were included. Cross-sectional analyses were conducted from March to June 2022.

EXPOSURES: Family history (across 1 or 2 prior generations) and polygenic risk of depression.

MAIN OUTCOMES AND MEASURES: Neurocognitive tests at follow-up. Regression models were adjusted for confounders and corrected for multiple comparisons.

RESULTS: A total of 57 308 participants were studied, including 87 from TGS (42 [48%] female; mean [SD] age, 19.7 [6.6] years), 10 258 from ABCD (4899 [48%] female; mean [SD] age, 12.0 [0.7] years), 1064 from Add Health (584 [49%] female; mean [SD] age, 37.8 [1.9] years), and 45 899 from UK Biobank (23 605 [51%] female; mean [SD] age, 64.0 [7.7] years). In the younger cohorts (TGS, ABCD, and Add Health), family history of depression was primarily associated with lower performance in the memory domain, and there were indications that this may be partly associated with educational and socioeconomic factors. In the older UK Biobank cohort, there were associations with processing speed, attention, and executive function, with little evidence of education or socioeconomic influences. These associations were evident even in participants who had never been depressed themselves. Effect sizes between familial risk of depression and neurocognitive test performance were largest in TGS; the largest standardized mean differences in primary analyses were -0.55 (95% CI, -1.49 to 0.38) in TGS, -0.09 (95% CI, -0.15 to -0.03) in ABCD, -0.16 (95% CI, -0.31 to -0.01) in Add Health, and -0.10 (95% CI, -0.13 to -0.06) in UK Biobank. Results were generally similar in the polygenic risk score analyses. In UK Biobank, several tasks showed statistically significant associations in the polygenic risk score analysis that were not evident in the family history models.

CONCLUSIONS AND RELEVANCE: In this study, whether assessed by family history or genetic data, depression in prior generations was associated with lower cognitive performance in offspring. There are opportunities to generate hypotheses about how this arises through genetic and environmental determinants, moderators of brain development and brain aging, and potentially modifiable social and lifestyle factors across the life span.

PMID:37074691 | DOI:10.1001/jamapsychiatry.2023.0716

AJOB Empir Bioeth. 2023 Apr 19:1-11. doi: 10.1080/23294515.2023.2201479. Online ahead of print.

ABSTRACT

BACKGROUND: Despite the bourgeoning of digital tools for bioethics research, education, and engagement, little research has empirically investigated the impact of interactive visualizations as a way to translate ethical frameworks and guidelines. To date, most frameworks take the format of text-only documents that outline and offer ethical guidance on specific contexts. This study’s goal was to determine whether an interactive-visual format supports frameworks in transferring ethical knowledge by improving learning, deliberation, and user experience.

METHODS: An experimental comparative study was conducted with a pre-, mid-, and post-test design using the online survey platform Qualtrics. Participants were university based early-stage health researchers who were randomly assigned to either the control condition (text-only document) or the experimental condition (interactive-visual). The primary outcome variables were learning, (measured using a questionnaire), deliberation (using cases studies) and user experience (measured using the SED/UD Scale). Analysis was conducted using descriptive statistics and mixed-effects linear regression.

RESULTS: Of the 80 participants, 44 (55%) used the text-only document and 36 (45%) used the interactive-visual. Results of the knowledge-test scores showed a statistically significant difference between participants’ post-test scores, indicating that the interactive-visual format better supported understanding, acquisition, and application of the framework’s knowledge. Findings from the case studies showed both formats supported ethical deliberation. Results further indicated the interactive-visual provided an overall better episodic and remembered user experience compared with the text-only document.

CONCLUSIONS: Our findings show that ethical frameworks formatted with interactive and visual qualities provide a more pleasing user experience and are effective formats for ethics learning and deliberation. These findings have implications for practitioners developing and deploying ethical frameworks and guidelines (e.g., in educational or employee-onboarding settings), in that the knowledge generated can lead to more effective dissemination practices of normative guidelines and health data ethics concepts.

PMID:37074681 | DOI:10.1080/23294515.2023.2201479

Environ Sci Pollut Res Int. 2023 Apr 19. doi: 10.1007/s11356-023-26511-6. Online ahead of print.

ABSTRACT

The significant increase in the human population and the associated industrial wastes have a widespread impact on coastal areas. It is important to monitor trace elements that affect food safety and pose a potential consumer health threat. All over the Black Sea coast, people enjoy consuming whiting as both meat and roe. In February 2021, whitings were caught by bottom trawling from four different locations on the coasts of Kastamonu, Sinop (Sarıkum, Adabaşı), and Samsun in the southern Black Sea region. The meat and roe extracts obtained from whiting samples were analyzed through an optical emission spectrophotometer (ICP-MS). Trace element concentrations of whiting meat and roe in this study were Zn > Fe > Sr > As > Al > Se > B > Mn > Cu > Hg > Li > Ni > Ba > Pb > Cr > Cd and Zn > Fe > Al > As > Cu > Sr > Mn > Se > B > Ba > Li > Ni > Hg > Cr > Pb > Cd, respectively. These amounts were lower than the acceptable values accepted by the EU Commission. In case of whiting and roe consumption of a maximum of three portions (860.33 g) for Adabaşı, six portions for Kastamonu (1432.37 g), three portions for Samsun (828.55 g), and five portions (1253.04 g) for Sarıkum per month do not pose a health risk.

PMID:37074608 | DOI:10.1007/s11356-023-26511-6

Environ Sci Pollut Res Int. 2023 Apr 19. doi: 10.1007/s11356-023-26865-x. Online ahead of print.

NO ABSTRACT

PMID:37074602 | DOI:10.1007/s11356-023-26865-x

Odontology. 2023 Apr 19. doi: 10.1007/s10266-023-00814-z. Online ahead of print.

ABSTRACT

To investigate the effect of ELVAX polymer subgingival implants incorporated with echistatin peptide on incisor reimplanted tooth in rats. Forty-two male Wistars rats were divided into two groups: echistatin-treated rats (E) and control rats (C). The animals had their right maxillary incisors extracted and treated according to the International Association of Dental Traumatology replantation protocol. The extra-alveolar dry period was 30 and 60 min, and the post-surgical experimental periods were 15, 60, and 90 days. The samples were stained with H&E and analyzed for the presence of an inflammatory response, incidence of resorptions, and dental ankylosis. Results were statistically analyzed (p < 0.05). The presence of inflammatory resorption was significantly higher in group C at 30 and 60 min extra-alveolar time, in the 15-day postoperative period as compared with the E group (p < 0.05). Dental ankylosis was significantly more prevalent in group E in 30 min extra-alveolar time and 15 days postoperative period (p < 0.05). However, in 60 min extra-alveolar time and 60 days postoperative period, dental ankylosis was more prevalent in C group (p < 0.05). The use of ELVAX subgingival implants with echistatin demonstrated therapeutic potential in preventing the experimental resorption process after replantation of maxillary incisors in rats.

PMID:37074599 | DOI:10.1007/s10266-023-00814-z

Eur Geriatr Med. 2023 Apr 19. doi: 10.1007/s41999-023-00779-w. Online ahead of print.

ABSTRACT

INTRODUCTION: Functional status is one of the most important issues of geriatric care. Polypharmacy seems to be a modifiable factor associated with functional decline in older adults. However, the impact of pharmacotherapy optimization on the activities of daily living in patients undergoing geriatric rehabilitation has not been investigated prospectively so far.

METHODS: This post hoc analysis of a subsample of the VALFORTA study included individuals only undergoing geriatric rehabilitation with a length of in-hospital stay of at least 14 days. Medication was modified according to the FORTA rules in the intervention group while in the control group standard drug treatment was applied. Both groups received comprehensive geriatric treatment.

RESULTS: The intervention and control groups consisted of 96 and 93 individuals respectively. They did not differ according to basic data except for age and Charlson Comorbidity Index (CCI) on admission. On discharge, activities of daily living (Barthel index, BI) were improved in both groups. An increase of at least 20 points of the BI was observed in 40% of patients in the intervention group and in 12% of patients in the control group (p< 0.001). Logistic regression analysis with an increase of at least 20 BI-points was significantly and independently associated with patient group (2.358, p< 0.02), BI on admission (0.957, p< 0.001), and the CCI (0.793, p< 0.041).

CONCLUSION: This post hoc analysis of a subsample of older individuals hospitalized for geriatric rehabilitation demonstrates a significant additional improvement in activities of daily living by modification of medication according to FORTA.

REGISTRATION: DRKS-ID: DRKS00000531.

PMID:37074562 | DOI:10.1007/s41999-023-00779-w

Eur Geriatr Med. 2023 Apr 19. doi: 10.1007/s41999-023-00781-2. Online ahead of print.

ABSTRACT

PURPOSE: The primary aim was to determine the incidence of intracranial hemorrhage (ICH) after mild traumatic brain injury (mTBI) in patients aged ≥ 65 years. The secondary aim was to identify risk factors for intracranial lesions and evaluate the need for in-hospital observation in this age group.

METHODS: This observational retrospective single-center study included all patients aged ≥ 65 years who were referred to our clinic for oral and plastic maxillofacial surgery following mTBI over a five-year period. Demographic and anamnesis data, clinical and radiological findings, and treatment were analyzed. Acute and delayed ICH and patient outcomes during hospitalization were evaluated using descriptive statistical analysis. A multivariable analysis was performed to find associations between CT findings and clinical data.

RESULTS: A total of 1,062 patients (55.7% male, 44.2% female) with a mean age of 86.3 years were included in the analysis. Ground-level fall was the most frequent cause of trauma (52.3%). Fifty-nine patients (5.5%) developed an acute traumatic ICH, and 73 intracerebral lesions were radiologically observed. No association was detected between ICH rate and antithrombotic medication (p = 0.4353). The delayed ICH rate was 0.09% and the mortality rate was 0.09%. Significant risk factors for increased ICH were a Glasgow Coma Scale score of < 15, loss of consciousness, amnesia, cephalgia, somnolence, dizziness, and nausea according to multivariable analysis.

CONCLUSION: Our study showed a low prevalence of acute and delayed ICH in older adults with mTBI. The ICH risk factors identified here should be considered when revising guidelines and developing a valid screening tool. Repeat CT imaging is recommended in patients with secondary neurological deterioration. In-hospital observation should be based on an assessment of frailty and comorbidities and not on CT findings alone.

PMID:37074561 | DOI:10.1007/s41999-023-00781-2

Endocrine. 2023 Apr 19. doi: 10.1007/s12020-023-03363-1. Online ahead of print.

ABSTRACT

PURPOSE: To investigate the effects of combination treatment with levothyroxine (LT4) and l- triiodothyronine (LT3) on left atrial volume (LAV), diastolic functions, and atrial electro-mechanical delays in LT4-treated women with low triiodothyronine (T3) levels.

METHODS: This prospective study consisted of 47 female patients between 18 and 65 years old treated at an Endocrinology and Metabolism outpatient clinic between February and April 2022 due to primary hypothyroidism. The study included patients with persistently low T3 levels in at least three measurements, despite LT4 treatment (1.6-1.8 mcg/kg/m²) for 23.13 ± 6.28 months with normal thyrotropin (TSH) and free tetraiodothyronine (fT4) levels. The combination therapy dose was as follows: the fixed LT4 dose (25 mcg) was removed from patients’ usual LT4 treatment [100 mcg (min-max, 75-150)], and a fixed LT3 dose (12.5 mcg) was added. Biochemical samples were taken, and an echocardiographic assessment was performed for patients upon their first admission, and after 195.5 ± 12.8 days of receiving LT3 (12.5 mcg) treatment.

RESULTS: There was a statistically significant reduction at left ventricle (LV) end-systolic diameter (27.69 ± 3.14, 27.13 ± 2.89, p = 0.035), left atrial (LA) maximum volume (14.73 ± 3.22, 13.94 ± 3.15, p = 0.009), LA minimum volume (7.84 ± 2.45, 6.84 ± 2.30, p < 0.001), LA vertical diameter (44.08 ± 6.92, 34.60 ± 4.31, <0.001), LA horizontal diameter (45.65 ± 6.88, 33.43 ± 4.51, p < 0.001), LAVI (50.73 ± 18.62, 41.0 ± 13.02, p < 0.001), total conduction time (103.69 ± 12.70, 79.82 ± 18.40, p < 0.001) after LT3 replacement (respectively pre-post- treatment and p value).

CONCLUSION: In conclusion, the findings of this study suggest that the addition of LT3 to LT4 treatment may lead to improvements in LAVI and atrial conduction times in patients with low T3. However, further research with larger patient groups and exploration of different LT4 + LT3 dose combinations is needed to better understand the effects of combined hypothyroidism treatment on cardiac functions.

PMID:37074560 | DOI:10.1007/s12020-023-03363-1

J Psycholinguist Res. 2023 Apr 19. doi: 10.1007/s10936-023-09944-5. Online ahead of print.

ABSTRACT

The prominent role of allophonic cues in English speech segmentation has widely been recognized by phonologists and psycholinguists. However, very meager inquiry was devoted to analysing the perception of these noncontrastive allophonic cues by Arab EFL learners. Accordingly, the present study is an attempt to examine the exploitation of allophonic cues, mainly aspiration, glottalization and approximant devoicing to English word junctures by 40 Jordanian PhD students. Moreover, it aims to find out which allophonic cues are perceived more accurately during the segmentation process and if there is any evidence for Universal Grammar markedness. The experiment is led through a forced-choice identification task adopted from Altenberg (Second Lang Res 21:325-358, 2005) and Rojczyk et al. (Res Lang 1:15-29, 2016). The results of ANOVA unveiled that there is a statistically significant difference between the three types of allophonic cues, viz. aspiration, glottalization and approximant devoicing. This implies that the participants outperformed in stimuli marked by glottalization than by aspiration and approximant devoicing. This result provided further evidence for the universality of glottalization as a boundary cue in English speech segmentation. Overall, the Jordanian PhD students failed in perceiving the allophonic cues accurately and exploiting them to detect word boundaries. The present inquiry has the potential to provide several recommendations for syllabus designers, and second/foreign language teachers and learners.

PMID:37074538 | DOI:10.1007/s10936-023-09944-5