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1.
Mol Psychiatry ; 2024 Jul 06.
Article in English | MEDLINE | ID: mdl-38971895

ABSTRACT

Previous studies have shown an association between the thalamocortical dysconnectivity and treatment-resistant depression (TRD). Whether a single subanesthetic dose of ketamine may change thalamocortical connectivity among patients with TRD is unclear. Whether these changes in thalamocortical connectivity is associated with the antidepressant and antisuicidal effects of ketamine treatment is also unclear. Two resting-state functional MRIs were collected in two clinical trials of 48 patients with TRD (clinical trial 1; 32 receiving ketamine, 16 receiving a normal saline placebo) and 48 patients with TRD and strong suicidal ideation (clinical trial 2; 24 receiving ketamine, 24 receiving midazolam), respectively. All participants underwent rs-fMRI before and 3 days after infusion. Seed-based functional connectivity (FC) was analyzed in the left/right thalamus. FCs between the bilateral thalamus and right middle frontal cortex (BA46) and between the left thalamus and left anterior paracingulate gyrus (BA8) increased among patients in the ketamine group in clinical trials 1 and 2, respectively. FCs between the right thalamus and bilateral frontal pole (BA9) and between the right thalamus and left rostral paracingulate gyrus (BA10) decreased among patients in the ketamine group in clinical trials 1 and 2, respectively. However, the associations between those FC changes and clinical symptom changes did not survive statistical significance after multiple comparison corrections. Whether ketamine-related changes in thalamocortical connectivity may be associated with ketamine's antidepressant and antisuicidal effects would need further investigation. Clinical trials registration: UMIN Clinical Trials Registry (UMIN-CTR): Registration number: UMIN000016985 and UMIN000033916.

2.
Org Lett ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949643

ABSTRACT

A new self-cyclopropanation of 1,3-diphenylpropane-1,3-dione, leading to tetrasubstituted cyclopropane containing three contiguous stereogenic centers with high stereoselectivity, has been achieved through violet-light-emitting diode-irradiated photocatalysis, featuring both cycloaddition and a distinctive rearrangement. Diverging from conventional cyclopropanation pathways, this reaction yields a tetrasubstituted cyclopropane through unprecedented rearrangement and cascade reactions.

3.
Nature ; 630(8017): 744-751, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38867042

ABSTRACT

DNA base damage is a major source of oncogenic mutations1. Such damage can produce strand-phased mutation patterns and multiallelic variation through the process of lesion segregation2. Here we exploited these properties to reveal how strand-asymmetric processes, such as replication and transcription, shape DNA damage and repair. Despite distinct mechanisms of leading and lagging strand replication3,4, we observe identical fidelity and damage tolerance for both strands. For small alkylation adducts of DNA, our results support a model in which the same translesion polymerase is recruited on-the-fly to both replication strands, starkly contrasting the strand asymmetric tolerance of bulky UV-induced adducts5. The accumulation of multiple distinct mutations at the site of persistent lesions provides the means to quantify the relative efficiency of repair processes genome wide and at single-base resolution. At multiple scales, we show DNA damage-induced mutations are largely shaped by the influence of DNA accessibility on repair efficiency, rather than gradients of DNA damage. Finally, we reveal specific genomic conditions that can actively drive oncogenic mutagenesis by corrupting the fidelity of nucleotide excision repair. These results provide insight into how strand-asymmetric mechanisms underlie the formation, tolerance and repair of DNA damage, thereby shaping cancer genome evolution.


Subject(s)
DNA Damage , DNA Repair , DNA-Directed DNA Polymerase , DNA , Mutagenesis , Mutation , Animals , Humans , Mice , Alkylation/radiation effects , Cell Line , DNA/chemistry , DNA/genetics , DNA/metabolism , DNA/radiation effects , DNA Adducts/chemistry , DNA Adducts/genetics , DNA Adducts/metabolism , DNA Adducts/radiation effects , DNA Damage/genetics , DNA Damage/radiation effects , DNA Repair/genetics , DNA Repair/physiology , DNA Replication , DNA-Directed DNA Polymerase/metabolism , Mutagenesis/genetics , Mutagenesis/radiation effects , Mutation/genetics , Mutation/radiation effects , Neoplasms/genetics , Transcription, Genetic , Ultraviolet Rays/adverse effects
4.
J Formos Med Assoc ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38918083

ABSTRACT

OBJECTIVES: To elucidate the prevalence of overt, occult and no demonstrated (ND) stress urinary incontinence (SUI) in women with advanced-stage cystoceles. STUDY DESIGN: Between November 2011 and January 2017, all women with ≥stage 2 cystoceles were retrospectively enrolled. Overt SUI was diagnosed before the prolapse reduction test, and occult SUI was diagnosed when urine leakage was noted after a reduction test with vaginal gauze. Otherwise, a diagnosis of ND-SUI was made. MAIN OUTCOME MEASURES: The prevalence, clinical and urodynamic findings of overt SUI, occult SUI, and ND-SUI. RESULTS: In 480 enrolled women, 62% had overt SUI, 17% had occult SUI, and 21% had ND-SUI. The occult SUI group had the most advanced prolapse. The pad weight results after prolapse reduction (37.3 ± 44.3 vs. 13.4 ± 21.9, p < 0.05), the bladder capacity (243 ± 54 vs. 273 ± 48, p < 0.001), and questionnaires regarding life quality were significantly different between the overt SUI and the occult SUI groups. Bladder oversensitivity (BO) was the most common urodynamic diagnosis (389/480, 81%), especially in overt SUI, while urodynamic stress incontinence (56/480, 12%) and detrusor overactivity (60/480, 13%) were uncommon. The cutoff value of stage 3 uterine prolapse was the strongest predictor for predicting occult SUI (sensitivity = 30.3%, specificity = 78.5%; area = 0.60, 95% CI: 0.52-0.68). CONCLUSIONS: SUI occurs in a ratio of 3:1:1 among cases with overt, occult, and no demonstrable symptoms. BO is the most common urodynamic diagnosis. Pad test with prolapse reduction remains an important tool, especially for coexistent stage 3 uterine prolapse.

5.
J Fish Dis ; : e13982, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38899543

ABSTRACT

Edwardsiella anguillarum, a highly virulent species within the Edwardsiella genus, causes significant mortality in milkfish farms in Taiwan. This study aimed to investigate the comparison of milkfish susceptibility, a newly identified host species in Taiwanese aquaculture, with other species Nile tilapia (Oreochromis niloticus) and Asian seabass (Lates calcarifer), to E. anguillarum, elucidating its pathogenicity across both seawater and freshwater aquaculture environments. The results showed milkfish exhibited the highest mortality rate of 85% within 48 h of infection, whereas Nile tilapia exhibited a mortality rate of 70% between the second- and tenth-day post challenge, and seabass exhibited a mortality rate of 25% between the second- and sixth-day post challenge. Gross lesions observed in milkfish included splenomegaly and haemorrhage, whereas Nile tilapia exhibited signs of ascites, exophthalmia and brain haemorrhage. Seabass displayed spleen granulomas and haemorrhage at the injection site. Histopathological analysis revealed common features across all three species, including multifocal necrosis, bacterial presence in the necrotic areas, serositis and oedema. Asian seabass also exhibited chronic lesions in the form of splenic granulomas. This study highlights the high susceptibility of milkfish and Nile tilapia to E. anguillarum, emphasizing the urgent need for further investigation into targeted vaccine development for these fish species. These results not only deepen our understanding of the differing levels of pathogenicity among the three species but also offer valuable insights for improving disease prevention and management strategies in aquaculture, including those applied within polyculture systems and for the maintenance of aquaculture water environments.

6.
Org Lett ; 26(26): 5447-5452, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38896796

ABSTRACT

Interest in electrocatalytic bioconjugation reactions has surged, particularly for modifying tryptophan and tyrosine residues in proteins. We used a cost-effective graphite felt electrode and low-current methodology to achieve selective bioconjugation of tryptophan with thiophenols, yielding up to 92%. This method exclusively labeled tryptophan residues and incorporated fluorinated tryptophan for NMR analysis. Eight polypeptides, including lanreotide and leuprorelin, were effectively coupled, demonstrating the method's versatility and potential for novel diagnostic and therapeutic agents.


Subject(s)
Peptides , Tryptophan , Tryptophan/chemistry , Peptides/chemistry , Electrochemical Techniques , Molecular Structure , Somatostatin/chemistry , Somatostatin/analogs & derivatives , Peptides, Cyclic/chemistry , Electrodes
7.
Article in English | MEDLINE | ID: mdl-38800864

ABSTRACT

OBJECTIVE: Female voiding dysfunction with cystocele have been widely studied, but there are no data regarding women without cystoceles. The present study aimed to evaluate the prevalence of detrusor underactivity (DU) and bladder outlet obstruction (BOO) without cystoceles in a large sample size. METHODS: This was a retrospective cohort study. Between April 1996 and September 2018, 602 neurologically intact women with voiding dysfunction without cystoceles were enrolled. Detrusor pressure (DU) at the maximum flow rate (PdetQmax) <20 cmH2O, maximum flow rate (Qmax) <15 mL/s, and a bladder voiding efficiency <90% and BOO (PdetQmax ≥40 cmH2O and Qmax <12 mL/s) were diagnosed by urodynamic study. Otherwise, a non-DU/BOO diagnosis was made. The prevalence of DU and BOO was the primary outcome. The secondary outcomes were the analyses of the differences between these three groups in objective UDS parameters and subjective questionnaires and bladder diary parameters. RESULTS: This study included 100 (17%) women with DU, 60 (10%) with BOO, and 442 (73%) with a non-DU/BOO diagnosis. DU increased with age, but BOO decreased as age increased. The women in the DU group were older, had higher parity and pad weights, and lower PdetQmax, maximum urethral closure pressure, and functional profile length than the BOO group. The urodynamic findings did not correlate well to subjective questionnaire parameters. None of the symptoms revealed a significant difference between the groups. The retrospective design was the limitation of the study. CONCLUSION: The prevalence of DU increased with age in women with voiding dysfunction without advanced cystoceles. Conversely, BOO decreased with age. Prevalence intersected in the fourth decade. Diagnosis requires urodynamic evaluation, as subjective symptoms are inconclusive.

8.
Article in English | MEDLINE | ID: mdl-38710644

ABSTRACT

BACKGROUND: Lactic acid bacteria may be used as probiotics to prevent or treat various diseases, and Lactobacillus delbrueckii has an inhibitory effect on the development of atopic diseases. OBJECTIVE: This study explored the effects of L. delbrueckii subsp. lactis strain LDL557 administration on a mouse asthma model resulting from Dermatophoides pteronyssinus (Der p) sensitization and investigated the associated gut microbiota. METHODS: Der p-sensitized and challenged BALB/c mice were orally administered with three different doses of live (low, 107 colony-forming units (CFU); medium, 108 CFU; high, 109 CFU) and heat-killed (109 cells) LDL557 in 200 µL of PBS daily, starting 2 weeks before Der p sensitization and lasting 4 weeks. After the allergen challenge, airway responsiveness to methacholine and the influx of inflammatory cells to the lungs were assessed. The gut microbiome was obtained by sequencing the V3-V4 region of the 16S rRNA gene from mice stool samples. RESULTS: LDL557 in the live (109 CFU) and heat-killed (109 cells) conditions reduced the airway hyper-responsiveness after stimulation with methacholine, inflammatory cell infiltration, and mucus production. These effects were similar to those in groups treated with dexamethasone. No significant change in the gut microbiota was observed after LDL557 treatment, except for the tendency of heat-killed LDL557 to change the gut microbial profile to a greater extent than live LDL557. CONCLUSION: In summary, we found that live and heat-killed LDL557 had the beneficial effect of preventing Der p-induced allergic inflammation in a mouse model of asthma.

9.
Article in English | MEDLINE | ID: mdl-38710643

ABSTRACT

BACKGROUND: Atopic dermatitis (AD) is a chronic inflammatory skin disorder affecting up to 20% of children in developed countries. Although probiotics have shown promise as adjuvant treatments for AD, their mechanisms are not well understood. OBJECTIVE: Building upon our previous studies, we investigated whether Lactobacillus gasseri and its moonlighting glyceraldehyde 3-phosphate dehydrogenase (GAPDH), namely LGp40, could be beneficial in AD management. METHODS: In AD mouse models (SKH and C57BL/6J mice) with ovalbumin (OVA) and Dermatophagoides pteronyssinus (Der p) allergens, aligning with the "outside-in" and "inside-out" hypotheses, we administered L. gasseri orally and LGp40 intraperitoneally to investigate their protective effects. The evaluation involved measuring physiological, pathological, and immune function parameters. To delve deeper into the detailed mechanism of LGp40 protection in AD, additional assays were conducted using human skin keratinocytes (HaCaT) and monocytes (THP1) cell lines. RESULTS: L. gasseri and LGp40 enhanced skin barrier function and increased skin moisture retention. They also led to reduced infiltration of Langerhans cells in the dermis and mitigated skewed Th2 and Th17 immune responses. Moreover, LGp40 inhibited allergen-induced keratinocyte apoptosis through the blockade of the caspase-3 cascade and reduced the NLR family pyrin domain containing 3 (NLRP3) inflammasome in macrophages. These inhibitions were achieved through the activation of the peroxisome proliferator-activated receptor gamma (PPARγ) pathway. CONCLUSION: The results of this study provide a novel insight into the mechanism of action of probiotics in the prevention and treatment for allergic disorders through the moonlighting GAPDH protein.

10.
Autism Res ; 17(6): 1187-1204, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38794898

ABSTRACT

Evidence suggests core autism trait consistency in older children, but development of these traits is variable in early childhood. The Social Responsiveness Scale (SRS) measures autism-related traits and broader autism phenotype, with two age-dependent forms in childhood (preschool, 2.5-4.5 years; school age, 4-18 years). Score consistency has been observed within forms, though reliability across forms has not been evaluated. Using data from the Environmental Influences on Child Health Outcomes (ECHO) program (n = 853), preschool, and school-age SRS scores were collected via maternal report when children were an average of 3.0 and 5.8 years, respectively. We compared reproducibility of SRS total scores (T-scores) and agreement above a clinically meaningful cutoff (T-scores ≥ 60) and examined predictors of discordance in cutoff scores across forms. Participant scores across forms were similar (mean difference: 3.3 points; standard deviation: 7), though preschool scores were on average lower than school-age scores. Most children (88%) were classified below the cutoff on both forms, and overall concordance was high (92%). However, discordance was higher in cohorts following younger siblings of autistic children (16%). Proportions of children with an autism diagnoses were also higher among those with discordant scores (27%) than among those with concordant scores (4%). Our findings indicate SRS scores are broadly reproducible across preschool and school-age forms, particularly for capturing broader, nonclinical traits, but also suggest that greater variability of autism-related traits in preschool-age children may reduce reliability with later school-age scores for those in the clinical range.


Subject(s)
Social Behavior , Humans , Child, Preschool , Child , Female , Male , Reproducibility of Results , Adolescent , Autism Spectrum Disorder , Child Health , Autistic Disorder
11.
Fish Shellfish Immunol ; 150: 109663, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38821228

ABSTRACT

Persistent nocardiosis has prompted exploration of the effectiveness of heterologous approaches to prevent severe infections. We have previously reported the efficacy of a nucleic acid vaccine in protecting groupers from highly virulent Nocardia seriolae infections. Ongoing research has involved the supplementation of recombinant cholesterol oxidase (rCho) proteins through immunization with a DNA vaccine to enhance the protective capacity of orange-spotted groupers. Recombinant rCho protein exhibited a maturity and biological structure comparable to that expressed in N. seriolae, as confirmed by Western blot immunodetection assays. The immune responses observed in vaccinated groupers were significantly higher than those observed in single-type homologous vaccinations, DNA or recombinant proteins alone (pcD:Cho and rCho/rCho), especially cell-mediated immune and mucosal immune responses. Moreover, the reduction in N. seriolae occurrence in internal organs, such as the head, kidney, and spleen, was consistent with the vaccine's efficacy, which increased from approximately 71.4 % to an undetermined higher percentage through heterologous vaccination strategies of 85.7 %. This study underscores the potential of Cho as a novel vaccine candidate and a heterologous approach for combating chronic infections such as nocardiosis.


Subject(s)
Bacterial Vaccines , Fish Diseases , Nocardia Infections , Nocardia , Animals , Nocardia Infections/veterinary , Nocardia Infections/prevention & control , Nocardia Infections/immunology , Nocardia/immunology , Fish Diseases/prevention & control , Fish Diseases/immunology , Bacterial Vaccines/immunology , Bacterial Vaccines/administration & dosage , Vaccines, DNA/immunology , Vaccines, DNA/administration & dosage , Bass/immunology , Cholesterol Oxidase/immunology , Cholesterol Oxidase/genetics , Recombinant Proteins/immunology , Recombinant Proteins/administration & dosage
12.
J Nutr ; 154(7): 2157-2166, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38740185

ABSTRACT

BACKGROUND: We previously reported that delayed allergenic food introduction in infancy did not increase food allergy risk until age 4 y within our prospective cohort. However, it remains unclear whether other aspects of maternal or infant diet play roles in the development of childhood food allergy. OBJECTIVES: We examined the relationship between maternal pregnancy and infant dietary patterns and the development of food allergies until age 8 y. METHODS: Among 1152 Singapore Growing Up in Singapore Towards healthy Outcomes study mother-infant dyads, the infant's diet was ascertained using food frequency questionnaires at 18 mo. Maternal dietary patterns during pregnancy were derived from 24-h diet recalls. Food allergy was determined through interviewer-administered questionnaires at regular time points from infancy to age 8 y and defined as a positive history of allergic reactions, alongside skin prick tests at 18 mo, 3, 5, and 8 y. RESULTS: Food allergy prevalence was 2.5% (22/883) at 12 mo and generally decreased over time by 8 y (1.9%; 14/736). Higher maternal dietary quality was associated with increased risk of food allergy (P ≤ 0.016); however, odds ratios were modest. Offspring food allergy risk ≤8 y showed no associations with measures of infant diet including timing of solids/food introduction (adjusted odds ratio [aOR]: 0.90; 95% confidence interval [CI]: 0.42, 1.92), infant's diet quality (aOR: 0.93; 95% CI: 0.88, 0.99) or diet diversity (aOR: 0.84; 95% CI: 0.6, 1.19). Most infants (89%) were first introduced to cow milk protein within the first month of life, while egg and peanut introduction were delayed (58.3% introduced by mean age 8.8 mo and 59.8% by mean age 18.1 mo, respectively). CONCLUSIONS: Apart from maternal diet quality showing a modest association, infant's allergenic food introduction, diet quality, and dietary diversity were not associated with food allergy development in this Asian pediatric population. Interventional studies are needed to evaluate the efficacy of these approaches to food allergy prevention across different populations.


Subject(s)
Diet , Food Hypersensitivity , Humans , Female , Food Hypersensitivity/epidemiology , Singapore/epidemiology , Infant , Pregnancy , Male , Child, Preschool , Prospective Studies , Adult , Child , Risk Factors , Cohort Studies , Maternal Nutritional Physiological Phenomena , Infant Food , Infant Nutritional Physiological Phenomena , Prevalence , Dietary Patterns
13.
Singapore Med J ; 65(4): 211-219, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38650059

ABSTRACT

ABSTRACT: Climate change, particularly increasing temperature, changes in rainfall, extreme weather events and changes in vector ecology, impacts the transmission of many climate-sensitive infectious diseases. Asia is the world's most populous, rapidly evolving and diverse continent, and it is already experiencing the effects of climate change. Climate change intersects with population, sociodemographic and geographical factors, amplifying the public health impact of infectious diseases and potentially widening existing disparities. In this narrative review, we outline the evidence of the impact of climate change on infectious diseases of importance in Asia, including vector-borne diseases, food- and water-borne diseases, antimicrobial resistance and other infectious diseases. We also highlight the imperative need for strategic intersectoral collaboration at the national and global levels and for the health sector to implement adaptation and mitigation measures, including responsibility for its own greenhouse gas emissions.


Subject(s)
Climate Change , Communicable Diseases , Humans , Asia/epidemiology , Communicable Diseases/epidemiology , Public Health , Vector Borne Diseases/epidemiology , Animals , Foodborne Diseases/epidemiology , Waterborne Diseases/epidemiology
14.
J Fish Dis ; 47(8): e13957, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38665053

ABSTRACT

Global ornamental fish transportation ranging from hours to days can produce multiple stress factors impact fish health and cause mortality. Clownfish, particularly Amphiprion ocellaris, are among the most traded saltwater ornamental fish. Vibrio includes several pathogenic strains that affect aquatic animals. Consequently, prophylactic treatment of the water or fish is recommended. In this study, six Vibrio strains including V. alginolyticus, V. parahaemolyticus and V. harveyi isolated from sick A. ocellaris and one V. harveyi strain from a sick East Asian fourfinger threadfin (Eleutheronema rhadinum) were tested for their sensitivity to a popular disinfectant, chlorine dioxide (ClO2). The results showed that 0.25 ppm ClO2 effectively suppressed five of the seven tested Vibrio strains for 24 h; however, 0.1 ppm ClO2 is safer for A. ocellaris. Meanwhile, ClO2 2.5 ppm reduced the bacterial counts to below 3.3 × 105 CFU/mL for 24 hours. The LC50 of ClO2 for A. ocellaris was 0.87 ppm at 10 min and 0.72 ppm at 24 h post treatment. Mild changes in water quality, including dissolved oxygen (DO), temperature and pH, were recorded during the trial. More research is necessary to understand the sensitivity of various aquatic animal pathogens to ClO2 and its toxicity to different aquatic animals.


Subject(s)
Chlorine Compounds , Disinfectants , Fish Diseases , Oxides , Vibrio Infections , Vibrio , Chlorine Compounds/pharmacology , Animals , Oxides/pharmacology , Fish Diseases/microbiology , Fish Diseases/prevention & control , Vibrio/drug effects , Disinfectants/pharmacology , Vibrio Infections/veterinary , Vibrio Infections/prevention & control , Perciformes , Anti-Bacterial Agents/pharmacology
15.
Dermatitis ; 2024 Apr 17.
Article in English | MEDLINE | ID: mdl-38634841

ABSTRACT

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease. However, few studies have investigated brain changes associated with chronic inflammation. We hypothesized that chronic inflammation might be related to brain structural alterations in patients with AD. Objectives: To investigate the association between disease severity (Eczema Area and Severity Index [EASI]), proinflammatory cytokines, and differences in brain gray matter (GM) volume in patients with AD. Methods: Nineteen patients with AD and 19 age- and sex-matched healthy subjects were enrolled. All participants underwent clinical assessment and brain magnetic resonance imaging. Voxel-based morphometry was performed to analyze GM volume differences. Results: Patients with AD exhibited significantly decreased GM volume in many brain regions, such as bilateral precentral gyrus, right frontal pole, and right middle temporal gyrus (P < 0.001), compared with healthy subjects. Notably, in patients with AD, the GM volume in right middle temporal gyrus was negatively associated with both EASI score and proinflammatory cytokines (sIL-2R [soluble interleukin 2 receptor] and TNF-α receptor-1), whereas the GM volume in left precentral gyrus was negatively associated with both EASI score and proinflammatory cytokines (sIL-2R and CRP). Conclusion: Patients with AD demonstrated significant brain GM volume reduction in many brain regions, which is related to disease severity and proinflammatory cytokines.

16.
Nat Commun ; 15(1): 3594, 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38678011

ABSTRACT

Recurrent DNA break clusters (RDCs) are replication-transcription collision hotspots; many are unique to neural progenitor cells. Through high-resolution replication sequencing and a capture-ligation assay in mouse neural progenitor cells experiencing replication stress, we unravel the replication features dictating RDC location and orientation. Most RDCs occur at the replication forks traversing timing transition regions (TTRs), where sparse replication origins connect unidirectional forks. Leftward-moving forks generate telomere-connected DNA double-strand breaks (DSBs), while rightward-moving forks lead to centromere-connected DSBs. Strand-specific mapping for DNA-bound RNA reveals co-transcriptional dual-strand DNA:RNA hybrids present at a higher density in RDC than in other actively transcribed long genes. In addition, mapping RNA polymerase activity uncovers that head-to-head interactions between replication and transcription machinery result in 60% DSB contribution to the head-on compared to 40% for co-directional. Taken together we reveal TTR as a fragile class and show how the linear interaction between transcription and replication impacts genome stability.


Subject(s)
DNA Breaks, Double-Stranded , DNA Replication , Genomic Instability , Transcription, Genetic , Animals , Mice , Neural Stem Cells/metabolism , DNA/metabolism , DNA/genetics , Replication Origin , Telomere/metabolism , Telomere/genetics , Centromere/metabolism , Centromere/genetics
17.
Acta Neuropsychiatr ; : 1-8, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38623725

ABSTRACT

OBJECTIVE: Divergent thinking is a critical creative cognitive process. Its neural mechanisms have been well-studied through structural and functional imaging in healthy individuals but are less explored in patients with bipolar disorder (BD). Because of the traditional link between creativity and BD, this study investigated the structural correlates of divergent thinking in patients with BD through surface-based morphometry. METHODS: Fifty-nine patients diagnosed with BD I or BD II (35.3 ± 8.5 years) and 56 age- and sex-matched controls (33.9 ± 7.4 years) were recruited. The participants underwent structural magnetic resonance imaging and an evaluation of divergent thinking by using the Chinese version of the Abbreviated Torrance Test for Adults (ATTA). FreeSurfer 7.0 was used to generate thickness and surface area maps for each participant. Brainwise regression of the association between cortical thickness or surface area and ATTA performance was conducted using general linear models. RESULTS: Divergent thinking performance did not differ significantly between the patients with BD and the healthy controls. In these patients, total ATTA score was negatively correlated with cortical thickness in the right middle frontal gyrus, right occipital, and left precuneus but positively correlated with the surface area of the right superior frontal gyrus. By contrast, total ATTA scores and cortical thickness or surface area were not significantly correlated among the controls. CONCLUSION: The findings indicate that divergent thinking involves cerebral structures for executive control, mental imagery, and visual processing in patients with BD, and the right prefrontal cortex might be the most crucial of these structures.

18.
Pediatr Res ; 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38622260

ABSTRACT

BACKGROUND: The Modified Checklist for Autism in Toddlers (M-CHAT) is a common pediatric screening tool with mixed accuracy findings. Prior evidence supports M-CHAT screening for developmental concerns, especially in toddlers born preterm. This study examined M-CHAT accuracy in a large, nationwide sample. METHODS: 3393 participants from the Environmental influences on Child Health Outcomes (ECHO) program were included. Harmonized M-CHAT (M-CHAT-H) results were compared with parent-reported autism diagnosis and autism-related characteristics to assess accuracy for term and preterm children, together and separately. Generalized estimating equations, clustering for ECHO cohort and controlling for demographic covariates, were used to examine associations between developmental and behavioral characteristics with M-CHAT-H accuracy. RESULTS: Sensitivity of the M-CHAT-H ranged from 36 to 60%; specificity ranged from 88 to 99%. Positive M-CHAT-H was associated with more developmental delays and behavior problems. Children with severe motor delays and more autism-related problems were more likely to have a false-negative M-CHAT-H. Children with fewer behavior problems and fewer autism-related concerns were more likely to have a false-positive screen. CONCLUSION: The M-CHAT-H accurately detects children at low risk for autism and children at increased risk with moderate accuracy. These findings support use of the M-CHAT-H in assessing autism risk and developmental and behavioral concerns in children. IMPACT: Previous literature regarding accuracy of the Modified Checklist for Autism in Toddlers (M-CHAT) is mixed but this study provides evidence that the M-CHAT performs well in detecting children at low risk for autism and consistently detects children with developmental delays and behavioral problems. The M-CHAT moderately detects children at increased risk for autism and remains a useful screening tool. This study examines M-CHAT accuracy in a large-scale, nationwide sample, examining associations between screening accuracy and developmental outcomes. These findings impact pediatric screening for autism, supporting continued use of the M-CHAT while further elucidating the factors associated with inaccurate screens.

19.
Arch Psychiatr Nurs ; 48: 36-42, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38453280

ABSTRACT

This cross-sectional study investigates the self-reported emotional distress of medical, nursing, dental, pharmacy, and public health students and identifies gender-related differences through an online survey. The data of 364 students were analyzed using Pearson correlation coefficients and multiple logistic regression. Emotional distress was more prevalent among female respondents (11.7 %) than male (3.8 %) respondents. The stigma, isolation, and depression experienced by female respondents influenced their emotional distress, whereas only the depression of male respondents influenced their emotional distress. Our findings suggest that mental health professionals should consider gender-specific factors when developing interventions for the study population to minimize emotional distress.


Subject(s)
Psychological Distress , Students , Humans , Male , Female , Cross-Sectional Studies , Sex Factors , Students/psychology , Surveys and Questionnaires
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