Early Onset Research Articles

All-cause and cause-specific mortality risk and loss in life expectancy associated with incident type 2 diabetes onset age and duration.

Evidence on type 2 diabetes onset age and duration on mortality risk has been limited by short follow-up, inadequate control for confounding, missing repeated measurements, and inability to cover the full range of onset age, duration, and major causes of death. Moreover, scarce data dissect how type 2 diabetes onset age and duration shape life expectancy. We evaluate prospectively these topics based on 270,075 eligible participants in the Nurses' Health Studies and Health Professionals Follow-up Study, leveraging repeated measurements throughout up to 40 years of follow-up. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). In fully adjusted analyses, incident early onset type 2 diabetes (diagnosed <40 years of age) was associated with significantly higher mortality from all-causes (HR, 95% CI was 3.16, 2.64-3.79; vs. individuals without type 2 diabetes), cardiovascular disease (6.56, 4.27-10.1), respiratory disease (3.43, 1.38-8.51), neurodegenerative disease (5.13, 2.09-12.6), and kidney disease (8.55, 1.98-36.9). The relative risk elevations declined dramatically with each higher decade of age at diagnosis for deaths from most of these causes, though the absolute risk difference increased continuously. A substantially higher cumulative incidence of mortality and a greater loss in life expectancy were associated with younger age at type 2 diabetes diagnosis. Longer disease duration was associated with generally higher relative and absolute risk of mortality. Early onset of type 2 diabetes and longer disease duration are associated with substantially increased risk of all-cause and cause-specific mortality and greater loss in life expectancy.

Influence of pseudoxanthoma elasticum on the lipid profile and prognostic implications.

Background: Pseudoxanthoma elasticum (PXE) is a rare, inherited disease characterised by specific skin lesions, progressive loss of vision and early onset atherosclerosis. Atherosclerosis in PXE leads to an increased rate of vascular occlusion and severe intermittent claudication. Although genetically determined, the individual course of PXE is highly variable. Up to now, there is no sufficient parameter to identify individuals at risk of rapid disease progression. This present study focused the lipid profile of patients with PXE and its possible influence on the clinical severity of peripheral artery disease (PAD). Patients and methods: 112 patients with PXE were retrospectively screened. Patients without a complete lipid profile consisting of total cholesterol (TC), triglycerides (TGC), high-density lipoprotein (HDL), low-density lipoprotein (LDL) and Lipoprotein(a) (Lp[a]) where excluded as well as patients with already initiated lipid-lowering therapy. 52 patients met the inclusion criteria. An age-adjusted ordinal regression model was applied to determine the association of each lipid fraction with the severity of PAD assessed as Fontaine classification. Results: The lipid profile of patients with PXE was unremarkable (TGC: 135.8±105.8 mg/dl; TC: 172.5±44.4 mg/dl; HDL: 63.0±18.2 mg/dl; Lp[a]: 64.7±93.5 nmol/l). Ordinal regression showed a significant association of Lp(a) with the severity of PAD with an odds ratio of 1.01 (1.00-1.02; p = 0.004), whereas the other fractions of the lipid profile had no significant influence. Conclusions: This study provides the largest evaluation of blood lipids up to now and the first characterization of Lp(a) levels in patients with PXE. We were able to provide first evidence of a correlation between elevated levels of Lp(a) and the severity of PAD. The present results suggest that determination of Lp(a) in early stages of PXE could help to identify patients at risk of rapid disease progression and with the need of intensified walking exercise training.

"GLI1 Subcellular Localization and Overexpression as Prognostic Factors for Disease-Free Survival in Colorectal Carcinoma".

Glioma-associated oncogene homolog-1 (GLI1) is amplified in human glioblastoma, and there is growing evidence suggesting its significant role in tumor development and metastasis. Our aim was to investigate the role of the GLI-1 gene in the progression of colorectal cancer (CRC) and its correlation with various clinicopathological features. Additionally, we examined the impact of the GLI-1 gene and other factors on the prognosis of CRC. We analyzed a total of 98 confirmed CRC cases and adjacent normal tissue controls. Patients suspected of having colon cancer underwent a colonoscopy and targeted biopsy, while those with rectal cancer underwent CT scans and MRI. GLI1 expression was detected using real-time PCR assay, Western blotting, and immunohistochemistry. The GLI1 gene was observed to be overexpressed in tumor tissues at both the protein and mRNA levels (p < 0.05). In addition, GLI1 overexpression was significantly associated with various factors such as tumor invasion (T3/T4), presence of lymph nodes, lymph node metastasis (LNM), stage (III/IV), tumor site (colon), tumor size (≥ 3cm), localization (nucleocytoplasmic), strong staining intensity and recurrence (p < 0.05). The results of survival analysis showed that the patients with overexpression of GLI1 had a significantly lower DFS rate which was 21months compared to those with normal expression who had 31months (p < 0.05). Moreover, individuals with early onset disease (15months) were more likely to have cytoplasmic localization of the GLI1 gene as opposed to nucleo-cytoplasmic localization of GLI1 which presented late-onset disease( 23months) (p < 0.05). Finally, Stage and PNI (p < 0.05) were found to independently affect outcomes of CRC according to Cox regression analysis. High expression of GLI-1 in CRC is associated with adverse pathology and poor prognosis for patients. The correlation between cytoplasmic localization of GLI-1 and reduced disease-free survival holds potential for guiding prognosis and treatment. Further research is needed to develop strategies targeting GLI-1 for improved outcomes.

Suppressing UBE2N ameliorates Alzheimer's disease pathology through the clearance of amyloid beta.

Aging is one of the risk factors for the early onset of Alzheimer's disease (AD). We previously discovered that the age-dependent increase in Ubiquitin Conjugating Enzyme E2 N (UBE2N) plays a role in the accumulation of misfolded proteins through K63 ubiquitination, which has been linked to AD pathogenesis. However, the impact of UBE2N on amyloid pathology and clearance has remained unknown. We observed the elevated UBE2N during the amyloid beta (Aβ) generation in the brains of 5×FAD, APP/PS1 mice, and patients with AD, in comparison to healthy individuals. UBE2N overexpression exacerbated amyloid deposition in 5×FAD mice and senescent monkeys, whereas knocking down UBE2N via CRISPR/Cas9 reduced Aβ generation and cognitive deficiency. Moreover, pharmacological inhibition of UBE2N ameliorated Aβ pathology and subsequent transcript defects in 5×FAD mice. We have discovered that age-dependent expression of UBE2N is a critical regulator of AD pathology. Our findings suggest that UBE2N could serve as a potential pharmacological target for the advancement of AD therapeutics. Ubiquitin Conjugating Enzyme E2 N (UBE2N) levelwas elevated during amyloid beta (Aβ) deposition in AD mouse and patients' brains. UBE2N exacerbated Aβ generation in the AD mouse and senescent monkey. Drug inhibition of UBE2N ameliorated Aβ pathology and cognitive deficiency.

Infantile and Very Early Onset Inflammatory Bowel Disease: A Multicenter Study.

This study described disease characteristics and long-term outcomes in patients diagnosed with very early onset inflammatory bowel disease (VEOIBD) (diagnosed before 6 years of age) and infantile-IBD (before 2 years). Cases from 21 centers worldwide diagnosed with VEOIBD (2008-2018), with minimum 2 years of follow-up, were retrospectively reviewed. The cohort included 243 patients (52% males, median follow-up of 5.8 [range 2-18] years, including 69 [28%]) with infantile-IBD. IBD subtypes included Crohn's disease (CD), ulcerative colitis (UC), or IBD-unclassified (IBDU) in 30%, 59%, and 11%, respectively. Among patients with CD, 94% had colonic involvement, and among patients with UC/IBDU, 75% had pancolitis. Patients with infantile-IBD presented with higher rates of IBDU, lower hemoglobin and albumin levels, and higher C-reactive protein, and had lower response rates to first-induction therapy and corticosteroids therapy (P < .05 for all). Colectomy and diversion surgeries were performed in 11% and 4%, respectively, with no significant differences between age groups. Corticosteroid-free remission rates were 74% and 78% after 3 and 5 years, respectively, and 86% at end of follow-up. Genetic testing was performed in 96 (40%) patients. Among tested population, 15 (16%) were identified with monogenic disease. This group demonstrated lower response rates to induction therapies, higher rates of surgical intervention, and higher rates of major infections (P < .05 for all). Patients with VEOIBD, including infantile-IBD, exhibit low rate of complications and surgical interventions at the long term. Patients with monogenic IBD are at risk for more severe disease course.

The pulmonary-vascular-stump filling defect on CT post lung tumor resection: a predictor of cancer progression

BackgroundTo explore the pulmonary-vascular-stump filling-defect on CT and investigate its association with cancer progression.MethodsRecords in our institutional database from 2018 to 2022 were retrospectively analyzed to identify filling-defects in the pulmonary-vascular-stump after lung cancer resection and collect imaging and clinical data of patients.ResultsAmong the 1714 patients analyzed, 95 cases of filling-defects in the vascular stump after lung cancer resection were identified. After excluding lost-to-follow-up cases, a total of 77 cases were included in the final study. Morphologically, the filling-defects were dichotomized as 46 convex-shape and 31 concave-shape cases. Concave defects exhibited a higher incidence of increase compared to convex defects (51.7% v. 9.4%, P = 0.001). Among 61 filling defects in the pulmonary arterial stump, four (6.5%) increasing concave defects showed the nuclide concentration on PET and extravascular extension. The progression-free survival (PFS) time differed significantly among the concave, convex, and non-filling-defect groups (log-rank P < 0.0001), with concave defects having the shortest survival time. Multivariate Cox proportional hazards analysis indicated that the shape of filling-defects independently predicted PFS in early onset on CT (HR: 0.46; 95% CI: 0.39–1.99; P = 0.04). In follow-ups, the growth of filling-effects was an independent predictor of PFS (HR: 0.26; 95% CI: 0.11–0.65; P = 0.004).ConclusionsCertain filling-defects in the pulmonary-arterial-stump post lung tumor resection exhibit malignant growth. In the early onset of filling-defects on CT, the concave-shape independently predicted cancer-progression, while during the subsequent follow-up, the growth of filling-defects could be used independently to forecast cancer-progression.

Prosthetic Valve Endocarditis: A Retrospective Cohort Study Conducted at “Dr. Carol Davila” Central Military Emergency University Hospital in Bucharest

Objective: To evaluate patients with prosthetic valves who developed infective endocarditis by comparing treatment outcomes in both early- and late-onset IE episodes following prosthetic valve replacement surgery. This study sought to conduct a comprehensive assessment of the efficacy of these methodologies. The insights derived from this assessment can be utilized to enhance the quality of care for individuals with infective endocarditis who have undergone prosthetic valve replacement surgery. Results: During the period of investigation (January 2017–December 2022), 78 patients diagnosed with infective endocarditis (IE) on a prosthetic valve were admitted to the Infectious Diseases Department of the “Dr. Carol Davila” Central Military Emergency University Hospital in Bucharest. In 28 patients (35.8%), the onset of PVE occurred within 12 months of surgery (early onset), whereas in 50 patients (64.2%), the onset occurred more than 12 months after surgery (late onset). The mortality rate was 35.9% (53.6% among the early onset patients and 26% among the late-onset patients). Among patients who received surgical and medical therapy, the mortality rate was 29.6%, whereas among those who received only medical therapy, a 39.2% mortality rate was reported. According to the extracted data, antibiotic therapy was successful in 72.6% of the patients. In contrast, a combination of surgical and drug-based approaches resulted in a cure in 76.1% of patients. The most common etiological agent was Staphylococcus aureus (38.5%), followed by Enterococcus faecalis (26.9%) and Streptococcus mitis (10.3%). The mortality rate of patients infected with S. aureus was 29.2%, indicating the severity of this infectious agent. Conclusions: Prosthetic valve endocarditis (PVE) is a serious condition associated with a high mortality rate both in the short and long term. Regardless of the therapy used, the risk of death remains high.

Demographic, clinical, and social characteristics of anal cancer among patients stratified by age (

BackgroundAnal cancer is increasing globally, with a high number of new cases occurring in highly developed countries, including the U.S. The incidence of anal cancer is higher among people living with HIV (PLHIV), and the U.S. South continues to see higher HIV incidence rates and lagging HPV vaccination rates. We aimed to identify factors associated with early onset anal cancer in Alabama which may help explain cancer disparities in the South. MethodsUsing a cross-sectional study design, we examined demographic, clinical, and social characteristics among anal cancer patients stratified by diagnosis age (<50 and ≥50 years) in the Alabama cancer registry between 2012 and 2018. We used Wilcoxon rank sums and Pearson chi-square tests to assess associations between age at diagnosis, demographic (i.e., sex, race, marital status), clinical (i.e., BMI, HIV infection, site, stage, and histological type), and social (i.e. social vulnerability) characteristics, and multivariable logistic regression to estimate the odds of early onset cancer. ResultsAmong 519 patients with anal cancer in Alabama, 92 (17.7 %) were diagnosed at <50 years. The majority of patients were female (66.5 %) and White (83.4 %). Male sex, Black race, and HIV infection were associated with younger age at diagnosis. Black patients had a 4-fold increased odds of early onset anal cancer compared to White patients (AOR=4.39, CI=1.54–12.49). Black patients disproportionately lived in areas with higher social vulnerability. About 42 % of patients in areas with the highest social vulnerability were diagnosed with stage 3 or 4 cancer. About 8 % of cases were among people aged 35–44 years, which is close to double the proportion of anal cancer cases in this age group in the U.S. (4.7 %). ConclusionsPatients who are Black, male, and PLHIV may be at higher risk of early onset anal cancer compared to other populations in the South.

Understanding gender-responsive needs of girls in the Children and Young People Secure Estate (CYPSE): menstrual cycle considerations

Purpose The current study aimed to examine the population of girls in two secure children’s homes (SCHs) in the North East of England to consider the impact of menstruation on girls’ physical, mental and emotional wellbeing within secure settings. Gender-responsive approaches and understanding gender differences are central to trauma-informed provision within the Children and Young People Secure Estate (CYPSE). Whilst trauma-informed approaches are central, it could be argued that basic gender differences, such as the menstrual cycle, are currently being overlooked within research and practice. Design/methodology/approach A case file audit examined documentation of 24 girls who were admitted across both sites between January 2022 and January 2023. Findings Of the sample (n = 24), 50% had information recorded regarding their menstrual cycle during admission assessments. Six girls (25%) disclosed experiencing irregular menstruation. Painful cramping was noted by two girls (8%). One girl (4%) disclosed heavy bleeding, and menorrhagia (abnormal heavy bleeding) was reported for one further girl (4%). One girl (4%) disclosed early onset menarche. Case formulations tended to focus less on girls’ menstrual cycles or the potential impact of this on wellbeing. However, 100% of case formulations considered the potential impact of trauma and/or disrupted attachment on girls’ presentations. Originality/value The results indicate the impact of menstrual cycles on girls’ physical, mental and emotional wellbeing may benefit from much further consideration. Implications are presented alongside directions for future research.

The infants’ gut microbiome: setting the stage for the early onset of obesity

In the past three decades, dietary and lifestyle changes worldwide have resulted in a global increase in the prevalence of obesity in both adults and children. Known to be highly influenced by genetic, environmental and lifestyle factors, obesity is characterized by a low-grade chronic inflammation that contributes to the development of other metabolic diseases such as diabetes and cardiovascular disease. Recently, the gut microbiome has been added as a cause/contributor to the development of obesity. As differences in the microbiome between obese and normoweight individuals have been observed, we set out to determine whether infants harbor an obesogenic microbiome early on and whether the pre-pregnancy status of the mother (obese or normoweight) is correlated to their infant’s microbiome composition. Using shotgun sequencing, we analyzed stool samples throughout the first year of life from infants born to obese (n = 23 participants, m = 104 samples) and normoweight (n = 23 participants, m = 99 samples) mothers. We found that the infants’ microbiome diversity at taxonomic and functional levels was significantly influenced by time (ANOVA p &amp;lt; 0.001) but not by the mother’s pre-pregnancy status. Overall, no deterministic succession of taxa or functions was observed. However, infants born to obese mothers were found to have a significantly higher Bacillota/Bacteroidota ratio (p = 0.02) at six months, were significantly depleted from six months old of the well-established obesity biomarkers Akkermansia municiphila and Faecalibacterium prausnitzii (p &amp;lt; 0.01), and were at one week old, significantly enriched in pathways such as the UDP-N-acetyl-D-glucosamine biosynthesis II (p = 0.02) involved in leptin production, suggesting perhaps that there may exist some underlying mechanisms that dictate the development of an obesogenic microbiota early on.

Childhood interstitial lung diseases: current understanding of the classification and imaging findings.

Childhood interstitial lung diseases (chILDs) encompass a diverse group of disorders with a high mortality rate and severe respiratory morbidities. Recent investigations have revealed that the classification of adult ILDs is not valid for chILDs, particularly for ILDs of early onset. Therefore, Children's Interstitial Lung Disease Research Cooperative of North America proposed a new classification of chILDs for affected children under 2years of age, and later another classification for affected individuals between 2 and 18years of age. In this review, we provide an overview of the imaging findings of chILDs by classification. Most infantile ILDs have unique clinical, radiological, and molecular findings, while the manifestation of pediatric ILDs overlaps with that of adult ILDs.

MYO5B gene mutations may promote the occurrence of very early onset inflammatory bowel disease: a case report

BackgroundWith recent advances in gene sequencing technology, more than 60 genetic mutations associated with very early onset inflammatory bowel disease (VEO-IBD) have been reported. Most of the genes are associated with immune deficiencies. The Myosin 5B (MYO5B) gene is primarily involved in cell motility and material transport which is associated with congenital intractable diarrhea and cholestasis. No studies have examined the relationship between the MYO5B gene and VEO-IBD. We report a case of a child with a mutation in the MYO5B gene who was diagnosed with VEO-IBD, then we investigated the association between the MYO5B gene and VEO-IBD.Case presentationA 7-month-old baby girl with a chief complaint of “blood in the stool for more than 4 months and vaginal pus and blood discharge for 3 weeks” was diagnosed with VEO-IBD, and her symptoms improved after treatment with mesalazine. The whole-exome sequencing was performed with peripheral blood. Immunohistochemistry was performed on the terminal ileal tissue. Western blotting, quantitative polymerase chain reaction (Q-PCR) and immunofluorescence were performed with cultured organoid tissue from the terminal ileum. Whole-exome sequencing identified heterozygous missense of MYO5B variant of unknown significance (p. [I769N]; [T1546M]). Immunohistochemistry revealed a significant decrease in the expression of MYO5B protein in the terminal ileum of the child with MYO5B mutation; Q-PCR revealed a decrease in the mRNA levels of occludin and ZO-1 and both the mRNA levels and protein levels of MYO5B was downregulated in the patient. Immunofluorescence images showed that MYO5B gene mutation disrupted the apical delivery of transporters SGLT1, NHE3 and AQP7.ConclusionsMYO5B gene mutation leading to the downregulation of MYO5B protein may promote the occurrence of VEO-IBD by decreasing mRNA and protein levels of intestinal tight junction genes and dislocating the apical transporters.

The association between sleep quality and accelerated epigenetic aging with metabolic syndrome in Korean adults

BackgroundHealthy sleep is vital for maintaining optimal mental and physical health. Accumulating evidence suggests that sleep loss and disturbances play a significant role in the biological aging process, early onset of disease, and reduced lifespan. While numerous studies have explored the association between biological aging and its drivers, only a few studies have examined its relationship with sleep quality. In this study, we investigated the associations between sleep quality and epigenetic age acceleration using whole blood samples from a cohort of 692 Korean adults. Sleep quality of each participant was assessed using the validated Pittsburgh Sleep Quality Index (PSQI), which encompassed seven domains: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbance, use of sleep medication, and daytime dysfunction. Four epigenetic age accelerations (HorvathAgeAccel, HannumAgeAccel, PhenoAgeAccel, and GrimAgeAccel) and the pace of aging, DunedinPACE, were investigated for epigenetic aging estimates.ResultsAmong the 692 participants (good sleepers [n = 441, 63.7%]; poor sleepers [n = 251, 36.3%]), DunedinPACE was positively correlated with PSQI scores in poor sleepers (γ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\gamma$$\\end{document}=0.18, p < 0.01). GrimAgeAccel (β\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta$$\\end{document}=0.18, p = 0.02) and DunedinPACE (β\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\beta$$\\end{document}=0.01, p < 0.01) showed a statistically significant association with PSQI scores only in poor sleepers by multiple linear regression. In addition, every one-point increase in PSQI was associated with a 15% increase in the risk of metabolic syndrome (MetS) among poor sleepers (OR = 1.15, 95% CI = 1.03–1.29, p = 0.011). In MetS components, a positive correlation was observed between PSQI score and fasting glucose (γ\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\gamma$$\\end{document}= 0.19, p < 0.01).ConclusionsThis study suggests that worsening sleep quality, especially in poor sleepers, is associated with accelerated epigenetic aging for GrimAgeAccel and DundinePACE with risk of metabolic syndrome. This finding could potentially serve as a promising strategy for preventing age-related diseases in the future.

Clinical features and underlying etiology of children with Lennox-Gastaut syndrome.

Lennox-Gastaut Syndrome (LGS) is characterized by the presence of multiple seizure types and encompasses a heterogenous group of etiologies. The aim of our study was to evaluate the etiological profile of LGS and investigate seizure outcomes based on different clinical variables. The clinical features, neuroimaging findings, genetic testing and other testing results of LGS patients were systematically reviewed. The identifiable etiology was categorized as either acquired or nonacquired. Univariate and multivariate regression analyses were performed to explore the association between clinical variables and seizure outcome at the last follow-up. We enrolled 156 patients diagnosed with LGS, of whom 66% were male. The mean age of patients was 34.2months and the median follow-upduration was 29.5months (interquartile range = 14-56.25months). The initial seizure type was epileptic spasm in 61 patients, among which 33 of them met the criteria for infantile epileptic spasm syndrome. All patients underwent neuroimaging test, with 25% falling into the acquired structural category. Etiology could be identified in 84 individuals, including pathogenetic variants found in 34 out of 117 patients with nonacquired etiology. CHD2 mutations were most frequently observed among these pathogenetic variants. At the last follow-up, favorable outcomes were observed in 27 patients. The identification of etiology emerged as a significant determinant influencing LGS outcome; specifically, patients with unknown etiology had a higher likelihood of experiencing favorable outcomes compared to those with known cause (p = 0.041). Early onset age and longer epilepsy duration significantly increased the odds of an unfavorable outcome (p = 0.006 and 0.024). We present novel data on the clinical and etiological spectrum of LGS, with determined etiology observed in over half of the patients. Epileptic spasms were found to be more prevalent than tonic seizures as seizure onset types in LGS. The presence of a known etiology, earlier age at onset, and longer duration of epilepsy were associated with a poorer long-term epileptological outcome.

Postural instability and lower extremity dysfunction in upper motor neuron-dominant amyotrophic lateral sclerosis

BackgroundUpper motor neuron-dominant ALS (UMND ALS) is recognized to have early onset and good prognosis, but may have a rapid decline in motor function due to gait instability in the early stage. We investigated changes in lower extremity function in UMND ALS, particularly UMND ALS patients accompanied with postural instability or repeated falls (UMND ALS plus).ResultsAmong the 2,353 ALS patients reviewed, 211 (9.0%) had UMND ALS. UMND ALS had a longer diagnosis delay and restricted symptoms. Although UMND ALS patients had better lower extremity function and strength than matched classic ALS patients on first evaluation, there was no difference in the time of needing assistance or not being able to walk after disease onset. In contrast, UMND ALS plus has severe UMN symptoms and a more rapid decline in motor function. The lower extremity function was no better than that in the matched classic ALS. The prognosis of UMND ALS and UMND ALS plus were significantly better than those of overall ALS.ConclusionUMND ALS has restricted symptoms but has a rapid decline in lower extremity function in the early stage of the disease. The motor function decline of UMND ALS plus is as fast as classic ALS. Whether these patients represent a distinct subgroup of ALS deserves further investigation.

Atopic dermatitis in Ethiopian children: a multicenter study of clinical severity, characteristics, and sociodemographic factors

BackgroundAtopic dermatitis (AD) is a chronic relapsing, pruritic, inflammatory skin disease. Assessing the characteristics and risk factors of severe AD is central to healthcare workers’ understanding and subsequent education of patients for the most optimal outcomes. The clinical characteristics are known to vary depending on populations and regions. AD has been well-documented in the global North in mainly Caucasian populations, while very few studies have been conducted on African patients residing in Africa. This study assessed the clinical characteristics, severity, and sociodemographic factors of children with AD in Southern Ethiopia.MethodsA hospital-based cross-sectional study was conducted among 461 children and their caregivers in four randomly selected hospitals in Southern Ethiopia from October 2022 to September 2023. A systematic sampling technique was used to enroll study participants. Clinical profile and sociodemographic data were collected by trained data collectors. The Scoring Atopic Dermatitis (SCORAD) index tool was used. The descriptive analysis was performed to characterize study participants. Univariate and ordinary logistic regression were used to identify factors associated with the SCORAD index score. The OR with 95% was used to show the strength of association, and a p-value of &amp;lt;0.05 was used to declare the level of significance.ResultOut of 461 AD-diagnosed children, 212 (46%) were girls and 249 (54%) were boys. In the sample of pediatric patients, 149 (32.3%) exhibited mild AD, 231 (46.2%) presented with moderate, and 99 (21.5%) showed signs and symptoms of severe AD. All patients had itching. Dryness of skin, excoriation, and erythema, followed by lichenification, were the most observed signs. In the ordinary logistic regression model, age onset of the disease [AOR 95% CI 1.95 (1.3–2.94)], sex of caregiver or family [AOR 95% CI 0.61 (0.41–0.90)], family atopy history [AOR 95% CI 0.64 (0.44–0.93)], mother education status [95% CI 2.45 (1.1–5.47)], and use of herbal medication [AOR 95% CI 0.50 (0.33–0.79)] were significantly associated with the severity of AD.ConclusionIn this study, 68% of children were found to have moderate-to-severe AD. Early onset, maternal education, familial atopy history, sex of caregiver, and use of herbal medication were independent predictors of severe AD in children. We recommend further investigation into these variables for their potential to serve as markers to assess the severity of AD and improve the care and management of children with AD in Ethiopia.

Sustained North Atlantic warming drove anomalously intense MIS 11c interglacial

The Marine Isotope Stage (MIS) 11c interglacial and its preceding glacial termination represent an enigmatically intense climate response to relatively weak insolation forcing. So far, a lack of radiometric age control has confounded a detailed assessment of the insolation-climate relationship during this period. Here, we present 230Th-dated speleothem proxy data from northern Italy and compare them with palaeoclimate records from the North Atlantic region. We find that interglacial conditions started in subtropical to middle latitudes at 423.1 ± 1.3 thousand years (kyr) before present, during a first weak insolation maximum, whereas northern high latitudes remained glaciated (sea level ~ 40 m below present). Some 14.5 ± 2.8 kyr after this early subtropical onset, peak interglacial conditions were reached globally, with sea level 6–13 m above present, despite weak insolation forcing. We attribute this remarkably intense climate response to an exceptionally long (~15 kyr) episode of intense poleward heat flux transport prior to the MIS 11c optimum.

Circular walking is useful for assessing the risk of falls in early progressive supranuclear palsy.

Progressive supranuclear palsy (PSP) is characterized by early onset postural instability and frequent falls. Circular walking necessitates dynamic postural control, which is impaired in patients with PSP. We aimed to explore gait parameters associated with the risk of falls in patients with PSP, focusing on circular walking. Sixteen drug-naïve patients with PSP, 22 drug-naïve patients with Parkinson's disease (PD), and 23 healthy controls were enrolled. Stride lengths/velocities and their coefficients of variation (CV) during straight and circular walking (walking around a circle of 1-m diameter) were measured under single-task and cognitive dual-task conditions. Correlation analysis was performed between gait parameters and postural instability and gait difficulty (PIGD) motor subscores, representing the risk of falls. Patients with PSP had significantly higher CVs of stride lengths/velocities during circular walking than those during straight walking, and the extent of exacerbation of CVs in patients with PSP was larger than that in patients with PD under single-task conditions. Stride lengths/velocities and their CVs were significantly correlated with PIGD motor subscores in patients with PSP only during single-task circular walking. In addition, patients with PSP showed progressive decrements of stride lengths/velocities over steps only during single-task circular walking. Worse gait parameters during circular walking are associated with an increased risk of falls in patients with PSP. Circular walking is a challenging task to demand the compromised motor functions of patients with PSP, unmasking impaired postural control and manifesting sequence effect. Assessing circular walking is useful for evaluating the risk of falls in patients with early PSP.

Comparative evaluation of disease dynamics in wild boar and domestic pigs experimentally inoculated intranasally with the European highly virulent African swine fever virus genotype II strain “Armenia 2007”

Since the reintroduction of African swine fever virus (ASFV) in Europe in 2007 and its subsequent spread to Asia, wild boar has played a crucial role in maintaining and disseminating the virus. There are significant gaps in the knowledge regarding infection dynamics and disease pathogenesis in domestic pigs and wild boar, particularly at the early infection stage. We aimed to compare domestic pigs and wild boar infected intranasally to mimic natural infection with one of the original highly virulent genotype II ASFV isolates (Armenia 2007). The study involved euthanising three domestic pigs and three wild boar on days 1, 2, 3, and 5 post-infection, while four domestic pigs and four wild boar were monitored until they reached a humane endpoint. The parameters assessed included clinical signs, macroscopic lesions, viremia levels, tissue viral load, and virus shedding in nasal and rectal swabs from day 1 post-infection. Compared with domestic pigs, wild boar were more susceptible to ASFV, with a shorter incubation period and earlier onset of clinical signs. While wild boar reached a humane endpoint earlier than domestic pigs did, the macroscopic lesions were comparatively less severe. In addition, wild boar had earlier viremia, and the virus was also detected earlier in tissues. The medial retropharyngeal lymph nodes were identified as key portals for ASFV infection in both subspecies. No viral genome was detected in nasal or rectal swabs until shortly before reaching the humane endpoint in both domestic pigs and wild boar, suggesting limited virus shedding in acute infections.

Topical Treatment and Aesthetic Procedures in Management of Acne Vulgaris

Acne vulgaris is a common, chronic inflammatory skin disease affecting up to 80% of young adults and adolescents. The pathogenesis of acne is multifactorial and involves the pilosebaceous units of the skin. As a result of the disease process, skin lesions such as open and closed comedones, nodules, pustules, and papules appear on the skin. In recent years, acne has been increasingly observed in younger patients, which is associated with the earlier onset of puberty. Moreover, acne is increasingly diagnosed in individuals over 20 years of age, particularly in women, which is referred to as adult female acne (AFA). Effective and rapid implementation of treatment is crucial to prevent complications such as post-inflammatory hyperpigmentation and acne scars, as well as to mitigate the negative psychological impact of the disease on patients. The article discusses both topical treatment and aesthetic medicine procedures in the management of acne vulgaris. Topical treatments include the use of retinoids, antibiotics, benzoyl peroxide, clascoterone, dapsone, azelaic acid, and combination therapies. Aesthetic procedures such as chemical peels, microdermabrasion, photodynamic therapy, blue light therapy, and laser therapies can be beneficial as adjunctive treatments. The article also addresses the issue of acne as a comorbid condition in patients seeking aesthetic medicine treatments, even if it is not the primary reason for their visit.