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Objective: Despite our understanding of Sertoli cell function and the state of spermatogenesis, the underlying mechanisms remain unclear. This study was conducted to compare the effects of orchiectomy and steroid treatment on fertility in testicular atrophy occurring after testicular torsion.Methods: Thirty-three rats were divided into four groups. The atrophy, orchiectomy, and atrophy-steroid groups each contained nine rats, while the control group contained six. The left testes were rotated 720º, and atrophy was observed. In the atrophy-steroid rats, orchiectomy was performed after atrophy, and 1 mg/kg steroid was injected. Each male rat was housed with five female rats for 6 days. The fertility of the male rats was evaluated based on the pregnancy of the female rats. Left and right orchiectomies were performed to determine the tissue Johnsen score (JS) and the serum inhibin B (IB) level.Results: JS values were significantly lower in the atrophy, orchiectomy, and atrophy-steroid groups than in the control group (pp>0.05). Similarly, no significant differences in IB level or fertility percentage were found between the atrophy and orchiectomy rats (p>0.05).Conclusion: In unilateral testicular atrophy, which can occur in the prepubertal period due to various causes, orchiectomy does not appear to benefit fertility, as indicated by IB, JS, and the fertility percentage.

Introduction Differences in brain network connectivity may reflect the capability of the neurological substrate to compensate for brain damage and preserve cognitive function (cognitive reserve). We examined the associations between white matter connectivity, brain damage markers, and cognition in a population sample of middle-aged individuals. Methods A total of 4759 participants from The Maastricht Study (mean age = 59.2, SD = 8.7, 50.2% male) underwent cognitive testing and diffusion magnetic resonance imaging (dMRI), from which brain volume, structural connectivity, and vascular damage were quantified. Multivariable linear regression was used to investigate whether connectivity modified the association between brain damage and cognition, adjusted for demographic and cardiometabolic risk factors. Results More atrophic and vascular brain damage was associated with worse cognition scores. Increasing connectivity moderated the negative association between damage and cognition (chi(2) = 8.64, df = 3, p

Funder: Alzheimer Society of Canada; Id: http://dx.doi.org/10.13039/501100000143, Funder: Weston Brain Institute; Id: http://dx.doi.org/10.13039/100012479, Funder: Fonds de Recherche du Québec ‐ Santé, Funder: Canadian Institutes of Health Research; Id: http://dx.doi.org/10.13039/501100000024, Funder: NIHR Rare Diseases Translational Research Collaboration, Funder: Deutsche Forschungsgemeinschaft; Id: http://dx.doi.org/10.13039/501100001659, Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.

Following traumatic brain injury (TBI), cerebral metabolic dysfunction, characterized by an elevated cerebral microdialysis (CMD) lactate/pyruvate (LP) ratio, is associated with poor outcome. However, the exact pathophysiological mechanisms underlying this association are not entirely established. In this pre-planned analysis of the BIOmarkers of AXonal injury after Traumatic Brain Injury (BIO-AX-TBI) prospective study, we investigated any associations of LP ratio with brain structure volume change rates at 1 year. Fourteen subjects underwent acute-phase (0-96 h post-TBI) CMD monitoring and had longitudinal magnetic resonance imaging (MRI) quantification of brain volume loss between the subacute phase (14 days to 6 weeks) and 1 year after TBI, recalculated as an annual rate. On average, CMD showed an elevated (>25) LP ratio (31 [interquartile range (IQR) 24-34]), indicating acute cerebral metabolic dysfunction. Annualized whole brain and total gray matter (GM) volume change rates were abnormally reduced (-3.2% [-9.3 to -2.2] and -1.9% [-4.4 to 1.7], respectively). Reduced annualized total GM volume correlated significantly with elevated CMD LP ratio (Spearman's rho = -0.68, p-value = 0.01) and low CMD glucose (rho = 0.66, p-value = 0.01). After adjusting for age, admission Glasgow Coma Scale (GCS) score and CT Marshall score, CMD LP ratio remained strongly associated with 1-year total GM volume change rate (p < 0.001; multi-variable analysis). No relationship was found between WM volume changes and CMD metabolites. We demonstrate a strong association between acute post-traumatic cerebral metabolic dysfunction and 1-year gray matter atrophy, reinforcing the role of CMD LP ratio as an early biomarker of poor long-term recovery after TBI.

Objective To measure the cranial volume differences from 15 different parts in the follow-up of relapsing-remitting multiple sclerosis (RRMS) patients and correlate them with clinical parameters. Methods Forty-seven patients with RRMS were included in the study. Patients were grouped into two categories; low Expanded Disability Status Scale (EDSS) (< 3; group 1), and moderate-high EDSS (≥ 3; group 2). Patients were evaluated with Beck Depression Inventory (BDI), Montreal Cognitive Assessment (MOCA), Symbol Digit Modalities Test(SDMT), Fatigue Severity Scale (FSS), and calculated Annualized Relapse Rate (ARR) scores. Magnetic resonance imaging (MRI) was performed with a 1.5T MRI device (Magnetom AERA, Siemens, Erlangen, Germany) twice in a 1-year period. Volumetric analysis was performed by a free, automated, online MRI brain volumetry software. The differences in volumetric values between the two MRI scans were calculated and correlated with the demographic and clinical parameters of the patients. Results The number of attacks, disease duration, BDI, and FSS scores were higher in group 2; SDMT was higher in group 1. As expected, volumetric analyses have shown volume loss in total cerebral white matter in follow-up patients (p < 0.001). In addition, putaminal volume loss was related to a higher number of attacks. Besides, a negative relation between FSS with total amygdala volumes, a link between atrophy of globus pallidus and ARR, and BDI scores was found with the aid of network analysis. Conclusions Apart from a visual demonstration of volume loss, cranial MRI with volumetric analysis has a great potential for revealing covert links between segmental volume changes and clinical parameters. Resumo Objetivo Medir as diferenças de dominância craniana de 15 regiões diferentes no seguimento de pacientes com esclerose múltipla recorrente-remitente (EMRR) e correlacioná-las com parâmetros clínicos. Métodos Quarenta e sete pacientes com EMRR foram incluídos no estudo. Os pacientes foram agrupados em duas categorias; EDSS baixo (< 3; grupo 1) e EDSS médio-alto (≥ 3; grupo 2). Os pacientes foram avaliados com o Inventário de Depressão de Beck (BDI, na sigla em inglês), Montreal Cognitive Assessment (MOCA, na sigla em inglês), Symbol Digit Modality Tests (SDMT, na sigla em inglês), Fatigue Severity Scale (FSS, na sigla em inglês) e taxa de ataque anual (ARR, na sigla em inglês). Duas ressonâncias magnéticas (RMs) foram feitas em um ano com um aparelho de imagem de 1,5 T MR (Magnetom AERA, Siemens, Erlangen, Alemanha). A análise de volume foi realizada com um software de medição mestre cerebral de RM gratuito e automatizado. As diferenças volumétricas entre os dois exames de RM foram calculadas e correlacionadas com os parâmetros demográficos e clínicos dos pacientes. Resultados Número de crises, duração da doença, escores BDI e FSS foram mais elevados no grupo 2; as pontuações do SDMT foram maiores no grupo 1. Como esperado, as análises volumétricas mostraram perda total de volume de substância branca no seguimento (p < 0,001). Além disso, a perda da dominância putaminal foi associada ao maior número de ataques. Além disso, uma relação negativa entre FSS e volume total da amígdala, e uma correlação entre ARR e BDI e atrofia do globo pálido foi determinada com a ajuda da análise de rede. Conclusões Além da demonstração visual da perda de volume, a RM com análise volumétrica tem grande potencial para revelar alterações segmentares dominantes e conexões ocultas entre parâmetros clínicos.

Background: Chorea-acanthocytosis (ChAc) is the most common type of neuroacanthocytosis syndromes. Characteristic movement disorders of ChAc are choreiform movements affecting both trunk and extremities. Acanthocytosis in peripheral blood smear, elevated serum creatine kinase, atrophy of heads of caudate nuclei and dilation of the anterior horn of the lateral ventricles in magnetic resonance imaging could assist the diagnosis of ChAc. Objective: We aimed to report on the use of acupuncture to successfully improve ChAc symptoms. Method: A patient with definite ChAc was admitted, who had suffered from involuntary tongue protrusion for about 10 years. Acupuncture treatment was administrated for 3 times a week for 2 months. The chorea tremor control area, Baihui (GV20), Sishencong (EX-HN1), Shenting (GV24), Benshen (GB13, bilateral), Yintang (GV29), Neiguan (PC6, bilateral), Tongli (HT5, bilateral), Zusanli (ST36, bilateral), Sanyinjiao (SP6, bilateral), Dicang (ST4, bilateral), Chengjiang (CV24), Lianquan (CV23), Jinjin (EX-HN12) and Yuye (EX-HN13) were selected as acupunture points. Results: Previous drug dosage was reduced and the frequency of involuntary tongue protrusion was significantly reduced. Other clinical symptoms were also well controlled. Peripheral blood smear still indicated an increased proportion of red lineage, but blood analyses revealed improvement at follow-up. Conclusions: For patients who do not response well to conventional medical treatments, acupuncture might be used as an alternative treatment for symptoms related to ChAc.

Homocysteine (Hcy) is a vascular risk factor associated with cognitive impairment and cerebrovascular disease but has also been implicated in Alzheimer's disease (AD). Using multivariate Scaled Subprofile Model (SSM) analysis, we sought to identify a network pattern in structural neuroimaging reflecting the regionally distributed association of plasma Hcy with subcortical gray matter (SGM) volumes and its relation to other health risk factors and cognition in 160 healthy older adults, ages 50-89. We identified an SSM Hcy-SGM pattern that was characterized by bilateral hippocampal and nucleus accumbens volume reductions with relative volume increases in bilateral caudate, pallidum, and putamen. Greater Hcy-SGM pattern expression was associated with greater white matter hyperintensity (WMH) volume, older age, and male sex, but not with other vascular and AD-related risk factors. Mediation analyses revealed that age predicted WMH volume, which predicted Hcy-SGM pattern expression, which, in turn, predicted cognitive processing speed performance. These findings suggest that the multivariate SSM Hcy-SGM pattern may be indicative of cognitive aging, reflecting a potential link between vascular health and cognitive dysfunction in healthy older adults.

To describe characteristics of indocyanine green (ICG) angiographic plaques in the nonexudative fellow eye of White patients with unilateral treatment-naïve exudative neovascular age-related macular degeneration through optical coherence tomography (OCT) and OCT angiography (OCTA).In this retrospective cross-sectional study, nonexudative eyes with ICG angiographic plaques were analyzed by OCT B-scans for the sensitivity of a double-layer sign, a pigment epithelium detachment, outer retinal atrophy, hyperreflective dots, and subretinal hyperreflective material (SRHM). The ICG angiographic plaque was matched with a macular neovascularization in OCTA en face scans and color-coded B scans.In total, 35 ICG angiographic plaques in 33 of 291 (11%) nonexudative eyes were diagnosed. OCT revealed 27 double-layer sign (78%), eight pigment epithelium detachment (23%), 8 outer retinal atrophy (23%), eight hyperreflective dots (23%), and one subretinal hyperreflective material (3%). OCTA confirmed a macular neovascularization in 28 plaques (80%): 7 (20%) in en face scans, 3 (9%) in color-coded B scans, and 18 (51%) in both. The area size in OCTA was significantly smaller than that of ICG angiography ( P = 0.002).The diagnosis of an ICG angiographic plaque in nonexudative fellow eyes of Whites with unilateral treatment-naïve exudative neovascular age-related macular degeneration was highly suggestive of a typical macular neovascularization type 1 as characterized by OCT and OCTA.

Alcohol-associated liver disease (ALD) is a worldwide health problem, of which the effective treatment is still lacking. Both detrimental and protective roles of adipose tissue have been implicated in ALD. Although alcohol increases adipose tissue lipolysis to promote alcohol-induced liver injury, alcohol also activates brown adipose tissue (BAT) thermogenesis as an adaptive response in protecting against alcohol-induced liver injury. Moreover, aging and obesity are also risk factors for ALD. In the present study, we investigated the effects of autophagy receptor protein SQSTM1/p62 on adipose tissue and obesity in alcohol-induced liver injury in both young and aged mice.Young and aged whole-body SQSTM1/p62 knockout (KO) and their age-matched wild-type (WT) mice were subjected to chronic plus binge (Gao-binge) alcohol feeding. Blood, adipose and liver tissues were collected for biochemical and histologic analysis.Aged but not young SQSTM1/p62 KO mice had significantly increased body weight and fat mass compared with the matched WT mice. Gao-binge alcohol feeding induced white adipose atrophy and decreased levels of SQSTM1/p62 levels in adipose tissue in aged WT mice. SQSTM1/p62 KO aged mice were resistant to Gao-binge alcohol-induced white adipose atrophy. Alcohol feeding increased the expression of thermogenic genes in WT mouse BAT, which was significantly blunted in SQSTM1/p62 KO aged mice. Alcohol-fed aged SQSTM1/p62 KO mice showed significantly higher levels of serum alanine aminotransferase, hepatic triglyceride, and inflammation compared with young and aged WT mice fed with alcohol. Alcohol-fed SQSTM1/p62 KO mice also increased secretion of proinflammatory and angiogenic adipokines that may promote alcohol-induced liver injury.Loss of SQSTM1/p62 in aged mice leads to obesity and impairs alcohol-induced BAT adaptation, resulting in exacerbated alcohol-induced liver injury in mice.

Parkinson's disease (PD) is a multifaceted neurodegenerative disorder accompanied by mild cognitive impairment (MCI) as a crucial nonmotor manifestation. Event-related oscillations (EROs) are suggested to reflect cognitive status associated with subcortical structures in neurodegenerative conditions. In this study, 36 individuals with PD-MCI and 32 PD-CN were compared with 60 healthy control (HC) participants using visual EROs by measures of event-related spectral perturbation and inter-trial coherence, along with subcortical gray matter volumes based on the FIRST algorithm. Cross-correlations among electrophysiological, neuropsychological, and structural parameters were investigated exploratively. Both PD-MCI and PD-CN patients had diminished delta and alpha phase-locking than HC, however, electrophysiological abnormalities were more pronounced in PD-MCI over frontal, central, parietal, and temporal locations in almost all frequency bands, accompanied by bilateral thalamus, hippocampus, and right putamen atrophy. PD-CN had lower hippocampal volumes than HC, without exhibiting any subcortical differences from PD-MCI. Lastly, EROs showed low-to-high correlations with structural and neuropsychological measures. These findings may highlight the complex interplay between electrophysiological, neuropsychological, and structural parameters in detected abnormalities of PD-CN and PD-MCI. Dokuz Eylül Üniversitesi

In brief Maternal obesity plus high-fat diet in breastfeeding induces stromal hyperplasia and diffuse acinar atrophy in the rat prostate at aging, related to dyslipidemia and testosterone reduction. The high-lipid nutritional environment from intrauterine and throughout life favors the development of prostatic intraepithelial neoplasia and aggravated degenerative alterations in the gland. Abstract Maternal obesity and high-fat diet (HFD) affect permanently prostate histophysiology in adulthood, but the consequences during aging are unknown. Here, we evaluated the prostate alterations in middle-aged rats subjected to a high-lipid nutritional environment (HLE) in different ontogenetic periods. Wistar rats (56 weeks of age) were assigned into groups exposed to standard nutrition (C) or HLE during gestation (G), gestation and lactation (GL), from lactation onward (L), from weaning onward (W) and from gestation onward (AL). HLE in the periods after weaning consisted of HFD (20% fat), and during gestation and lactation it also included previous maternal obesity induced by the HFD. HLE increased total cholesterol and triglyceride levels in all groups and led to insulin resistance in GL and AL and obesity in L. Serum testosterone levels decreased ~67% in GL, ~146% in L and W, and ~233% in AL. Histological and stereological analysis revealed an increment of the stromal compartment and collagen fibers in the prostates of all HLE groups, as well as degenerative lesions, such as cell vacuolation and prostate concretions. HLE aggravated acinar atrophy in G, GL, and L, and in AL it reached more than 50% of the prostate area for most animals. The foci of prostatic intraepithelial neoplasia increased in AL. Tissue expression of androgen receptor did not vary among groups, except for a higher stromal expression for G and GL. Even when restricted to gestation and lactation, HLE induces diffuse acinar atrophy in the aging prostate and worsens degenerative and premalignant lesions when it continues throughout life.

Primary progressive apraxia of speech (PPAOS) is a neurodegenerative motor speech disorder affecting the ability to produce speech. If agrammatic aphasia is present, it can be referred to as the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA). We investigated whether resting-state functional MRI (rs-fMRI) connectivity from disease ‘epicenters’ correlated with longitudinal grey matter atrophy and hypometabolism in nfvPPA and PPAOS. Eighteen nfvPPA and 23 PPAOS patients underwent clinical assessment, structural MRI, rs-fMRI, and [(18)F] fluorodeoxyglucose (FDG)-PET at baseline and ~2 years follow-up. Rates of neurodegeneration in nfvPPA and PPAOS correlated with functional connectivity to the premotor, motor, and frontal cortex. Connectivity to the caudate and thalamus was more strongly associated with rates of hypometabolism than atrophy. Connectivity to the left Broca’s area was more strongly associated with rates of atrophy and hypometabolism in nfvPPA. Finally, functional connectivity to a network of regions, and not to a single epicenter, correlated with rates of neurodegeneration in PPAOS and nfvPPA, suggesting similar biological mechanisms driving disease progression, with regional differences related to language.

To identify the risk factors associated with myopic macular neovascularization (mMNV)-related complications in patients treated with intravitreal anti-VEGF agents.Longitudinal cohort study.Myopic eyes (n = 313) with active mMNV and median (interquartile range) follow-up of 42 months (interquartile range, 18-68 months) after initiation of anti-VEGF treatment.Data regarding patients' clinical and mMNV-related characteristics were collected at baseline. Subsequent OCT scans were inspected for mMNV-related complications. Best-measured visual acuity (BMVA) values were retrieved from each visit.Incidence rate and hazard ratio (HR, with 95% confidence interval [CI]) of risk factors for fibrosis and macular atrophy calculated with Kaplan-Meier curves and Cox regression models. Crude incidence of macular hole (MH). Longitudinal BMVA changes.Five-year incidence of fibrosis, atrophy, and MH were 34%, 26%, and 8%, respectively. The rate of fibrosis was 10.3 (95% CI, 8.25-12.6) per 100 person-years. Risk factors were subfoveal mMNV location (HR [95% CI] = 12.7 [2.70-56.7] vs. extrafoveal, P = 0.001) and intraretinal fluid at baseline (HR [95% CI] = 1.75 [1.05-2.98], P = 0.03). The rate of macular atrophy was 6.5 (95% CI, 5-8.3) per 100 person-years. Risk factors were diffuse (HR, 2.20 vs. tessellated fundus; 95% CI, 1.13-5.45; P = 0.02) or patchy chorioretinal atrophy (HR, 3.17 vs. tessellated fundus; 95% CI, 1.32-7.64; P = 0.01) at baseline and more numerous anti-VEGF injections before baseline (HR, 1.21; 95% CI, 1.06-1.38 for each treatment; P = 0.005). Eyes with fibrosis and macular atrophy had faster BMVA decay over follow-up. Twenty eyes (6%) developed MH. Two subtypes of MH were identified: "atrophic" and "tractional."Myopic MNV-related complications are common in the long term despite initially successful treatment and have detrimental effects on visual acuity. Insights into their incidence and risk factors may help for future treatments to mitigate sight-threatening outcomes.

Background: Despite highly effective treatment strategies for patients with relapsing-remitting multiple sclerosis (RRMS), long-term neurodegeneration and disease progression are often considerable. Accurate blood-based biomarkers that predict long-term neurodegeneration are lacking. Objective: To assess the predictive value of serum neurofilament-light (sNfL) and serum contactin-1 (sCNTN1) for long-term magnetic resonance imaging (MRI)–derived neurodegeneration in natalizumab-treated patients with RRMS. Methods: sNfL and sCNTN1 were measured in an observational cohort of natalizumab-treated patients with RRMS at baseline (first dose) and at 3 months, Year 1, Year 2, and last follow-up (median = 5.2 years) of treatment. Disability progression was quantified using “EDSS-plus” criteria. Neurodegeneration was measured by calculating annualized percentage brain, ventricular, and thalamic volume change (PBVC, VVC, and TVC, respectively). Linear regression analysis was performed to identify longitudinal predictors of neurodegeneration. Results: In total, 88 patients (age = 37 ± 9 years, 75% female) were included, of whom 48% progressed. Year 1 sNfL level (not baseline or 3 months) was associated with PBVC (standardized (std.) β = −0.26, p = 0.013), VVC (standardized β = 0.36, p Conclusion: Year 1 (but not baseline) sNfL level was predictive for long-term brain atrophy in patients treated with natalizumab. sCNTN1 level did not show a clear predictive value.

The aim of this case report is to present the multimodal imaging characteristics of pigmented paravenous retinochoroidal atrophy (PPRCA) in a pediatric patient with cystoid macular edema (CME). A 7-year-old girl was admitted to our clinic with complaints of mild blurred vision and poor night vision. Best corrected visual acuity was 10/10 in both eyes. Fundus examination showed atrophic areas around the optic nerve and along the retinal vessels in both eyes. A few small dot-shaped paravenous pigmentations were observed in the mid-peripheral retina. Fundus autofluorescence was consistent with PPRCA. Spectral-domain optical coherence tomography (OCT) revealed the presence of CME and loss of the outer retinal layers outside the macula, with intact retinal layers in the macula. OCT angiography revealed normal choriocapillaris vasculature and flow. The patient was followed up for 6 months but showed no change in CME or clinical appearance. CME without ocular inflammation is an unusual finding of PPRCA and may suggest the involvement of chronic or latent inflammation in the etiology of PPRCA. © 2022 by Turkish Ophthalmological Association.

To characterize and distinguish non-neovascular deep retinal age-related microvascular anomalies (DRAMA) from type 3 macular neovascularization (MNV) using volume rendering of OCT and OCT angiography (OCTA).Retrospective, consecutive case series.Consecutive patients with age-related macular degeneration (AMD) exhibiting de novo non-neovascular abnormalities within the deep vascular plexus (DCP), as detected using high-resolution (High-Res) spectral-domain (SD) and swept-source (SS) OCT or OCTA. Patients with retinal vascular alterations attributable to other disease entities were excluded.Complete ophthalmic examination and multimodal imaging, including confocal fundus photography (CFP), SD-OCT, High-Res SD-OCT and OCTA, and volume-averaged SS-OCTA. The volume renderings of High-Res OCTA and averaged SS-OCTA were used to analyze capillary abnormalities and inflow or outflow connectivity pathways.The primary outcomes were the characteristics of capillary abnormalities (number, size, shape, reflectivity, and location) and inflow or outflow connectivity pathways. The secondary outcomes were nearby changes in CFP and structural OCT (hyperreflective foci [HRF], outer retinal atrophy, and retinal pigment epithelium [RPE] atrophy).From 8 eyes of 8 patients, 2 subtypes of DRAMA were identified: small-diameter perifoveal capillary dilations with hyperreflective walls within the inner nuclear layer (type 1, n = 4) and vascular outpouchings, typically multiple, extending posteriorly into the Henle fiber layer, with reflectivity similar to adjacent normal retinal capillaries (type 2, n = 10). Four eyes had both subtypes of DRAMA. The 3-dimensional visualization of OCTA data demonstrated DRAMA corresponding to the dilations of DCP capillaries without direct inflow or outflow connections to the superficial plexus. Fundus photographs showed circular red dots in 3 eyes, all corresponding to type 1 DRAMA. In all the cases, DRAMA colocalized with HRF. No lesions were found anterior to the areas of the RPE or outer retina atrophy. Asymptomatic intraretinal exudation varied through a follow-up duration of up to 6 years, with no lesions progressing to type 3 MNV.In eyes with non-neovascular AMD, DRAMA include 2 types of capillary dilations occurring without the remodeling of the surrounding vascular network. Deep retinal age-related microvascular anomalies can resemble microvascular changes due to other causes and can masquerade as type 3 MNV. Mild intraretinal exudation can vary during follow-up, without progression to type 3 MNV.

Radiological evidence of focal pancreatic parenchymal atrophy (FPPA) may presage early pancreatic ductal adenocarcinoma (PDAC) development. We aimed to clarify the incidence of FPPA and the clinicopathological features of PDAC with FPPA before diagnosis.Data on endoscopic ultrasound-guided fine-needle biopsies and surgical samples from 170 patients with pancreatic cancer histologically diagnosed between 2014 and 2019 were extracted from the pathology database of Komagome Hospital and Juntendo University hospital and retrospectively evaluated together with 51 patients without PDAC.FPPA was identified in 47/170 (28%) patients before PDAC diagnosis and in 2/51 (4%) patients in the control group (P 0.01). The median duration from FPPA detection to diagnosis was 35 (interquartile range [IQR]:16-63) months. In 24/47 (51%) patients with FPPA, the atrophic area resolved. The lesion was in the head and body/tail in 7/40 and 67/56 of the patients with (n = 47) and without FPPA (n = 123), respectively (P 0.001). Histopathologically confirmed non-invasive lesions in the main pancreatic duct and a positive surgical margin in the resected specimens occurred in 53% vs. 21% (P = 0.078) and 29% vs. 3% (P = 0.001) of the groups, respectively. The PDAC patients with FPPA accompanied by a malignant pancreatic resection margin had high-grade pancreatic intraepithelial neoplasia.FPPA occurred in 28% of the PDAC group at 35 months prediagnosis. The FPPA area resolved before PDAC onset. Benchmarking previous images of the pancreas with the focus on FPPA may enable prediction of PDAC. PDAC with FPPA involves widespread high-grade pancreatic intraepithelial neoplasia requiring a wide surgical margin for surgical excision.

In contrast to Alzheimer's disease (AD)-related pathology, the influence of comorbid limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) or argyrophilic grains (AG) on structural imaging in Lewy body disease (LBD) has seldom been evaluated.This study aimed to investigate whether non-AD limbic comorbidities, including LATE-NC and AG, cause cortical atrophy in LBD.Seventeen patients with pathologically confirmed LBD with lower Braak neurofibrillary tangle stage (IV) and 10 healthy controls (HC) were included. Based on the presence of comorbid LATE-NC or AG, LBD patients were subdivided into nine patients with these proteinopathies (mixed LBD [mLBD]) and eight without (pure LBD [pLBD]). In addition to clinical feature evaluation, gray matter atrophy on voxel-based morphometry was compared between the two LBD and HC groups.The mean age at antemortem magnetic resonance imaging of the mLBD patients was higher than that of the pLBD patients (84.3 ± 3.9 vs. 76.5 ± 10.5; p = .046). Irrespective of the presence or absence of comorbid LATE-NC or AG, all patients were clinically diagnosed with probable dementia with Lewy bodies or Parkinson's disease with dementia, respectively. Compared to the pLBD group, the mLBD group showed more conspicuous cortical atrophy of the bilateral hippocampus, amygdala, and temporal pole.Non-AD limbic comorbidities, including LATE-NC and AG, are associated with limbic and temporal atrophy in older patients with LBD. Therefore, the possibility of non-AD limbic comorbidities should be considered in the diagnosis of elderly patients with dementia with clinical symptoms of LBD and medial temporal atrophy.

Our study demonstrates a novel pericyte-based therapy for the injured kidney. The beneficial effect of pericyte delivery appears to be mediated by ameliorating oxidative stress, inflammation, cellular apoptosis, and senescence in the stenotic kidney and improved tissue hypoxia, vascular loss, fibrosis, and tubular atrophy. Our data may form the basis for pericyte-based therapy, and additional research studies are needed to gain further insight into their role in improving renal function.

Objective: Radiation therapy is commonplace for cancer treatment but often results in fibrosis and atrophy of surrounding soft tissue. Decellularized adipose matrices (DAMs) have been reported to i...

To investigate key morphometric features identifiable on routine preoperative computed tomography (CT) imaging indicative of incisional hernia (IH) formation following abdominal surgery.IH is a pervasive surgical disease that impacts all surgical disciplines operating in the abdominopelvic region and affecting 13% of patients undergoing abdominal surgery. Despite the significant costs and disability associated with IH, there is an incomplete understanding of the pathophysiology of hernia.A cohort of patients (n=21,501) that underwent colorectal surgery was identified, and clinical data and demographics were extracted, with a primary outcome of IH. Two datasets of case-control matched pairs were created for feature measurement, classification, and testing. Morphometric linear and volumetric measurements were extracted as features from anonymized preoperative abdominopelvic CT scans. Multivariate Pearson testing was performed to assess correlations among features. Each feature's ability to discriminate between classes was evaluated using 2-sided paired t testing. A support vector machine was implemented to determine the predictive accuracy of the features individually and in combination.Two hundred and twelve patients were analyzed (106 matched pairs). Of 117 features measured, 21 features were capable of discriminating between IH and non-IH patients. These features are categorized into three key pathophysiologic domains: 1) structural widening of the rectus complex, 2) increased visceral volume, 3) atrophy of abdominopelvic skeletal muscle. Individual prediction accuracy ranged from 0.69 to 0.78 for the top 3 features among 117.Three morphometric domains identifiable on routine preoperative CT imaging were associated with hernia: widening of the rectus complex, increased visceral volume, and body wall skeletal muscle atrophy. This work highlights an innovative pathophysiologic mechanism for IH formation hallmarked by increased intra-abdominal pressure and compromise of the rectus complex and abdominopelvic skeletal musculature.

Hypertrophic and keloid scars are common skin conditions resulting from abnormal wound healing. They can cause itching, pain and have a negative physical and psychological impact on patients' lives. Different approaches are used aiming to improve these scars, including intralesional corticosteroids, surgery and more recently, laser therapy. Since laser therapy is expensive and may have adverse effects, it is critical to evaluate the potential benefits and harms of this therapy for treating hypertrophic and keloid scars.To assess the effects of laser therapy for treating hypertrophic and keloid scars.In March 2021 we searched the Cochrane Wounds Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL EBSCO Plus and LILACS. To identify additional studies, we also searched clinical trials registries for ongoing and unpublished studies, and scanned reference lists of relevant included studies as well as reviews, meta-analyses, and health technology reports. There were no restrictions with respect to language, date of publication, or study setting.We included randomised controlled trials (RCTs) for treating hypertrophic or keloid scars (or both), comparing laser therapy with placebo, no intervention or another intervention.Two review authors independently selected studies, extracted the data, assessed the risk of bias of included studies and carried out GRADE assessments to assess the certainty of evidence. A third review author arbitrated if there were disagreements.We included 15 RCTs, involving 604 participants (children and adults) with study sample sizes ranging from 10 to 120 participants (mean 40.27). Where studies randomised different parts of the same scar, each scar segment was the unit of analysis (906 scar segments). The length of participant follow-up varied from 12 weeks to 12 months. All included trials had a high risk of bias for at least one domain: all studies were deemed at high risk of bias due to lack of blinding of participants and personnel. The variability of intervention types, controls, follow-up periods and limitations with report data meant we pooled data for one comparison (and only two outcomes within this). Several review secondary outcomes - cosmesis, tolerance, preference for different modes of treatment, adherence, and change in quality of life - were not reported in any of the included studies. Laser versus no treatment: We found low-certainty evidence suggesting there may be more hypertrophic and keloid scar improvement (that is scars are less severe) in 585-nm pulsed-dye laser (PDL) -treated scars compared with no treatment (risk ratio (RR) 1.96; 95% confidence interval (CI): 1.11 to 3.45; two studies, 60 scar segments). It is unclear whether non-ablative fractional laser (NAFL) impacts on hypertrophic scar severity when compared with no treatment (very low-certainty evidence). It is unclear whether fractional carbon dioxide (CO

Acne scars lead to physical and psychological problems for young adults therefore they should be treated effectively. Fractional carbon dioxide (FCL) and radiofrequency (FRFL) lasers have been both used for acne scars. The aim of this study was to evaluate the effectivity and satisfaction of combined FCL and FRFL treatment for acne scars and evaluate effect of these treatments especially on atrophic scar types retrospectively. A total of 41 patients with acne scars who received FCL + FRFL were included in this study. Photographs of patients before treatment and 1 month following the last treatment session were scored by the other blinded clinician, according to the ECCA acne scar scoring method. A significant decrease was noted in clinical scores after the treatment. Side effects were minimal and acceptable. When comparing atrophic scars to erythematous ones laser treatment was more effective for atrophic types. In conclusion, our findings revealed that laser treatment with FCL + FRFL for acne scars is successful, effective and comfortable. These combination is more effective in atrophic type acne scars.

Objective Olfactory dysfunction is an important clinical feature in patients with multiple sclerosis (MS). The incidence and extent of olfactory dysfunction are reportedly higher in secondary progressive (SP) MS than in relapsing and remitting (RR) MS. We investigated the use of olfactory dysfunction for evaluating the disease status of Japanese patients with MS. Methods Olfactory identification was evaluated using the Odor Stick Identification Test for the Japanese (OSIT-J) in patients with RRMS (n=40) and SPMS (n=11) and compared the findings with those of healthy controls (n=40). Patients with RRMS for more than 10 years (L-RRMS, n=10) were included in the RRMS group. The cognitive function was evaluated using the Japanese version of the Wechsler Adult Intelligence Scale, 3rd edition. The third ventricle width (3rd VW) was measured as a marker of central brain atrophy using magnetic resonance imaging. Results SPMS patients had significantly lower OSIT-J scores than RRMS and L-RRMS patients. More SPMS patients had OSIT-J scores below the lower limit of the normal score (LLN) than RRMS patients. The LLN effectively discriminated between RRMS and SPMS (sensitivity 70%, specificity 91.5%, area under the curve 0.933, 95% confidence interval 0.874-1.000). Patients with SPMS had a significantly lower processing speed and larger 3rd VW than those with RRMS or L-RRMS. Conclusion The olfactory dysfunction was worse, along with cognitive impairment and brain atrophy, in SPMS patients than in RRMS patients, independent of disease duration, in our Japanese population. This directly reflected the disease progression and may have been able to distinguish SPMS from RRMS, independent of ethnic and cultural background.

IntroductionAutogenous bone grafting (ABG)–combined or not with Le Fort I osteotomy (LFIO)–and zygomatic implants (ZI) are two reliable techniques for the fixed rehabilitation of atrophic maxillae. ZI allow a reduced treatment duration with no need to graft, immediate loading and in principle less morbidity. The aim of this retrospective study was to compare these two protocols on oral health-related quality of life (OHRQoL). We also discussed implant and prosthetic survival rates, and biological complications.Material and methodsAll patients who benefited from ZI or ABG with conventional implants (CI) for a fixed maxillary rehabilitation, from November 2011 to April 2019, were included: 21 patients in the ABG group and 22 in the ZI group. OHRQoL was evaluated postoperatively by OHIP-14 questionnaire.ResultsOHIP-14 median scores were respectively 6.5 (interquartile range [IQR] 2.0–13.0) and 6.0 (IQR 3.0–10.0) without significant difference (p = 0.97). Implant/prosthetic survival rates were 97.9%/100% and 97.1%/95.5%. Biological complications rates were 33.3% and 36.4% without significant difference (p = 0.83).DiscussionThe type of surgery or prosthesis does not seem to affect final OHRQoL, implant and prosthetic survival rates or biological complications rates.

Statement of problem Rehabilitation of edentulous patients with severe maxillary atrophy is a clinical challenge. Although several treatment options are available, the implant-supported overdenture has been widely advocated. However vertical insertion implant-supported overdentures have drawbacks, including wear, aging, and the continuous maintenance of retention systems. Whether an implant-supported overdenture with a horizontal insertion pathway can overcome these problems is unclear. Purpose The purpose of this observational study was to determine the clinical and biological behavior of a new type of implant-supported overdenture with a horizontal insertion pathway over a mean clinical follow-up period of 6 years. Material and methods Ten study participants with an atrophic maxilla underwent rehabilitation with horizontal overdentures supported by 6 implants. Follow-up visits were scheduled at 3 months, 6 months, and annually thereafter. The variables analyzed were implant and prosthetic survival, peri-implant tissue behavior, mechanical complications, and patient satisfaction. Results The follow-up period ranged from 5 to 8 years, mean ±standard deviation 6.3 ±1.2 years. A total of 60 implants and 10 horizontal overdentures were placed. The clinical survival of the implants was 98.3% (mean peri-implant bone loss, 1.3 ±0.4 mm) and was 80% of the prostheses. Overall, mean patient satisfaction as assessed with a visual analog scale was 7.4, with 8.5 for esthetics and 9.5 for function. Conclusions The horizontal implant-supported overdenture provided a functional alternative to conventional prostheses.

The scar's appearance and psychological burden are the most esthetically challenging issues in acne vulgaris. This study investigated the effectiveness and safety profile of combined radiofrequency-assisted subcision, which, even though effective on both Icepeak and Rolling subtypes, is only mildly effective on boxcar lesions, and polycaprolactone-based dermal filler with collagen stimulation potency in managing atrophic postacne scars.Our quasi-experimental single-arm study, after the inclusion of 10 cases over the age of 18 with moderate to severe mixed atrophic facial acne scarring, was carried out in two 3-month separate sessions, during and after the intended intervention of which the experienced lesion improvements and also adverse events were documented. Moreover, all cases were followed for 3 months after the last session, evaluating the differences in the mentioned outcomes.We found the combined intervention to be highly effective in improving the intended outcomes, with the total number of acne lesions (p-value0.001), along with the total number of Ice peak (p-value = 0.002), Rolling (p-value0.001), and boxcar (p-value = 0.023) lesions demonstrating statistically significant changes.Radiofrequency-assisted subcision combined with polycaprolactone-based dermal fillers can be an effective intervention in managing postacne scars. However, we recommend that randomized clinical trials with larger sample sizes be carried out for a more precise conclusion.

VPS13D is a recently described gene. Worldwide, only 15 families with 23 affected individuals have been reported with a VPS13D-based disease. Mutated VPS13D causes a complex phenotype with a hyperkinetic movement disorder and ataxia, especially in childhood onset disease. The clinical phenotype of the rare adult-onset cases consists of cerebellar ataxia and/or spastic paraplegia. Here, we report the extensive clinical, laboratory and genetic findings of two offspring from consanguineous parents, with ages of disease onset at 57 and 49 with VPS13D-based ataxia. Although conventional magnetic resonance imaging showed mild cerebellar and cerebral atrophy, diffusion tensor imaging, applied for the first time for VPS13D patients, revealed prominent atrophy in U fibers and cerebellopontine tracts. Whole exome sequencing analysis revealed a biallelic Ala4210Val mutation in the VPS13D, reported only once in the literature. Complementary screening of our in-house database consisting of 295 ataxia and hereditary spastic paraplegia patients revealed two further ataxia patients with novel VPS13D variants. Screening the control cohort for VPS13D variants revealed one asymptomatic individual carrying a novel VPS13D variant. In this study, the phenotypic spectrum of VPS13D-based disease is expanded with the description of pre-senile onset predominant ataxia. Further, with the additional novel mutations described, the report is expected to contribute to the understanding of the yet elusive phenotype-genotype correlations in the rare VPS13D-based movement disorder.

To report on the prevalence of intraocular inflammation after subretinal voretigene neparvovec (VN) administration.Retrospective review of medical files.All patients receiving VN in Denmark.Twelve patients received VN gene therapy as standard of care for biallelic RPE65-related retinal disease. Bilateral treatment was performed in 11 patients and unilateral treatment in 1 patient. Patients were followed clinically before and after VN administration using functional measurements (visual acuity, full-field scotopic threshold test, visual fields) and structural evaluations (fundus imaging [color and autofluorescence], OCT, slit-lamp).Signs of intraocular inflammation, including vitritis and outer retinal infiltrates.Vitritis was observed in 9 of 23 eyes receiving VN. The median time to resolution of vitritis from the time of treatment was 89 days. Four eyes also presented with outer retinal infiltrates at the time of vitritis. Inflammation subsided on immunosuppressant therapy. The presence of inflammation did not adversely affect visual outcome after VN therapy. In 1 eye, outer retinal infiltrates were demonstrated to precede later development of atrophy.Patients undergoing subretinal gene therapy need to be closely monitored for signs of inflammation. Although we did not observe a detrimental effect on visual function in eyes with inflammation, it seems wise to treat it appropriately because it may lead to atrophy of the retinal pigment epithelium and outer retina. Also, it seems advisable to reduce the inflammatory load, such as using a surgical technique that minimizes residual viral vectors in the vitreous body.

To report a case of a pituitary macroadenoma that presented with bilateral intraretinal hyporeflective spaces located primarily in the inner nuclear layer on the macular SD-optical coherence tomography.Case report.Based on the findings of a macular SD-optical coherence tomography, a 53-year-old man was considered as having cystoid macular edema secondary to a retinovascular condition. He was treated with intravitreal vascular endothelial growth factor inhibitors and corticosteroids with no improvement. Confrontation visual fields suggested a bitemporal defect. MRI confirmed the presence of a nonsecreting pituitary macroadenoma compressing the optic chiasm.Not all intraretinal hyporeflective spaces in the optical coherence tomography are secondary to a retinal vascular condition. Hyporeflective spaces in the inner nuclear layer on optical coherence tomography imaging that do not leak on fluorescein angiography may be secondary to optic atrophy from chiasmal compression.

Intravaginal dehydroepiandrosterone (DHEA) is a locally metabolised estrogen and androgen precursor, licensed in 2018 in the EU for moderate to severe vulvovaginal atrophy in postmenopausal women. A literature search revealed four original trials suitable for appraisal, three evaluating change in dyspareunia or dryness as a primary outcome, one evaluated safety as a primary outcome. In two trials of 255 and 558 women without cancer, the benefit of placebo (nightly vaginal suppositories with a lipophilic base) was a 0.9 and 1 point reduction in dyspareunia as measured on a 3 point scale, an unvalidated outcome measure. With nightly DHEA, dyspareunia was reduced by an additional 0.4 points compared to placebo. When 464 women with gynaecological cancer were randomised, those using nightly plain moisturiser gel reported a reduction of ‘most bothersome symptom’ (either dyspareunia or dryness) of 1.5 points on a 3 point scale. Those using nightly DHEA reported an additional symptom reduction of 0.3 points. This is also an unvalidated outcome measure. Data evaluating the efficacy of DHEA over placebo is unconvincing and based on unvalidated primary outcome measures that also do not reflect the complex psycho-sexual and socio-cultural components of genitourinary menopausal symptoms. The efficacy and safety data excluded women taking systemic HRT, applies to postmenopausal, not perimenopausal, women and had relatively short follow up. It is important further independent trials use sophisticated and validated assessment tools to better establish the efficacy, safety and cost effectiveness of intravaginal DHEA in clinically representative groups of women before being routinely prescribed.

Objectives The clinical impact of brain microstructural abnormalities in multiple sclerosis (MS) remains elusive. We aimed to characterize the topography of longitudinal relaxation rate (R1) and quantitative susceptibility (χ) changes, as indices of iron and myelin, together with brain atrophy, and to clarify their contribution to cognitive and motor disability in MS. Methods In this cross-sectional study, voxel-based morphometry, and voxel-based quantification analyses of R1 and χ maps were conducted in gray matter (GM) and white matter (WM) of 117 MS patients and 53 healthy controls. Voxel-wise between-group differences were assessed with nonparametric permutation tests, while correlations between MRI metrics and clinical variables (global disability, cognitive and motor performance) were assessed both globally and voxel-wise within clusters emerging from the between-group comparisons. Results MS patients showed widespread R1 decrease associated with more limited modifications of χ, with atrophy mainly involving deep GM, posterior and infratentorial regions (p < 0.02). While R1 and χ showed a parallel reduction in several WM tracts (p < 0.001), reduced GM R1 values (p < 0.001) were associated with decreased thalamic χ (p < 0.001) and small clusters of increased χ in the caudate nucleus and prefrontal cortex (p < 0.02). In addition to the atrophy, χ values in the cingulum and corona radiata correlated with global disability and motor performance, while focal demyelination correlated with cognitive performance (p < 0.04). Conclusions We confirmed the presence of widespread R1 changes, involving both GM and WM, and atrophy in MS, with less extensive modifications of tissue χ. While atrophy and χ changes are related to global and motor disability, R1 changes are meaningful correlates of cognition. Key Points • Compared to healthy controls, multiple sclerosis patients showed R1 and χ changes suggestive of iron increase within the basal ganglia and reduced iron and myelin content within (subnuclei of) the thalamus. • Thalamic volume and χ changes significantly predicted clinical disability, as well as pulvinar R1 and χ changes, independently from atrophy. • Atrophy-independent R1 and χ changes, suggestive of thalamic iron and myelin depletion, may represent a sensitive marker of subclinical inflammation.

Background: People with a migration background are underrepresented in dementia research and disfavored in assessment and treatment, and many foreign-born individuals with dementia remain undiagnosed. Objective: The aim of this study was to examine whether there is inequality in the clinical assessment of dementia between native and foreign-born individuals in Sweden. Methods: Information was gathered retrospectively from a cohort of 91 native and 36 foreign-born patients attending four memory clinics in Skåne, Sweden. Data included information on cognitive test results, cerebrospinal fluid biomarkers, scores at structural imaging scales of global cortical atrophy (GCA), medial temporal lobe atrophy (MTA) and the Fazekas scale, laboratory measures of thyroid-stimulating hormone, calcium, albumin, homocysteine, hemoglobin, cobalamin (vitamin B12), and folate (vitamin B9), contact with health care, and treatment. Results: Foreign-born patients had lower educational level and scored lower on Mini-Mental State Examination and Clock Drawing Test (p

Background: The effects of B vitamins on mild cognitive impairment (MCI) patients’ cognition have been mixed, suggesting the existence of moderating factors. Objective: A post hoc analysis of a negative B vitamin trial was performed to examine the potential modulating effect of regional brain atrophy on the cognitive response to B vitamins in MCI patients. Methods: In the 24-month randomized trial, 279 MCI outpatients took 500μ#x03BC;g methylcobalamin and 400μ#x03BC;g folic acid once per day or placebo tablets once per day. Sixty-four aspirin users were excluded from analysis as aspirin use has been found to have significant negative interaction effects. Subjects were followed up at months 12 and 24. The primary cognitive outcome was clinical dementia rating scale sum of boxes (CDR_SOB). In a subgroup of 83 subjects, MRI brain scans were performed at baseline to estimate regional brain atrophy ratios. Results: Among the trial subjects who had MRI data, B vitamin supplementation had no significant effect on CDR_SOB, despite having significant homocysteine lowering effects. The atrophy ratio of the left frontal lobe significantly moderated the effect of B vitamin supplementation on CDR_SOB, after adjusting for confounders, in that B vitamin supplementation was associated with lower CDR_SOB scores (i.e., better cognitive function) at the 24th month among those patients with above median atrophy ratios, but not among those with lower atrophy ratios, in the left frontal lobe. Conclusion: B vitamins may be more effective in slowing down cognitive decline in MCI patients with atrophy in the left frontal lobe.

Measures of atrophy in the whole brain can be used to reliably assess treatment effect in clinical trials of patients with multiple sclerosis (MS). Trials assessing the effect of treatment on grey matter (GM) and white matter (WM) atrophy are very informative, but hindered by technical limitations. This study aimed to measure GM and WM volume changes, using a robust longitudinal method, in patients with relapsing MS randomized to cladribine tablets 3.5 mg/kg or placebo in the CLARITY study.We analysed T1-weighted magnetic resonance sequences using SIENA-XL, from 0 to 6 months (cladribine, n = 267; placebo, n = 265) and 6 to 24 months (cladribine, n = 184; placebo, n = 186). Mean percentage GM and WM volume changes (PGMVC and PWMVC) were compared using a mixed-effect model.More GM and WM volume loss was found in patients taking cladribine versus those taking placebo in the first 6 months of treatment (PGMVC: cladribine: -0.53 vs. placebo: -0.25 [p = 0.045]; PWMVC: cladribine: -0.49 vs. placebo: -0.34 [p = 0.137]), probably due to pseudoatrophy. However, over the period 6 to 24 months, GM volume loss was significantly lower in patients on cladribine than in those on placebo (PGMVC: cladribine: -0.90 vs. placebo: -1.27 [p = 0.026]). In this period, volume changes in WM were similar in the two treatment arms (p = 0.52).After a short period of pseudoatrophy, treatment with cladribine 3.5 mg/kg significantly reduced GM atrophy in comparison with placebo. This supports the relevance of GM damage in MS and may have important implications for physical and cognitive disability progression.

To evaluate the performance of a deep learning model for hippocampal sclerosis classification on the clinical dataset and suggest plausible visual interpretation for the model prediction.T2-weighted oblique coronal images of the brain MRI epilepsy protocol performed on patients were used. The training set included 320 participants with 160 no, 100 left and 60 right hippocampal sclerosis, and cross-validation was implemented. The test set consisted of 302 participants with 252 no, 25 left and 25 right hippocampal sclerosis. As the test set was imbalanced, we took an average of the accuracy achieved within each group to measure a balanced accuracy for multiclass and binary classifications. The dataset was composed to include not only healthy participants but also participants with abnormalities besides hippocampal sclerosis in the control group. We visualized the reasons for the model prediction using the layer-wise relevance propagation method.When evaluated on the validation of the training set, we achieved multiclass and binary classification accuracy of 87.5% and 88.8% from the voting ensemble of six models. Evaluated on the test sets, we achieved multiclass and binary classification accuracy of 91.5% and 89.76%. The distinctly sparse visual interpretations were provided for each individual participant and group to suggest the contribution of each input voxel to the prediction on the MRI.The current interpretable deep learning-based model is promising for adapting effectively to clinical settings by utilizing commonly used data, such as MRI, with realistic abnormalities faced by neurologists to support the diagnosis of hippocampal sclerosis with plausible visual interpretation.

Cancer-derived exosomes are involved in the development of cancer cachexia. Carnosol, which exhibited ameliorating effects on cancer cachexia of C26 tumour-bearing mice in our previous study, alleviated atrophy of C2C12 myotubes induced by exosomes of C26 tumour cells in the present study. MiR-183-5p was found to be rich in C26 cells and C26 exosomes, and miR-183-5p mimic could directly induce atrophy of C2C12 myotubes. Carnosol at 5 to 20 μM could dose-dependently ameliorate the myotube atrophy induced by miR-183-5p. Four and a half LIM domain protein 1 (FHL1) was shown to be the direct target of miR-183-5p. Increase in myostatin, p-Smad3, MuRF-1, Atrogin-1, HIF-1α and p-STAT3 and decrease in mitochondrial respiration were also induced by miR-183-5p mimic in C2C12 myotubes. Carnosol could not affect the decrease in FHL-1 and the activation of STAT3 pathway but could significantly alleviate the increase in myostatin, p-Smad3, MuRF-1, Atrogin-1 and the decrease in mitochondrial respiration induced by miR-183-5p. The protective effects of carnosol on myotubes against atrophy of C2C12 myotubes induced by miR-183-5p, based on both its inhibiting effects on MuRF-1 and Atrogin-1-mediated protein degradation and its ability of keeping the mitochondrial respiration, might contribute to its ameliorating effects on cancer cachexia.

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a very rare neurodegenerative lysosomal storage disorder. Progression is rapid and irreversible, making early diagnosis crucial for timely treatment. A group of pediatric neurologists and neuroradiologists with expertise in CLN2 convened to discuss early electroencephalogram (EEG) and magnetic resonance imaging (MRI) findings in CLN2 diagnosis. Of 18 CLN2 cases, 16 (88.9%) had background slowing and 16 (88.9%) had epileptiform discharges on initial EEG. Seven of 17 (41.2%) patients who received intermittent low-frequency photic stimulation had a photoparoxysmal response. Initial MRIs showed subtle cerebellar (n = 14, 77.8%) or cerebral (n = 9, 50.0%) atrophy, white matter abnormalities (n = 11, 61.1%), and basal ganglia T2 hypointensity (n = 6, 33.3%), which became more apparent on follow-up MRI. The recognition of even subtle cerebellar atrophy and white matter signal changes in children aged 2-5 years who present with language delay, new-onset seizures, and an EEG with epileptiform discharges and background slowing should prompt investigation for CLN2. Because these early signs are not unique to CLN2, genetic testing is essential early in the diagnostic journey.

BACKGROUND AND OBJECTIVE: Macular atrophy (MA) contributes to declining vision during prolonged anti-vascular endothelial growth factor (VEGF) treatment in neovascular age-related macular degeneration (nAMD) so greater understanding of its incidence, evolution, and impact on visual acuity is merited. MATERIALS AND METHODS: This is a retrospective review of nAMD patients receiving anti-VEGF therapy for ≥ 5 years. Near-infrared reflectance images and vision data were extracted every 6 months. MA lesion areas were measured using ImageJ. RESULTS: Vision showed a mean decline of −1.2 letters/year. Eyes with MA showed a greater decrease of −1.6 letters/year compared to eyes without MA (−0.7 letters/year). Cumulative incidence of MA was 38% at 5 years. MA was significantly associated with declining vision, showing a −0.7 letter decrease for every 1 mm 2 increase in lesion size. CONCLUSION: Over a 5-year course of nAMD treatment, MA affected most eyes, and MA progression was significantly associated with vision decline. [ Ophthalmic Surg Lasers Imaging Retina 2022;53:546–552.]

Background Brain atrophy is suggested to impair the potential for functional recovery after acute ischemic stroke. We assessed whether the effect of endovascular treatment is modified by brain atrophy in patients with acute ischemic stroke due to large vessel occlusion. Methods We used data from MR CLEAN, a multicenter trial including patients with acute ischemic stroke due to anterior circulation large vessel occlusion randomized to endovascular treatment plus medical care (intervention) versus medical care alone (control). We segmented total brain volume (TBV) and intracranial volume (ICV) on baseline non-contrast computed tomography (n = 410). Next, we determined the degree of atrophy as the proportion of brain volume in relation to head size (1 − TBV/ICV) × 100%, analyzed as continuous variable and in tertiles. The primary outcome was a shift towards better functional outcome on the modified Rankin Scale expressed as adjusted common odds ratio. Treatment effect modification was tested using an interaction term between brain atrophy (as continuous variable) and treatment allocation. Results We found that brain atrophy significantly modified the effect of endovascular treatment on functional outcome (P for interaction = 0.04). Endovascular treatment led to larger shifts towards better functional outcome in the higher compared to the lower range of atrophy (adjusted common odds ratio, 1.86 [95% CI: 0.97–3.56] in the lowest tertile vs. 1.97 [95% CI: 1.03–3.74] in the middle tertile vs. 3.15 [95% CI: 1.59–6.24] in the highest tertile). Conclusion Benefit of endovascular treatment is larger in the higher compared to the lower range of atrophy, demonstrating that advanced atrophy should not be used as an argument to withhold endovascular treatment.

Purpose We have demonstrated that deletion of fibroblast growth factor receptor 2 gene (Fgfr2) leads to Meibomian gland (MG) atrophy in an inducible conditional knockout mouse model, referred as Fgfr2CKO. Herein, we investigated whether MG spontaneously recovers after atrophy in this model. Methods Two months old Fgfr2CKO mice were injected peritoneally once or twice of doxycycline (Dox) at 80 μg/gm of body weight to induce MG atrophy of various severities via Fgfr2 deletion. Recovery of acinar and ductal tissues was monitored by meibography, lipid staining and immunofluorescence against keratin-6a in MG whole-mount. Biomarkers for acinar and ductal differentiation and proliferation were also examined by immunostaining. Results Single Dox injection in Fgfr2CKO mice caused severe acinar and moderate ductal atrophy. Severe ductal shortening or loss occurred after second Dox injection, presumably related to the reported slower cycling of the ductal epithelia. Spontaneous acinar regrowth after atrophy was observed over a period of 60 days in both injection regimens. However, less robust acinar recovery was associated with more disrupted ductal structures in twice injected Fgfr2CKO mice. Conclusions Our current findings further substantiate the role of FGFR2 in MG homeostasis, and suggest that FGFR2-signaling may provide a potential strategy for regenerating acini from age-related MG dysfunction in humans. Our data demonstrated that spontaneous MG recovery depends on the extent of ductal atrophy, suggesting that ductal epithelia may provide the progenitor cells for acinar regeneration. Nonetheless, the role of ductal tissue as the source of acinar progenitors awaits further investigation.

Catatonia is a debilitating psychomotor disorder. Previous neuroimaging studies have used small samples with inconsistent results. The authors aimed to describe the structural neuroradiological abnormalities in clinical magnetic resonance imaging (MRI) brain scans of patients with catatonia, comparing them with scans of psychiatric inpatients without catatonia. They report the largest study of catatonia neuroimaging to date.In this retrospective case-control study, neuroradiological reports of psychiatric inpatients who had undergone MRI brain scans for clinical reasons were examined. Abnormalities were classified by lateralization, localization, and pathology. The primary analysis was prediction of catatonia by presence of an abnormal MRI scan, adjusted for age, sex, Black race-ethnicity, and psychiatric diagnosis.Scan reports from 79 patients with catatonia and 711 other psychiatric inpatients were obtained. Mean age was 36.4 (SD=17.3) for the cases and 44.5 (SD=19.9) for the comparison group. Radiological abnormalities were reported in 27 of 79 cases (34.2%) and in 338 of 711 in the comparison group (47.5%) (odds ratio [OR]=0.57, 95% confidence interval [CI]=0.35, 0.93; adjusted OR=1.11, 95% CI=0.58, 2.14). Among the cases, most abnormal scans had bilateral abnormalities (N=23, 29.1%) and involved the forebrain (N=25, 31.6%) and atrophy (N=17, 21.5%).Patients with catatonia were commonly reported to have brain MRI abnormalities, which largely consisted of diffuse cerebral atrophy rather than focal lesions. No evidence was found that these abnormalities were more common than in other psychiatric inpatients undergoing neuroimaging, after adjustment for demographic variables. Study limitations included a heterogeneous control group and selection bias in requesting scans.

Research evidences suggest that diverse forms of programmed cell death (PCD) are involved in the helicobacter pylori (H. pylori)-induced gastric inflammation and disorders.To characterize occurrences and phenotypes of necroptosis in gastric cells in H. pylori infected gastritis and atrophic specimens.Occurrences and phenotypes of necroptosis in gastric cells were immunohistochemically characterized with receptor-interacting protein kinase 3 (RIPK3) antibody in both human H. pylori infected gastric gastritis, atrophic specimens, and transgenic mice.Increased populations of RIPK3-positive cells were observed in both gastric glands and lamina propria in H. pylori infected human oxyntic gastritis and atrophic specimens. Phenotypic analysis revealed that many RIPK3-positive cells were H An increased population of RIPK3-positive cells was observed in several types of gastric cells, future studies that define the effects and mechanisms of PCD implicated in the development of H. pylori induced gastric disorders are needed.

To compare the enlargement rates of geographic atrophy (GA) over 5 years of follow-up with those of macular atrophy (MA) associated with macular neovascularization (MNV).Retrospective, longitudinal, comparative case series.Consecutive series of patients with age-related macular degeneration and GA (dry) or with MA and MNV.Atrophic regions detected on serial registered fundus autofluorescence images were semiautomatically delineated, and the measurements of these areas were recorded every 6 ± 3 months for the first 2 years of follow-up and at yearly intervals for up to 5 years.Annual raw and square root-transformed rates of atrophy growth.The study included 117 eyes of 95 patients (61 in the GA cohort and 56 in the MA cohort); 100% and 38.5% of the eyes completed 2 and 5 years of follow-up, respectively. The mean size of lesions at baseline was similar between the 2 groups (raw: 1.74 vs. 1.53 mmThe presence of MNV was associated with a slower rate of expansion, resulting in overall smaller areas of atrophy over time. These findings support the hypothesis that MNV may protect against the progression of atrophy.

Cases of neglect in dogs are among the forensic cases submitted most commonly for postmortem examination. Starvation is a form of primary protein-energy malnutrition in which the availability of food is severely restricted or absent; cachexia is a form of protein-energy malnutrition secondary to progressive metabolic derangement during chronic diseases. Despite both conditions leading to an emaciated appearance of the cadaver, discrimination between the two is crucial in forensic cases. We hypothesized that among emaciated dogs, the degree of liver atrophy in starved animals is higher than in cachectic ones, and that this can be investigated microscopically, regardless of the degree of cadaver decomposition. We studied 46 animals: 23 starved, 11 cachectic, and 12 control dogs. Portal tracts were identified by the presence of a bile duct and associated vascular structures recognizable by a thin rim of collagen still visible regardless of the degree of cadaver decomposition. The number of portal tracts per lpf (10×) was used as an indirect measure of atrophy. The number of portal tracts in starved dogs was significantly higher ( p < 0.01) compared to both cachectic and control dogs, indicating a higher degree of liver atrophy in starvation. Measuring the density of portal tracts offers a reliable additional tool for discrimination between starvation and cachexia.

To determine the clinical and imaging characteristics, natural course, and surgical outcomes of pathologic myopic eyes with an extreme macular schisis simulating a retinal detachment (EMSSRD).The data of 617 highly myopic eyes with myopic traction maculopathy were studied. The diagnosis of EMSSRD in the optical coherence tomography images was made based on a high elevation of the retina (500 µ m), less obvious columnar structures, and the presence of thin remnants of outer retinal tissues above the retinal pigment epithelium.Among 617 eyes, 25 eyes had an EMSSRD. All of the eyes with an EMSSRD had macular atrophy caused by myopic macular neovascularization. In the five eyes they had progressed to MHRD, the retinal detachment started away from the macular atrophy. Among the 10 eyes which required surgery, there was no significant difference in the presurgical and postsurgical best-corrected visual acuity between the eyes operated because of a worsening of the EMSSRD and the eyes operated because of a progression to MHRD.In severely myopic eyes with macular neovascularization-related macular atrophy, a novel condition termed EMSSRD can be present. The optical coherence tomography images resemble those of a MHRD except the presence of thin remnants of the retina remaining on the retinal pigment epithelium.

Progressive supranuclear palsy (PSP) and idiopathic normal pressure hydrocephalus (iNPH) share several clinical and radiological features, making the differential diagnosis challenging. In this study, we aimed to differentiate between these two diseases using a machine learning approach based on cortical thickness and volumetric data.Twenty-three iNPH patients, 50 PSP patients and 55 control subjects were enrolled. All participants underwent a brain 3T-MRI, and cortical thickness and volumes were extracted using Freesurfer 6 on T1-weighted images and compared among groups. Finally, the performance of a machine learning approach with random forest using the extracted cortical features was investigated to differentiate between iNPH and PSP patients.iNPH patients showed cortical thinning and volume loss in the frontal lobe, temporal lobe and cingulate cortex, and thickening in the superior parietal gyrus in comparison with controls and PSP patients. PSP patients only showed mild thickness and volume reduction in the frontal lobe, compared to control subjects. Random Forest algorithm distinguished iNPH patients from controls with AUC of 0.96 and from PSP patients with AUC of 0.95, while a lower performance (AUC 0.76) was reached in distinguishing PSP from controls.This study demonstrated a more severe and widespread cortical involvement in iNPH than in PSP, possibly due to the marked lateral ventricular enlargement which characterizes iNPH. A machine learning model using thickness and volumetric data led to accurate differentiation between iNPH and PSP patients, which may help clinicians in the differential diagnosis and in the selection of patients for shunt procedures.

Background: Type 2 diabetes mellitus (T2DM) is known to be associated with cognitive decline and brain structural changes. This study systematically reviews and estimates human brain volumetric differences and atrophy associated with T2DM.Methods: PubMed, PsycInfo and Cochrane Library were searched for brain imaging studies reporting on brain volume differences between individuals with T2DM and healthy controls. Data were examined using meta-analysis, and association between age, sex, diabetes characteristics and brain volumes were tested using meta-regression.Results: A total of 14,605 entries were identified; after title, abstract and full-text screening applying inclusion and exclusion criteria, 64 studies were included and 42 studies with compatible data contributed to the meta-analysis (n=31,630; mean age 71.0 years; 44.4% male; 26,942 control; 4,688 diabetes). Individuals with T2DM had significantly smaller total brain volume, total grey matter volume, total white matter volume and hippocampal volume (approximately 1% to 4%); meta-analyses of smaller samples focusing on other brain regions and brain atrophy rate in longitudinal investigations also indicated smaller brain volumes and greater brain atrophy associated with T2DM. Meta-regression suggests that diabetes-related brain volume differences start occurring in early adulthood, decreases with age and increases with diabetes duration.Conclusion: T2DM is associated with smaller total and regional brain volume and greater atrophy over time. These effects are substantial and highlight an urgent need to develop interventions to reduce the risk of T2DM for brain health.

Atrophy in the striatum is a hallmark of Huntington's disease (HD), including the period before clinical motor diagnosis (before-CMD), but it extends to other subcortical structures. The study of the covariation of these structures could improve the detection of disease-related longitudinal progression before-CMD, provide mechanistic insights of the disease, and potentially be used to obtain accurate prospective estimates of atrophy before-CMD and early after-CMD.We analyzed data from 337 before-CMD individuals, 236 healthy control subjects, and 95 early after-CMD individuals from three studies, and we used nine subcortical regions volumes in two analyses. First, we discriminated before-CMD from healthy control trajectories by integrating volume changes from these regions. Second, we estimated prospective atrophy before-CMD and early after-CMD by considering the influence of a region's present volume over the future volume of another one.Before-CMD progression was robustly detected across studies. Indeed, detection of before-CMD progression improved when multiple structures were integrated, as opposed to analyzing the striatum alone, likely because of the reduced partial correlation between caudate and thalamic volume change before-CMD. Our multivariate atrophy prediction model found a thalamus-caudate association that is consistent with this pattern, which yields an improved caudate atrophy prediction in early after-CMD.This study is the first attempt to validate before-CMD multivariate subcortical change detection across studies and to do multivariate prospective atrophy prediction in HD. These models achieve improved performance by detecting a dissociation between caudate and thalamic atrophy trajectories, and they provide a possible mechanistic understanding of the dynamics of HD. © 2022 International Parkinson and Movement Disorder Society.