Psoriasis confined strictly to vitiligo areas – a Koebner‐like phenomenon?

Vitiligo and psoriasis are both common skin disorders. However, psoriasis strictly confined to pre-existing vitiligo areas is rare and suggests a causal relationship. We report here on two patients with a strict anatomical colocalization of vitiligo and psoriasis. The histopathological examinations showed typical changes for both diseases together with a dense infiltrate of CD4+ and CD8+ T cells. By immunohistochemistry, intracytoplasmatic granzyme B and tumour necrosis factor alpha (TNF-alpha) were detected within the T-cell population, suggesting the functional activity of these cells and the creation of a local T helper 1 (Th1)-cytokine milieu. Additionally, in one patient we could identify anti-melanocytic T cells by tetramer staining and enzyme-linked immunospot (ELISPOT) analysis. These skin-infiltrating lymphocytes might trigger, by the local production of Th-1 cytokines such as TNF-alpha and interferon-gamma (IFN-gamma), the eruption of psoriatic plaques in patients with a genetic predisposition for psoriasis.     

Divergent Histopathological Networks of Frontotemporal Degeneration Proteinopathy Subytpes

Network analyses inform complex systems such as human brain connectivity, but this approach is seldom applied to gold-standard histopathology. Here, we use two complimentary computational approaches to model microscopic progression of the main subtypes of tauopathy versus TDP-43 proteinopathy in the human brain. Digital histopathology measures were obtained in up to 13 gray matter (GM) and adjacent white matter (WM) cortical brain regions sampled from 53 tauopathy and 66 TDP-43 proteinopathy autopsy patients. First, we constructed a weighted non-directed graph for each group, where nodes are defined as GM and WM regions sampled and edges in the graph are weighted using the group-level Pearson''s correlation coefficient for each pairwise node comparison. Additionally, we performed mediation analyses to test mediation effects of WM pathology between anterior frontotemporal and posterior parietal GM nodes. We find greater correlation (i.e., edges) between GM and WM node pairs in tauopathies compared with TDP-43 proteinopathies. Moreover, WM pathology strongly correlated with a graph metric of pathology spread (i.e., node-strength) in tauopathies (r = 0.60, p < 0.03) but not in TDP-43 proteinopathies (r = 0.03, p = 0.9). Finally, we found mediation effects for WM pathology on the association between anterior and posterior GM pathology in FTLD-Tau but not in FTLD-TDP. These data suggest distinct tau and TDP-43 proteinopathies may have divergent patterns of cellular propagation in GM and WM. More specifically, axonal spread may be more influential in FTLD-Tau progression. Network analyses of digital histopathological measurements can inform models of disease progression of cellular degeneration in the human brain.SIGNIFICANCE STATEMENT In this study, we uniquely perform two complimentary computational approaches to model and contrast microscopic disease progression between common frontotemporal lobar degeneration (FTLD) proteinopathy subtypes with similar clinical syndromes during life. Our models suggest white matter (WM) pathology influences cortical spread of disease in tauopathies that is less evident in TDP-43 proteinopathies. These data support the hypothesis that there are neuropathologic signatures of cellular degeneration within neurocognitive networks for specific protienopathies. These distinctive patterns of cellular pathology can guide future efforts to develop tissue-sensitive imaging and biological markers with diagnostic and prognostic utility for FTLD. Moreover, our novel computational approach can be used in future work to model various neurodegenerative disorders with mixed proteinopathy within the human brain connectome.     

Importance of the pacing mode in the initiation of ventricular tachyarrhythmia in a canine model of chronic myocardial infarction

The use of unipolar anodal or bipolar pacing, as compared with unipolar cathodal pacing, purportedly increases the likelihood of inducing inadvertent ventricular fibrillation in susceptible patients. In this study, the ability to initiate sustained ventricular tachycardia or fibrillation with unipolar cathodal, unipolar anodal and bipolar pacing modes was compared using programmed ventricular stimulation at 82 subendocardial periinfarction sites in 11 dogs with chronic myocardial infarction. The late diastolic excitability threshold was significantly higher and the ventricular refractory period was significantly shorter (p less than 0.001) with anodal pacing (mean 0.62 mA, 156 ms, respectively) than with pacing in either the cathodal (0.12 mA, 174 ms) or the bipolar (0.13 mA, 173 ms) mode. At a current intensity twice that of the excitability threshold, the introduction of one or two extrastimuli induced ventricular tachycardia and ventricular fibrillation comparably among the three pacing modes. However, when three extrastimuli were used, ventricular fibrillation was induced with anodal pacing twice as frequently (50 [61%] of 82 sites) as with either of the other two pacing modes (each 23 [28%] of 82 sites, p less than 0.001), whereas the induction of ventricular tachycardia remained comparable with anodal pacing (15 [18%] of 82 sites) and cathodal and bipolar pacing (each 14 [17%] of 82 sites). Furthermore, a similarly high incidence of inducibility of ventricular fibrillation was observed with both cathodal pacing (56 [68%] of 82 sites) and bipolar pacing (40 [49%] of 82 sites) when an increased current equal to twice the anodal excitability threshold (1.23 mA) was used.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ophthalmic manifestations in the COVID-19 clinical spectrum

Purpose:The aim of this study was to determine the frequency and various types of ophthalmic manifestation of patients with COVID-19.Methods:This is a prospective observational study conducted on patients with SARS-Co-V-2 infection, at a dedicated tertiary COVID-19 hospital in South India from April 1 to July 31, 2020. At the time of their admission to the COVID hospital, demographic data such as name, age, sex was recorded. A thorough history regarding the onset, duration, progression, nature of symptoms and its associated factors, medication history, treatment history were elicited and documented. Ocular examination was performed under torchlight by an ophthalmologist posted for COVID duty. Further investigations including imaging were sought for, depending on clinical indications. Serial follow-up examinations of all patients were carried out every 72 hours or when patients complained of any ocular symptoms whichever earlier, until discharge. All relevant data were compiled and statistically analyzed.Results:A total of 2742 patients were examined. Of them, 1461 (53.28%) were males and 1281 (46.72%) were females. The mean age (±SD) was 39.46 ± 17.63 years. None of the patients in our study had any ocular symptoms or signs as the presenting complaint at the time of their admission. On subsequent follow-up, only 20 (0.72%) developed ocular manifestations, of which 19 (95%) had features suggestive of Bilateral viral conjunctivitis. However, 1 (5%) patient had orbital cellulitis secondary to pansinusitis.Conclusion:Ophthalmic manifestations in the clinical spectrum of COVID-19 infection are uncommon and unlikely to be the presenting clinical impression. However, it has broadened our view to a wider spectrum of COVID-19 presentations enhancing our clinical acumen for staunch detection of COVID-19 suspects in our daily practice, augmenting early diagnosis and management and also break the chain of transmission for the greater good of humanity.     

A Danish population-based twin study on autism spectrum disorders

Genetic epidemiological studies of Autism Spectrum Disorders (ASDs) based on twin pairs ascertained from the population and thoroughly assessed to obtain a high degree of diagnostic validity are few. All twin pairs aged 3–14 years in the nationwide Danish Twin Registry were approached. A three-step procedure was used. Five items from the “Child Behaviour Checklist” (CBCL) were used in the first screening phase, while screening in the second phase included the “Social and Communication Questionnaire” and the “Autism Spectrum Screening Questionnaire”. The final clinical assessment was based on “gold standard” diagnostic research procedures including diagnostic interview, observation and cognitive examination. Classification was based on DSM-IV-TR criteria. The initial sample included 7,296 same-sexed twin pairs and, after two phases of screening and clinical assessment, the final calculations were based on 36 pairs. The probandwise concordance rate for ASD was 95.2 % in monozygotic (MZ) twins (n = 13 pairs) and 4.3 % in dizygotic (DZ) twins (n = 23 pairs). The high MZ and low DZ concordance rate support a genetic aetiology to ASDs.     

Alzheimer's disease: mismatch between amyloid plaques and neuritic plaques

Isocortical amyloid deposits and neurofibrillary changes were studied using selective silver staining methods. Amyloid was found in plaque-like formations varying in size and shape. The distribution pattern of these plaques as seen in the silver-stained preparations was identical to that recognized by A4 protein (amyloid) immunostaining. Consecutive sections stained for amyloid and neurofibrillary changes revealed the absence of intraneuronal cytoskeleton abnormalities within the boundaries of many of the amyloid plaques. Congo red preparations did not show these plaques and the tissue within the range of the plaques did not reveal any conspicuous neuropil distortions and/or glial cell accumulations. Hence, a considerable proportion of the amyloid plaques do not correspond to and should carefully be distinguished from 'primitive', 'mature', and 'burned out' types of neuritic (senile) plaques.     

Delayed activation of quiescent donor hematopoietic stem cells in the host marrow cavity by anti-host monoclonal antibody

To understand the mechanisms controlling hematopoietic engraftment in untreated, normal recipients, we investigated the fate of parental, donor hematopoietic stem cells after apparent graft failures in unconditioned F1 hybrid recipient mice. By administering an anti-host H- 2K monoclonal antibody, which targets host cells but spares the donor, we found that chimerism could be induced by delayed conditioning in animals with apparent graft failure. Engraftment kinetics in the host were followed by typing individual colony forming unit-- granulocyte/macrophage (CFU-GM) colonies for their origin and showed that parental cells, which were otherwise virtually absent, become promptly detectable within the marrow cavity after antibody administration. Marrow transfers to secondary hosts suggested that parental stem cells were present in the marrow of the untreated recipients. These findings establish that the elimination of all parental cells cannot account for the absence of peripheral blood chimerism in the unconditioned F1 hybrid recipient. Thus, viable and functional donor stem cells, which remain quiescent in the host marrow, can be activated by a selective conditioning regimen and can rescue an apparent graft failure. The selective activation in vivo of marked stem cells in an unirradiated microenvironment may be a useful system to study the regulation of cellular proliferation within the marrow cavity.