COVID‐19 as a Blood Clotting Disorder Masquerading as a Respiratory Illness: A Cerebrovascular Perspective and Therapeutic Implications for Stroke Thrombectomy

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) as the name suggests was initially thought to only cause a respiratory illness. However, several reports have been published of patients with ischemic strokes in the setting of coronavirus disease 2019 (COVID‐19). The mechanisms of how SARS‐CoV‐2 results in blood clots and large vessel strokes need to be defined as it has therapeutic implications. SARS‐CoV‐2 enters the blood stream by breaching the blood‐air barrier via the lung capillary adjacent to the alveolus, and then attaches to the angiotensin‐converting enzyme II receptors on the endothelial cells. Once SARS‐CoV‐2 enters the blood stream, a cascade of events (Steps 1‐8) unfolds including accumulation of angiotensin II, reactive oxygen species, endothelial dysfunction, oxidation of beta 2 glycoprotein 1, formation of antiphospholipid antibody complexes promoting platelet aggregation, coagulation cascade, and formation of cross‐linked fibrin blood clots, leading to pulmonary emboli (PE) and large vessel strokes seen on angiographic imaging studies. There is emerging evidence for COVID‐19 being a blood clotting disorder and SARS‐CoV‐2 using the respiratory route to enter the blood stream. As the blood‐air barrier is breached, varying degrees of collateral damage occur. Although antiviral and immune therapies are studied, the role of blood thinners in the prevention, and management of blood clots in Covid‐19 need evaluation. In addition to ventilators and blood thinners, continuous aspiration and clot retrieval devices (approved in Europe, cleared in the United States) or cyclical aspiration devices (approved in Europe) need to be considered for the emergent management of life‐threatening clots including PE and large vessel strokes.     

A prospective study of bipolar disorder in children and adolescents from India

Bipolar disorder in adults is known to run an episodic course. However, little information exists on the long-term naturalistic course of bipolar disorder in juvenile populations. The present study was undertaken with the objectives of (i) documenting the rates of recovery and relapse, (ii) identifying the predictors of recovery and relapse and (iii) assessing the rates of comorbid conditions. A total of 30 subjects with onset of bipolar illness (according to DSM-III-R criteria) in childhood and adolescence were assessed systematically at baseline and 4 to 5 years later. All 30 subjects (100%) had recovered from their index episodes and none had exhibited chronicity. Twenty of the 30 subjects (67%) had relapsed, with most relapses occurring within 2 years of recovery from index episodes. No predictors of recovery and relapse could be identified. Conduct disorder was the only comorbid diagnosis in two subjects (7%). The main implication of our study, in view of the high rates of relapse in the crucial developmental phase of a young individual, is that long-term maintenance medication should be considered in juvenile bipolar patients, even if it is a first episode.     

The compositional and physicochemical homogeneity of male femoral cortex increases after the sixth decade

The temporal and spatial fluctuations in the dynamics of secondary osteonal remodeling impart heterogeneity to the compositional quality of bone. Bone mineral density (BMD) fails to reflect this heterogeneity as being a single score, and thus it cannot resolve the overlap between healthy individuals and those who experience fractures. Such information on tissue heterogeneity is lacking in the literature. In the current study, specimens were prepared from mid-diaphyseal portions of human femora (N = 16, age range 52–85 years old) and grouped based on the anatomical location (anterior, lateral, medial and posterior quadrants). Raman microscopy was used to obtain multiple measurements from each specimen which allowed the construction of histograms of mineralization, crystallinity and carbonation. The coefficient of variation (COV) and skewness were extracted from histograms as measures of heterogeneity. Results demonstrated that average mineralization of the medial quadrant and the data pooled over quadrants significantly increased with age. The mean carbonation increased within the observed age range for the pooled data. The variations of values about the mean became tighter for mineralization, crystallinity and type-B carbonation with age, indicating an overall reduction in compositional heterogeneity of aging femoral cortex. Skewness values indicated that the distributions of histograms were not Gaussian. We conclude that age-related changes in mean tissue composition are confounded with changes in the variation of tissue make-up about the mean. Future studies will establish as to whether compositional heterogeneity correlates with the mechanical strength of bone.     

Does latitude as a zeitgeber affect the course of bipolar affective disorder?

Background

Bipolar disorder (BD) is characterized by recurrent episodes of mood dysregulations and depression is considered as the most frequent form of relapse. However, there is some evidence that in tropical countries, the course might be different with fewer depressive episodes. This study aims to examine the frequency of depressive and manic episodes in a sample of subjects with BD from India.

Methods

Index subjects and a reliable informant (a family member) were interviewed with Diagnostic Interview for Genetic studies and a life chart was drawn to ascertain the episodes of illness in addition to reviewing their clinical case records. The mean total episode frequency and the mean manic and depressive episode frequency were estimated for this study.

Results

Data on the total episode number and number of manic and depressive episodes separately was available in 439 subjects. The subjects had been ill for 7.45 years, had experienced an average of 3.29 episodes of mania and 1.08 episodes of depression. Thus episodes of mania were seen to be more frequent.

Conclusion

It has been increasingly recognized that circadian rhythm abnormalities could play an important role in the relapse and symptom expression of bipolar disorder. The mania predominance in the course of BD in this population contrasts from the depressive predominance in other studies. We suggest that this phenomenon could be a function of latitudinal gradient in the expression of BD using the zeitgeber hypothesis.     

Role of estrogen receptor signaling required for endometriosis-like lesion establishment in a mouse model

Endometriosis results from ectopic invasion of endometrial tissue within the peritoneal cavity. Aberrant levels of the estrogen receptor (ER), ERα and ERβ, and higher incidence of autoimmune disorders are observed in women with endometriosis. An immunocompetent mouse model of endometriosis was used in which minced uterine tissue from a donor was dispersed into the peritoneal cavity of a recipient. Wild-type (WT), ERα-knockout (αERKO), and βERKO mice were donors or recipients to investigate the roles of ERα, ERβ, and estradiol-mediated signaling on endometriosis-like disease. Mice were treated with vehicle or estradiol, and resulting location, number, and size of endometriosis-like lesions were assessed. In comparison with WT lesions in WT hosts, αERKO lesions in WT hosts were smaller and fewer in number. The effect of ER status and estradiol treatment on nuclear receptor status, proliferation, organization, and inflammation within lesions were examined. αERKO lesions in WT hosts did not form distal to the incision site, respond to estradiol, or proliferate but did have increased inflammation. WT lesions in αERKO hosts did respond to estradiol, proliferate, and show decreased inflammation with treatment, but surprisingly, progesterone receptor expression and localization remained unchanged. Only minor differences were observed between WT lesions in βERKO hosts and βERKO lesions in WT hosts, demonstrating the estradiol-mediated signaling responses are predominately through ERα. In sum, these results suggest ER in both endometriosis-like lesions and their environment influence lesion characteristics, and understanding these interactions may play a critical role in elucidating this enigmatic disease.     

Global multi‐center and multi‐modal magnetic resonance imaging study of obsessive‐compulsive disorder: Harmonization and monitoring of protocols in healthy volunteers and phantoms

ObjectivesWe describe the harmonized MRI acquisition and quality assessment of an ongoing global OCD study, with the aim to translate representative, well‐powered neuroimaging findings in neuropsychiatric research to worldwide populations.MethodsWe report on T1‐weighted structural MRI, resting‐state functional MRI, and multi‐shell diffusion‐weighted imaging of 140 healthy participants (28 per site), two traveling controls, and regular phantom scans.ResultsHuman image quality measures (IQMs) and outcome measures showed smaller within‐site variation than between‐site variation. Outcome measures were less variable than IQMs, especially for the traveling controls. Phantom IQMs were stable regarding geometry, SNR, and mean diffusivity, while fMRI fluctuation was more variable between sites.ConclusionsVariation in IQMs persists, even for an a priori harmonized data acquisition protocol, but after pre‐processing they have less of an impact on the outcome measures. Continuous monitoring IQMs per site is valuable to detect potential artifacts and outliers. The inclusion of both cases and healthy participants at each site remains mandatory.     

Glomus intravagale tumour—a case report

Paragangliomas are uncommon tumours arising from chemoreceptor organs. Those arising in relation to the vagus nerve are referred to as Glomus intravagale or vagal body tumours. They are rare tumours accounting for only 3% of Head & Neck paragangliomas. A case of Glomus intravagale tumour is presented both in view of its rarity and to stress its differentiation from a carotid body tumour which in this case was possible only at the time of surgery.