Time is ticking for TikTok tics: A retrospective follow-up study in the post-COVID-19 isolation era.

INTRODUCTION: During the COVID-19 pandemic, an influx of adolescents presented worldwide with acute onset of functional tic-like behaviors (FTLBs). Our goal was to evaluate psychosocial factors around onset, to elucidate outcomes after pandemic isolation protocols were lifted, and to examine therapy and medication management. METHODS: A retrospective review was performed of 56 patients ages 10-18 years with new-onset FTLBs seen at Boston Children's Hospital beginning in March 2020. Demographic factors, medical history, and treatment were evaluated. Patient outcomes were determined retrospectively based on the Clinical Global Impression Improvement (CGI-I) and Severity (CGI-S) scales from follow-up visits. CGI-I scores assessed the progression of FTLBs; CGI-S assessed overall function. RESULTS: Ninety-six percent of patients were female-assigned at birth with high rates of comorbid anxiety (93%) and depression (71%). Forty-five percent were gender-diverse. Based on scales that assessed FTLBs (CGI-I) and overall functioning (CGI-S), up to 79% of patients improved independent of comorbid diagnosis or treatment. Evidence-based tic-specific treatments were not more effective than other treatments. A subset of patients had improvement in their FTLBs but not in their general functioning and continued to have other psychosomatic presentations. CONCLUSION: While many patients' FTLBs improved, it is critical to remain alert to patients' overall function and to assess for other functional neurological disorders and mental health concerns. The tendency of FTLBs to improve in this population, independent of treatment, highlights the unique pathophysiology of FTLBs. Future research on contributing psychosocial factors and specific treatment protocols will allow optimal support for these patients.

Languages and future-oriented economic behavior-Experimental evidence for causal effects.

Studies have shown that the use of languages which grammatically associate the future and the present tends to correlate with more future-oriented behavior. We take an experimental approach to go beyond correlation. We asked bilingual research participants, people fluent in two languages (12 language pairs) which differ in the way they encode time, to make a set of future-oriented economic decisions. We find that participants addressed in a language in which the present and the future are marked more distinctly tended to value future events less than participants addressed in a language in which the present and the future are similarly marked. In an additional experiment, bilingual research participants (seven language pairs) were asked to choose whether they wish to complete a more enjoyable task first or later (delayed gratification). When addressed in a language in which the present and the future are marked more distinctly, participants tended to prefer immediate gratification more than when addressed in a language in which the present and the future are marked less distinctly. We shed light on the mechanism in a within-person experiment in which bilingual research participants (nine language pairs) were asked to spatially mark the distance between the present and the future. When participants were addressed in a language in which the present and the future are marked more distinctly, they tended to express more precise temporal beliefs compared with when addressed in a language in which the present and the future are marked less distinctly.

Tourettic OCD: Current understanding and treatment challenges of a unique endophenotype.

Obsessive compulsive disorder (OCD) and chronic tic disorders (CTD) including Tourette Syndrome (TS) are often comorbid conditions. While some patients present with distinct symptoms of CTD and/or OCD, a subset of patients demonstrate a unique overlap of symptoms, known as Tourettic OCD (TOCD), in which tics, compulsions, and their preceding premonitory urges are overlapping and tightly intertwined. The specific behaviors seen in TOCD are typically complex tic-like behaviors although with a compulsive and partially anxious nature reminiscent of OCD. TOCD is not classified within the Diagnostic and Statistical Manual of Mental Disorders fifth edition (DSM-5) as an independent diagnostic entity, but mounting evidence suggests that TOCD is an intermediate neuropsychiatric disorder distinct from either TS or OCD alone and as such represents a unique phenomenology. In this review of TOCD we discuss clinical, genetic, environmental, neurodevelopmental, and neurocircuit-based research to better characterize our current understanding of this disorder. TOCD is characterized by earlier age of onset, male predominance, and specific symptom clusters such as lower tendency toward compulsions related to checking, cleaning, and reassurance seeking and higher tendency toward compulsions such as rubbing, tapping, or touching associated with symmetry concerns or thoughts of exactness. Functional magnetic resonance imaging (fMRI) imaging suggests that TOCD symptoms may arise from involvement of an intermediate neurocircuitry distinct from classic OCD or classic CTD. Small cumulative contributions from multiple genetic loci have been implicated, as have environmental factors such as infection and perinatal trauma. In addition, this review addresses the treatment of TOCD which is especially complex and often treatment resistant and requires pharmacology and behavioral therapy in multiple modalities. Given the distressing impact of TOCD on patients' functioning, the goal of this review is to raise awareness of this distinct entity toward the goal of improving standards of care.

Trends in Real Estate Investment Trust Ownership of US Health Care Properties.

This cross-sectional study examines the prevalence and characteristics of real estate investment trust-owned health care properties in the US health care sector.

The effect of language on performance: do gendered languages fail women in maths?

Research suggests that gendered languages are associated with gender inequality. However, as languages are embedded in cultures, evidence for causal effects are harder to provide. We contribute to this ongoing debate by exploring the relationship between gendered languages and the gender gap in mathematics achievements. We provide evidence for causality by exploiting the prominent (but not exclusive) practice in gendered languages of using masculine generics to address women. In an experiment on a large representative sample of the Hebrew-speaking adult population in Israel, we show that addressing women in the feminine, compared to addressing them in the masculine, reduces the gender gap in mathematics achievements by a third. These effects are stronger among participants who acquired the Hebrew language early in childhood rather than later in life, suggesting that it is the extent of language proficiency that generates one's sensitivity to being addressed in the masculine or in the feminine. Moreover, when women are addressed in the masculine, their efforts (in terms of time spent on the maths test) decrease and they report feeling that "science is for men" more than when addressed in the feminine. We supplement the analysis with two experiments that explore the roles of general and task-specific stereotypes in generating these effects.

Those who tan and those who don't: A natural experiment on colorism.

Are darker-skinned workers discriminated against in the labor market? Studies using survey data have shown that darker skin tone is associated with increased labor market disadvantages. However, it is hard to refute the possibility that other factors correlated with skin tones might affect employment outcomes. To overcome this inherent limitation, we use a natural experiment: we utilize changes in one's own skin tone, generated by exposure to the sun, to explore the effect of skin tone on the tendency to be employed. We find that those people whose skin tone becomes darker by exposure to the sun (but not others) are less likely to be employed when the UV radiation in the previous three weeks in the area in which they reside is greater. These within-person findings hold even when controlling for the week, the year, the region, demographic characteristics and the occupation and industry one is employed in.

Brief ex vivo Fas-ligand incubation attenuates GvHD without compromising stem cell graft performance.

Graft versus host disease (GvHD) remains a limiting factor for successful hematopoietic stem cell transplantation (HSCT). T cells and antigen-presenting cells (APCs) are major components of the hematopoietic G-CSF mobilized peripheral blood cell (MPBC) graft. Here we show that a short incubation (2 h) of MPBCs with hexameric Fas ligand (FasL) selectively induces apoptosis of specific donor T cell subsets and APCs but not of CD34+ cells. FasL treatment preferentially induces apoptosis in mature T cell subsets which express high levels of Fas (CD95), such as T stem cell memory, T central memory, and T effector memory cells, as well as TH1 and TH17 cells. Anti-CD3/CD28 stimulated T cells derived from FasL-treated-MPBCs express lower levels of CD25 and secrete lower levels of IFN-γ as compared to control cells not treated with FasL. FasL treatment also induces apoptosis of transitional, naïve, memory and plasmablastoid B cells leading to a reduction in their numbers in the graft and following engraftment in transplanted mice. Most importantly, ex vivo treatment of MPBCs with FasL prior to transplant in conditioned NOD-scid IL2Rγnull (NSG) mice prevented GvHD while preserving graft versus leukemia (GvL) effects, and leading to robust stem cell engraftment.

[PLATELETS FUNCTION IN A DROP OF BLOOD: FLOW CYTOMETRY ANALYSIS COMPARED TO PLATELET AGGREGATION].

INTRODUCTION: Light transmission aggregometry (LTA) is the most commonly used test for the diagnosis of platelet function disorders, but requires large amounts of blood samples and normal platelet count. OBJECTIVES: To compare flow cytometric (FC) platelet function testing to standard LTA in the general population, in patients treated with anti-platelets drugs and in term and preterm neonates. METHODS: Platelet function was assessed with LTA and FC using PAC1 binding and p-selectin expression, as platelet activation markers, in response to agonist activation. A comparison between LTA and FC was performed in a Clopidogrel treated patient, before and after (24 and 72 hours) loading the drug. The platelet activation markers PAC1 and p-selectin, were compared in umbilical cord blood samples of in-term and preterm neonates. RESULTS: ADP-induced platelet aggregation was comparable to p-selectin expression assayed by FC (r=0.79-0.86) as measured before and after Clopidogrel loading. Both tests showed good response to Clopidogrel in 72 hours but not in 24 hours after its loading. Preterm cord blood platelets showed decreased ADP-induced activation in both activation markers: PAC1 and p-selectin, but only p-selectin reached statistical significance. We identified possible platelet activation markers in response to commonly used agonists' stimulation for FC analysis. CONCLUSIONS: FC analysis of platelet function has added value in the diagnosis of impaired platelet function and anti-platelet drug response. Using FC enables us to test platelet function in minimal blood volume and regardless of platelet count. Identification of the unique activation marker for each agonist is prerequisite for FC analysis of platelet function.

How many cents on the dollar? Women and men in product markets.

Gender inequality in contemporary U.S. society is a well-documented, widespread phenomenon. However, little is known about gender disparities in product markets. This study is the first to use actual market data to study the behavior of women and men as sellers and buyers and differences in market outcomes. We analyze a unique and large data set containing all eBay auction transactions of most popular products by private sellers between the years 2009 and 2012. Women sellers received a smaller number of bids and lower final prices than did equally qualified men sellers of the exact same product. On average, women sellers received about 80 cents for every dollar a man received when selling the identical new product and 97 cents when selling the same used product. These findings held even after controlling for the sentiments that appear in the text of the sellers' listings. Nonetheless, it is worth noting that this gap varied by the type of the product being sold. As a policy, eBay does not reveal the gender of users. We attribute the price differences to the ability of buyers to discern the gender of the seller. We present results from an experiment that shows that people accurately identify the gender of sellers on the basis of typical information provided in postings. We supplement the analysis with an additional off-eBay experiment showing that, in a controlled setting, people are willing to pay less for money-value gift cards when they are sold by women rather than men.

Impaired migration capacity in monocytes derived from patients with Gaucher disease.

Gaucher disease (GD) is characterized by glucocerebroside (GC) accumulation due to defective activity of the glucocerebrosidase (GlcCerase) enzyme. Monocytes and macrophages exhibit the highest GlcCerase activity and are most prominently affected by GC engorgement. As GD patients tend to exert various immune system-related changes, this study was designed to investigate potential effects of monocyte dysfunction on these alterations. Monocytes were isolated from peripheral blood mononuclear cells (PBMCs) of untreated GD patients and healthy volunteers. Monocyte migration capacity towards SDF1α was assessed. The GD patients exhibited reduced numbers of monocytes and decreased capability of SDF1α-dependent monocyte migration. Evaluation of CXCR4, the SDF1α receptor, revealed reduced expression of surface CXCR4 on GD-derived monocytes, despite similar CXCR4 mRNA transcript levels in the monocytes of healthy volunteers and GD patients. Reduction of surface CXCR4 was accompanied by increased intracellular CXCR4 levels in patient monocytes. This elevated intracellular CXCR4 might reflect significantly increased SDF1α concentrations characterizing patients' serum and the lysosomal impairment of GD, resulting in decreased degradation of CXCR4. Different distributions of CXCR4 expression observed in the two groups explain impaired SDF1α-dependent monocyte migration. Reduced numbers and impaired migration capacity of GD-derived monocytes could contribute to abnormal inflammation and GD-associated immune alterations seen in these patients.

Dendritic cell cancer vaccines: from the bench to the bedside.

The recognition that the development of cancer is associated with acquired immunodeficiency, mostly against cancer cells themselves, and understanding pathways inducing this immunosuppression, has led to a tremendous development of new immunological approaches, both vaccines and drugs, which overcome this inhibition. Both "passive" (e.g. strategies relying on the administration of specific T cells) and "active" vaccines (e.g. peptide-directed or whole-cell vaccines) have become attractive immunological approaches, inducing cell death by targeting tumor-associated antigens. Whereas peptide-targeted vaccines are usually directed against a single antigen, whole-cell vaccines (e.g. dendritic cell vaccines) are aimed to induce robust responsiveness by targeting several tumor-related antigens simultaneously. The combination of vaccines with new immuno-stimulating agents which target "immunosuppressive checkpoints" (anti-CTLA-4, PD-1, etc.) is likely to improve and maintain immune response induced by vaccination.

Anti-CD20 monoclonal antibodies: beyond B-cells.

Anti-CD20 monoclonal antibodies (MoAbs), employed in treating CD20⁺ lymphomas and autoimmune diseases, appear to have broader functions than just eradicating malignant B-cells and decreasing autoantibody production. Rituximab-induced T-cell inactivation, reported both in-vitro and in-vivo, may contribute to the increased risk of T-cell-dependent infections, observed in patients receiving this therapy. T-cell polarization into a suppressive phenotype, often observed in patients receiving rituximab for autoimmune disorders, was reported to be associated with prolonged remissions. Elimination of B-cells serving as antigen-presenting cells, thereby causing impaired T-cell activation, could play a significant role in induction of these changes. Direct binding of rituximab to a CD20dim T-cell population, inducing its depletion, may contribute to the decreased T-cell activation following rituximab therapy. Further investigation of the complex network through which rituximab and new anti-CD20 MoAbs act, would advance the employment of these agents in different clinical settings.

A subset of CD8+ T cells acquiring selective suppressive properties may play a role in GvHD management.

Difficulty in segregating graft-versus-tumor effect (GvT) from graft-versus-host disease (GvHD) remains a major limitation of allogeneic stem cell transplantation (Allo SCT). Naturally occurring regulatory T cells have been suggested to suppress alloreactive T cells involved in GvHD; however, their non-selective suppressive effect raises concern regarding probable attenuation of the GvT effect. Recent studies suggested inducible CD8 (iCD8) cells to be useful in suppressing autoimmune reactions, although their function in the Allo SCT setting has not been fully explored. The current study assessed in-vitro the properties of iCD8 T cells, generated in response to allogeneic dendritic cells (DCs), imitating the Allo SCT conditions. CD25(-) peripheral blood mononuclear cells (PBMCs) were stimulated with allogeneic DCs in mixed lymphocyte culture (MLC). The resultant iCD8(+)CD25(+) population was isolated and assessed for phenotypic markers, cytokine expression profile, cell proliferation, inhibitory capacity and anti-viral response. The generated CD8(+)CD25(+)FOXP3(+) T cells selectively inhibited the primary allogeneic response, without attenuating T cell response against other stimuli, such as mitogens or a cytomegalovirus (CMV) recall antigen. In conclusion, iCD8(+)CD25(+) cells suppress allogeneic stimulation, while maintaining the capacity to respond to infectious pathogens. These cells could be potentially efficient in the Allo SCT setting, where GvHD prevention is required.

Allogeneic stem cell transplantation for patients with chronic myeloid leukemia: risk stratified approach with a long-term follow-up.

The use of allogeneic stem cell transplantation (SCT) for chronic myeloid leukemia (CML) was almost abandoned in recent years for very effective targeted therapy with tyrosine kinase inhibitors (TKIs). However, approximately one third of patients still need another treatment including SCT. 38 consecutive CML patients were treated (most in preimatinib era) with allogeneic SCT, using partial T cell depletion (TCD) and preemptive donor lymphocyte infusion (DLI), without post-transplant graft-versus-host disease (GvHD) prophylaxis. Conditioning included busulfan, cyclophosphamide, antithymocytic globulin, and fludarabine followed by donor stem cell transfusion. With a median follow up of 90.5 months (1-134), 32 patients are alive. 97% engrafted. 5-year leukemia free survival (LFS) and overall survival (OS) were 78.95% and 84.2%, respectively. All patients are in major molecular remission and 78% in complete molecular remission. Transplant-related mortality (TRM) was 13%. Twenty-four patients received DLI for residual disease. Acute GvHD, mostly Grades I-II, occurred in 18% of patients post-transplant and in 24% of patients receiving DLI. In conclusion, the risk-adapted approach using only partial TCD and preemptive escalated dose of DLI precluded the need for immunosuppressive medications and reduced the risk of significant GvHD without compromising engraftment and long-term disease control. Am. J. Hematol. 2012. © 2012 Wiley Periodicals, Inc.

Distinct compartments of the proepicardial organ give rise to coronary vascular endothelial cells.

The proepicardial organ is an important transient structure that contributes cells to various cardiac lineages. However, its contribution to the coronary endothelium has been disputed, with conflicting data arising in chick and mouse. Here we resolve this conflict by identifying two proepicardial markers, Scleraxis (Scx) and Semaphorin3D (Sema3D), that genetically delineate heretofore uncharacterized proepicardial subcompartments. In contrast to previously fate-mapped Tbx18/WT-1-expressing cells that give rise to vascular smooth muscle, Scx- and Sema3D-expressing proepicardial cells give rise to coronary vascular endothelium both in vivo and in vitro. Furthermore, Sema3D(+) and Scx(+) proepicardial cells contribute to the early sinus venosus and cardiac endocardium, respectively, two tissues linked to vascular endothelial formation at later stages. Taken together, our studies demonstrate that the proepicardial organ is a molecularly compartmentalized structure, reconciling prior chick and mouse data and providing a more complete understanding of the progenitor populations that establish the coronary vascular endothelium.

Rituximab-induced direct inhibition of T-cell activation.

BACKGROUND: Rituximab, an anti-CD20 monoclonal antibody, is reported to increase the T-cell-dependent infection risk. The current study was designed to investigate whether rituximab interferes with T-cell activation. PATIENTS AND METHODS: Patients with non-Hodgkin lymphoma receiving 4-6 courses of 375 mg/m(2) rituximab underwent detailed assessment of T-cell activation pre- and post-rituximab. A similar analysis assessed the in vitro effect of rituximab on T-cell activation in response to allogeneic dendritic cells (allo-DCs) and other stimuli. RESULTS: Patients receiving rituximab exhibited a significant decline in IL-2 and IFN-γ levels in peripheral blood, most prominent after repeated rituximab courses. Evaluation at 3 months after rituximab therapy showed restoration of inflammatory cytokine production. Similarly, in vitro stimulation of peripheral blood mononuclear cells in the presence of rituximab resulted in a significant decrease in T-cell activation markers, inflammatory cytokine production and proliferative capacity. These effects were also observed using B-cell-depleted T cells (CD3(+)CD25(-)CD19(-)) and were accompanied with disappearance of CD3(+)CD20(dim) T-cell population. CONCLUSION: Rituximab administration results in transient, dose-dependent T-cell inactivation. This effect is obtained even in B-cell absence and may increase the infection risk.