All in the Family as a Single Shareholder of an S Corporation

Subject to a few exceptions, a corporation that has elected to be taxed under subchapter S of chapter 1 of subtitle A of title 26 of the United States tax code is not taxed on its net income. Instead, the income, deductions, credits, and other tax items of an S corporation pass through to its shareholders on a pro rata basis. To qualify for subchapter S treatment, an electing corporation must satisfy the requirements that are set forth in section 1361, one of which is that the corporation can have no more than 100 shareholders. One aspect of that requirement is the focus of this article

In vivo confinement promotes collective migration of neural crest cells

Collective cell migration is fundamental throughout development and in many diseases. Spatial confinement using micropatterns has been shown to promote collective cell migration in vitro, but its effect in vivo remains unclear. Combining computational and experimental approaches, we show that the in vivo collective migration of neural crest cells (NCCs) depends on such confinement. We demonstrate that confinement may be imposed by the spatiotemporal distribution of a nonpermissive substrate provided by versican, an extracellular matrix molecule previously proposed to have contrasting roles: barrier or promoter of NCC migration. We resolve the controversy by demonstrating that versican works as an inhibitor of NCC migration and also acts as a guiding cue by forming exclusionary boundaries. Our model predicts an optimal number of cells in a given confinement width to allow for directional migration. This optimum coincides with the width of neural crest migratory streams analyzed across different species, proposing an explanation for the highly conserved nature of NCC streams during development

Comorbidity of obsessive-compulsive disorder and schizotypal personality disorder: Clinical response and treatment resistance to pharmacotherapy in a 3-year follow-up naturalistic study

The present study aims to analyze the clinical and socio-demographic characteristics of patients with obsessive-compulsive disorder (OCD) in comorbidity with schizotypal personality disorder (SPD), as well as the response rate to pharmacological treatments. OCD+SPD patients had a younger age at onset, a higher probability to have more severe obsessive-compulsive symptoms, a higher rate of schizophrenia spectrum disorders in their first-degree relatives, and a poorer insight compared to OCD patients. During the 3-year follow-up period, these patients showed a lower rate of recovery, thus requiring augmentation with different psychotropic medications, including low doses of antipsychotics. Our findings suggest that the comorbidity of OCD and SPD causes a poor treatment response, and a reduced probability to recover using standard pharmacological treatment strategies. Further investigations are needed to identify alternative strategies, including psychoeducation and cognitive behavioral therapy, to manage such frequent comorbidity in clinical practice

Duration of untreated illness predicts 3-year outcome in patients with obsessive-compulsive disorder: A real-world, naturalistic, follow-up study

Duration of untreated illness (DUI) is a predictor of outcome in psychotic and affective disorders. The few available data on the effect of DUI in obsessive-compulsive disorder (OCD) suggest an association between longer DUI and poorer response to treatments. This is a real-world, naturalistic, follow-up study evaluating the impact of DUI on long-term clinical outcomes. The sample consists of 83 outpatients with OCD with a mean DUI of 7.3 (5.8) years. Patients with symmetry/ordering cluster symptoms were younger at onset of the disease (20.4 ± 7.9 vs. 27.8 ± 10.6; p<.05, d = 0.79), had a longer duration of the illness (10.1 ± 4.6 vs. 6.8 ± 4.6, p<.05; d = 0.53) and a longer DUI (7.9 ± 6.5 vs. 5.4 ± 3.6, p<.05, d = 0.49) compared to patients not presenting with those symptoms. Fifty-nine patients completed the follow-up, and 33.9% (N = 20) met the criteria for partial remission, scoring <15 at the Y-BOCS for at least eight weeks. Patients in partial remission for more than 40% of the follow-up were defined as “good outcome” and they had a significantly shorter DUI compared to patients with “poor outcome”. Access to adequate treatments is highly delayed in patients with OCD. DUI is strongly associated with poor treatment outcomes. Therefore, strategies to ensure an early diagnosis and treatment are needed

Detailed analysis of the cell-inactivation mechanism by accelerated protons and light ions

Published survival data for V79 cells irradiated by monoenergetic protons, helium-3, carbon, and oxygen ions and for CHO cells irradiated by carbon ions have been analyzed using the probabilistic two-stage model of cell inactivation. Three different classes of DNA damages formed by traversing particles have been distinguished, namely severe single-track damages which might lead to cell inactivation directly, less severe damages where cell inactivation is caused by their combinations, and damages of negligible severity that can be repaired easily. Probabilities of single ions to form these damages have been assessed in dependence on their linear energy transfer (LET) values. Damage induction probabilities increase with atomic number and LET. While combined damages play crucial role at lower LET values, single-track damages dominate in high-LET regions. The yields of single-track lethal damages for protons have been compared with the Monte Carlo estimates of complex DNA lesions, indicating that lethal events correlate well with complex DNA double-strand breaks. The decrease in the single-track damage probability for protons of LET above approx. 30 keV/$\mu$m, suggested by limited experimental evidence, is discussed, together with the consequent differences in the mechanisms of biological effects between protons and heavier ions. Applications of the results in hadrontherapy treatment planning are outlined.Comment: submitted to Physics in Medicine and Biolog

MEK1/2 regulate normal BCR and ABL1 tumor-suppressor functions to dictate ATO response in TKI-resistant Ph+ leukemia

Resistance to tyrosine kinase inhibitors (TKIs) remains a clinical challenge in Ph-positive variants of chronic myeloid leukemia. We provide mechanistic insights into a previously undisclosed MEK1/2/BCR::ABL1/BCR/ABL1-driven signaling loop that may determine the efficacy of arsenic trioxide (ATO) in TKI-resistant leukemic patients. We find that activated MEK1/2 assemble into a pentameric complex with BCR::ABL1, BCR and ABL1 to induce phosphorylation of BCR and BCR::ABL1 at Tyr360 and Tyr177, and ABL1, at Thr735 and Tyr412 residues thus provoking loss of BCR's tumor-suppression functions, enhanced oncogenic activity of BCR::ABL1, cytoplasmic retention of ABL1 and consequently drug resistance. Coherently, pharmacological blockade of MEK1/2 induces dissociation of the pentameric MEK1/2/BCR::ABL1/BCR/ABL1 complex and causes a concurrent BCRY360/Y177, BCR::ABL1(Y360/Y177) and cytoplasmic ABL1(Y412/T735) dephosphorylation thereby provoking the rescue of the BCR's anti-oncogenic activities, nuclear accumulation of ABL1 with tumor-suppressive functions and consequently, growth inhibition of the leukemic cells and an ATO sensitization via BCR-MYC and ABL1-p73 signaling axes activation. Additionally, the allosteric activation of nuclear ABL1 was consistently found to enhance the anti-leukemic effects of the MEK1/2 inhibitor Mirdametinib, which when combined with ATO, significantly prolonged the survival of mice bearing BCR::ABL1-T315I-induced leukemia. These findings highlight the therapeutic potential of MEK1/2-inhibitors/ATO combination for the treatment of TKI-resistant leukemia

Validity and reliability of the Structured Clinical Interview for the Trauma and Loss Spectrum (SCI-TALS)

Background. DSM-IV identifies three stress response disorders (acute stress Disorder (ASD), post-traumatic stress Disorder (PTSD) and adjustment disorders (AD)) that derive from specific life events. An additional condition of complicated grief (CG), well described in the literature, is triggered by bereavement. This paper reports on the reliability and validity of the Structured Clinical Interview for Trauma and Loss Spectrum (SCI-TALS) developed to assess the spectrum of stress response. The instrument is based on a spectrum model that emphasizes soft signs, low-grade symptoms, subthreshold syndromes, as well as temperamental and personality traits comprising clinical and subsyndromal manifestations. Methods. Study participants, enrolled at 6 Italian Departments of Psychiatry located at six sites, included consecutive patients with PTSD, 44 with CG and a comparative group of 48 unselected controls. Results. We showed good reliability and validity of the SCI-TALS. Domain scores were significantly higher in participants with PTSD or CG compared to controls. There were high correlations between specific SCI-TALS domains and corresponding scores on established measures of similar constructs. Participants endorsing grief and loss events reported similar scores on all instruments, except those with CG who scored significantly higher on the domain of grief reactions. Conclusion. These findings provide strong support for the internal consistency, the discriminant validity and the reliability of the SCI-TALS. These results also support the existence of a specific grief-related condition and the proposal that different forms of stress response have similar manifestations

Did we learn something positive out of the COVID-19 pandemic? Post-traumatic growth and mental health in the general population

Abstract Background When facing a traumatic event, some people may experience positive changes, defined as posttraumatic growth (PTG). Methods Understanding the possible positive consequences of the pandemic on the individual level is crucial for the development of supportive psychosocial interventions. The present paper aims to: 1) evaluate the levels of PTG in the general population; 2) to identify predictors of each dimension of post-traumatic growth. Results The majority of the sample (67%, N = 13,889) did not report any significant improvement in any domain of PTG. Participants reported the highest levels of growth in the dimension of appreciation of life (2.3 ± 1.4), while the lowest level was found in the spiritual change (1.2 ± 1.2). Female participants reported a slightly higher level of PTG in areas of personal strength (p < .002) and appreciation for life (p < .007) compared to male participants, while no significant association was found with age. At the multivariate regression models, weighted for the propensity score, only the initial week of lockdown (between 9-15 April) had a negative impact on the dimension of relating to others (B = -.107, 95% CI = -.181 to -.032, p < .005), while over time no other effects were found. The duration of exposure to lockdown measures did not influence the other dimensions of PTG. Conclusions The assessment of the levels of PTG is of great importance for the development of ad hoc supportive psychosocial interventions. From a public health perspective, the identification of protective factors is crucial for developing ad-hoc tailored interventions and for preventing the development of full-blown mental disorders in large scale

Children’s perceptions of dissimilarity in parenting styles are associated with internalizing and externalizing behavior

The purpose of this study was to examine the relationship between children’s perception of dissimilarity in parenting styles, and internalizing and externalizing problems in children. Children from the general population (n = 658) reported on the level of emotional warmth, rejection, and overprotection of both parents by filling out the child version of the Egna Minnen Beträffande Uppfostran (EMBU-C) and mothers completed the child behavior checklist (CBCL). Intraclass correlations were computed as measures of dissimilarity between parenting styles of mothers and fathers. Children’s perceived dissimilarity in parental emotional warmth is associated with internalizing and externalizing problems (β = 0.092, p < 0.05; β = 0.091, p < 0.05). Perceived dissimilarity between parents’ overprotection is associated with externalizing problems (β = 0.097, p < 0.05). Perceived dissimilarity between parenting styles is associated with externalizing and internalizing problems, over and above the effects of the level of the parenting styles. The results highlight the negative consequences of perceived dissimilarity between parents. To conclude, children have more internalizing and externalizing problems when they perceive their parents as more dissimilar in parenting styles

6-Sulphated Chondroitins Have a Positive Influence on Axonal Regeneration

Chondroitin sulphate proteoglycans (CSPGs) upregulated in the glial scar inhibit axon regeneration via their sulphated glycosaminoglycans (GAGs). Chondroitin 6-sulphotransferase-1 (C6ST-1) is upregulated after injury leading to an increase in 6-sulphated GAG. In this study, we ask if this increase in 6-sulphated GAG is responsible for the increased inhibition within the glial scar, or whether it represents a partial reversion to the permissive embryonic state dominated by 6-sulphated glycosaminoglycans (GAGs). Using C6ST-1 knockout mice (KO), we studied post-injury changes in chondroitin sulphotransferase (CSST) expression and the effect of chondroitin 6-sulphates on both central and peripheral axon regeneration. After CNS injury, wild-type animals (WT) showed an increase in mRNA for C6ST-1, C6ST-2 and C4ST-1, but KO did not upregulate any CSSTs. After PNS injury, while WT upregulated C6ST-1, KO showed an upregulation of C6ST-2. We examined regeneration of nigrostriatal axons, which demonstrate mild spontaneous axon regeneration in the WT. KO showed many fewer regenerating axons and more axonal retraction than WT. However, in the PNS, repair of the median and ulnar nerves led to similar and normal levels of axon regeneration in both WT and KO. Functional tests on plasticity after the repair also showed no evidence of enhanced plasticity in the KO. Our results suggest that the upregulation of 6-sulphated GAG after injury makes the extracellular matrix more permissive for axon regeneration, and that the balance of different CSs in the microenvironment around the lesion site is an important factor in determining the outcome of nervous system injury