Subcortical shape alterations in major depressive disorder: Findings from the ENIGMA major depressive disorder working group

Alterations in regional subcortical brain volumes have been investigated as part of the efforts of an international consortium, ENIGMA, to identify reliable neural correlates of major depressive disorder (MDD). Given that subcortical structures are comprised of distinct subfields, we sought to build significantly from prior work by precisely mapping localized MDD-related differences in subcortical regions using shape analysis. In this meta-analysis of subcortical shape from the ENIGMA-MDD working group, we compared 1,781 patients with MDD and 2,953 healthy controls (CTL) on individual measures of shape metrics (thickness and surface area) on the surface of seven bilateral subcortical structures: nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, and thalamus. Harmonized data processing and statistical analyses were conducted locally at each site, and findings were aggregated by meta-analysis. Relative to CTL, patients with adolescent-onset MDD (≤ 21 years) had lower thickness and surface area of the subiculum, cornu ammonis (CA) 1 of the hippocampus and basolateral amygdala (Cohen's d = ?0.164 to ?0.180). Relative to first-episode MDD, recurrent MDD patients had lower thickness and surface area in the CA1 of the hippocampus and the basolateral amygdala (Cohen's d = ?0.173 to ?0.184). Our results suggest that previously reported MDD-associated volumetric differences may be localized to specific subfields of these structures that have been shown to be sensitive to the effects of stress, with important implications for mapping treatments to patients based on specific neural targets and key clinical features.     

Breast Conservation After Neoadjuvant Chemotherapy

Background Tumor downstaging by preoperative neoadjuvant chemotherapy in patients with locally advanced breast tumors allows breast conservation in women who were previously candidates for mastectomy. Nevertheless, lumpectomy success in such cases cannot be fully achieved. The aim of this study was to create a quantitative tool for preoperative evaluation of the success of breast conservation in such patients.Methods The study population included 100 consecutive patients with stage II and III breast cancer who were designated for lumpectomy and 19 patients who were designated for mastectomy. All patients received neoadjuvant therapy. Breast-conserving surgery was offered in accordance with clinical and esthetic criteria. Demographic details and clinical, imaging, and pathologic information were collected from medical files. A decision protocol for classifying patients to lumpectomy or mastectomy was built by using the Classification and Regression Trees procedure based on preoperative characteristics.Results Three factors were found to be the main predictors for successful breast conservation: absence of diffuse microcalcifications as seen in the pretreatment mammogram, a postchemotherapy tumor size of < 25 mm, and the existence of a circumscribed lesion on mammography.Conclusions The use of these criteria as a basis for decision on the type of surgery may decrease the performance of unnecessary procedures.     

Thermal,Mechanical, and Acoustic Properties of Polydimethylsiloxane Filled with Hollow Glass Microspheres

Polydimethylsiloxane (PDMS) is the most widely used silicon-based polymer due to its versatility and its various attractive properties. The fabrication of PDMS involves liquid phase cross-linking to obtain hydrophobic and mechanically flexible material in the final solid form. This allows to add various fillers to affect the properties of the resulting material. PDMS has a relatively low Thermal Conductivity (TC), in the order of 0.2 W/mK, which makes it attractive for thermal insulation applications such as sealing in construction. Although a further decrease in the TC of PDMS can be highly beneficial for such applications, most research on the thermal properties of PDMS composites have focused on fillers that increase the TC rather than decrease it. In the present work, we propose a simple and reliable method for making a PDMS-based composite material with significantly improved thermal insulation properties, by adding hollow glass microspheres (HGMs) to the mixture of the liquid base and the cross-linker (10:1 ratio), followed by degassing and heat-assisted crosslinking. We obtained a 31% reduction of thermal conductivity and a 60% increase in the elastic modulus of samples with HGM content of 17% by weight. At the same time, the sound insulation capacity of the PDMS-HGM composite is slightly decreased in comparison to pure PDMS, as a result of its lower density. Finally, the wettability of the samples had no dependence on HGM content.     

TREC/KREC Levels and T and B Lymphocyte Subpopulations in COVID-19 Patients at Different Stages of the Disease

Background: T and B cell-mediated immunity can be assessed using T cell receptor excision circle (TREC) and Kappa-deleting recombination excision circle (KREC) analysis, respectively, and successful implementation of this method requires evaluation of the correlation between the TREC frequencies and T cell subsets as well as KREC levels and B lymphocyte subsets. The aim of the present study was to evaluate the correlation between the TREC/KREC concentrations and T/B lymphocyte subsets at different stages of COVID-19. Methods: We examined 33 patients in the acute stage of COVID-19 (including 8 patients with poor outcomes) and 33 COVID-19 survivors. TREC/KREC concentrations were measured using quantitative real-time PCR. T/B lymphocyte subsets were determined using flow cytometry. Results: Blood TREC and KREC levels were found to be significantly lower in the acute stage of COVID-19 compared to control values. Moreover, a zero blood TREC level was a predictor of a poor disease outcome. Reductions in CD3⁺CD4⁺CD45RO⁻CD62L⁻ and CD3⁺CD8⁺CD45RO⁻CD62L⁻ T cell counts (as well as in the main fractions of B1 and B2 B cells) indicated a favorable outcome in COVID-19 patients in the acute stage of the disease. Decreased CD3⁺CD4⁺CD45RO⁻CD62L⁺ and CD3⁺CD8⁺CD45RO⁻CD62L⁺ T cell frequencies and increased CD3⁺CD8⁺CD45RO⁻CD62L⁻ cell counts were found to indicate a poor outcome in patients with acute COVID-19. These patients were also found to have increased B1 cell counts while demonstrating no changes in B2 cell counts. The levels of effector T cell subsets an naïve B cells were normal in COVID-19 survivors. The most pronounced correlations between TREC/KREC levels and T/B cell subsets counts were observed in COVID-19 survivors: there were positive correlations with naïve T and B lymphocytes and negative correlations with central and effector memory T cell subsets. Conclusions: The assessment of correlations between TREC and T cell subsets as well as KREC levels and B cell subset counts in patients with acute COVID-19 and COVID-19 survivors has shown that blood concentrations of TREC and KREC are sensitive indicators of the stage of antigen-independent differentiation of adaptive immunity cells. The results of the TREC and KREC analysis correlated with the stages of COVID-19 and differed depending on the outcome of COVID-19.     

Self-reinforcing loop mechanism in epilepsy

The evidence for a mutual dependence between convulsive activity and duration of the paradoxical sleep (PS) can be found from the literature. Convulsions diminish the PS time, on the other hand, PS restriction increases the sensitivity to convulsion-inducing stimuli. In epilepsy, the operation of this positive feedback loop mechanism is possibly promoted by elevated levels of enkephalin and norepinephrine that are characteristic of epileptics. The above supports the convulsions–PS interplay representing a relevant therapeutic target in epilepsy. In this connection, usage of PS duration increasing hypnotics like thalidomide, in combination with enkephalin and norepinephrine antagonists is thought to be of special importance.     

Tension-type Headache and Migraine in Multiple Sclerosis

We review the evidence for a link between multiple sclerosis (MS) and two of the most common primary headache disorders: tension-type headache and migraine. We argue that the association between migraine and MS is biologically plausible and is confirmed by most studies. We discuss possible explanations for the association. First, we consider the possibility that the association is spurious. Next, we consider unidirectional causal models in which one of the conditions increases the risk of the other. A bidirectional model would suggest that each disease predisposes to the other. Alternatively, genetic or environmental risk factors shared by each condition may account for the association between them. We also address the question of whether coexisting migraine or tension-type headache in a patient with MS affects the symptom profile, clinical course, and radiographic characteristics of MS.     

Toxicological evaluation of a chicory root extract.

An Ames test and a 28-day sub-chronic toxicity study in male and female Sprague-Dawley rats were conducted to evaluate the safety of a chicory root extract being investigated as a therapeutic for inflammation. Chicory extract had no mutagenic activity in the Ames test although it was cytotoxic to certain strains of Salmonella at higher doses with and without metabolic activation. For the 28-day rat study, measurements included clinical observations, body weights, food consumption, clinical pathology, gross necropsy and histology. There were no treatment-related toxic effects from chicory extract administered orally at 70, 350, or 1000 mg/kg/day. Since there were no observed adverse effects of chicory extract in these studies, the NOAEL for the extract is 1000 mg/kg/g administered orally for 28 days.     

Occupational exposure to cotton dust in cottonseed oil mills

Air samples were collected at breathing height in the hulling-separation department of a modern cottonseed oil mill in Uzbekistan. The average elutriated mass concentration measured by standard cotton dust samplers was 4.6 mg/m3, much lower than the average total dust concentration measured by stationary personal samplers, 12.49 mg/m3, and by personal samplers attached to workers, 14.53 mg/m3. Differences in readings among the vertical elutriators, stationary personal samplers, and roving personal samplers are attributed to the distinct sampling nature and dynamics of these samplers. The data suggest that most of the dust consisted of particles larger than 15 microm, the particle size cutoff of the vertical elutriator. Differences in readings among stationary and roving personal samplers are statistically significant, presumably representing biased sampling by the roving personal samplers of regions characterized by high dust concentration (due to machines malfunctioning), the nonstatic nature of the sampling, and the interaction between the sampler and the worker (the personal cloud). Cotton dust concentrations in the hulling-separation room were nonuniform, peaking in front of and between the huller-separator pairs. The high total mass readings show that workers were exposed to very high levels of nonthoracic airborne dust, which upon inhalation tends to deposit in the extrathoracic airways. The high elutriated mass concentrations suggest that workers were exposed to respirable cotton dust at levels higher than 1 mg/m3 mean concentration, the current Occupational Safety and Health Administration (OSHA) Permissible Exposure Limit (PEL) for cotton dust. Regressions between dust concentrations measured by stationary vertical elutriators and by personal samplers attached to workers serve for estimating the potential occupational exposure to cotton dust of workers in the hulling-separation room.