Stereoisomeric semiconducting radical cation salts of chiral bis(2-hydroxypropylthio)ethylenedithioTTF with tetrafluoroborate anions

The new chiral TTF-based donor molecule bis(2-hydroxypropylthio)ethylenedithiotetrathiafulvalene has produced enantiopure R,R and S,S radical cation salts with the tetrafluoroborate anion as well as the nearly isostructural meso/racemate mixture. The enantiopure R,R or S,S salts are both 1:1 semiconducting salts with activation energies of 0.19–0.24 eV, both crystallising in the orthorhombic space group C2221. The semiconducting salt containing both meso and racemic donor cations has a very similar crystal structure but crystallising in the monoclinic space group C2/c (β = 91.39°) with similar S⋯S interactions but a smaller activation energy of 0.15–0.17 eV. This is in contrast to previous families of this type where the disordered racemate has a larger activation energy than its enantiopure salts

Transcription of toll-like receptors 2, 3, 4 and 9, FoxP3 and Th17 cytokines in a susceptible experimental model of canine Leishmania infantum infection

Canine leishmaniosis (CanL) due to Leishmania infantum is a chronic zoonotic systemic disease resulting from complex interactions between protozoa and the canine immune system. Toll-like receptors (TLRs) are essential components of the innate immune system and facilitate the early detection of many infections. However, the role of TLRs in CanL remains unknown and information describing TLR transcription during infection is extremely scarce. The aim of this research project was to investigate the impact of L. infantum infection on canine TLR transcription using a susceptible model. The objectives of this study were to evaluate transcription of TLRs 2, 3, 4 and 9 by means of quantitative reverse transcription polymerase chain reaction (qRT-PCR) in skin, spleen, lymph node and liver in the presence or absence of experimental L. infantum infection in Beagle dogs. These findings were compared with clinical and serological data, parasite densities in infected tissues and transcription of IL-17, IL-22 and FoxP3 in different tissues in non-infected dogs (n = 10), and at six months (n = 24) and 15 months (n = 7) post infection. Results revealed significant down regulation of transcription with disease progression in lymph node samples for TLR3, TLR4, TLR9, IL-17, IL-22 and FoxP3. In spleen samples, significant down regulation of transcription was seen in TLR4 and IL-22 when both infected groups were compared with controls. In liver samples, down regulation of transcription was evident with disease progression for IL-22. In the skin, upregulation was seen only for TLR9 and FoxP3 in the early stages of infection. Subtle changes or down regulation in TLR transcription, Th17 cytokines and FoxP3 are indicative of the silent establishment of infection that Leishmania is renowned for. These observations provide new insights about TLR transcription, Th17 cytokines and Foxp3 in the liver, spleen, lymph node and skin in CanL and highlight possible markers of disease susceptibility in this model

The labor market effects of technology shocks

We analyze the effects of neutral and investment-specific technology shocks on hours worked and unemployment. We characterize the response of unemployment in terms of job separation and job finding rates. We find that job separation rates mainly account for the impact response of unemployment while job finding rates for movements along its adjustment path. Neutral shocks increase unemployment and explain a substantial portion of unemployment and output volatilityinvestment-specific shocks expand employment and hours worked and mostly contribute to hours worked volatility. We show that this evidence is consistent with the view that neutral technological progress prompts Schumpeterian creative destruction, while investment specific technological progress has standard neoclassical feature

Transgenic Expression of Soluble Human CD5 Enhances Experimentally-Induced Autoimmune and Anti-Tumoral Immune Responses

CD5 is a lymphoid-specific transmembrane glycoprotein constitutively expressed on thymocytes and mature T and B1a lymphocytes. Current data support the view that CD5 is a negative regulator of antigen-specific receptor-mediated signaling in these cells, and that this would likely be achieved through interaction with CD5 ligand/s (CD5L) of still undefined nature expressed on immune or accessory cells. To determine the functional consequence of loss of CD5/CD5L interaction in vivo, a new transgenic mouse line was generated (shCD5EμTg), expressing a circulating soluble form of human CD5 (shCD5) as a decoy to impair membrane-bound CD5 function. These shCD5EμTg mice showed an enhanced response to autologous antigens, as deduced from the presentation of more severe forms of experimentally inducible autoimmune disease (collagen-induced arthritis, CIA; and experimental autoimmune encephalitis, EAE), as well as an increased anti-tumoral response in non-orthotopic cancer models (B16 melanoma). This enhancement of the immune response was in agreement with the finding of significantly reduced proportions of spleen and lymph node Treg cells (CD4+CD25+FoxP3+), and of peritoneal IL-10-producing and CD5+ B cells, as well as an increased proportion of spleen NKT cells in shCD5EμTg mice. Similar changes in lymphocyte subpopulations were observed in wild-type mice following repeated administration of exogenous recombinant shCD5 protein. These data reveal the relevant role played by CD5/CD5L interactions on the homeostasis of some functionally relevant lymphocyte subpopulations and the modulation of immune responses to autologous antigens

Correlates of tobacco cessation counseling among Hispanic physicians in the US: a cross-sectional survey study.

BACKGROUND: Physician advice is an important motivator for attempting to stop smoking. However, physicians\u27 lack of intervention with smokers has only modestly improved in the last decade. Although the literature includes extensive research in the area of the smoking intervention practices of clinicians, few studies have focused on Hispanic physicians. The purpose of this study was to explore the correlates of tobacco cessation counseling practices among Hispanic physicians in the US. METHODS: Data were collected through a validated survey instrument among a cross-sectional sample of self-reported Hispanic physicians practicing in New Mexico, and who were members of the New Mexico Hispanic Medical Society in the year 2001. Domains of interest included counseling practices, self-efficacy, attitudes/responsibility, and knowledge/skills. Returned surveys were analyzed to obtain frequencies and descriptive statistics for each survey item. Other analyses included: bivariate Pearson\u27s correlation, factorial ANOVAs, and multiple linear regressions. RESULTS: Respondents (n = 45) reported a low level of compliance with tobacco control guidelines and recommendations. Results indicate that physicians\u27 familiarity with standard cessation protocols has a significant effect on their tobacco-related practices (r = .35, variance shared = 12%). Self-efficacy and gender were both significantly correlated to tobacco related practices (r = .42, variance shared = 17%). A significant correlation was also found between self-efficacy and knowledge/skills (r = .60, variance shared = 36%). Attitudes/responsibility was not significantly correlated with any of the other measures. CONCLUSION: More resources should be dedicated to training Hispanic physicians in tobacco intervention. Training may facilitate practice by increasing knowledge, developing skills and, ultimately, enhancing feelings of self-efficacy

A comparison of familial and sporadic Alzheimer's disease

Using a liberal criterion, a conservative probability-based criterion, and a criterion for autosomal dominant inheritance, we classified 36%, 13.5%, and 6.4% of 311 patients, respectively, as having familial Alzheimer's disease (FAD). The mean age of onset was over 70 years for all three categories of FAD. FAD and sporadic Alzheimer's disease (SAD) cases did not differ in clinical features, incidence of risk factors for dementia, or MRI or PET features. We observed earlier age of onset of AD to be related positively to longer duration of disease. Except for the autosomal dominant AD group, there was an earlier age of onset in FAD probands. The inheritance of AD from mothers was from 1.7 to 3.6 times more frequent than from fathers. Among SAD patients only, we found a preponderance of women, who were more frequently affected than would be expected from the male/female ratio in the general population of the same average age. Language performance tended to be less affected in FAD than in SAD patients, contrary to some previous reports.</jats:p

Alzheimer's disease : Interaction of apolipoprotein E genotype, family history of dementia, gender, education, ethnicity, and age of onset

We evaluated 197 patients with predominantly late-onset Alzheimer's disease (AD) who belonged to several ethnic groups and analyzed the relationship of age of onset of AD to the presence or absence of several risk factors in this entire group of patients. The apolipoprotein E (apoE) epsilon 4 allele frequency, which was 29% in all patients (compared with the reported population mean of 13.7%, p &lt; 0.001, did not vary significantly between ethnic groups but declined significantly with increasing age. The apoE epsilon 2 allele frequency was 3%, compared with the reported population mean of 7.4% (p = 0.001). The frequency of a positive family history of dementia in first-degree relatives (FH+) (overall 45%) did not vary significantly between ethnic groups. ApoE epsilon 4-positive (epsilon 4+) patients tended to have a higher FH+ rate (58%) than apoE epsilon 4-negative (epsilon 4-) patients (40%) (p = 0.02). When the potential risk factors of gender, education, FH+ status, and epsilon 4+ status were examined together in a multiple linear-regression analysis, FH+ and epsilon 4+ status (but not gender or education) were significant (they were both associated with an earlier age of onset of AD). In a post-hoc analysis, we found a reduced age of onset in women, but not men, who were both FH+ and epsilon 4+. Additionally, those probands who were epsilon 4+ were more likely to inherit the disease from their mothers than their fathers. The mechanism by which epsilon 4+ and FH+ status operate as risk factors may be by their effect on the age of onset of AD.NEUROLOGY 1996;46: 1575-1579</jats:p

Maternal SARS-CoV-2, Placental Changes and Brain Injury in 2 Neonates

Long-term neurodevelopmental sequelae are a potential concern in neonates following in utero exposure to severe acute respiratory syndrome coronavirus disease 2 (SARS-CoV-2). We report 2 neonates born to SARS-CoV-2 positive mothers, who displayed early-onset (day 1) seizures, acquired microcephaly, and significant developmental delay over time. Sequential MRI s howed severe parenchymal atrophy and cystic encephalomalacia. At birth, neither infant was SARS-CoV-2 positive (nasopharyngeal swab, reverse transcription polymerase chain reaction), but both had detectable SARS-CoV-2 antibodies and increased blood inflammatory markers. Placentas from both mothers showed SARS-CoV-2-nucleocapsid protein and spike glycoprotein 1 in the syncytiotrophoblast, fetal vascular malperfusion, and significantly increased inflammatory and oxidative stress markers pyrin domain containing 1 protein, macrophage inflammatory protein 1 βη, stromal cell-derived factor 1, interleukin 13, and interleukin 10, whereas human chorionic gonadotropin was markedly decreased. One infant (case 1) experienced sudden unexpected infant death at 13 months of age. The deceased infant's brain showed evidence of SARS-CoV-2 by immunofluorescence, with colocalization of the nucleocapsid protein and spike glycoprotein around the nucleus as well as within the cytoplasm. The constellation of clinical findings, placental pathology, and immunohistochemical changes strongly suggests that second-trimester maternal SARS-CoV-2 infection with placentitis triggered an inflammatory response and oxidative stress injury to the fetoplacental unit that affected the fetal brain. The demonstration of SARS-CoV-2 in the deceased infant's brain also raises the possibility that SARS-CoV-2 infection of the fetal brain directly contributed to ongoing brain injury. In both infants, the neurologic findings at birth mimicked the presentation of hypoxic-ischemic encephalopathy of newborn and neurologic sequelae progressed well beyond the neonatal period