High Dietary Phosphate Intake Induces Development of Ectopic Calcifications in a Murine Model of Familial Tumoral Calcinosis

Familial tumoral calcinosis is characterized by ectopic calcifications due to persistent hyperphosphatemia. The most common genetic cause of the disease is mutations in GALNT3, encoding a glycosyltransferase involved in a posttranslational modification of fibroblast growth factor 23 (FGF23). The Galnt3 knockout mouse we developed was hyperphosphatemic due to low intact Fgf23 levels, but did not develop any apparent calcifications on a standard rodent diet. We therefore tested the hypothesis that a further challenge with a high phosphate diet could induce ectopic calcifications in Galnt3 knockout mice. Mice were fed either normal (0.6%) or high (1.65%) phosphate diet for 20 weeks beginning from weaning at 3 weeks. The high phosphate diet did not affect serum phosphorus concentration. However, regardless of the dietary phosphate contents, serum phosphorus levels were consistently elevated in Galnt3 knockout mice. The mice on the high phosphate diet had slightly low serum calcium, but significantly high alkaline phosphatase, parathyroid hormone (PTH), and calcium in the kidney. Although none of Galnt3 knockout mice on the normal phosphate diet developed calcifications, calcifications appeared in approximately one‐half of the mice on the high phosphate diet by 12 weeks. Calcified masses were most often found around the neck and on the back and as large as 9.9 mm in length. These data indicate that dietary phosphate load has major impact on the development of ectopic calcifications in tumoral calcinosis. © 2014 American Society for Bone and Mineral Research.     

Reduced Levels of Vasopressin and Reduced Behavioral Modulation of Oxytocin in Psychotic Disorders

Oxytocin (OT) and arginine vasopressin (AVP) exert robust influence on social affiliation and specific cognitive processes in healthy individuals. Abnormalities in these neuroendocrine systems have been observed in psychotic disorders, but their relation to impairments in behavioral domains that these endocrines modulate is not well understood. We compared abnormalities of OT and AVP serum concentrations in probands with schizophrenia (n = 57), schizoaffective disorder (n = 34), and psychotic bipolar disorder (n = 75); their first-degree relatives without a history of psychosis (n = 61, 43, 91, respectively); and healthy controls (n = 66) and examined their association with emotion processing and cognition. AVP levels were lower in schizophrenia (P = .002) and bipolar probands (P = .03) and in relatives of schizophrenia probands (P = .002) compared with controls. OT levels did not differ between groups. Familiality estimates were robust for OT (h ² = 0.79, P = 3.97e−15) and AVP (h ² = 0.78, P = 3.93e−11). Higher levels of OT were associated with better emotion recognition (β = 0.40, P < .001) and general neuropsychological function (β = 0.26, P = .04) in healthy controls as expected but not in any proband or relative group. In schizophrenia, higher OT levels were related to greater positive symptom severity. The dissociation of OT levels and behavioral function in all proband and relative groups suggests that risk and illness factors associated with psychotic disorders are not related to reduced OT levels but to a disruption in the ability of physiological levels of OT to modulate social cognition and neuropsychological function. Decreased AVP levels may be a marker of biological vulnerability in schizophrenia because alterations were seen in probands and relatives, and familiality was high.Key words: oxytocin, vasopressin, schizophrenia, bipolar disorder, emotion recognition     

Drug refusal skills training does not enhance outcomes of African American adolescents with substance use problems

In prior research by Witkiewitz and colleagues, African American adults receiving refusal skills training (RST) had fewer heavy drinking days and were categorized as having more successful outcomes. This study extends findings to adolescents receiving the Adolescent Community Reinforcement Approach (A-CRA). Propensity score matching was used to create three groups equivalent on baseline characteristics, including: African Americans receiving refusal skills training (AA + RST; n = 214), African Americans not receiving RST (AA-RST; n = 212), and Caucasians receiving RST (CA + RST; n = 214). In propensity weighted regression models that controlled for overall A-CRA exposure, racial group by RST status was not a significant predictor of substance use frequency or abstinence/early remission outcomes. Higher exposure to A-CRA, however, was a significant predictor of both outcomes. Universal receipt of RST may not improve the outcomes of African American adolescents with substance use problems, and outcomes may be driven more by the overall number of A-CRA procedures received.     

Thapsigargin Is a Broad-Spectrum Inhibitor of Major Human Respiratory Viruses: Coronavirus,Respiratory Syncytial Virus and Influenza A Virus

The long-term control strategy of SARS-CoV-2 and other major respiratory viruses needs to include antivirals to treat acute infections, in addition to the judicious use of effective vaccines. Whilst COVID-19 vaccines are being rolled out for mass vaccination, the modest number of antivirals in use or development for any disease bears testament to the challenges of antiviral development. We recently showed that non-cytotoxic levels of thapsigargin (TG), an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) Ca²⁺ ATPase pump, induces a potent host innate immune antiviral response that blocks influenza A virus replication. Here we show that TG is also highly effective in blocking the replication of respiratory syncytial virus (RSV), common cold coronavirus OC43, SARS-CoV-2 and influenza A virus in immortalized or primary human cells. TG’s antiviral performance was significantly better than remdesivir and ribavirin in their respective inhibition of OC43 and RSV. Notably, TG was just as inhibitory to coronaviruses (OC43 and SARS-CoV-2) and influenza viruses (USSR H1N1 and pdm 2009 H1N1) in separate infections as in co-infections. Post-infection oral gavage of acid-stable TG protected mice against a lethal influenza virus challenge. Together with its ability to inhibit the different viruses before or during active infection, and with an antiviral duration of at least 48 h post-TG exposure, we propose that TG (or its derivatives) is a promising broad-spectrum inhibitor against SARS-CoV-2, OC43, RSV and influenza virus.     

Massive cross-modal cortical plasticity and the emergence of a new cortical area in developmentally blind mammals

In the current investigation, the neurophysiological organization of the neocortex was examined in adult animals that were bilaterally enucleated very early in life, before the retino-geniculo-cortical pathway was established. Our results indicate that some aspects of development of cortical fields are not mediated by specific sensory inputs. However, the current study also demonstrates that peripheral innervation plays a large role in the organization of the neocortex, as cortical territories normally involved in visual processing are completely captured by the auditory and somatosensory system. Thus, a large degree of phenotypic variability in cortical organization can be accomplished solely by removing or modifying sensory inputs.     

Preparedness Planning for Emergencies Among Postpartum Women in Arkansas During 2009

PurposeHaving an emergency plan may reduce negative effects of disaster on the health of postpartum women and their infants. However, little is known about the prevalence of emergency plans among postpartum women. In 2009, Arkansas added a question to the Pregnancy Risk Assessment Monitoring System surveillance system about whether women who gave birth that year had an emergency plan. In this study, we first describe the sociodemographic characteristics, disaster experience, and region of residence of postpartum women in Arkansas who indicated that they had an emergency plan for their families in 2009, and second, examine associations between sociodemographic characteristics and disaster experience and the presence of an emergency plan.MethodsMultivariable logistic regression (n = 1,173) was conducted to examine associations between maternal race/ethnicity, sociodemographic characteristics, region of residence, disaster experience, and having a disaster plan. We adjusted for maternal education, federal poverty level, and family size in our final model.FindingsForty-eight percent (n = 559) of women reported having an emergency plan. Hispanic women were less likely to report having a plan compared with non-Hispanic White women (n = 102 [10%]; adjusted prevalence ratio [aPR], 0.6; 95% confidence interval [CI], 0.4–0.9). Families with five or more members were more likely to have a plan compared with smaller families (n = 123 [11%]; aPR, 1.3; 95% CI, 1.1–1.6).ConclusionsPolicymakers and public health practitioners can use these results to promote emergency planning among postpartum women in Arkansas, with special outreach to postpartum women who are Hispanic or have smaller families.