Indian Boarding School Experience, Substance Use, and Mental Health among Urban Two-Spirit American Indian/Alaska Natives

Background: Systematic efforts of assimilation removed many Native children from their tribal communities and placed in non-Indian-run residential schools. Objectives: To explore substance use and mental health concerns among a community-based sample of 447 urban two-spirit American Indian/Alaska Native adults who had attended boarding school as children and/or who were raised by someone who attended boarding school. Method: Eighty-two respondents who had attended Indian boarding school as children were compared to respondents with no history of boarding school with respect to mental health and substance use. Results: Former boarding school attendees reported higher rates of current illicit drug use and living with alcohol use disorder, and were significantly more likely to have attempted suicide and experienced suicidal thoughts in their lifetime compared to non-attendees. About 39% of the sample had been raised by someone who attended boarding school. People raised by boarding school attendees were significantly more likely to have a general anxiety disorder, experience posttraumatic stress disorder symptoms, and have suicidal thoughts in their lifetime compared to others.     

Pregnancy in women on chronic dialysis: a review

The frequency of pregnancy in women on dialysis is extremely low, but the percentage of successful pregnancies in this context has increased over the years, with some studies placing the survival rate above 70%. These pregnancies are not exempt from both maternal and foetal complications, and so their management requires the joint efforts of nephrologists, gynaecologists, nurses, and nutritionists. Currently, we have been unable to establish consistent systematic treatment from both nephrological and gynaecological specialists in these patients. The main changes that need to be made are: increased time on dialysis, maintaining low levels of pre-dialysis urea, avoiding: maternal hypertension and hypotension, anaemia, urinary tract infections, and fluctuations in electrolytes. Adequate foetal monitoring is also necessary.     

Relationship between ABO blood groups and von Willebrand factor,ADAMTS13 and factor VIII in patients undergoing hemodialysis

Several studies have demonstrated that non-O blood groups subjects present an increased VTE risk as compared to those carrying O blood group. The aim of this study was to investigate the ABO blood groups influence on factor VIII (FVIII) activity, von Willebrand factor (VWF), and ADAMTS13 plasma levels in patients undergoing hemodialysis (HD). Patients undergoing HD (N=195) and 80 healthy subjects (control group) were eligible for this cross-sectional study. The ABO blood group phenotyping was performed by the reverse technique. FVIII activity was measured through coagulometric method, and VWF and ADAMTS13 antigens were assessed by ELISA. FVIII activity and VWF levels were significantly higher and ADAMTS13 levels was decreased in HD patients, as compared to healthy subjects (P < 0.001, in three cases). HD patients carrying non-O blood groups showed a significant increase in FVIII activity (P = 0.001) and VWF levels (P < 0.001) when compared to carriers of O blood group. However, no significant difference was observed in ADAMTS13 levels (P = 0.767). In the control group, increased in FVIII activity (P = 0.001) and VWF levels (P = 0.002) and decreased in ADAMTS13 levels (P = 0.005) were observed in subjects carrying non-O blood groups as compared to carriers of O blood group.Our data confirmed that ABO blood group is an important risk factor for increased procoagulant factors in plasma, as FVIII and VWF. Admitting the possible role of kidneys in ADAMTS13 synthesis or on its metabolism, HD patients were not able to increase ADAMTS13 levels in order to compensate the increase of VWF levels mediated by ABO blood groups. Considering that non-O blood groups constitute a risk factor for thrombosis, it is reasonable to admit that A, B and AB HD patients need a careful and continuous follow-up in order to minimize thrombotic events.     

Risk of multiple myeloma is associated with polymorphisms within telomerase genes and telomere length

Compelling biological and epidemiological evidences point to a key role of genetic variants of the TERT and TERC genes in cancer development. We analyzed the genetic variability of these two gene regions using samples of 2,267 multiple myeloma (MM) cases and 2,796 healthy controls. We found that a TERT variant, rs2242652, is associated with reduced MM susceptibility (OR = 0.81; 95% CI: 0.72–0.92; p = 0.001). In addition we measured the leukocyte telomere length (LTL) in a subgroup of 140 cases who were chemotherapy‐free at the time of blood donation and 468 controls, and found that MM patients had longer telomeres compared to controls (OR = 1.19; 95% CI: 0.63–2.24; p_trend = 0.01 comparing the quartile with the longest LTL versus the shortest LTL). Our data suggest the hypothesis of decreased disease risk by genetic variants that reduce the efficiency of the telomerase complex. This reduced efficiency leads to shorter telomere ends, which in turn may also be a marker of decreased MM risk.     

Enhancement of ionizing radiation response by histamine in vitro and in vivo in human breast cancer

The radioprotective potential of histamine on healthy tissue has been previously demonstrated. The aims of this work were to investigate the combinatorial effect of histamine or its receptor ligands and gamma radiation in vitro on the radiobiological response of 2 breast cancer cell lines (MDA-MB-231 and MCF-7), to explore the potential molecular mechanisms of the radiosensitizing action and to evaluate the histamine-induced radiosensitization in vivo in a triple negative breast cancer model. Results indicate that histamine significantly increased the radiosensitivity of MDA-MB-231 and MCF-7 cells. This effect was mimicked by the H₁R agonist 2-(3-(trifluoromethyl)phenyl)histamine and the H₄R agonists (Clobenpropit and VUF8430) in MDA-MB-231 and MCF-7 cells, respectively. Histamine and its agonists enhanced radiation-induced oxidative DNA damage, DNA double-strand breaks, apoptosis and senescence. These effects were associated with increased production of reactive oxygen species, which correlated with the inhibition of catalase, glutathione peroxidase and superoxide dismutase activities in MDA-MB-231 cells. Histamine was able also to potentiate in vivo the anti-tumoral effect of radiation, increasing the exponential tumor doubling time. We conclude that histamine increased radiation response of breast cancer cells, suggesting that it could be used as a potential adjuvant to enhance the efficacy of radiotherapy.     

Mechanisms of cerebral vasospasm and cerebral ischaemia in subarachnoid haemorrhage

Subarachnoid haemorrhage (SAH) is a cerebrovascular emergency associated with significant morbidity and mortality. SAH is characterized by heterogeneity, interindividual variation and complexity of pathophysiological responses following extravasation of blood from cerebral circulation. The purpose of this review is to integrate previously established pre-existing factors, pathophysiological pathways and to develop a concept map of mechanisms of SAH-induced cerebral vasospasm and delayed cerebral ischaemia using a systematic approach. We conducted an extensive mapping of a hypothesized sequence of pathophysiological events. Documentation of supporting evidence was done alongside a concept map building. After finalizing the model, we conducted an analysis of the consequences and connections of pathophysiological events. We included the findings of experimental research, focusing on pathophysiological processes. We focused on SAH-induced cerebral vasospasm and delayed cerebral ischaemia as a component of cerebral injury and potential systemic consequences. SAH-induced brain injury occurs within 72 h following haemorrhage. Pathophysiology of cerebral vasospasm may include reduction in NO production, direct activation of calcium channels, upregulating genes involved with inflammation and extracellular matrix remodelling, triggering oxidative stress and free radical damage to smooth muscle and lipid peroxidation of cell membranes, cortical spreading depolarizations, sympathetic activation, finally resulting in the failure of cerebral autoregulation, microthrombosis and cerebral ischaemic injury. This cascade of events might explain why medical therapy often fails to reverse resistant cerebral vasospasm and to prevent cerebral ischaemia.