Sex Differences in Oxidative Stress-Mediated Reductions in Microvascular Endothelial Function in Young Adult e-Cigarette Users.

BACKGROUND: Chronic electronic-cigarette (EC) use is reported to decrease vascular endothelial function. However, the mechanism(s) mediating this reduction remain unclear. In this study, we examined endothelium- and NO-dependent dilation, and the role of oxidative stress in attenuating these responses, in healthy young EC users (n=20, 10 males/10 females) compared with healthy controls (n=20, 10 males/10 females). We hypothesized that EC would have reduced endothelium- and NO-dependent dilation and administration of the superoxide scavenger tempol would increase these responses in EC. We further hypothesized that female EC would have the greatest reductions in endothelium- and NO-dependent dilation. METHODS: We assessed microvascular endothelium-dependent vasodilator function in vivo by measurement of cutaneous vascular conductance (%CVCmax) responses to a standardized local heating protocol in control and 10 µM tempol-treated sites. After full expression of the local heating response, 15 mM NG-nitro-L-arginine methyl ester (NO synthase inhibition) was perfused. RESULTS: EC had significantly reduced endothelium- (73±15 versus 87±9%CVCmax; P<0.001) and NO-dependent (48±17% versus 62±15%; P=0.011) dilation. Tempol perfusion increased endothelium-dependent (84±12%CVCmax P=0.01) and NO-dependent (63±14% P=0.005) dilation in EC but had no effect in healthy control. Within female sex, EC had lower endothelium-dependent (71±13 versus 89±7%CVCmax; P=0.002) and NO-dependent (50±6 versus 69±11%; P=0.005) dilation compared with healthy control, and tempol augmented endothelium-dependent (83±13%CVCmax; P=0.002) and NO-dependent (62±13%; P=0.015) dilation. There were no group or treatment differences within male sex. CONCLUSION: Healthy young adult EC users have reduced microvascular endothelium-dependent and NO-dependent dilation, driven by greater reductions in female EC users, and mediated in part by superoxide.

Enhancing an HIV index case testing passive referral model through a behavioural skills-building training for healthcare providers: a pre-/post-assessment in Mangochi District, Malawi.

INTRODUCTION: Although knowledge of HIV positivity is a necessary step towards engagement in HIV care, more than one quarter of HIV-positive Malawians remain unaware of their HIV status. Testing the sexual partners, guardians and children of HIV-positive persons (index case finding or ICF) is a promising way of identifying HIV-positive persons unaware of their HIV status. ICF can be passive where the HIV-positive individual (index) invites a partner (or contact) for HIV testing or active where a health provider assists the index with partner notification and offers HIV testing to the partner. Strategies to improve passive ICF have not been thoroughly studied. We describe the impact of a behavioural skills-building training to enhance healthcare workers' (HCWs) implementation of Malawi's passive ICF programme. METHODS: In June 2017, HCWs from 36 health facilities in Mangochi were oriented to Malawi's ICF programme and began implementation. In February and April 2018, a total of 573 HCWs from these facilities received further training from the Tingathe Programme. The training focused on eliciting more untested sexual contacts from indexes and better equipping indexes on issuing "family referral slips" to contacts. Monthly programmatic data were abstracted from clinical registers from October 2017 to July 2018. Monthly programmatic indicators were collected from the Index Case Testing Register and the HIV Counselling and Testing Register and were entered into a data set with one record per facility per month. T-tests were used to compare the means of these indicators. RESULTS: During the ten-month study period, there were 200 facility-months observed before and 124 facility-months observed after training. The mean number of indexes identified per facility-month remained stable after training (pre = 18.9, post = 21.2, p = 0.74), but the mean number of sexual partners listed per facility-month (pre = 6.3, post = 10.6, p < 0.001) increased. The mean number of contacts who received HIV testing (pre = 11.1, post = 24.8, p < 0.001) and the mean number of HIV-positive contacts identified per facility-month (pre = 1.3, post = 2.3, p < 0.001) also increased. CONCLUSIONS: A brief behavioural skills-building training impacted a range of meaningful outcomes, including identification of HIV-positive individuals in a passive ICF programme. Such approaches could facilitate the identification of HIV-positive persons unaware of their HIV status, a necessary step for engagement in HIV care.

Ethnic disparity in breast cancer survival in southern Thai women.

BACKGROUND: Breast cancer has the highest incidence in women of all cancers and its burden is expected to continue to increase worldwide, especially in middle-income countries such as Thailand. The southern region of Thailand is unique in that it is comprised of 30% Muslims, whereas the rest of Thailand is 95% Buddhist. Breast cancer incidence and survival differ between these religious groups, but the association between clinical subtype of breast cancer and survival has not yet been assessed. METHODS: Here we characterized differences in breast cancer survival with consideration to clinical subtype by religious group (Muslim Thai and Buddhist Thai women). We compared distributions of age, stage and clinical subtype and assessed overall survival by religion. RESULTS: Our findings show that Muslim Thai women with breast cancer are diagnosed at a younger age, at later stages and have shorter overall survival times compared to Buddhist Thai women with breast cancer. We also observe a higher proportion of triple negative tumors characterized in Muslim Thai women. CONCLUSIONS: Our findings confirm previous studies that have shown lower survival rates in Muslim Thai women compared to Buddhist women with breast cancer and offer novel information on subtype distribution. To date, this is the first study assessing clinical subtypes in southern Thailand by religious status. IMPACT: Our findings are critical in providing information on the role of clinical subtype in cancer disparities and provide evidence from the Southeast Asian region for global studies on breast cancer survival.

Identification of latent safety threats using high-fidelity simulation-based training with multidisciplinary neonatology teams.

BACKGROUND: Latent safety threats (LSTs) are errors in design, organization, training, or maintenance that may contribute to medical errors and have a significant impact on patient safety. The investigation described in this article was conducted as part of a larger prospective, longitudinal evaluation using laboratory- and in situ simulation-based training sessions to improve technical and nontechnical skills of neonatal ICU (NICU) providers at a Level III academic NICU. METHODS: Simulations were performed in laboratory (4 scenarios per session) and in situ (1 scenario per session) settings with multidisciplinary neonatology teams. Facilitators and subjects identified LSTs during standardized debriefings immediately following each scenario After enrollment, facilitators classified LSTs into equipment, medication, personnel, resource, or technical skill. Pervasive team knowledge gaps were further subclassified into lack of awareness or understanding, procedure performed incorrectly, omission of necessary action, or inappropriate action. RESULTS: In a 19-month period of enrollment (August 2009-March 2011), 177 subjects of 202 NICU providers were trained in the laboratory, 135 of whom participated in the in situ sessions. In the laboratory, 22 sessions were completed, with 70 LSTs identified (0.8 LSTs per scenario). During the 16 in situ sessions, 29 LSTs (1.8 LSTs per scenario) were identified. The 99 LSTs were reported to NICU leadership, leading to 19 documented improvements. CONCLUSIONS: The NICU setting has a high rate of previously unidentified LSTs. Conducting in situ scenarios allows for the identification of novel LSTs not detected in the simulation laboratory. The subsequent clinical improvements made to the actual clinical care environment are the best objective evidence of the benefits of simulation-based multidisciplinary team training.

Acute glial activation by stab injuries does not lead to overt damage or motor neuron degeneration in the G93A mutant SOD1 rat model of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease where motor neurons within the brain and spinal cord are lost, leading to paralysis and death. Recently, a correlation between head trauma and the incidence of ALS has been reported. Furthermore, new invasive neurosurgical studies are being planned which involve inserting needles directly to the spinal cord. We therefore tested whether acute trauma to the spinal cord via a knife wound injury would lead to accelerated disease progression in rodent models of ALS (SOD1(G93A) rats). A longitudinal stab injury using a small knife was performed within the lumbar spinal cord region of presymptomatic SOD1(G93A) rats. Host glial activation was detected in the lumbar area surrounding a micro-knife lesion at 2 weeks after surgery in both wild type and SOD1(G93A) animals. However, there was no sign of motor neuron loss in the injured spinal cord of any animal and normal motor function was maintained in the ipsilateral limb. These results indicate that motor neurons in presymptomatic G93A animals are not affected by an invasive puncture wound injury involving reactive astrocytes. Furthermore, acute trauma alone does not accelerate disease onset or progression in this ALS model which is important for future strategies of gene and cell therapies directly targeting the spinal cord of ALS patients.