Anxiety, stress, and depression in Australian pregnant women during the COVID-19 pandemic: A cross sectional study.

BACKGROUND: The COVID-19 pandemic necessitated rapid responses by health services to suppress transmission of the virus. AIM: This study aimed to investigate predictors of anxiety, stress and depression in Australian pregnant women during the COVID-19 pandemic including continuity of carer and the role of social support. METHODS: Women aged 18 years and over in their third trimester of pregnancy were invited to complete an online survey between July 2020 and January 2021. The survey included validated tools for anxiety, stress, and depression. Regression modelling was used to identify associations between a range of factors including continuity of carer, and mental health measures. FINDINGS: 1668 women completed the survey. One quarter screened positive for depression, 19% for moderate or higher range anxiety, and 15.5% for stress. The most significant contribution to higher anxiety, stress, and depression scores was a pre-existing mental health condition, followed by financial strain and a current complex pregnancy. Protective factors included age, social support, and parity. DISCUSSION: Maternity care strategies to reduce COVID-19 transmission restricted women's access to their customary pregnancy supports and increased their psychological morbidity. CONCLUSION: Factors associated with anxiety, stress and depression scores during the COVID-19 pandemic were identified. Maternity care during the pandemic compromised pregnant women's support systems.

A unified call to action from Australian nursing and midwifery leaders: ensuring that Black lives matter.

Nurses and midwives of Australia now is the time for change! As powerfully placed, Indigenous and non-Indigenous nursing and midwifery professionals, together we can ensure an effective and robust Indigenous curriculum in our nursing and midwifery schools of education. Today, Australia finds itself in a shifting tide of social change, where the voices for better and safer health care ring out loud. Voices for justice, equity and equality reverberate across our cities, our streets, homes, and institutions of learning. It is a call for new songlines of reform. The need to embed meaningful Indigenous health curricula is stronger now than it ever was for Australian nursing and midwifery. It is essential that nursing and midwifery leadership continue to build an authentic collaborative environment for Indigenous curriculum development. Bipartisan alliance is imperative for all academic staff to be confident in their teaching and learning experiences with Indigenous health syllabus. This paper is a call out. Now is the time for Indigenous and non-Indigenous nurses and midwives to make a stand together, for justice and equity in our teaching, learning, and practice. Together we will dismantle systems, policy, and practices in health that oppress. The Black Lives Matter movement provides us with a 'now window' of accepted dialogue to build a better, culturally safe Australian nursing and midwifery workforce, ensuring that Black Lives Matter in all aspects of health care.

Flightless I exacerbation of inflammatory responses contributes to increased colonic damage in a mouse model of dextran sulphate sodium-induced ulcerative colitis.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by cytokine driven inflammation that disrupts the mucosa and impedes intestinal structure and functions. Flightless I (Flii) is an immuno-modulatory protein is a member of the gelsolin family of actin-remodelling proteins that regulates cellular and inflammatory processes critical in tissue repair. Here we investigated its involvement in UC and show that Flii is significantly elevated in colonic tissues of patients with inflammatory bowel disease. Using an acute murine model of colitis, we characterised the contribution of Flii to UC using mice with low (Flii+/-), normal (Flii+/+) and high Flii (FliiTg/Tg). High levels of Flii resulted in significantly elevated disease severity index scores, increased rectal bleeding and degree of colon shortening whereas, low Flii expression decreased disease severity, reduced tissue inflammation and improved clinical indicators of UC. Mice with high levels of Flii had significantly increased histological disease severity and elevated mucosal damage with significantly increased inflammatory cell infiltrate and significantly higher levels of TNF-α, IFN-γ, IL-5 and IL-13 pro-inflammatory cytokines. Additionally, Flii overexpression resulted in decreased ß-catenin levels, inhibited Wnt/ß-catenin signalling and impaired regeneration of colonic crypts. These studies suggest that high levels of Flii, as is observed in patients with UC, may adversely affect mucosal healing via mechanisms involving Th1 and Th2 mediated tissue inflammation and Wnt/ß-catenin signalling pathway.

Oxytocin by intranasal and intravenous routes reaches the cerebrospinal fluid in rhesus macaques: determination using a novel oxytocin assay.

Oxytocin (OT) is a potential treatment for multiple neuropsychiatric disorders. As OT is a peptide, delivery by the intranasal (IN) route is the preferred method in clinical studies. Although studies have shown increased cerebrospinal fluid (CSF) OT levels following IN administration, this does not unequivocably demonstrate that the peripherally administered OT is entering the CSF. For example, it has been suggested that peripheral delivery of OT could lead to central release of endogenous OT. It is also unknown whether the IN route provides for more efficient entry of the peptide into the CSF compared to the intravenous (IV) route, which requires blood-brain barrier penetration. To address these questions, we developed a sensitive and specific quantitative mass spectrometry assay that distinguishes labeled (d5-deuterated) from endogenous (d0) OT. We administered d5 OT (80 IU) to six nonhuman primates via IN and IV routes as well as IN saline as a control condition. We measured plasma and CSF concentrations of administered and endogenous OT before (t=0) and after (t=10, 20, 30, 45 and 60 min) d5 OT dosing. We demonstrate CSF penetrance of d5, exogenous OT delivered by IN and IV administration. Peripheral administration of d5 OT did not lead to increased d0, endogenous OT in the CSF. This suggests that peripheral administration of OT does not lead to central release of endogenous OT. We also did not find that IN administration offered an advantage compared to IV administration with respect to achieving greater CSF concentrations of OT.

Oseltamivir in influenza outbreaks in care homes: challenges and benefits of use in the real world.

BACKGROUND: Respiratory virus infections, including influenza, are an important cause of potentially avoidable hospital admissions in the elderly. Although recent reviews have questioned the efficacy of oseltamivir in the prevention of transmission, it has been a central part of the authors' strategy to manage outbreaks in residential homes. AIM: To evaluate the management of respiratory virus infection outbreaks in residential homes, with particular emphasis on the logistics and effectiveness of antiviral prophylaxis with oseltamivir. METHODS: A descriptive analysis was undertaken from a retrospective survey of records held on a local database for three northern hemisphere influenza seasons from 2010 to 2013. RESULTS: In total, 75 respiratory outbreaks were reported from 590 care homes during the study period; of these, the aetiological agent was confirmed as influenza in 35 outbreaks. Overall attack, hospital admission and death rates for influenza were 29.7%, 5.3% and 3.3%, respectively. A further 10 outbreaks were caused by parainfluenza, human metapneumovirus or respiratory syncytial virus in combination with each other or rhinovirus, and six outbreaks were caused by rhinovirus alone. No agent was identified for the remaining 24 outbreaks. CONCLUSIONS: Early public health involvement can lead to rapid termination of outbreaks of respiratory virus infections in residential homes. Although the use of oseltamivir is expensive, the data suggest that it does have some benefits as prophylaxis in this setting. Trials are needed to determine the most clinically and cost-effective interventions to control outbreaks in residential homes and avoid hospital admissions.

Circulating tumour cells: the evolving concept and the inadequacy of their enrichment by EpCAM-based methodology for basic and clinical cancer research.

Increasing evidence suggests that circulating tumour cells (CTCs) are responsible for metastatic relapse and this has fuelled interest in their detection and quantification. Although numerous methods have been developed for the enrichment and detection of CTCs, none has yet reached the 'gold' standard. Since epithelial cell adhesion molecule (EpCAM)-based enrichment of CTCs offers several advantages, it is one of the most commonly used and has been adapted for high-throughput technology. However, emerging evidence suggests that CTCs are highly heterogeneous: they consist of epithelial tumour cells, epithelial-to-mesenchymal transition (EMT) cells, hybrid (epithelial/EMT(+)) tumour cells, irreversible EMT(+) tumour cells, and circulating tumour stem cells (CTSCs). The EpCAM-based approach does not detect CTCs expressing low levels of EpCAM and non-epithelial phenotypes such as CTSCs and those that have undergone EMT and no longer express EpCAM. Thus, the approach may lead to underestimation of the significance of CTCs, in general, and CTSCs and EMT(+) tumour cells, in particular, in cancer dissemination. Here, we provide a critical review of research literature on the evolving concept of CTCs and the inadequacy of their enrichment by EpCAM-based technology for basic and clinical cancer research. The review also outlines future perspectives in the field.

Induction of apoptosis by the medium-chain length fatty acid lauric acid in colon cancer cells due to induction of oxidative stress.

BACKGROUND: Fatty acids are classified as short-chain (SCFA), medium-chain (MCFA) or long-chain and hold promise as adjunctive chemotherapeutic agents for the treatment of colorectal cancer. The antineoplastic potential of MCFA remains underexplored; accordingly, we compared the MCFA lauric acid (C12:0) to the SCFA butyrate (C4:0) in terms of their capacity to induce apoptosis, modify glutathione (GSH) levels, generate reactive oxygen species (ROS), and modify phases of the cell cycle in Caco-2 and IEC-6 intestinal cell lines. METHODS: Caco-2 and IEC-6 cells were treated with lauric acid, butyrate, or vehicle controls. Apoptosis, ROS, and cell cycle analysis were determined by flow cytometry. GSH availability was assessed by enzymology. RESULTS: Lauric acid induced apoptosis in Caco-2 (p < 0.05) and IEC-6 cells (p < 0.05) compared to butyrate. In Caco-2 cells, lauric acid reduced GSH availability and generated ROS compared to butyrate (p < 0.05). Lauric acid reduced Caco-2 and IEC-6 cells in G0/G1and arrested cells in the S and G2/M phases. Lauric acid induced apoptosis in IEC-6 cells compared to butyrate (p < 0.05). Butyrate protected IEC-6 cells from ROS-induced damage, whereas lauric acid induced high levels of ROS compared to butyrate. CONCLUSION: Compared to butyrate, lauric acid displayed preferential antineoplastic properties, including induction of apoptosis in a CRC cell line.

Guidelines for the public health management of typhoid and paratyphoid in England: practice guidelines from the National Typhoid and Paratyphoid Reference Group.

OBJECTIVES: The Typhoid and Paratyphoid Reference Group (TPRG) was convened by the Health Protection Agency (HPA) and the Chartered Institute of Environmental Health (CIEH) to revise guidelines for public health management of enteric fever. This paper presents the new guidelines for England and their rationale. METHODS: Methods include literature reviews including grey literature such as audit data and case studies; analysis of enhanced surveillance data from England, Wales and Northern Ireland; review of clearance and screening schedules in use in other non-endemic areas; and expert consensus. RESULTS: The evidence and principles underpinning the new guidance are summarised. Significant changes from previous guidance include: • Algorithms to guide risk assessment and management, based on risk group and travel history; • Outline of investigation of non-travel cases; • Simplified microbiological clearance schedules for cases and contacts; • Targeted co-traveller screening and a "warn and inform" approach for contacts; • Management of convalescent and chronic carriers. CONCLUSIONS: The guidelines were launched in February 2012. Feedback has been positive: the guidelines are reported to be clear, systematic, practical and risk-based. An evaluation of the guidelines is outlined and will add to the evidence base. There is potential for simplification and consistency between international guidelines.

Control measures for invasive group A streptococci (iGAS) outbreaks in care homes.

OBJECTIVES: The incidence of invasive group A streptococcal infections (iGAS) is increasing in Europe, with a particularly high morbidity and mortality in the elderly. Control of outbreaks in care homes is therefore important; but is unclear how best to manage these incidents. We attempted to identify which control measures are most likely to be effective. METHODS: We undertook literature searches using PubMed and Google Scholar and contacted colleagues in Health Protection Units in England for unpublished outbreaks. RESULTS: We identified 31 outbreaks; of which 20 had sufficient detail for further analysis. Overall carriage rates of GAS in care home residents identified in outbreak investigations were 4.7%, and in staff 3.2%. In 8 outbreaks mass antibiotic prophylaxis was offered, in 9 selective prophylaxis only and in 3 none at all. Surveillance swabbing had limited influence on decisions regarding prophylaxis. A few papers mentioned the role of environmental contamination and the risk from an affected roommate. CONCLUSIONS: Pooling of results from these outbreaks failed to suggest any clear advantage to either a selective or mass antibiotic prophylaxis strategy in controlling spread. Systematic investigation and data collection from future outbreaks could be of benefit in informing future policy.

Screening for traumatic brain injury in an offender sample: a first look at the reliability and validity of the Traumatic Brain Injury Questionnaire.

OBJECTIVE: To assess the reliability and validity of the Traumatic Brain Injury Questionnaire (TBIQ) for assessing history of traumatic brain injury (TBI) in an offender population. SETTING/PARTICIPANTS: Offenders (118 women and 107 men) from 6 federal prison facilities in 3 geographic regions. MEASURES: TBIQ and multiple measures of cognitive and behavioral functioning. RESULTS: Preliminary results indicated good test-retest reliability for lifetime history of head injury, good internal consistency for symptom severity and frequency scales, and good criterion validity for frequency of head injury and frequency and severity of symptoms. CONCLUSION: The TBIQ holds promise as an instrument for the assessment of TBI history in offender populations.

Infection control failures in a dental surgery--dilemmas in incident management.

Three separate incidents involving failure of decontamination of dental instruments were reported to our Unit in less than one year. We describe the risk assessment we undertook for the likelihood of detecting transmission of a blood borne virus infection. Even where 4000 patients attended the same dentist for seven years, there was no certainty of detecting even one person infected by the decontamination failure, while several people who had acquired infection by other routes would be identified. We conclude that these findings suggest that notifying patients is not usually justified.

Deficiency of invariant natural killer T cells in coeliac disease.

BACKGROUND: Immunoregulatory invariant natural killer (iNK) T cells rapidly produce interleukin (IL)-4 and other cytokines that suppress a Th1 response and are deficient in some autoimmune diseases. AIM: The aim of this study was to investigate any deficiency of iNK T cells in coeliac disease. METHODS: Blood was collected from 86 subjects with coeliac disease and from 152 healthy control subjects for investigation of Valpha24+ T cells by flow cytometry. iNK T cells were assessed by Valpha24 and alpha-galactosylceramide/CD1d tetramer markers in 23 normal controls and 13 subjects with coeliac disease. Intracellular IL-4 was measured after anti-CD3 antibody stimulation. Duodenal biopsies were obtained in a subgroup of subjects with coeliac disease and control subjects for Valpha24 mRNA expression using relative PCR and for Valpha24+ T cells by immunofluorescence. RESULTS: The mean numbers of circulating Valpha24+ T cells and iNK T cells in coeliac disease were 27% (p<0.001) and 16% (p<0.001), respectively, of levels in control subjects. After in vitro anti-CD3 stimulation, numbers of IL-4+ producing iNK T cells from subjects with coeliac disease were unchanged but increased by 21% in control subjects. In subjects with coeliac disease, Valpha24 mRNA intestinal expression was reduced to 17% (p<0.001) by relative PCR and numbers of intestinal Valpha24+ T cells were 16% (p<0.01) of levels in control subjects. CONCLUSIONS: We conclude that Valpha24+ T cells and iNK T cells are deficient in coeliac disease. We speculate that this deficiency could contribute to the failure of immunological oral tolerance that seems to underlie this disease.

Reversal of supersensitive striatal dopamine D1 receptor signaling and extracellular signal-regulated kinase activity in dopamine-deficient mice.

Lesions of dopaminergic nigrostriatal neurons cause supersensitivity to dopamine in the striatum. Previous work has shown that such supersensitivity, an important aspect of rodent models of Parkinson's disease, is associated with anatomically abnormal patterns in the activation of extracellular signal-regulated kinase. After lesions of dopaminergic neurons, dopamine D1-receptor agonists activate extracellular signal-regulated kinase in the dorsal striatum, something not observed in intact animals. Here we used a more selective method of dopamine depletion. Dopamine-deficient mice, in which the tyrosine hydroxylase gene is specifically inactivated in dopaminergic neurons, were used to investigate dopamine D1-receptor-mediated activation of extracellular signal-regulated kinase. In wild-type mice, acute treatment with a dopamine D1-receptor agonist results in activation of extracellular signal-regulated kinase in the nucleus accumbens without activation in the dorsal striatum. In contrast, in dopamine-deficient mice, dopamine D1-receptor-agonist treatment results in activation of extracellular signal-regulated kinase not only in the nucleus accumbens, but also throughout most of the dorsal striatum. Chronic replacement of dopamine by repeated injection of L-DOPA for 36 h reverses this supersensitive extracellular signal-regulated kinase activation. This reversal displays a dorsal to ventral progression such that, by 36 h, extracellular signal-regulated kinase activation is virtually restricted to the nucleus accumbens, as in wild-type mice. The reversal of dopamine D1-receptor activation of extracellular signal-regulated kinase in dopamine-deficient mice following chronic L-DOPA treatment shows that the lack of dopamine, rather than absence of other factors secreted from dopaminergic neurons, is responsible for dopamine supersensitivity.

Relationship between dose of methotrexate, apoptosis, p53/p21 expression and intestinal crypt proliferation in the rat.

Previous studies have shown that apoptosis is induced by cytotoxic chemotherapy and precedes hypoproliferation of intestinal crypt cells. However, the relationship between the degree of intestinal apoptosis and crypt cell hypoproliferation may not be directly related. The purpose of this study was to investigate the relationship between apoptosis and hypoproliferation with increasing doses of chemotherapy. Eleven groups of breast cancer-bearing DA rats were treated with two doses of methotrexate (MTX) i. m. at varying concentrations (0.5, 1.5, 2.5 and 5.0 mg/kg) or saline (control). Animals were killed at 6 or 24 h following treatment. The small and large intestines were examined for apoptosis, villous area (small intestine), crypt length and mitotic count per crypt. Immunohistochemical expression of p53 and p21(waf1/cip1) (p21) were examined quantitatively. Data were analysed using Peritz' F-test. Low dose MTX (0.5 mg/kg) did not change p53 expression at 6 h but induced a 15-fold increase in apoptosis in the crypts of the small intestine. This was associated with only a minor reduction in crypt cell proliferation. Higher doses of MTX increased p53 expression and caused a lower (7-fold) but more prolonged peak of apoptosis that was accompanied by reduced villous area, shortened crypts and a more profound reduction in crypt cell proliferation. Unlike the small intestine, apoptosis in the colon was 10-fold lower, proportional to the dose of MTX and did not induce overt damage. Expression of p21 did not change with any dose at either timepoint. We conclude that apoptosis is not always associated with crypt cell hypoproliferation and that the small intestine can recover after low dose MTX despite a heightened peak of apoptosis of crypt cells.

Survey of local immunisation training in England--the case for setting national standards.

In June 2003 a questionnaire on immunisation training was sent to the 302 primary care trusts (PCTs) in England to ascertain the frequency and content of immunisation training being offered to healthcare professionals. Fifty-four per cent of the 227 trusts (75%) who replied were concerned about their ability to deliver an immunisation programme. Contributing factors included the lack of a designated training lead, shortage of specialist input, available time, and funding. Of PCTs, 33/219 (15%) were not providing immunisation training sessions for practice nurses, 28/219 (13%) for health visitors, and 30/219 (14%) for school nurses; 67/219 (31%) had no sessions organised for general practitioners. Most 138/175 (79%) PCTs would welcome the introduction of some national minimum standards for immunisation training to assist them in setting up and maintaining a programme, and allocating sufficient resources to it.

Jails as important but constrained venues for addressing women's health.

Women in US jails have many social and health risks that merit attention from public health agencies. This article: (1) reviews national and local data on this population for indicators of social disadvantage and of several health risks/conditions (substance abuse, risky sex, and mental illness), (2) describes the impact of federal mandatory sentencing for drug violations and recent developments in states on the numbers of incarcerated women, (3) outlines the similarities and differences between jails and prisons, focusing on characteristics of jails that facilitate and constrain intervention and evaluation activities, and (4) adds lessons learned in six years of experience in county and state jails in Texas.

Effect of breast milk and weaning on epithelial growth of the small intestine in humans.

Breast feeding and weaning are important physiologically significant luminal events that influence the growth of the small intestine in humans. A variety of factors including genetic preprogramming, systemic and local hormones, and permissive factors contribute and modulate intestinal growth. Here, we offer a view that integrates some of these factors, especially those relating to breast feeding and weaning.