A systematic review of gut microbiota composition in observational studies of major depressive disorder, bipolar disorder and schizophrenia.

The emerging understanding of gut microbiota as 'metabolic machinery' influencing many aspects of physiology has gained substantial attention in the field of psychiatry. This is largely due to the many overlapping pathophysiological mechanisms associated with both the potential functionality of the gut microbiota and the biological mechanisms thought to be underpinning mental disorders. In this systematic review, we synthesised the current literature investigating differences in gut microbiota composition in people with the major psychiatric disorders, major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia (SZ), compared to 'healthy' controls. We also explored gut microbiota composition across disorders in an attempt to elucidate potential commonalities in the microbial signatures associated with these mental disorders. Following the PRISMA guidelines, databases were searched from inception through to December 2021. We identified 44 studies (including a total of 2510 psychiatric cases and 2407 controls) that met inclusion criteria, of which 24 investigated gut microbiota composition in MDD, seven investigated gut microbiota composition in BD, and 15 investigated gut microbiota composition in SZ. Our syntheses provide no strong evidence for a difference in the number or distribution (α-diversity) of bacteria in those with a mental disorder compared to controls. However, studies were relatively consistent in reporting differences in overall community composition (ß-diversity) in people with and without mental disorders. Our syntheses also identified specific bacterial taxa commonly associated with mental disorders, including lower levels of bacterial genera that produce short-chain fatty acids (e.g. butyrate), higher levels of lactic acid-producing bacteria, and higher levels of bacteria associated with glutamate and GABA metabolism. We also observed substantial heterogeneity across studies with regards to methodologies and reporting. Further prospective and experimental research using new tools and robust guidelines hold promise for improving our understanding of the role of the gut microbiota in mental and brain health and the development of interventions based on modification of gut microbiota.

Influence of food and lifestyle on the risk of developing inflammatory bowel disease.

BACKGROUND: The Barwon area in Australia has one of the highest incidence rates of inflammatory bowel disease (IBD) and therefore is an ideal location to study the impact of environmental exposures on the disease's development. AIM: To study these exposures prior to the development of IBD in a population-based cohort. METHOD: One hundred and thirty-two incident cases (81 Crohn disease (CD) and 51 ulcerative colitis (UC)) from an IBD registry and 104 controls replied to the International Organization of Inflammatory Bowel Diseases environmental questionnaire. This included 87 questions about pre-illness exposures that included childhood illnesses, vaccinations, breastfeeding, house amenities, pets and swimming, diet and smoking. RESULTS: The factors associated with CD included smoking (odds ratio (OR): 1.42, confidence interval (CI): 1-2.02, P = 0.029); childhood events, including tonsillectomy (OR: 1.74, CI: 1.15-2.6, P = 0.003) and chicken pox infection (OR: 3.89, CI: 1.61-9.4, P = 0.005) and pre-diagnosis intake of frequent fast food (OR: 2.26, CI: 1.76-4.33, P = 0.003). In UC, the risk factors included smoking (OR: 1.39, CI: 1.1-1.92, P = 0.026) and pre-diagnosis intake of frequent fast food (OR: 2.91, CI: 1.54-5.58, P < 0.001), and high caffeine intake was protective (OR: 0.51, 95% CI: 0.3-0.87, P = 0.002). Other protective exposures for UC included high fruit intake (OR: 0.59, CI: 0.4-0.88, P = 0.003) and having pets as a child (OR: 0.36, CI: 0.2-0.79, P = 0.001). CONCLUSION: This first Australian population-based study of environmental risk factors confirms that smoking, childhood immunological events and dietary factors play a role in IBD development; while high caffeine intake and pet ownership offer a protective effect.

Intravenous cyclophosphamide as a therapeutic option for severe refractory gastric antral vascular ectasia in systemic sclerosis.

Gastric antral vascular ectasia (GAVE) is a rare but important cause of upper gastrointestinal bleeding. It is commonly associated with autoimmune conditions such as systemic sclerosis, and standard treatment involves both supportive measures, as well as endoscopic interventional therapies. While the current therapies are effective for most patients, a few patients develop severe and refractory bleeding. Herein we report two cases of refractory GAVE in patients with diffuse scleroderma, which improved significantly after the administration of intravenous cyclophosphamide. One of these cases is, to our knowledge, the first reported case of cyclophosphamide being used specifically for the treatment of refractory GAVE.

Clinical selection criteria can predict futile intervention in patients referred for percutaneous endoscopic gastrostomy insertion.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG) placement is performed in a patient group with high mortality in the short and medium term. For a significant proportion of patients, the procedure provides no increase in survival. There are no standardised assessment tools available to determine the clinical appropriateness of PEG placement, nor any to predict clinical outcome. AIM: The study aims to determine whether clinical assessment, by a trained dietitian, of the appropriateness of PEG placement is predictive of mortality in the short and medium terms. METHODS: A prospective audit was undertaken of all requests for PEG placement at a single large, publicly funded Australian tertiary hospital. The clinical appropriateness of each request was assessed by a trained dietitian, and data on age, sex, reason for referral, comorbidities and satisfaction of assessment criteria were collected, and patient outcome and survival were compared for all patients according to whether a PEG was inserted or not. Main outcome measures were mortality at 30 and 150 days after referral. RESULTS: During the period 2005-2008, 198 patients were referred for PEG; 94 were assessed as appropriate referrals, 104 as inappropriate. Eighty-four patients who underwent gastrostomy, after being assessed as appropriate, had significantly reduced mortality at 30 days (96.4% vs 74.6%, P < 0.0001) and 150 days (82.1% vs 57.9%, P = 0.0001) compared with all other patients. Patients who received PEG despite contrary advice had no significant survival advantage, at 30 days or 150 days, over patients who did not receive PEG. CONCLUSION: The application of selection criteria by trained assessors improves patient selection for PEG insertion and predicts mortality at early and later time points, by identifying patients unlikely to benefit from PEG. The group of patients who received a gastrostomy despite an adverse assessment had no mortality benefit - in these patients, the procedure may have been futile.

Venous thromboembolism and underutilisation of anticoagulant thromboprophylaxis in hospitalised patients with inflammatory bowel disease.

BACKGROUND: Venous thromboembolism (VTE) is a well-recognised extra-intestinal manifestation of inflammatory bowel disease (IBD). Despite the widespread support for anticoagulant prophylaxis in hospitalised IBD patients, the utilisation and efficacy in clinical practice are unknown. AIMS: The aim of this study was to assess the prevalence and clinical features of VTE among hospitalised IBD patients and ascertain whether appropriate thromboprophylaxis had been administered. METHODS: All patients with a discharge diagnosis of Crohn disease or ulcerative colitis and VTE were retrospectively identified using International Classification of Diseases, tenth revision codes from medical records at our institution from July 1998 to December 2009. Medical records were then reviewed for clinical history and utilisation of thromboprophylaxis. Statistical analysis was performed by Mann-Whitney test and either χ(2) tests or Fisher's exact tests. RESULTS: Twenty-nine of 3758 (0.8%) IBD admissions suffered VTE, 13 preadmission and 16 during admission. Of these 29 admissions (in 25 patients), 24% required intensive care unit and 10% died. Of the 16 venous thrombotic events that occurred during an admission, eight (50%) did not receive anticoagulant thromboprophylaxis and eight (50%) occurred despite thromboprophylaxis. Most thromboembolism despite prophylaxis occurred post-intestinal resection (n = 5, 63%). CONCLUSION: Thromboprophylaxis is underutilised in half of IBD patients suffering VTE. Prescription of thromboprophylaxis for all hospitalised IBD patients, including dual pharmacological and mechanical prophylaxis in postoperative patients, may lead to a reduction in this preventable complication of IBD.

Staphylococcus aureus bacteraemia: evaluation of the role of transoesophageal echocardiography in identifying clinically unsuspected endocarditis.

Staphylococcus aureus bacteraemia (SAB) is an important cause of community and nosocomial sepsis, with a significant mortality rate. Infective endocarditis (IE) is a serious complication, occurring in up to 25 % of cases. Transoesophageal echocardiography (TOE) significantly improves the sensitivity of diagnosis. We compared the sensitivity and specificity of clinical evaluation alone in diagnosing IE. We evaluated all adult patients with SAB at our centre from 1998 to 2006 in order to determine what proportion of clinically unsuspected cases were diagnosed with IE on TOE. IE was defined according to modified Duke criteria. The median age of the patients was 68 years, 77 % were male and the majority of cases did not have a known pre-existing condition. Twenty-one percent were methicillin-resistant Staphylococcus aureus (MRSA). Intravascular device was the most common cause of bacteraemia. TOE was performed in 144 (100 %) of the cases. IE was suspected clinically in 15 % of cases, and the overall prevalence of possible or definite IE on TOE-inclusive Duke criteria was 29 % (n = 41). Following TOE, 22 (15 %) cases were reclassified as either possible or definite endocarditis. TOE detected a vegetation in 37 (90 %) of the 41 cases of IE. Nineteen (46 %) were not suspected clinically by Duke criteria. Sensitivity improved in the presence of pre-existing valve lesion or community acquisition. The overall in-hospital mortality was 10 %. There is a high incidence of endocarditis in SAB and a large percentage of cases are not evident on clinical grounds. TOE evaluation is indicated for all medically suitable adult patients with SAB in order to improve the detection of endocarditis.

Prediction of delirium using data mining: A systematic review.

Delirium remains a significant cause of morbidity, mortality and economic burden to society. "Big data" refers to data of significantly large volume, obtained from a variety of resources, which is created and processed at high velocity. We conducted a systematic review and meta-analysis exploring whether big data could predict the incidence of delirium of patients in the inpatient setting. Medline, Embase, the Cochrane Library, Web of Science, CINAHL, clinicaltrials.gov, who.int and IEEE Xplore were searched using MeSH terms "big data", "data mining", "delirium" and "confusion" up to 30th September 2019. We included both randomised and observational studies. The primary outcome of interest was development of delirium and the secondary outcomes of interest were type of statistical methods used, variables included in the mining algorithms and clinically important outcomes such as mortality and length of hospital stay. The quality of studies was graded using the CHARMs checklist. Six retrospective single centre observational studies were included (n = 178,091), of which 17, 574 participants developed delirium. Studies were of generally of low to moderate quality. The most commonly studied method was random forest, followed by support vector machine and artificial neural networks. The model with best performance for delirium prediction was random forest, with area under receiver operating curve (AUROC) ranging from 0.78 to 0.91. Sensitivity ranged from 0.59 to 0.81 and specificity ranged from 0.73 to 0.92. Our systematic review suggests that machine-learning techniques can be utilised to predict delirium.

Stimulation of primary in vitro IgE antibody responses in culture of human peripheral mononuclear cells.

Experiments are presented herein that demonstrate the capacity to stimulate human peripheral mononuclear cells to synthesize and secrete significant quantities of IgE molecules in vitro by exposure to appropriate concentrations of 2,4-dinitrophenyl (DNP)-protein conjugates, pokeweed mitogen (PWM), or a combination of DNP-proteins and PWM. Cultures stimulated in this fashion synthesize increased quantities of both total IgE and DNP-specific IgE antibody molecules. This in vitro human IgE antibody system should provide a useful tool for further exploration of regulatory control of IgE responses in both normal humans and those manifesting various forms of IgE-mediated allergic disorders.

Effects of cochlear ablation on amino acid concentrations in the chinchilla posteroventral cochlear nucleus, as compared to rat.

Using a microchemical approach, we measured changes of amino acid concentrations in the chinchilla caudal posteroventral cochlear nucleus (PVCN) after cochlear ablation to determine to what extent slow decreases of glutamate and aspartate concentrations after carboplatin treatment resulted from slower effects of cochlear damage in chinchillas than in rats and guinea pigs, as opposed to effects of carboplatin treatment being slower than those of cochlear ablation. Our results indicate that both factors are involved: decreases of glutamate and aspartate concentrations after cochlear ablation are much slower in chinchillas than in rats and guinea pigs, but they are much faster than the decreases after carboplatin treatment. Further, aspartate and glutamate concentrations in the chinchilla caudal PVCN decreased by larger amounts after cochlear ablation than in rats or guinea pigs, and there was a transient increase of aspartate concentration at short survival times. Detailed mapping of amino acid concentrations in the PVCN of a chinchilla with 1 month survival after cochlear ablation and a rat with 7 days' survival indicated that the reductions of glutamate and aspartate occurred throughout the PVCN but were somewhat larger in ventral and caudal parts in chinchilla. Any decreases in the adjacent granular region were very small. There were also sustained bilateral decreases in concentrations of other amino acids, notably GABA and glycine, in the caudal PVCN of cochlea-ablated chinchillas but not rats. The effects of cochlear ablation on the concentrations of most of these other amino acids in chinchilla caudal PVCN differed from those of carboplatin treatment. Thus, although a major effect of auditory nerve damage on the cochlear nucleus-decreases of glutamate and aspartate concentrations-occurs across species and types of lesions, the details of timing and magnitude and the effects on other amino acids can vary greatly.

Immunoglobulin E-rheumatoid factor in the serum of patients with rheumatoid arthritis, asthma, and other diseases.

A solid-phase radioimmunoassay was developed to detect immunoglobulin (Ig)E antibodies that bound to human IgG. IgE-rheumatoid factor activity was found in the serum of 18 of 20 patients with seropositive rheumatoid arthritis, 1 of 4 patients with seronegative rheumatoid arthritis, 3 of 32 patients with seronegative rheumatoid arthritis, 3 of 32 patients with asthma, and in 1 patient with hypocomplementemic vasculitis and iodide sensitivity. Immunopathologic implications of IgE-rheumatoid factor are discussed.

A rapid screening assay for detection of IgE-binding factors in humans.

During the last few years studies in rats and mice have demonstrated IgE-binding factors, some of which have IgE-selective regulatory activities. This prompted us to develop a rapid, sensitive screening assay for measuring IgE-binding factors in humans. The principle of the assay is to measure the degree of inhibition of binding between anti-human IgE antibodies and human IgE. Thus, 200 pg IgE plus testing samples were added to each well precoated with anti-human IgE antiserum. After an overnight incubation, the wells were washed and radiolabeled anti-IgE antibodies were added to the wells. Under the optimum conditions, the assay can detect 10(-11)M anti-human IgE antibodies. With this assay, we have been able to detect IgE-binding factors in the supernatants of 2 human B cell lines which bear Fc receptors for IgE (FcR epsilon) on their surface membranes (e.g., WIL-2 and RPMI 8866), but not in the supernatants of DAUDI cells (a human cell line without FcR epsilon). Furthermore, the IgE-binding factors of WIL-2 cells were specifically adsorbed to, and eluted from, IgE-coupled Sepharose, but not BSA-Sepharose. These findings prove that the inhibition factors are indeed human IgE-binding factors, and that the assay described herein is a specific and sensitive screening assay for detecting human IgE-binding factors.

Treatment of an influenza A outbreak in a teaching nursing home. Effectiveness of a protocol for prevention and control.

The safety and efficacy of current ACIP guidelines for the prevention and control of influenza in nursing home populations are uncertain. An outbreak of influenza A/Sichuan (H3N2) in a teaching nursing home during 1988 gave us the opportunity to evaluate the effectiveness of an influenza vaccination and amantadine prophylaxis protocol. Over 13 days, 12 of 60 residents developed influenza. Prior influenza vaccination had been given to 94% of the residents. Protection from infection occurred in those tested who had antibody levels greater than or equal to 1:16 to the A/Leningrad (H3N2) antigen contained in the standard 1987-88 trivalent vaccine. However, five of 17 vaccinated residents who were tested had antibody levels less than or equal to 1:16 at the start of the outbreak. Amantadine (less than or equal to 100 mg/day) was given to all but one resident starting on the third day of the outbreak, and to employees starting on the sixth day of the outbreaks. Seven residents developed illness after the start of amantadine, although amantadine appeared to ameliorate their symptoms. Although amantadine was generally well tolerated by residents, employees receiving amantadine identified a high incidence of side effects and only 44% of employees took at least 70% of the prescribed amantadine. In our opinion, early detection and protocol-directed intervention probably abated a more severe influenza outbreak. Therefore we support existing recommendations that formal nursing home policies be established to ensure that residents and employees receive annual influenza vaccine and that chemoprophylaxis be used when outbreaks of influenza A are suspected.

Sporicidal activity of chemical and physical tissue fixation methods.

AIMS: The effects of alcohol based fixation and microwave stimulated alcohol fixation were investigated on spores of Bacillus stearothermophilus and Bacillus subtilis (var. niger). METHODS: Spores were exposed to 10% formalin, or different concentrations of various alcohol containing fixatives (Kryofix/Spuitfix). Adequate controls were also set up in conjunction with the test solutions. The spores were immersed with and without adjunctive microwave stimulation in the various solutions tested. Possible surviving spores were recovered in revival broth and after incubation, and Gram staining viable counts were performed. RESULTS: Alcohol based fixatives did not have a sporicidal effect on B stearothermophilus or B subtilis (var. niger) spores, and microwave stimulated alcohol fixation at 450 W and up to 75 degrees C did not have a sporicidal effect. CONCLUSIONS: When alcohol based fixatives are used for fixation, precautions should be taken with the material thus treated, as it may contain viable spores or other pathogens, which are destroyed after 24 hours of formalin treatment. Of the physicochemical methods tested involving microwaving, none was successful in eliminating viable spores from the test material.