Probiotic supplementation and associated infant gut microbiome and health: a cautionary retrospective clinical comparison.

While probiotics are a multi-billion dollar industry, there is little evidence to show that supplementing infants provides any health benefits. We conducted an observational study where 35 of 86 participating mothers self-administered probiotics during breastfeeding, as well as directly to their infants. The primary objective was to determine if probiotic exposure influenced the infants' fecal microbiome while the secondary objective assessed associated changes to the mothers' breast milk immunity and infant health. Analysis of infant fecal microbiome throughout the first 6 months of life revealed that probiotics were associated with higher abundances of Bifidobacterium at week 1 only. Short-chain fatty acid production and predicted metagenomic functions of the microbial communities were not altered. While probiotics did not alter breast milk immune markers, fecal sIgA responses were higher among probiotic supplemented infants. Surprisingly, this was not associated with better health outcomes, as the probiotic cohort had higher incidences of mucosal-associated illnesses as toddlers. This retrospective clinical comparison suggests that probiotic exposure during infancy has limited effects on gut microbial composition yet is associated with increased infection later in life. These correlative findings caution against probiotic supplementation during infancy until rigorous controlled follow-up studies determining their safety and efficacy have occurred.

The goblet cell-derived mediator RELM-ß drives spontaneous colitis in Muc2-deficient mice by promoting commensal microbial dysbiosis.

Intestinal goblet cells are potentially key players in controlling susceptibility to ulcerative colitis (UC). Although impaired mucin (Muc2) production by goblet cells increases microbial stimulation of the colonic mucosa, goblet cells secrete other mediators that may influence or promote UC development. Correspondingly, Muc2-deficient ((-/-)) mice develop spontaneous colitis, concurrent with the dramatic upregulation of the goblet cell mediator, resistin-like molecule-beta (RELM-ß). Testing RELM-ß's role, we generated Muc2(-/-)/Retnlb(-/-) mice, finding that RELM-ß deficiency significantly attenuated colitis development and symptoms compared with Muc2(-/-) mice. RELM-ß expression in Muc2(-/-) mice strongly induced the production/secretion of the antimicrobial lectin RegIIIß, that exerted its microbicidal effect predominantly on Gram-positive Lactobacillus species. Compared with Muc2(-/-)/Retnlb(-/-) mice, this worsened intestinal microbial dysbiosis with a selective loss of colonic Lactobacilli spp. in Muc2(-/-) mice. Orally replenishing Muc2(-/-) mice with murine Lactobacillus spp., but not with a probiotic formulation containing several human Lactobacillus spp. (VSL#3), ameliorated their spontaneous colitis in concert with increased production of short-chain fatty acids. These studies demonstrate that the goblet cell mediator RELM-ß drives colitis in Muc2(-/-) mice by depleting protective commensal microbes. The ability of selective commensal microbial replacement to ameliorate colitis suggests that personalized bacterial therapy may prove beneficial for treatment of UC.

The Impact of a 24-h Ultra-Marathon on Circulatory Endotoxin and Cytokine Profile.

The study aimed to determine circulatory endotoxin concentration, cytokine profile, and gastrointestinal symptoms of ultra-endurance runners (UER, n=17) in response to a 24-h continuous ultra-marathon competition (total distance range: 122-208 km) conducted in temperate ambient conditions (0-20 °C) in mountainous terrain. Body mass and body temperature were measured, and venous blood samples were taken before and immediately after competition. Samples were analysed for gram-negative bacterial endotoxin, C-reactive protein, cytokine profile, and plasma osmolality. Gastrointestinal symptoms were also monitored throughout competition. Mean exercise-induced body mass loss was (mean±SD) 1.7±1.8% in UER. Pre- and post-competition plasma osmolality in UER was 286±11 mOsmol·kg(-1) and 286±9 mOsmol·kg(-1), respectively. Pre- to post-competition increases (p<0.05) were observed for endotoxin (37%), C-reactive protein (2832%), IL-6 (3 436%), IL-1ß (332%), TNF-α (35%), IL-10 (511%), and IL-8 (239%) concentrations in UER, with no change in the control group (CON; n=12) observed (p>0.05). Gastrointestinal symptoms were reported by 75% of UER, with no symptoms reported by CON. IL-10 (r=0.535) and IL-8 (r=0.503) were positively correlated with gastrointestinal symptoms. A 24-h continuous ultra-marathon competition in temperate ambient conditions resulted in a circulatory endotoxaemia and pro-inflammatory cytokinaemia, counteracted by a compensatory anti-inflammatory response.

Maternal exposure to fish oil primes offspring to harbor intestinal pathobionts associated with altered immune cell balance.

Our previous studies revealed that offspring from rat dams fed fish oil (at 8% and 18% energy), developed impaired intestinal barriers sensitizing the colon to exacerbated injury later in life. To discern the mechanism, we hypothesized that in utero exposure to fish oil, rich in n-3 polyunsaturated fatty acid (PUFA), caused abnormal intestinal reparative responses to mucosal injury through differences in intestinal microbiota and the presence of naïve immune cells. To identify such mechanisms, gut microbes and naïve immune cells were compared between rat pups born to dams fed either n-6 PUFA, n-3 PUFA or breeder chow. Maternal exposure to either of the PUFA rich diets altered the development of the intestinal microbiota with an overall reduction in microbial density. Using qPCR, we found that each type of PUFA differentially altered the major gut phyla; fish oil increased Bacteroidetes and safflower oil increased Firmicutes. Both PUFA diets reduced microbes known to dominate the infant gut like Enterobacteriaceae and Bifidobacteria spp. when compared to the chow group. Uniquely, maternal fish oil diets resulted in offspring showing blooms of opportunistic pathogens like Bilophila wadsworthia, Enterococcus faecium and Bacteroides fragilis in their gut microbiota. As well, fish oil groups showed a reduction in colonic CD8+ T cells, CD4+ Foxp3+ T cells and arginase+ M2 macrophages. In conclusion, fish oil supplementation in pharmacological excess, at 18% by energy as shown in this study, provides an example where excess dosing in utero can prime offspring to harbor intestinal pathobionts and alter immune cell homeostasis.

The impact of a 24-h ultra-marathon on salivary antimicrobial protein responses.

Depressed oral respiratory mucosal immunity and increased incidence of upper respiratory symptoms are commonly reported after bouts of prolonged exercise. The current study observed the impact of a 24-h continuous overnight ultra-marathon competition (distance range: 122-208 km; ambient temperature range: 0-20 °C) on salivary antimicrobial protein responses and incidence of upper respiratory symptoms. Body mass, unstimulated saliva and venous blood samples were taken from ultra-endurance runners (n=25) and controls (n=17), before and immediately after competition. Upper respiratory symptoms were assessed during and until 4-weeks after event completion. Samples were analyzed for salivary IgA, lysozyme, α-amylase and cortisol in addition to plasma osmolality. Decreased saliva flow rate (p<0.001), salivary IgA (p<0.001) and lysozyme (p=0.015) secretion rates, and increased salivary α-amylase secretion rate (p<0.001) and cortisol responses (p<0.001) were observed post-competition in runners, with no changes being observed in controls. No incidences of upper respiratory symptoms were reported by participants. A 24-h continuous overnight ultra-marathon resulted in the depression of some salivary antimicrobial protein responses, but no incidences of upper respiratory symptoms were evident during or following competition. Salivary antimicrobial protein synergism, effective management of non-infectious episodes, maintaining euhydration, and (or) favourable environmental influences could have accounted for the low prevalence of upper respiratory symptoms.

Investigation of occult hip fractures: the use of CT and MRI.

AIM: At present there is no data looking at modern multislice computerised tomography (CT) in the investigation of occult hip fracture. The aim of this study was to retrospectively compare the reports of patients sent for magnetic resonance imaging (MRI) or CT with negative radiographs and a clinical suspicion of a fractured neck of femur. METHODS: All patients presenting to the hospital with a clinical suspicion of a hip fracture but initial negative radiographs over a three-year period were included. Patients were either investigated with an MRI scan or CT scan. The presence of a fracture, the requirement for surgery, and any further requirement for imaging were recorded. RESULTS: Over three years 92 patients were included of which 61 were referred for a CT and 31 for an MRI. Thirty-four patients were found to have a fracture. Of these, MRI picked up a fracture in 36% and CT in 38% of referrals. DISCUSSION: Up to 10% of proximal femur fractures may be missed on initial radiographs. Current guidelines state patients should be offered MRI if hip fracture is suspected despite negative hip radiographs. Our findings show that modern multislice CT may be comparable with MRI for detecting occult fracture.

The effectiveness of discontinuing iron-containing prenatal multivitamins on reducing the severity of nausea and vomiting of pregnancy.

Nausea and vomiting of pregnancy (NVP) is experienced by the majority of pregnant women, and can negatively affect a women's quality of life. It has been suggested in observational studies that iron-containing prenatal multivitamins may increase the severity of NVP. The objective of this study was to determine whether decreasing iron exposure can mitigate NVP symptoms. Data were collected from a prospective cohort at the Motherisk Program in Toronto. Women (n = 97) seeking advice on managing severe NVP were advised to discontinue prenatal multivitamin administration and switch to folic acid, an adult multivitamin or a children's chewable multivitamin. Two-thirds (63 out of 97) (p < 0.001) of those women qualitatively reported an improvement in NVP symptoms after discontinuation of iron-containing prenatal multivitamins. These findings were verified quantitatively using both the pregnancy-unique quantification of emesis and nausea (PUQE) (p < 0.001) and well-being (p < 0.001) scoring systems. This is the first interventional study showing that discontinuation of iron results in improvement of NVP symptoms. Our data suggest that avoiding iron-containing prenatal multivitamins in the first trimester is effective in improving NVP symptoms in the majority of pregnant women suffering from morning sickness.

Adult and paediatric basic life support: an update for the dental team.

The aim of this paper is to review the current Resuscitation Council (UK) basic life support guidelines. The main changes made to the guidelines published in 2000 are that for adult basic life support no initial rescue breaths should be delivered before commencing chest compressions and that the compression to ventilation ratio should be 30:2 irrespective of the number of rescuers. For children over the age of one year, two rescuers should provide life support with a compression to ventilation ratio of 15:2. There is still a need to deliver rescue breaths before starting compressions in the child patient.

The transmissible spongiform encephalopathies (prion diseases): a review for dental surgeons.

The transmissible spongiform encephalopathies (prion diseases) are a fatal group of neurological diseases characterised by the accumulation of an abnormal form of prion protein in the brain. In humans, these disorders occur in sporadic, acquired and familial forms. Outbreaks of bovine spongiform encephalopathy, predominantly in the United Kingdom, and the emergence of a clinically and pathologically distinct human prion disease, variant CJD, has generated much interest in the transmissible spongiform encephalopathies. As the agent is detectable in lymphoid and neural tissue in variant CJD, clinicians should be aware of the possibility of cross infection of the causative agent. This is particularly important because the abnormal prion protein is resistant to routine sterilisation procedures. This article reviews the transmissible spongiform encephalopathies, and summarises guidelines concerning prevention of crossinfection when treating patients with or at risk of developing prion disease.

Time course of the effect of nifedipine therapy and its discontinuation on [Ca2+]i and phagocytosis of polymorphonuclear leukocytes from hemodialysis patients.

The abnormalities in [Ca2+]i and phagocytosis of polymorphonuclear leukocytes (PMNLs) from hemodialysis (HD) patients are significantly improved by their treatment with nifedipine. However, the rapidity with which this agent induces its beneficial effect and whether these derangements re-emerge after cessation of therapy are not known. We studied 5 HD patients before, during and after treatment with nifedipine. Before treatment with this agent, the basal levels of [Ca2+]i of PMNLs were markedly elevated 73 +/- 3.6 nM (normal: 42 +/- 0.09 nM) and their phagocytic ability markedly reduced (73 +/- 7.4 micrograms oil/10(7) PMNLs/min (normal: 153 +/- 3.8 micrograms oil/10(7) PMNLs/min). After 1 month of therapy, [Ca2+]i fell significantly (p < 0.01) to 53 +/- 1.0 nM with further decrement of a value of 40 +/- 0.9 nM by the end of 3 months of treatment. The levels of [Ca2+]i rose significantly (p < 0.01) to 61 +/- 2.1 nM after 1 month of cessation of therapy and were 69 +/- 2.5 nM by the end of 5 months; these values are not different from those observed before therapy. Phagocytosis improved significantly (p < 0.01) after 1 month of nifedipine therapy (107 +/- 3.9 micrograms oil/10(7) PMNLs/min) with no further improvement during the other 2 months of therapy. Only modest decrement in phagocytosis occurred during the first 3 months after cessation of nifedipine administration; marked and significant impairment (p < 0.01) in phagocytosis (80 +/- 2.6 micrograms oil/10(7) PMNLs/min) became evident at the end of the fifth month. The results show that (1) nifedipine treatment of HD patients rapidly reversed the elevation in [Ca2+]i of their PMNLs but discontinuation of the therapy is followed by rapid re-emergence of the elevation in the [Ca2+]i of the PMNLs; (2) nifedipine therapy causes rapid and significant, but only partial, improvement of phagocytosis, by PMNL of HD patients; almost 5 months is needed before a significant deterioration in phagocytosis becomes evident after stopping nifedipine treatment; (3) the elevation in [Ca2+]i of PMNLs of HD patients plays an important role in the pathogenesis of impaired phagocytosis but is only partially responsible for their derangement, and (4) the beneficial effect of nifedipine therapy on phagocytosis makes this drug a useful therapeutic tool to aid HD patients in their fight against infection.

Transmission of HIV-1 infection by oroanal intercourse.

We report the cases of two homosexual men, one of whom is believed to have been infected with HIV-1 during oroanal intercourse with the other, his only current sexual partner. Both patients had sero-conversion illnesses with similar symptoms and signs, and of similar duration. The practise of oroanal intercourse is known to be associated with the transmission of enteric infections and has been implicated in the epidemiology of Kaposi's sarcoma. These well-documented cases indicate that HIV-1 may also be transmitted by this route and supports a cautious approach to recommendations regarding "safer" sex.

Attitudes and experiences of human immunodeficiency virus-positive patients to surgery and surgeons.

The issues regarding screening and identification of patients at risk for human immunodeficiency virus (HIV) infection before surgery continue to be discussed, and there is a need for information regarding attitudes of both surgeons and patients to this issue. A population of HIV-positive patients attending a genitourinary medicine clinic were given an anonymous questionnaire to review their experiences of attending for operation. Of 174 patients who replied, 52 had undergone a total of 65 procedures. In all but three of the operations, the HIV status was made known to the surgeon.

Multiple prostatic abscesses presenting with urethral discharge.

Prostatic abscess has become less common, is now usually related to urinary tract infection, and is a rare cause of urethral discharge. The case is described of a man with prostatic abscesses caused by Staphylococcus aureus possibly related to recent skin abrasions. Transrectal ultrasound was used to make the diagnosis and to facilitate repeated drainage with a successful outcome.

T cell responses to peptides covering the gag p24 region of HIV-1 occur in HIV-1 seronegative individuals.

We demonstrate that peptides (16 amino acids long) covering the sequence of the HIV-1 core protein p24 induce significant proliferation in peripheral blood mononuclear cells (PBMC) of several (greater than 50%) healthy seronegative volunteers as well as seronegative homosexual men. The nature of this response was characterized and compared with those of HIV-infected patients. Several peptides induced responses; however, the most frequent responses in both seropositive and seronegative individuals were noted to the following peptides: 1 and 2 (aa 133-157); 6 and 7 (aa 183-207); 15 (aa 273-287); and 17 and 18 (aa 293-317). The response pattern was related to the disease stage of the patients; seronegative individuals as well as asymptomatic seropositive individuals (CDC II/III) responded to low concentrations of several peptides, but symptomatic patients (CDC IV) only responded to high concentrations of a few peptides. Cell separation studies of PBMC from healthy volunteers showed that the responding cells were CD4+ and expressed the CD45RO differentiation antigen. Furthermore, cord-blood mononuclear cells with less than 5% of CD45RO T cells did not proliferative to any of the peptides. Finally, CD4+ T cell lines specific for both peptides and p24 protein were successfully established from the PBMC of seronegative individuals confirming the data obtained with freshly isolated cells. These studies therefore suggest that the CD4+ cell response to p24 is not strictly disease related, instead, the response may be due to priming of the host with cross-reactive antigens.

Alcohol consumption--a risk factor for hemorrhagic and non-hemorrhagic stroke.

PURPOSE: The risks of alcohol consumption and its association with stroke were studied in 621 patients with stroke and 573 control subjects using case-control methods. PATIENTS AND METHODS: Patients with stroke were subdivided into 193 with subarachnoid hemorrhage, 91 with intracerebral hemorrhage, and 337 with cerebral infarction. Data on recent alcohol consumption were obtained by questionnaire in patients with stroke and compared with data from an occupational screening survey in control subjects. RESULTS: Relative risks, adjusted for confounding variables, exhibited J-shaped associations with increasing levels of alcohol consumption classified into four categories--abstainer, 1 to 90 g, 100 to 390 g, and greater than or equal to 400 g weekly). The individual risks were 1, 0.7, 0.5, and 1.3 for subarachnoid hemorrhage; 1.0, 0.6, 0.5., and 2.5 for intracerebral hemorrhage, and 1.0, 0.6, 0.7, and 2.4 for cerebral infarction for men and women combined. CONCLUSIONS: The results suggest that low levels of alcohol consumption may have some protective effect upon the cerebral vasculature, whereas heavy consumption predisposes to both hemorrhagic and non-hemorrhagic stroke.

No effect of zidovudine on hepatitis B virus replication in homosexual men with symptomatic HIV-1 infection.

Zidovudine triphosphate inhibits the hepatitis B virus (HBV) DNA polymerase (DNAp) in vitro. Serial measurements of serum HBV DNAp activity and HBV DNA were made in 14 consecutive male homosexual patients starting zidovudine for symptomatic HIV-1 infection. Median duration of treatment was 15 weeks (range 2-72). In the 13 patients with detectable DNAp/DNA pre-treatment, no significant change in either measure of viral replication was observed during the first 16 weeks of treatment compared with the 13 weeks prior to treatment. The lack of response may be due to the opposing effect of immunosuppression, or to a failure of in vivo activity.