Inflammation-associated nitrate facilitates ectopic colonization of oral bacterium Veillonella parvula in the intestine.

Colonization of the intestine by oral microbes has been linked to multiple diseases such as inflammatory bowel disease and colon cancer, yet mechanisms allowing expansion in this niche remain largely unknown. Veillonella parvula, an asaccharolytic, anaerobic, oral microbe that derives energy from organic acids, increases in abundance in the intestine of patients with inflammatory bowel disease. Here we show that nitrate, a signature metabolite of inflammation, allows V. parvula to transition from fermentation to anaerobic respiration. Nitrate respiration, through the narGHJI operon, boosted Veillonella growth on organic acids and also modulated its metabolic repertoire, allowing it to use amino acids and peptides as carbon sources. This metabolic shift was accompanied by changes in carbon metabolism and ATP production pathways. Nitrate respiration was fundamental for ectopic colonization in a mouse model of colitis, because a V. parvula narG deletion mutant colonized significantly less than a wild-type strain during inflammation. These results suggest that V. parvula harness conditions present during inflammation to colonize in the intestine.

Comparative analysis of paediatric and adult surgically drained dental infections at a university teaching hospital.

In the United Kingdom (UK) the estimated prevalence of dental infection involving the supporting bone is 2%, and from 2014-2015 there were 2281 admissions in England alone due to dental abscess. We undertook an analysis of 184 dental abscesses that required surgical drainage, as there is surprisingly little in the literature on the subject. This was a retrospective study of 184 consecutive patients with dental abscesses who were admitted between January 2016 and September 2019. On admission, all patients had orthopantomograms (OPG) and baseline blood tests. Surgical drainage was performed under a general or local anaesthetic and a pus swab sent for culture and sensitivity. The submandibular space was the most commonly involved site and paediatric patients most often presented with buccal space abscesses. A lower molar tooth was the cause in 132 patients. White blood cells (WBC) and C-reactive protein (CRP) were both raised in 63.6% (n=117), but were normal in 4.9% (n=9). The remaining patients had either raised WBC (2.7%) or CRP (28.8%). Streptococcus milleri was the most common organism isolated in 66.6% (n=42). There was no association between CRP or WBC values and duration of hospital stay. Paediatric patients had a shorter duration of admission (1.96 days vs 2.81 days) and significantly lower CRP values (120.9 vs 45.7; p=0.001). The submandibular space was the commonest site involved and mandibular molars the most frequent source of infection. An elevated CRP value appeared to be a more sensitive indicator of infection in this study population. Adult and paediatric patients present in a different manner.

Natural killer NKG2A and NKG2D in patients with colorectal cancer.

BACKGROUND: Natural-killer group 2 (NKG2), a characteristic receptor of natural killer (NK) cell family, assumes a vital role in modulating NK cytotoxic function. We aimed to detect mRNA expression of both NKG2A and NKG2D in serum NK cells obtained from colorectal cancer (CRC) patients. METHODS: We enrolled 36 patients with newly diagnosed CRC, as well as 15 group matched healthy individuals. The patients were further classified into: 23 non-metastatic CRC (group 1) and 13 metastatic CRC (group 2). We detected the expression of NKG2A and NKG2D serum levels for all participants utilizing real-time polymerase chain reaction (RT-PCR). RESULTS: NKG2D and NKG2A mRNA levels in peripheral blood mononuclear cells (PBMCs) were significantly elevated in patients with CRC compared to controls (P<0.01). NKG2D or NKG2A showed sensitivity (77.8, 83.33%) and specificity (73.33, 100%) respectively using receiver-operating characteristic (ROC) curve analysis for discrimination between patients and controls, whereas group 1 and group 2 showed no statistical significant difference in NKG2D and NKG2A levels (P>0.05). CONCLUSIONS: Our work is one of the first research that could detect an increase in NKG2D in CRC. In spite of their defensive role in tumor immune surveillance, NKG2D and NKG2A and their ligands could have misused as tumor survival tool, empowering immune avoidance and suppression.

Staff and ambient radiation dose resulting from therapeutic nuclear medicine procedures.

With associated cure rates in excess of 90%, targeted 131I radioactive iodine therapy has clearly improved thyroid cancer survival. Thus said, potential radiation risks to staff represent a particular concern, current study seeking to determine the radiation exposure of staff from 131I patients during hospitalization, also estimating accumulated dose and related risk to staff during preparation of the radioactive iodine. In present study made over the three-month period 1st February to 1st May 2017, a total of 69 patient treatments were investigated (comprising a cohort of 46 females and 23 males), this being a patient treatment load typically reflective of the workload at the particular centre for such treatments. The patients were administered sodium iodide 131I, retained in capsules containing activities ranging from 370 to 5550 MBq at the time of calibration, radioiodine activity depends on many factors such as gender, clinical indication, body mass index and age. The staff radiation dose arising from each patient treatment was measured on three consecutive days subsequent to capsule administration. In units of µSv, the mean and dose-rates range at distances from the patients of 5 cm, 1 m and 2 m were 209 ±â€¯73 (165-294), 6.8 ±â€¯2 (5.3-9.5) and 0.9 ±â€¯0.3 (0.7-1.2). The annual dose (also measured in units of µSv), based on annual records of doses, for medical physicists, technologists and nurses were 604, 680 and 1000 µSv respectively. In regard to current practice and workload, staff exposures were all found to be below the annual dose limit for radiation workers.

Caffeine intake decreases oxidative stress and inflammatory biomarkers in experimental liver diseases induced by thioacetamide: Biochemical and histological study.

Liver disease remains a significant global health problem. Increased caffeine consumption has been associated with a lower prevalence of chronic liver disease. This study aimed to investigate the modifying effects of caffeine on liver injury induced by thioacetamide (TAA) administration in male rats and the possible underlying mechanisms. Forty adult male rats were equally classified into four groups: control group, received only tap water; caffeine-treated group, received caffeine (37.5 mg/kg per day); TAA-treated group, received intraperitoneal (i.p.) TAA (200 mg/kg b.w.) twice a week; and caffeine + TAA-treated group, received combined TAA and caffeine in the same previous doses. After eight weeks of treatment, blood samples were collected for biochemical analysis and liver specimens were prepared for histological and immunohistochemical studies and for assessment of oxidative stress. TAA induced liver toxicity with elevated liver enzymes and histological alterations, fatty changes, apoptosis, and fibrosis evidenced by increased immunohistochemical reaction to matrix metalloproteinase-9 (MMP-9) and collagen type IV in hepatocytes. Also, the levels of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in serum were significantly elevated. Co-treatment with caffeine and TAA restored normal liver structure and function. Caffeine provided an anti-fibrogenic, anti-inflammatory, and antioxidant effect that was associated with recovery of hepatic histological and functional alterations from TAA-induced hepatotoxicity.

Differential effects of eugenol against hepatic inflammation and overall damage induced by ischemia/re-perfusion injury.

Liver injuries, liver tumor resection, and liver transplantation are known to be responsible for ischemia/reperfusion (I/R) injury that, in turn, gives rise to liver damage. This study was undertaken to investigate the possible protective effect of eugenol against the damage induced by I/R in rat livers as well as to explore possible mechanisms of action. Male rats were divided into four groups: sham-operated, I/R only, and two groups that received 10 or 100 mg eugenol/kg/day (Eug10 and Eug100, respectively) for 15 days by gavage and were then subjected to I/R, i.e. an ischemia induced for 45 min followed by re-perfusion for 6 h. The rats were euthanized and liver tissues and blood collected for examination. The results showed that I/R induced massive hepatic structural and functional damage. Eug10-treated rats had improvement in both liver function and structure, and inhibition of I/R-induced increases in serum myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, as well as hepatic nuclear factor-κB (NF-κB) p65 and caspase-3 expression. Eug10 treatment also inhibited the degree of loss in reduced glutathione (GSH) and of rise in malondialdehyde (MDA) levels in liver tissues induced by I/R. In contrast, augmentation of liver damage induced by I/R was noted in Eug100-treated rats, with these hosts displaying significant increases in oxidant, inflammatory, and apoptotic markers relative to levels seen in I/R-only rats. The results of the present study provide the first evidence that a low dose of eugenol may protect the liver against I/R injury in part by decreasing levels of lipid peroxidation, down-regulating inflammatory mediators, and inhibiting apoptosis, and that a larger dose amplifies the liver injury via oxidant and inflammatory effects.

Addition of an anti-rotation screw to the dynamic hip screw for femoral neck fractures.

The authors investigated the use of an anti-rotation screw with the dynamic hip screw (DHS) during internal fixation of Garden I and II femoral neck fractures. Sixty-five patients with Garden I and II femoral neck fractures (mean age, 70 years) were treated with internal fixation at the authors' institution. In 31 patients, a 2-hole DHS was used alone (group 1), and in 34 patients, the DHS was combined with an anti-rotation screw placed in the cranial part of femoral head and neck (group 2). Patients' preinjury function and mental level were assessed using the Barthel index and the Abbreviated Mental test, respectively. The outcome measures included cost implications, operative time, and intraoperative radiation dose. The modified Harris Hip Score and a radiological assessment were performed at a mean of 11 months (range, 8-24 months) postoperatively. The use of the anti-rotation screw was associated with a longer operative time (mean, 44.54 minutes in group 1 vs 51.52 minutes in group 2; P<.0001) and more fluoroscopy screening (mean dose area product, 28.39 cGy/cm(2) in group 1 vs 44.33 cGy/cm(2) in group 2; P=.03). The additional cost of using an anti-rotation screw was £106 ($170) per case. No difference existed between the 2 groups with regard to radiological union, onset of avascular necrosis, and rate of revision surgeries. An anti-rotation screw, used with the dynamic hip screw, involves extra costs, prolongs operative time, and requires more intraoperative fluoroscopy screening but offers no advantages with regard to fracture union.

The relationship between genetic variability and the susceptibility of Biomphalaria alexandrina snails to Schistosoma mansoni infection

In the present study, Biomphalaria snails collected from five Egyptian governorates (Giza, Fayoum, Kafr El-Sheikh, Ismailia and Damietta), as well as reference control Biomphalaria alexandrina snails from the Schistosome Biological Supply Center (SBSC) (Theodor Bilharz Research Institute, Egypt), were subjected to species-specific polymerase chain reaction (PCR) assays to identify the collected species. All of the collected snails were found to be B. alexandrina and there was no evidence of the presence of Biomphalaria glabrata. Randomly amplified polymorphic DNA (RAPD)-PCR assays showed different fingerprints with varying numbers of bands for the first generation (F1) of B. alexandrina snail populations (SBSC, Giza, Fayoum, Kafr El-Sheikh, Ismailia and Damietta). The primer OPA-1 produced the highest level of polymorphism and amplified the greatest number of specific bands. The estimated similarity coefficients among the B. alexandrina populations based on the RAPD-PCR profiles ranged from 0.56 (between SBSC and Ismailia snails) to 0.72 (between Ismailia and Kafr El-Sheikh snails). Experimental infection of the F1 of progeny from the collected snails with Schistosoma mansoni (SBSC strain) showed variable susceptibility rates ranging from 15% in the Fayoum snail group to 50.3% in SBSC snails. A negative correlation was observed between the infection rates in the different snail groups and the distances separating their corresponding governorates from the parasite source. The infection rates of the snail groups and their similarity coefficients with SBSC B. alexandrina snails were positively correlated. The variations in the rates of infection of different B. alexandrina groups with S. mansoni, as well as the differences in the similarity coefficients among these snails, are dependent not only on the geographical distribution of the snails and the parasite, but also on the genetic variability of the snails. Introduction of this variability into endemic areas may reduce the ability of the parasite to infect local hosts and consequently reduce schistosomiasis epidemiology.

The Caenorhabditis elegans Eph receptor activates NCK and N-WASP, and inhibits Ena/VASP to regulate growth cone dynamics during axon guidance.

The Eph receptor tyrosine kinases (RTKs) are regulators of cell migration and axon guidance. However, our understanding of the molecular mechanisms by which Eph RTKs regulate these processes is still incomplete. To understand how Eph receptors regulate axon guidance in Caenorhabditis elegans, we screened for suppressors of axon guidance defects caused by a hyperactive VAB-1/Eph RTK. We identified NCK-1 and WSP-1/N-WASP as downstream effectors of VAB-1. Furthermore, VAB-1, NCK-1, and WSP-1 can form a complex in vitro. We also report that NCK-1 can physically bind UNC-34/Enabled (Ena), and suggest that VAB-1 inhibits the NCK-1/UNC-34 complex and negatively regulates UNC-34. Our results provide a model of the molecular events that allow the VAB-1 RTK to regulate actin dynamics for axon guidance. We suggest that VAB-1/Eph RTK can stop axonal outgrowth by inhibiting filopodia formation at the growth cone by activating Arp2/3 through a VAB-1/NCK-1/WSP-1 complex and by inhibiting UNC-34/Ena activity.

Live birth rate in fresh and frozen embryo transfer cycles in women with endometriosis.

OBJECTIVES: To test the hypothesise that the treatment protocol used for preparation of the endometrium for frozen embryo transfer (ET) has a beneficial effect on the disorganised endometrium in women with endometriosis and leads to a higher pregnancy rate. STUDY DESIGN: We performed a retrospective, database-searched cohort study. Relevant information was collected from the electronic records of women who underwent IVF/ICSI between 1/1/2000 and 31/12/2008 in our unit. Endometriosis patients formed the study group. The rest of the women formed the control group. The two groups were subdivided, depending on whether they had fresh or frozen ET. The main outcome was live birth rate (LBR). Secondary outcomes were clinical pregnancy rate (CPR) and miscarriage rate (MR). Comparisons were performed by Chi-square and Mann-Whitney tests (SPSS 16.0). RESULTS: A total of 3763 fresh and 3523 frozen ET IVF cycles were included in our study, of which 415 (5.7%) were due to endometriosis related subfertility. In the non-endometriosis group, fresh ET had significantly higher LBR, CBR and MR than frozen ET. In women with endometriosis, down-regulated frozen ET cycles had a markedly high LBR and CPR (16.9%, 18.2%), comparable to the LBR and CPR of fresh ET cycles in the same group (19.5%, 20.2%). No significant differences were found in the LBR and CPR in fresh ET cycles between the study and the control group. In frozen ET, however, the CPR was significantly higher in the endometriosis group (18.2% versus 12.7%, P=0.048). CONCLUSION: Unlike the general IVF population, in women with endometriosis undergoing IVF, the preparation of the endometrium for frozen ET with GnRH agonists compared to fresh cycles is associated with higher LBR (16.9% versus 11.9%) and a significantly higher CPR (18.2% versus 12.7%, P=0.048). These results suggest that, in cases of endometriosis, the combined effect of GnRHa on the endometrium and the low level of ovarian steroids may simultaneously offer a better endometrial environment for implantation which may lead to better outcomes.

The C. elegans nck-1 gene encodes two isoforms and is required for neuronal guidance.

The NCK adaptor proteins are composed entirely of SH3 and SH2 domains and serve as protein interaction bridges for several receptors during signal transduction events. Here we report the molecular and genetic analysis of the Caenorhabditis elegans nck-1 gene. C. elegans nck-1 encodes two isoforms: NCK-1A and a shorter isoform that lacks the first SH3 domain, NCK-1B. C. elegans nck-1 mutants exhibit defects in axon guidance and neuronal cell position, as well as defects in the excretory canal cell, gonad, and male mating. NCK-1 is broadly expressed in neurons and epithelial cells with NCK-1B being the most abundant isoform. NCK-1A and NCK-1B share a similar expression pattern in parts of the nervous system, but also have independent expression patterns in other tissues. Interestingly, NCK-1B is localized to the nuclei of many cells. Genetic rescue experiments show that NCK-1 functions cell autonomously and, in general, either NCK-1A or NCK-1B is sufficient to function in axon guidance. However, there appears to be specific roles for each isoform, for example NCK-1B is required for HSN cell migration while NCK-1A is required for efficient male mating. Genetic epistasis experiments show that NCK-1 functions redundantly with the LAR Receptor Tyrosine Phosphatase, PTP-3, and the Netrin receptor UNC-40.