Integration of a battery of biomarkers to evaluate the health status of field-collected frogs of Leptodactylus luctator living in ecosystems with different anthropogenic disturbances.

Amphibians are the most threatened group of vertebrates because they have certain biological and ecological characteristics that make them sensitive to environmental changes. The aim of this study was to evaluate the health status of field-collected adult frogs of Leptodactylus luctator (Amphibia, Anura) living in sites with different anthropogenic disturbances (florihorticulture, petrochemical industry and sewage discharges) and a reference site without any detectable influence of such activities. To this end, a battery of 21 biomarkers (hematological, biochemical and individual biomarkers) was studied using a multivariate approach that allows us to evaluate the relationship between them and provide information on their usefulness. The frogs at the florihorticulture, petrochemical and sewage discharges sites exhibited several biomarkers far from homeostasis. In addition, we identified 11 of 21 biomarkers that were useful indicators of the health status of the frogs and allowed discrimination between study sites in the following order: lymphocytes (98 %), neutrophils (45 %), hemoglobin (42 %), monocytes (41 %), fat body index (35 %), eosinophils (35 %), hepatosomatic index (33 %), mean corpuscular hemoglobin (32 %), thrombocytes (27 %), catalase in liver (26 %), and GST in liver (26 %). The results suggest that hematological biomarkers contribute the most to site separation, whereas biochemical biomarkers contribute the least. The integral interpretation of the results also allowed us to diagnose the different health status of L. luctator: The frogs from the petrochemical industry were the most negatively affected, followed by the frogs from the sewages discharges and finally the frogs from the florihorticulture and reference sites. This is the first field study with anurans in which so many biomarkers were examined.

Impact of pre-operative MRI on surgical management of screening digital breast tomosynthesis-detected invasive lobular carcinoma.

PURPOSE: The purpose of this study is to determine the impact of pre-operative MRI on surgical management of screening digital breast tomosynthesis (DBT)-detected invasive lobular carcinoma (ILC). METHODS: A retrospective medical record analysis was conducted of women with screening DBT-detected ILC and subsequent surgery from 2017-2021. Clinical, imaging, and pathological features were compared between women who did and did not undergo MRI, and between women with and without additional disease detected on MRI, using the Pearson's chi-squared test and Wilcoxon signed-rank test. Concordance between imaging and surgical pathology sizes was also evaluated. RESULTS: Of 125 women (mean age 67 years, range 44-90) with screening-detected ILC, MRI was obtained in 62 women (49.6%) with a mean age of 63 years (range 45-80). Compared to women without MRI, women who had MRI examinations were younger, more likely to have dense breast tissue, and more likely to undergo mastectomy initially rather than lumpectomy (p < 0.001-0.01). Eighteen biopsies were performed based on MRI findings, of which 55.6% (10/18) were malignant. Conventional imaging more frequently underestimated ILC span at the biopsy site than MRI, using a 25% threshold difference (17.5% [7/40] versus 58.5% [24/41], p < 0.001). MRI detected more extensive disease at the biopsy site in six patients (9.7%, 6/62), additional ipsilateral disease in six patients (9.7%, 6/62), and contralateral disease in one patient (1.6%, 1/62). MRI therefore impacted surgical management in 21.0% (13/62) of patients. CONCLUSION: MRI led to the detection of additional disease, thus impacting surgical management, in one-fifth of patients with ILC.

A multicentre, randomised trial comparing schedules of G-CSF (filgrastim) administration for primary prophylaxis of chemotherapy-induced febrile neutropenia in early stage breast cancer.

BACKGROUND: The optimal duration of filgrastim as primary febrile neutropenia (FN) prophylaxis in early breast cancer patients is unknown, with 5, 7 or 10 days being commonly prescribed. This trial evaluates whether 5 days of filgrastim was non-inferior to 7/10 days. PATIENTS AND METHODS: In this randomised, open-label trial, early breast cancer patients who were to receive filgrastim as primary FN prophylaxis were randomly allocated to 5 versus 7 versus 10 days of filgrastim for all chemotherapy cycles. A protocol amendment in November 2017 allowed subsequent patients (N = 324) to be randomised to either 5 or 7/10 days. The primary outcome was a composite of either FN or treatment-related hospitalisations. Secondary outcomes included chemotherapy dose reductions, delays and discontinuations. Analyses were carried out by per protocol (primary) and intention-to-treat, and the non-inferiority margin was set at 3% for the risk of having FN and/or hospitalisation per cycle of chemotherapy. RESULTS: Patients (N = 466) were randomised to receive 5 (184, 39.5%), or 7/10 (282, 60.5%) days of filgrastim. In our primary analysis, the difference in risk of either FN or treatment-related hospitalisation per cycle was -1.52% [95% confidence interval (CI): -3.22% to 0.19%] suggesting non-inferiority of a 5-day filgrastim schedule compared with 7/10-days. The difference in events per cycle for FN was 0.11% (95% CI: -1.05 to 1.27) while for treatment-related hospitalisations it was -1.68% (95% CI: -2.73% to -0.63%). The overall proportions of patients having at least one occurrence of either FN or treatment-related hospitalisation were 11.8% and 14.96% for the 5- and 7/10-day groups, respectively (risk difference: -3.17%, 95% CI: -9.51% to 3.18%). CONCLUSION: Five days of filgrastim was non-inferior to 7/10 days. Given the cost and toxicity of this agent, 5 days should be considered standard of care. CLINICALTRIALS. GOV REGISTRATION: NCT02428114 and NCT02816164.

Lactobacillus fermentum and Lactobacillus plantarum increased gut microbiota diversity and functionality, and mitigated Enterobacteriaceae, in a mouse model.

Probiotics should bring 'balance' to the intestinal microbiota by stimulating beneficial bacteria, whilst mitigating adverse ones. Balance can also be interpreted as high alpha-diversity. Contrary, Escherichia coli is often regarded as an adverse component of the resident intestinal microbiota. The aim of the present study was to implement a mouse model for in vivo screening of Lactobacillus-strains for ability to increase gut-microbiota diversity and to mitigate E. coli. Mice were divided into six groups, two dietary control-groups and four groups administered strains of Lactobacillus fermentum and/or Lactobacillus plantarum. All animals were pre-treated with antibiotics, and E. coli in order to equalise the microbiota from the start. After 7 weeks of Lactobacillus administration, the animals were sacrificed: DNA was extracted from caecum tissue, and the microbiota composition was analysed with terminal restriction fragment length polymorphism (T-RFLP) and 16S rRNA gene sequencing. The diversity of the caecal microbiota decreased when the dietary carbohydrate source was limited to corn starch. Conversely, the diversity was restored by Lactobacillus-supplements. The tested combinations of two Lactobacillus strains exerted different influences, not only on the taxonomic level, but also on the inferred microbiome functions. The mixture of L. fermentum GOS47 and L. fermentum GOS1 showed potential for anti-inflammatory activity and short chain fatty acid production. On the other hand, co-administration of L. fermentum GOS57 and L. plantarum GOS42 significantly decreased the viable count of Enterobacteriaceae. These results warrant further investigation of the tested strains as candidates for probiotics. Furthermore, the findings demonstrated that the current experimental animal model is suitable for in vivo studies of the effect of bacterial supplements on the gut-microbiota.

Pre-treatment microbial Prevotella-to-Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention.

This corrects the article DOI: 10.1038/ijo.2017.220.

Pre-treatment microbial Prevotella-to-Bacteroides ratio, determines body fat loss success during a 6-month randomized controlled diet intervention.

On the basis of the abundance of specific bacterial genera, the human gut microbiota can be divided into two relatively stable groups that might have a role in personalized nutrition. We studied these simplified enterotypes as prognostic markers for successful body fat loss on two different diets. A total of 62 participants with increased waist circumference were randomly assigned to receive an ad libitum New Nordic Diet (NND) high in fiber/whole grain or an Average Danish Diet for 26 weeks. Participants were grouped into two discrete enterotypes by their relative abundance of Prevotella spp. divided by Bacteroides spp. (P/B ratio) obtained by quantitative PCR analysis. Modifications of dietary effects of pre-treatment P/B group were examined by linear mixed models. Among individuals with high P/B the NND resulted in a 3.15 kg (95% confidence interval (CI): 1.55; 4.76, P<0.001) larger body fat loss compared with ADD, whereas no differences was observed among individuals with low P/B (0.88 kg (95% CI: -0.61; 2.37, P=0.25)). Consequently, a 2.27 kg (95% CI: 0.09; 4.45, P=0.041) difference in responsiveness to the diets were found between the two groups. In summary, subjects with high P/B ratio appeared more susceptible to lose body fat on diets high in fiber and whole grain than subjects with a low P/B ratio.

Predictors of Multigland Disease in Primary Hyperparathyroidism: A Scoring System with 4D-CT Imaging and Biochemical Markers.

BACKGROUND AND PURPOSE: Multigland disease represents a challenging group of patients with primary hyperparathyroidism. Additional lesions may be missed on imaging because they are not considered or are too small to be seen. The aim of this is study was to identify 4D-CT imaging and biochemical predictors of multigland disease. MATERIALS AND METHODS: This was a retrospective study of 155 patients who underwent 4D-CT and successful surgery with a biochemical cure that compared patients with multigland and single-gland disease. Variables studied included the size of the largest lesion on 4D-CT, the number of lesions prospectively identified on 4D-CT, serum calcium levels, serum parathyroid hormone levels, and the Wisconsin Index (the product of serum calcium and parathyroid hormone levels). Imaging findings and the Wisconsin Index were used to calculate a composite multigland disease scoring system. We evaluated the predictive value of individual variables and the scoring system for multigland disease. RESULTS: Thirty-six patients with multigland disease were compared with 119 patients with single-gland disease. Patients with multigland disease had significantly lower Wisconsin Index scores, smaller lesion size, and a higher likelihood of having either multiple or zero lesions identified on 4D-CT (P ≤ .01). Size cutoff of <7 mm had 85% specificity for multigland disease, but including other variables in the composite multigland disease score improved the specificity. Scores of ≥4, ≥5, and 6 had specificities of 81%, 93%, and 98%, respectively. CONCLUSIONS: The composite multigland disease scoring system based on 4D-CT imaging findings and biochemical data can identify patients with a high likelihood of multigland disease. Communicating the suspicion for multigland disease in the radiology report could influence surgical decision-making, particularly when considering re-exploration in a previously operated neck or initial limited neck exploration.

TL1A regulates TCRγδ+ intraepithelial lymphocytes and gut microbial composition.

TL1A is a proinflammatory cytokine, which is prevalent in the gut. High TL1A concentrations are present in patients with inflammatory bowel disease (IBD) and in IBD mouse models. However, the role of TL1A during steady-state conditions is relatively unknown. Here, we used TL1A knockout (KO) mice to analyse the impact of TL1A on the intestinal immune system and gut microbiota. The TL1A KO mice showed reduced amounts of small intestinal intraepithelial TCRγδ(+) and CD8(+) T cells, and reduced expression of the activating receptor NKG2D. Moreover, the TL1A KO mice had significantly reduced body weight and visceral adipose tissue deposits, as well as lower levels of leptin and CXCL1, compared with wild-type mice. Analysis of the gut microbial composition of TL1A KO mice revealed a reduction of caecal Clostridial cluster IV, a change in the Firmicutes/Bacteroidetes ratio in caecum and less Lactobacillus spp. in the mucosal ileum. Our results show that TL1A deficiency impacts on the gut microbial composition and the mucosal immune system, especially the intraepithelial TCRγδ(+) T-cell subset, and that TL1A is involved in the establishment of adipose tissue. This research contributes to a broader understanding of TL1A inhibition, which is increasingly considered for treatment of IBD.

Imaging-detected incidental thyroid nodules that undergo surgery: a single-center experience over 1 year.

BACKGROUND AND PURPOSE: Incidental thyroid nodules are commonly seen on imaging, and their work-up can ultimately lead to surgery. We describe characteristics and pathology results of imaging-detected incidental thyroid nodules that underwent surgery. MATERIALS AND METHODS: A retrospective review was performed of 303 patients who underwent thyroid surgery over a 1-year period to identify patients who presented with incidental thyroid nodules on imaging. Medical records were reviewed for the types of imaging studies that led to detection, nodule characteristics, and surgical pathology. RESULTS: Of 303 patients, 208 patients (69%) had surgery for thyroid nodules. Forty-seven of 208 patients (23%) had incidental thyroid nodules detected on imaging. The most common technique leading to detection was CT (47%). All patients underwent biopsy before surgery. The cytology results were nondiagnostic (6%), benign (4%), atypia of undetermined significance or follicular neoplasm of undetermined significance (23%), follicular neoplasm or suspicious for follicular neoplasm (19%), suspicious for malignancy (17%), and diagnostic of malignancy (30%). Surgical pathology was benign in 24 of 47 (51%) cases of incidental thyroid nodules. In the 23 incidental cancers, the most common histologic type was papillary (87%), the mean size was 1.4 cm, and nodal metastases were present in 7 of 23 cases (30%). No incidental cancers on imaging had distant metastases. CONCLUSIONS: Imaging-detected incidental thyroid nodules led to nearly one-fourth of surgeries for thyroid nodules, and almost half were initially detected on CT. Despite indeterminate or suspicious cytology results that lead to surgery, more than half were benign on final pathology. Guidelines for work-up of incidental thyroid nodules detected on CT could help reduce unnecessary investigations and surgery.

Prevalence of the polar vessel sign in parathyroid adenomas on the arterial phase of 4D CT.

BACKGROUND AND PURPOSE: The "polar vessel" sign has been previously described on sonography of parathyroid adenomas. We estimated the 4D CT prevalence of the polar vessel sign and determined features of parathyroid adenomas that are associated with this sign. MATERIALS AND METHODS: Twenty-eight consecutive patients with parathyroid adenomas underwent 4D CT between 2008 and 2012 at 2 institutions. 4D CT images were reviewed for the presence of the polar vessel sign and a second vascular finding of an enlarged ipsilateral inferior thyroid artery. The polar vessel sign was correlated with adenoma weight and size and arterial phase CT attenuation. RESULTS: Thirty-two parathyroid adenomas in 28 patients were studied, with a mean adenoma weight of 0.66 ± 0.65 g, a mean maximal CT diameter of 11.1 ± 4.9 mm, and a mean arterial attenuation of 148 ± 47 HU. The polar vessel sign was seen in 20/32 (63%) adenomas. Adenomas with a polar vessel had higher arterial phase attenuation than adenomas without a polar vessel (163 and 122 HU, respectively, P < .01). Size and weight were not significantly different for adenomas with and without polar vessels. An enlarged inferior thyroid artery was seen in only 2/28 (7%) patients with unilateral disease. CONCLUSIONS: The polar vessel sign was present in nearly two-thirds of parathyroid adenomas on 4D CT and was more likely to be present in adenomas that had greater arterial phase enhancement. This sign can be used along with enhancement characteristics to increase the radiologist's confidence that a visualized lesion is a parathyroid adenoma rather than a thyroid nodule or lymph node.

Bifidogenic effect of whole-grain wheat during a 12-week energy-restricted dietary intervention in postmenopausal women.

BACKGROUND/OBJECTIVES: Consumption of whole-grain products is known to have beneficial effects on human health. The effects of whole-grain products on the intestinal microbiota and intestinal integrity have, however, only been studied limitedly. We investigate changes of the human gut microbiota composition after consumption of whole-grain (WW) or refined wheat (RW) and further study effects on gut wall integrity. SUBJECTS/METHODS: Quantitative PCR was used to determine changes in the gut bacterial composition in postmenopausal women following a 12-week energy-restricted dietary intervention with WW (N=38) or RW (N=34). Intestinal integrity was determined by measuring trans-epithelial resistance (TER) across a Caco-2 cell monolayer, following exposure to faecal water. RESULTS: No significant differences in microbiota composition were observed between the two dietary groups; however, the whole-grain intervention increased the relative abundance of Bifidobacterium compared to baseline, supporting a prebiotic effect of whole-grain wheat. Faecal water increased TER independent of dietary intervention, indicating that commensal bacteria produce metabolites that generally provide a positive effect on intestinal integrity. Combining microbiota composition data from the run-in period with its effect on TER revealed a tendency for a negative correlation between the relative abundance of Bifidobacterium and TER (P=0.09). This contradicts previous findings but supports observations of increased Salmonella infection in animal models following treatment with bifidogenic prebiotics. CONCLUSIONS: The present study shows that whole-grain wheat consumption increases the abundance of bifidobacteria compared to baseline and may have indirect effects on the integrity of the intestinal wall.

Germination and conjugation of Bacillus thuringiensis subsp. israelensis in the intestine of gnotobiotic rats.

AIMS: To study the ability of Bacillus thuringiensis subsp. israelensis spores to germinate and subsequently transfer a conjugative plasmid in the intestinal tract of gnotobiotic rats. METHODS AND RESULTS: Germination was studied by feeding germ-free rats with spores of a B. thuringiensis strain harbouring a plasmid encoding green fluorescent protein (GFP), which enabled quantification of germinated bacteria by flow cytometry. To study in vivo conjugation, germ-free rats were first associated with a B. thuringiensis recipient strain and after 1 week an isogenic donor strain harbouring the conjugative plasmid pXO16 was introduced. Both strains were given as spores and transfer of pXO16 was observed from the donor to the recipient strain. CONCLUSIONS: Bacillus thuringiensis is able to have a full life cycle in the intestine of gnotobiotic rats including germination of spores, several cycles of growth and sporulation of vegetative cells. For the first time conjugative plasmid transfer in a mammalian intestinal tract was shown between two B. thuringiensis strains. SIGNIFICANCE AND IMPACT OF THE STUDY: Strains of B. thuringiensis are used worldwide to combat insect pests, and this study brings new insights into the nature of B. thuringiensis showing the potential of the bacteria to germinate and transfer DNA in the mammalian intestinal tract.

The public health response to a case of Lassa fever in London in 2000.

OBJECTIVES: Evaluation of the Department of Health 1996 guidance, the Memorandum on the Management and Control of Viral Haemorrhagic Fevers. METHODS: Description of the public health management in 2000 of the fifth UK patient confirmed to have Lassa fever. RESULTS: Delayed risk categorisation of the patient occurred for a variety of reasons. DH Guidance was followed once infection control advice was sought. Active surveillance of 125 contacts was extremely resource intense, involving over 3000 communications. Self-monitoring by healthcare workers should be considered in future. Advice on use of ribavirin prophylaxis is not included in the Memorandum, nor advice or templates for information sheets for contacts. Information sheets are now available from the Health Protection Agency in the event of future cases. International aspects not adequately addressed include the need for reliable risk assessment to be carried out before patients are medically evacuated from the country of origin, and the steps required to repatriate UK nationals. Effective and efficient communication is required between national and international organisations involved in such incidents. CONCLUSIONS: If guidelines are unclear or impracticable they will not be followed. It is important that lessons are learned and documented and that national guidance be regularly reviewed.

Outbreak of isoniazid resistant tuberculosis in north London.

BACKGROUND: A description is given of a major outbreak of isoniazid monoresistant tuberculosis (TB) chiefly in north London, including prisons. The earliest case was diagnosed in 1995 with most cases appearing after 1999. METHODS: Confirmation of a local cluster of cases was confirmed by restriction fragment length polymorphism (RFLP IS6110) typing or "rapid epidemiological typing" (RAPET). Further cases were found by retrospective analysis of existing databases, prospective screening of new isolates, and targeted epidemiological case detection including questionnaire analysis. RESULTS: By the end of 2001, 70 confirmed cases in London had been linked with a further 13 clinical cases in contacts and nine epidemiologically linked cases outside London. The epidemic curve suggests that the peak of the outbreak has not yet been reached. Cases in the outbreak largely belong to a social group of young adults of mixed ethnic backgrounds including several individuals from professional/business backgrounds. Compared with other cases of TB reported to the enhanced surveillance scheme in London during 1999-2001, the cases are more likely to be of white (26/70 (37%) v 1308/7666 (17%)) or black Caribbean ethnicity (17/70 (24%) v 312/7666 (4%)), born in the UK (41/70 (59%) v 1335/7666 (17%)), and male (52/70 (74%) v 4195/7666 (55%)). Drug misuse and/or prison detention are factors common to many cases. CONCLUSIONS: The investigation of the outbreak revealed significant problems on an individual patient and population based level including difficulties with contact tracing, compliance, and the risk of developing multidrug resistance. This incident has demonstrated the value of molecular strain typing in investigating an extensive outbreak of TB. This is the first documented outbreak involving a UK prison.

Nonlinear optical effects in a two-dimensional photonic crystal containing one-dimensional Kerr defects.

The nonlinear optical effects induced by a one-dimensional (1D) line defect, made of Kerr material, in a 2D photonic crystal are studied. Comprehensive ab initio numerical simulations based on the finite-difference time-domain method show efficient third-harmonic generation in a photonic crystal waveguide consisting of the 1D defect line. The relationship between the third harmonic generation process and the nonlinear modal properties of the waveguide is discussed. We investigate optical limiting in such a device, that is, control of the transmitted power as a function of the Kerr-induced variation of the refractive index. Power dependent spectral changes in such a device and its use as a frequency selector are also examined.

[Experiences with loco-regional fibrinolytic therapy of deep venous thrombosis with defined drainage management]. / Erfahrungen mit der loco-regionalen Fibrinolysetherapie bei tiefen Venenthrombosen mit definiertem Drainagemanagement.

From 1989 to September 1997 1184 patients with deep vein thrombosis were treated. 606 (51.2%) received a specific therapy with loco-regional lysis. The application of two cycles of 20 mg Alteplase within 8 hours prevailed in combination with 1000 IE heparin per hour. In absence or lack of therapeutical effect further cycles of 20 or 40 mg of Alteplase were given. In the time free from lysis the patients received 30,000 IE heparin/24 hours depending on the individual aPTT (1.5-2.5 times prolonged). We developed a special drainage-management using perforans-veins during the loco-regional lysis. Complete lysis resulted in nearly half of the cases and in another third there was a lysis of more than 50%. Complications were observed in 5.8% of the patients, 4% due to heparinization. Importantly no life-threatening bleeding like gastrointestinal or cerebral bleeding or pulmonary embolism occurred. According to our data we conclude that the loco-regional lytic effect tends to be better than using systemical lysis, the risks are minimized and patient monitoring and treatment is much simpler.

Screening for Corynebacterium diphtheriae.

A throat swab from a 9 year old girl with pharyngitis yielded a non-toxigenic strain of Corynebacterium diphtheriae var mitis and Streptococcus group G. C pseudodiphtheriticum was isolated from the throats of two of her four brothers. In each case the isolate was sent to the reference laboratory before full identification. The growth was found to be mixed for one brother; the other isolate being a toxin producing C diphtheriae var gravis. The child was asymptomatic and the case proves that all colonial types on the Hoyles plate should be identified.

Analysis of the molecular specificities of anti-class II monoclonal antibodies by using L cell transfectants expressing HLA class II molecules.

Expressible HLA class II alpha- and beta-chain cDNA were used for DNA-mediated gene transfer to produce L cell transfectants expressing single types of human class II molecules. Cloned transfectants expressing nine different class II molecules were isolated: DR alpha: DR1 beta I, DR alpha: DR4 beta I, DR alpha: DR5 beta I, DR alpha: DR5 beta III (DRw52), DR alpha: DR7 beta I, DR alpha: DR4/7 beta IV (DRw53), DQ7 alpha: DQw2 beta, DQ7 alpha: DQw3 beta, and DPw4 alpha: DPw4 beta. These class II-expressing transfectants were used to analyze by flow cytometry the molecular specificities of 20 anti-class II mAb. These analyes indicate that some mAb are more broadly reactive than was previously thought based on immunochemical studies. In contrast, the narrow molecular specificities of other anti-class II mAb were confirmed by this approach. Transfectants expressing human class II molecules should be valuable reagents for studies of B cell and T cell defined epitopes on these molecules.