A Preliminary Study on Hepatoprotective, Hypolipidemic and Aortic Morphometric Effects of Omega-3-Rich Fish Oil in Hypercholesterolemic Mice.

This study aims to evaluate the hepatoprotective, hypolipidemic and aortic morphometric effects of fish oil rich in omega-3 in hypercholesterolemic BALB/c mice. This is an experimental model that included 16 male BALB/c mice (Mus musculus) divided into three groups (G1 (standard commercial chow and 0.9% saline solution), G2 (hypercholesterolemic diet and 0.9% saline solution) and G3 (hypercholesterolemic diet and fish oil)) for 8 weeks. There was no significant difference in the treatment with omega-3-rich fish oil in the lipid profile (p > 0.05). In the histological analysis, group G2 detected the presence of hepatitis and liver tissue necrosis, but this was not observed in group G3. As for the morphometry in the light area of the vessel, the G1 group had a higher score (2.62 ± 0.36 mm2) when compared to G2 (2.10 ± 0.16 mm2) and G3 (2.26 ± 0.25 mm2) (p < 0.05). The vessel wall thickness did not differ between the groups (p > 0.05). It is concluded that supplementation with fish oil rich in omega-3 carried out in this study may have a protective effect on liver tissue, but it has not yet improved the lipid and morphometric profile. Despite this research being preliminary, it is a relevant study with future prospects for improving the doses of EPA and DHA in order to better elucidate the benefits of fish oil in models of dyslipidemia.

Strength of hip muscles and bradykinesia contribute to walking speed over a long distance, but not a short distance, in people with mild Parkinson's disease: An observational study.

BACKGROUND: Bradykinesia and postural instability contribute to walking limitations in people with Parkinson's disease (PD), but the contribution of muscle strength to walking speed has not been examined extensively. RESEARCH QUESTION: Does strength of the major lower limb muscles contribute to walking speed over short and long distances in people with PD? METHOD: na. DESIGN: A cross-sectional, observational study. PARTICIPANTS: 50 people with mild PD. OUTCOME MEASURES: Maximum isometric strength of the flexors and extensors of the lower limb was measured using hand-held dynamometry. Flexed posture, postural instability and bradykinesia were measured using the MDS-UPDRS part III. Walking speed was measured during the 10-m Walk Test and 6-min Walk Test. RESULTS: Univariate analysis revealed that age, bradykinesia, flexed posture, and hip, knee and ankle weakness were all significantly correlated with walking speed over short and long distances. Multiple regression analysis revealed that age, bradykinesia, flexed posture and weakness of the hip and knee muscles together accounted for 47% of the variance in walking speed over a short distance, with age (R2 = 0.11, p = 0.003) making a significant independent contribution. Age, bradykinesia, flexed posture and strength of the hip and knee muscles together accounted for 56% of the variance in walking speed over a long distance. Age (R2 = 0.12, p = 0.001), weakness of the hip muscles (R2 = 0.12, p = 0.001) and bradykinesia (R2 = 0.04, p = 0.04) made significant, independent contributions to the variance in walking speed over a long distance. SIGNIFICANCE: In people with mild PD, weakness of the hip muscles and bradykinesia only make a significant relative contribution to walking speed over a long distance. Therefore, in people with normal walking speed over a short distance the 6-min Walk Test could be measured to more effectively identify the impact of motor impairments on walking.

Who is dying from COVID-19 in the United Kingdom? A review of cremation authorisations from a single South Wales' crematorium.

Only studies in the UK on individuals dying from coronavirus disease 2019 (COVID-19) in hospital have been published, to date. Cremation law requires collection of clinical information that can improve understanding of deaths in both hospital and community settings. Age, sex, date and place of death, occupation, comorbidities and where infection acquired was recorded for all deaths from COVID-19, between 6 April and 30 May, for whom an application was made for cremation at a South Wales' crematorium. Of 752 cremations, 215 (28.6%) were COVID-19 (115 (53.5%) male and 100 (46.5%) female). Median age was 82 years (youngest patient 47 and the oldest 103 years). Over half the deaths (121/215: 56.3%) were over 80 years. Males' odds of dying in hospital, rather than the community were 1.96 times that of females (95% confidence intervals (CI) 1.03-3.74, P = 0.054) despite being of similar age and having a similar number of comorbidities. Only 21 (9.8%) of 215 patients had no comorbidities recorded. Patients dying in care homes were significantly older than those dying in hospital (median 88 years (interquartile (IQ) range 82-93 years) vs. 80 years (IQ range 71-87 years): P < 0.0001). Patients dying in hospital had significantly more comorbidities than those dying in care homes (median 2: IQ range 1-3 vs. 1: IQ range 1-2: P < 0.001). Sixty three (29.3%) of infections were hospital acquired and a further 55 (25.6%) acquired in care homes. In a series, of hospital and community deaths, persons over 80 with an average two comorbidities predominated. Men were more likely to die in hospital. Half the infections were acquired in hospitals or care homes with implications for management of the pandemic.

Minibeam radiation therapy: A micro- and nano-dosimetry Monte Carlo study.

PURPOSE: Minibeam radiation therapy (MBRT) is an innovative strategy based on a distinct dose delivery method that is administered using a series of narrow (submillimetric) parallel beams. To shed light on the biological effects of MBRT irradiation, we explored the micro- and nanodosimetric characteristics of three promising MBRT modalities (photon, electron, and proton) using Monte Carlo (MC) calculations. METHODS: Irradiation with proton (100 MeV), electron (300 MeV), and photon (effective energy of 69 keV) minibeams were simulated using Geant4 MC code and the Geant4-DNA extension, which allows the simulation of energy transfer points with nanometric accuracy. As the target of the simulations, cells containing spherical nuclei with or without a detailed description of the DNA (deoxyribonucleic acid) geometry were placed at different depths in peak and valley regions in a water phantom. The energy deposition and number of events in the cell nuclei were recorded in the microdosimetry study, and the number of DNA breaks and their complexity were determined in the nanodosimetric study, where a multi-scale simulation approach was used for the latter. For DNA damage assessment, an adapted DBSCAN clustering algorithm was used. To compare the photon MBRT (xMBRT), electron MBRT (eMBRT), and proton MBRT (pMBRT) approaches, we considered the treatment of a brain tumor located at a depth of 75 mm. RESULTS: Both mean energy deposition at micrometric scale and DNA damage in the "valley" cell nuclei were very low as compared with these parameters in the peak region at all depths for xMBRT and at depths of 0 to 30 mm and 0 to 50 mm for eMBRT and pMBRT, respectively. Only the charged minibeams were favorable for tumor control by producing similar effects in peak and valley cells after 70 mm. At the micrometer scale, the energy deposited per event pointed to a potential advantage of proton beams for tumor control, as more aggressive events could be expected at the end of their tracks. At the nanometer scale, all three MBRT modalities produced direct clustered DNA breaks, although the majority of damage (>93%) was composed of isolated single strand breaks. The pMBRT led to a significant increase in the proportion of clustered single strand breaks and double-strand breaks at the end of its range as compared to the entrance (7% at 75 mm vs 3% at 10 mm) in contrast to eMBRT and xMBRT. In the latter cases, the proportions of complex breaks remained constant, irrespective of the depth and region (peak or valley). CONCLUSIONS: Enhanced normal tissue sparing can be expected with these three MBRT techniques. Among the three modalities, pMBRT offers an additional gain for radioresistant tumors, as it resulted in a higher number of complex DNA damage clusters in the tumor region. These results can aid understanding of the biological mechanisms of MBRT.

A large Great Britain-wide outbreak of STEC O157 phage type 8 linked to handling of raw leeks and potatoes.

Between December 2010 and July 2011, 252 cases of STEC O157 PT8 stx1 + 2 infection were reported in England, Scotland and Wales. This was the largest outbreak of STEC reported in England and the second largest in the UK to date. Eighty cases were hospitalized, with two cases of haemolytic uraemic syndrome and one death reported. Routine investigative data were used to generate a hypothesis but the subsequent case-control study was inconclusive. A second, more detailed, hypothesis generation exercise identified consumption or handling of vegetables as a potential mode of transmission. A second case-control study demonstrated that cases were more likely than controls to live in households whose members handled or prepared leeks bought unwrapped [odds ratio (OR) 40, 95% confidence interval (CI) 2·08-769·4], and potatoes bought in sacks (OR 13·13, 95% CI 1·19-145·3). This appears to be the first outbreak of STEC O157 infection linked to the handling of leeks.

Intermittent dosing of aromatase inhibitors (AI) to improve tolerance in postmenopausal women: a rationale for future clinical studies.

A significant proportion of post-menopausal, patients treated with AI reports side-effects, especially bone pain. In such patients, the difficulties to treat pain and to clearly identify its causes may lead to treatment discontinuation. Ageing is associated with physiological modifications that may impair drug pharmacokinetics (PKs). The elimination can be altered, with decreased drug clearance (CL), resulting in an increased exposure to the drug, reflected by increased AUCs. The reported increases in AI exposure being around 50 %, an intermittent dosing schedule of 1 administration every other day could result in a similar drug exposure as compared to the usual daily schedule.

Liver metastases from breast cancer: Surgical resection or not? A case-matched control study in highly selected patients.

AIM: To determine whether, in a highly selected patient population, medical treatment combined with surgical resection of liver metastases from breast cancer is associated with improved survival compared with medical treatment alone. PATIENTS AND METHODS: Between 1988 and 2007, 100 liver resections for metastatic breast cancer were performed at Institut Curie, 51 of which met the criteria for inclusion in this case-control study. With the exception of bone metastases, patients with other distant metastasis sites were excluded. Surgery was only performed in patients with stable disease or disease responding to medical treatment evaluated by imaging evaluation. Surgical cases were individually matched with 51 patients receiving medical treatment only. All patients had 4 or fewer resectable liver metastases. The study group was matched with the control group for age, year of breast cancer diagnosis, time to metastasis, TNM stage, hormone receptor status and breast cancer tumour pathology. RESULTS: Univariate analysis confirmed a survival advantage for patients lacking bone metastases and axillary lymphadenopathy at the time of breast cancer diagnosis and for surgically treated patients. Multivariate analysis indicated that surgery and the absence of bone metastases were associated with a better prognosis. A multivariate Cox model adapted for paired data showed a RR = 3.04 (CI: 1.87-4.92) (p < 0.0001) in favour of surgical treatment. CONCLUSION: Surgical resection of liver metastases from primary breast cancer appears to provide a survival benefit for highly selected patients.

Subclinical infection and asymptomatic carriage of gastrointestinal zoonoses: occupational exposure, environmental pathways, and the anonymous spread of disease.

Asymptomatic carriage of gastrointestinal zoonoses is more common in people whose profession involves them working directly with domesticated animals. Subclinical infections (defined as an infection in which symptoms are either asymptomatic or sufficiently mild to escape diagnosis) are important within a community as unknowing (asymptomatic) carriers of pathogens do not change their behaviour to prevent the spread of disease; therefore the public health significance of asymptomatic human excretion of zoonoses should not be underestimated. However, optimal strategies for managing diseases where asymptomatic carriage instigates further infection remain unresolved, and the impact on disease management is unclear. In this review we consider the environmental pathways associated with prolonged antigenic exposure and critically assess the significance of asymptomatic carriage in disease outbreaks. Although screening high-risk groups for occupationally acquired diseases would be logistically problematical, there may be an economic case for identifying and treating asymptomatic carriage if the costs of screening and treatment are less than the costs of identifying and treating those individuals infected by asymptomatic hosts.

The standard tangential fields used for breast irradiation do not allow optimal coverage and dose distribution in axillary levels I-II and the sentinel node area.

BACKGROUND: Recent data from ACOSOG Z0011 and NSABP B32 trials suggested no need for axillary lymph node dissection (ALND) in patients with micrometastatic involvement of the sentinel lymph node (SLN). The low rate of axillary recurrence was attributed to the axilla coverage by the tangential fields (TgFs) irradiation and systemic therapy. This study aimed to evaluate dose distribution and coverage of the axilla levels I-II and the SLN area. PATIENTS AND METHODS: One hundred and nine patients were analyzed according to three groups: group 1 (50 Gy; n = 18), group 2 (60 Gy; n = 34) and group 3 (66 Gy; n = 57). Patients were treated using the standard (STgF; n = 22) or high (HTgF; n = 87) TgF. RESULTS: The median doses delivered to level I using HTgF versus STgF were 33 and 20 Gy (P = 0.0001). The mean dose delivered to the SLN area was only 28 Gy. Additionally, the SLN area was totally included in the HTgF in 1 out of 12 patients who had intraoperative clip placement in the SNL area. CONCLUSIONS: TgFs provide a limited coverage of the axilla and the SNLB area. This information should be considered when only TgFs are planned to target the axilla in patients with a positive SLN without ALND. Standardization of locoregional radiotherapy in this situation is urgently needed.

Extreme water-related weather events and waterborne disease.

Global climate change is expected to affect the frequency, intensity and duration of extreme water-related weather events such as excessive precipitation, floods, and drought. We conducted a systematic review to examine waterborne outbreaks following such events and explored their distribution between the different types of extreme water-related weather events. Four medical and meteorological databases (Medline, Embase, GeoRef, PubMed) and a global electronic reporting system (ProMED) were searched, from 1910 to 2010. Eighty-seven waterborne outbreaks involving extreme water-related weather events were identified and included, alongside 235 ProMED reports. Heavy rainfall and flooding were the most common events preceding outbreaks associated with extreme weather and were reported in 55·2% and 52·9% of accounts, respectively. The most common pathogens reported in these outbreaks were Vibrio spp. (21·6%) and Leptospira spp. (12·7%). Outbreaks following extreme water-related weather events were often the result of contamination of the drinking-water supply (53·7%). Differences in reporting of outbreaks were seen between the scientific literature and ProMED. Extreme water-related weather events represent a risk to public health in both developed and developing countries, but impact will be disproportionate and likely to compound existing health disparities.

Seroprevalence and risk factors associated with Escherichia coli O157 in a farming population.

Evidence suggests that frequent and direct exposure to domestic animals has made farmers less susceptible to symptomatic Escherichia coli O157 infection than other members of the community. We have quantified the seroprevalence of antibodies to E. coli O157 lipopolysaccharide (LPS) from a representative cohort of farm workers in three geographically distinct regions of the United Kingdom during two sampling rounds over a 2-year period. All participants completed a questionnaire to determine the range and extent of recent animal contact alongside other potential occupational and environmental exposure routes. A total of 31/946 (3.3%) serum samples contained antibodies to E. coli O157 LPS (from both rounds combined). On the second sampling round, a significant difference in seropositivity was apparent between the three regions, with enhanced seroprevalence linked to recent contact with beef cattle, having a private water supply and contact with a child under 5 years old. Only five seropositive people reported symptoms of a gastrointestinal tract infection, although these symptoms were mild. These results further support the premise of acquired immunity to E. coli O157 associated with prolonged antigenic exposures within the farming environment.

Outcome in early cervical cancer following pre-operative low dose rate brachytherapy: a ten-year follow up of 257 patients treated at a single institution.

OBJECTIVE: To report the outcome of preoperative low dose rate uterovaginal brachytherapy (LDR-UVBT) followed by radical surgery in the treatment of early cervical carcinoma. METHODS: 257 patients treated at Institut Curie from 1985 to 2008 for cervical carcinoma less than 4cm (FIGO stages Ib1, IIA and IIB) were studied. Patients received preoperative LDR-UVBT followed by hysterectomy Piver II type, with pelvic lymph nodes dissection (PLND). Predictive factors for pathological response to brachytherapy were analyzed with logistic regression, as well as survival rates. RESULTS: 44% of patients had residual tumor, 4.3% of patients had parametrial invasion and 17.9% of patients had lymph node involvement. Predictive factors for an incomplete pathological response were: initial clinical tumor size 20mm (OR 2.1), pN1 (OR 2.77), glandular carcinoma (OR 2.51) and lymphovascular invasion (OR 4.35). 7.4% and 2.7% of patients had respectively grade 2 and grade 3 post-therapeutic late complications. Median follow up was 122 months [1-282]. Five-year actuarial overall survival and disease free survival were respectively 83% CI [78.3-87.5] and 80.9% CI [76.3-85.7]. In multivariate analysis, factors affecting significantly the overall survival and disease free survival rates were: lymph node involvement (RR 4.53 and 8.96 respectively), parametrial involvement (RR 5.69 and 5.62 respectively), smoking (RR 3.07 and 2.63 respectively). CONCLUSIONS: Preoperative LDR-UVBT results in good disease control with a low complications rate. Its accuracy could be improved by a better selection of patients. Lymph nodes and parametrial evaluation remains a challenging issue that should be achieved with imaging and minimal invasive surgery.

Management of exposed, infected implant-based breast reconstruction and strategies for salvage.

INTRODUCTION: Complications of implant-based breast reconstruction are rare but mastectomy flap necrosis and peri-implant infection are the most frequent and remain an important cause of early implant failure. This study aimed to compare the results of three different management strategies employed to deal with these complications at our institution. PATIENTS AND METHODS: A consecutive series of 71 infected/exposed prostheses in 68 patients over a 20-year period were analysed. Management strategies included explantation and delayed reconstruction, implant salvage and explantation and immediate autologous reconstruction. RESULTS: Only 19 of 45 (42%), managed with implant removal, went on to delayed reconstruction. Methods of delayed reconstruction were distributed equally between implant-only, implant and autologous tissue and autologous-only reconstructions. The implant was successfully salvaged in nine cases, but reducing the implant size or introducing new tissue as a flap increased the success from 45% to 53%. Three patients with infected implant-only breast reconstruction underwent explantation and immediate conversion to autologous-only reconstructions. CONCLUSIONS: All the three interventions reviewed here have their place in the management of infected implant-based breast reconstructions. It is noteworthy that following implant removal, the likelihood of the patient proceeding to delayed reconstruction of any kind is similar to the likelihood of successful salvage (42% vs. 45%). This study population had high numbers of exposed implants in irradiated fields. Reducing implant size or introducing new tissue in the form of a flap increases the chances of successful implant salvage. In the presence of mild infection, removal of exposed/infected implants and immediate conversion to an autologous-only reconstruction can prove to be successful.

Two waves of pandemic influenza A(H1N1) 2009 in Wales--the possible impact of media coverage on consultation rates, April-December 2009.

In the United Kingdom, the influenza A(H1N1) 2009 pandemic had a distinct two-wave pattern of general practice consultations for influenza-like illness (ILI). We describe the epidemiology of the influenza pandemic in Wales between April and December 2009 using integrated data from a number of independent sources: GP surveillance, community virology surveillance, hospital admissions and deaths, and media enquiries monitoring. The first wave peaked in late July at 100 consultations per 100,000 general practice population and attracted intensive media coverage. The positivity rate for the A(H1N1)2009 influenza did not exceed 25% and only 44 hospitalisations and one death were recorded. By contrast, the second wave peaked in late October and although characterised by lower ILI consultation rates (65 consultations per 100,000 general practice population) and low profile media activity, was associated with much higher positivity rates for pandemic influenza A(H1N1)2009 (60%) and substantially more hospital admissions (n=379) and deaths (n=26). The large number of ILI-related consultations during the first wave in Wales probably reflected the intensive media activity rather than influenza virus circulating in the community. Data from community surveillance schemes may therefore have considerably overestimated the true incidence of influenza. This has implications for the future interpretation of ILI surveillance data and their use in policy making, and underlines the importance of using integrated epidemiological, virological and hospital surveillance data to monitor influenza activity.

Salmonella enterica serovar Agona European outbreak associated with a food company.

We investigated an international outbreak of Salmonella Agona with a distinct PFGE pattern associated with an Irish Food company (company X) producing pre-cooked meat products sold in various food outlet chains in Europe. The outbreak was first detected in Ireland. We undertook national and international case-finding, food traceback and microbiological investigation of human, food and environmental samples. We undertook a matched case-control study on Irish cases. In total, 163 cases in seven European countries were laboratory-confirmed. Consumption of food from food outlet chains supplied by company X was significantly associated with being a confirmed case (mOR 18·3, 95% CI 2·2-149·2) in the case-control study. The outbreak strain was isolated from the company's pre-cooked meat products and production premises. Sufficient evidence was gathered to infer the vehicles of infection and sources of the outbreak and to justify the control measures taken, which were plant closure and food recall.