Negligible In Vitro Recovery of Macromolecules from Microdialysis Using 100 kDa Probes and Dextran in Perfusion Fluid.

Microdialysis is applied in neurointensive care to monitor cerebral glucose metabolism. If recoverable, macromolecules may also serve as biomarkers in brain disease and provide clues to their passage across the blood-brain barrier. Our study aimed to investigate the in vitro recovery of human micro- and macromolecules using microdialysis catheters and perfusion fluids approved for clinical use. In vitro microdialysis of a bulk solution containing physiological or supraphysiological concentrations of glucose, lactate, pyruvate, human IgG, serum albumin, and hemoglobin was performed using two different catheters and perfusion fluids. One had a membrane cut-off of 20 kDa and was used with a standard CNS perfusion fluid, and the other had a membrane cut-off of 100 kDa and was perfused with the same solution supplemented with dextran. The flow rate was 0.3 µl/min. We used both push and push-pull methods. Dialysate samples were collected at 2-h intervals for 6 h and analyzed for relative recovery of each substance. The mean relative recovery of glucose, pyruvate, and lactate was > 90% in all but two sets of experiments. In contrast, the relative recovery of human IgG, serum albumin, and hemoglobin from both bulk solutions was below the lower limit of quantification (LLOQ). Using a push-pull method, recovery of human IgG, serum albumin, and hemoglobin from a bulk solution with supraphysiological concentrations were above LLOQ but with low relative recovery (range 0.9%-1.6%). In summary, exchanging the microdialysis setup from a 20 kDa catheter with a standard perfusion fluid for a 100 kDa catheter with a perfusion solution containing dextran did not affect the relative recovery of glucose and its metabolites. However, it did not result in any useful recovery of the investigated macromolecules at physiological levels, either with or without a push-pull pump system.

Factors associated with successful tobacco use cessation among teachers in Bihar state, India: a mixed-method study.

Although tobacco use is declining in several countries including India (dropping from 35% in 2009-10 to 29% 2016-17 among adults)-it still poses a huge burden on India, as the world's second largest consumer of tobacco products. In Bihar state, with a prevalence of 25%, the Bihar School Teachers Study (BSTS) successfully enlisted teachers as role models for encouraging quitting and changing social norms pertaining to tobacco. The study used a mixed-methods approach to identify factors associated with teachers' quitting. Qualitative data were collected through focus groups with teachers and school principals. Quantitative data were collected through a written survey administered to school personnel post-intervention. Key findings from focus groups were that teachers and principals quit using tobacco and promoted cessation because they wanted to model positive behaviors; specific information about tobacco's harms aided cessation; and the BSTS intervention facilitated a school environment that supported quitting. Survey results indicated teachers who reported knowing people who quit using tobacco in the prior year were far more likely to quit as were teachers who reported that their school's tobacco policy was completely enforced. The combination of qualitative and quantitative data yielded important insights with strong implications for future interventions.

Scaling up a tobacco control intervention in low resource settings: a case example for school teachers in India.

Research on processes of bringing effective tobacco control interventions to scale to increase quit rates among tobacco users is uncommon. This study examines processes to bring to scale one such intervention for school teachers, i.e. Tobacco Free Teacher-Tobacco Free Society (TFT-TFS). This intervention provides a foundation for an effective and low cost approach to promote cessation through schools. The present study was conducted in the states of Bihar and Maharashtra in 2014 using quantitative and qualitative methods. Focus group discussions (FGDs) were analysed using immersion crystallization method. The data presented are from a survey of 291 principals and seven FGDs. This study examined characteristics of principals and teachers, organizational environment, external environmental factors and program characteristics to determine facilitators and barriers for successful dissemination and implementation of the TFT-TFS program. Some facilitators were, incorporation of the program in existing channels like staff meetings and trainings, certification and recognition by the department of education; while some barriers were routine time bound duties (mainly teaching) of teachers and prevalence of tobacco use among teachers and administrators. Principals and teachers expressed a need and high level of interest in the adoption and implementation of the TFT-TFS program in their schools.

Mortality in cancer patients previously diagnosed with herpes zoster in the hospital setting: a nationwide cohort study.

BACKGROUND: Herpes zoster (HZ) is associated with underlying immunodeficiency and may thereby predict mortality of subsequent cancer. METHODS: By using Danish nationwide medical databases, we identified all cancer patients with a prior hospital-based HZ diagnosis during 1982-2011 (n=2754) and a matched cancer cohort without prior HZ (n=26 243). We computed adjusted mortality rate ratios (aMRRs) associating prior HZ with mortality following cancer. RESULTS: Prior HZ was associated with decreased mortality within the year after cancer diagnosis (aMRR 0.87; 95% confidence interval (CI): 0.81-0.93), but not thereafter (aMRR 1.07; 95% CI: 0.99-1.15). However, prior HZ predicted increased mortality throughout the entire follow-up among patients aged <60 years (aMRR 1.39; 95% CI: 1.15-1.68) and those with disseminated HZ (aMRR 1.18; 95% CI: 1.01-1.37). The increased mortality rates were observed primarily for haematological and immune-related cancers. CONCLUSIONS: Overall, HZ was not a predictor of increased mortality following subsequent cancer.

Tobacco use among low-income housing residents: does hardship motivate quit attempts?

PURPOSE: The purpose of this study was to examine material hardship among smokers to determine whether such hardship was positively associated with current attempts to quit tobacco use. METHODS: We analyzed cross-sectional data from the Health in Common (HIC) study, an observational study to investigate social and physical determinants of cancer risk-related behaviors among residents of low-income housing in three cities in the Boston metropolitan area. In this study, three indicators of hardship were used: food hardship, financial hardship, and material hardship (food and financial hardship combined). Logistic regression models were used to obtain the odds of currently trying to quit among current smokers in the HIC (n = 170) across hardship types experienced, adjusting for sociodemographic and psychosocial factors. RESULTS: Fully adjusted models revealed no statistically significant association between trying to quit tobacco use and indicators of material hardship: food hardship and financial hardship present (OR 1.33 (0.42-4.2); food hardship and no financial hardship OR 3.83 (0.97-15.13); and financial hardship but no food hardship OR 0.5 (0.1-2.39). CONCLUSIONS: These findings suggest that even in the presence of material hardship, low-income housing resident tobacco users are not more likely to quit tobacco use; therefore, cessation efforts focused on the financial benefits of quitting may be insufficient to motivate quit attempts among low-income smokers.

Experiences recruiting Indian worksites for an integrated health protection and health promotion randomized control trial in Maharashtra, India.

This article provides an overview of the recruitment strategies utilized in the Mumbai Worksites Tobacco Control Study, a cluster randomized trial testing the effectiveness of an integrated tobacco control and occupational safety and health program in Indian manufacturing worksites. From June 2012 to June 2013, 20 companies were recruited. Companies were identified using association lists, referrals, internet searches and visits to industrial areas. Four hundred eighty companies were contacted to validate information, introduce the study and seek an in-person meeting with a company representative. Eighty-three company representatives agreed to meet. Of those 83 companies, 55 agreed to a formal 'pitch meeting' with key decision makers at the company. Seventy-seven recruitment 'pitches' were given, including multiple meetings in the same companies. If the company was interested, we obtained a letter of participation and employee roster. Based on this experience, recommendations are made that can help inform future researchers and practitioners wishing to recruit Indian worksites. When compared with recruitment of US manufacturing worksites, recruitment of Indian worksites lacked current industrial lists of companies to serve as a sampling frame, and required more in-person visits, incentives for control companies and more assurances around confidentiality to allow occupational safety and health experts into their worksite.

Tracking intervention delivery in the 'Tobacco-Free Teachers/Tobacco-Free Society' program, Bihar, India.

In health education and behavior change interventions, process tracking monitors the delivery of an intervention and its receipt to the intended audience. A randomized controlled trial in the state of Bihar, India was conducted to help school teachers become tobacco free through appropriately designed intervention program and delivery system. We describe the results from process tracking of this intervention delivery. The intervention program was centred on six topics delivered in each school through 12 sessions over 6 successive months. The program deliverers recorded the process measures as total number of sessions and program-components implemented (fidelity); time spent conducting sessions (dose) and proportion of teachers attending at least one session (reach). The outcome measures (teachers' exposure to intervention messages and tobacco policy adoption) were assessed post-intervention. All 12 sessions were delivered in 33 out of 36 schools. Thirty-one schools implemented all six program components. In 18 schools, ≥95% of the teachers participated in one or more sessions. Thirty-three schools received 12 or more hours of dose. In 29 schools, 100% teachers reported exposure to all program messages. Tobacco policy was adopted by all schools. Thus, the intervention was generally delivered as planned and it had a positive impact on teachers and schools.

Heritability assessment of cartilage metabolism. A twin study on circulating procollagen IIA N-terminal propeptide (PIIANP).

OBJECTIVE: The aim of this investigation was to estimate the heritability of circulating collagen IIA N-terminal propeptide (PIIANP) by studying mono- and dizygotic healthy twin pairs at different age and both genders. DESIGN: 598 monozygotic (MZ) and dizygotic (DZ) twin individuals aged 18-59 years were recruited from the Danish Twin Registry. PIIANP was measured by competitive ELISA. The similarity of circulating PIIANP among MZ and DZ twins was assessed by intraclass correlations according to traits. The heritability was estimated by variance component analysis accounting for additive and dominant genetic factors as well as shared and non-shared environment but ignoring epistasis (genetic inter-locus interaction) and gene-environment interaction. RESULTS: The intraclass correlation of PIIANP in MZ and DZ twins was 0.69 (0.60-0.76) and 0.46 (0.34-0.58) respectively indicating a significant genetic impact on PIIANP in serum. Additive genetic effects explained 45% (21-70%), shared environment 24% (7-53%) and non-shared environment 31% (24-39%) of the total variance. The heritability estimate did not differ across ages and between genders. CONCLUSIONS: The study shows that approximately 45% of the collagen IIA synthesis as assessed by the collagen IIA N-terminal propeptide in serum is attributable to genetic effectors while individual and shared environment account for 24% and 31% respectively. The heritability does not differ between genders or according to age.

Source attribution of human campylobacteriosis in Denmark.

SUMMARY This study assesses the contribution of different sources of human campylobacteriosis in Denmark using two different source-attribution approaches. In total, 794 non-human isolates and 406 isolates from human cases (domestic, travel related, and cases with unknown travel history) were collected. Isolates were characterized by multilocus sequence typing, flaA typing and susceptibility to antibiotics. Both models used indicate that the major burden of human campylobacteriosis in Denmark originates from the domestic broiler chicken reservoir. The second most important reservoir was found to be cattle. The Asymmetric Island model attributed 52% [95% credibility interval (CrI) 37-67] to Danish chicken, 17% (95% CrI 3-33) to imported chicken, and 17% (95% CrI 7-28) to cattle. Similarly, the Campylobacter source-attribution model apportioned 38% (95% CrI 28-47) to Danish chicken, 14% (95% CrI 10-18) to imported chicken, and 16% (95% CrI 7-25) to cattle. The addition of flaA type as an extra discriminatory typing parameter did not change the attribution of cases markedly.

A long-lasting outbreak of Salmonella Typhimurium U323 associated with several pork products, Denmark, 2010.

This paper shows that control of foodborne disease outbreaks may be challenging even after establishing the source of infection. An outbreak of Salmonella Typhimurium U323 infections occurred in Denmark from March to September 2010, involving 172 cases. Before the detection of human cases, several positive isolates of the outbreak strain had been found in a particular pig slaughterhouse and thus early traceback, investigation and control measures were possible. Several batches of pork and pork products were recalled and the slaughterhouse was closed twice for disinfection. No single common food item was identified as the outbreak source, but repeated isolation of the outbreak strain from the slaughterhouse environment and in pork and products as well as patient interviews strongly suggested different pork products as the source of infection. Furthermore, a matched case-control study identified a specific ready-to-eat spreadable pork sausage (teewurst) as the source of a sub-outbreak (matched odds ratio 17, 95% confidence interval 2·1-130).

Patient-reported outcomes after single-incision versus traditional laparoscopic cholecystectomy: a randomized prospective trial.

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) is a newer approach that may be a safe alternative to traditional laparoscopic cholecystectomy (TLC) based on retrospective and small prospective studies. As the demand for single-incision surgery may be driven by patient perceptions of benefits, we designed a prospective randomized study using patient-reported outcomes as our end points. METHODS: Patients deemed candidates for either SILC or TLC were offered enrollment in the study. After induction of anesthesia, patients were randomized to SILC or TLC. Preoperative characteristics and operative data were recorded, including length of stay (LOS). Pain scores in recovery and for 48 h and satisfaction with wound appearance at 2 and 4 weeks were reported by patients. We used the gastrointestinal quality of life index (GIQLI) survey preoperatively and at 2 and 4 weeks postoperatively to assess recovery. Procedural and total hospital costs per case were abstracted from hospital billing systems. RESULTS: Mean age of the study group was 44.1 years (±14.8), 87% were Caucasian, and 77% were female, with no difference between groups. Operative times were longer for SILC (median = 57 vs. 47 min, p = 0.008), but mean LOS was similar (6.8 ± 4.2 h SILC vs. 6.2 ± 4.8 h TLC, p = 0.59). Operating room cost and encounter cost were similar. GIQLI scores were not significantly different preoperatively or at 2 or 4 weeks postoperatively. Patients reported higher satisfaction with wound appearance at 2 weeks with SILC. There were no differences in pain scores in recovery or in the first 48 h, although SILC patients required significantly more narcotic in recovery (19 mg morphine equivalent vs. 11.5, p = 0.03). CONCLUSIONS: SILC is a longer operation but can be done at the same cost as TLC. Recovery and pain scores are not significantly different. There may be an improvement in patient satisfaction with wound appearance. Both procedures are valid approaches to cholecystectomy.

Association between local indoor smoking ordinances in Massachusetts and cigarette smoking during pregnancy: a multilevel analysis.

OBJECTIVE: To estimate the association between local clean indoor air ordinances and prenatal maternal smoking across 351 municipalities in Massachusetts before the 2004 statewide ban and to test the effect of time since ordinance adoption on the association. METHODS: The authors linked 2002 birth certificate data of women who gave birth in the state and reported a Massachusetts residence (n=67,584) to a database of indoor smoking ordinances in all municipalities. Multilevel regression models accounting for individual- and municipality-level variables estimate the associations between the presence of local smoking ordinances, strength of the ordinances, time since ordinance adoption and prenatal smoking. RESULTS: Compared with those living in municipalities with no ordinances, women living in municipalities with a smoking ordinance had lower odds of prenatal smoking (OR=0.72, CI=0.53 to 0.98). No effect was found for 100% smoke-free ordinances. For the analyses testing the effect of time, pregnant women living in municipalities with ordinances enacted >2 years were less likely to smoke than those in municipalities with more recent (<1 year) ordinances. CONCLUSIONS: Preventing smoking among women of reproductive age is a public health priority. This study suggests that indoor smoking ordinances were associated with lower prenatal smoking prevalence and the favourable effect increased over time. Findings highlight the public health benefit of tobacco control policies.

Real-time monitoring of Salmonella enterica in free-range geese.

Free-range geese were sampled longitudinally and Salmonella isolates characterized to reveal highly diverging colonization dynamics. One flock was intermittently colonized with one strain of Salmonella enterica serovar Enteritidis from 2 weeks of age, while in another, S. enterica serovar Mbandaka appeared after 9 weeks, without dissemination but with multiple serovars appearing at later stages.

Single-incision laparoscopic cholecystectomy: a comparison with the gold standard.

BACKGROUND: Single-incision laparoscopic cholecystectomy (SILC) may be a comparable alternative to conventional multiport laparoscopic cholecystectomy (LC). This study compared procedural outcomes and costs between SILC and LC. METHODS: A retrospective review of patients undergoing SILC over an 8-month period was performed. A cohort of LC patients from the same surgeons over the preceding 8 months was used as historic controls. Demographics, comorbidities, diagnosis, operative data, pain control in the recovery room, complications, length of hospital stay, and cost were compared between the two groups. RESULTS: Of the 285 patients, 177 underwent LC and 108 underwent SILC. The mean age was 49.7 years for the LC patients and 48.2 years for the SILC patients (p = 0.44). Two of the LC patients underwent conversion to open surgery. None of SILC patients were converted to open procedure, although nine had additional ports placed. After multivariate adjustment, SILC was associated with a 15% longer operative time (p = 0.053) and a 66% shorter hospital stay (p = 006) than LC. Biliary dyskinesia and biliary colic were independently associated with shorter operative times and a reduced hospital stay. No significant differences were noted in pain score, narcotics used in the postanesthesia care unit (PACU), 30-day complication rates (1.7 vs 1.9%; p = 1), hospital charges, or cost between the two groups. CONCLUSIONS: Single-incision LC is safe, significantly reduces the hospital stay, and is an acceptable alternative to traditional LC. Although further study is warranted, initial results indicate that SILC may offer the most benefit for outpatient procedures.

Circadian rhythm and the influence of physical activity on circulating surfactant protein D in early and long-standing rheumatoid arthritis.

Surfactant protein D (SP-D) belongs to the collectin family and has pro-and anti-inflammatory capacities depending on its oligomerization. Previously, circulating SP-D was shown to be decreased in early rheumatoid arthritis (RA) and negatively correlated to disease activity. This study aimed at assessing the diurnal rhythmicity and the influence of physical activity on circulating SP-D in patients with RA at different stages compared with healthy individuals. Patients with early RA (ERA) with disease duration <6 months and with long-standing RA (LRA) with disease duration 5-15 years were included in two sub-studies. Healthy individuals served as controls. Diurnal variation: blood samples were collected every 3 h from 7 a.m to 10 p.m and the following morning. Physical activity: blood sampling was done before and after standardized physical challenge. SP-D was measured by ELISA. SP-D exhibited diurnal variation in healthy controls (n = 15) and in patients with ERA (n = 9) and LRA (n = 9) with peak values at 10 a.m. and nadir in the evening (controls: P < 0.001, ERA: P = 0.004 and LRA: P = 0.009). Three hours after cessation of physical activity, SP-D decreased below pre-exercise levels in both ERA (n = 10), LRA (n = 10) and controls (n = 13) (ERA: P < 0.001, LRA: P < 0.001 and controls: P = 0.005). In patients with RA, the decline was already observed 1 h post-exercise. Circulating SP-D exhibits diurnal variation both in patients with RA at different stages and in healthy controls. SP-D in serum decreases following physical activity in health and RA disease. This study underscores the need of standardized blood sampling conditions in future studies on SP-D.

Comparisons of abdominal wall reconstruction for ventral hernia repairs, open versus robotic.

The surgical complexities of our current population have pushed the technological limits of healthcare, urging for minimally invasive approaches. For ventral hernias, in particular, robotic assisted laparoscopic repairs have been met with conflict. Cost and longer operative times are among the arguments against robotic surgery, although thorough evaluation of patient outcomes could potentially advocate for use of this tool. We attempted to approach this by retrospectively reviewing our own data. We reviewed charts between September 2016 and February 2017 of patients receiving complex hernia repairs, either a standard open repair (SOR) or robotic-assisted repair (RAR). Data collected included preoperative, perioperative, and postoperative care. Of the 43 patients reviewed, 16 were SOR, versus 27 RAR. Patients were comparable in age, gender, BMI, diabetes as a comorbidity; average hernia defect size was similar between the two groups. Although operative times were longer in the RAR group, estimated blood loss (EBL) was less. Hospital stay was also shorter in the RAR group, at 3.0 ± 1.9 days versus 9.6 ± 8.4 days for the OAR group. Of those requiring critical care management, only one patient had a robotic assisted repair, versus half of the patients who received an open repair. Of the patients who presented to the emergency department within 30 days of surgery, each group had four patients, and two from the OAR group required admission. Our data is consistent with other literature supporting shorter lengths of stays. Although the robotic approach did required a longer operative time, the resulting improved patient outcomes support this technique for complex ventral hernia repairs.

Increasing antiviral activity of surfactant protein d trimers by introducing residues from bovine serum collectins: dissociation of mannan-binding and antiviral activity.

Collectins contribute to host defence through interactions with glycoconjugates on pathogen surfaces. We have prepared recombinant trimeric neck and carbohydrate recognition domains (NCRD) of collectins, and we now show that the NCRD of bovine conglutinin and CL-46 (like that of CL-43) have greater intrinsic antiviral activity for influenza A virus (IAV) than the human SP-D NCRD (hSP-D-NCRD). The three serum collectins differ from SP-D by having insertions adjacent to amino acid 325 and substitution of hydrophobic residues for arginine 343. We previously showed that a three amino acid (RAK) insertion, as found in CL-43, increases antiviral activity and mannan-binding activity of the hSP-D-NCRD, while the substitution of valine at 343, as in conglutinin, more strongly increased these activities. Mannan-binding activity of collectins has been considered to predict for ability to bind to high mannose glycans on viruses or other pathogens. We now show, however, that combined mutants containing the RAK insertion and R343V or R343I substitutions have greatly increased mannan-binding ability, but lower IAV binding or inhibiting activity than mutants containing R343V or R343I substitutions only. These findings indicate differences in the recognition of glycan structures of mannan and IAV by the NCRD and emphasize the importance of the flanking sequences in determining the differing interactions of human SP-D and bovine serum collectins with mannose-rich glycoconjugates on IAV and other pathogens. Of interest, we show conservation of some monoclonal antibody-binding epitopes between bovine collectin NCRD and hSP-D, suggesting shared structural motifs.

Phage typing of Salmonella Typhimurium - is it still a useful tool for surveillance and outbreak investigation?

Phage typing has for decades been useful as a phenotypical, definitive method for epidemiological characterisation of Salmonella Typhimurium. The system recommended by the World Health Organization (WHO) Collaborative Centre for phage typing of Salmonella has, however, become rather complex, and the present study illustrates the challenges of sufficient standardisation of the interpretation of lysis results to make sure that the same strain is assigned to the same phage type in different laboratories. Even though molecular typing methods will replace phenotypic characterisation methods in the future, it is our opinion that phage typing will remain for some time a useful tool to strengthen global Salmonella surveillance. Therefore, improved standardisation and quality assurance is essential to obtain a robust and harmonized method that allows comparison of results between laboratories.

Elevated plasma surfactant protein D (SP-D) levels and a direct correlation with anti-severe acute respiratory syndrome coronavirus-specific IgG antibody in SARS patients.

Pulmonary SP-D is a defence lectin promoting clearance of viral infections. SP-D is recognized to bind the S protein of SARS-CoV and enhance phagocytosis. Moreover, systemic SP-D is widely used as a biomarker of alveolar integrity. We investigated the relation between plasma SP-D, SARS-type pneumonia and the SARS-specific IgG response. Sixteen patients with SARS, 19 patients with community-acquired pneumonia (CAP) (Streptococcus pneumonia) and 16 healthy control subjects were enrolled in the study. Plasma SP-D and anti-SARS-CoV N protein IgG were measured using ELISA. SP-D was significantly elevated in SARS-type pneumonia [median (95% CI), 453 (379-963) ng/ml versus controls 218 (160-362) ng/ml, P < 0.05] like in patients with CAP. SP-D significantly correlated with anti-SARS-CoV N protein IgG (r(2) = 0.5995, P = 0.02). The possible re-emergence of SARS or SARS-like infections suggests a need for minimal traumatic techniques for following the alveolar compartment, e.g. during testing of antivirals. We suggest that monitoring systemic SP-D may be useful in monitoring the alveolar integrity in SARS-type pneumonia. The significant correlation between plasma SP-D and anti-SARS-CoV-specific antibodies support the role for SP-D in interlinking innate and adaptive immune pathways.

Occurrence and characterization of Salmonella enterica subspecies enterica serovar 9,12:l,v:- strains from Bulgaria, Denmark, and the United States.

In 2006, Salmonella enterica serovar I 9,12:l,v:- emerged in Bulgaria. The aim of this study was to characterize Salmonella serovar I 9,12:l,v:- isolates from Bulgaria, Denmark, and the United States. We compared isolates of Salmonella I 9,12:l,v:- and diphasic serovars with similar antigenic formulas by pulsed-field gel electrophoresis (PFGE) and antimicrobial susceptibility. The phase 2 flagellin gene (fljB) was also sequenced for selected isolates. By PFGE, the Salmonella I 9,12:l,v:- isolates from Bulgaria were indistinguishable from the isolate from the United States and distinct from isolates from Denmark; furthermore, several Salmonella I 9,12:l,v:- were indistinguishable from an isolate of Salmonella serovar Goettingen. Sequence analysis showed 100% sequence identity with known H:e,n,z15 sequences of Salmonella Goettingen, which has the antigenic formula I 9,12:l,v:e,n,z15. The study indicated that Salmonella I 9,12:l,v:- is a monophasic variant of Salmonella Goettingen and is present in different countries and on different continents.