Transatlantic spread of highly pathogenic avian influenza H5N1 by wild birds from Europe to North America in 2021.

Highly pathogenic avian influenza (HPAI) viruses of the A/Goose/Guangdong/1/1996 lineage (GsGd), which threaten the health of poultry, wildlife and humans, are spreading across Asia, Europe, Africa and North America but are currently absent from South America and Oceania. In December 2021, H5N1 HPAI viruses were detected in poultry and a free-living gull in St. John's, Newfoundland and Labrador, Canada. Our phylogenetic analysis showed that these viruses were most closely related to HPAI GsGd viruses circulating in northwestern Europe in spring 2021. Our analysis of wild bird migration suggested that these viruses may have been carried across the Atlantic via Iceland, Greenland/Arctic or pelagic routes. The here documented incursion of HPAI GsGd viruses into North America raises concern for further virus spread across the Americas by wild bird migration.

Sustained virological response following chronic hepatitis C treatment is associated with improvement in insulin resistance.

BACKGROUND: Insulin resistance (IR) is a key factor in the development of hepatic steatosis and fibrosis in chronic hepatitis C virus infection. Little is known about the impact of viral clearance on IR. AIM: The aim of this study was to determine the impact of viral clearance on IR. METHODS: Eighty-six patients treated according to standard clinical practice at an Australian teaching hospital between 2003 and 2007 were prospectively studied. Demographic, biochemical and histological data were collected. RESULTS: The mean pretreatment homeostatic model assessment-IR (HOMA-IR) was similar in the sustained virological response (SVR) and non-SVR groups (2.7 ± 0.5 and 2.8 ± 0.4, respectively), and both values were consistent with significant IR. There was a significant improvement in HOMA-IR (from 3.0 ± 1.0 to 2.2 ± 0.5, P = 0.04) at the end of treatment in the SVR group only. This trended towards significance at 6 months post-treatment. Multiple regression analysis found improvement in both gamma-glutamyl transpeptidase and alanine aminotransferase predicted improvement in HOMA-IR when controlled for other potential factors (P = 0.01). CONCLUSIONS: Hepatitis C virus clearance is associated with improvement in IR. Although baseline hepatic fibrosis is a predictor of IR, changes in IR appear to be independent of changes in liver fibrosis. Treatment-related improvement in gamma-glutamyl transpeptidase and alanine aminotransferase seen with improved IR may be a possible marker of reduction of hepatic oxidative stress.

Altered temporal characteristics of the rectoanal inhibitory reflex in patients with abdominal distension.

The rectoanal inhibitory reflex (RAIR) is important in gas and stool evacuation. We examined RAIR features in patients with chronic constipation who exhibited bloating with and without abdominal distension, to determine whether alterations in RAIR may be a factor in the pathogenesis of abdominal distension. Seventy-five female patients with chronic constipation with or without abdominal distension were included in the study. The presence or absence of abdominal distension was assessed according to the Rome II questionnaire. All patients underwent both RAIR and rectal sensitivity testing, and specific RAIR parameters were analyzed. Patients were divided into two groups: abdominal bloating with distension (D, n = 55) and abdominal bloating without distension (ND, n = 20). D had a longer time to the onset of anal sphincter inhibition (latency of inhibition) (P = 0.03) compared with ND. In logistic regression analysis, a combination of age, latency of inhibition and the time measured from onset of inhibition to the point of maximum inhibition predicted abdominal distension (P = 0.002). There were no differences between groups for the time from point of maximum inhibition to recovery and for the percentage of internal anal sphincter relaxation. This is the first study to examine the role of RAIR in patients with abdominal distension. Female patients with constipation and abdominal distension exhibited differences in the temporal characteristics of, but not in the degree of, anal sphincter relaxation compared with patients without distension. Since this study was uncontrolled, further studies are necessary to determine the contribution of altered anorectal reflexes to abdominal distension.

Estimation of lean body weight in older women with hip fracture.

OBJECTIVE: Lean body weight (LBW) decreases with age while total body fat increases, resulting in altered drug pharmacokinetics. A semi-mechanistic equation estimating LBW using height, weight and sex has been developed for potential use across a wide range of body compositions. The aim of this study was to determine the ability of the LBW equation to estimate dual energy x-ray absorptiometry-derived fat free mass (FFM(DXA)) in a population of older women with recent hip fracture. METHODS: Baseline, four and 12 month data obtained from 23 women enrolled in the Sarcopenia and Hip Fracture study were pooled to give 58 measurements. LBW was estimated using the equation: LBW (kg) = (9270 x Wt) / (8780 + (244 x BMI)). Body composition was classified as: 'normal' (BMI <25kg/m(2) and not sarcopenic), 'overweight-obese' (BMI >25kg/m(2) and not sarcopenic), 'sarcopenic' (sarcopenic and BMI <25kg/m(2)), or 'sarcopenic-obese' (sarcopenic and BMI >25kg/m(2)). The ability of the LBW equation to predict FFMDXA was determined graphically using Bland-Altman plots and quantitatively using the method of Sheiner and Beal. RESULTS: The mean ± SD age of female participants women was 83±7 years (n=23). Sarcopenia was frequently observed (65.2%). Bland-Altman plots demonstrated an underestimation by the LBW equation compared to FFMDXA. The bias (95% CI) and precision (95% CI) calculated using the method of Sheiner and Beal was 0.5kg (-0.7, 1.66kg) and 4.4kg (-3.7, 12.4kg) respectively for pooled data. CONCLUSION: This equation can be used to easily calculate LBW. When compared to FFMDXA, the LBW equation resulted in a small underestimation on average in this population of women with recent hip fracture. The degree of bias may not be clinically important although further studies of larger heterogeneous cohorts are needed to investigate and potentially improve the accuracy of this predictive equation in larger clinical cohorts.

Prolonged balloon expulsion is predictive of abdominal distension in bloating.

OBJECTIVES: Abdominal bloating and distension are common in patients with constipation. The precise mechanism of abdominal distension remains uncertain. We hypothesized that constipated patients with bloating plus distension exhibit a greater degree of anorectal dysfunction, potentially affecting gas evacuation, than those without distension. Therefore, our aim was to evaluate anorectal function and other clinical features in patients with constipation who exhibit bloating with and without distension. METHODS: In all, 88 female patients with abdominal bloating and either non-diarrhea irritable bowel syndrome (IBS) or functional constipation were included in the study. The presence or absence of abdominal distension was assessed according to the Rome II questionnaire, and all patients underwent comprehensive clinical assessment and anorectal function studies. RESULTS: Patients were divided into two groups: abdominal bloating with distension (D; n=53) and abdominal bloating without distension (ND; n=35). D featured a prolonged balloon expulsion time (P=0.005), a higher resting anal sphincter pressure (P=0.002), and a higher maximum anal sphincter squeeze pressure (P=0.015) than ND. They also experienced more bloating (P<0.001), more abdominal pain (P=0.004), harder stools (P=0.01), and more incomplete emptying (P=0.005). In logistic regression modeling, prolonged balloon expulsion time was a significant predictor of abdominal distension (P=0.018). CONCLUSIONS: This is the first study to show that prolonged balloon expulsion time predicts abdominal distension in patients with bloating and constipation. Hence, ineffective evacuation of gas and stool associated with prolonged balloon expulsion may be an important mechanism underlying abdominal distension.

Evidence for pelvic floor dyssynergia in patients with irritable bowel syndrome.

PURPOSE: Although functional constipation is known to often manifest concomitant features of pelvic floor dyssynergia, the nature of pelvic floor symptoms and anorectal dysfunction in non-diarrhea predominant irritable bowel syndrome is less clear. This study aims to compare anorectal sensorimotor function and symptoms of patients who have non-diarrhea predominant irritable bowel syndrome with those who have functional constipation. METHODS: We studied 50 consecutive female patients referred with constipation and 2 or more symptoms of pelvic floor dyssynergia, who also satisfied Rome II criteria for either non-diarrhea predominant irritable bowel syndrome (n = 25; mean age, 47 +/- 3 y) or functional constipation (n = 25; 49 +/- 3 y). Assessments included the Rome II Integrative Questionnaire, a validated constipation questionnaire, Hospital Anxiety and Depression scale, visual analog scores for satisfaction with bowel habit and for impact on quality of life, and a comprehensive anorectal physiology study. RESULTS: Both groups displayed physiological evidence of pelvic floor dyssynergia; but patients with non-diarrhea predominant irritable bowel syndrome exhibited a higher prevalence of abnormal balloon expulsion (P < .01) and less paradoxical anal contraction with strain (P = .045) than patients with functional constipation. These patients with irritable bowel syndrome also reported more straining to defecate (P = .04), a higher total constipation score (P = .02), lower stool frequency (P = .02), a trend toward harder stools (P = .06), and less satisfaction with bowel habit (P = .03) than patients with functional constipation. CONCLUSION: Patients with non-diarrhea predominant irritable bowel syndrome with symptoms of pelvic floor dyssynergia exhibit overall pelvic floor dyssynergia physiology similar to that of patients with functional constipation. Certain features, however, such as abnormal balloon expulsion, may be more prominent in the patients with irritable bowel syndrome. Therapeutic modalities, such as biofeedback, that are effective in patients with functional constipation with pelvic floor dyssynergia should therefore be considered in selected patients with irritable bowel syndrome with pelvic floor dyssynergia.

Colorectal responses to distension and feeding in patients with spinal cord injury.

The role of the central nervous system in enteroenteric motor reflexes remains controversial. Our aims were as follows: 1) to evaluate colorectal, rectocolic, gastrocolonic, and gastrorectal reflex responses in patients with cervical spinal cord injury (SCI) and 2) to compare these responses with those in healthy subjects. In six patients with SCI (5 male, 42 +/- 4 yr) and six healthy control subjects (5 male, 36 +/- 5 yr), 2-min phasic distensions were performed randomly via dual-barostat balloons in the colon and rectum. Continuous colonic and rectal balloon volumes were recorded during distensions and after a 1,000-kcal liquid meal. Mean balloon volumes were recorded before, during, and after phasic distensions and over 60 min postprandially. The colorectal response was similar in control subjects and SCI patients (rectal volume reduction = 28 +/- 11% and 15 +/- 5% in SCI patients and healthy subjects, respectively); the rectocolic response was variable. The gastrocolonic response was present in all subjects (colonic volume reduction = 49 +/- 4% and 44 +/- 3% in SCI patients and healthy subjects, respectively), with a time effect in the first 30 min (P < 0.0001) and a group effect in the second 30 min (P < 0.004). The gastrorectal response was present in four SCI patients and five healthy subjects (rectal volume reduction = 38 +/- 4% and 41 +/- 3% in SCI patients and healthy subjects, respectively), with a time effect in the first 30 min (P < 0.0001) but no group effect in the second 30 min. Intact neural transmission between the spinal cord and higher centers is not essential for normal colorectal motor responses to feeding and distension; however, a degree of central nervous system and neurohormonal modulation of these responses is likely.

Immunity of cattle following vaccination with a Mannheimia haemolytica chimeric PlpE-LKT (SAC89) protein.

UNLABELLED: We developed several chimeric PlpE-leukotoxin (LKT) constructs containing the major epitope of Mannheimia haemolytica outer membrane lipoprotein PlpE (epitope R2) and the neutralizing epitope of M. haemolytica LKT (NLKT) [Ayalew et al. Mannheimia haemolytica chimeric protein vaccine composed of the major surface-exposed epitope of outer membrane lipoprotein PlpE and the neutralizing epitope of leukotoxin. Vaccine 2008;26(38):4955-61]. Vaccination of mice with these PlpE-LKT chimeric proteins stimulated anti-PlpE antibodies that caused complement-mediated bacteriolysis of M. haemolytica as well as neutralizing anti-LKT antibodies. Chimeric protein SAC89, which contains two copies of R2 and two copies of NLKT, generally stimulated the best overall responses in mice. The objectives of the current study were: (1) to determine through a dose titration study if vaccination of cattle with SAC89 stimulated antibodies to both PlpE and LKT and (2) evaluate SAC89-induced immunity against experimental M. haemolytica challenge of cattle. In the dose titration study, vaccine doses ranged from 100 to 400 microg. SAC89 significant anti-M. haemolytica surface and LKT antibodies were detected following vaccination with each dose. The vaccination/challenge study was conducted with 30 weaned beef cattle distributed among four groups: Control (no vaccine), 100 microg SAC89, M. haemolytica Bacterin, and SAC89+M. haemolytica bacterin. On day 42 after two vaccinations, cattle were challenged transthoracically with M. haemolytica. There was significant reduction (p<0.05) in lesion scores for the SAC89+bacterin-vaccinated group (74.6% reduction compared to control lesion scores) when compared to the other groups (34.7% and 35.6% reduction compared to control lesion scores). Evaluation of antibody responses demonstrated that the control group failed to develop antibody responses to M. haemolytica surface antigens or to LKT. Bacterin-vaccinated cattle developed anti-M. haemolytica antibodies after the second vaccination. SAC89- and SAC89+bacterin-vaccinated groups developed significant antibody responses 14 days after the first vaccination and further significant increases in antibodies after the second vaccination. CONCLUSIONS: Vaccination with the chimeric protein SAC89 in conjunction with a M. haemolytica bacterin stimulated significant protection against a severe transthoracic challenge with the bacterium.

Photopolymerized hydrogel carriers for live vaccine ballistic delivery.

Photopolymerized poly(ethylene glycol) (PEG)-crosslinked hydrogels were assessed for their ability to serve as a payload vehicle to deliver a viable bacterial vaccine (Brucella abortus strain RB51 (RB51) to bison in Yellowstone National Park) ballistically using thermoplastic degradable Biobullets. PEG modified with degradable glycolide or lactide oligomers capped with photopolymerizable methacrylate groups served to crosslink the hydrogel vaccine carrier inside commercial hydroxypropylcellulose Biobullets. Release of 1 microm diameter model fluorescent particles from hydrogels followed known degradation trends for glycolide- and lactide-modified PEG hydrogels. All particles were released from PEG-co-glycolide hydrogels after approximately 10 days and PEG-co-lactide hydrogels after approximately 45 days following gel degradation. Minimal particle release was observed from pure PEG dimethacrylate hydrogels over 40 days. P. aeruginosa (strain PAO1) and RB51 live vaccines exhibit excellent viability following exposure to photopolymerization encapsulation within these gel matrices. Hydrogels photopolymerized into the payload chamber of Biobullets exhibit similar ballistic properties to commercially available Biobullets and penetrate and remain intact when fired intramuscularly into live elk for release of their gel payload in the host.

Effects of 20-mg oestradiol implant therapy on bone mineral density, fat distribution and muscle mass in postmenopausal women.

This 64-week prospective cohort trial evaluated the effects of 20-mg oestradiol implants, replaced every 4 months, in healthy postmenopausal women aged 45-65 years. Of 20 implant and 14 control subjects who remained in the trial at 32 weeks, 13 implant and seven controls continued to 64 weeks, with no baseline differences between completing and dropout subjects. At 64 weeks, implant subjects displayed increases of 5.4-7.6% in spine and hip bone mineral density ( p<0.05 versus controls). The abdominal fat-to-lean soft tissue ratio decreased by 18% in implant subjects ( p<0.001), but did not change in controls ( p<0.05 implants versus controls). Neither group displayed significant changes in weight, %fat or appendicular skeletal muscle mass. The 32-week data were consistent with these results. Hence, oestradiol implant therapy can reduce abdominal adiposity and could lower the risk of obesity-related metabolic disorders.

Body composition of Aboriginal Australian women: comparison with age-matched Caucasians.

Although Aboriginal Australians (AA) exhibit an android fat deposition profile and suffer from a high incidence of type 2 diabetes, a comprehensive body composition assessment of AA has not yet been reported. The body composition of 16 non-diabetic AA women and 16 healthy age- and weight-matched Caucasian women (C) showed no significant ethnic differences in height, total body bone mineral density, total and appendicular skeletal muscle mass, and % fat. The abdominal fat-to-lean soft tissue ratio correlated more highly with age in AA ( r=0.79, p<0.001) than in C ( r=0.59, p<0.05) and with % fat in AA ( r=0.67, p<0.01) than in C ( r=0.54, p<0.05). However, analysis of variance showed that the difference between the two ethnic groups was not significant. Key findings are that dual-energy X-ray absorptiometry can accurately assess adiposity, and that hip girth should emerge as a valid predictor of central adiposity, in AA women.

Esophageal dysmotility and acid sensitivity in patients with mitral valve prolapse and chest pain.

Mitral valve prolapse (MVP) patients often experience non-cardiac chest pain. The aims of this study were to determine, in patients with non-cardiac chest pain: (i) whether esophageal dysmotility is more common in patients with MVP than in patients without MVP; and (ii) if acid sensitivity is an important cause of the chest pain in MVP patients. Esophageal manometry and acid perfusion testing were performed in 277 consecutive patients with non-cardiac chest pain. Patients with MVP (13 female, one male; mean age 49 years) were more likely (P = 0.01) to have esophageal dysmotility, while acid perfusion was less likely (P < 0.05) to provoke their chest pain, than in patients without MVP. The most common esophageal motor abnormalities detected in patients with and without MVP were diffuse esophageal spasm (prevalence, 57%) and non-specific motor disorder (prevalence, 9%), respectively. This study, the first large prospective series examining possible esophageal sensorimotor correlates of chest pain in MVP patients, demonstrates that in the absence of a cardiac cause for chest pain, a specific esophageal motility disorder should be excluded, rather than assuming the chest pain is likely to be due to acid sensitivity.

Total body protein in chronic diseases and in aging.

Substantial losses of total body protein (TBP) can occur in chronic diseases and in aging. Such losses impact negatively on immunity and quality of life, and on growth rates in children. Direct measurements of total body nitrogen (TBN) monitor the integrated changes in TBP over time and allow comparison with normal subjects. TBN assessment via neutron capture analysis is therefore the gold-standard method of TBP estimation, so that risk factors for protein deficit can be identified and patient management optimized. The nitrogen index (NI) can be used to predict prognostic outcome: an NI < 0.9 is associated with substantial wasting in HIV disease, an NI < 0.8 predicts significant pathophysiology in chronic renal failure, and a low NI is predictive of neutropenia in breast-cancer patients. These findings emphasize the central importance of adequate protein stores in recovery from disease or in maintaining quality of life. Aging appears to involve a gradual loss of TBP throughout adulthood. Cross-sectional data suggest that TBP declines curvilinearly with age, such that there is an accelerated decline after 65 years of age. However, longitudinal data are scarce, and little is known about the relative loss of visceral protein, as opposed to skeletal muscle protein. More clearly-defined data are essential if the effects of aging per se are to be separated from the effects of chronic disease. A further complication is the knowledge that physical activity also declines with age. Thus sarcopenia, the loss of skeletal muscle mass, could primarily result from disuse rather than aging. The economic impact of unsuccessful aging places a pressing need for multicompartment data in longitudinal study designs.

Plasma sample preparation by ultrafiltration for FTIR analysis.

Total body water (TBW) may be significantly altered with disease. Isotope dilution techniques, considered to be the "gold standard" methods for measuring TBW, are expensive, time consuming and require considerable expertise, especially during the sample preparatory phase. In this study, a new method, ultrafiltration (UF), was hypothesised to be an efficient alternative to vacuum sublimation (VS) in the preparation of plasma samples for Fourier Transform Infra Red (FTIR) determination of TBW. Deuterium Oxide (D2O) concentrations were prepared in human plasma and subjected to both techniques. FTIR analysis was carried out on the resulting VS and UF solutions and on D2O concentrations in distilled water. The resulting absorbance values were then statistically compared. Urea concentrations prepared in D2O-containing plasma were also compared to "blank" plasma to investigate the effect of high plasma urea concentration on the resulting H2O/D2O mixture obtained during UF Paired t-tests showed that the VS plasma samples (p=0.003), but not the UF samples (p=0.9), were significantly different to D2O standards prepared in distilled water. While there was no evidence of an effect of urea on UF at low (0.4 g/L) D2O concentration, a marginal (p=0.04) effect occurred at a higher (1.6 g/L) D2O level. Throughput of samples was much more efficient with the UF technique. These findings indicate that the new UF method is an accurate, more efficient method of plasma sample preparation than the VS method in the FTIR determination of TBW.

Strategic planning: the basics and benefits.

Strategic planning can help a medical practice take an honest look at itself in light of the changes taking place in its environment and within the practice itself. The objective is for the group to design a plan, or road map, to its envisioned future. For medical practices, strategic planning is a four part process: 1) gaining buy-in for the process itself from the leadership and physicians; 2) gathering pertinent data about the group's environment through external resources, and about the group itself through interviews and surveys of physicians; 3) conducting a facilitated off-site retreat of key physicians and leaders in order to review data, discuss issues and develop a one to two year action plan; and, 4) carrying out the action plan developed at the retreat and measuring its outcomes. A follow-up mini-retreat about six months after the first retreat is highly recommended, as is instituting a process of sharing of the results and outcomes of the plan with all members of the organization.

Determination of skeletal muscle and fat-free mass by nuclear and dual-energy x-ray absorptiometry methods in men and women aged 51-84 y (1-3).

BACKGROUND: Skeletal muscle mass (SMM) and fat-free mass (FFM) are important variables in nutritional studies. Accurate techniques for measuring these variables have not been thoroughly validated in elderly subjects. OBJECTIVES: The objectives of this study were to 1) compare SMM values derived from dual-energy X-ray absorptiometry (DXA) with those calculated by a nuclear method from total body potassium (TBK) and total body nitrogen (TBN) measurement (both: KN) in older subjects, and 2) assess the accuracy of FFM measurement by DXA in these subjects. DESIGN: TBK, TBN, DXA (model XR36; Norland, Fort Atkinson, WI), bioimpedance, and anthropometric measurements were performed on healthy women (n = 50) and men (n = 25) aged 51-84 y. RESULTS: Mean SMM by KN was not significantly different from SMM by DXA in either sex. SMM by KN predicted SMM by DXA with an SEE of 2.1 kg (r = 0.95, P < 0.0001 for women and men together). In the men, FFM by DXA agreed well with FFM estimated by TBK, skinfold thicknesses, bioimpedance analysis, and a multicompartment model. In women, FFM by DXA was 4-5 kg less than that by the other methods (P < 0.01). Truncal fat was related to intermethod FFM differences (r = 0.58, P < 0.0001). CONCLUSIONS: These data indicate that 1) either the nuclear or the DXA method can be applied to estimate SMM in healthy older subjects, and 2) the Norland DXA instrument significantly underestimates FFM in older women, in part, because of the influence of truncal adiposity.

Detection of Staphylococcus aureus in milk by use of polymerase chain reaction analysis.

OBJECTIVE: To evaluate polymerase chain reaction (PCR) analysis for detection of Staphylococcus aureus (nuc gene) in fresh and formalin-preserved milk. SAMPLE POPULATION: Samples from 80 lactating sheep and 100 lactating dairy cows. PROCEDURE: 4 lactating sheep were inoculated with S aureus by intramammary infusion. A set of primers specific for the nuc gene of S aureus was used to develop a PCR technique, and modification of the rapid boil method was used to isolate bacterial DNA. Milk was obtained from experimentally infected sheep before and after infusion with S aureus, and from the 100 cows and remaining 76 sheep. Samples were screened by bacteriologic culture and PCR. To validate the PCR assay, S aureus or other pathogens were added to distilled water and "normal" sheep milk samples, with and without formalin. RESULTS: The PCR assay was 100% specific for S aureus when known negative and positive samples were tested. Sensitivity was 100% for samples with added S aureus or other pathogens. Sensitivity was lower for samples obtained from experimentally infected sheep, but increased from 53% to 90% with increased washing of target DNA. CONCLUSIONS: The PCR technique based on the nuc gene is able to detect S aureus in sheep milk yields results faster than does traditional culturing, is highly specific, and is able to detect S aureus in formalin-fixed milk samples. CLINICAL RELEVANCE: The assay is particularly suitable for analysis of samples shipped or stored without refrigeration. Although antibiotics in milk may inhibit growth in culture, they should not affect the results of the PCR assay.