COVID-19 exposure and diagnosis among college student drinkers: links to alcohol use behavior, motives, and context.

The COVID-19 pandemic is a public health crisis. College student alcohol use is highly prevalent and primarily occurs in social settings where risk for COVID-19 transmission is heightened. This study explored the associations between alcohol use frequency, quantity, motives, and context with: (i) quarantine due to COVID-19 exposure and (ii) a positive diagnosis for COVID-19. A sample of n = 409 college student drinkers completed an online survey about their health and behaviors during the Fall 2020 semester. Since the start of the semester, 36% of students quarantined and 13% of students received a COVID-19 diagnosis. More frequent alcohol use was associated with increased odds of both quarantine and COVID-19 diagnosis. More frequent drinking for social motives was associated with increased likelihood of quarantine, and more frequent drinking for conformity motives was associated with increased likelihood of COVID-19 diagnosis. Participants who often drank alone or with a small group of friends were about half as likely to have quarantined, while those who often drank with a large group of friends were almost twice as likely to have quarantined. Participants who often drank in a bar or nightclub had almost three times the odds of a COVID-19 diagnosis. Frequent alcohol use and drinking for social and conformity motives and in certain contexts are linked to increased likelihood of COVID-19 exposure and diagnosis. Alcohol use prevention efforts, coupled with messaging to discourage large social gatherings in public places, might help to mitigate the spread of COVID-19 among college students.

Traumatic pedestrian and bicyclist injuries associated with intoxication.

BACKGROUND: Drug and alcohol use are risk factors for trauma among operators of motor vehicles and contribute to trauma in pedestrians and bicyclists. We describe the prevalence of drug and alcohol use and clinical consequences in a cohort of pedestrians and bicyclists with trauma. METHODS: We analyzed a 25-month data set of 916 trauma team activations from January 2017-January 2019 at an urban, level I trauma center. Blood ethanol levels and urine toxicology screens were obtained in 94 pedestrian and bicyclist trauma activations. We compared pedestrians or bicyclists with a positive urine or blood screen (n = 69) to those with negative screens (n = 25). We conducted a retrospective chart review to determine mechanism of injury, injury pattern, and disposition from the emergency department (ED). RESULTS: Overall, 38 (55%) of injured patients with positive screen were pedestrians and 31 (45%) were bicyclists. Fentanyl was the most commonly detected drug (n = 38; 40%), followed by opiates (n = 27; 29%), and tetrahydrocannabiol (THC) (n = 23; 25%). Twenty-one patients were positive for ethanol. Pedestrians and bicyclists with positive toxicology screens were significantly more likely to sustain fractures (p < .01), require an operative procedure (p < .05), or intensive care unit admission (p < .05). CONCLUSION: Our study builds on previous literature which suggests that intoxicated bicyclists and pedestrians suffer frequent and more severe injury than their sober counterparts. Public health campaigns should educate bicyclists and pedestrians about the risks of cycling or walking in areas of road traffic while under the influence of alcohol or illicit drugs.

Training method for animal-based measures in dairy cattle welfare assessments.

Quantitative assessments of animal welfare are increasingly being used in the dairy industry. It is important to have good precision and accuracy within and among assessors. This study explored the effectiveness of a 3-d training workshop for animal-based measures (ABM) of welfare in dairy cows, in which 14 people were trained to evaluate 6 ABM, specifically hock injuries (HI), lameness (LM), body condition score (BCS), and udder, flank, and leg cleanliness (collectively CLN). All scoring systems were modified to a dichotomous outcome, acceptable or unacceptable. Acceptable HI included no swelling or hair loss, unacceptable HI included swelling or scab; acceptable BCS was >2 on a 5-point scale, unacceptable BCS was ≤2. Acceptable CLN was up to minor splashing, unacceptable CLN was distinct plaques to a solid manure plaque. Lameness was evaluated using locomotion score or in-stall lameness score (SLS) in tiestalls; unacceptable LM was ≥3 (lameness score) on a 5-point scale, where 3 equals mild lameness or ≥2 of 4 behavioral in-stall lameness score indicators were detected. Classroom instruction took place on d 1 of training. Day 2 consisted of group assessment of LM (n = 25 cows), and HI, CLN, and BCS (n = 30 cows), and individual assessment of HI, CLN, and BCS (n = 20 cows) were performed. Day 3 included individual assessments of HI, CLN, and BCS (n = 33 cows), and individual video assessment of LM (n = 27 cows). An additional training video for LM was sent to trainees 3 wk after the workshop, and another follow-up assessment of LM took place via video (n = 37 cows). Repeatability and accuracy of the trainees was assessed using Fleiss's κ (FK) and Byrt's κ (BK) to examine group-level inter-rater agreement and expert-trainee agreement, respectively. The kappa systems use a scale of poor (<0), slight (0.01 to 0.20), fair (0.21 to 0.40), moderate (0.41 to 0.61), substantial (0.61 to 0.80), or almost perfect (0.81 to 1.00). At the conclusion of the workshop, FK was 0.66 for HI and 0.43 for LM, and BK mean (and range) was 0.85 (0.63 to 1.00) for HI and 0.66 (0.56 to 0.85) for LM. Each trainee achieved perfect agreement for BCS [BK mean = 1.00 (1.00 to 1.00)] and each trainee achieved almost perfect agreement for CLN [BK mean 0.90 (0.82 to 0.94)]. After the follow-up video and 3 wk of experience, trainees achieved a FK of 0.66 and a BK mean of 0.74 (0.62 to 0.89) for LM. In conclusion, multiple assessors can achieve substantial agreement for ABM with adequate training.

Technical note: Assessing lameness in tie-stalls using live stall lameness scoring.

Video stall lameness scoring (SLS) has been shown to be comparable to video locomotion scoring for evaluating lameness in dairy cows housed in tie-stalls and may be a more practical and easier method to measure lameness in a herd. We compared live SLS to video SLS and to live locomotion scoring. A total of 685 lactating cows subsampled from 27 commercial dairy herds were examined for lameness through live and video SLS. Cows scored with the live or video SLS system were scored for 4 behavioral indicators while still in their stall: weight shifting (shift), standing on the edge of the stall (edge), uneven weight bearing while standing (rest), and uneven weight bearing while moving from side to side (uneven). Two observers live scored and video scored for SLS. Lameness prevalence from video SLS and live SLS were similar (31 vs. 30%, respectively). Prevalence of the behavioral indicators varied from 0.59 to 58.2%. Sensitivity and specificity of live SLS was calculated using video SLS as the gold standard for lameness detection in tie-stalls. Sensitivity of live SLS was 0.83 and specificity was 0.94. False positives and false negatives for lameness were 14.4 and 16.8%, respectively. When comparing the prevalence of lameness measured through video or live SLS at the herd level, live SLS for lameness was correlated to video SLS (r = 0.91) with a Cohen's kappa coefficient of 0.79 (95% confidence limit = 0.73-0.84). Average exact agreement in the behavior indicators observed ranged from 80 to 100%. A subsample of 250 cows from 5 herds were scored for live SLS and live locomotion by a third observer. Intra- and interobserver reliability for live SLS and live locomotion scoring were found to have a kappa coefficient of 0.53 (95% confidence limit = 0.43-0.64) when determining a cow as lame through SLS or locomotion scoring. Live SLS was correlated with live locomotion scoring (r = 0.92). However, lameness prevalence was lower when using live SLS (28.4%) compared with locomotion scoring (38%). In summary, live SLS may be an acceptable method to replace video SLS to identify lame cows and rank tie-stall herds in terms of lameness prevalence without having to remove the cows from their stalls or view videos to score; however, it may underestimate lameness prevalence compared with locomotion scoring methods.

Effect of following recommendations for tiestall configuration on neck and leg lesions, lameness, cleanliness, and lying time in dairy cows.

Cow comfort in tiestalls is directly affected by stall dimensions, for which some recommendations exist. To evaluate how well Canadian dairy farms with tiestalls complied with recommendations for stall dimensions, as well as the effect of compliance on cow comfort and cleanliness, we assessed lactating Holstein cows (n = 3,485) on 100 tiestall dairy farms for neck and leg lesions, lameness, and cleanliness and measured time spent lying down. Data on stall dimensions (width and length of the stall, position and height of the tie rail, length of the chain, and height of the manger curb) were recorded for each cow. The majority of cows were housed in stalls smaller than recommended. The prevalence of lesions and lameness was high (neck, 33%; knee, 44%; hock; 58%, lameness, 25%) and the prevalence of dirtiness was low (udder, 4%; flank, 11%; legs, 4%). Chains shorter than recommended increased the risk of neck, knee, and hock lesions. A tie rail further back in the stall than recommended increased the risk of neck, knee, and hock lesions and reduced the frequency of lying bouts and the risk of a dirty udder. A tie rail set lower than recommended decreased the risk of neck lesions and lameness and increased lying time and lying bout frequency. Stalls narrower in width than recommended increased the risk of neck injuries and lameness and reduced the daily duration of lying time and the risk of a dirty flank and legs. Stalls shorter in length than recommended increased the risk of knee lesions and reduced lying bout frequency and the risk of a dirty udder. The majority of farms do not follow recommendations for stall dimensions (with the exception of tie rail height), and the lack of compliance is associated with increased risk of lesions and lameness and can affect lying time. Recommended stall dimensions tend to reduce cleanliness, but the prevalence of dirty cows remains very low.

A comparison of the effects of medical Qigong and standard exercise therapy on symptoms and quality of life in patients with advanced cancer.

PURPOSE: Patients with advanced cancer frequently experience anxiety, depression and poor quality of life (QOL), as well as physical symptoms such as fatigue and weakness. Physical exercise has potential to help control these symptoms but the optimal training prescription is still not clear. We performed a study comparing medical Qigong (QG) and standard endurance and strength training (SET) in patients with advanced stage non-small cell lung (NSCLC) and gastrointestinal (GI) cancers. METHODS: A randomized, cross-over study was performed in patients with advanced NSCLC and GI cancers receiving or eligible for chemotherapy. Patients received supervised QG or SET twice-weekly for 6 weeks. Psychological functioning, QOL, symptoms and physical functioning were assessed before and after each intervention period. RESULTS: Nineteen patients completed both interventions. Comparing interventions revealed no difference between QG and SET on change in anxiety or depression scores or QOL. However, SET treatment was better at improving perceived strength (P = 0.05) and walking distance (P = 0.02). The order in which interventions were performed had a significant impact on the improvement in certain symptoms (sleep quality, breathlessness, P < 0.05), QOL (P = 0.01) and walking distance (P = 0.008). In all cases, the beneficial effects of the exercise interventions were markedly reduced during the second interval. CONCLUSIONS: QG and SET are equivalent in their impact on many aspects of psychological function in cancer patients. However, SET leads to greater improvements in exercise capacity and helps reduce some symptoms. The reduction in beneficial effect of SET on exercise function when offered as the second intervention is a new finding that warrants further study.

Reasons for Electronic Nicotine Delivery System use and smoking abstinence at 6†months: a descriptive study of callers to employer and health plan-sponsored quitlines.

OBJECTIVE: Describe cigarette smoking abstinence among employer and health plan-sponsored quitline registrants who were not using Electronic Nicotine Delivery Systems (ENDS), were using ENDS to quit smoking or were using ENDS for other reasons at the time of quitline registration. METHODS: We examined 6029 quitline callers aged ≥18 years who smoked cigarettes at registration, and completed ≥1 counselling calls, baseline ENDS use questions and a 6-month follow-up survey (response rate: 52.4%). 30-day point prevalence smoking quit rates (PPQRs) were assessed at 6-month follow-up (ENDS-only users were considered quit). Data were weighted for non-response bias. Logistic regression analyses controlled for participant characteristics and programme engagement. RESULTS: At registration, 13.8% of respondents used ENDS (7.9% to quit smoking, 5.9% for other reasons). 30-day PPQRs were: 55.1% for callers using ENDS to quit, 43.1% for callers using ENDS for other reasons, and 50.8% for callers not using ENDS at registration. Callers using ENDS for other reasons were less likely to quit than other groups (adjusted ORs=0.65-0.77); quit rates did not significantly differ between non-ENDS users and those using ENDS to quit. Among callers using ENDS to quit at baseline, 40% used ENDS regularly at follow-up. CONCLUSIONS: ENDS users not using ENDS to quit smoking were less successful at quitting at 6-month follow-up compared with callers using ENDS to quit smoking and callers who did not use ENDS at programme registration. Incorporating reasons for ENDS use may be important for future studies examining the role of ENDS in tobacco cessation.

Prevalence of and risk factors for hock and knee injuries on dairy cows in tiestall housing in Canada.

Leg injuries on dairy cows are a common and highly visible welfare concern on commercial dairy farms. With greater attention being placed on food animal welfare and limited research being conducted on tiestall farms, this study aimed to identify prevalence and risk factors for hock and knee injuries on dairy cows housed in tiestall barns in Ontario (n=40) and Quebec (n=60). A sample of 40 cows was purposively selected per farm and several animal- and farm-based measures were taken. Both hocks and both knees on each cow were scored as injured (presence of lesions or swelling) or not injured (no alterations or hair loss), and the highest score of each of the 2 knees and the 2 hocks was considered the cow's hock or knee score. Possible animal- and farm-based risk factors were incorporated into 2 separate multivariable logistic models for hock injuries and knee injuries respectively at the cow level. Mean (±SD) percentage of cow with hock injuries per farm was found to be 56±18% and mean percentage of knee injuries per farm was found to be 43±23%. Animal-based factors found to be associated with a greater odds of hock injuries at the cow level were increased days in milk (DIM), lower body condition score (BCS), lameness, higher parity, higher cow width, median lying bout duration, and median number of lying bouts. Environmental factors found to be associated with hock injuries at the cow level were province, stall width, tie rail position, stall base, chain length, and age of stall base. Animal-based factors found to be associated with knee injuries at the cow level were DIM, BCS, and median lying time. Environmental factors found to be associated with knee injuries at the cow level were stall width, chain length, province, stall base, and bed length. Quadratic and interaction terms were also identified between these variables in both the hock and knee models. This study demonstrates that hock and knee injuries are still a common problem on tiestall dairy farms in Canada. Several animal- and housing-based factors contribute to their presence. Further research to confirm causal relationships between these factors would help identify the cause of knee and hock injuries and determine how to best reduce the incidence of injuries in cows on commercial tiestall dairy farms in Canada.

Associations between lying behavior and lameness in Canadian Holstein-Friesian cows housed in freestall barns.

Lying behavior is an important measure of comfort and well-being in dairy cattle, and changes in lying behavior are potential indicators and predictors of lameness. Our objectives were to determine individual and herd-level risk factors associated with measures of lying behavior, and to evaluate whether automated measures of lying behavior can be used to detect lameness. A purposive sample of 40 Holstein cows was selected from each of 141 dairy farms in Alberta, Ontario, and Québec. Lying behavior of 5,135 cows between 10 and 120 d in milk was automatically and continuously recorded using accelerometers over 4 d. Data on factors hypothesized to influence lying behavior were collected, including information on individual cows, management practices, and facility design. Associations between predictor variables and measures of lying behavior were assessed using generalized linear mixed models, including farm and province as random and fixed effects, respectively. Logistic regression models were used to determine whether lying behavior was associated with lameness. At the cow-level, daily lying time increased with increasing days in milk, but this effect interacted with parity; primiparous cows had more frequent but shorter lying bouts in early lactation, changing to mature-cow patterns of lying behavior (fewer and longer lying bouts) in late lactation. In barns with stall curbs >22 cm high, the use of sand or >2 cm of bedding was associated with an increased average daily lying time of 1.44 and 0.06 h/d, respectively. Feed alleys ≥ 350 cm wide or stalls ≥ 114 cm wide were associated with increased daily lying time of 0.39 and 0.33 h/d, respectively, whereas rubber flooring in the feed alley was associated with 0.47 h/d lower average lying time. Lame cows had longer lying times, with fewer, longer, and more variable duration of bouts compared with nonlame cows. In that regard, cows with lying time ≥ 14 h/d, ≤ 5 lying bouts per day, bout duration ≥ 110 min/bout, or standard deviations of bout duration over 4 d ≥ 70 min had 3.7, 1.7, 2.5, and 3.0 higher odds of being lame, respectively. Factors related to comfort of lying and standing surfaces significantly affected lying behavior. Finally, we inferred that automated measures of lying behavior could contribute to lameness detection, especially when interpreted in the context of other factors known to affect lying behavior, including those associated with the individual cow (e.g., parity and stage of lactation) or environment (e.g., stall surface).

Prevalence of subscapularis tears and accuracy of shoulder ultrasound in pre-operative diagnosis.

PURPOSE: Subscapularis tears can be difficult to diagnose and their treatment requires advanced arthroscopic skills. The objective of this study was to find the prevalence of subscapularis tears on arthroscopic examination of shoulders with rotator cuff pathology and to determine the accuracy of pre-operative ultrasound in diagnosing these tears. METHOD: Ultrasound and intra-operative reports of 236 patients who underwent shoulder arthroscopy for rotator cuff pathology by the senior author at his institution were compared. Prevalence of subscapularis tear was noted and classified using Lafosse classification system. Ultrasound reports and intra-operative findings were compared to determine the accuracy, sensitivity and specificity of ultrasound in detecting subscapularis tears. RESULTS: The prevalence of subscapularis tears in patients needing rotator cuff repair was found to be 31.4 %. A total of 6.4 % of patients needing a rotator cuff repair had an isolated subscapularis tear. The sensitivity of ultrasound was 39.5 % and specificity 93.1 % in detection of these tears. The overall accuracy of ultrasound was 75.8 %. Sensitivity of ultrasound was low (42.8 %) for smaller (type 1 and 2) tears and higher (79 %) for larger (types 3, 4, 5) tears. The overall positive predictive value of USS was 73.1 % and negative predictive value 76.4 %. CONCLUSION: The shoulder surgeon should be skilled in diagnosing and repairing subscapularis tendon tears arthroscopically and cannot completely rely on pre-operative ultrasound scans in ruling out smaller tears as its sensitivity in diagnosing smaller tears is quite low. Unsettling anterior shoulder pain with a normal ultrasound may need further arthroscopic evaluation to rule out missed subscapularis tears.

Prevalence of lameness and associated risk factors in Canadian Holstein-Friesian cows housed in freestall barns.

Lameness is a severe welfare problem and a production-limiting disease in dairy farming. The objectives of this study were to determine prevalence of lameness and investigate cow- and herd-level factors associated with lameness in dairy cows housed in freestall barns in 3 Canadian provinces. A purposive sample of 40 Holstein-Friesian cows was selected from each of 141 dairy farms in Québec, Ontario, and Alberta. In total, 5,637 cows were scored once for lameness (presence of limping when walking). Data collected included information on individual cows (hock lesions, claw length, body condition score, parity, days in milk, and milk production), management practices (floor and stall cleaning routine, bedding routine, and footbath practices), and facility design (stall dimensions, stall base and bedding type, width of feed alley, flooring type, and slipperiness) hypothesized to be risk factors for lameness. Multilevel mixed logistic regression models were constructed (including farm as a random effect and province as a fixed effect). Herd-level lameness prevalence ranged from 0 to 69% (mean = 21%). Lameness prevalence increased with increasing parity; compared with first parity, cows in parity 2, 3, and ≥ 4 had 1.6, 3.3, and 4 times, respectively, higher odds of being lame. Furthermore, the odds of lameness were 1.6 times greater in cows with low body condition score (≤ 2.5) than in cows with a higher body condition score. In addition, injured hocks and overgrown claws were associated with 1.4- and 1.7-fold increased odds of being lame, respectively, whereas every 1 kg increase in daily milk production was associated with a 3% decrease in the odds of being lame. Lameness prevalence was higher in herds with ≤ 100 cows, but lower in barns with a sand or dirt stall base, or with bedding ≥ 2 cm deep. Cows exposed to very slippery floors had 2 times the odds of being lame compared with cows exposed to nonslippery floors. We attributed the wide range of lameness prevalence to the great variability in facilities and management practices among farms. Finally, we inferred that the prevalence of lameness could be decreased by improving management of multiparous, thin, or injured cows and by adopting management practices intended to improve cow comfort, namely the floor's slip resistance and the stall's lying surface.

Development and validation of a VISA tendinopathy questionnaire for greater trochanteric pain syndrome, the VISA-G.

BACKGROUND: Greater trochanteric pain syndrome (GTPS) is common, resulting in significant pain and disability. There is no condition specific outcome score to evaluate the degree of severity of disability associated with GTPS in patients with this condition. OBJECTIVE: To develop a reliable and valid outcome measurement capable of evaluating the severity of disability associated with GTPS. METHODS: A phenomenological framework using in-depth semi structured interviews of patients and medical experts, and focus groups of physiotherapists was used in the item generation. Item and format clarification was undertaken via piloting. Multivariate analysis provided the basis for item reduction. The resultant VISA-G was tested for reliability with the inter class co-efficient (ICC), internal consistency (Cronbach's Alpha), and construct validity (correlation co-efficient) on 52 naïve participants with GTPS and 31 asymptomatic participants. RESULTS: The resultant outcome measurement tool is consistent in style with existing tendinopathy outcome measurement tools, namely the suite of VISA scores. The VISA-G was found to be have a test-retest reliability of ICC2,1 (95% CI) of 0.827 (0.638-0.923). Internal consistency was high with a Cronbach's Alpha of 0.809. Construct validity was demonstrated: the VISA-G measures different constructs than tools previously used in assessing GTPS, the Harris Hip Score and the Oswestry Disability Index (Spearman Rho:0.020 and 0.0205 respectively). The VISA-G did not demonstrate any floor or ceiling effect in symptomatic participants. CONCLUSION: The VISA-G is a reliable and valid score for measuring the severity of disability associated GTPS.

Bradykinin-activated contractile signalling pathways in human myometrial cells are differentially regulated by arrestin proteins.

Bradykinin is associated with infections and inflammation, which given the strong correlation between uterine infection and preterm labour may imply that it could play a role in this process. Therefore, we investigated bradykinin signalling, and the roles that arrestin proteins play in their regulation in human myometrial cells. Bradykinin induced rapid, transient intracellular Ca(2+) increases that were inhibited following B2 receptor (B2R) antagonism. Arrestin2 or arrestin3 depletion enhanced and prolonged bradykinin-stimulated Ca(2+) responses, and attenuated B2R desensitisation. Knockdown of either arrestin enhanced B2R-stimulated ERK1/2 signals. Moreover, depletion of either arrestin elevated peak-phase p38-MAPK signalling, yet only arrestin3 depletion prolonged B2R-induced p38-MAPK signals. Arrestin2-knockdown augmented bradykinin-induced cell movement. Bradykinin stimulates pro-contractile signalling mechanisms in human myometrial cells and arrestin proteins play key roles in their regulation. Our data suggest bradykinin not only acts as an utertonin, but may also have the potential to enhance the contractile environment of the uterus.

Prevalence of and factors associated with hock, knee, and neck injuries on dairy cows in freestall housing in Canada.

Injuries are a widespread problem in the dairy industry. The objective of this study was to determine the prevalence of and explore the animal-based and environmental factors associated with hock, knee, and neck injuries on dairy cows in freestall housing in Ontario and Alberta, Canada. Freestall dairy farms in the provinces of Ontario (n=40) and Alberta (n=50) were visited for cross-sectional data collection. A purposive sample of 40 lactating Holstein cows was selected for detailed observation on each farm. Cows were scored for hock, knee, and neck injuries on a 3- or 4-point scale, combining the attributes of hair loss, broken skin, and swelling and with a higher score indicating a more severe injury. The highest hock and highest knee score were used in the analysis. Animal-based and environmental measures were taken to explore which factors were associated with injury. Overall, the prevalence of cows with at least one hock, knee, and neck injury was 47, 24, and 9%, respectively. Lame cows had a greater odds of hock injury [odds ratio (OR)=1.46] than nonlame cows, whereas cows with fewer days in milk (DIM) had reduced odds of hock injury compared with those >120 DIM (OR=0.47, 0.64, and 0.81 for <50, 50-82, and 83-120 DIM, respectively). The odds of hock injury was lower on sand (OR=0.07) and concrete (OR=0.44) stall bases in comparison to mattresses. Conversely, the odds of knee injury was greater on concrete (OR=3.19) stall bases compared with mattresses. Cows in parity 1 (OR=0.45 and 0.27 for knee and neck injury, respectively) and 2 (OR=0.49 and 0.40 for knee and neck injury, respectively) had lower odds of knee and neck injury compared with cows in parity 4+. Low feed rail heights increased the odds of neck injury (OR=76.71 for rails between 128 and 140 cm and OR=43.82 for rails ≤128 cm). The odds of knee injury was greater on farms where any cows were observed slipping or falling when moving into the holding area for milking (OR=2.69) and lower on farms with rubber flooring in the alley along the feed bunk compared with bare concrete floors (OR=0.19). These results demonstrate that individual animal characteristics, as well as barn design and animal management, are associated with hock, knee, and neck injuries. These data can help to guide investigations into causes and prevention of injuries.

Distinct and overlapping functional roles of Src family kinases in mouse platelets.

BACKGROUND AND OBJECTIVES: Src family kinases (SFKs) play a critical role in initiating and propagating signals in platelets. The aims of this study were to quantitate SFK members present in platelets and to analyze their contribution to platelet regulation using glycoprotein VI (GPVI) and intregrin αIIbß3, and in vivo. METHODS AND RESULTS: Mouse platelets express four SFKs, Fgr, Fyn, Lyn and Src, with Lyn expressed at a considerably higher level than the others. Using mutant mouse models, we demonstrate that platelet activation by collagen-related peptide (CRP) is delayed and then potentiated in the absence of Lyn, but only marginally reduced in the absence of Fyn or Fgr, and unaltered in the absence of Src. Compound deletions of Lyn/Src or Fyn/Lyn, but not of Fyn/Src or Fgr/Lyn, exhibit a greater delay in activation relative to Lyn-deficient platelets. Fibrinogen-adherent platelets show reduced spreading in the absence of Src, potentiation in the absence of Lyn, but no change in the absence of Fyn or Fgr. In mice double-deficient in Lyn/Src or Fgr/Lyn, the inhibitory role of Lyn on spreading on fibrinogen is lost. Lyn is the major SFK-mediating platelet aggregation on collagen at arterial shear and its absence leads to a reduction in thrombus size in a laser injury model. CONCLUSION: These results demonstrate that SFKs share individual and overlapping roles in regulating platelet activation, with Lyn having a dual role in regulating GPVI signaling and an inhibitory role downstream of αIIbß3, which requires prior signaling through Src.

Src family kinases are essential for primary aggregation by G(i) -coupled receptors.

INTRODUCTION AND BACKGROUND: Adrenaline stimulates biphasic aggregation in plasma through the G(i) -coupled α(2A) -adrenoreceptor. In the present study, we demonstrate that both primary and secondary wave aggregation induced by adrenaline in plasma is blocked by two structurally distinct inhibitors of Src family kinases, dasatinib and PD0173952. METHODS AND RESULTS: In contrast, primary aggregation is partially inhibited or unaffected in the presence of inhibitors of cyclo-oxygenase, phosphoinositide (PI) 3-kinases, and P2Y(1) and P2Y(12) ADP receptors, although secondary aggregation is abolished. The ability of adrenaline to inhibit adenylyl cyclase and to synergize with platelet agonists in mediating platelet activation in plasma is retained in the presence of Src family kinase inhibition. Moreover, adrenaline does not activate Src family kinases, as determined by western blotting of their regulatory tyrosines, suggesting that constitutive signaling from Src family kinases may underlie their role in activation. Adrenaline is widely used in clinical laboratories for investigation of patients with suspected bleeding disorders. In a group of 90 unrelated patients with a clinically diagnosed platelet bleeding disorder, we identified four who did not exhibit primary wave aggregation in response to adrenaline, although the catecholamine potentiated the response to other agonists, and five who failed to undergo secondary wave aggregation. In contrast, adrenaline stimulated biphasic aggregation in 60 controls. All of the patients with a defective response to adrenaline had impaired ADP-induced platelet activation. CONCLUSIONS: The present results indicate a previously unappreciated role for Src family kinases in mediating G(i) signaling in plasma, and demonstrate heterogeneity in response to adrenaline in patients with a clinically diagnosed platelet disorder.

Clinical decision-making in hypertension using an automated (BpTRU) measurement device.

Mercury sphygmomanometers are being removed from clinical practice in the United States due to environmental concerns about mercury toxicity. Accurate blood pressure measurement is central to high-quality hypertension management. In this study of 106 patients, the BpTRU(TM) device was compared to nurse blood pressure measurements that complied with all the JNC VII/American Heart Association guidelines in evaluation of a random casual blood pressure. The intermethod difference in systolic blood pressure was +1.8+/-5.1 mmHg, and for diastolic blood pressure it was 4.8+/-5.1 mmHg (both P<0.001). For the primary study end point of clinical decision-making, there was 92% (97/106) agreement between the hypertension nurse specialist and the BpTRU (kappa 0.8280, 95% confidence interval, 0.721-0.9350). The oscillometric blood pressure measurement with the BpTRU is recommended as a replacement for poorly performed auscultatory blood pressure measurement in clinical practice.

Intestinal permeability is increased in a proportion of spouses of patients with Crohn's disease.

OBJECTIVE: Increased small intestinal permeability has been found in patients with Crohn's disease and in a proportion of their healthy relatives. This may reflect a shared environment or shared genes. The finding of abnormal permeability in the healthy spouses of patients would favor an environmental cause for this observation. METHODS: The healthy spouses of patients with Crohn's disease attending three gastroenterology clinics were invited to participate. Eligible subjects consumed a 350-ml solution containing lactulose, mannitol, and sucrose before bedtime. All overnight urine was collected, assayed by high performance liquid chromatography, and the ratio of fractional excretion of lactulose to mannitol was calculated as an index of permeability. The results were compared with those of a previously determined control group. RESULTS: Sixty spouses completed the study. Increased permeability was present in eight (13.3%, 95% CI = 6.0-24.6%). The presence of increased permeability was not related to age, gender, duration of cohabitation, alcohol use, nonsteroidal anti-inflammatory drug use or to disease activity in the patient with Crohn's disease. There was a nonsignificant trend for abnormal permeability to occur in those spouses cohabiting with the patient with Crohn's disease at the time of disease diagnosis (p = 0.128). CONCLUSIONS: Small intestinal permeability is increased in a proportion of healthy spouses of patients with Crohn's disease. The presence of abnormal permeability studies in patients with Crohn's disease and a proportion of their healthy close contacts suggests that this phenomenon is caused by environmental factors.

Axonal regeneration and functional recovery after complete spinal cord transection in rats by delayed treatment with transplants and neurotrophins.

Little axonal regeneration occurs after spinal cord injury in adult mammals. Regrowth of mature CNS axons can be induced, however, by altering the intrinsic capacity of the neurons for growth or by providing a permissive environment at the injury site. Fetal spinal cord transplants and neurotrophins were used to influence axonal regeneration in the adult rat after complete spinal cord transection at a midthoracic level. Transplants were placed into the lesion cavity either immediately after transection (acute injury) or after a 2-4 week delay (delayed or chronic transplants), and either vehicle or neurotrophic factors were administered exogenously via an implanted minipump. Host axons grew into the transplant in all groups. Surprisingly, regeneration from supraspinal pathways and recovery of motor function were dramatically increased when transplants and neurotrophins were delayed until 2-4 weeks after transection rather than applied acutely. Axonal growth back into the spinal cord below the lesion and transplants was seen only in the presence of neurotrophic factors. Furthermore, the restoration of anatomical connections across the injury site was associated with recovery of function with animals exhibiting plantar foot placement and weight-supported stepping. These findings suggest that the opportunity for intervention after spinal cord injury may be greater than originally envisioned and that CNS neurons with long-standing injuries can reinitiate growth, leading to improvement in motor function.

Giant cell myocarditis, in a patient with Crohn's disease, treated with etanercept--a tumour necrosis factor-alpha antagonist.

Cardiac disease in association with inflammatory bowel disease (IBD) is uncommon. Reports include pericarditis, pericardial effusion, myocarditis, myocardial infarction, endocarditis and arrythmias. Myocardial inflammation related to IBD may be due to a drug hypersensitivity reaction or micronutrient deficiency, or may be secondary to the underlying IBD as an extraintestinal manifestation. In this setting, myocarditis usually presents as congestive heart failure and/or refractory arrhythmia. Prognosis varies among reported cases, including complete recovery, remission with recurrence and fatal disease. Treatment of myocarditis has included aminosalicylates and immunosuppressive medications. Recently, newer therapies for IBD have been developed, such as tumour necrosis factor-alpha (TNF-a) antagonists. The present report describes a case of a 46-year-old man with clinical and endoscopic evidence of moderately active colonic Crohn's disease who developed congestive heart failure due to giant cell myocarditis. Little clinical improvement occurred with immunosuppressive therapy. Only after the addition of etanercept, a TNF-a p75 receptor antagonist, did complete clinical resolution occur. These authors conclude that the use of TNF-a antagonists may be considered in the treatment of life-threatening extraintestinal manifestations of inflammatory bowel disease.