Trends in prevalence and characteristics of post-neonatal cerebral palsy cases: a European registry-based study.
The present paper aims to analyze trends over time in prevalence of cerebral palsy of post-neonatal origin, to investigate whether changes are similar according to severity and to describe the disability profile by etiology. Post-neonatal cases, birth years 1976 to 1998, were identified from the Surveillance of Cerebral Palsy in Europe collaboration (19 population-based registries). A recognized causal event occurring between 28 days and 24 months of age was considered to define the cases. Trends in prevalence were explored using graphical methods (Lowess and Cusum control chart) and modeled with negative binomial regressions. Over the study period, 404 cases were identified as post-neonatal cases (5.5% of the total). Mean prevalence rate was 1.20 per 10,000 live births (95% CI [1.08-1.31]). A significant downward trend was observed (p=0.001), with an accentuated decrease in the 1990 s. The prevalence of severe cases which account for around one third of the total also significantly decreased over time (p<0.001). In 46% of cases, an infectious aetiology was reported; the corresponding prevalence significantly decreased since 1989. No significant decrease was observed for the rate of cases due to a vascular episode or of traumatic origin. Our results emphasize the need of large population-based surveillance systems to reliably monitor trends in prevalence in rare subgroups of children like those with acquired cerebral palsy. The decrease of the overall prevalence as well as those of the most severe cases may be partly due to public health actions targeted to prevent such events.


The role of epsilon-aminocaproic acid in reducing bleeding after cardiac operation: a double-blind randomized study.
Sixty patients scheduled for elective coronary artery bypass graft operations were randomly assigned to receive epsilon-aminocaproic acid or placebo to test whether antifibrinolytic therapy would decrease postoperative bleeding. A small but significant decrease in bleeding was observed in the treated group without complications resulting from treatment with epsilon-aminocaproic acid.


Wnt signaling behaves as a "master regulator" in the osteogenic and adipogenic commitment of human amniotic fluid mesenchymal stem cells.
Human amniotic fluid mesenchymal stem cells (huAFMSCs) are emerging as a promising therapeutic option in regenerative medicine. Here, we characterized huAFMSC phenotype and multipotentiality. When cultured in osteogenic medium, huAFMSC displayed a significant increase in: Alkaline Phosphatase (ALP) activity and mRNA expression, Alizarin Red S staining and Runx2 mRNA expression; whereas maintaining these cells in an adipogenic culture medium gave a time-dependent increase in PPARγ and FABP4 mRNA expression, glycerol-3-phosphate dehydrogenase (GPDH) activity and positivity to Oil Red Oil staining. These results confirm that huAFMSCs can differentiate toward osteogenic and adipogenic phenotypes. The canonical Wnt/ßcatenin signaling pathway appears to trigger huAFMSC osteoblastogenesis, since during early phases of osteogenic differentiation, the expression of Dishevelled-2 (Dvl-2), of the non-phosphorylated form of ß-catenin, and the phosphorylation of glycogen synthase kinase-3ß (GSK3ß) at serine 9 were upregulated. On the contrary, during adipogenic differentiation Dvl-2 expression decreased, whereas that of ß-catenin remained unchanged. This was associated with a late increase in GSK3ß phosphorylation. Consistent with this scenario, huAFMSCs exposure to Dickkopf-1, a selective inhibitor of the Wnt signaling, abolished Runx2 and ALP mRNA upregulation during huAFMSC osteogenic differentiation, whereas it enhanced FABP4 expression in adipocyte-differentiating cells. Taken together, these results unravel novel molecular determinants of huAFMSC commitment towards osteoblastogenesis, which may represent potential targets for directing the differentiation of these cells and improving their use in regenerative medicine.


Immune Checkpoint Inhibitor Rechallenge and Resumption: a Systematic Review.
The reintroduction of immune checkpoint inhibitors (ICIs) after disease progression (rechallenge) or immune-related adverse events (irAEs) recovering (resumption) raises questions in terms of efficacy and safety. Here, we reviewed literature data about ICIs rechallenge/resumption in cancer patients along with their clinical characteristics to explore those factors associated with better outcomes. Heterogenous results were pointed out across rechallenge studies with an overall response rate between 0 and 54%, and a progression free survival ranged from 1.5 to 12.9 months and an overall survival between 6.5 and 23.8 months. Better outcomes have been recorded in patients with good ECOG PS, longer duration of initial ICI, discontinuation reason of initial ICI other than progression, and those who received ICI sequence other than the switch between anti-PD1 and anti-PDL1. Studies about ICI resumption highlighted that certain types of irAEs were more likely to relapse at retreatment. These results suggest that ICI rechallenge/resumption can be an interesting strategy for selected patients.


A comparison of undergraduate clinical ophthalmology learning methods: smart phone television display versus slit-lamp teaching telescope.
To compare medical students' preference of smart phone television display (SPTD) to a slit-lamp teaching telescope (SLTT) in undergraduate clinical ophthalmology education. This is a randomized, crossover, comparative study. Pairs of medical students were randomly assigned to 2 teaching sessions using either SPTD first followed by SLTT or in reverse order. Students were asked to give feedback on the 2 teaching devices by answering 6 questions using a numeric rating score from 1 to 10. All participating students were sent the results of the study 1 month after the completion of the study and were asked to reflect upon the outcome. Thirty-eight students were recruited. The overall satisfaction scores were significantly higher for SPTD than SLTT (8.6 ± 1.4 vs 7.5 ± 1.0, p < 0.01). The students preferred SPTD compared with SLTT in terms of "visualization" (8.5 ± 1.4 vs 7.0 ± 1.3, p < 0.01), "ocular sign description" (8.4 ± 1.3 vs 7.2 ± 1.2, p < 0.01), "ocular anatomy understanding" (8.3 ± 1.2 vs 7.6 ± 1.2, p < 0.01), and "confidence in identifying clinical signs" (8.4 ± 1.2 vs 7.5 ± 1.2, p < 0.01). A larger proportion of the students gave higher scores to SPTD compared with SLTT in all questions. All students who responded to the follow-up questionnaire (n = 14) agreed with our interpretation of the data and would support the use of SPTD in undergraduate clinical ophthalmology teaching. Our study has demonstrated that the utility of SPTD as a teaching aid can significantly increase the satisfaction of undergraduate medical students during their ophthalmology attachment. It offers specific practical advantages in teaching medical students over the traditional SLTT.


Model refinement increases confidence levels and clinical agreement when commissioning a three-dimensional secondary dose calculation system.
Evaluate custom beam models for a second check dose calculation system using statistically verifiable passing criteria for film analysis, DVH, and 3D gamma metrics. Custom beam models for nine linear accelerators for the Sun Nuclear Dose Calculator algorithm (SDC, Sun Nuclear) were evaluated using the AAPM-TG119 test suite (5 Intensity Modulated Radiation Therapy (IMRT) and 5 Volumetric Modulated Arc Therapy (VMAT) plans) and a set of clinical plans. Where deemed necessary, adjustments to Multileaf Collimator (MLC) parameters were made to improve results. Comparisons to the Analytic Anisotropic Algorithm (AAA), and gafchromic film measurements were performed. Confidence intervals were set to 95% per TG-119. Film gamma criteria were 3%/3 mm (conventional beams) or 3%/1 mm (Stereotactic Radiosurgery [SRS] beams). Dose distributions in solid water phantom were evaluated based on DVH metrics (e.g., D95, V20) and 3D gamma criteria (3%/3 mm or 3%/1 mm). Film passing rates, 3D gamma passing rates, and DVH metrics were reported for HD MLC machines and Millennium MLC Machines. For HD MLC machines, SDC gamma film agreement was 98.76% ± 2.30% (5.74% CL) for 6FFF/6srs (3%/1 mm), and 99.80% ± 0.32% (0.83% CL) for 6x (3%/3 mm). For Millennium MLC machines, film passing rates were 98.20% ± 3.14% (7.96% CL), 99.52% ± 1.14% (2.71% CL), and 99.69% ± 0.82% (1.91% CL) for 6FFF, 6x, and 10x, respectively. For SDC to AAA comparisons: HD MLC Linear Accelerators (LINACs); DVH point agreement was 0.97% ± 1.64% (4.18% CL) and 1.05% ± 2.12% (5.20% CL); 3D gamma agreement was 99.97% ± 0.14% (0.30% CL) and 100.00% ± 0.02% (0.05% CL), for 6FFF/6srs and 6x, respectively; Millennium MLC LINACs: DVH point agreement was 0.77% ± 2.40% (5.47% CL), 0.80% ± 3.40% (7.47% CL), and 0.07% ± 2.15% (4.30% CL); 3D gamma agreement was 99.97% ± 0.13% (0.29% CL), 99.97% ± 0.17% (0.36% CL), and 99.99% ± 0.06% (0.12% CL) for 6FFF, 6x, and 10x, respectively. SDC shows agreement well within TG119 CLs for film and redundant dose calculation comparisons with AAA. In some models (SRS), this was achieved using stricter criteria. TG119 plans can be used to help guide model adjustments and to establish clinical baselines for DVH and 3D gamma criteria.


Denitrosation of N-nitrosodimethylamine and N-nitrosomethylurea by liver microsomes from trout (Salmo gairdneri Rich.).
N-Nitrosodimethylamine and N-nitrosomethylurea are partially metabolized to nitrite and formaldehyde by trout liver microsomes. Results show that the denitrosation pathway of both N-nitroso derivatives is NADPH-dependent, requires molecular oxygen, and is inhibited by common inhibitors of microsomal enzyme activities.


Changes in the vascular beta-adrenoceptor-activated signalling pathway in 2Kidney-1Clip hypertensive rats.
1. beta-Adrenoceptor (beta-AR)-mediated vasodilation, which plays an important physiological role in the regulation of vascular tone, is decreased in two-kidney, one clip (2K-1C) renal hypertension. In this study, downstream pathways related to vascular beta-AR activation were evaluated in 2K-1C rats. 2. Relaxation responses to isoprenaline, forskolin and 8-Br-cAMP were diminished in aortas without endothelium from 2K-1C when compared to those in normotensive two kidney (2K). Basal adenosine-3',5'-monophosphate (cAMP), as well as isoprenaline-induced increase in cAMP levels, was not different between 2K and 2K-1C aortas. 3. Contractile responses to caffeine, after depletion and reloading of intracellular Ca(2+) stores, were greater in 2K-1C than in 2K. The presence of isoprenaline during the Ca(2+)-reloading period abolished the differences between groups by increasing caffeine contraction in 2K without changing this response in 2K-1C aortas. Inhibition of the sarcolemmal Ca(2+)ATPase with thapsigargin markedly attenuated isoprenaline vasodilation in both 2K and 2K-1C and abolished the differences between groups. 4. Blockade of ATP-sensitive K(+) channels (K(ATP)) channels with glibenclamide significantly decreased isoprenaline vasodilation in 2K-1C without affecting this response in 2K. Both vascular gene and protein expression of protein kinase A (PKA), as well as phosphoserine-containing proteins, were increased in 2K-1C vs 2K rats. 5. In conclusion, decreased isoprenaline vasodilation in 2K-1C hypertensive rats is related to impaired modulation of the sarcolemmal Ca(2+)ATPase activity. Moreover, K(ATP) channels may play a compensatory role on isoprenaline-induced relaxation in renal hypertension. Both Ca(2+)ATPase and K(ATP) channel functional alterations, associated with decreased beta-AR vasodilation, are paralleled by an upregulation of protein kinase A (PKA) and phosphoserine proteins expression.


Analysis of non-typeable Haemophilus influenzae in invasive disease reveals lack of the capsule locus.
Among invasive Haemophilus influenzae, unencapsulated strains have largely surpassed the previously predominant serotype b (Hib) because of Hib vaccination. Isolates without the genomic capsule (cap) locus are designated non-typeable H. influenzae (NTHi). They are different from capsule-deficient variants that show deletion of the capsule transport gene bexA within the cap locus. The frequency of capsule-deficient variants in invasive disease is unknown. We analysed 783 unencapsulated invasive isolates collected over 5 years in Germany and found no single capsule-deficient isolate. Invasive unencapsulated strains in Germany were exclusively NTHi. A negative serotyping result by slide agglutination was therefore highly predictive for NTHi.


Characteristics of falls producing hip fractures in nonagenarians.
To evaluate the characteristics associated with falls causing hip fracture in patients 90 years of age or older (nonagenarians). A second objective was to compare these characteristics with those present in younger patients (65-79 year-olds). Prospective, observational study. Six hospitals in Barcelona (Spain) and its surrounding area. 105 nonagenarians diagnosed with hip fracture after a fall. Most patients were women (78; 74%), with a mean age of 92.2+/-2 years. All of them were living in the community, except for eight institutionalized patients. 221 patients aged 65 to 79 composed the younger patient's comparison group. Characteristics of falls causing hip fracture were analyzed: location, time and the risk factor for the fall, classified as intrinsic, extrinsic or combined. The mean number of falls in the previous year was 1.5 - 22% of the patients reported having fallen two or more times. Falls usually happened while at home (70%) and during the day (64%). An intrinsic risk factor was considered the most likely cause in 37% of the cases, an extrinsic risk factor in 35%, and a combination in 28%. Multiple stepwise logistic regression analysis showed that nonagenarians were characterized by lower BI scores, more falls happening during night time, a higher use of, benzodiazepines and diuretics, and a lower use of non-benzodiazepinic hypnotics. Most falls causing hip fracture in nonagenarians happen during the day and at home. Falls in nonagenarians happening more frequently during nighttime, and these oldest subjects had lower BI scores, and a higher use of benzodiazepines and diuretics and less use of non-benzodiazepines hypnotics compared with the younger patients.


Spatial quantitative vectorcardiography in aortic stenosis: correlation with hemodynamic findings.
Thirty-four patients with hemodynamically documented valvar aortic stenosis without congestive heart failure were studied by the corrected Frank lead system vectorcardiography, with special emphasis on the angular characteristics of spatial R max to define the severity of the lesion. Spatial QRS-T angle demonstrated a highly significant correlation with the peak left ventricular systolic pressure (r = 0.72, P less than 0.001) and a significant correlation with peak transvalvar aortic gradient (r = 0.49, P less than 0.01). Furthermore, all patients with a QRS-T angle of more than 90 degrees had significant aortic stenosis (TVG greater than or equal to 50 mm Hg). The peak left ventricular systolic pressure and transvalvar aortic gradient also demonstrated a significant negative correlation with azimuth angle (r = -0.36 and -0.34, respectively; P less than 0.05) and a positive correlation with spatial R max magnitude (r = 0.38 and 0.41, respectively; P less than 0.05). There was no correlation between elevation angle of spatial R max and left ventricle systolic pressure or transvalvar aortic gradient. Our study indicates that spatial quantitative vectorcardiographic angular characteristics, particularly spatial QRS-T angle, may be a useful adjunct to other noninvasive techniques to assess the severity of valvar aortic stenosis.


The use of topical oral antibiotics in head and neck prophylaxis: is it justified?
Systemic antibiotic therapy is widely used for prophylaxis in major head and neck surgery, but the efficacy of topical oral antibiotic therapy has not been adequately investigated. A pilot, placebo-controlled, double-blind crossover study using six healthy adult male volunteers was performed to assess the influence of topical clindamycin on oral flora. Samples of saliva were cultured for aerobic and anaerobic bacteria immediately before, and at 1- and 4-hour intervals after, rinsing the mouth with a solution of either placebo or clindamycin. Quantitative analysis demonstrated significantly reduced levels of both aerobic and anaerobic bacteria after use of the topical antibiotic at both the 1- and 4-hour intervals. It is postulated that topical clindamycin, by reducing concentrations of oral flora, may also reduce the incidence of regional infection following major upper aerodigestive tract surgery.


A rare case of isolated myoclonus in an elderly male without a history of epilepsy.
Through this case report we attempt to highlight the presentation, initial investigation and management of lingual myoclonus as well as consolidate relevant literature. We present a unique case of a 72-year-old man who was admitted to the hospital for a sudden onset episodic speech arrest. Lingual myoclonus, an isolated movement disorder, manifested as an intermittent expressive aphasia secondary to the intrusion-protrusion movements of his tongue. During this time, the patient remained conscious and was able to continue to follow commands. Initial diagnostic evaluation with a CT scan, MRI and EEG failed to illicit a clear underlying etiology and the patient was empirically treated with valproic acid with complete resolution of his symptoms. This unusual presentation represents a rare disorder which is not well described in literature. Initial evaluation of which required excluding associated etiologies including strokes, seizures, medications/toxins or CNS infections. Without a clear etiology on initial diagnostic evaluation, the patient was empirically treated as no clear guidelines exist. This case presentation is an attempt to add to the current understanding of lingual myoclonus.


The antiadipogenic effect of macrophage-conditioned medium depends on ERK1/2 activation.
The proatherogenic state of obesity is associated with hypertrophied adipocytes that may arise because of deficient adipogenesis. Macrophages infiltrate adipose tissue as a function of obesity and may release factors that attenuate adipogenesis. Macrophage-conditioned medium inhibits human and 3T3-L1 adipocyte differentiation in culture, but underlying molecular mechanisms have yet to be defined. Exposure of 3T3-L1 cells throughout the 8-day period of differentiation to medium conditioned by THP-1 macrophages (THP-1-MacCM) blocked adipogenesis. Triacylglycerol (TG) accumulation and induction of peroxisome proliferator-activated receptor gamma and fatty acid synthase protein levels were inhibited by 59% (n = 4, P < .001), 29% (n = 4, P < .01), and 47% (n = 4, P < .01), respectively. THP-1-MacCM had no effect when added after the first 2 days of differentiation, indicating that early exposure of its targets must be needed to inhibit 3T3-L1 adipogenesis. Cell enumeration revealed a 44% decrease in clonal expansion compared with standard differentiation (n = 3, P < .01). Addition of THP-1-MacCM to 3T3-L1 preadipocytes increased ERK1/2 phosphorylation by 6.5-fold (n = 3, P < .01). PD98059 (an inhibitor of the ERK1/2 pathway) impaired the negative effect of THP-1-MacCM on TG accumulation, indicated by an inhibition of 25% vs 69% (n = 3, P < .001), without altering fatty acid synthase or peroxisome proliferator-activated receptor gamma levels. Our data implicate ERK1/2 as an important signaling mediator for the inhibitory effect of THP-1-MacCM on TG accumulation during 3T3-L1 adipogenesis.


Migration and the cancer burden of New Jersey blacks.
A migrant study of black residents of New Jersey shows that the burden of cancer mortality is attributable mostly to southern-born blacks who moved to New Jersey. In strong contrast, low rates were evident among foreign-born blacks. We suggest followup studies for minority populations.


Persistent trigeminal artery: unusual associated abnormalities.
Multiple cases of vascular abnormalities associated with the persistent trigeminal artery or a variant thereof are presented. A persistent otic artery variant is the only known such case in the literature.


Secondary stroke prevention: from guidelines to clinical practice.
Stroke remains a leading cause of mortality and is associated with substantial morbidity in the United States. The majority of strokes are of ischemic origin, with an atherothrombotic trigger, and the clinical manifestation of atherothrombosis depends on the affected vascular site. The systemic nature of atherosclerosis means that stroke patients are at increased risk of ischemic events in several vascular beds, including cerebral, coronary and peripheral sites. Because stroke patients are at heightened risk of more ischemic events, secondary prevention is an important therapeutic goal. Recently, the American Heart Association and its division, the American Stroke Association, released new evidence-based guidelines for secondary stroke prevention in patients with ischemic stroke or transient ischemic attack. The new guidelines emphasize an individualized, patient-oriented approach to treatment based on clinical evidence. Evidence-based recommendations are set forth for the management of risk factors, including hypertension, dyslipidemia and diabetes, through lifestyle modifications and pharmacological interventions. The purpose of this paper is to review the topic of stroke prevention in light of current guidelines and clinical implementation patterns for primary care physicians, and to discuss new and emerging clinical evidence, with a focus on antiplatelet treatment.


Comparative effects of open-lung positive end-expiratory pressure (PEEP) and fixed PEEP on respiratory system compliance in the isoflurane anaesthetised healthy dog.
This study was performed to assess the effects of open-lung positive end-expiratory pressure (OL-PEEP) following stepwise recruitment manoeuvre (RM) and those of a fixed PEEP of 5 cm H2O without previous RM on respiratory system compliance (Crs) and selected cardiovascular variables in healthy dogs under general anaesthesia. Forty-five healthy client-owned dogs undergoing surgery were anaesthetised and mechanically ventilated (tidal volume, VT = 10-12 mL/kg; PEEP = 0 cm H2O) for 1 min (baseline) and randomly allocated into zero positive end-expiratory pressure (ZEEP), PEEP (5 cm H2O) and OL-PEEP treatment groups. In the OL-PEEP group, a stepwise RM was performed and the individual OL-PEEP was subsequently applied. The Crs, heart rate (HR) and non-invasive mean arterial pressure (NIMAP) were registered at baseline and then every 10 min during 60 min. In the ZEEP group, Crs decreased from baseline. In the PEEP group, Crs was not different from either baseline or ZEEP group values. In the OL-PEEP group, Crs was higher than both baseline and ZEEP group values at all time points as well as of those in the PEEP group during at least 20 min after RM. There were no differences for HR and NIMAP between groups. A clinically relevant hypotension following RM was observed in 40% of dogs. Therefore, an individually set OL-PEEP following stepwise RM improved Crs in anaesthetised healthy dogs, although transient but clinically relevant hypotension was observed during RM in some dogs. Fixed PEEP of 5 cm H2O without previous RM did not improve Crs, although it prevented it from decreasing.


Peritraumatic tonic immobility predicts a poor response to pharmacological treatment in victims of urban violence with PTSD.
Tonic immobility is the last defense against predation in animals and is characterized by paralysis and analgesia. In humans, it has only been reported in women victims of sexual abuse. This study evaluated the prevalence of peritraumatic tonic immobility (PTI) in patients with PTSD and investigated its association with response to treatment. Victims of urban violence with PTSD diagnosed through the SCID-IV (n=23) underwent a naturalistic pharmacological treatment according to the recommended guidelines for PTSD. The Post-Traumatic Stress Disorder Checklist--Civilian Version (PCL-C) and the Clinical Global Impressions (CGI) Severity scores were applied at baseline and endpoint. PTI was assessed using the Tonic Immobility Scale. PTI was reported by both genders in 43% of the sample. Patients with PTI responded significantly poorly to treatment than those without it, either considering the PCL-C or the CGI scores. This study probed PTI retrospectively and was based on a small sample recruited in a tertiary clinic. We have expanded the scope of the two previous investigations on PTI by showing its occurrence also in men and during non-sexual violence. In addition, the finding of a significant relationship between PTI and poor response to treatment of PTSD indicates that PTI may carry a prognostic value in this disorder and suggests that PTI should be routinely assessed in traumatized patients.


Ruptured abdominal aortic aneurysm: categorization of sonographic findings and report of 3 new signs.
The purpose of this study was to categorize the sonographic findings seen in patients with a ruptured abdominal aortic aneurysm (AAA) and to describe 3 previously undescribed sonographic findings. From January 1997 to December 2003, we evaluated 388 consecutive patients with an AAA (transverse aortic diameter >30 mm). Among these patients, 29 had surgical or computed tomographic demonstration of aneurysm rupture. The remaining 359 were asymptomatic and had no evidence of AAA rupture at follow-up. Findings recognized among 29 positive cases included AAA deformation (n = 12), luminal thrombus inhomogeneity (n = 20), clear interruption of a luminal thrombus (n = 5), retroperitoneal hematoma (n = 22), and hemoperitoneum (n = 11). In addition, 3 previously unreported findings were noted: an intraluminal floating thrombus layer (n = 8), a parietal hypoechoic focus due to aneurysm wall interruption (n = 3), and a para-aortic hypoechoic area adjacent to the bleeding side (n = 4). Aside from AAA deformation and thrombus heterogeneity, no other signs were recognized among subjects with a nonruptured aneurysm. In the past, sonography has been used mainly to rapidly confirm aneurysm presence in the clinical setting of a patient with a suspected rupture. Instead, this retrospective series shows how this imaging technique can frequently identify several direct and indirect signs of aneurysm rupture itself. Moreover, 3 new indicators of AAA rupture have been observed.


A risk profile of elite Australian athletes who use illicit drugs.
Much of the literature investigating the relationship between sports participation and substance use has focused upon student populations, with little focus being given to athletes who participate at elite levels. Identifying why some athletes may be at a greater risk for substance use can help in the design and implementation of prevention initiatives. Data for the current study was from 1684 self-complete surveys with elite Australian athletes. Eight percent (n=134) of the sample reported the use of at least one of the six illicit drugs under investigation (ecstasy, cannabis, cocaine, meth/amphetamine, ketamine and GHB) in the past year. Having been offered or having had the opportunity to use illicit drugs in the past year, knowing other athletes who use drugs and identifying as a 'full-time athlete' were significant predictors of past-year illicit drug use, while having completed secondary education or a post-school qualification was associated with a lower likelihood of past-year illicit drug use. Athletes are part of a sportsnet that includes family, coaches, support staff and other athletes, and these relationships may encourage the use, supply and demand for drugs. The current findings suggest that relationships with some of those in the sportsnet may play an important role when understanding illicit drug use among elite athletes. As education appears to be associated with a lower likelihood of illicit drug use among this group, initiatives should encourage athletes to engage in off-field pursuits which may also help prepare them for life after sport.


A gender-focused perspective on health service utilization in comorbid bipolar I disorder and alcohol use disorders: results from the national epidemiologic survey on alcohol and related conditions.
This study compares health service utilization by individuals with comorbid lifetime bipolar I disorder and lifetime alcohol use disorders (AUD) to that of individuals with either diagnosis alone, using nationally representative data. The 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions was used to identify respondents with bipolar I disorder only (BD-only; N = 636), AUD only (N = 11,068), and comorbid bipolar I disorder and AUD (BD-AUD; N = 775). Diagnoses were generated using the National Institute on Alcohol Abuse and Alcoholism Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. The 3 groups were compared with respect to self-reported health service utilization. For both men and women, respondents in the BD-AUD group were significantly more likely than AUD-only respondents to report any alcohol-related service utilization (p < .001). BD-AUD respondents were significantly more likely to report bipolar disorder-related hospital admissions as compared with BD-only respondents among males only (p = .009). Within the BD-AUD group, males reported significantly greater utilization of AUD treatment only (p < .001), and females reported significantly greater utilization of bipolar disorder treatment only (p < .001) and significantly greater likelihood of utilizing mental health services overall (p < .001). There was no gender difference in the proportion of respondents who utilized both AUD and bipolar disorder services. As expected, individuals with comorbid bipolar I disorder and AUD utilize significantly more mental health services than individuals with either disorder alone. The primary original finding is that among those with comorbid bipolar I disorder and AUD, bipolar I disorder is more likely to go untreated among males and AUD is more likely to go untreated among females. Gender may be an important factor to consider in future health service planning for comorbid bipolar I disorder and AUD.


Correction to: Hormonal contraceptives and risk of ischemic stroke in women with migraine: a consensus statement from the European Headache Federation (EHF) and the European Society of Contraception and Reproductive Health (ESC).
Following the publication of this article [1], the authors noticed that they incorrectly reported the Absolute risk of ischemic stroke in women aged 20 to 44 years in relation to the use of hormonal contraception and migraine status due to a miscalculation. They apologize for this misreported result.


Stress-induced facilitation of acoustic startle after d-amphetamine administration.
Administration of d-amphetamine enhanced the startle response to an auditory stimulus. In contrast to saline treated mice, startle activity after amphetamine administration did not wane with repeated exposure to the auditory stimulus. Rather, the effects of amphetamine on startle activity increased as a function of stimulus presentation. Whereas exposure to isolation stress or inescapable shock had no effect on startle activity, both types of stress potentiated the effects of amphetamine on startle arousal. The observation that stress sensitized animals to later amphetamine administration is consistent with the effects of stress on other amphetamine behaviors, e.g., stereotypy. Results were related to the development of dopamine post-synaptic receptor supersensitivity after exposure to stress and were discussed in terms of the role played by stress in the expression of behavioral arousal, in the etiology of schizophrenia.


An azobenzene-containing metal-organic framework as an efficient heterogeneous catalyst for direct amidation of benzoic acids: synthesis of bioactive compounds.
An azobenzene-containing zirconium metal-organic framework was demonstrated to be an effective heterogeneous catalyst for the direct amidation of benzoic acids in tetrahydrofuran at 70 °C. This finding was applied to the synthesis of several important, representative bioactive compounds.


Cardiac allograft vasculopathy after heart transplantation: Is it really ominous?
Cardiac allograft vasculopathy (CAV) remains a major impediment to long-term survival after heart transplantation (HT). We investigated the incidence, disease course, and risk factors for CAV. Among 399 patients who underwent HT between November 1992 and July 2014, 297 survivors were reviewed. Endpoints were CAV development and the composite outcome of death or re-HT. During 5.6±5.2 years, CAV was detected in 54 patients: 45 (83.3%), 8 (14.8%), and 1 (1.8%) patients for CAV 1, 2, and 3, respectively. At 1, 5, and 10 years, 99.0%, 82.4%, and 60.3% of patients were free of CAV, respectively. Only four patients (7.4%) showed progression over 4.8±2.1 years' follow-up. The presence of CAV did not affect the composite outcome (P=.89). Predictors of CAV included donor age (HR1.06, 95% CI: 1.03-1.10: P<.001), recipient age (1.03 [1.003-1.06]; P=.03), ischemic time >240 minutes (3.15 [1.36-7.28], P=.007), postoperative renal replacement therapy (RRT) (7.1 [2.3-21.8]; P=.001), and triglyceride level at 1 year post-HT (1.005 [1.002-1.008], P=.003). CAV incidence after HT appears acceptable, with most cases being stationary and inconsequential for survival. Development of CAV seems to be influenced by donor and recipient age, ischemic time, postoperative RRT, and high triglyceride level.


Otologic use of porcine small intestinal submucosal graft (biodesign): A MAUDE database review.
To review and summarize reported adverse events related to the use of porcine small intestine submucosal grafts (Biodesign™) in otologic procedures. Retrospective cross-sectional analysis. Food and Drug Administration's Manufacturer and User Facility Device Experience (MAUDE) database. The MAUDE database was queried for all medical device reports (MDR) related to otologic use of Biodesign™ (Cook Medical, Bloomington, IN) from January 2016 to November 2022. Adverse events (AEs) were identified by reviewing all reports with the basic search term "Biodesign" and "Biodesign, Otologic". Reports were individually reviewed and categorized with special attention to AEs. A total of 500 reports were reviewed. Since FDA approval of Biodesign™ in 2016, there have been 5 adverse events reported for use of Biodesign™ during otologic surgery (tympanoplasty, n = 3; stapes surgery, n = 2). All reported events described patient injury, and all cases required at least one revision surgery. Four cases described significant foreign body inflammatory reactions. Complications included hearing loss (n = 3), severe otalgia (n = 2), persistent perforation (n = 2), vertigo (n = 2), and facial paralysis (n = 1). The use of porcine small intestinal submucosal graft has been thought to be a safe and effective option for otologic surgery, with the advantage of availability without graft harvest in minimally invasive endoscopic surgery. However, foreign body or granulomatous reactions have been documented and should be considered prior to its use in otologic surgery.


Pilot-Scale Assessment of a Novel Farrowing Creep Area Supplementary Heat Source.
Pre-weaning morality (PWM) is attributed to a poor creep area microclimate and causes major economic and productivity losses for the US swine industry. Piglets need supplementary heat to overcome a high surface area to body weight ratio and minimal thermoregulation. A pilot-scale study was conducted to evaluate a semi-enclosed heated microclimate (SEHM) as a supplementary heat source for farrowing creep areas over six farrowing cycles (from January to July 2019) in two rooms with 24 farrowing stalls in each room. Six SEHMs (each SEHM covers two stalls) were randomly distributed to each room and compared to heat lamps (HLs) for productivity and electricity usage. Data from 113 (SEHM) and 101 litters (HL) showed no significant difference between treatments in average daily gain (p = 0.26), 252.4 ± 8.0 g hd-1 d-1 (SEHM) and 260.3 ± 8.1 g hd-1 d-1 (HL) and PWM (p = 0.08), 9.67% ± 0.82% (SEHM) and 12.04% ± 0.87% (HL). However, a significant difference (p = 0.02) was noted in the PWM attributed to over-lay mortalities, 4.05% ± 0.76% (SEHM) compared to 6.04% ± 0.78% (HL). The SEHM electricity averaged 3.25 kWh d-1 (2.91, 3.59 kWh d-1; 95% CI), which was significantly different (p < 0.01) from the HL equivalent (125 W bulb; 6 kWh d-1).


Restricted expression of protocadherin 2A in the developing mouse brain.
Protocadherins are cell-cell adhesion molecules that are thought to be involved in neural development. Here, we report the expression pattern of protocadherin 2A (Pc2A) in the developing mouse brain as determined by the in situ hybridization technique. In the postnatal day 2 brain, various regions expressed Pc2A including the cerebellar cortex, ventral posterior thalamic nucleus, dorsal lateral geniculate nucleus, hippocampus and cerebellum (Purkinje cells). In particular, some ependymal cells that form the lining of the lateral ventricle and the third ventricle and floor plate cells lining the fourth ventricle showed prominent expression. In the adult brain, strong expression was restricted to the Purkinje cells. Expression in other areas of the adult brain was down-regulated to a faint level, and only a weak signal was detected in regions such as the retina, olfactory bulb, dentate gyrus of the hippocampus, and in some parts of the medial eminence. These observations suggest that Pc2A is expressed in various regions of the brain in a developmentally regulated manner.


Methylmalonyl-CoA mutase encoding gene of Sinorhizobium meliloti.
A cluster of genes on megaplasmid pRmeSU47b, bhbA-D, is required for growth on the polyhydroxyalkanoate degradation pathway intermediates 3-hydroxybutyrate and acetoacetate as sole carbon source. DNA sequence analysis of the bhbA gene indicated that it encoded a protein of 712 amino acids (aa) (78kDa) which appeared to be a homodimeric methylmalonyl-CoA mutase enzyme (EC 188.8.131.52). Cell-free extract of a bhbA::Tn5 mutant was devoid of methylmalonyl-CoA mutase activity, thus confirming the identity of the bhbA-encoded enzyme. The reason for the requirement of methylmalonyl-CoA mutase activity for operation of the polyhydroxyalkanoate degradation pathway is not immediately apparent. Situated immediately upstream of bhbA, in the same orientation, is a gene which is predicted to encode a protein that exhibits remarkable sequence similarity to the alpha subunit of propionyl-CoA carboxylase (EC 220.127.116.11). A mutation in this gene did not affect ability to grow on 3-hydroxybutyrate as sole carbon source. Downstream of, and oriented towards bhbA, was identified a member of the GNTR class of transcriptional regulator-encoding genes. It is not yet known whether this regulatory protein is directly involved in modulation of bhbA expression.


Anterior talofibular ligament remnant quality is important for achieving a stable ankle after arthroscopic lateral ankle ligament repair.
The relationship between ligament remnant quality and postoperative outcomes after arthroscopic lateral ankle ligament repair for chronic lateral ankle instability is controversial. This study aimed to determine whether the signal intensity of the anterior talofibular ligament on preoperative magnetic resonance imaging and ligament remnant quality identified on arthroscopy are associated with recurrent ankle instability after arthroscopic lateral ankle ligament repair. A total of 68 ankles from 67 patients with chronic lateral ankle instability who underwent arthroscopic lateral ankle ligament repair were retrospectively studied. The signal intensity of the anterior talofibular ligament was evaluated using T2-weighted magnetic resonance imaging. Arthroscopy was used to evaluate the thickness and mechanical resistance of the anterior talofibular ligament by hook palpation and to classify ankles into two groups: the present anterior talofibular ligament group with adequate mechanical resistance and the absent anterior talofibular ligament group with no mechanical resistance. The outcomes included recurrent ankle instability (respraining of the operated ankle after surgery) and Self-Administered Foot Evaluation Questionnaire scores. Thirteen ankles were diagnosed with recurrent ankle instability. Patients with a high anterior talofibular ligament T2 signal intensity experienced more recurrent ankle instability than those with a low intensity. As determined via arthroscopy, the absent anterior talofibular ligament group had a higher rate of recurrent ankle instability than the present anterior talofibular ligament group. There were no significant differences in Self-Administered Foot Evaluation Questionnaire scores between patients with high and low anterior talofibular ligament T2 signal intensity, as well as between absent and present anterior talofibular ligament groups based on arthroscopy. Poor quality of the anterior talofibular ligament remnant could result in recurrent ankle instability after arthroscopic lateral ankle ligament repair. Therefore, when treating chronic lateral ankle instability, surgeons should consider ligament quality. IV.


Escape from intermittent repellers: periodic orbit theory for crossover from exponential to algebraic decay.
We apply periodic orbit theory to study the asymptotic distribution of escape times from an intermittent map. The dynamical zeta function exhibits a branch point which is associated with an asymptotic power law escape. By an analytic continuation technique we compute a pair of complex conjugate zeroes beyond the branch point, associated with a preasymptotic exponential decay. The crossover time from an exponential to a power law is also predicted. The theoretical predictions are confirmed by numerical simulation. Applications to conductance fluctuations in quantum dots are discussed.


Magnesium deficiency in heart failure patients with diabetes mellitus.
To assess the serum magnesium level in heart failure patients with diabetes mellitus. A case-control study was conducted at Basic Medical Sciences Institute (BMSI), Jinnah Postgraduate Medical Centre (JPMC), Karachi, in collaboration with National Institute of Cardiovascular Diseases (NICVD), Karachi, from April 2003 to December 2003. The study included 45 diagnosed cases of heart failure with diabetes mellitus, between the age group 35-65 years. Serum magnesium and glucose levels were estimated and compared by using the student "t" test and p value (<0.01, <0.05, <0.001) were used to analyze the statistical significance. Out of 45 cases of heart failure, 15 were diabetic. Of these, eleven (73.3%) had low serum magnesium (<1.8 mg/dl), one (6.7%) was within normal range (1.8-2.0 mg/dl) and three (20%) were in the high level range(>2.0 mg/dl). The study showed low serum magnesium level in heart failure patients with diabetes mellitus.


Development and validation of an obstetric early warning system model for use in low resource settings.
The use of obstetric early-warning-systems (EWS) has been recommended to improve timely recognition, management and early referral of women who have or are developing a critical illness. Development of such prediction models should involve a statistical combination of predictor clinical observations into a multivariable model which should be validated. No obstetric EWS has been developed and validated for low resource settings. We report on the development and validation of a simple prediction model for obstetric morbidity and mortality in resource-limited settings. We performed a multivariate logistic regression analysis using a retrospective case-control analysis of secondary data with clinical indices predictive of severe maternal outcome (SMO). Cases for design and validation were randomly selected (n = 500) from 4360 women diagnosed with SMO in 42 Nigerian tertiary-hospitals between June 2012 and mid-August 2013. Controls were 1000 obstetric admissions without SMO diagnosis. We used clinical observations collected within 24 h of SMO occurrence for cases, and normal births for controls. We created a combined dataset with two controls per case, split randomly into development (n = 600) and validation (n = 900) datasets. We assessed the model's validity using sensitivity and specificity measures and its overall performance in predicting SMO using receiver operator characteristic (ROC) curves. We then fitted the final developmental model on the validation dataset and assessed its performance. Using the reference range proposed in the United Kingdom Confidential-Enquiry-into-Maternal-and-Child-Health 2007-report, we converted the model into a simple score-based obstetric EWS algorithm. The final developmental model comprised abnormal systolic blood pressure-(SBP > 140 mmHg or < 90 mmHg), high diastolic blood pressure-(DBP > 90 mmHg), respiratory rate-(RR > 40/min), temperature-(> 38 °C), pulse rate-(PR > 120/min), caesarean-birth, and the number of previous caesarean-births. The model was 86% (95% CI 81-90) sensitive and 92%- (95% CI 89-94) specific in predicting SMO with area under ROC of 92% (95% CI 90-95%). All parameters were significant in the validation model except DBP. The model maintained good discriminatory power in the validation (n = 900) dataset (AUC 92, 95% CI 88-94%) and had good screening characteristics. Low urine output (300mls/24 h) and conscious level (prolonged unconsciousness-GCS < 8/15) were strong predictors of SMO in the univariate analysis. We developed and validated statistical models that performed well in predicting SMO using data from a low resource settings. Based on these, we proposed a simple score based obstetric EWS algorithm with RR, temperature, systolic BP, pulse rate, consciousness level, urinary output and mode of birth that has a potential for clinical use in low-resource settings..


Clinical effects of continuous microwave for postoperative septic wound treatment: a double-blind controlled trial.
Continuous microwave (CM) has already been shown to be effective in treating various pathologic states. The aim of this trial was to study the curative effect of this new physical method on the course of postoperative suppurative and inflammatory processes in patients who underwent abdominal surgery. In this study, 141 patients with postoperative purulent wounds (predominantly caused by pyogenic Staphylococcus aureus) were randomized into two groups: 71 patients received local CM therapy (group A), and the other 70 patients received a placebo treatment using a similar but ineffective device (group B, controls). In this double-blind study, criteria for wound healing in both patient groups were evaluated. Results demonstrated that wound clearance was significantly accelerated in group A (treated with CM) compared with group B (controls): 5.6 +/- 0.6 versus 10.2 +/- 0.5 days (mean +/- standard deviation), respectively. Similarly, initial epithelization was significantly forced in group A compared with group B: 7.0 +/- 0.4 versus 12.8 +/- 0.6 days, respectively; and granulation appeared after 4.9 +/- 0.2 versus 8.7 +/- 0.4 days of postoperative treatment, respectively. Daily decrease of wound surface area was significantly higher in group A than in group B (7.1% versus 3.2%). On the fifth postoperative day of treatment, the number of microorganisms was considerably lower (10(5) per gram of tissue) in patients treated with CM than in controls. The results of this controlled clinical trial suggest that low-intensity CM is an effective postoperative treatment of purulent wounds after abdominal surgery. Further investigations may elucidate the underlying mechanisms in detail and optimize the curative effects in surgical practice.


Life events are important in the course of hopelessness-a 2-year follow-up study in a general population.
The association between life events and hopelessness in a general population is unknown. The aim of this study was to examine the course of hopelessness and how positive and negative life events are associated with it. This was a 2- year follow-up study among general population adults, excluding any with a mental disorder. The impact of 15 occasional life events during the follow-up was assessed and the course of hopelessness measured with the Beck Hopelessness Scale (HS). Four percent of the study subjects with no hopelessness at baseline and 56% of those with hopelessness at baseline reported hopelessness on follow-up. In multiple logistic regression analyses, a notable worsening of the subjective financial situation was revealed as the most important life event, both in becoming hopeless during the follow-up (OR 5.07; 95% CI 2.20-11.7) and in continued hopelessness (OR 7.51, 95% CI 2.19-25.8). Moreover, considerable interpersonal conflicts at work (OR 3.29, 95% CI 1.17-9.27) were associated with becoming hopeless. However, a notable positive change in common living conditions (OR 0.16, 95% CI 0.04-0.74) was found to be a protective factor against becoming hopeless. All these variables remained significant even when adjusted for change in depression scores (BDI). Hopelessness may be persistent in a general population. The impact of life events, especially a notable worsening of the subjective financial situation, is important in becoming or remaining hopeless.


Resting-state functional connectivity within orbitofrontal cortex and inferior frontal gyrus modulates the relationship between reflection level and risk-taking behavior in internet gaming disorder.
Internet gaming disorder (IGD) has become an increasing mental health issue worldwide. Previous studies indicated that IGD was related to maladaptive risk-taking behavior. However, the relationship among risk-taking behavior, reflection level, and resting-state functional connectivity (rsFC) between brain regions in IGD individuals remains unclear. The current study combined resting-state fMRI and the Devil task to investigate this issue. The behavioral results suggested that IGD participants exhibited increased risk-taking behavior in the Devil task than healthy controls. Moreover, IGD participants' risk-taking behavior was positively correlated with their reflection level. As for fMRI results, IGD participants showed stronger rsFC between orbitofrontal cortex (OFC) and inferior frontal gyrus (IFG) than healthy controls. Additionally, the mediation analyses revealed that, among IGD participants, the rsFC between OFC and IFG fully mediated the relationship between reflection level and risk-taking behavior. Together, the current study highlighted that the altered rsFC between OFC and IFG in IGD individuals modified the relationship between their reflection level and risk-taking behavior, which might contribute to the understanding of neural mechanisms underlying risk-taking behavior in IGD individuals.


Cortisol secretion in the elderly. Influence of age, sex and cardiovascular disease in a Chinese population.
Adrenal function and aging have been the object of intense interest in recent years. In this study we analyzed morning (08:00 h) serum cortisol concentrations from a sample of Chinese subjects aged from 31 to 110 years. These levels differed according to age, health status and sex, although the sex difference was confirmed only among the healthy elderly. These results suggest that age (older than 60 years), disease and male sex are associated with increased morning serum cortisol levels in a Chinese population.


Helicobacter pylori invades the gastric mucosa and translocates to the gastric lymph nodes.
Helicobacter pylori has been considered to be non-invasive and to rarely infiltrate the gastric mucosa, even though there is an active Th1 immune response in the lamina propria of the H. pylori-infected stomach. To elucidate whether H. pylori invades the lamina propria and translocates to the gastric lymph nodes, we examined H. pylori in formalin-fixed and paraffin-embedded tissue sections of stomach and gastric lymph nodes obtained from 51 cancer patients using real-time PCR and immunohistochemistry (IHC) with a novel anti-H. pylori monoclonal antibody that recognizes lipopolysaccharides. Fresh gastric lymph nodes were used to culture for H. pylori. In 46 patients with H. pylori in the stomach, the bacterium was found in the lymph nodes from 21 patients by culture, 37 patients by PCR, and 29 patients by IHC. H. pylori captured by macrophages was found in the lamina propria of 39 patients. In the lymph nodes, the bacterium was found in many macrophages and a few interdigitating dendritic cells at the paracortical areas. H. pylori was also found in the intracellular canaliculi of parietal cells in 21 patients, but intracytoplasmic invasion into gastric epithelial cells was not identified. When compared to the commercially available anti-H. pylori antibodies, the novel antibody showed the highest sensitivity to detect H. pylori-positive macrophages, whereas no difference was found for H. pylori in the mucous layer. The H. pylori-positive macrophages in the lamina propria correlated with chronic gastritis as well as translocation of such cells to the lymph nodes. These results suggest that H. pylori-induced gastric epithelial damage allows the bacteria to invade the lamina propria and translocate to the gastric lymph nodes, which may chronically stimulate the immune system. The bacteria captured by macrophages, whether remaining alive or not, may contribute to the induction and development of H. pylori-induced chronic gastritis.


Tracing type 1 diabetic Tibet miniature pig's bone marrow mesenchymal stem cells in vitro by magnetic resonance imaging (1).
Traditional cell-tracking methods fail to meet the needs of preclinical or clinical research. Thus, the aim of the present study was to establish a new method of double labeling bone marrow mesenchymal stem cells (BMSCs) from type 1 diabetic (T1D) minipigs with super-paramagnetic iron oxide (SPIO) and enhanced green fluorescent protein (eGFP) and tracing them using MRI in vitro. Isolated BMSCs from T1D minipigs were labeled with eGFP and different concentrations of SPIO. The effects of lentivirus (LV)-eGFP transfection and SPIO on the viability and growth curves of BMSCs were determined by Trypan blue exclusion, the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide assay and flow cytometry. Cellular ultrastructure was evaluated by transmission electron microscopy. Magnetic resonance imaging was used to evaluate BMSCs labeled with SPIO-eGFP complexes 6 weeks after labeling. Expression of eGFP in BMSCs peaked 96 h after transfection with LV-eGFP. Prussian blue staining revealed scattered blue granules in the cytoplasm of SPIO-labeled cells. Transmission electron microscopy revealed that the dense granules aggregated mainly in secondary lysosomes. On MRI, T2* -weighted imaging was far more sensitive for SPIO-labeled BMSCs than other image sequences 3 and 6 weeks after the cells had been labeled with SPIO-eGFP. We have developed a relatively simple and safe method for double labeling of BMSCs from T1D minipigs using SPIO and LV-eGFP and tracing them in vitro by MRI for 6 weeks.


Surgical marking pen dye inhibits saphenous vein cell proliferation and migration in saphenous vein graft tissue.
Markers containing dyes such as crystal violet (CAS 548-62-9) are routinely used on the adventitia of vein bypass grafts to avoid twisting during placement. Because little is known about how these dyes affect vein graft healing and function, we determined the effect of crystal violet on cell migration and proliferation, which are responses to injury after grafting. Fresh human saphenous veins were obtained as residual specimens from leg bypass surgeries. Portions of the vein that had been surgically marked with crystal violet were analyzed separately from those that had no dye marking. In the laboratory, they were split into easily dissected inner and outer layers after removal of endothelium. This cleavage plane was within the circular muscle layer of the media. Cell migration from explants was measured daily as either (1) percentage of migration-positive explants, which exclusively measures migration, or (2) number of cells on the plastic surrounding each explant, which measures migration plus proliferation. Cell proliferation and apoptosis (Ki67 and TUNEL staining, respectively) were determined in dye-marked and unmarked areas of cultured vein rings. The dose-dependent effects of crystal violet were measured for cell migration from explants as well as for proliferation, migration, and death of cultured outer layer cells. Dye was extracted from explants with ethanol and quantified by spectrophotometry. There was significantly less cell migration from visibly blue compared with unstained outer layer explants by both methods. There was no significant difference in migration from inner layer explants adjacent to blue-stained or unstained sections of vein because dye did not penetrate to the inner layer. Ki67 staining of vein in organ culture, which is a measure of proliferation, progressively increased up to 6 days in nonblue outer layer and was abolished in the blue outer layer. Evidence of apoptosis (TUNEL staining) was present throughout the wall and not different in blue-stained and unstained vein wall segments. Blue outer layer explants had 65.9 ± 8.0 ng dye/explant compared with 2.1 ± 1.3 for nonblue outer layer explants. Dye applied in vitro to either outer or inner layer explants dose dependently inhibited migration (IC50∼10 ng/explant). The IC50s of crystal violet for outer layer cell proliferation and migration were 0.1 and 1.2 μg/mL, whereas the EC50 for death was between 1 and 10 μg/mL. Crystal violet inhibits venous cell migration and proliferation, indicating that alternative methods should be considered for marking vein grafts.


Novel amyloid-beta pathology C. elegans model reveals distinct neurons as seeds of pathogenicity.
Protein misfolding and aggregation are hallmarks of neurodegenerative diseases such as Alzheimer's disease (AD). In AD, the accumulation and aggregation of tau and the amyloid-beta peptide Aβ1-42 precedes the onset of AD symptoms. Modelling the aggregation of Aβ is technically very challenging in vivo due to its size of only 42 aa. Here, we employed sub-stoichiometric labelling of Aβ1-42 in C. elegans to enable tracking of the peptide in vivo, combined with the "native" aggregation of unlabeled Aβ1-42. Expression of Aβ1-42 leads to severe physiological defects, neuronal dysfunction and neurodegeneration. Moreover, we can demonstrate spreading of neuronal Aβ to other tissues. Fluorescence lifetime imaging microscopy enabled a quantification of the formation of amyloid fibrils with ageing and revealed a heterogenic yet specific pattern of aggregation. Notably, we found that Aβ aggregation starts in a subset of neurons of the anterior head ganglion, the six IL2 neurons. We further demonstrate that cell-specific, RNAi-mediated depletion of Aβ in these IL2 neurons systemically delays Aβ aggregation and pathology.


Technical and clinical evaluation of an electrochemistry glucose meter: experience in a diabetes center.
The Sensorex (Metertech, Taipei, Taiwan), an electrochemical blood glucose meter, is designed for self-monitoring of blood glucose (BG) concentrations in capillary blood through the use of an electrochemical test strip. The intra-assay coefficients of variation of Sensorex were 5.2, 5.4, and 4.7% at BG levels of 46, 154 and 302 mg/dl respectively. The BG concentrations tested by Sensorex were correlated well with those by YSI method (r approximately/= 0.85, P < 0.0001). The intraclass correlation coefficients (rI) between the results obtained by Sensorex and YSI were 0.84 in capillary blood and 0.69 in venous whole blood, which indicated good agreement between both methods. The Sensorex was evaluated by error grid analysis and revealed 'acceptance' results. In field test, the Sensorex results obtained by lay users were in concordance with those by trained technicians (rI = 0.87). Our data show that the Sensorex glucometer is reliable and easy to use. We also demonstrate a practical clinical approach for the evaluation of a novel SMBG system.


Braid configuration designed for fiber-packed capillary in microscale sample preparation.
A novel miniaturized sample preparation device with braid-type extraction medium was successfully developed. Introducing a set of bundles of fine synthetic filaments as the materials of the braid-type extraction medium and also the application of an appropriate tension during the braiding process, the outer diameter of the resulting braid has been controlled. Optimization of the tension enables an easy preparation of a group of braids that can be well-compatible to various internal diameters of capillaries to be packed. The extraction conditions were systematically optimized, and the efficient extraction was confirmed under the optimized conditions. All the parameters affects the desorption efficiency were also optimized, where typical extraction efficiency was more than 90% for the extraction of phenanthrene (1.0 μg/mL) in water. The extracted analyte was desorbed sufficiently by employing a sequential pumping process of two organic solvents. During the preparation of the braid, a different type of fibrous materials could be inserted to the opening at the center of the braid. Taking advantage of this feature of the braid, a stainless steel wire was inserted into the center of the braid. By applying low voltages to the stainless steel wire, a heat-assisted desorption of the extracted analyte was also studied. Experimentally complete desorption (higher than 99.0%) was obtained with the voltage application of 2 V. The lowest limit of quantification (LOQ) and the lowest limit of detection (LOD) for phenanthrene were 0.048 and 0.014 μg/mL, respectively.


Simultaneous multislice imaging with slice-multiplexed RF pulses.
A method for simultaneous multislice imaging is presented that uses a multislice RF pulse that imparts a different linear phase profile to each slice. During readout, slices are unaliased by using extra slice-select gradient lobes, which rephase and dephase individual slices one at a time. Compared to other simultaneous slice methods, this method avoids distortion by slice-select gradients, and does not require extra views or additional hardware. However, because one echo per slice is required, the method requires a longer read period. This can cause non-ideal rephasing of the individual slices due to susceptibility gradients, which manifests itself as crosstalk between slices. There is also a concomitant increase in the minimum TR of the sequence. The method is demonstrated with phantom and in vivo images using gradient-echo and spin-echo versions.


Comparison of nasopharyngeal aspirate and nasal swab specimens for detection of respiratory syncytial virus in different settings in a developing country.
To compare detection of respiratory syncytial virus (RSV) for diagnostic purposes using nasopharyngeal aspirate (NPA) and nasal swabs (NS) in different clinical settings in a community study in Guinea-Bissau. During 1996-98 paired specimens were obtained from 635 children under 5 years of age (median: 274 days; interquartile range: 144-453 days) with symptoms of lower respiratory infections (LRI). The specimens were analysed by an enzyme-linked immunosorbent assay for RSV antigen in Guinea-Bissau and re-analysed in Denmark using the same assay. The gold standard for RSV antigen detection was defined as any test being positive. RSV antigen was detected in 84 (13%) children, the prevalence being 19% (41/219) among infants aged < 6 months, 12% (22/184) in infants aged 6-11 months, and 9% (21/230) in older children. Sensitivity of antigen detection was higher in NPA (92% in analyses in Guinea-Bissau and 98% in Denmark) than in NS (63% in analyses in Guinea-Bissau, 71% in Denmark). Specificity of RSV antigen detection was equally high in NPA and NS (99-100%). Time since onset of symptoms was significantly shorter in RSV antigen positive than negative samples. Sensitivity did not depend on clinical setting or age of the child. Using NS samples was associated with a 27-31% reduction in sensitivity compared with NPA specimens. As NPAs are costly and considered a nuisance by the population, it might be cost-effective in larger epidemiological studies to lose 25-30% in sensitivity but be able to collect samples from a much larger population.


Additions to the checklist of Scoliidae, Sphecidae, Pompilidae and Vespidae of Peru, with notes on the endemic status of some species (Hymenoptera, Aculeata).
The first checklist of the Peruvian Hymenoptera listed 1169 species and subspecies of aculeate wasps, including 173 species of Pompilidae, seven of Scoliidae, 39 of Sphecidae and 403 of Vespidae. Herein are reported 32 species as new for Peru based mainly on the collection of the Natural History Museum, London. The loss of the endemic status of two species is also reported: Entypus peruvianus (Rohwer) (Pompilidae: Pepsinae) and Omicron ruficolle schunkei Giordani Soika (Vespidae: Eumeninae).


A threefold rise in widespread extreme rain events over central India.
Socioeconomic challenges continue to mount for half a billion residents of central India because of a decline in the total rainfall and a concurrent rise in the magnitude and frequency of extreme rainfall events. Alongside a weakening monsoon circulation, the locally available moisture and the frequency of moisture-laden depressions from the Bay of Bengal have also declined. Here we show that despite these negative trends, there is a threefold increase in widespread extreme rain events over central India during 1950-2015. The rise in these events is due to an increasing variability of the low-level monsoon westerlies over the Arabian Sea, driving surges of moisture supply, leading to extreme rainfall episodes across the entire central subcontinent. The homogeneity of these severe weather events and their association with the ocean temperatures underscores the potential predictability of these events by two-to-three weeks, which offers hope in mitigating their catastrophic impact on life, agriculture and property.Against the backdrop of a declining monsoon, the number of extreme rain events is on the rise over central India. Here the authors identify a threefold increase in widespread extreme rains over the region during 1950-2015, driven by an increasing variability of the low-level westerlies over the Arabian Sea.


Sexual dimorphism in the fibers of a "clasp" muscle of Xenopus laevis.
When antibodies specific to fast-twitch, slow-twitch, and slow-tonic myosins were used to stain the clasp muscle, m. sternoradialis, of Xenopus laevis, three predominant fiber types were identified in both males and females. Three fiber types can also be distinguished by the diameters and conduction velocities of their motor nerves. Significant differences in the numbers of slow-tonic fibers were identified between the genders and between control and castrated male animals. This finding suggests that these slow-tonic fibers, which probably dominate the clasp reflex during mating, may be under hormonal control.


Molecular biology and genetics of lymphomas.
This article summarizes molecular and genetic features of B-cell non-Hodgkin lymphoma and focuses on diffuse large B-cell lymphoma, Burkitt lymphoma, follicular lymphoma, and mantle cell lymphoma. In each of these entities, hallmark genetic aberrations, cytogenetic characteristics, and alterations of single genes that might be involved in the pathogenesis and molecular evolution of the tumor are described. Recent results from gene-expression profiling studies are incorporated that are relevant for the classification of lymphoma entities, the prediction of their clinical behavior, and the identification of deregulated signal-transduction pathways that might represent potential targets in future therapeutic approaches.


The revised cardiac risk index is associated with morbidity and mortality independent of injury severity in elderly patients with rib fractures.
Risk factors for mortality and in-hospital morbidity among geriatric patients with traumatic rib fractures remain unclear. Such patients are often frail and demonstrate a high comorbidity burden. Moreover, outcomes anticipated by current rubrics may reflect the influence of multisystem injury or surgery, and thus not apply to isolated injuries in geriatric patients. We hypothesized that the Revised Cardiac Risk Index (RCRI) may assist in risk-stratifying geriatric patients following rib fracture. All geriatric patients (age ≥65 years) with a conservatively managed rib fracture owing to an isolated thoracic injury (thorax AIS ≥1), in the 2013-2019 TQIP database were assessed including demographics and outcomes. The association between the RCRI and in-hospital morbidity as well as mortality was analyzed using Poisson regression models while adjusting for potential confounders. 96,750 geriatric patients sustained rib fractures. Compared to those with RCRI 0, patients with an RCRI score of 1 had a 16% increased risk of in-hospital mortality [adjusted incidence rate ratio (adj-IRR), 95% confidence interval (CI): 1.16 (1.02-1.32), p=0.020]. An RCRI score of 2 [adj-IRR (95% CI): 1.72 (1.44-2.06), p<0.001] or ≥3 [adj-IRR (95% CI): 3.07 (2.31-4.09), p<0.001] was associated with an even greater mortality risk. Those with an increased RCRI also exhibited a higher incidence of myocardial infarction, cardiac arrest, stroke, and acute respiratory distress syndrome. Geriatric patients with rib fractures and an RCRI ≥1 represent a vulnerable and high-risk group. This index may inform the decision to admit for inpatient care and can also guide patient and family counseling as well as computer-based decision-support.


Membrane voltage modulates the GABA(A) receptor gating in cultured rat hippocampal neurons.
The kinetics of GABAergic currents in neurons is known to be modulated by the membrane voltage but the underlying mechanisms have not been fully explored. In particular, the impact of membrane potential on the GABA(A) receptor gating has not been elucidated. In the present study, the effect of membrane voltage on current responses elicited by ultrafast GABA applications was studied in cultured hippocampal neurons. The current to voltage relationship (I-V) for responses to saturating [GABA] (10 mM) showed an inward rectification (slope conductance at positive voltages was 0.62 +/- 0.05 of that at negative potentials). On the contrary, I-V for currents evoked by low [GABA] (1 microM) showed an outward rectification. The onset of currents elicited by saturating [GABA] was significantly accelerated at positive potentials. Analysis of currents evoked by prolonged applications of saturating [GABA] revealed that positive voltages significantly increased the rate and extent of desensitization. The onsets of current responses to non-saturating [GABA] were significantly accelerated at positive voltages indicating an enhancement of the binding rate. However, at low [GABA] at which the onset rate is expected to approach an asymptote set by opening/closing and unbinding rates, no significant modification of current onset by voltage was observed. Quantitative analysis based on model simulations indicated that the major effect of membrane depolarization was to increase the rates of binding, desensitization and of opening as well as to slightly reduce the rate of exit from desensitization. In conclusion, we provide evidence that membrane voltage affects the GABA(A) receptor microscopic gating.


Reproductive concerns and contributing factors in women of childbearing age with systemic lupus erythematosus.
Reproductive concerns are common in women of childbearing age with systemic lupus erythematosus (SLE) with inadequate disclosure. This study aimed to investigate the contributing factors of reproductive concerns and to evaluate their impact on health-related quality of life. One hundred eighty women of childbearing age with SLE were enrolled in this cross-sectional study in Affiliated Hospital of Nantong University from March 2021 to December 2021. A series of questionnaires were conducted: Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), the Hospital Anxiety and Depression Scale (HADS), the Multidimensional Fatigue Inventory (MFI-20), Female Sexual Distress Scale-Revised (FSDS-R), Family Assessment Device (APGAR), the Medical Coping Modes Questionnaire (MCMQ), the Short-Form 36 (SF-36), and the Chinese version of Reproductive Concerns After Cancer (RCAC). Independent t test, one-way ANOVA, Mann-Whitney U test, Pearson/Spearman, and multiple linear stepwise regression were used to analyze the data. The results indicated that female SLE patients were more concerned about the child's health and personal health than becoming pregnant, fertility potential, partner disclose and acceptance; SLE patients with the characteristics of living in rural residence, having no reproductive history, fearing unexpected pregnancy, sexual distress, and depression showed more serious fertility concerns. Meanwhile, most female SLE patients adopted active confrontation when facing reproductive concerns, and these patients were significantly lower in the dimension score of mental related quality of life. Our study demonstrated that female SLE patients should be paid more attention to their fertility concerns and effective intervention measures should be carried out to relieve their reproductive concerns, so as to improve their long-term quality of life if their disease condition permits.


Pulmonary arterial pseudoaneurysm as an unusual complication of pulmonary actinomycosis: Two case reports.
We report 2 cases of pulmonary actinomycosis complicated by a pseudoaneurysm. In Case 1, a 67-year-old man visited a hospital 7 months ago because of hemoptysis. CT revealed a suspected lung abscess in the left lingular segment; however, no diagnosis was confirmed by bronchoscopy. A CT scan taken after heavy hemoptysis showed a pseudoaneurysm within the consolidation of the same segment. On the same day, embolization of the left bronchial and intercostal arteries was performed. Left lingulectomy was performed 5 days later, and pulmonary actinomycosis was diagnosed histologically. Case 2 was a 51-year-old man with a 2-year history of cough and intermittent hemoptysis. CT showed a lesion with a cavity suggesting an abscess 3 months previously, and antibiotic treatment was started. After the appearance of massive hemoptysis, embolization was performed for a pseudoaneurysm seen on bronchial arteriography. Four days later, a left lower lobectomy was performed, and pulmonary actinomycosis was histologically diagnosed. Pseudoaneurysms are commonly associated with tuberculosis; however, only one report of pseudoaneurysms has been associated with pulmonary actinomycosis. Appropriate treatment should be selected according to the type of pseudoaneurysm and the risk of recurrent hemoptysis. Angiography and embolization are essential tools in diagnosing and treating pulmonary arterial pseudoaneurysms; however, surgical intervention may also be an option in some cases to ensure a good long-term outcome.


A phosphorylated 34-kDa protein and a subpopulation of polyhedrin are thiol linked to the carbohydrate layer surrounding a baculovirus occlusion body.
Surrounding baculovirus occlusion bodies is an electron-dense layer reported to be composed of carbohydrate which we term calyx. Incubation of Autographa californica nuclear polyhedrosis virus occlusion bodies (AcMNPV OBs) with dilute alkaline saline (DAS) followed by centrifugation at 12,000 g resulted in the sedimentation of calyx material which contained pp34, residual polyhedrin (p32), and entrapped occluded virions (DAS P-12 fraction). Incubation of the DAS P-12 fraction with sodium dodecyl sulfate (SDS) resulted in solubilization of the entrapped virions and the majority of p32, while calyx material, pp34, and some p32 remained sedimentable at 12,000 g. Immunofluorescence microscopy of DAS-solubilized OBs using monoclonal antibody to pp34 and p32 revealed that both pp34 and p32 are closely associated with the calyx. When DAS P-12 fractions were resuspended in SDS and reducing agent, not only were the entrapped virions solubilized, but pp34 and the remaining p32 were also liberated, indicating that pp34 and a subpopulation of p32 are associated with the calyx via thiol linkages. Immunoblot analysis and peptide mapping demonstrated that pp34 is neither immunologically nor structurally related to p32. The kinetics of pp34 synthesis were also examined by immunoprecipitation of infected cell polypeptides using pp34-specific monoclonal antibody. pp34 was detected initially 15 hr postinfection (p.i.) and continued to be phosphorylated until 60-70 hr p.i. This study demonstrates that the AcMNPV calyx has a proteinaceous component and we propose that other occluded baculoviruses may also have a calyx-associated protein analogous to pp34.


Patient-centered care in chronic disease management: a thematic analysis of the literature in family medicine.
The objective was to provide a synthesis of the results of the research and discourse lines on main dimensions of patient-centered care in the context of chronic disease management in family medicine, building on Stewart et al.'s model. We developed search strategies for the Medline, Embase, and Cochrane databases, from 1980 to April 2009. All articles addressing patient-centered care in the context of chronic disease management in family medicine were included. A thematic analysis was performed using mixed codification, based on Stewart's model of patient-centered care. Thirty-two articles were included. Six major themes emerged: (1) starting from the patient's situation; (2) legitimizing the illness experience; (3) acknowledging the patient's expertise; (4) offering realistic hope; (5) developing an ongoing partnership; (6) providing advocacy for the patient in the health care system. The context of chronic disease management brings forward new dimensions of patient-centered care such as legitimizing the illness experience, acknowledging patient expertise, offering hope and providing advocacy. Chronic disease management calls for the adaptation of the family physician's role to patients' fluctuating needs. Literature also suggests the involvement of the family physician in care transitions as a component of patient-centered care.


Laboratory automation reduces time to report of positive blood cultures and improves management of patients with bloodstream infection.
The impact on time to results (TTR) and clinical decisions was evaluated for mono-microbial positive blood cultures (BC) processed using the BD Kiestra Work Cell Automation (WCA) system. Positive BC were processed by the WCA system by full-automatic subculture on solid media and digital imaging after 8 h of incubation (8-h method) followed by identification (ID) and antimicrobial susceptibility testing (AST). To evaluate the accuracy of the 8-h method, ID and AST from 8-h and overnight incubated colonies were compared for the same organisms. To evaluate its clinical impact, results from 102 BC processed by the 8-h method (cases) were compared with those from 100 BC processed by overnight incubation method (controls) in a comparable period. Identification after 8-h and overnight incubation gave concordant results in 101/102 (99.0%) isolates. Among a total of 1379 microorganism-antimicrobial combinations, categorical agreement was 99.4% (1371/1379); no very major error, 7 major errors, and one minor error were observed. TTR in cases (32.8 h ± 8.3 h) was significantly (p < 0.001) shorter than in controls (55.4 h ± 13.3 h). A significant reduction was observed for duration of empirical therapy (cases 54.8 h ± 23.3 h vs controls 86.9 h ± 34.1 h, p < 0.001) and 30-day crude mortality rate (cases 16.7% vs controls 29.0%, p < 0.037). Automation and 8-h digital reading of plates from positive BC, followed by ID and AST, greatly reduce TTR and shorten the duration of antimicrobial empiric therapy, possibly improving outcome in patients with mono-microbial bloodstream infections.


Annexin II binds progastrin and gastrin-like peptides, and mediates growth factor effects of autocrine and exogenous gastrins on colon cancer and intestinal epithelial cells.
We and others have reported the presence of novel progastrin (PG)/gastrin receptors on normal and cancerous intestinal cells. We had earlier reported the presence of 33-36 kDa gastrin-binding proteins on cellular membranes of colon cancer cells. The goal of the current study was to identify the protein(s) in the 33-36 kDa band, and analyse its functional significance. A carbodiimide crosslinker was used for crosslinking radio-labeled gastrins to membrane proteins from gastrin/PG responsive cell lines. Native membrane proteins, crosslinked to the ligand, were solubulized and enriched by >1000-fold, and analysed by surface-enhanced laser desorption/ionization-time of flight-mass spectrometry. The peptide masses were researched against the NCBInr database using the ProFound search engine. Annexin II (ANX II) was identified, and confirmed by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry. As HCT-116 cells express autocrine PG, the in situ association of PG with ANX II was demonstrated in pulldown assays. Direct binding of PG with ANX II was confirmed in an in vitro binding assay. In order to confirm a functional importance of these observations, sense and anti-sense (AS) ANX II RNA-expressing clones of intestinal epithelial (IEC-18) and human colon cancer (HCT-116) cell lines were generated. AS clones demonstrated a significant loss in the growth response to exogenous (IEC-18) and autocrine (HCT-116) PG. We have thus discovered that membrane-associated ANX II binds PG/gastrins, and partially mediates growth factor effects of the peptides.


Levels of uric acid and increased diastolic blood pressure: Risk factors for atrial fibrillation in patients older than 60 years.
To characterize the maximum P-wave duration (Pmax) and P-wave dispersion (PWD) according to blood pressure (BP) and uric acid (UA) levels in geriatric patients. An analytical study was performed in 83 patients aged over 60 years treated at the Family Medical Office 5 of the Aracelio Rodríguez Castellón Polyclinic, in Cienfuegos, Cuba between January and December 2015. The sample was divided into two groups (patients with hyperuricemia and patients with normal UA levels). We found a linear and significant correlation between diastolic BP and Pmax in patients with hyperuricemia (r=0.695; p=0.026), but not in patients with normal UA (r=0.048; p=0.757). A linear and significant correlation was demonstrated between diastolic BP and PWD in patients with hyperuricemia (r=0.657; p=0.039), but not in patients with normal UA (r=0.054; p=0.730). There is correlation between diastolic BP and Pmax plus PWD in elderly patients with hyperuricemia.


Cultured neurones from the mature bovine mediobasal hypothalamus contain LHRH but not catecholamine.
The in vitro culture of mature neurones from bovine mediobasal hypothalamus (MBH) is reported, providing a model for studies of mammalian neurosecretion at the cellular level. Explant tissue cultures of mature bovine MBH containing the arcuate nucleus were examined for LHRH, ACTH and catecholamines with a view to investigating the control of prolactin and gonadotropin secretion. LHRH immunoreactivity was found in both neuronal and non-neuronal cells in the outgrowth monolayer region of the explant. Neurones in this region appeared able to attach to a substrate and regenerate, in monolayer culture, well developed neurites characterized by beaded swellings as observed in vivo. Neither ACTH immunoreactivity nor catecholamine fluorescence was detected. Cultured neurones and astrocytes were labelled by tetanus toxin and anti-GFAP, respectively. Double labelling of cultures with tetanus toxin and anti-LHRH demonstrated the neuronal nature of many LHRH-immunoreactive cells. Radio-immunoassay data confirmed the presence of LHRH in the cultures but application of 60 mM KC1 failed to evoke hormone release. These studies have confirmed the view of previous workers that hypothalamic control of prolactin secretion in the bovine may be very different from that thought to occur in non-ruminants such as the rat and guinea pig. Finally, this work demonstrates that a cultured system from the mature bovine may prove a good model for study of neuronal regulation of gonadotropin secretion by the bovine mediobasal hypothalamus.


Morphological and functional electrophysiological evidence of relative spinal cord tethering in adolescent idiopathic scoliosis.
Magnetic resonance (MR) imaging and multiplanar reconstruction was used to evaluate the morphology and relative position of the spinal cord in adolescent idiopathic scoliosis (AIS). To determine the longitudinal and cross-sectional morphology of spinal cord in AIS subjects versus normal controls and their correlation with relative position of cerebellar tonsils and somatosensory cortical evoked potentials (SSEP). Our previous studies revealed significantly reduced spinal cord to vertebral column length ratios in AIS patients with severe scoliotic curves suggesting the presence of disproportional growth between the neural and skeletal system. A possible neural origin of etiopathogenesis of AIS is suggested. MR multiplanar reconstruction was performed in 97 adolescent girls (35 moderate, 26 severe AIS with right-sided thoracic/thoracolumbar curve, and 36 age-matched controls). Measurements of the ratio of anteroposterior (AP) and transverse (TS) diameter of the cord, the concave and convex lateral cord space (LCS) were obtained at the apical level in AIS subjects. Same parameters were obtained in normal controls at matched vertebral levels. Correlations were made with cord to vertebral column length ratio, cerebellar tonsil position and SSEP findings. AP/TS cord ratio and LCS ratio were increased in AIS subjects in the presence of reduced spinal cord to vertebral length ratio when compared with normal controls (P < 0.05). The above ratios were exaggerated in AIS subjects with abnormal SSEP findings. The AP/TS cord ratio and LCS ratio were negatively correlated with the cord to vertebral column length ratio (rho = -0.410 and -0.313, P < 0.01) and cerebellar tonsillar level (rho = -0.309 and -0.432, P < 0.01). Our study suggests presence of tethering and increased tension along the longitudinal axis of spinal cord with associated morphologic changes of cross-sectional shape and relative position of the cord.


Flavodoxin overexpression confers tolerance to oxidative stress in beneficial soil bacteria and improves survival in the presence of the herbicides paraquat and atrazine.
To determine whether expression of a cyanobacterial flavodoxin in soil bacteria of agronomic interest confers protection against the widely used herbicides paraquat and atrazine. The model bacterium Escherichia coli, the symbiotic nitrogen-fixing bacterium Ensifer meliloti and the plant growth-promoting rhizobacterium Pseudomonas fluorescens Aur6 were transformed with expression vectors containing the flavodoxin gene of Anabaena variabilis. Expression of the cyanobacterial protein was confirmed by Western blot. Bacterial tolerance to oxidative stress was tested in solid medium supplemented with hydrogen peroxide, paraquat or atrazine. In all three bacterial strains, flavodoxin expression enhanced tolerance to the oxidative stress provoked by hydrogen peroxide and by the reactive oxygen species-inducing herbicides, witnessed by the enhanced survival of the transformed bacteria in the presence of these oxidizing agents. Flavodoxin overexpression in beneficial soil bacteria confers tolerance to oxidative stress and improves their survival in the presence of the herbicides paraquat and atrazine. Flavodoxin could be considered as a general antioxidant resource to face oxidative challenges in different micro-organisms. The use of plant growth-promoting rhizobacteria or nitrogen-fixing bacteria with enhanced tolerance to oxidative stress in contaminated soils is of significant agronomic interest. The enhanced tolerance of flavodoxin-expressing bacteria to atrazine and paraquat points to potential applications in herbicide-treated soils.


Laparoscopic ileo-cecectomy for ileo-ceco-colic double intussusception due to a cecal adenoma harboring multifocal high grade dysplasia in a 24 years old male: A case report.
Intestinal Intussusception is defined as invagination of the intussusceptum into the intussuscepien, and is responsible of 1% of all bowel obstructions. It is rare in adults and common in children. It is mostly due to organic causes in adults that form lead points. Enteroenteric intussusception is the most common type. Signs and symptoms are more classic in children but nonspecific in adults. Usually diagnosis is made intraoperatively, while abdomino-pelvic CT scan is the best preoperative imaging modality. Intestinal Intussusception in adults, especially when the colon is involved, is best treated by surgical resection. A 24 years old previously healthy male with no surgical or documented familial history presenting for severe crampy abdominal pain and distention, obstipation and palpable right lower quadrant abdominal mass. Abdominal Multi-slice CT diagnosed an ileo-colic intussusception without signs of bowel suffering. Laparoscopic ileo-cecetomy. Final Pathology showed a 4 cm cecal tubular adenomatous polyp with multifocal high grade dysplasia. Intestinal intussusception in adults is an interesting rare entity that have the interest of general surgeons. Malignant lesions can be lead-points and they form a great counterpart among other colonic lesions. Minimally invasive laparoscopic surgery is gaining interest in management, and surgical resection remains the gold standard while reduction before surgery is debatable and can be considered in selected cases.


Regulation of sarcolemmal Na(+)/H(+) exchange by hydrogen peroxide in adult rat ventricular myocytes.
To characterise the effects of exogenous H(2)O(2) on sarcolemmal Na(+)/H(+) exchanger (NHE) activity and determine the roles of extracellular signal-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38 MAPK) and protein kinase C (PKC) in observed effects. Sarcolemmal H(+) efflux rate (J(H)) was determined by microepifluorescence at a pH(i) of 6.70 in adult rat ventricular myocytes, after two consecutive acid pulses in HCO(3)(-)-free medium; before the second pulse, cells (n=7-10/group) were exposed to H(2)O(2) or vehicle and the change in J(H) (DeltaJ(H)) was used to quantify the change in NHE activity. ERK and p38 MAPK activities were determined by immunoblotting with phosphospecific antibodies. Relative to control, DeltaJ(H) was increased by a 10-min exposure to 100, but not 1 or 10 microM H(2)O(2) (1000 microM was not tolerated); 3 or 6 min exposure to 100 microM H(2)O(2) was without effect. ERK and p38 MAPK activities were both increased by 100 microM H(2)O(2) (peak at 6 min); the ERK kinase inhibitor PD98059 (10 microM), but not the p38 MAPK inhibitor SB203580 (1 microM), inhibited the H(2)O(2)-induced increase in DeltaJ(H). H(2)O(2)-induced ERK activation was inhibited not only by PD98059 (10 microM), but also by the non-selective tyrosine kinase inhibitor genistein (3-100 microM), the EGF receptor kinase inhibitor AG1478 (3-300 nM) and the Src family kinase inhibitor PP2 (0.1-10 microM). The PKC inhibitors GF109203X (0.3-10 microM) and chelerythrine (1-30 microM) were without effect on ERK activation, although the former abolished the H(2)O(2)-induced increase in DeltaJ(H). Our data demonstrate that, in adult rat ventricular myocytes, (i) hydrogen peroxide stimulates sarcolemmal NHE activity, (ii) this response requires activation of ERK and PKC, but not p38 MAPK, (iii) ERK activation occurs through tyrosine kinase-mediated, but PKC-independent, mechanisms


Long-term patency of the right internal mammary artery used as a coronary bypass conduit and the effect of the recipient vessel.
This study reviewed our experience with the long-term patency of the right internal mammary coronary artery (RIMA) bypass graft in 58 patients over 1 year. Thirty-one percent (n = 18) of patients had obstructive lesions in the RIMA. In vessels with any lesion, the percent stenosis was 85.5% (range 30% to 100%). Eleven of 38 patients (28%) with right-sided recipient vessels had significant stenosis, whereas 21% of left-sided recipient vessels had significant stenosis of the RIMA. When compared with left internal mammary artery grafting, the long-term patency of the RIMA was lower than expected and warrants larger prospective studies.


What do people do before going to bed? A study of bedtime procrastination using time use surveys.
Bedtime procrastination (BP) is defined as going to bed later than intended despite absence of external reasons. This study investigated sleep and psychological factors associated with BP in young adults, and further compared how high and low BP groups spend their time over 24 h and also 3 h prior to bedtime using time use surveys. Young adults (N = 106) from the community were classified as either high (n = 54) or low (n = 52) BP group based on the Bedtime Procrastination Scale. All participants were asked to complete questionnaires on insomnia, depression, anxiety, stress, and chronotype, in addition to keeping a 7-day sleep diary and completing time use surveys over 48 h. Participants were 61.3% female, mean age 22.7 (±2.89) years old. Individuals in the high BP group reported significantly more depression, anxiety, and insomnia, went to bed later, woke up later, and had more eveningness tendencies compared to the low BP group. Results from the time use surveys revealed that the high BP group spent significantly more time engaging in leisure and social activity with the majority of time spent using media over 24 h compared to the low BP group. Finally, the high BP group spent on average approximately 451% (or 61 min) more time per day on their smartphone 3 h prior to bedtime compared to the low BP group. Our results suggest that BP is negatively associated with sleep and mood, and should be considered a serious health-interfering behavior.


Resection of middle petroclival meningioma via combined anterior transpetrosal and retrosigmoid approaches at two separate stages: 3D operative video.
Surgical access to the petroclival region poses a challenge to neurosurgeons. A wide range of approaches has been demonstrated in the past. In this video, the authors present a 69-year-old male patient who presented with 3-month history of worsening left-sided numbness. The tumor was totally removed in 2 sessions via anterior transpetrosal and retrosigmoid approaches, respectively. The authors demonstrate 2 separate skull base approaches to resect a petroclival meningioma and discuss pitfalls and problems of management for challenging meningiomas. The authors suggest that surgical approaches to petroclival meningiomas should be selected based on an individual case. A skull base team should be versatile in performing all these approaches. The video can be found here: https://youtu.be/BCVrn3TeNvE .


Spätzle, a signaling molecule that interacts with pathogen-associated molecules and Toll-like receptor in Portunus trituberculatus.
Spätzle is a crucial ligand for Toll-like receptor (TLR) that triggers the activation of TLR signal pathway in insects. In this study, open reading frames (ORFs) of two spätzles were cloned from Portunus trituberculatus (PtSpz1 and PtSpz2). Both of PtSpzs contained the typical cystine-knot domain of spätzle. Tissue distribution analysis showed that both of PtSpzs were predominantly expressed in the gills. Transcriptional levels of the two PtSpzs in hemocytes and gill rapidly increased at 3 h and 6 h post Vibrio alginolyticus challenge, respectively. The two PtSpzs could bind to several pathogen-associated molecules including lipopolysaccharide (LPS), peptidoglycan (PGN) and envelope proteins of white spot syndrome virus (WSSV). Moreover, the two PtSpzs could directly interact with the extracellular leucine-rich repeats (LRR) domain of TLR. This study revealed that spätzle could interact with pathogen-associated molecules and TLR of host, which may be two important steps for spätzle to deliver signals into host cells.


Effect of haemodilution on experimental cerebral oedema in cats.
The effect of haemodilution with Dextran 60 on experimental cerebral oedema produced by the modified method of Ishii, Hayner, Kelly & Evans (1959) is described. The intracranial pressure was measured from the cisterna magna or epidurally in the parieto-occipital region. In the group of cats subjected to haemodilution, with a haematocrit of 27.20 +/- 1.48%, the intracranial pressure first increased by 500% and, after 1.5 h, began to fall gradually so that at the end of the experiment it was only 160% of initial value. In the other experimental group in which haemodilution with a haematocrit of 27.40 +/- 1.14% was started after 6 h of the experiment, the intracranial pressure gradually fell for the next 6 h from 350% of initial value of 200% of initial value after 12 h. It was concluded that haemodilution slows down the development of cerebral oedema, and can be employed in the treatment of fully developed oedema.