[68Ga]Ga-DOTA-TATE uptake in subacute stroke following craniotomy for meningioma: a diagnostic tool for stroke?
Gallium 68 (68Ga) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid labelled octreotate ([68Ga]Ga-DOTA-TATE) positron emission tomography (PET) is an established imaging technique for identifying tumours of neuroendocrine origin and meningiomas; the radiotracer binds to somatostatin receptor type 2 (SSTR2), which is richly expressed by these malignancies. Here, we present a rare case hinting at novel ischaemic stroke detection by [68Ga]Ga-DOTA-TATE PET scan. The scan was performed 14 days post resection of an atypical meningioma with the intention to assess the extent of residual tumour for radiosurgical treatment of the operative cavity. Surprisingly, the [68Ga]Ga-DOTA-TATE PET-avid region corresponded to an area of perioperative subacute ischaemic stroke detected by MRI. This case corroborates the two previously reported cases of incidental detection of ischaemic stroke during routine [68Ga]Ga-DOTA-TATE PET imaging, collectively suggesting the need for caution when interpreting the imaging findings. A possible underlying mechanism for [68Ga]Ga-DOTA-TATE uptake in stroke is increased SSTR2 expression by macrophages recruited into infarcted tissue.


Psychological interventions for overweight or obesity.
Overweight and obesity are global health problems which are increasing throughout the industrialised world. If left unchecked, they will continue to contribute to the ever increasing noncommunicable disease burden. To assess the effects of psychological interventions for overweight or obesity as a means of achieving sustained weight loss. Studies were obtained from searches of multiple electronic bibliographic databases. The date of the latest search was June 2003. Trials were included if the fulfilled the following criteria: 1) they were randomised controlled clinical trials of a psychological intervention versus a comparison intervention, 2) one of the outcome measures of the study was weight change measured by any method, 3) participants were followed for at least three months, 4) the study participants were adults (18 years or older) who were overweight or obese (BMI > 25 kg/m(2)) at baseline. Two people independently applied the inclusion criteria to the studies identified and assessed study quality. Disagreement was resolved by discussion or by intervention of a third party. Meta-analyses were performed using a fixed effect model. A total of 36 studies met the inclusion criteria and were included in the review. Overall, 3495 participants were evaluated. The majority of studies assessed behavioural and cognitive-behavioural weight reduction strategies. Cognitive therapy, psychotherapy, relaxation therapy and hypnotherapy were assessed in a small number of studies. Behaviour therapy was found to result in significantly greater weight reductions than placebo when assessed as a stand-alone weight loss strategy (WMD -2.5 kg; 95% CI -1.7 to -3.3). When behaviour therapy was combined with a diet / exercise approach and compared with diet / exercise alone, the combined intervention resulted in a greater weight reduction. Studies were heterogeneous however the majority of studies favoured combining behaviour therapy with dietary and exercise interventions to improve weight loss. Increasing the intensity of the behavioural intervention significantly increased the weight reduction (WMD -2.3 kg; 95% CI -1.4 to - 3.3). Cognitive-behaviour therapy, when combined with a diet / exercise intervention, was found to increase weight loss compared with diet / exercise alone (WMD -4.9 kg; 95% CI -7.3 to - 2.4). No data on mortality, morbidity or quality of life were found. People who are overweight or obese benefit from psychological interventions, particularly behavioural and cognitive-behavioural strategies, to enhance weight reduction. They are predominantly useful when combined with dietary and exercise strategies. The bulk of the evidence supports the use of behavioural and cognitive-behavioural strategies. Other psychological interventions are less rigorously evaluated for their efficacy as weight loss treatments.


Efficacy of manipulation for non-specific neck pain of recent onset: design of a randomised controlled trial.
Manipulation is a common treatment for non-specific neck pain. Neck manipulation, unlike gentler forms of manual therapy such as mobilisation, is associated with a small risk of serious neurovascular injury and can result in stroke or death. It is thought however, that neck manipulation provides better results than mobilisation where clinically indicated. There is long standing and vigorous debate both within and between the professions that use neck manipulation as well as the wider scientific community as to whether neck manipulation potentially does more harm than good. The primary aim of this study is to determine whether neck manipulation provides more rapid resolution of an episode of neck pain than mobilisation. 182 participants with acute and sub-acute neck pain will be recruited from physiotherapy, chiropractic and osteopathy practices in Sydney, Australia. Participants will be randomly allocated to treatment with either manipulation or mobilisation. Randomisation will occur after the treating practitioner decides that manipulation is an appropriate treatment for the individual participant. Both groups will receive at least 4 treatments over 2 weeks. The primary outcome is number of days taken to recover from the episode of neck pain. Cox regression will be used to compare survival curves for time to recovery for the manipulation and mobilisation treatment groups. This paper presents the rationale and design of a randomised controlled trial to compare the effectiveness of neck manipulation and neck mobilisation for acute and subacute neck pain.


Juvenile Hormone Is Required in Adult Males for Drosophila Courtship.
Juvenile Hormone (JH) has a prominent role in the regulation of insect development. Much less is known about its roles in adults, although functions in reproductive maturation have been described. In adult females, JH has been shown to regulate egg maturation and mating. To examine a role for JH in male reproductive behavior we created males with reduced levels of Juvenile Hormone Acid O-Methyl Transferase (JHAMT) and tested them for courtship. JHAMT regulates the last step of JH biosynthesis in the Corpora Allata (CA), the organ of JH synthesis. Males with reduced levels of JHAMT showed a reduction in courtship that could be rescued by application of Methoprene, a JH analog, shortly before the courtship assays were performed. In agreement with this, reducing JHAMT conditionally in mature flies led to courtship defects that were rescuable by Methoprene. The same result was also observed when the CA were conditionally ablated by the expression of a cellular toxin. Our findings demonstrate that JH plays an important physiological role in the regulation of male mating behavior.


Antibody-dependent enhancement of feline infectious peritonitis virus infection in feline alveolar macrophages and human monocyte cell line U937 by serum of cats experimentally or naturally infected with feline coronavirus.
Infection of the type II feline infectious peritonitis virus (FIPV) strain 79-1146 to primary feline alveolar macrophages and human monocyte cell line U937 was enhanced by the sera of cats experimentally infected with the 79-1146 strain, but not those of cats infected with KU-2 or UCD-1 strain of type I FIPV. The experiments using sera of cats with feline infectious peritonitis (FIP) and of cats naturally infected with feline coronavirus (FCoV) revealed that infection of the FIPV 79-1146 strain to the U937 cells was enhanced only by the sera of cats infected with type II FIPV or feline enteric coronavirus. The samples positive for antibody-dependent enhancement (ADE) activity had high neutralizing antibody titers against the FIPV 79-1146 strain and the samples negative for ADE activity had low neutralizing antibody titers. These findings support the previous results where a monoclonal antibody with neutralizing activity had high ADE activity, suggesting that there was a close relationship between the neutralization and enhancement sites. And then it is also suggested that ADE of infection is likely to be induced by re-infection with the same serotype of virus in type II FIPV infection. Furthermore, U937 cells are considered useful and can be substituted for the feline macrophages for determining ADE of FIPV-infection.


Response of the portal vein of spontaneous hypertensive rats to intracellular pH.
The effect of intracellular pH perturbations on the portal vein preparations of spontaneously hypertensive rats and their control Wistar Kyoto rats was investigated. Intracellular alkalinity induced by application of 20 mM NH4Cl or 20 mM trimethylamine produced dilatation of both preparations. Intracellular acidity induced by washout of the previous ammonium and trimethylamine solutions or by application of 20 mM sodium propionate solution caused constriction of both preparations. These responses of the portal veins of both animals to intracellular pH variations were qualitatively the same in nonactivated preparations and in preparations precontracted with 26 mM K+ or 1 microM norepinephrine. Recovery from acidic constrictions induced by washout of ammonium and trimethylamine solutions was significantly slower in spontaneous hypertensive rats than in Wistar Kyoto rats preparations. Conceivably, a lower intracellular pH in the vascular smooth muscle of the resistance vessels of hypertensive patients, as compared to normotensive individuals, may partly account for the hypertensive phenomena.


Hepatitis B virus DNA in Kaposi sarcoma.
DNA extracted from Kaposi sarcoma biopsies was analyzed for the presence of hepatitis B viral (HBV) DNA sequences by Southern blot hybridization. The probes used were (i) molecularly cloned subgenomic fragments of HBV DNA and (ii) HBV DNA extracted from Dane particles that included DNA sequences that encode hepatitis B surface antigen and core antigen. The limited study reported here demonstrates that HBV DNA exists mainly in an episomal state in the Kaposi sarcoma tissue and that these DNA forms are different from those found in hepatitis B virion. The presence of various DNA forms suggests that HBV DNA is engaged in DNA replication, which implies that the tissue is infected with HBV.


Facilitation of A[delta]-fiber-mediated acute pain by repetitive transcranial magnetic stimulation.
Repetitive transcranial magnetic stimulation (rTMS) of the motor cortex modulates acute and chronic pain perception. The authors previously showed that rTMS over the primary motor cortex (M1) inhibited capsaicin-induced acute pain ascending through C-fibers. To investigate the effects of 1-Hz rTMS over M1 on acute experimentally induced pain mediated by Adelta-fibers (i.e., another type of acute pain). The authors examined whether rTMS over M1 affected laser evoked potentials (LEPs) in 13 normal subjects using thulium: yttrium-aluminum-garnet laser stimulation. Subjective pain-rating scores and LEPs obtained under three different conditions--rTMS, realistic sham stimulation, and a control condition with no stimulation--were compared. The authors found that 1-Hz rTMS over M1 significantly aggravated the subjective pain and enhanced the N2-P2 amplitudes compared with the sham or control sessions. Because the pain-rating scores and the N2-P2 amplitudes correlated positively, the N2-P2 amplitudes in the present study can be regarded as the cortical correlate of subjective pain. Together with the authors' previous study on C-fiber pain, this facilitatory effect of repetitive transcranial magnetic stimulation on Adelta-fiber-mediated further strengthens the notion of a relationship between repetitive transcranial magnetic stimulation over M1 and pain perception.


Sleep structure in sleep bruxism: A polysomnographic study including bruxism activity phenotypes across sleep stages.
The aim of the study was to assess sleep structure, phenotypes related to bruxism activity and basic respiratory parameters among a large group of participants with sleep bruxism and without obstructive sleep apnea. Adult participants with clinical suspicion of sleep bruxism and with no other significant medical history were recruited. Video-polysomnography was performed to detect masseter muscles activity. Polysomnographic scoring was performed according to the American Academy of Sleep Medicine Criteria. Finally, 146 participants were included. The participants were divided into three subgroups: severe, mild and no sleep bruxism. There were no differences in total sleep time, sleep latency, sleep efficiency, wake duration after sleep onset, rapid eye movement, and measured respiratory parameters. The severity of sleep bruxism contributed to the increased intensity of all sleep bruxism phenotypes in almost all sleep stages, apart from tonic and mixed activity in non-rapid eye movement stage 3 sleep (slow-wave sleep). Those with bruxism spent more time in rapid eye movement sleep compared to controls; there were no differences in non-rapid eye movement sleep stages. The results confirmed that sleep bruxism does not significantly affect sleep duration, efficiency and continuity (in terms of sleep-wake cycles). Sleep bruxism contributes to a higher percentage of rapid eye movement sleep in the total sleep time. Those with bruxism present more frequent episodes during all stages of sleep; however, in the case of slow-wave sleep, tonic and mixed activity observed in participants with sleep bruxism are comparable to those of healthy people.


The role of chemokine receptor 4 and its ligand stromal cell derived factor 1 in breast cancer.
Breast tumour cells express the chemokine receptor C-X-C chemokine receptor type 4 (CXCR4) and frequently metastasize to organs with an abundant source of CXCR4 ligand, stromal cell derived factor1 (SDF1). For this reason, CXCR4/SDF1 has garnered much interest as a target for therapeutic intervention. The present study is an attempt to correlate the CXCR4/SDF1 expression patterns with clinicopathological factors, patient survival, and its coexistence and response to 17-β estradiol (E2) and 4-hydoxytamoxifen (4OHT) in breast cancer cells. Immunohistochemistry and Reverse Transcriptase-Polymerase Chain Reaction were performed to assess the protein and gene level expressions of CXCR4 and SDF1 in normal and tumour breast tissue. The effect of E2 and 4OHT on expression of CXCR4 and SDF1 in breast cancer cells were assessed using RT-PCR, Immunofluorescence microscopy and colocalization. The CXCR4 and SDF1 were over expressed and have a significant correlation with each other as well as with histological grade, tumour size and poor survival of patients. The study also showed a modulatory effect of E2 and 4OHT on the expression and colocalization of CXCR4/SDF1 in breast cancer cells. The correlation of CXCR4/SDF1 with other parameters and modulatory effect of E2 and 4OHT on the expression and colocalization of CXCR4/SDF1 in breast cancer cells are likely to open up new avenues for the successful management of this malignancy.


Effective size of density-dependent populations in fluctuating environments.
Reliable estimates of effective population size Ne are of central importance in population genetics and evolutionary biology. For populations that fluctuate in size, harmonic mean population size is commonly used as a proxy for (multi-) generational effective size. This assumes no effects of density dependence on the ratio between effective and actual population size, which limits its potential application. Here, we introduce density dependence on vital rates in a demographic model of variance effective size. We derive an expression for the ratio Ne/N in a density-regulated population in a fluctuating environment. We show by simulations that yearly genetic drift is accurately predicted by our model, and not proportional to 1/(2N) as assumed by the harmonic mean model, where N is the total population size of mature individuals. We find a negative relationship between Ne/N and N. For a given N, the ratio depends on variance in reproductive success and the degree of resource limitation acting on the population growth rate. Finally, our model indicate that environmental stochasticity may affect Ne/N not only through fluctuations in N, but also for a given N at a given time. Our results show that estimates of effective population size must include effects of density dependence and environmental stochasticity.


Development of an Alu-based, QSY 7-labeled primer PCR method for quantitation of human DNA in forensic samples.
Determining the amount of human DNA extracted from a crime scene sample is an important step in DNA profiling. The forensic community relies almost entirely upon a technique (slot blot) to quantitate human DNA that is imprecise, time consuming, and labor intensive. This paper describes the development of a new technique based on PCR amplification of a repetitive Alu sequence. Specific primers were used to amplify a 124-bp fragment of Alu sequence; amplification was detected by SYBR Green I staining in a fluorescent plate reader. To reduce background in the plate reader assay, QSY-7 labeled primers were utilized. The assay was tested on animal DNAs, human blood spots, mock crime samples, and degraded DNA in comparison with the slot blot technique. The QSY Alu assay has a dynamic range of 10 ng to 10 pg, and is sensitive, specific, fast, quantitative, and comparable in cost to the slot blot assay.


alpha-adrenergic stimulation of respiration in isolated rat hepatocytes.
1. The alpha-adrenergic agonists noradrenaline (in the presence of beta-blocker) and phenylephrine cause a transient stimulation of the respiration in isolated rat hepatocytes. After a lag period of 12s, this activation first attains its maximal value (+24%) for about 1 min and then falls to a sustained value (+15%). The effect is blocked by the alpha-antagonists phenoxybenzamine and phentolamine. It is dose-dependent, with an half-maximal stimulation by 16 nM-noradrenaline, which is similar to that found for other cell responses to the hormone. 2. Vasopressin and ATP, which in common with alpha-agonists are believed to increase intracellular [Ca2+], induce similar activation in the respiration rate. 3. The alpha-adrenergic-mediated respiration depends on extracellular Ca2+. The activation is decreased or abolished when extracellular [Ca2+] is decreased by adding EGTA, or when the Ca2+ antagonists Mn2+ and La3+ are present in the incubation medium. 4. It is suggested that the activation of the mitochondrial respiration rate results from the increase in cytosolic Ca2+ concentration, presumably via Ca2+ influx or Ca2+ release from the plasma membrane or endoplasmic reticulum.


A comparative safety review of targeted therapies for acute myeloid leukemia.
Acute myeloid leukemia (AML) treatment has primarily focused on 7 + 3 chemotherapy, but in the last decade there has been a significant increase in new therapies, mostly targeted agents, approved for the treatment of AML. We performed a comparative analysis of the unique safety profile of each of these new agents. We conducted a review of the current literature on public databases (PubMed, ClinicalTrials.gov, and U.S. Food and Drug Administration) regarding new AML drugs that were approved from 2017 to 2023. The diagnosis of AML typically carries a poor prognosis but with an increase in the number of drugs that are now available, patients' outcomes are improving. With novel mechanisms of action, the use of these agents introduces different safety profiles, occasionally with adverse events not previously seen with standard chemotherapy or at different frequencies. An understanding of the drugs available and the safety concerns associated with each one is crucial to selecting the best available option for each patient, and early recognition and appropriate management of drug-related adverse effects.


OSKIRA-4: a phase IIb randomised, placebo-controlled study of the efficacy and safety of fostamatinib monotherapy.
OSKIRA-4 evaluated the efficacy of fostamatinib monotherapy versus placebo on the signs and symptoms of rheumatoid arthritis over 6 weeks by Disease Activity Score C reactive protein (DAS-28(CRP)) and assessed non-inferiority to adalimumab monotherapy at Week 24 by DAS-28(CRP). Overall, 279 patients not currently taking disease-modifying antirheumatic drugs were randomised to: (A) fostamatinib 100 mg twice daily for 24 weeks plus placebo injection every 2 weeks (PBOI); (B) fostamatinib 100 mg twice daily for 4 weeks, then 150 mg once daily up to Week 24, plus PBOI; (C) fostamatinib 100 mg twice daily for 4 weeks, then 100 mg once daily up to Week 24, plus PBOI; (D) adalimumab 40 mg every 2 weeks for 24 weeks, plus oral placebo twice daily; or (E) oral placebo twice daily for 6 weeks, plus PBOI, then a switch to arm A or B. Fostamatinib demonstrated a significant improvement in DAS-28(CRP) score from baseline versus placebo at Week 6 for arms A and B, but not C. Fostamatinib was significantly less effective than adalimumab at Week 24 based on DAS-28(CRP). Adverse events observed with fostamatinib treatment were consistent with those reported in previous studies, including hypertension and diarrhoea. Fostamatinib demonstrated efficacy as monotherapy, showing superior DAS-28(CRP) score changes between baseline and 6 weeks when compared with placebo in treatment arms A and B. However, all fostamatinib regimens demonstrated inferior responses compared with adalimumab at Week 24. Clinicaltrials.gov: NCT01264770.


Epitaxial graphene on SiC{0001}: advances and perspectives.
We review here recent progress on epitaxial graphene grown on a SiC substrate. Epitaxial graphene can be easily grown by heating the SiC single crystal in a high vacuum or in an inert gas atmosphere. The SiC surfaces used for graphene growth contain Si- and C-terminated faces. On the Si-face, homogeneous and clean graphene can be grown with a controlled number of layers, and the carrier mobility reaches as high as several m(2) V s(-1), although this is reduced by the presence of the substrate steps. On the C-face, although the number of layers is not homogeneous, twisted bilayer graphene can be grown, which is expected to be the technique of choice to modify the electronic structure of graphene. From the application point of view, graphene on SiC will be the platform used to fabricate high-speed electronic devices and dense graphene nanoribbon arrays, which will be used to introduce a bandgap.


Separation of normal and premalignant cervical epithelial cells using confocal light absorption and scattering spectroscopic microscopy ex vivo.
Confocal light absorption and scattering spectroscopic (CLASS) microscopy can detect changes in biochemicals and the morphology of cells. It is therefore used to detect high-grade cervical squamous intraepithelial lesion (HSIL) cells in the diagnosis of premalignant cervical lesions. Forty cervical samples from women with abnormal Pap smear test results were collected, and twenty cases were diagnosed as HSIL; the rest were normal or low-grade cervical squamous intraepithelial lesion (LSIL). The enlarged and condensed nuclei of HSIL cells as viewed under CLASS microscopy were much brighter and bigger than those of non-HSIL cells. Cytological elastic scattered light data was then collected at wavelengths between 400 and 1000 nm. Between 600 nm to 800 nm, the relative elastic scattered light intensity of HSIL cells was higher than that of the non-HSIL. Relative intensity peaks occurred at 700 nm and 800 nm. CLASS sensitivity and specificity results for HSIL and non-HSIL compared to cytology diagnoses were 80% and 90%, respectively. This study demonstrated that CLASS microscopy could effectively detect cervical precancerous lesions. Further study will verify this conclusion before the method is used in clinic for early detection of cervical cancer.


Variant callers for next-generation sequencing data: a comparison study.
Next generation sequencing (NGS) has been leading the genetic study of human disease into an era of unprecedented productivity. Many bioinformatics pipelines have been developed to call variants from NGS data. The performance of these pipelines depends crucially on the variant caller used and on the calling strategies implemented. We studied the performance of four prevailing callers, SAMtools, GATK, glftools and Atlas2, using single-sample and multiple-sample variant-calling strategies. Using the same aligner, BWA, we built four single-sample and three multiple-sample calling pipelines and applied the pipelines to whole exome sequencing data taken from 20 individuals. We obtained genotypes generated by Illumina Infinium HumanExome v1.1 Beadchip for validation analysis and then used Sanger sequencing as a "gold-standard" method to resolve discrepancies for selected regions of high discordance. Finally, we compared the sensitivity of three of the single-sample calling pipelines using known simulated whole genome sequence data as a gold standard. Overall, for single-sample calling, the called variants were highly consistent across callers and the pairwise overlapping rate was about 0.9. Compared with other callers, GATK had the highest rediscovery rate (0.9969) and specificity (0.99996), and the Ti/Tv ratio out of GATK was closest to the expected value of 3.02. Multiple-sample calling increased the sensitivity. Results from the simulated data suggested that GATK outperformed SAMtools and glfSingle in sensitivity, especially for low coverage data. Further, for the selected discrepant regions evaluated by Sanger sequencing, variant genotypes called by exome sequencing versus the exome array were more accurate, although the average variant sensitivity and overall genotype consistency rate were as high as 95.87% and 99.82%, respectively. In conclusion, GATK showed several advantages over other variant callers for general purpose NGS analyses. The GATK pipelines we developed perform very well.


Treatment of cancer in adolescents and young adults: is affordability a concern?
Progress in the treatment of cancers in young people has resulted in an increasing success rate in curing the different forms of malignant diseases. The mission of the CPAC/C(17) Task Force on Adolescents and Young Adults (AYA) with cancer is to ensure prompt, equitable access to the best care; establish research priorities to optimize health outcomes and health-related quality of life; and mitigate current disparities of care through advances in treatment, education, and research. Although these goals are important, the mission statement seems to ignore an important factor: "affordability," or the ability to achieve these goals due to scarcity of resources. In this article, the role of economics in helping decision makers decide on resource allocation is discussed. Also described is the economic basis for the healthcare problem; the inability of the current methodology of cost-effectiveness to provide information that can help improve resource allocation in health; and how economics should be used to promote efficient use of healthcare resources. The author argued that "affordability" should be recognized in the mission statement. Recognizing "affordability" means recognizing the need to justify the transfer (or allocation) of additional resources to AYA cancer, which requires demonstration that the value of what is gained from the use of these resources in AYA cancer exceeds the value of what is forgone by using them elsewhere. This will also require making explicit the values or equity criteria to which society subscribes.


From an isolated right ventricular thrombus to the diagnosis of the hypereosinophilic syndrome.
This case concerns a 58-year-old male who presented with abdominal pain, anorexia, nausea, and exertional dyspnea of one month's duration. On further evaluation peripheral eosinophilia was conspicuous and eosinophilic infiltration was found in the gastrointestinal system and bone marrow. Echocardiography showed an isolated right ventricular thrombus with tricuspid valve involvement. Cardiac magnetic resonance imaging helped to confirm the diagnosis of cardiac involvement in hypereosinophilic syndrome without requiring a cardiac biopsy.


Prevalence of soil-transmitted helminths and associated risk factors among primary school children in Kandahar, Afghanistan: A cross-sectional analytical study.
Soil-transmitted helminth (STH) infections are global health problem, especially in low-income countries. Main objectives of this study were to estimate the prevalence and intensity of STH and its risk factors among school children in Kandahar city of Afghanistan. This was a school-based cross-sectional analytical study, with data collected during eight-month-period (May-December, 2022) from 6- and 12-years old school children in Kandahar city, Afghanistan. All the stool samples were examined by saline wet mount method and Kato-Katz technique. Data were analyzed by using descriptive statistics, Chi square test, and multivariate logistic regression. A total of 1275 children from eight schools of Kandahar city were included in this study. Mean age of these children was 8.3 years with 53.3% boys. The overall prevalence of any intestinal parasitic infection was 68.4%. The overall prevalence of STH infection was 39.1%, with Ascaris lumbricoides (29.4%) as the most prevalent STH species. Mean intensity of overall STH infection was 97.8. Multivariate logistic regression revealed playing barefoot (AOR 1.6, 95% CI 1.1-2.2), not washing hands after defecating and before eating (AOR 1.3, 95% CI 1.0-1.7), having untrimmed nails (AOR 1.4, 95% CI 1.1-1.8), and belonging to poor families (AOR 1.3, 95% CI 1.0-1.7) as the risk factors associated with the predisposition of school children for getting STH in Kandahar city of Afghanistan. There is high prevalence of STH among school children of Kandahar city in Afghanistan. Most of the risk factors are related to poverty, decreased sanitation, and improper hygiene. Improvement of socioeconomic status, sanitation, and health education to promote public awareness about health and hygiene together with periodic mass deworming programs are better strategies for the control of STH infections in Afghanistan.


Leukoencephalopathy with calcifications and cysts: A case report.
Leukoencephalopathy with calcifications and cysts (LCC) is an uncommon entity characterized by edematous leukoencephalopathy, cerebral calcifications, and parenchymal cysts. Due to its rarity, the clinical, radiological, and histopathological features have yet to be well elucidated. The first case is a 35-year-old female who was asymptomatic. A giant intracranial cyst was incidentally detected radiologically, and it was slowly growing in the recent 10 years. The second case is a 20-year-old female who presented with a 1-month history of headache. Brain computed tomography showed multiple asymmetric calcifications in the bilateral basal ganglia and white matter. Magnetic resonance imaging revealed a cyst in the right parietal lobe. They were diagnosed with LCC. The first patient underwent surgical resection of the intracranial cyst, and the second patient received a stereotactic biopsy. The patients performed well postoperatively. LCC can be found at any age. A young age seems to be associated with severer symptoms. The clinical manifestations can be variable and aggressive. The potential pathogenic basis still needs further research.


Dietary restrictions for patients with neutropenia: a survey of institutional practices.
To describe institutional practices related to dietary restrictions for patients with neutropenia to determine whether restrictions are used and when they are implemented and discontinued. Descriptive survey. 156 institutions belonging to the Association of Community Cancer Centers. Mailed survey. Of the institutions surveyed, 78% (n = 120) placed patients with neutropenia on restricted diets. Participating institutions responded that patients were placed on restricted diets at a variety of different white blood cell and neutrophil counts, including neutrophils < 1,000 (43%) and < 500 (46%). The majority of institutions (92%) placed patients on restricted diets once neutropenia was documented, while only 9% of institutions restricted diets when cancer treatment was initiated. Of the participating institutions, 83% (n = 96) restricted diets only when patients were neutropenic rather than throughout the duration of the chemotherapy regimen. The most commonly restricted foods were fresh fruits and juices (92%), fresh vegetables (95%), and raw eggs (74%). Few institutions restricted tap water (12%). Wine was restricted at 39% of institutions, and beer was restricted at 40% of institutions. The role of diet in the development of infection in patients with neutropenia is unclear. This unclear role contributes to the variation in dietary restrictions among institutions. Additional research should focus on dietary factors contributing to neutropenic infections and establishing criteria for implementation of specific dietary modifications. Nursing assessment should include nutritional status and risk factors for neutropenia and bacterial translocation. Nursing protocols for neutropenic dietary restrictions should be based on research findings.


[COVID-19 and stress-related disorders].
Since the WHO declared the COVID-19 outbreak a pandemic, the most actual problem has been a change in the lifestyle of the population of Russia and the rest of the world. Fear of illness, self-isolation/quarantine, and decreased quality of life have dramatically increased the level of stress-related disorders in the population. The main mental disorders arising from stress refer to anxiety disorders (post-traumatic stress disorder (PTSD), panic disorder, agoraphobia, social phobia, generalized anxiety disorder), obsessive-compulsive disorder, depressions of varying severity and conversion reactions. The symptoms and early warning signs of stress-related disorders may be chronic or episodic. Stress-related disorders are corrected with psychotropic therapy, which aims to restore the balance of neurotransmitters. Current first choice agents for the treatment of both pathological anxiety and depression are selective serotonin reuptake inhibitors (SSRIs). During the pandemic, the SSRI fluvoxamine is of special interest. Its mechanisms of action are recognized as potentially useful for treating COVID-19 infection. Two studies confirming the efficacy and safety of fluvoxamine in the treatment of coronavirus infection are described.


Left Ventricular Summit-Concept, Anatomical Structure and Clinical Significance.
The left ventricular summit (LVS) is a triangular area located at the most superior portion of the left epicardial ventricular region, surrounded by the two branches of the left coronary artery: the left anterior interventricular artery and the left circumflex artery. The triangle is bounded by the apex, septal and mitral margins and base. This review aims to provide a systematic and comprehensive anatomical description and proper terminology in the LVS region that may facilitate exchanging information among anatomists and electrophysiologists, increasing knowledge of this cardiac region. We postulate that the most dominant septal perforator (not the first septal perforator) should characterize the LVS definition. Abundant epicardial adipose tissue overlying the LVS myocardium may affect arrhythmogenic processes and electrophysiological procedures within the LVS region. The LVS is divided into two clinically significant regions: accessible and inaccessible areas. Rich arterial and venous coronary vasculature and a relatively dense network of cardiac autonomic nerve fibers are present within the LVS boundaries. Although the approach to the LVS may be challenging, it can be executed indirectly using the surrounding structures. Delivery of the proper radiofrequency energy to the arrhythmia source, avoiding coronary artery damage at the same time, may be a challenge. Therefore, coronary angiography or cardiac computed tomography imaging is strongly recommended before any procedure within the LVS region. Further research on LVS morphology and physiology should increase the safety and effectiveness of invasive electrophysiological procedures performed within this region of the human heart.


A complex regulatory landscape involved in the development of mammalian external genitals.
Developmental genes are often controlled by large regulatory landscapes matching topologically associating domains (TADs). In various contexts, the associated chromatin backbone is modified by specific enhancer-enhancer and enhancer-promoter interactions. We used a TAD flanking the mouse HoxD cluster to study how these regulatory architectures are formed and deconstructed once their function achieved. We describe this TAD as a functional unit, with several regulatory sequences acting together to elicit a transcriptional response. With one exception, deletion of these sequences didn't modify the transcriptional outcome, a result at odds with a conventional view of enhancer function. The deletion and inversion of a CTCF site located near these regulatory sequences did not affect transcription of the target gene. Slight modifications were nevertheless observed, in agreement with the loop extrusion model. We discuss these unexpected results considering both conventional and alternative explanations relying on the accumulation of poorly specific factors within the TAD backbone.


The "halo effect" in Korea: change in practice patterns since the introduction of robot-assisted laparoscopic radical prostatectomy.
Acquisition of the da Vinci surgical system (Intuitive Surgical, Mountain View, USA) has enabled robot-assisted surgery to become an acceptable alternative to open radical prostatectomy (ORP). Implementation of robotics at a single institution in Korea induced a gradual increase in the number of performances of robot-assisted laparoscopic radical prostatectomy (RALP) to surgically treat localized prostate cancer. We analyzed the impact of robotic instrumentation on practice patterns among urologists and explain the change in value in ORP and RALP-the standard treatment and the new approach or innovation of robotic technology. The overall number of prostatectomies has increased over time because the number of RALPs has grown drastically whereas the number of OPRs did not decrease during the period of evaluation. Our experience emphasizes the potential of RALP to become the gold standard in the treatment of localized prostate cancer in various parts of the world.


Cardiometabolic risk factors in vegans; A meta-analysis of observational studies.
There is increasing evidence that plant based diets are associated with lower cardiovascular risk. To evaluate effects of a vegan compared to an omnivorous diet on cardio-metabolic risk factors. Meta-analysis of observational studies published between 1960 and June 2018 that reported one or more cardio-metabolic risk factors in vegans and controls eating an omnivorous diet were undertaken. Macro-nutrient intake and cardio-metabolic risk factors were compared by dietary pattern. The Newcastle Ottawa Scale (NOS) was used to assess the quality of each study. The inverse-variance method was used to pool mean differences. Statistical analyses were performed using RevMan software version 5•2 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen. 40 studies with 12 619 vegans and 179 630 omnivores were included. From food frequency questionnaires in 28 studies, vegans compared to omnivores consumed less energy (-11%, 95% confidence interval -14 to -8) and less saturated fat (- 51%, CI -57 to -45). Compared to controls vegans had a lower body mass index (-1.72 kg/m2, CI -2.30 to -1.16), waist circumference (-2.35 cm, CI -3.93 to -0.76), low density lipoprotein cholesterol (-0.49 mmol/L CI -0.62 to -0.36), triglycerides (-0.14 mmol/L, CI -0.24 to -0.05), fasting blood glucose (-0.23 mmol/, CI -0.35 to -0.10), and systolic (-2.56 mmHg, CI -4.66 to -0.45) and diastolic blood pressure (-1.33 mmHg, CI -2.67 to -0.02), p<0.0001 for all. Results were consistent for studies with < and ≥ 50 vegans, and published before and after 2010. However in several large studies from Taiwan a vegan diet was not associated with favourable cardio-metabolic risk factors compared to the control diets. In most countries a vegan diet is associated with a more favourable cardio- metabolic profile compared to an omnivorous diet.


The effect of host admixture on wild house mouse gut microbiota is weak when accounting for spatial autocorrelation.
The question of how interactions between the gut microbiome and vertebrate hosts contribute to host adaptation and speciation is one of the major problems in current evolutionary research. Using bacteriome and mycobiome metabarcoding, we examined how these two components of the gut microbiota vary with the degree of host admixture in secondary contact between two house mouse subspecies (Mus musculus musculus and M. m. domesticus). We used a large data set collected at two replicates of the hybrid zone and model-based statistical analyses to ensure the robustness of our results. Assuming that the microbiota of wild hosts suffers from spatial autocorrelation, we directly compared the results of statistical models that were spatially naive with those that accounted for spatial autocorrelation. We showed that neglecting spatial autocorrelation can strongly affect the results and lead to misleading conclusions. The spatial analyses showed little difference between subspecies, both in microbiome composition and in individual bacterial lineages. Similarly, the degree of admixture had minimal effects on the gut bacteriome and mycobiome and was caused by changes in a few microbial lineages that correspond to the common symbionts of free-living house mice. In contrast to previous studies, these data do not support the hypothesis that the microbiota plays an important role in host reproductive isolation in this particular model system.


Life-cycle flow of mercury and recycling scenario of fluorescent lamps in Japan.
We summarized the mercury flow of mercury-containing products from their manufacture to their disposal in Japan and discussed the current management of mercury-containing hazardous household waste (HHW). The mercury flow originating from these products was estimated to be about 10-20 tonnes annually, about 5 tonnes of which was attributable to fluorescent lamps, the major mercury-containing product in Japan. The recent rapid increase in digital home electronics with liquid crystal displays (e.g.,televisions, personal computers, mobile phones, and digital cameras) has led to a marked increase in the production of backlights, which are also fluorescent and contain mercury. Most of the annual flow was disposed of as waste, with only 0.6 tonnes Hg recovered. The mercury flow for end-of-life fluorescent lamps (excluding backlights) was analyzed under three scenarios for Kyoto, Japan for 2003: the present condition scenario, the improved recycling scenario, and the complete recycling scenario. Under the present condition scenario, mercury flow was calculated to be 34 kg Hg for incineration, 21 kg Hg for landfill, and only 4 kg Hg for recycling. The complete recycling scenario shows a simple flow, with all mercury recycled. Under this scenario for Kyoto, we calculated that a cyclic system having 47 kg of mercury (3.5 tonnes Hg in Japan) could be established if all fluorescent lamps (excluding those stored in residences) were collected and recycled. Mercury is a HHW priority chemical, and we need to limit its use and establish a closed-loop system. There are currently no regulations to achieve this, and the management of most HHWs is left to local governments. Therefore, products are disposed of in landfills or incinerated, except for some that are voluntarily collected and recycled. In order to recycle all of the waste fluorescent lamps, we must have a complete recycling system that has a high rate of public participation in collection. We also must have a closed-loop system of mercury recovery and reuse in which all stakeholders participate. Furthermore, it is important to share information and policies regarding fluorescent lamp recycling and related technologies with other countries, especially those in other countries, where fluorescent lamps are becoming more popular because of their high energy efficiency and long life. Also, it is important to develop mercury free and energy efficient lamps including LEDs (light emitting diodes).


Effectiveness of Alberta Family Integrated Care on infant length of stay in level II neonatal intensive care units: a cluster randomized controlled trial.
Parents of infants in neonatal intensive care units (NICUs) are often unintentionally marginalized in pursuit of optimal clinical care. Family Integrated Care (FICare) was developed to support families as part of their infants' care team in level III NICUs. We adapted the model for level II NICUs in Alberta, Canada, and evaluated whether the new Alberta FICare™ model decreased hospital length of stay (LOS) in preterm infants without concomitant increases in readmissions and emergency department visits. In this pragmatic cluster randomized controlled trial conducted between December 15, 2015 and July 28, 2018, 10 level II NICUs were randomized to provide Alberta FICare™ (n = 5) or standard care (n = 5). Alberta FICare™ is a psychoeducational intervention with 3 components: Relational Communication, Parent Education, and Parent Support. We enrolled mothers and their singleton or twin infants born between 32 0/7 and 34 6/7 weeks gestation. The primary outcome was infant hospital LOS. We used a linear regression model to conduct weighted site-level analysis comparing adjusted mean LOS between groups, accounting for site geographic area (urban/regional) and infant risk factors. Secondary outcomes included proportions of infants with readmissions and emergency department visits to 2 months corrected age, type of feeding at discharge, and maternal psychosocial distress and parenting self-efficacy at discharge. We enrolled 654 mothers and 765 infants (543 singletons/111 twin cases). Intention to treat analysis included 353 infants/308 mothers in the Alberta FICare™ group and 365 infants/306 mothers in the standard care group. The unadjusted difference between groups in infant hospital LOS (1.96 days) was not statistically significant. Accounting for site geographic area and infant risk factors, infant hospital LOS was 2.55 days shorter (95% CI, - 4.44 to - 0.66) in the Alberta FICare™ group than standard care group, P = .02. Secondary outcomes were not significantly different between groups. Alberta FICare™ is effective in reducing preterm infant LOS in level II NICUs, without concomitant increases in readmissions or emergency department visits. A small number of sites in a single jurisdiction and select group infants limit generalizability of findings. ClinicalTrials.gov Identifier NCT02879799 , retrospectively registered August 26, 2016.


Neurones in the ventrolateral pons are required for post-hypoxic frequency decline in rats.
1. The breathing pattern following acute hypoxia (arterial O2 pressure (Pa,O2), 27.4 +/- 7.7 mmHg) was measured in intact, anaesthetized and spontaneously breathing adult rats (n = 4) and in anaesthetized, vagotomized, paralysed and ventilated animals (n = 14). Measurements were made both before and after bilateral lesions or chemical inactivation of neurones in the lateral pons. Respiratory motor activity was recorded as an index of the respiratory cycle. We tested the hypothesis that the ventrolateral pons is required for expression of post-hypoxic frequency decline, defined as a decrease in respiratory frequency below steady-state baseline levels following brief exposures to hypoxia. 2. We identified an area in the ventrolateral pons where brief (1 ms) low current (< or = 20 microA) pulses evoked a short-latency inhibitor of phrenic nerve activity. At this site, bilateral electrical or chemical lesions (n = 3) were performed, or neural activity was inhibited by focal injections of 10 mM muscimol (n = 9). In six control animals, neural activity was inhibited by muscimol injections into the lateral pons, dorsal to the target site. 3. Prior to pontine intervention, respiratory frequency decreased below baseline levels following 20-110 s of 8% O2. The decrease in frequency resulted from a prolongation of expiration (up to 276%), which gradually returned to baseline levels (tau = 45 s). 4. Following lesions or inhibition of neural activity in the ventrolateral pons, baseline inspiratory (TI) and expiratory (TE) durations were altered, albeit minimally, in the animals with intact vagus nerves. Expiratory duration following hypoxia was not different from baseline levels either in vagotomized (P = 0.18) or intact (P > 0.05) animals. In contrast, injections of muscimol at more dorsal sites did not alter the decrease in frequency normally seen following hypoxia. 5. Histological examination revealed that effective lesion or injection sites were within the lateral pontine tegmental field and included portions of the noradrenergic A5 cell group. 6. We conclude that the mechanism responsible for post-hypoxic frequency decline involves an active neural process that depends on the integrity of the ventrolateral pons.


Therapeutic Effects of Methanol Extract from Euphorbia kansui Radix on Imiquimod-Induced Psoriasis.
The roots of Euphorbia kansui, which belong to the family Euphorbiaceae, have been used as a traditional medicine for the treatment of various diseases such as diabetes, ascites, and leukemia. Recently, it was reported that the methylene chloride fraction of E. kansui radix (EKC) regulated the differentiation of Th17 cells and alleviated the symptoms of Th17-related inflammatory bowel disease. Imiquimod (IMQ), a TLR7/8 agonist, has been used to induce psoriasis in a mouse model. In this study, we evaluated the effect of EKC in an IMQ-induced psoriasis model. EKC effectively inhibited the production of interleukin-17A and interferon-γ in vitro. On this basis, EKC was administered to an animal model of psoriasis. Acanthosis and the infiltration of inflammatory cells into the dermis were significantly reduced by EKC. EKC also inhibited the expression of IL-17A, IL-22, IL-23, IL-12, and RAR-related orphan receptor gamma t (RORγt) in the spleen, skin-draining lymph nodes, and the skin. Additionally, EKC inhibited the activity of dendritic cells but not that of keratinocytes. In conclusion, EKC ameliorated the symptoms of psoriasis through inhibition of Th17 differentiation and activation of dendritic cells. These effects are expected to be beneficial in the treatment and prevention of psoriasis.


Peptide YY inhibits meal-stimulated pancreatic and gastric secretion.
Peptide YY was recently isolated from porcine intestine and shown to exhibit marked structural homology with pancreatic polypeptide, a potent inhibitor of pancreatic exocrine secretion. We have examined the effects of infused peptide YY on gastric and pancreatic secretion in four mongrel dogs with gastric and pancreatic fistulas. A 15% liver extract meal was instilled intragastrically, and normal saline or one of three doses of peptide YY (200, 400, and 800 pmol X kg-1 X h-1) was infused into a peripheral vein. All three doses of peptide YY significantly inhibited meal-stimulated pancreatic fluid and bicarbonate secretion, with the lowest dose inhibiting secretion by 44.5 +/- 3.5 and 53.6 +/- 8.5%, respectively. Pancreatic protein secretion and gastric acid secretion were significantly inhibited by the two highest doses. The 200, 400, and 800 pmol X kg-1 X h-1 doses of peptide YY were associated with increments in peripheral blood of 201 +/- 24, 357 +/- 50, and 971 +/- 139 pM, respectively. These values compared with mean increments of 86.3 +/- 8.5 pM after a meat meal and 403 +/- 63 pM after intestinally perfused oleic acid. The present studies demonstrate that peptide YY inhibits gastric and pancreatic secretion and suggest that peptide YY may be the gastric and pancreatic inhibitor in ileocolonic mucosa that is released by perfusion of the intestine with oleic acid.


Characterization of acid-sensing ion channel expression in oligodendrocyte-lineage cells.
Acid-sensing ion channels (ASICs) are widely expressed in neurons, where they serve in pain and mechanical sensation, and contribute to learning and memory. Six ASIC subunit proteins form homo- or heteromeric channel complexes with distinct physiological properties. Of such complexes, only monomeric ASIC1a channels are Ca2+ permeable. Prior pharmacologic and genetic studies have shown that ASIC1a channel inactivation markedly diminishes CNS susceptibility to ischemic damage. Here, we characterize ASIC expression in oligodendrocyte lineage cells (OLC) by molecular, electrophysiological, calcium imaging, and immunofluorescence techniques. ASIC1a, ASIC2a, and ASIC4 mRNAs were expressed in cultured rat OLC, with steady-state levels of each of these mRNAs several-fold higher in oligodendroglial progenitors than in mature oligodendroglia. ASIC transcripts were also detected in brain white matter, and ASIC1a protein expression was detected in white matter oligodendroglia. Inactivating, proton-gated, amiloride-sensitive OLC currents were detected by whole-cell voltage clamp. These currents showed profound tachyphylaxis with slow recovery, and were predominantly blocked by psalmotoxin, indicating that homomeric ASIC1a comprised a large fraction of functional ASIC in the cultured OLC. ASIC activation substantially depolarized OLC plasma membrane in current clamp studies, and elicited transient elevations in intracellular Ca2+ in imaging studies. Thus, OLC ASIC1a channels provide a means by which an acid shift in CNS extracellular pH, by diminishing plasma membrane potential and increasing Ca2+ permeability, can activate OLC signaling pathways, and may contribute to OLC vulnerability to CNS ischemia.


Breakfasts high in protein, fat or carbohydrate: effect on within-day appetite and energy balance.
To compare the effect of isoenergetically-dense, high-protein (HP), high-fat (HF) or high-carbohydrate (HC) breakfasts (at 08.30) on subjective hunger, fullness and appetite (measured hourly on a 100 mm visual analogue scale), macronutrient balance and ad libitum energy intake (EI), at a test meal (13.30) and throughout the rest of the day (until 23.00). Six men each spent 24 h in a whole-body indirect calorimeter on three separate occasions during which they received breakfasts designed to match 75% of BMR and that comprised, on average 3.1 MJ of protein (HP), carbohydrate (HC) or fat (HF), respectively, the remainder being split between the other two macronutrients. Every item of the ad libitum diet comprised 13% protein, 40% fat and 47% carbohydrate by energy, with an energy density of 550 kJ/100 g. Subjectively-rated pleasantness did not differ between the breakfasts, or any of the subsequent ad libitum meals. Subjective hunger was significantly greater during the hours between breakfast and lunch after the HF (26) treatment relative to the HP (18) or HC (18 mm) meals (P < 0.001), although the HP treatment suppressed hunger to a greater extent than the other two treatments over 24 h. However, mean ad libitum lunch intakes were similar at 5.38, 5.30 and 5.18 MJ (NS) on the HP, HC and HF treatments, respectively. After-lunch intakes were also very similar at 6.14, 6.18 and 5.83 MJ (NS). Mean 24-h energy expenditure amounted to 11.12, 11.14 and 10.93 MJ, respectively, producing energy balances of 5.71, 5.83 and 5.04 MJ (NS), respectively. The HP, HF and HC breakfasts led to enhanced P, F and C oxidation, respectively (P < 0.003). Large HP, HC or HF breakfasts led to detectable changes in hunger that were not of sufficient magnitude to influence lunch-time intake 5 h later, or EI for the rest of the day. A single positive balance of each macronutrient can be buffered by oxidation and storage capacity, without leading to changes in meal-to-meal EI, when subjects feed ad libitum on unfamiliar diets of fixed composition.


SF-36v2 norms and its' discriminative properties among healthy households of tuberculosis patients in Malaysia.
The aim of the study was to obtain norms of the SF-36v2 health survey and the association of summary component scores with socio-demographic variables in healthy households of tuberculosis (TB) patients. All household members (18 years and above; healthy; literate) of registered tuberculosis patients who came for contact tracing during March 2010 to February 2011 at the respiratory clinic of Penang General Hospital were invited to complete the SF-36v2 health survey using the official translation of the questionnaire in Malay, Mandarin, Tamil and English. Scoring of the questionnaire was done using Quality Metric's QM Certified Scoring Software version 4. Multivariate analysis was conducted to uncover the predictors of physical and mental health. A total of 649 eligible respondents were approached, while 525 agreed to participate in the study (response rate = 80.1 %). Out of consenting respondents, 46.5 % were male and only 5.3 % were over 75 years. Internal consistencies met the minimum criteria (α > 0.7). Reliability coefficients of the scales were always less than their own reliability coefficients. Mean physical component summary scale scores were equivalent to United States general population norms. However, there was a difference of more than three norm-based scoring points for mean mental component summary scores indicating poor mental health. A notable proportion of the respondents was at the risk of depression. Respondents aged 75 years and above (p = 0.001; OR 32.847), widow (p = 0.013; OR 2.599) and postgraduates (p < 0.001; OR 7.865) were predictors of poor physical health while unemployment (p = 0.033; OR 1.721) was the only predictor of poor mental health. The SF-36v2 is a valid instrument to assess HRQoL among the households of TB patients. Study findings indicate the existence of poor mental health and risk of depression among family caregivers of TB patients. We therefore recommend that caregivers of TB patients to be offered intensive support and special attention to cope with these emotional problems.


The effects of 12 weeks Pilates-inspired exercise training on functional performance in older women: A randomized clinical trial.
Recent scientific evidence supports the benefits of Pilates exercises on postural balance and muscle strength of older persons. However, their effects on other aspects of physical fitness, which are also important for independent living in older age, are still unknown. To investigate the effects of a 12-week Pilates-inspired exercise program on the functional performance of community-dwelling older women. Forty community-dwelling older women were randomly enrolled in a Pilates-inspired exercise training (2 times/week, 60 min/session) (PG, n = 21, 66.0 ± 1.4yrs) or kept in the control group (CG; n = 19, 63.3 ± 0.9yrs). The Pilates exercises were conducted in small groups and performed on mats (using accessories such as exercise rubber bands, swiss and exercise balls). The functional performance on one-leg stance (OLS), timed up and go (TUG), five-times-sit-to-stand (STS) and 6-min walk (6 MW) tests was evaluated before and after the 12-week Pilates training or control follow-up period. After 12 weeks, time effects were observed for STS (p = 0.03) and 6 MW tests (p < 0.01). Only among PG subjects did the time spent to rise from a chair and return to a seated position decrease significantly (2.0 s faster, p = 0.02) and the distance walked in 6 min increase (∼30 m, p < 0.01). OLS and TUG performance remained unaltered in both groups. Pilates-inspired exercises improved dynamic balance, lower-extremity strength and aerobic resistance in community-dwelling older women. Therefore, it may be a potentially effective exercise regimen to maintain physical fitness in old age.


First description of DHA-1 ampCbeta-lactamase in Proteus mirabilis.
This report describes the first occurrence of the DHA-1 ampCbeta-lactamase gene in Proteus mirabilis. The organism was isolated from the vaginal flora of a pregnant woman in a French hospital. The DHA-1 beta-lactamase gene was identified on the basis of phenotypic characteristics, PCR amplification and sequencing. Antagonism between cefoxitin and the other cephalosporins suggested inducible production of the DHA-1 enzyme.


Transient elevation of ST-segment due to pneumothorax and pneumopericardium.
ST-segment elevation, observed in the critically ill patients, almost always raises the suspicion of ischemic heart disease. However, nonischemic myocardial and non-myocardial problems in these patients may also lead to ST-segment elevation. Pneumothorax and pneumopericardium have been rarely reported as a cause of transient ST-segment elevation. The authors report the case of a patient admitted to the emergency care unit because of a respiratory failure requiring mechanical ventilatory support. As the patient showed signs of clinical deterioration, a pneumothorax was clinically diagnosed. Chest radiography after thorax drainage also disclosed a pneumopericardium. The 12-lead electrocardiogram recorded before the thoracic drainage revealed an ST-segment elevation, which normalized after the surgical procedure. Ischemic myocardial biomarkers were negative. The authors call attention to the right-sided pneumothorax associated with pneumopericardium as an unusual cause of ST-segment elevation.


HIF-1 inhibition decreases systemic vascular remodelling diseases by promoting apoptosis through a hexokinase 2-dependent mechanism.
Vascular remodelling diseases are characterized by the presence of proliferative and apoptosis-resistant vascular smooth muscle cells (VSMC). There is evidence that pro-proliferative and anti-apoptotic states are characterized by metabolic remodelling (a glycolytic phenotype with hyperpolarized mitochondria) involving Akt pathway activation by circulating growth factors. Hypoxia-inducible factor-1 (HIF-1) is involved in different vascular diseases. Since this transcription factor is implicated in metabolic responses, we hypothesized that HIF-1 activity could be involved in vascular remodelling in response to arterial injury. Our findings indicate that growth factors, such as platelet-derived growth factor (PDGF), activate the Akt pathway (measured by immunoblot) in human carotid artery VSMC. Activation of this pathway increased HIF-1 activation (measured by immunoblot), leading to increased glycolysis in VSMC. Expression and mitochondrial activity of hexokinase 2 (HXK2), a primary initiator of glycolysis, are increased during HIF-1 activation. The mitochondrial activity of HXK2 in VSMC led to the hyperpolarization of mitochondrial membrane potential (measured by tetramethylrhodamine methyl-ester perchlorate) and the suppression of apoptosis (measured by TUNEL assay and 3 activity), effects that are blocked by HIF-1 inhibition. Additionally, HIF-1 inhibition also decreased VSMC proliferation (proliferating cell nuclear antigen and Ki-67 assays). In vivo, we demonstrate that localized HIF-1 inhibition, using a dominant-negative HIF-1α adenoviral construct, prevented carotid artery post-injury remodelling in rats. We propose that HIF-1 is centrally involved in carotid artery remodelling in response to arterial injury and that localized inhibition of HIF-1 may be a novel therapeutic strategy to prevent carotid stenosis.


An untargeted multi-technique metabolomics approach to studying intracellular metabolites of HepG2 cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.
In vitro cell systems together with omics methods represent promising alternatives to conventional animal models for toxicity testing. Transcriptomic and proteomic approaches have been widely applied in vitro but relatively few studies have used metabolomics. Therefore, the goal of the present study was to develop an untargeted methodology for performing reproducible metabolomics on in vitro systems. The human liver cell line HepG2, and the well-known hepatotoxic and non-genotoxic carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), were used as the in vitro model system and model toxicant, respectively. The study focused on the analysis of intracellular metabolites using NMR, LC-MS and GC-MS, with emphasis on the reproducibility and repeatability of the data. State of the art pre-processing and alignment tools and multivariate statistics were used to detect significantly altered levels of metabolites after exposing HepG2 cells to TCDD. Several metabolites identified using databases, literature and LC-nanomate-Orbitrap analysis were affected by the treatment. The observed changes in metabolite levels are discussed in relation to the reported effects of TCDD. Untargeted profiling of the polar and apolar metabolites of in vitro cultured HepG2 cells is a valid approach to studying the effects of TCDD on the cell metabolome. The approach described in this research demonstrates that highly reproducible experiments and correct normalization of the datasets are essential for obtaining reliable results. The effects of TCDD on HepG2 cells reported herein are in agreement with previous studies and serve to validate the procedures used in the present work.


Effect of water supply on growth and polyphenols of lemon balm (Melissa officinalis L.) and thyme (Thymus vulgaris L.).
A pot experiment was carried out with lemon balm (Melissa officinalis L.) and thyme (Thymus vulgaris L.). Different water supply was applied: 25%, 40% and 70% saturation of soil water capacity (SWC). Morphological traits, biomass and phenolic type active ingredients were investigated. Among the two species, main differences were registered in biomass and TPC. Lower SWC resulted in reduced biomass production of lemon balm, while the applied stress treatments did not effect the biomass of thyme. In lemon balm, highest TPC contents were measured in control plants both in shoots and roots but in thyme, the shoots showed a significantly increased TPC at the 25% SWC conditions. Neither the content of total flavonoids nor that of the rosmarinic acid was affected by the treatments. The antioxidant capacity proved to be in tight connection with the TPC in both species (r = 0.766-0.883). The rosmarinic acid content of lemon balm plants contributed to the antioxidant capacity, as well (r = 0.679-0.869).


Neoplasia in zebrafish (Danio rerio) treated with 7,12-dimethylbenz[a]anthracene by two exposure routes at different developmental stages.
Using zebrafish, Danio rerio, initial pioneering work in the 1960s revealed carcinogen responsiveness of fish, yet very few subsequent tumorigenesis investigations have utilized this species. We exposed embryos (60 hours postfertilization) and fry (3 week posthatch) to 7,12-dimethylbenz[a]anthracene (DMBA) by immersion in aqueous solutions for 24 hours, at concentrations of 0-1 or 0-5 ppm (mg/L), respectively. Juvenile zebrafish 2 months posthatch were fed a diet containing 0-1,000 ppm DMBA for 4 months. Fish were sampled for histologic evaluation at 7-12 months after the onset of carcinogen treatment. Fry were most responsive to DMBA and showed the widest diversity of target tissues and histologic types of neoplasia, having several types of epithelial, mesenchymal, and neural neoplasia. The principal target tissues for carcinogenic response were liver following embryo or fry exposure, with gill and blood vessel the second and third most responsive tissues in fry. Intestine was the primary target and gill a secondary target in fish that received dietary DMBA as juveniles. These studies indicate that young zebrafish are most responsive to DMBA, showing a greater diversity of neoplasm types than rainbow trout. Thus, zebrafish are a valuable model system in which to study mechanistic aspects of the carcinogenesis process.


Risk factors for recent transmission of Mycobacterium tuberculosis.
In recent decades, the decline of tuberculosis has stopped in Western Europe, mainly due to increased immigration from high-prevalence countries. The objective of the current study was to identify risk factors for developing tuberculosis following recent infection, in order to better target interventions. Strains from 861 culture-positive cases, diagnosed in Norway in 1994-1999, were analysed by use of restriction fragment length polymorphism (RFLP). A cluster was defined as two or more isolates with identical RFLP patterns. Risk factors for being part of a cluster were identified by univariate and multivariate analysis. A total of 134 patients were part of a cluster. These constituted 5% Asian-born, 18% Norwegian-born, 24% European-born and 29% African-born patients. Four independent risk factors for being part of a cluster were identified: being born in Norway, being of young age, being infected with an isoniazid-resistant strain and being infected with a multidrug-resistant strain. Transmission of tuberculosis may be further reduced by improving case management, contact tracing, preventive treatment, screening of immigrants and access to health services for the foreign-born population.


Effect of 30% hydrogen peroxide on marginal integrity of silorane-based versus methacrylate-based composite restorations.
The aim of this study was to assess the effect of 30% hydrogen peroxide on the microleakage of class V cavities restored with either a silorane-based composite or two methacrylate-based composites. A total of 96 standard class V cavities (1.5 × 2 × 3 mm) were prepared on the buccal surface of sound extracted human premolars with both enamel and dentin margins and randomly assigned into three groups of Filtek P90 (group A) with its respective bonding (P90 system adhesive), Filtek Z250 (group B) and Filtek Z350XT (group C), both with Adper Prompt L-Pop bonding. The teeth were subjected to thermocycling (1000×, 5-55ºC) and half of them randomly underwent bleaching (30% hydrogen peroxide, 15 min, three times), while the remaining half (control) were not bleached. Dye penetration was measured following immersion in 2% basic fuchsin for 24 h. Data were statistically analyzed using Kruskal-Wallis and Mann-Whitney U tests at 95% CI. No significant differences were found between the composites in the control groups in enamel (P=0.171) or dentin (P=0.094) margins. After bleaching, microleakage of Z250 (at the occlusal (P=0.696) or gingival (P=0.867) margins), Z350 (at the occlusal (P=0.323) margin) and P90 (at the occlusal (P=0.316) or gingival (P=0.281) margins) did not change significantly. No significant differences were noted between the bleached and control subgroups of Z250 and P90 in enamel or dentin margins. Microleakage of Z350 composite was reduced at the gingival margin compared to the control group, but no significant difference was observed at the occlusal margin. Microleakage of silorane-based composite in gingival margin was significantly more than two metacrylate-based composites.


til-1: a novel proviral insertion locus for Moloney murine leukaemia virus in lymphomas of CD2-myc transgenic mice.
Moloney murine leukaemia virus (MoMLV) markedly accelerates thymic lymphoma development in mice carrying a transgene in which the human c-myc gene is linked to the CD2 locus control region. To investigate the mechanism of synergy and identify the genes which collaborate with myc in these clonal tumours, we analysed the sites of MoMLV insertion. Analysis of known viral integration loci revealed only a small number of insertions at bmi-1, pim-1 and ahi-1. Further cloning and hybridization analysis revealed a new common integration locus, designated til-1, which was occupied in 25 out of 77 lymphomas examined, with evidence of multiple clonal insertions in some cases. Mapping relative to established chromosomal markers in interspecific backcross mice located til-1 to mouse chromosome 17, distal to pim-1 and tic-1. These results suggest that the til-1 locus may harbour a novel myc-collaborating gene which acts as a target for activation in T cell lymphomas.


The accuracy of MRI in detecting pathological complete response following neoadjuvant chemotherapy in different breast cancer subtypes.
Pathological complete response (pCR) following neo-adjuvant chemotherapy (NACT) for breast cancer is associated with improved disease-free and overall survival in certain breast cancer subtypes. Magnetic Resonance Imaging (MRI) is increasingly used as standard to assess treatment response in patients receiving NACT. The aim of this study was to determine the clinical utility of MRI in accurately predicting pCR post-NACT. A single-centre, retrospective study was conducted in breast cancer patients, who received NACT between 2013 and 2020. Patients who had an MRI before and after NACT were included. Pathological and MRI radiological response rates to NACT were analyzed and MRI accuracy assessed in detecting pCR according to breast cancer subtype. One hundred and sixty-seven patients were included in the study. Forty-one of the 167 patients achieved pCR (24.6 %), with the highest proportion in HR- HER2+ subgroup (58.3 %), followed by triple negative breast cancer (TNBC) (35 %). Only 22.2 % and 10.5 % of patients with HR + HER2+ and HR + HER2-respectively achieved pCR. The overall accuracy of MRI in predicting pCR after NACT was 77.3 %. The greatest accuracy was in TNBC (87.5 %) with a specificity and positive predictive value (PPV) of 100 % and the highest number of correctly diagnosed complete responses (14 of 40). MRI was less accurate in predicting response rates in HR + HER2- (PPV 91.2 %) and HR + HER2+ groups (PPV 90.5 %). MRI performed significantly better in predicting complete response in TNBC compared to HR + HER2-subtype (p = 0.0057). MRI is a clinically useful adjunct in assessing pCR following NACT and appears to predict pathological response more accurately in TNBC compared to HR + HER2-breast cancer subtypes. This has significant clinical implications in terms of surgical planning, adjuvant treatment options and prognosis.


Corneal donor material selection.
The authors conducted the first long-range study to demonstrate possible negative effects on the recipients of corneal transplantation from donors who had died of a systemic malignancy or of chronic neurologic disease. The results are reported of a long-term retrospective analysis of 73 patients who received 86 grafts from donors with various systemic malignancies. These patients were followed for a mean of 127 months. There was no evidence of the transfer of the same malignancy to any of the recipients. There was no increased incidence of malignancy or earlier mortality in our patient population when compared with a reference population. Graft infection, endophthalmitis, or local tumor growth was not observed. The authors state that at the present time there is no basis for excluding donors dying of systemic malignancy as a source of material for use in keratoplasty. The authors examined the case histories of six patients who received grafts from donors who had died of a neurological disease with a suspected viral etiology. In a follow-up period ranging from 120 to 174 months, no evidence of neurologic disease developed in any of the patients. The sample was too small to provide data necessary for drawing conclusions concerning the safety of the use of material from this source. The authors strongly advise excluding any patient with a neurologic disease of suspected viral etiology as a source of corneal donor material.


Expression of the inhibitory receptor ILT3 on dendritic cells is dispensable for induction of CD4+Foxp3+ regulatory T cells by 1,25-dihydroxyvitamin D3.
1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) is a secosteroid hormone that renders dendritic cells (DCs) tolerogenic, favoring the induction of regulatory T cells. Induction of DCs with tolerogenic properties by 1,25(OH)(2)D(3) is associated with increased selective expression of immunoglobulin-like transcript 3 (ILT3), suggesting its involvement in the immunoregulatory properties of this hormone. Here we show an in vivo correlate of the increased ILT3 expression on DCs in healing psoriatic lesions following topical treatment with the 1,25(OH)(2)D(3) analog calcipotriol. Analysis of DC subsets reveals a differential regulation of ILT3 expression by 1,25(OH)(2)D(3), with a marked up-regulation in myeloid DCs but no effect on its expression by plasmacytoid DCs. A regulatory role for ILT3 expressed on DCs is indicated by the increased interferon-gamma (IFN-gamma) secretion promoted by anti-ILT3 addition to cultures of DCs and T cells, but this effect is blunted in 1,25(OH)(2)D(3)-treated DCs, suggesting ILT3-independent mechanisms able to regulate T-cell activation. Although ILT3 expression by DCs is required for induction of regulatory T cells, DC pretreatment with 1,25(OH)(2)D(3) leads to induction of CD4(+)Foxp3(+) cells with suppressive activity irrespective of the presence of neutralizing anti-ILT3 monoclonal antibody (mAb), indicating that ILT3 expression is dispensable for the capacity of 1,25(OH)(2)D(3)-treated DCs to induce regulatory T cells.


Migratory birds along the Mediterranean - Black Sea Flyway as carriers of zoonotic pathogens.
At the crossroad between Europe, Asia, and Africa, Bulgaria is part of the Mediterranean - Black Sea Flyway (MBSF) used by millions of migratory birds. In this study, bird species migrating through Bulgaria were investigated as carriers of zoonotic pathogens. In total, 706 birds belonging to 46 species were checked for the presence of various bacterial pathogens (Campylobacter, Yersinia, Salmonella, Listeria, Escherichia coli, Staphylococcus aureus, Francisella tularensis, Coxiella burnetii, Borrelia burgdorferi, and Brucella spp.). From 673 birds we investigated fecal samples, from the remaining 33, blood samples. We detected Campylobacter 16S rDNA gene in 1.3% of birds, but none were of pathogenic Campylobacter jejuni and Campylobacter coli species. Escherichia coli 16S rDNA gene was found in 8.8% of the birds. Out of 34 birds that transported Yersinia enterocolitica strains (5.05%), only 1 carried a pathogenic isolate. Three birds (0.4%) were carriers of nonpathogenic Salmonella strains. Four avian samples (0.6%) were positive for Listeria monocytogenes and 1 (0.15%) was positive for Brucella spp. None of the birds tested carried the tick-borne pathogens C. burnetii or B. burgdorferi sensu lato. Antibiotic-resistant strains were detected, suggesting that migratory birds could be reservoirs and spreaders of bacterial pathogens as well as antibiotic resistance genes.


Autologous blood perfusion for myocardial protection during coronary angioplasty: a feasibility study.
During coronary angioplasty, inflation of the balloon within the coronary artery produces transient arterial occlusion and frequently results in myocardial ischemia. Delivery of oxygenated autologous blood to the myocardium at risk during inflation may help mitigate this ischemia. Accordingly, we investigated the feasibility and safety of infusing blood through the central lumen of a dilatation catheter around the guidewire using both a model in vitro and clinical trials. In the tests in vitro, fresh blood was infused at flow rates up to 120 ml/min. Hemolysis was minimal at flow rates of 60 ml/min or less (less than or equal to 0.92 +/- 0.18%), but increased exponentially at higher rates (13.64 +/- 2.37% at 120 ml/min, p less than .002). A similar pattern was observed for potassium release. Platelet and leukocyte counts did not vary significantly, and beta-thromboglobulin and muramidase remained at control levels. Although mean erythrocyte volume did not change, erythrocyte histograms and light microscopy demonstrated a subpopulation of red cell fragments averaging 25 to 40 fl in size at higher rates. A randomized, crossover clinical trial was next performed by delivery of blood perfusion at 60 ml/min to 15 patients undergoing coronary angioplasty. Levels of plasma hemoglobin, beta-thromboglobulin, lactate dehydrogenase, and potassium remained constant before and after the perfusion and the control inflations. The maximum pain score was significantly lower with the perfusion inflation (4.1 +/- 0.8 vs 6.0 +/- 0.9, p less than .003). Relative to baseline, the maximum ST segment elevation during the perfusion inflation (0.5 +/- 0.3 mm) was nearly one-fourth that during the control inflation (1.9 +/- 0.6 mm, p less than .02). Thus, myocardial protection with oxygenated autologous blood perfusion at rates of 60 ml/min appears to be a safe and effective technique that may permit increased inflation time and extend the range of coronary angioplasty to include individuals at high risk for the procedure.


Community composition of marine and brackish water ammonia-oxidizing consortia developed for aquaculture application.
To mitigate the toxicity of ammonia in aquaculture systems, marine and brackish water ammonia-oxidizing bacterial consortia have been developed and are used for activation of nitrifying bioreactors integrated to recirculating aquaculture systems. To shed more light on to these biological entities, diversity of both the consortia were analyzed based on random cloning of 16S rRNA gene and ammonia-oxidizing bacterial specific amoA gene sequences. The dendrograms of representative clones on the basis of amplified ribosomal DNA restriction analysis generated 22 and 19 clusters for marine and brackish water nitrifying consortia, respectively. Phylogenetic analysis demonstrated the presence of various autotrophic nitrifiers belonging to α-, β- and γ-Proteobacteria, anaerobic ammonia oxidizers, heterotrophic denitrifiers, Bacteroidetes, and Actinobacteria. Distribution patterns of the organisms within the two consortia were determined using the software Geneious and diversity indices were investigated using Mega 5.0, VITCOMIC and Primer 7. The abundance of ammonia oxidizers was found in the order of 2.21 ± 0.25 × 109 copies/g wet weight of marine consortium and 6.20 ± 0.23 × 107 copies/g of brackish water consortium. Besides, marine ammonia-oxidizing consortium exhibited higher mean population diversity and Shannon Wiener diversity than the brackish water counterparts.


Association between hospital procedure volume and early complications after pacemaker implantation: results from a large, unselected, contemporary cohort of the German nationwide obligatory external quality assurance programme.
Several studies demonstrated an inverse relationship between cardioverter-defibrillator implantation volume and complication rates, suggesting better outcomes for higher volume centres. However, the association of institutional procedural volume with patient outcomes for permanent pacemaker (PPM) implantation remains less known, especially in decentralized implantation systems. We performed retrospective examination of data on patients undergoing PPM from the German obligatory quality assurance programme (2007-12) to evaluate the relationship of hospital PPM volume (categorized into quintiles of their mean annual volume) with risk-adjusted in-hospital surgical complications (composite of pneumothorax, haemothorax, pericardial effusion, or pocket haematoma, all requiring intervention, or device infection) and pacemaker lead dislocation. Overall 430 416 PPM implantations were documented in 1226 hospitals. Systems included dual (72.8%) and single (25.8%) chamber PPM and cardiac resynchronization therapy (CRT) devices (1.1%). Complications included surgical (0.92%), and ventricular (0.99%), and atrial (1.22%) lead dislocation. Despite an increase in relatively complex procedures (dual chamber, CRT), there was a significant decrease in the procedural and fluoroscopy times and complications from lowest to highest implantation volume quintiles (P for trend <0.0001). The greatest difference was observed between the lowest (1-50 implantations/year-reference group) and the second-lowest (51-90 implantations/year) quintile: surgical complications [odds ratio (OR) 0.69; confidence interval (CI) 0.60-0.78], atrial lead dislocations (OR 0.69; CI 0.59-0.80), and ventricular lead dislocations (OR 0.73; CI 0.63-0.84). Hospital annual PPM volume was directly related to indication-based implantation of relatively more complex PPM and yet inversely with procedural times and rates of early surgical complications and lead dislocations. Thus, our data suggest better performance and lower complications with increasing procedural volume.


Level and duration of serum antibodies in cattle infected experimentally and naturally with bovine virus diarrhoea virus.
Neutralising serum antibodies against bovine virus diarrhoea virus (BVDV) were monitored for three years in 35 cattle that were infected with the virus as calves; 24 of the calves were inoculated intramuscularly or intranasally, and 11 contracted the infection naturally. All the experimentally infected calves seroconverted within 14 to 28 days after inoculation, and all the animals still had high serum levels of antibodies to BVDV three years after infection. Determinations of antibody levels in milk and blood samples excluded the possibility that the calves had been reinfected with BVDV during the study.


Differences in the Relaxometric Properties of Regioisomeric Benzyl-DOTA Bifunctional Chelators: Implications for Molecular Imaging.
The bifunctional chelator S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane- N, N', N″, N‴-1,4,7,10-tetraacetate (IB-DOTA) is on paper the most attractive of the commercially available bifunctional chelators for magnetic resonance imaging (MRI) applications. The preserved DOTA scaffold is known to produce extremely kinetically and thermodynamically robust chelates with the Gd3+ ion. Also, ligation through four acetate pendant arms should ensure that the rapid water exchange kinetics so, crucial to the function of an MRI contrast agent are retained. However, upon ligation of the Gd3+ ion, IB-DOTA differentiates into two distinct isomers defined by the positions of the benzylic substituent (corner or side). A relaxometric analysis of these two isomers revealed marked differences in the property and behavior of the two chelates. Most notably the side isomer is found to be substantially more likely to aggregate in aqueous solution than its corner counterpart. This aggregation results in higher relaxivity for the side isomer versus the corner isomer, an observation that potentially obscures the impact of differences in water exchange kinetics between the two isomers. The side isomer is composed of a significant fraction of a twisted square antiprismatic coordination geometry that exchanges water more rapidly than optimal (τM = 7 ns) for maximizing relaxivity. The impact of this excessively fast exchange is not observed in the relaxivity of the side isomer only because in isolation this chelate tumbles much more slowly than the corner isomer. However, this situation is not expected to persist when the chelate is employed in a typical bioconjugate. These results imply that the corner isomer of IB-DOTA may represent a better choice of bifunctional chelator for bioconjugation applications in which a large macromolecule is to be tagged for MRI applications.


Reconsideration of delayed gastric emptying in pancreaticoduodenectomy.
Literature reports indicate that the incidence of delayed gastric emptying (DGE) is higher after pylorus-preserving pancreaticoduodenectomy (PPPD) than after conventional pancreaticoduodenectomy (CPD), but DGE is traditionally diagnosed from patient-reported subjective sensations. Our clinical radiological experience suggests higher rates for physiological DGE post-CPD. We therefore sought to quantify rates of subjective DGE (sDGE, based on patient complaint) verses objective DGE (oDGE, based on scintography) post-CPD and post-PPPD. Contractile motility of post-PPPD residual stomach was also studied. For 21 PPPD and 33 CPD patients between October 1997 and June 2000, sDGE and oDGE data were collected preoperatively, on postoperative day 14, and 6 months postoperatively, with cholescintography for pylorus ring competency on postoperative day 14. The incidence of sDGE was higher for PPPD (42%) than for CPD (15%) at 14 days, with zero sDGE for both at 6 months. The incidence oDGE was higher for CPD (91%) than for PPPD (76%) at 14 days, with a 6-month incidence of 4.7% in PPPD but approximately 33% for CPD. Solid-phase emptying in PPPD showed that residual stomach retained partial gastric emptying function at 14 days but not at 6 months. Cholescintography showed abnormal pylorus closure function in 2 of 21 PPPD patients but was not related to DGE. Literature reports of higher DGE incidence post-PPPD are true only for subjective symptoms. Radiological measurement of oDGE shows that both CPD and PPPD manifest approximately 80% incidence of DGE in the early postoperative period. At 6 months, approximately 33% of CPD show persistent oDGE. We concluded that (1) the concept of DGE should distinguish between subjective and objective symptoms; (2) loss of distal stomach mechanoreceptors in CPD reduces patients sensation of oDGE, producing "silent" DGE; (3) both CPD and PPPD have high and approximately equal rates oDGE; (4) the previously unnoticed silent oDGE in CPD may contribute to the higher rates of ulceration and related morbidity in association with CPD.


Assessment of 16-month Sequelae Due to Dog Bites Originally Studied in a French Multicenter Survey from 2009 to 2011.
Every year in France dog bites lead to several thousand visits to emergency departments and numerous hospital admissions. This study aims to describe the sequelae 16 months after dog bites. Following an initial epidemiological study on the severity of 485 dog bites carried out in 8 hospital emergency departments between May 1, 2009, and June 30, 2010, a second study investigating sequelae 16 months after the bite was conducted among 298 patients between September 2010 and December 2011. Data concerning patients' sequelae were collected by telephone or email. Almost half of respondents (47%) reported sequelae; of those patients, most of these reports were aesthetic (9/10). There were more sequelae when the bite was located in the head region or the lower limbs. Sequelae were more frequent among women, when the weight of the biting dog was higher, and when the initial severity of the bite was greater. On the other hand, the link between the patient and the dog, the sex of the dog, the type of aggression, and the age of the patient (< 15 years or ≥ 15 years) had no impact on the occurrence of sequelae. One patient in 7 still experienced pain 16 months after the bite; women were more likely to experience pain at that timepoint. No articles on dog bite sequelae were found in the literature. The dissemination of these results among professionals (veterinarians and doctors) and the general population will contribute to making dog owners more aware of the risk of bites and the means of avoiding them.


Comparison of ultrasonic and histopathological features of carotid artery stenosis.
Besides the degree of carotid artery stenosis, the composition of the plaque may help to predict the thromboembolic risk. Low echogenicity on ultrasound and hemorrhage into the atheroma demonstrated histopathologically have been shown to be associated with a higher risk of embolism. Twenty-nine consecutive patients with carotid artery stenosis and scheduled for carotid endarterectomy were investigated preoperatively by B-mode ultrasound. Post-operatively the endarterectomy specimens were examined histopathologically. Neither atheroma with hemorrhage nor atheroma without hemorrhage were significantly associated with echolucent ultrasound presentation. Out of the 10 lesions echolucent and homogeneous on ultrasound, six corresponded to atheroma with hemorrhage, two corresponded to atheroma with hemorrhage plus thrombus, two corresponded to fibrous plaque plus thrombus, and one corresponded to pure thrombus. Out of the 4 lesions heterogeneous and predominantly echolucent, one corresponded to atheroma without hemorrhage plus thrombus, one corresponded to atheroma with hemorrhage, one corresponded to atheroma with hemorrhage plus thrombus, one corresponded to atheroma with hemorrhage plus fibrous plaque. Seven out of the 18 atheromas with hemorrhage did not present as purely or predominantly echolucent lesions, six of them were even homogeneously echogenic. Plaque surface could not reliably be predicted by ultrasound. In our study, there was no significant correlation between ultrasound and histology of the lesion.


Involvement of Striatal Cholinergic Interneurons and M1 and M4 Muscarinic Receptors in Motor Symptoms of Parkinson's Disease.
Over the last decade, striatal cholinergic interneurons (ChIs) have reemerged as key actors in the pathophysiology of basal-ganglia-related movement disorders. However, the mechanisms involved are still unclear. In this study, we address the role of ChI activity in the expression of parkinsonian-like motor deficits in a unilateral nigrostriatal 6-hydroxydopamine (6-OHDA) lesion model using optogenetic and pharmacological approaches. Dorsal striatal photoinhibition of ChIs in lesioned ChAT(cre/cre) mice expressing halorhodopsin in ChIs reduces akinesia, bradykinesia, and sensorimotor neglect. Muscarinic acetylcholine receptor (mAChR) blockade by scopolamine produces similar anti-parkinsonian effects. To decipher which of the mAChR subtypes provides these beneficial effects, systemic and intrastriatal administration of the selective M1 and M4 mAChR antagonists telenzepine and tropicamide, respectively, were tested in the same model of Parkinson's disease. The two compounds alleviate 6-OHDA lesion-induced motor deficits. Telenzepine produces its beneficial effects by blocking postsynaptic M1 mAChRs expressed on medium spiny neurons (MSNs) at the origin of the indirect striatopallidal and direct striatonigral pathways. The anti-parkinsonian effects of tropicamide were almost completely abolished in mutant lesioned mice that lack M4 mAChRs specifically in dopamine D1-receptor-expressing neurons, suggesting that postsynaptic M4 mAChRs expressed on direct MSNs mediate the antiakinetic action of tropicamide. The present results show that altered cholinergic transmission via M1 and M4 mAChRs of the dorsal striatum plays a pivotal role in the occurrence of motor symptoms in Parkinson's disease. The striatum, where dopaminergic and cholinergic systems interact, is the pivotal structure of basal ganglia involved in pathophysiological changes underlying Parkinson's disease. Here, using optogenetic and pharmacological approaches, we investigated the involvement of striatal cholinergic interneurons (ChIs) and muscarinic receptor subtypes (mAChRs) in the occurrence of a wide range of motor deficits such as akinesia, bradykinesia, motor coordination, and sensorimotor neglect after unilateral nigrostriatal 6-hydroxydopamine lesion in mice. Our results show that photoinhibition of ChIs in the dorsal striatum and pharmacological blockade of muscarinic receptors, specifically postsynaptic M1 and M4 mAChRs, alleviate lesion-induced motor deficits. The present study points to these receptor subtypes as potential targets for the symptomatic treatment of parkinsonian-like motor symptoms.


Assessing Knowledge, Attitudes and Practices Towards COVID-19 Public Health Preventive Measures Among Patients at Mulago National Referral Hospital.
COVID-19 has become a major global health challenge, with Uganda reporting over 20,000 cases. There is, however, a scarcity of data on the perception of patients in Uganda towards the highly infectious disease. We aimed to assess the awareness, knowledge, attitudes, and practices towards COVID-19 preventive measures among patients at Mulago National Referral Hospital (MNRH), Uganda. A cross-sectional quantitative survey was conducted in August, 2020, among patients in surgical and medical wards at MNRH. An interviewer-administered, pre-validated questionnaire was used to collect data that was entered into Google Forms and analyzed using Microsoft Excel and STATA 16. Descriptive statistics was used to present data from univariate analysis. Patients whose knowledge and practice scores were greater or equal to the average score were regarded to have good knowledge and practices respectively. Chi-square, Fisher's Exact tests and binary logistic regression were used to assess factors associated with COVID-19 knowledge and practices. A P<0.05 was statistically significant. Overall, 114 patients were approached and 102 consented to participate. Most were females (53.8%), aged above 45 years (31.4%) with 40.2% reporting primary level as the highest level of education. About 55.9% (n=57) had adequate knowledge for COVID-19 and its related practices, and 52% (n=53) had good COVID-19 related practices. Knowledge significantly differed by marital status at bivariate analysis (P=0.020), however this lost significance at logistic regression. Female patients were thrice more likely to have good COVID-19 prevention practices compared to males (COR: 2.59, 95% CI: 1.2 to 5.8, P=0.020). Some 47 (46.1%) participants perceived that COVID-19 preventive measures were not difficult at all to observe. About half of the patients at Mulago National Referral Hospital lack adequate knowledge and practice on COVID-19 prevention. Continued patient education is required to increase knowledge which will in turn improve adherence to COVID-19 preventive practices.