Assessment of knowledge, perception, and practice patterns of Jordanian optometrists during COVID-19 pandemic: a cross-sectional online survey.
To investigate knowledge, risk perception, and attitude towards corona virus disease 2019 (COVID-19) and infection control measures among optometrists in Jordan. A cross-sectional survey was distributed through social media platforms to optometrists registered with the Jordanian syndicate and Jordanian association of optics. Information on participants' socio-demographic characteristics, knowledge of clinical features of COVID-19, risk assessment and infection control measures for preventing disease transmission were collected. A total of 135 optometrists (80 females and 55 males) with a mean age of 32±10y responded to the survey. Most optometrists were aware of COVID-19 symptoms, modes of transmission and measures for preventing COVID-19 and transmission in the ophthalmic setup. However, more than half of the optometrists did not receive any training about protection or infection control by their employers at their work place. Social media was the most common source of information on COVID-19 (76%). Most optometrists (85.2%) thought that the virus could be detected in tears, and 45.9% thought that red eye is a symptom of COVID-19. Optometrists in Jordan are aware of the clinical features and preventive measures related to COVID-19 infection. However, training on infection control is lacking and needs to be improved. Guidelines by international professional optometric associations should be promoted through regional and national associations to all registered optometrists and access to peer review. Journals should be encouraged to ensure that the knowledge about the pandemic is up to date and accurate.


Real-Life Outcome After Gene Replacement Therapy for Spinal Muscular Atrophy: A Multicenter Experience.
Onasemnogene abeparvovec-xioi (OA) has been available since 2019 as a gene replacement therapy for individuals with spinal muscular atrophy (SMA) under age two years. We aim to expand upon the sparse knowledge about its safety and clinical efficacy. The clinical outcome data of all the individuals with SMA who were treated with gene therapy in four tertiary hospitals in Israel were retrieved and analyzed. The study participants included 25 individuals who received the gene therapy between age 11 days and 23 months and whose median follow-up duration was 18.0 (interquartile range [IQR], 12.4 to 18.3) months. Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders scores increased by a median (IQR) of 13 (8 to 20) points at the last follow-up compared with baseline. None of the patients experienced regression in motor abilities after gene therapy, which was generally well tolerated. There was gradual improvement in motor function, especially among presymptomatic patients (P ≤ 0.001) whose disease duration was shorter (≤8 months) before receiving gene therapy (P ≤ 0.001) and who did not experience recurrent infections and illnesses in the months following treatment (P ≤ 0.001). OA was well tolerated and led to favorable functional motor outcomes at six to 24 months after treatment initiation. Better progress in motor function was observed in individuals who received OA earlier and who were presymptomatic, irrespective of the SMN2 copy number or type. Our results further strengthen the clinical efficacy of OA and reinforce the importance of early recognition of SMA via newborn screening programs.


Recent issues in antihypertensive drug therapy.
Results of recent large scale treatment trials have demonstrated that aggressive management of high blood pressure prevents progression of mild hypertension to the accelerated or malignant phase and reduces incidence of stroke, congestive heart failure, and left ventricular hypertrophy. These trials mostly have utilized a diuretic-based, stepped-care approach to drug therapy, however, and have not shown a consistent beneficial effect of treatment on coronary heart mortality. In addition, the results of studies such as MRFIT have raised questions about serious risks of diuretic treatment in selected patients. These concerns have led to increased use of nonpharmacologic approaches to lowering blood pressure in patients with mild hypertension, but most patients ultimately require drug therapy. Alternative agents to diuretics now being employed as monotherapy in mild hypertension include beta-blockers, calcium channel blockers, ACE inhibitors, alpha-blockers, alpha- and beta-blockers, and, to a lesser extent, centrally-acting sympatholytics and peripheral adrenergic antagonists. Rational use of these agents primarily is based on a careful evaluation of concomitant medical conditions (see Table 3), as well as their mode of action, relative side effects, ease of administration, and cost. Age and race recently have been found to be important determinants of antihypertensive response to agents such as diuretics, beta-blockers, calcium channel blockers, and ACE inhibitors (see Table 3) and appreciation of these relative differences may affect drug selection. When these factors are taken into account, an effective and well tolerated regimen can be tailored to the individual patient. It is hoped that aggressive treatment of hypertension in the future will cause a further decline in cardiovascular mortality in the United States.


Prenatal diagnosis of Nager syndrome in the third trimester of pregnancy and anatomopathological correlation.
Nager syndrome or acrofacial dysostosis is a rare and complex malformation characterized by ear anomalies, micrognathia, radial limb hypoplasia, and absence of the thumb or other fingers. Since the original description of the syndrome in 1948, there have only been four reports of prenatal diagnoses in the literature, all during the second trimester, and only two of them had anatomopathological correlations. We describe a case of Nager syndrome that was suspected in the third trimester of gestation and confirmed postnatally through pathology. The mother was white, 27 years old, and G5P2A2, with a family history of a brother with a harelip. She was referred to our service at 33 weeks of pregnancy with an ultrasound fetal diagnosis of musculoskeletal dysplasia associated with severe micrognathia and severe polyhydramnios. Birth was by means of cesarean section because of suspected fetal distress, which resulted in extraction of a live male fetus with Apgar 1/4, weight of 1,505 g, severe mandibular hypoplasia, low-set ears, severe upper-limb shortening, and absent left thumb. Death occurred 4 h after birth. Anatomopathological examination confirmed the diagnosis of Nager syndrome.


The one-year prevalence of nonspecific back pain in public primary health care establishments among 1.7 million people in western Sweden.
The one-year prevalence of diagnosed nonspecific back pain in Sweden is not known. Thus, this observational register-based study aimed to evaluate this prevalence by using data from the Region Västra Götaland, inhabiting 1.7 million people. Data from 2014 to 2018 were extracted from the VEGA database register. This register holds all health data from the publicly funded health care establishments in Region Västra Götaland. Aggregated data are presented as the one-year prevalence of unique individuals diagnosed with nonspecific back pain (i.e., the ICD-10 code M54). Stratification by health care level, gender, age, and M54 sub-diagnoses were made. Between 2014 and 2018, the annual prevalence of diagnosed nonspecific back pain in public primary health care increased from 4.8% to 6.0% (26% increase, P < 0.001, CI 25-27%). In 2018, the one-year prevalence was 7.2% among women and 4.8% among men (50% difference, P = 0.001, CI 49-52%). The one-year prevalence increased by age, and the highest figure (11%) was seen in the age group of 80-84. Low back pain, M54.5, was the most common sub-diagnosis. The one-year prevalence was significantly higher (P < 0.001) among women in all the M54 sub-diagnoses. The one-year prevalence of diagnosed nonspecific back pain was 6% in public primary health care in 2018 and has increased since 2014. Women were diagnosed considerably more frequently than men. Publicly funded rehabilitation efforts, as well as actions focusing on the prevention of back pain, is probably money well spent.


Contemporary minimal invasive surgical management of stones in children.
Pediatric urolithiasis has been more common over the past 20 years, and urologists have unique challenges in managing it surgically because this particular demographic is recognized as one of the high-risk categories for stone recurrence. Given this reality, care focuses on maintaining renal function, achieving total stone-free status, and most importantly avoiding stone recurrences. In this presented article, we aimed to make a comprehensive review of the current minimally invasive treatment of pediatric kidney stone disease. We evaluated the results of 74 studies following a comprehensive PubMed search till February 2023. This article was written by making use of current urology guidelines. Considering the reported occurrence of metabolic issues in up to 50% of cases in addition to the anatomic anomalies (about 30% of cases), the treatment of pediatric urolithiasis necessitates a full metabolic and urological examination on an individual basis. Timely management of metabolic imbalances and obstructive diseases is necessary. In addition to encouraging proper fluid consumption, it is advisable to improve urine volume and consider using medical therapeutics to raise urinary citrate levels. The location, content, and size of the stone(s), the morphology of the collecting system, the presence of urinary tract infection, as well as the presence of any obstruction, should all be taken into consideration while deciding on the best surgical procedure. All modern endourological methods are now used in the safe and efficient care of pediatric urolithiasis as a consequence of the obvious advancements in instrument technology and expanding expertise derived from adult patients. Other minimally invasive procedures, such as ureterorenoscopy and percutaneous nephrolithotomy, require more expertise and can be successfully applied with careful management for an excellent stone-free rate with minimal morbidity. Of these procedures, shock wave lithotripsy is still the first choice in the majority of cases with upper tract calculi. Open surgery will still be the therapy of choice for pediatric patients with complicated and big stones as well as anatomical anomalies.


Experiences and perspectives of individuals accessing CAR-T cell therapy: A qualitative analysis of online Reddit discussions.
Several chimeric antigen receptor (CAR-T) T-cell therapies have been approved for use for haematological malignancies. Despite known safety, access, and cost issues, little is known about how patients and caregivers understand novel treatments such as CAR-T and their associated uncertainties. We gathered data from Reddit, an online public social media site. We performed a keyword search in three relevant subreddit threads: r/cancer, r/lymphoma, r/leukemia. We systematically extracted threads and associated comments and reviewed against our inclusion criteria. We identified a total of 186 posts and 87 were included in the qualitative analysis from March 1, 2013, to April 15, 2021. Qualitative content analysis was used to identify themes. Of those excluded, 88 contained discussions of other immunotherapies and 11 were scientific profiles. We identified four themes: 1) navigating uncertainty with community, 2) finding a cure, 3) managing treatment-related uncertainties, and 4) overcoming uncertainties related to access. We found patients experience numerous barriers when seeking access to novel therapeutics, such as CAR-T therapies. The perceptions and struggles of patients and their families are relevant for developing technology assessments that are sensitive to patient experiences, as well as to inform policies for equitable resource allocation. Our study underscores the importance of balanced decision making between patients and physicians to ensure patients understand the risk and benefits of cancer treatments. Study investigators might evaluate trial participants based on patient demographics to ensure equitable access to studies for individuals in settings where internet access is less common.


Imaging of acute traumatic aortic tear in patients with an aberrant right subclavian artery.
This report describes the radiologic findings and discusses the clinical consequences of acute traumatic aortic tear occurring with an aberrant right subclavian artery. Identification of an aberrant right subclavian artery with acute traumatic aortic tear must be emphasized to reduce iatrogenic morbidity and mortality.


Kinetics of the early adaptive response to gamma rays: induction of a cellular radioprotective mechanism in murine leukocytes in vivo.
The aims of the study were to establish the kinetics of the early adaptive response and to determine the minimum adaptive dose of gamma rays capable of inducing this response. The minimum adaptive dose was determined by exposing groups of five BALB/c male mice to an adaptive dose of 0.005 or of 0.02 Gy gamma rays from a 137Cs source and challenge with 1.0 Gy 60 min later. The kinetics of adaptive response induction was established by exposing mice to an adaptive dose of 0.01 Gy, and subsequently to a challenge dose of 1.0 Gy at different times. Blood samples were collected from the tail immediately after exposure to the challenge dose, and the percentage of DNA-damaged cells and the extent of damaged were determined by single cell gel electrophoresis in 300 leukocytes per animal in five mice. The results confirms the capability of an in vivo induction of an early radioprotective process against the DNA-damage produced by gamma rays in murine leukocytes, and allows us to conclude that the minimum adaptive dose lies between 0.005 and 0.01 Gy of gamma rays, and the early adaptive response is induced as early as 30 min after the exposure and persists for at least 18 hr.


Stability of limbal stem cell deficiency after mechanical and thermal injuries in mice.
We studied the reproducibility and stability of limbal stem cell deficiency (LSCD) in mice following controlled injuries to the corneal and limbal epithelia. In one method, corneal and limbal epithelia were entirely removed with a 0.5 mm metal burr. In the other, limbus to limbus epithelial removal with the burr was followed by thermal injury to the limbus. These two methods were compared with a previously published one. Unwounded corneas were used as control. The corneas were examined monthly for three months by slit lamp with fluorescein staining. Immunofluorescence staining for cytokeratin 12 and 8 on corneal wholemount and cross sections were performed to determine the phenotype of the epithelium. Mechanical shaving of the epithelium, with or without thermal injury, resulted in a reproducible state of LSCD marked by superficial neovascularization, reduce of keratin 12 expression and presence of goblet cells on the cornea. The phenotype was stable in 100% of the eyes up to at least three months. Thermal injury produced a more severe phenotype with more significant stromal opacification. These corneal injury models may be useful for studying the mechanisms leading to limbal stem cell deficiency.


Culture confirmation of Listeria monocytogenes using tmRNA as a diagnostics target.
16s ribosomal RNA (rRNA) is routinely used to identify bacteria in direct detection culture confirmation assays. In some instances rRNA cannot be used as a target to distinguish between phylogenetically closely related bacteria. Here we evaluate an alternative target, transfer messenger RNA (tmRNA), for the culture confirmation of Listeria monocytogenes.


Suprasellar non-Langerhans cell histiocytosis (Erdheim-Chester disease)--a case report.
Erdheim-Chester disease (ECD) is an uncommon non-Langerhans cell histiocytosis that affects multiple body systems and can present clinically in a myriad of ways. An adult onset is most common with bony involvement and constitutional symptoms. We report the case of a 52-year-old female presenting with diabetes insipidus and a suprasellar mass on imaging, with no evidence of extracerebral involvement. Histopathology was consistent with ECD.


Effect of Tafamidis on Serum Transthyretin Levels in Non-Trial Patients With Transthyretin Amyloid Cardiomyopathy.
Transthyretin amyloid (ATTR) cardiomyopathy is slowed by tafamidis, which stabilizes the TTR molecule and reduces the formation of amyloidogenic oligomers. Stabilizers in clinical doses raise serum TTR, which may be a surrogate for the degree of stabilization. This study aims to determine, in a non-trial, unselected population of patients with ATTR cardiomyopathy, the effect of tafamidis on serum levels of TTR, and to compare these with published data of changes in TTR. TTR levels were measured before therapy and 3 to 12 months following initiation of tafamidis therapy in all patients seen between May 20, 2019, and March 1, 2021, who had a follow-up visits within 12 months of therapy initiation. Among 72 patients with ATTR cardiomyopathy (67 patients with wild-type and 5 patients with variant TTR), administration of tafamidis increased serum TTR from 21.8 mg ± 0.7 mg/dL to 29.3 ± 0.86 mg/dL, an increase of 34.5%. In 5 patients with variant TTR, the increase was 70.9%, compared to 32.0% in the wild-type patients. Mean N-terminal pro-brain natriuretic peptide increased over a mean follow-up of 21 ± 1.2 weeks, but the change was not statistically significant. Over the same period there was a small increase in high-sensitivity troponin T that was of borderline statistical significance (P = 0.057). Tafamidis consistently increases serum TTR levels in patients with ATTR cardiomyopathy, consistent with its effect on stabilizing TTR. Measurement of TTR level change post-TTR stabilizing therapy might be a surrogate for stabilization and could be a more accurate measure of drug efficacy than an in vitro nonphysiologic test of stabilization.


Community dynamics of carrion-attendant arthropods in tropical african woodland.
Carcasses are temporary resources which are unbredictable and inconsistent in their availability and locality. A recognisable community of interacting user arthrocods comprising sarcophages, coprophages, dermatophages, keratophages, detritivores, predators and parasites has evolved to exploit the carcass habitat. The large number of arthropods, close confinement, and limited duration of resources necessitates aggressive utilisation. The trophic relations, competition and successionary pattern of these arthropods is discussed. Several pathways to reduce competitive conflict are described. Succession at carcasses is viewed as being inherently different from the traditional concept as the habitat is non-replenishing and does not lead to a climax community.


Inactivation of fibroblast growth factor binding protein 3 causes anxiety-related behaviors.
The neurobiological mechanisms of emotional modulation and the molecular pathophysiology of anxiety disorders are largely unknown. The fibroblast growth factor (FGF) family has been implicated in the regulation of many physiological and pathological processes, which include the control of emotional behaviors. The present study examined mice with a targeted deletion of the fgf-bp3 gene, which encodes a novel FGF-binding protein, in animal models relevant to anxiety. To define the behavioral consequences of FGF-BP3 deficiency, we evaluated fgf-bp3-deficient mice using anxiety-related behavioral paradigms that provide a conflict between the desire to explore an unknown area or objects and the aversion to a brightly lit open space. The fgf-bp3-deficient mice exhibited alterations in time spent in the central area of the open-field arena, were less active in the lit areas of a light/dark transition test, and had a prolonged latency to feed during a novelty-induced hypophagia test. These changes were associated with alterations in light-induced orbitofrontal cortex (OFC) activation in an extracellular signal-regulated kinase (ERK) pathway-dependent manner. These results demonstrate that FGF-BP3 is a potent mediator of anxiety-related behaviors in mice and suggest that distinct pathways regulate emotional behaviors. Therefore, FGF-BP3 plays a critical role in the regulation of emotional states and in the development of anxiety disorders and should be investigated as a therapeutic target for anxiety disease in humans.


Discussing weight with obese primary care patients: physician and patient perceptions.
To evaluate patient-provider agreement on whether weight and related behaviors were discussed during routine visits. Post-visit survey assessments of patients and providers. Obese patients make up the majority of all patients seen in primary care (PC). The patients and physicians were recruited at the time of PC visits. Percent patient-physician agreement and patient, provider and practice characteristics associated with agreement. Patients (456) and physicians (30) agreed about whether or not they discussed weight, physical activity (PA), and diet for 61% of office visits. There was disagreement on one of the items (weight, PA, or diet) for 23% of office visits, and for 2 or more of the items for 16% of the visits. Agreement was relatively greater for discussing weight than for discussing diet or physical activity. Physicians reported discussing weight issues more often than did patients. Overall patient-physician agreement was 0.51-0.59 (weighted Kappa statistic). In a multivariate analyses of factors associated with patient-physician agreement, health insurance (odds ratio [OR]=3.67, p value = 0.002), physician description of patient weight status (OR = 2.27, p value = 0.002), patient report of how weight relates to health (OR = 1.70, p value = 0.04), and female patient gender (OR = 1.62, p = value = 0.02) were significantly related to agreement. Patients and providers disagreed about whether or not weight issues were discussed in a large number of primary care encounters in this study. Physicians may be able to improve care for their obese patients by focusing discussions on specific details of diet and physical activity behaviors, and by clarifying that patients perceive weight-related information has been shared.


Assessment of water quality and ecosystem health of a canal system during the lockdown period.
The impacts of the lockdown period on water quality and ecosystem health in an artificial canal water system were investigated from the rapidly growing Kozhikode City in India. The ecosystem health is measured in terms of water quality indicators such as pH, electrical conductivity (EC), dissolved oxygen (DO), biological oxygen demand (BOD) and Escherichia coli (E. coli) during the pre-lockdown and lockdown period. The study reveals the massive improvement of the ecosystem health of the canal in terms of DO, BOD, and E. coli during the lockdown period. DO values were improved from anoxic (0 mg/L) to oxic (> 5 mg/L), BOD reduced from 31 to 0.7 mg/L as well as E. coli at major urban stretches were 800 MPN/100 mL, which was observed to be absent during the lockdown period. Urban stretches of the canal implicitly proved that the lockdown period was not sufficient to recover the natural ecosystem condition of the canal system. Principal component analysis revealed that the ecosystem health of the canal majorly governs two factors, such as the weathering process and anthropogenic waste sources. The study advocates the policy makers that temporary pollution source control in a timely interval may heal the environment and is useful to the regulatory bodies for suggesting the pollution source control mechanism.


Endothelial GLP-1 (Glucagon-Like Peptide-1) Receptor Mediates Cardiovascular Protection by Liraglutide In Mice With Experimental Arterial Hypertension.
Cardiovascular outcome trials demonstrated that GLP-1 (glucagon-like peptide-1) analogs including liraglutide reduce the risk of cardiovascular events in type 2 diabetes mellitus. Whether GLP-1 analogs reduce the risk for atherosclerosis independent of glycemic control is challenging to elucidate as the GLP-1R (GLP-1 receptor) is expressed on different cell types, including endothelial and immune cells. Approach and Results: Here, we reveal the cardio- and vasoprotective mechanism of the GLP-1 analog liraglutide at the cellular level in a murine, nondiabetic model of arterial hypertension. Wild-type (C57BL/6J), global (Glp1r-/-), as well as endothelial (Glp1rflox/floxxCdh5cre) and myeloid cell-specific knockout mice (Glp1rflox/floxxLysMcre) of the GLP-1R were studied, and arterial hypertension was induced by angiotensin II. Liraglutide treatment normalized blood pressure, cardiac hypertrophy, vascular fibrosis, endothelial dysfunction, oxidative stress, and vascular inflammation in a GLP-1R-dependent manner. Mechanistically, liraglutide reduced leukocyte rolling on the endothelium and infiltration of myeloid Ly6G-Ly6C+ and Ly6G+Ly6C+ cells into the vascular wall. As a consequence, liraglutide prevented vascular oxidative stress, reduced S-glutathionylation as a marker of eNOS (endothelial NO synthase) uncoupling, and increased NO bioavailability. Importantly, all of these beneficial cardiovascular effects of liraglutide persisted in myeloid cell GLP-1R-deficient (Glp1rflox/floxxLysMcre) mice but were abolished in global (Glp1r-/-) and endothelial cell-specific (Glp1rflox/floxxCdh5cre) GLP-1R knockout mice. GLP-1R activation attenuates cardiovascular complications of arterial hypertension by reduction of vascular inflammation through selective actions requiring the endothelial but not the myeloid cell GLP-1R.


Fatty liver is an independent risk factor for the development of Type 2 diabetes in Korean adults.
To investigate whether fatty liver per se is an independent risk factor of incident type 2 diabetes mellitus (T2DM) in Koreans. We examined the clinical and laboratory data of 5372 non-diabetic participants (3670 men and 1702 women; age 46.8 +/- 8.4 years, range 20-79 years) who underwent voluntary medical check-ups in 2000 and follow-up examinations in 2005. Two hundred and thirty-three participants (4.3%) developed T2DM after 5 years. Univariate analysis showed that the development of diabetes was associated with: male sex; family history of diabetes; smoking; older age; higher body mass index (BMI), systolic and diastolic blood pressure, fasting plasma glucose (FPG), hepatic enzymes, total cholesterol and triglycerides; lower HDL cholesterol; and the presence of fatty liver on ultrasonography at baseline. In multiple logistic regression models, after adjusting for age, sex and alcohol consumption, patients with fatty liver were at significantly higher risk of developing T2DM compared to those without fatty liver [relative risk (RR) 3.92, 95% confidence interval (CI) 2.89-5.31]. After further adjustment for smoking, BMI, triglycerides, HDL cholesterol, FPG, alanine aminotransferase and ultrasonographer, fatty liver remained significantly associated with the development of T2DM (RR 1.51, 95% CI 1.04-2.20). Patients with moderate to severe fatty liver had higher risk ratios than patients with mild fatty liver. Exclusion of frequent drinkers did not attenuate the association. Fatty liver on ultrasonography is associated with the development of T2DM, independently of classical risk factors, in Korean adults.


Chemokine profiling in children and adults with symptomatic and asymptomatic respiratory viral infections.
Molecular diagnosis; Viral infection; Chemokines; Disease prognosis; CXCL10; CXCL11; CCL3; CCL4; CCL5; Random forest.


Background gamma-oscillations in neuronal networks with interhemisphere connections.
Results obtained in studies of the high-frequency components of EEG recordings and in modeling, determining the conditions for the appearance of gamma oscillations in interneuronal interactions, were compared with features of the background gamma oscillations recorded in the activity of interacting neurons located in symmetrical loci of the right and left hemisphere motor areas in anesthetized rats. Similarities in high frequencies extracted from EEG recordings and in the most commonly observed gamma oscillation frequencies suggested that these oscillations may represent one of the mechanisms underlying the high-frequency EEG component. Published modeling data indicating that the formation of these oscillations involves reciprocal inhibitory connections, along with our own data that interhemisphere oscillations are seen 1.5 times more commonly than ipsilateral oscillations, suggested that transcallosal inhibition is more effective than inhibition between neighboring cells. Simultaneously extracted background oscillations in the interacting activity of callosal cells and neighboring cells could be different, as could those characterizing the activity of individual neurons. It is suggested that these differences underlie the functional heterogeneity of local cortical neuronal networks and explain the fact that these networks contain various types of inhibitory neurons.


Treatment of severe, recalcitrant, major aphthous stomatitis with adalimumab.
We describe an 18-year-old man with a 7-year history of severe major aphthous stomatitis refractory to multiple standard therapies who responded completely to therapy with adalimumab, a fully humanized monoclonal antibody against tumor necrosis factor alpha (TNF-alpha).


Ultrastructure of nuclear condensation and localization of DNA and proteins in spermatozoa of a dasyurid marsupial, Sminthopsis crassicaudata.
In the dasyurid marsupial, Sminthopsis crassicaudata, the mature spermatozoon has an inner homogeneous (C1) and a peripheral indented (C2) region. Using DNase-gold conjugates, and biotinylated genomic DNA probes, DNA was found to occur in both C1 and C2 regions. The morphogenesis of the spermatozoon nucleus was investigated using ultrastructural and cytochemical studies. Spermiogenesis was divided into 15 steps. By step 10, condensation of the C1 region was complete, and at the caudal extremity of the spermatid nucleus, the nuclear envelope enclosed an electron-lucent space. This space and the surrounding nuclear envelope became very enlarged at step 11. At this stage, a plate of approximately 70 nm in thickness was present along the caudal segment of the C1 region; this "nuclear mantle" did not bind DNase-gold conjugates but stained for lysine-rich proteins using alcoholic phosphotungstic acid. Chromatin condensation resumed at step 12 with the appearance of spherical chromatin structures peripheral to the C1 chromatin. These structures then partially coalesced and the indentations of the C2 region were observed. The expanded nuclear envelope at the caudal extremity persisted in caput epididymal spermatozoa. Spherical inclusions within it did not bind to DNase-gold conjugates but stained for lysine-rich proteins. As the sperm traveled down the epididymis, these inclusions amassed near the nuclear pores and were then removed from the nucleus. In addition, the nuclear mantle was found to have disappeared by the time the spermatozoa reached the corpus epididymidis.


A power efficient actively shielded two-channel transverse MRI gradient coil numerical design.
Large and fast electrical current pulses are typically applied to conventional single-channel transverse MR gradient coils. However, these pulses result in a significant amount of power losses and heating of the coils. Previously, we presented a cylindrical multi-channel Z-gradient coil design that has better power efficiency compared to the single-channel design. In this work, we further investigate the DC power advantage for a two-channel actively-shielded transverse cylindrical gradient coil over the single-channel design. The conventional coil quadrants are radially divided into two sections, one for each channel, for both the primary and shielding surfaces. The symmetric inner sections of both the primary and shielding coils are assigned to the first channel, while the outer enclosing sections for each quadrant are assigned to the second channel. Discrete wire design is employed, where quasi-elliptic functions are used to parameterize the turns of each section. The coil geometric parameters, section size, number of turns, and turn locations are used as the design optimization parameters. The coils are optimized to maximize the coil's efficiency while keeping the linearity error less than 10% and the shielding ratio above 85%. The design procedure is employed to design both the single and two-channel transverse gradient coils for comparison. Eleven different two-channel configurations having different section sizes were investigated. Results show that the power used to drive the most power-efficient two-channel coil is less than that of the single-channel design by ∼25%. Moreover, the two-channel configuration showed slightly better shielding efficiency.


JAK2 mutation in essential thrombocythaemia: clinical associations and long-term prognostic relevance.
Clinical correlates and long-term prognostic relevance of the JAK2(V617F) mutation was studied in 150 patients with essential thrombocythaemia (ET) from a single institution and followed for a median of 11.4 years. During this period, thrombotic complications were documented in 62 patients (41.3%) and transformation into acute myeloid leukaemia (AML), polycythaemia vera (PV), or myelofibrosis with myeloid metaplasia (MMM) occurred in 4 (2.7%), 8 (5.3%), and 15 (10%) patients, respectively. JAK2(V617F) was detected in either archived bone marrow or blood cells from 73 patients (48.7%) but none were homozygous for the mutant allele. Parameters at diagnosis that were significantly associated with the presence of JAK2(V617F) included advanced age and higher counts of both haemoglobin and leucocytes. During follow-up, patients with the mutation were more likely to transform into PV but the incidences of AML, MMM, or thrombotic events were similar between patients with and without the mutation. Multivariate analysis identified advanced age, higher haemoglobin level, and thrombosis history but not the presence of JAK2(V617F) as independent predictors of inferior survival. Therefore, although the presence of JAK2(V617F) in ET appears to promote a PV phenotype, it might not carry treatment-relevant information.


Effects of repeated sprinting on hamstring shear modulus pattern and knee flexor neuromuscular parameters.
The purpose of the present study was to examine the acute effects of a maximum repeated sprint protocol on (1) hamstring shear modulus and (2) knee flexor neuromuscular parameters such as peak torque (PT) and rate of torque development (RTD). Muscle shear modulus was assessed in 18 healthy males using shear wave elastography at rest and during 30° isometric knee flexion at 20% of maximal voluntary isometric contraction, before and after a 10 × 30 m repeated sprint protocol. There was a 9% decrease in average speed between the fastest and slowest sprint (p < 0.001; d = 2.27). A pre-post decrease was observed in PT (p = 0.004; η2p = 0.399) and in the 0-50 ms (p = 0.042; η2p = 0.222), and 50-100 ms (p = 0.028; η2p = 0.254) RTD periods. For the active shear modulus, the only significant change after the sprint task was in the biceps femoris long head (BFlh) with an increase of 10% (Pre: 26.29 ± 8.89 kPa; Post: 28.93 ± 8.31 kPa; p = 0.015; d = 0.31). The present study provides evidence that repeated sprinting leads to significant decreases in average speed, PT, early RTD (0-50 ms; 50-100 ms), and to an increase in BFlh active shear modulus without changing the shear modulus of the other hamstrings muscles.


Association between malnutrition and stroke-associated pneumonia in patients with ischemic stroke.
Malnutrition is associated with a high risk of mortality in adults with ischemic stroke (IS). This study aimed to investigate the relationship between malnutrition and the risk of stroke-associated pneumonia (SAP) as only a few studies examined the relationship between malnutrition and the risk of SAP in IS. Patients were included from emergency departments of five tertiary hospitals in the REtrospective Multicenter study for Ischemic Stroke Evaluation (REMISE) study from January 2020 to December 2020. Malnutrition was defined according to the Controlling Nutritional Status (CONUT), Geriatric Nutritional Risk Index (GNRI), and Prognostic Nutritional Index (PNI) systems. Multivariable logistic regression analysis was used to explore the association between malnutrition and risk of SAP. We enrolled 915 patients with IS, 193 (14.75%), 495 (54.1%), and 148 (16.2%) of whom were malnourished according to the PNI, CONUT, and GNRI scores, respectively. SAP occurred in 294 (32.1%) patients. After adjusting for confounding influencing factors in the logistic regression analysis, malnutrition (moderate and severe risk vs. absent malnutrition) was independently associated with an increased risk of SAP based on the PNI (odds ratio [OR], 5.038; 95% confidence interval [CI] 2.435-10.421, P < 0.001), CONUT (OR, 6.941; 95% CI 3.034-15.878, P < 0.001), and GNRI (OR, 2.007; 95% CI 1.186-3.119, P = 0.005) scores. Furthermore, adding malnutrition assessment indices to the A2DS2 score significantly improved the ability to predict SAP by analysis of receiver operating characteristic curves and net reclassification improvement. Malnutrition was notably prevalent in patients with IS and independently associated with an increased risk of SAP. Further studies are required to identify the effect of interventions on malnutrition to reduce the risk of SAP.


Separation of etoposide phosphate and methotrexate by capillary zone electrophoresis using UV detection with a high sensitivity cell.
Etoposide phosphate and methotrexate are important anti-tumor chemotherapeutic agents. Our previously presented capillary zone electrophoresis (CZE) method using a high sensitivity cell (Z-cell) for quantitative analysis in biological media (urine, plasma) showed good precision and accuracy. The present results show that the investigation using a capillary with high sensitivity cell led to an approximately 10-fold improvement of the detection limit compared to standard capillaries. Plasma and urine samples were analyzed by using a calibration curve for drug concentrations between 0.1 and 100 microg/mL. Good detection limits and good relative standard deviations of the migration times and of the peak areas were observed in these experiments.


Capturing the Unsaid: Nurses' Experiences of Identifying Mental Ill-Health in Older Men in Primary Care-A Qualitative Study of Narratives.
This study describes nurses' experiences in identifying mental ill-health in older men in primary care. The aging population is growing in Sweden and life expectancy is increasing. Age is a risk factor for mental ill-health. Older men are over-represented in deaths from suicide. When older men seek primary care, it is often because of somatic symptoms and rarely for mental health issues. A questionnaire with five open questions was answered by 39 nurses from 10 primary care centres and subjected to inductive qualitative content analysis. The results revealed a main theme-capturing the unsaid-and two categories: (1) feeling secure in the role, with three subcategories (building trust, daring to ask and interpreting signs); and (2) the need for resources, with two subcategories (time and continuity, and finding support in collaboration). The results confirm that nurses in primary care play a key role in identifying mental ill-health in older men. There is a need for resources in the form of time, competence and collaboration with other professionals and patients' relatives. This strategy will establish best practice and provide evidence-based care to facilitate improvements in older men's mental health and prevent suicide.


Changes in B-lymphocyte stimulator protein levels during treatment with albinterferon alfa-2b in patients with chronic hepatitis C who have failed previous interferon therapy.
The pharmacodynamics of albinterferon alfa-2b (alb-IFN), a novel recombinant protein consisting of interferon-α-2b genetically fused to human albumin, was evaluated in patients with chronic hepatitis C with a previous non-response to interferon-α-based therapy. B-lymphocyte stimulator (BLyS) is an essential in vivo regulator of B-lymphocyte homeostasis. This analysis examined the relationship between serum BLyS level and virologic response across a range of alb-IFN doses. In all, 115 patients were randomized initially to three alb-IFN treatment arms (900 and 1200 µg every two weeks [q2wk], and 1200 µg every four weeks) with weight-based ribavirin, followed by sequential enrollment in two higher dose arms (1500 and 1800 µg q2wk). Serum BLyS level was assessed by enzyme-linked immunosorbent assay. Serum BLyS levels at baseline were lower in African-Americans (P < 0.001). Significant BLyS inductions were observed at weeks 12 and 24 versus pretreatment; in general, serum BLyS levels returned to pretreatment levels following treatment completion. Induction of BLyS was greater in the highest dose group; a significant dose-response trend was observed at weeks 12 (P = 0.002) and 24 (P < 0.001), as well as a significant time trend, with further BLyS induction increases at week 24 versus 12 (P < 0.001). Week 24 BLyS level change correlated with hepatitis C virus RNA reduction (r = -0.28; P = 0.006), driven primarily by patients with BLyS increases > 400%, but did not correlate with sustained virologic response. Higher alb-IFN doses demonstrated dose-related BLyS increases, although the correlation with virologic response was modest.


Does academic authorship reflect gender bias in pediatric surgery? An analysis of the Journal of Pediatric Surgery, 2007-2017.
Gender representation in academic publications has been considered a surrogate for gender equity in medicine, although this concept has not been evaluated in pediatric surgery. First and last author genders for Journal of Pediatric Surgery articles from United States and/or Canadian institutions (2007, 2012, 2017) were identified. These data were compared to gender proportions for applicants to and matriculants in pediatric surgery fellowships as well as among American Pediatric Surgical Association (APSA) members. Authorship gender was identified for 632/640 primary articles (98.8%). From 2007 to 2017, the proportion of women as first authors increased from 33.0% to 53.9% (p < 0.001) and as last authors from 16.2% to 26.4% (p = 0.01). The proportion of women fellowship applicants rose from 35.9% to 57.6% (p < 0.001); among those who successfully matched the rise was nonlinear (20.5%-34.0%, p = 0.16). APSA junior and senior women membership proportions rose during the study period [from 28.1% to 43.4% (p = 0.06 for linear trend) and 17.9% to 24.4% (p = 0.005 for linear trend), respectively]. Over the past decade, the overall proportion of women authors in a leading academic pediatric surgery journal has increased significantly, although representation among last authors remains disproportionately low. The numbers of women applicants to pediatric surgery fellowship increased but there was not a concordant rise in the number of women accepted into training positions. Bibliometric analysis. n/a.


Tumor stroma: a complexity dictated by the hypoxic tumor microenvironment.
A lot of effort has been done to study how cancer cells react to low-oxygen tension, a condition known as hypoxia. Indeed, abnormal and dysfunctional blood vessels in the tumor are incapable to restore oxygenation, therefore perpetuating hypoxia, which, in turn, will fuel tumor progression, metastasis and resistance to antitumor therapies. Nevertheless, how stromal components including blood and lymphatic endothelial cells, pericytes and fibroblasts, as well as hematopoietic cells, respond to low-oxygen tension in comparison with their normoxic counterparts has been a matter of investigation in the last few years only and, to date, this field of research remains poorly understood. In general, opposing phenotypes can arise from the same stromal component when embedded in different tumor microenvironments, and, vice versa, different stromal components can have opposite reaction to the same tumor microenvironment. In this article, we will discuss the emerging link between tumor stroma and hypoxia, and how this complexity is translated at the molecular level.


Combining growth factor and stem cell therapy for amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease where motor neurons within the brain and spinal cord are lost, leading to paralysis and death. Certain growth factors should, in principle, be able to protect dying motor neurons. However, targeted delivery to the spinal cord or brain has been a constant problem. There is also accumulating evidence that glial cells might play a crucial role in maintaining motor neuron function and survival in ALS. Stem cells isolated and expanded in culture can be modified to release growth factors and generate glial cells following transplantation into the spinal cord or brain. As such, they might be able to both detoxify the local environment around dying motor neurons and deliver trophic factors. Here we examine the feasibility of translating these findings into new treatments for ALS patients.


RP11-480I12.5-004 Promotes Growth and Tumorigenesis of Breast Cancer by Relieving miR-29c-3p-Mediated AKT3 and CDK6 Degradation.
Pseudogenes have been reported to exert oncogenic or tumor-suppressive functions in cancer. However, the expression, role, and mechanism of pseudogene-derived RNAs in breast cancer remain unclear. The RNA levels and prognostic values of pseudogenes in breast cancer were determined. The levels of RP11-480I12.5 in cell lines and clinical samples were validated by quantitative real-time PCR. In vitro effects of RP11-480I12.5 on cell growth were measured by cell counting kit-8 (CCK-8) assay, colony formation assay, cell counting assay, and flow cytometry analysis. Xenograft model was established to detect its in vivo effect. The potential mechanism of RP11-480I12.5 was also studied by a combination of bioinformatic analysis and experimental confirmation. Finally, the possible functional parental genes of RP11-480I12.5 in breast cancer were explored. After a series of bioinformatic analyses, RP11-480I12.5 was selected as the most potential pseudogene in breast cancer. RP11-480I12.5 expression was significantly upregulated in breast cancer cell lines and clinical breast cancer tissues. Knockdown of RP11-480I12.5 markedly suppressed cell proliferation and colony formation, induced cell apoptosis of breast cancer in vitro, and inhibited tumor growth in vivo. Four transcripts of RP11-480I12.5 (001/002/003/004) were identified. Only overexpression of RP11-480I12.5-004 significantly enhanced cell growth of breast cancer both in vitro and in vivo. RP11-480I12.5-004 mainly located in cytoplasm and increased AKT3 and CDK6 mRNA expression, at least in part, by competitively binding to miR-29c-3p. Six parental genes of RP11-480I12.5 were found, among which TUBA1B and TUBA1C were statistically linked to RP11-480I12.5 expression, possessed prognostic values, and were upregulated in breast cancer. Our findings suggested that pseudogene-derived long non-coding RNA (lncRNA) RP11-480I12.5-004 promoted growth and tumorigenesis of breast cancer via increasing AKT3 and CDK6 expression by competitively binding to miR-29c-3p.


[Home accidents associated with anosmia].
To assess the risk of home accidents related to severe hyposmia. A questionnaire, completed by 57 hyposmic patients and 49 control subjects with a normal sense of smell, asked about four specific types of olfactory-related home accidents: undetected fires, undetected gas leaks, consumption of spoiled food, and incidents of food burning. Level of olfactory function was determined by olfactory testing (Biolfa). Olfactory testing revealed that 60% of the patients were anosmic and 40% had severe hyposmia. They reported cooking-related accidents most often (63%), followed by eating spoiled food (51%), inability to detect a gas leak (47%) and inability to smell a fire (26%). All these accidents were significantly more frequent than in the control population (p<10(-4)). This paper, the first in the European literature and the second in the international literature, shows that patients with severely impaired olfaction are more likely to experience related accidents than those with normal olfactory function.


Evaluation of fluoroscopic cases qualifying as potential fluoroscopic sentinel events.
To address the risk of radiation injury during interventional procedures, the Joint Commission has defined prolonged fluoroscopy resulting in a cumulative skin dose of 15 Gy or more to a single field as a reviewable sentinel event. The goal of this work is to present a system for identifying potential fluoroscopic sentinel events (FSE) and describing common case characteristics. Criteria based on fluoroscopic time (FT) > 150 minutes and reference air kerma (RAK) > 6 Gy were used to identify potential sentinel events. Case information including procedure type, number of procedures, and radiation dose parameters was recorded. Peak skin dose (PSD) was calculated by a medical physicist. Values were compared between procedure types and the relationship between FT, RAK, and PSD was evaluated. Between 2008 and 2011, 183 events exceeding the investigation criteria were identified in three interventional categories: cardiology (54%), neuroradiology (31%), and vascular (16%). The average number of procedures/patient was 1.7 ± 0.1, with the majority (59.6%) having undergone only one procedure. Most cases could be identified using the RAK criterion alone (96.7%). Based on the PSD/RAK ratio, a threshold RAK of 7.5 Gy would effectively identify all cases that would exceed 15 Gy in PSD. Radiation delivered during interventional cases can place patients at risk of cutaneous radiation injury and potential sentinel events. Using appropriate thresholds to determine which cases require detailed investigation allows efficient utilization of department resources for identifying sentinel events.


Late auditory evoked potentials can occur without brain stem potentials.
The sequence of early, middle and late auditory evoked potentials is well known. However, it is unknown whether the late (60-250 msec) potentials can occur independently of the early, brain stem potentials. Therefore, in 6 subjects with markedly abnormal or absent brain stem potentials, we recorded two of the late potentials: the vertex potential and the T-complex. The latter is a putative product of auditory cortex. Both of these potentials were clearly evident in all patients in spite of the absence of or marked abnormalities in brain stem potentials.


Evaluation and comparison of risk-based and universal prenatal HCV screening programs in Alberta, Canada.
Canadian clinical practice guidelines currently recommend risk-based screening for HCV in pregnant individuals. However, no provinces or territories have ever compared the effectiveness of risk-based vs. universal screening for the prenatal diagnosis of HCV. We aimed to evaluate and compare HCV screening programs after implementing a universal population-level pilot program among prenatal patients in Alberta, Canada. The Alberta Prenatal Screening Program for Select Communicable Diseases was amended to include universal HCV antibody screening. Cohorts of pregnant individuals screened for HCV through risk-based or universal programs were generated over 1-year periods. HCV screening rates and prevalence were analyzed and compared between cohorts to evaluate the effectiveness of screening methods. Social and demographic risk factors for HCV-positive individuals were compared between screening cohorts to identify which populations may be overlooked with risk-based guidelines. HCV antibody screening rates were 11.9% and 99.9% among pregnant individuals in the risk-based and universal cohorts, respectively. HCV prevalence among the cohorts was 0.07% and 0.11% (difference = 0.04%, p = 0.032), with an average of 21 additional HCV-positive pregnant individuals identified annually with universal screening. HCV-positive pregnant patients diagnosed through universal screening were more likely to engage in high-risk sexual behaviours/sex work compared to those diagnosed through risk-based screening (47.6% vs. 12.5%, respectively p = 0.035), suggesting that these high-risk cases are being missed by risk-based screening. Universal HCV screening diagnoses significantly higher numbers of pregnant individuals infected with HCV compared to risk-based screening. Universal HCV screening or amending risk-based guidelines to incorporate more proxy variables for risk factors should be considered to improve prenatal HCV screening guidelines in Canada and help achieve HCV elimination in the next decade. HCV is a bloodborne pathogen that can cause severe liver disease and be vertically transmitted from a mother to her baby during pregnancy. Pregnant individuals in Alberta are currently only tested for HCV if they disclose engaging in activities that put them at risk of acquiring the infection (risk-based screening). Using a population-wide universal prenatal HCV screening program, our work shows that testing based on patient disclosed risk alone leads to the significant underdiagnosis of HCV in pregnant individuals and suggests individuals engaging in sex work or risky sexual behaviours are being overlooked by the current risk-based program. Our outcomes represent the first province-wide study to evaluate and compare prenatal HCV risk-based and universal screening programs in Canada and provide evidence to support the update of prenatal HCV screening policies across the country and in similar jurisdictions.


Investigations of face expertise in the social developmental disorders.
Patients with social developmental disorders (SDD), also known as autism spectrum disorders, may have impaired recognition of facial identity or facial expressions. Our goal was to determine whether SDDs were characterized by loss of a perceptual mechanism responsible for face expertise, as current theories suggest that such a loss should be selective for upright faces, disproportionately affect the perception of facial configuration, and possibly be more severe in the eye region. We tested a group of 24 adult patients with SDD with an oddity paradigm that required them to detect changes in facial configuration or feature color, in either the eyes or the mouth, in both upright and inverted faces. One group of subjects with SDD with normal famous face recognition had only a mild reduction in accuracy and a normal pattern of inversion effects. A second group of subjects with SDD with impaired famous face recognition had a severe reduction of accuracy. This deficit was not limited to upright faces. It affected the perception of feature configuration and feature color to a similar degree and both eye and mouth changes were discriminated poorly in upright faces. The impaired face recognition that is present in a subset of patients with social developmental disorders is accompanied by impaired face perception, and this impairment is not exclusive to upright faces, facial configuration, or the eye region. The reduced face processing skills in these subjects may be more consistent with recent computational models of face expertise than with classic dual-route hypotheses.


Septal bounce, vena cava plethora, and pericardial adhesion: informative two-dimensional echocardiographic signs in the diagnosis of pericardial constriction.
To assess the diagnostic value of three different two-dimensional echocardiographic signs of pericardial constriction (early diastolic septal bounce, plethora of the inferior vena cava with blunted respiratory response, and pericardial adhesion), two independent observers retrospectively evaluated echocardiograms in 100 patients, 39 of whom had pericardial constriction, 15 had hemodynamically insignificant pericardial thickening, 16 had restrictive cardiomyopathy, and 30 had normal hearts. Causes of pericardial disease included cardiac surgery, malignancy, and uremia. Sensitivity and specificity of the three signs for constriction were 62% and 93% for septal bounce, 79% and 80% for vena cava plethora, and 79% and 90% for pericardial adhesion, respectively. The presence of either vena cava plethora or pericardial adhesion increased sensitivity, whereas the presence of both plethora and adhesion increased specificity. Between the two readers, septal bounce was the most consistent and pericardial adhesion the least consistent sign. False positive results included right ventricular pacing or left bundle branch block (septal bounce), postpericardiotomy (pericardial adhesion), and right heart failure (vena cava plethora). False negative results were often caused by technical problems with imaging. We conclude that these three two-dimensional echocardiographic signs are useful in differentiating pericardial constriction from hemodynamically insignificant pericardial thickening or restrictive cardiomyopathy.


Advances in the Diagnosis of Equine Respiratory Diseases: A Review of Novel Imaging and Functional Techniques.
The horse, as a flight animal with a survival strategy involving rapid escape from predators, is a natural-born athlete with enormous functional plasticity of the respiratory system. Any respiratory dysfunction can cause a decline in ventilation and gas exchange. Therefore, respiratory diseases often lead to exercise intolerance and poor performance. This is one of the most frequent problems encountered by equine internists. Routine techniques used to evaluate respiratory tract diseases include clinical examination, endoscopic examination, radiographic and ultrasonographic imaging, cytological evaluation, and bacterial culture of respiratory secretions. New diagnostic challenges and the growing development of equine medicine has led to the implementation of advanced diagnostic techniques successfully used in human medicine. Among them, the use of computed tomography (CT) and magnetic resonance (MR) imaging significantly broadened the possibilities of anatomical imaging, especially in the diagnosis of upper respiratory tract diseases. Moreover, the implementation of spirometry, electrical impedance tomography (EIT), and impulse oscillation system (IOS) sheds new light on functional diagnostics of respiratory tract diseases, especially those affecting the lower part. Therefore, this review aimed to familiarize the clinicians with the advantages and disadvantages of the advanced diagnostic techniques of the equine respiratory tract and introduce their recent clinical applications in equine medicine.


Successful endoscopic stent placement as a bridge to surgery for colonic obstruction induced by bevacizumab-based chemotherapy.
The use of a self-expandable metallic stent (SEMS) as a bridge to surgery (BTS) for obstructive colorectal cancer is known to be effective. However, whether the use of a SEMS as a BTS for obstruction induced by effective chemotherapy (CTx) is useful is unknown. We present the case of a 54-year-old female patient with colorectal cancer who underwent SEMS placement as a BTS for colorectal obstruction induced by bevacizumab-based CTx. The patient was diagnosed as having transverse colon cancer with multiple liver metastases invading the inferior vena cava. Bevacizumab-based CTx was started; however, although it was effective, colonic obstruction occurred at the primary site after 31 months. A SEMS was placed as a BTS, and surgical resection of the primary lesion was performed after cessation of bevacizumab. However, the liver metastases remained unresectable. CTx was restarted after surgery, and 48-month survival was achieved. This case shows that SEMS placement as a BTS for colorectal obstruction induced by a good response to bevacizumab-based CTx was safe and beneficial. With the development of CTx and molecular-targeted agents, the frequency of colorectal obstruction associated with effective CTx is expected to increase. SEMS placement as a BTS might be one of the treatment options.


Pregnancy success following abdominal myomectomy for infertility.
There were 46 patients with primary infertility (34 patients) or secondary infertility (12 patients) with no other detectable cause except myomas. After myomectomy, 38% of the patients with primary infertility had full-term pregnancies and 50% of those with secondary infertility. Preoperative distortion of the endometrial cavity was not impressively correlated with the postoperative prognosis.


U1 small nuclear RNA-like sequences in human high molecular weight RNA.
Human U1 small nuclear RNA synthesis was shown earlier to be very sensitive to UV radiation. This led us to test for the possible presence of U1 RNA-like sequences in large RNAs. Human RNA was analyzed in gel blots hybridized with U1 DNA probes. A high molecular weight, heterodisperse RNA population was detected, which hybridizes both to a U1 RNA-coding region single-stranded DNA probe, and to a U1 gene fragment that contains only 6 nucleotides of flanking sequence. These large RNAs can be hybrid selected using immobilized U1 DNA, and have an average size of several kilobases. Additional observations support the claims that the high molecular weight RNA hybridization signal is not an aggregation artifact and that it is sequence specific.


Habitat use and ecological interactions of an introduced and a native species of Anolis lizard on Grand Cayman, with a review of the outcomes of anole introductions.
Since its introduction ten years ago, Anolis sagrei has spread over much of Grand Cayman and is now more common in some habitats than the native anole, A. conspersus. Interspecific differences in body size, perch height, and microclimatic preference may have facilitated the colonization. Nonetheless, competition may be occurring between the species; comparisons with studies of habitat use prior to the arrival of A. sagrei indicate that in open habitats, where A. sagrei is now abundant, A. conspersus perches higher, but in closed habitats, where A. sagrei is absent, no change in perch height is evident. Review of data concerning 23 Anolis introductions indicates that the presence or absence of an ecologically similar native species may be an important determinant of colonization success or failure.


Clinical considerations in the prescription of group, brief, long-term, and couples psychotherapy.
Differential clinical considerations for treatment prescription as an aspect of outpatient evaluation for psychotherapy is presented in overview. The indications and contraindications presented for each of the treatment modalities of group therapy, brief therapy, long-term therapy and couples therapy are based on psychotherapy evaluation, selection criteria and outcome research to date. The information and fund of knowledge of the psychiatrist about appropriate treatment prescription matched to the patient, his problems, and his motivation to work psychotherapeutically is an essential aspect of the initial evaluation.


Cerebral vascular dysfunction in methionine synthase-deficient mice.
Methionine synthase (MS) catalyzes the folate-dependent remethylation of homocysteine to methionine. We tested the hypothesis that deficiency of MS impairs endothelial function in mice heterozygous for disruption of the Mtr gene, which encodes MS. Plasma total homocysteine was similar in wild-type (Mtr(+/+)) and heterozygous (Mtr(+/-)) mice fed a control diet (4.5+/-0.3 and 5.3+/-0.4 micromol/L, respectively) and mildly elevated in Mtr(+/+) and Mtr(+/-) mice fed a low-folate (LF) diet (7.5+/-0.7 and 9.6+/-1.2 micromol/L, respectively; P<0.001 versus control diet). Dilatation of cerebral arterioles to the endothelium-dependent dilator, acetylcholine (10 micromol/L) was blunted in Mtr(+/-) mice compared with Mtr(+/+) mice fed the control diet (21+/-4 versus 32+/-4%; P<0.05). Both Mtr(+/+) and Mtr(+/-) mice exhibited impaired dilatation of cerebral arterioles to acetylcholine when they were fed the LF diet (12+/-2 and 14+/-2%, respectively; P<0.01 versus Mtr(+/+) mice fed the control diet). Elevated levels of superoxide and hydrogen peroxide were detected by confocal microscopy in cerebral arterioles of Mtr(+/-) mice fed the control diet and in both Mtr(+/+) and Mtr(+/-) mice fed the LF diet. These findings demonstrate that defective homocysteine remethylation caused by deficiency of either MS or folate produces oxidative stress and endothelial dysfunction in the cerebral microcirculation of mice.


Crystal structure of recombinant bovine neurocalcin.
The crystal structure of calcium-bound unmyristoylated bovine neurocalcin from Escherichia coli has been determined at 2.4 A resolution. The three-dimensional structure reveals a highly compact structure consisting of: (i) two pairs of calcium-binding EF-hands (EF1-EF2 and EF3-EF4); (ii) a calcium ion bound at EF2, EF3 and EF4 sites; and (iii) an EF1-hand that is disabled from calcium-binding due to a Cys-Pro sequence in the Ca2+-binding loop. The crystal structure of neurocalcin resembles photoreceptor recoverin in overall topology, however its EF2- and EF4-hands differ. Recently, neurocalcin in the calcium-bound state has been shown to stimulate mammalian rod outer segment membrane guanylate cyclase. A possible site for cyclase activity based on the three-dimensional structure is discussed.


Functionalized Fluorescent Nanodiamonds for Simultaneous Drug Delivery and Quantum Sensing in HeLa Cells.
Here, we present multifunctional fluorescent nanodiamonds (FNDs) for simultaneous drug delivery and free radical detection. For this purpose, we modified FNDs containing nitrogen vacancy (NV) centers with a diazoxide derivative. We found that our particles enter cells more easily and are able to deliver this cancer drug into HeLa cells. The particles were characterized by infrared spectroscopy, dynamic light scattering, and secondary electron microscopy. Compared to the free drug, we observe a sustained release over 72 h rather than 12 h for the free drug. Apart from releasing the drug, with these particles, we can measure the drug's effect on free radical generation directly. This has the advantage that the response is measured locally, where the drug is released. These FNDs change their optical properties based on their magnetic surrounding. More specifically, we make use of a technique called relaxometry to detect spin noise from the free radical at the nanoscale with subcellular resolution. We further compared the results from our new technique with a conventional fluorescence assay for the detection of reactive oxygen species. This provides a new method to investigate the relationship between drug release and the response by the cell via radical formation or inhibition.


Predictive testing for BRCA1/2: attributes, risk perception and management in a multi-centre clinical cohort.
The aim of this multi-centre UK study is to examine the attributes of a cohort offered predictive genetic testing for breast/ovarian cancer predisposition. Participants are adults unaffected with cancer from families with a known BRCA1/2 mutation. This is the first large multi-centre study of this population in the UK. The study evaluates mental health, perceived risk of developing cancer, preferred risk management options, and motivation for genetic testing. Participants were assessed when coming forward for genetic counselling prior to proceeding to genetic testing. Three hundred and twelve individuals, 76% of whom are female, from nine UK centres participated in the study. There are no gender differences in rates of psychiatric morbidity. Younger women (<50 years) are more worried about developing cancer than older women. Few women provide accurate figures for the population risk of breast (37%) or ovarian (6%) cancer but most think that they are at higher risk of developing breast (88%) and ovarian (69%) cancer than the average woman. Cancer related worry is not associated with perceived risk or uptake of risk management options except breast self-examination. The findings indicate that younger women may be particularly vulnerable at the time of the offer of a predictive genetic test.


Antihyperlipidemic Effects of Sour Cherries Characterized by Different In Vitro Antioxidant Power and Polyphenolic Composition.
The aims of the present study were to clarify in vivo effects of three sour cherry cultivars characterized by different polyphenolic composition in hyperlipidemic animals in a short term experiment. The three different sour cherry cultivars were chosen based on their total in vitro antioxidant capacity, total polyphenolic, monomeric anthocyanin and flavonoid content. Male Wistar rats were divided randomly into eight groups: rats kept on normal diet (control) and normal diet supplied with sour cherry powder of one of the three cultivars; others were kept on fat-rich diet and fat-rich diet supplied with sour cherry powder prepared from one of the three cultivars. The treatment lasted 10 days. Lyophilized sour cherry administered in the diet decreased both total cholesterol and LDL cholesterol levels, and increased the HDL cholesterol concentration in sera of hyperlipidemic animals. Significant differences were found in the efficacy of different sour cherry cultivars in case of hyperlipidemia. Sour cherries characterized by higher polyphenol content seem to have a more pronounced effect on serum cholesterol levels. Our results suggest that besides anthocyanins, colourless polyphenols also have lipid lowering effect.


Effect of Repeated Intranasal Administration of Different Doses of Insulin on Postoperative Delirium, Serum τ and Aβ Protein in Elderly Patients Undergoing Radical Esophageal Cancer Surgery.
Postoperative delirium is common after general anesthesia in older patients. However, there are currently no effective preventive measures. This study investigated the effect of repeated intranasal administration of different insulin doses before surgery on postoperative delirium in older patients with esophageal cancer, and the possible mechanism for its efficacy. In this randomized, placebo-controlled, double-blind, parallel-group study, 90 older patients were randomly assigned to either a Control (normal saline), Insulin 1 (20 U/0.5 mL intranasal insulin), or Insulin 2 (30 U/0.75 mL intranasal insulin) group. Delirium was assessed on postoperative days 1 (T2), 2 (T3), and 3 (T4) using the Confusion Assessment Method for the Intensive Care Unit. Serum τ and Aβ protein levels were measured at T0 (before insulin/saline administration), T1 (end of surgery), T2, T3 and T4. The Insulin 2 group had a significantly lower prevalence of delirium compared to the Control and Insulin 1 groups three days after surgery. Compared to baseline, τ and Aβ protein levels increased significantly at T1-T4. Compared to the Control group, the Insulin 1 and 2 groups had significantly lower τ and Aβ protein levels at T1-T4, and the Insulin 2 group had significantly lower levels than the Insulin 1 group at T1-T2. The administration of 30 U of intranasal insulin twice daily, from 2 days preoperatively until 10 minutes preanesthesia on the day of surgery, can significantly reduce postoperative delirium in older patients undergoing radical esophagectomy. It can also decrease postoperative τ and Aβ protein expression without causing hypoglycemia. This study was registered at the Chinese Clinical Trial Registry (www.chictr.org.cn, with the unique identifier: ChiCTR2100054245; December 11, 2021).


Predicting microbial traits with phylogenies.
Phylogeny reflects genetic and phenotypic traits in Bacteria and Archaea. The phylogenetic conservatism of microbial traits has prompted the application of phylogeny-based algorithms to predict unknown trait values of extant taxa based on the traits of their evolutionary relatives to estimate, for instance, rRNA gene copy numbers, gene contents or tolerance to abiotic conditions. Unlike the 'macrobial' world, microbial ecologists face scenarios potentially compromising the accuracy of trait reconstruction methods, as, for example, extremely large phylogenies and limited information on the traits of interest. We review 990 bacterial and archaeal traits from the literature and support that phylogenetic trait conservatism is widespread through the tree of life, while revealing that it is generally weak for ecologically relevant phenotypic traits and high for genetically complex traits. We then perform a simulation exercise to assess the accuracy of phylogeny-based trait predictions in common scenarios faced by microbial ecologists. Our simulations show that ca. 60% of the variation in phylogeny-based trait predictions depends on the magnitude of the trait conservatism, the number of species in the tree, the proportion of species with unknown trait values and the mean distance in the tree to the nearest neighbour with a known trait value. Results are similar for both binary and continuous traits. We discuss these results under the light of the reviewed traits and provide recommendations for the use of phylogeny-based trait predictions for microbial ecologists.


Neothalfine, a potent natural anti-tumor agent against metastatic colorectal cancer and its primary mechanism.
Neothalfine is a natural bisbenzylisoquinoline alkaloid with the abundant resource in medicinal plants and has not been reported its anti-tumor efficacy. In the present study, the anti-tumor efficacy was investigated and it showed broad-spectrum activity against several cancer cell lines, especially metastatic colorectal cancer (HCT116, SW620, T84) with the IC50 values of 7.2, 5.9, 8.2 nM, respectively, roughly equal to well-known anti-tumor agent docetaxel (4.0, 4.7, 2.7 nM) and nearly 1000 folds than CPT-11 (4.4, 5.1, 6.9 μM). Furthermore, neothalfine inhibited colorectal cell proliferation by resulting in cell cycle arrest at the G2/M phase and induced apoptosis through the dysfunction of mitochondria to trigger intrinsic apoptotic pathway by untargeted metabolomic method, mitochondrial membrane potential, and caspase-3/7 activity assay. Moreover, neothalfine damaged colorectal cancer clonal spheres expansion significantly at the concentration of 3.5 nM with nearly 1000 folds efficacy than CPT-11 (3.0 µM). The results supported that neothalfine might be an anti-tumor lead for further investigation.


Localization and in silico study of the vegetative insecticidal proteins Vip2S-Vip1S of Bacillus thuringiensis.
The Bacillus thuringiensis S1/4 strain was previously found to harbour vip1S, vip2S, and vip3 genes. Its plasmid curing led to the obtaining of four partially cured strains S1/4-2, S1/4-3, S1/4-7, and S1/4-9 (vip2S-vip1S (-), vip3 (+)), one strain S1/4-4 (vip2S-vip1S (+), vip3 (-)), and S1/4-0 strain lacking the three genes. Using these derivative strains as templates, PCR amplification and southern blot assay revealed that vip2S-vip1S operon and vip3 gene were localized on two different large plasmids. Bioinformatics studies showed that vip2S (1.356 kb), and vip1S (2.637 kb) genes are encoding by an operon consisting of two ORFs separated by an intergenic spacer of 4bp. Using the InterPro tool, Vip2S was found to belong to the family of Binary exotoxin A and Vip1S to bacterial exotoxin B. In silico modeling indicated that the 3D structure of Vip2S is a mixed α/β protein and proposed 3D-model of Vip1S. Bioassays of the partially cured strains supernatants showed a weak toxicity of S1/4-4 to the lepidopteran Spodoptera littoralis comparing to a better effect of S1/4-2, S1/4-3, S1/4-7, and S1/4-9, suggesting its eventual contribution to the toxicity. Nevertheless, the concentrated supernatant of S1/4-4 strain was not toxic against the coleopteran Tribolium castaneum.


Parental perception of malocclusion, its severity and aesthetic concerns in children with mixed dentition: A cross-sectional study.
This study aimed to associate the parents' perception of the need for treatment and the children's aesthetic concern, considering the influence of malocclusion severity levels. A population-based cross-sectional study was conducted with 770 children aged 8 to 10 years in the mixed dentition stage. A closed question sent to parents assessed the subjective orthodontic treatment need (outcome). Orthodontic Aesthetic Subjective Impact Score (OASIS) evaluated children's aesthetic concerns, and the Dental Aesthetic Index (DAI) diagnosed the anterior characteristics and malocclusion severity levels. Individual analyses were performed relating the outcome as independent variables. The variables with P<0.20 in the individual analyses were tested in multiple logistic regression models, and those with P<0.10 remained in the model. The adjusted odds ratio was estimated with a 95% confidence interval. Parents of children with higher aesthetic concerns are 1.82 times more likely to believe that their child needs orthodontic treatment (P<0.05). Parents of children with very severe malocclusion are 1.91 times more likely to perceive their child's need for orthodontic treatment (P<0.05). Parents of children with greater aesthetic concerns are more likely to perceive the need for orthodontic treatment, and very severe malocclusion also influences parents' perception of the need for orthodontic treatment.


Exfoliative sputum cytology of cancers metastatic to the lung.
Although largely replaced by fine-needle aspiration (FNA) and bronchoscopy, cytological examination of sputum for exfoliated malignant cells still is considered a valuable initial diagnostic test in patients presenting with a lung mass. Thirty-five cases of secondary/metastatic tumors involving the lung and diagnosed on sputum were retrospectively reviewed from our cytopathology files for a period of 22 yr (1980-2001). Clinical history and the relevant histopathological material were examined and correlated with the cytological findings. In all cases, a history of malignancy was known. Cytological diagnoses included colonic adenocarcinoma (7 cases); non-Hodgkin's lymphoma (NHL; 5 cases); malignant melanoma (MM; 5 cases); breast carcinoma (5 cases); Hodgkin's lymphoma (HL; 3 cases); pancreatic adenocarcinoma (2 cases); prostatic adenocarcinoma (2 cases); and 1 case each of urothelial carcinoma, endometrial carcinoma, renal cell carcinoma, hepatic small-cell carcinoma, squamous-cell carcinoma (cervix), and leiomyosarcoma (LMS). Cellular preservation was optimal in all cases. The smear background was relatively clean in 25 (71%) cases and predominantly inflamed and/or necrotic in 10 (29%) cases. In non-lymphoid tumors (27 cases), isolated single malignant cells were seen in 7 (26%) cases (all cases of MM and prostatic adenocarcinoma), whereas 20 (74%) cases displayed fragments with intact tumor architecture. Overall, only 10/35 (29%) cases showed noticeable tumor-cell necrosis. In one case (LMS), cell block sections were used for immunoperoxidase (IPOX) studies with positive staining for desmin and actin. Exfoliation of cancer cells in sputum from secondary tumors in the lung is a rare phenomenon in current-day practice, with metastatic colonic adenocarcinoma seen most commonly. Intact tumor architecture was observed in exfoliated cells in 75% of the cases.


The relationship of specific items on the Neuropsychiatric Inventory to caregiver burden in dementia: a systematic review.
Neuropsychiatric symptoms (NPSs) are common in dementia, and they have been identified as important care-recipient variables in terms of their impact on caregiver burden. The aim of this review was to describe how individual NPSs in dementia, assessed using the Neuropsychiatric Inventory, are associated with caregiver burden. We performed a systematic review of English language, peer-reviewed articles retrieved from MEDLINE, PSYCINFO, and EMBASE. A total of 13 studies met the inclusion criteria. Four studies examined the association between individual NPSs and caregiver burden using the Spearman rank correlation test, while three used Pearson's correlation test. Of the remaining studies, five used multiple regression analyses and one the chi-squared test. The majority of included studies did not differentiate between dementia subtypes in the analysis or mainly included only caregivers of people with Alzheimer's disease. The Clinical Dementia Rating score and mean Mini-Mental State Examination score indicate mild to moderate dementia. The majority of caregivers were women, most of whom were children (53.8%) or spouses (36%). The data indicated that irritability, followed by agitation, sleep disturbances, anxiety, apathy, and delusion seem to impact caregiver burden the most. Our principal finding is that irritability, agitation, sleep disturbances, anxiety, apathy, and delusion seem to exert the most impact on caregiver burden. Heterogeneity in the measures and statistical analyses used, however, makes it difficult to make conclusive interpretations. Future research in this field would benefit from standardization of the scientific methodology in use. Copyright © 2017 John Wiley & Sons, Ltd.


Hemodynamic and metabolic changes during and following operation.
During anesthesia and operation, there appears to be a common state wherein oxygen consumption is inadequate to meet intraoperative metabolic requirements. Although there is insufficient information to fully explain this problem, decreased intraoperative levels of cardiac output and oxygen delivery, altered intraoperative oxygen transport at the microcirculatory and cellular levels, and altered delivery of oxidative substrate are possible contributors. Anesthesia and operation thus appear to produce a physiologic pattern similar to other shock states. Postoperative physiologic changes include increased cardiac output and increased oxygen delivery, necessary to support increased oxygen consumption. These postoperative changes may represent compensatory physiologic responses to preoperative and intraoperative oxidative and metabolic deficits. There are also significant energy needs of the healing surgical wound. These additional energy requirements for wound healing add to the degree of increase in metabolism necessary for recovery from operation. The postoperative increase in oxygen consumption appears to be essential to reverse intraoperative deficits, and has been reported to have survival value. Clinically, a major goal of postoperative therapy should thus be to support these necessary physiologic compensations. Titration of postoperative therapy should therefore not be to "normal" physiologic endpoints, but to the supernormal cardiac output and oxygen transport necessary for recovery in postoperative patients.


Correlation of Subchondral Bone Density and Structure from Plain Radiographs with Micro Computed Tomography Ex Vivo.
Osteoarthritis causes changes in the subchondral bone structure and composition. Plain radiography is a cheap, fast, and widely available imaging method. Bone tissue can be well seen from plain radiograph, which however is only a 2D projection of the actual 3D structure. Therefore, the aim was to investigate the relationship between bone density- and structure-related parameters from 2D plain radiograph and 3D bone parameters assessed from micro computed tomography (µCT) ex vivo. Right tibiae from eleven cadavers without any diagnosed joint disease were imaged using radiography and with µCT. Bone density- and structure-related parameters were calculated from four different locations from the radiographs of proximal tibia and compared with the volumetric bone microarchitecture from the corresponding regions. Bone density from the plain radiograph was significantly related with the bone volume fraction (r = 0.86; n = 44; p < 0.01). Mean homogeneity index for orientation of local binary patterns (HI(angle,mean)) and fractal dimension of vertical structures (FD(Ver)) were related (p < 0.01) with connectivity density (HI(angle,mean): r = -0.73, FD(Ver): r = 0.69) and trabecular separation (HI(angle,mean): r = 0.73, FD(Ver): r = -0.70) when all ROIs were pooled together (n = 44). Bone density and structure in tibia from standard clinically available 2D radiographs are significantly correlated with true 3D microstructure of bone.


Impact and determinants of left ventricular function in patients undergoing primary percutaneous coronary intervention in acute myocardial infarction.
We evaluated the prognostic effect of baseline left ventricular function and the determinants of its recovery after acute myocardial infarction (AMI) treated by primary angioplasty. Left ventriculography was performed during the index procedure in 1,620 of 2,082 patients (78%) who underwent primary angioplasty for AMI in the CADILLAC trial. One-year survival rate was significantly lower in patients whose baseline left ventricular ejection fraction (LVEF) was <40% than in those whose LVEF was > or =40% (89.0% vs 97.2%, respectively, p <0.0001). The effect of baseline left ventricular dysfunction on mortality was confined to the first 3 months after AMI; thereafter, survival was independent of baseline LVEF. By multivariate analysis, baseline LVEF (hazard ratio 0.93, 95% confidence interval 0.90 to 0.97, p <0.001) and infarct zone regional wall motion (hazard ratio 2.67, 95% confidence interval 1.08 to 6.63, p = 0.03) were independent predictors of 1-year mortality. Seven-month convalescent LVEF was also directly related to baseline LVEF and inversely correlated with previous AMI, multivessel coronary disease, preprocedural Thrombolysis In Myocardial Infarction grade 0 to 2 flow, larger infarct artery diameter, and infarct artery restenosis at follow-up. In conclusion, baseline left ventricular function measured during the index procedure is a strong independent predictor of early and late survival after primary angioplasty. Simple clinical and angiographic features readily available at the time of primary angioplasty also predict convalescent LVEF and are thus of prognostic utility.


A survey of intestinal helminths of well-cared-for dogs in Jamaica, and their potential public health significance.
This study investigates the level of helminthic infestation in better-cared-for dogs in a middle-class community in suburban Kingston. A canine zoographic study was conducted, and fresh faecal deposits were collected and analysed for helminth life-cycle stages. The survey indicated that 73% (n = 93) of households in the study area owned one dog or more (mean = 1.4). Resident's attitudes towards canine management suggested that the dog population was, in general, restricted to the residential estate, and most owners claimed to have dewormed their dogs at least as young animals. Of 141 faecal specimens, 58% contained eggs or larvae of one or more of eight helminths: Uncinaria stenocephala (26%), Ancylostoma sp. (23%), Trichuris vulpis (9%), Toxocara canis (8%), Spirocerca lupi (6%), Strongyloides sp. (6%), Apophallus sp. (4%) and taeniids (1%). There was a high level of multiple infection in the host animals, with approximately one fifth of the infected samples containing three or more helminth types. Infection intensity was apparently low, but some dogs harboured heavy worm loads.


[Relation between serum lipoprotein metabolism and biliary lipid metabolism].
This review concern with recent results regarding interrelationships between serum lipoprotein and bile acid metabolism. First, changes in bile acid metabolism in primary hyperlipoproteinaemia type II and type IV are described. In addition, influences of lipid-lowering drugs such as sitosterol, cholestyramine/colestipol, neomycin, nicotinic acid, clofibrate and thyroxin on serum lipoproteins and biliary lipid metabolism are discussed. Changes in lipoprotein metabolism in disorders of bile acid metabolism and effects of primary and secundary bile acids on lipoprotein metabolism, hepatic cholesterol metabolism and intestinal cholesterol absorption are described. In the final discussion interrelationships between very low density lipoprotein - triglycerides and cholic acid metabolism as well as low density lipoprotein and chenodeoxycholic acid metabolism are stressed. The positive correlation between serum triglycerides and lithogenicity of bile is underlined and the possible significance of high density lipoprotein-cholesterol as precursor of biliary cholesterol is discussed.


The influence of trimethylamine on the concentration/odour intensity relations in hexanal.
Hexanal and trimethylamine are products formed in the process of fish deterioration and it is believed that both these substances contribute somehow to the typical off-flavour developing in the course of this process. In aqueous hexanal solutions and in hexanal solutions with added trimethylamine the intensity differences in the odour of hexanal and the difference thresholds for hexanal solutions were determined.


Studies on the mutator gene, mutT of Escherichia coli. Molecular cloning of the gene, purification of the gene product, and identification of a novel nucleoside triphosphatase.
The mutator gene, mutT, has been cloned into an expression vector and overproduced in Escherichia coli. The gene product has been purified to over 90% homogeneity as judged by gel electrophoresis and amino acid analysis. The amino acid composition of the protein and the sequence of the 20 amino acids of the N-terminal region agree well with the nucleotide sequence of the gene reported by Akiyama et al. (Akiyama, M., Horiuchi, T., and Sekiguchi, M. (1987) Mol. Gen. Genet. 206, 9-16) and indicate that the first of the potential initiation codons (position 164) of the open reading frame in the PvuII fragment carrying the mutT gene is the site of initiation of translation of the 15,000-Da polypeptide. A novel nucleoside triphosphatase activity which has a preference for dGTP is associated with the purified protein, and preliminary experiments are consistent with the notion that the mutT gene product is the enzyme responsible for this activity.


Prevalence of hypercalcemia in hospitalised patients: effects of "correction" for serum albumin values.
Hypercalcemia is ideally detected by the measurement of serum ionised calcium. Because this is not widely available, in common clinical practice "albumin-corrected" calcium values are often utilized. Our study investigated whether the method used to measure serum albumin concentration may significantly interfere in the derived serum calcium values and, consequently, in the identification of hypercalcemic patients. In 170 consecutive patients admitted to our Department of Internal Medicine we measured serum total calcium, total protein, and albumin by colorimetric method; albumin concentration was also derived by electrophoresis assessment. After correcting serum calcium for colorimetrically (CA) and electrophoretically (EA) measured albumin values, the detected frequencies of hypercalcemia were compared, utilizing different cut-off limits (i.e. 11.0, 10.4 and 10.2 mg/dl). In our patients, the CA values were significantly lower than EA levels. As a consequence, EA-corrected calcium, as well as total calcium concentration were significantly lower than CA-corrected values. This may also account for the very different prevalence of hypercalcemic patients identified by serum total, EA-corrected and CA-corrected calcium values. Our data therefore indicate the importance of the method of albumin measurement in the determination of "corrected" calcium concentration.


Ca2+ regulation in detrusor smooth muscle from developing fetal sheep bladders.
Sheep fetus is a useful model to study in utero bladder outflow obstruction but little is known about cell physiology of fetal bladders. To remedy this defect we have characterised intracellular Ca(2+) regulation in fetal sheep myocytes of different developmental ages. Fetal detrusor myocytes had a similar resting [Ca(2+)](i) to adult cells and exhibited transient [Ca(2+)](i) increases in response to carbachol, ATP, high-K, caffeine and low-Na. The carbachol transients were abolished by atropine and caffeine; the ATP response was blocked by alpha,beta-methylene ATP; high-K-evoked [Ca(2+)](i) rises were antagonised by verapamil. The maximal responses to carbachol, high-K, caffeine and low-Na in fetal cells were similar to those of adult counterparts, whilst the ATP response was smaller (p < 0.05). These variables were largely similar between the three gestational groups with the exception of ATP-induced response between early fetal and adult bladders (p < 0.05). Dose-response curves to carbachol demonstrated an increase of potency between mid-gestation and early adulthood (p < 0.05). These data show that muscarinic receptors coupled to intracellular Ca(2+) release, P2X receptor-linked Ca(2+) entry, depolarisation-induced Ca(2+) rise via L-type Ca(2+) channels, Na(+)/Ca(2+) exchange and functional intracellular Ca(2+) stores are all operational in fetal bladder myocytes. Whilst most of Ca(2+) regulators are substantially developed and occur at an early fetal age, a further functional maturation for cholinergic sensitivity and purinergic efficacy continues throughout to adulthood.


Direct evidence of acetylcholine releasing effect of serotonin in the Auerbach plexus.
The mode of action of serotonin on isolated longitudinal muscle strip with attached Auerbach plexus and on whole ileum preparation has been studied. Atropine, tetrodoxtoxin, morphine and alpha-adrenoceptor stimulants inhibited the contractions of the strips and whole ileum in response to serotonin. In the presence of atropine (2 X 10(-8) M) at 9 times higher concentration of serotonin was needed to produce the same contraction of the ileum as in control experiments. These facts indicate that the contractile effect of serotonin on the longitudinal muscle of ileum might be mediated via a cholinergic pathway. Direct evidence has also been provided that serotonin is capable of releasing acetylcholine from the Auerbach plexus. It is very likely that serotonin stimulates ganglion cells, which in fact leads to firing and, consequently, to an increase of acetylcholine release from the nerve terminals.


Intestinal ammonium production in the rat: the role of the colon, small intestine, and circulating glutamine.
The intestinal ammonium production and the intestinal uptake of circulating glutamine were investigated in anesthetized intact rats and rats with resected small intestine or colon by simultaneous measurements performed on portal and arterial blood. It was shown that ammonium release into the portal blood by the small intestine is of equal magnitude to that released by the colon, and that circulating glutamine participates in ammonium production by the small intestine. Increased levels of circulating glutamine induced by its i.v. infusion to intact rats were not accompanied by an increase in intestinal ammonium production.


Increased gamma band power during movement planning coincides with motor memory retrieval.
The retrieval of motor memory requires a previous memory encoding and subsequent consolidation of the specific motor memory. Previous work showed that motor memory seems to rely on different memory components (e.g., implicit, explicit). However, it is still unknown if explicit components contribute to the retrieval of motor memories formed by dynamic adaptation tasks and which neural correlates are linked to memory retrieval. We investigated the lower and higher gamma bands of subjects' electroencephalography during encoding and retrieval of a dynamic adaptation task. A total of 24 subjects were randomly assigned to a treatment and control group. Both groups adapted to a force field A on day 1 and were re-exposed to the same force field A on day 3 of the experiment. On day 2, treatment group learned an interfering force field B whereas control group had a day rest. Kinematic analyses showed that control group improved their initial motor performance from day 1 to day 3 but treatment group did not. This behavioral result coincided with an increased higher gamma band power in the electrodes over prefrontal areas on the initial trials of day 3 for control but not treatment group. Intriguingly, this effect vanished with the subsequent re-adaptation on day 3. We suggest that improved re-test performance in a dynamic motor adaptation task is contributed by explicit memory and that gamma bands in the electrodes over the prefrontal cortex are linked to these explicit components. Furthermore, we suggest that the contribution of explicit memory vanishes with the subsequent re-adaptation while task automaticity increases.


VIP elevates platelet cyclic AMP (cAMP) levels and inhibits in vitro platelet activation induced by platelet-activating factor (PAF).
Platelet-activating factor (PAF), a potent endogenous phospholipid released by a variety of mammalian cells, induces platelet activation in vivo and in vitro. Little is known, however, about the physiological modulation of its actions. We have examined the ability of two naturally occurring compounds which stimulate cAMP production, vasoactive intestinal peptide (VIP) and prostacyclin (PGI2), to inhibit PAF-induced platelet aggregation and secretion in vitro. Washed, [3H]serotonin-labeled, rabbit platelets were incubated 60 sec in the presence of VIP, PGI2 or 3-isobutyl-1-methylxanthine (IBMX) and subsequently stimulated with PAF. In separate studies, cAMP levels were determined in similar aliquots of platelets incubated for 30 sec with VIP, PGI2 or IBMX. VIP, PGI2 and IBMX inhibited platelet aggregation and secretion in a dose-dependent manner. Fifty percent inhibition was achieved at final concentrations of 1.7 X 10(6) M VIP, 3.6 X 10(6) M PGI2 and 6.5 X 10(5) M IBMX. IBMX potentiated the inhibitory effects of VIP and PGI2 on PAF-induced platelet activation. VIP and PGI2 elevated platelet cAMP levels four-fold and 50-fold, respectively, in the presence of 10(3) M IBMX. These findings demonstrate that VIP inhibits PAF-induced platelet activation, with a potency comparable to that of PGI2.