Small intestinal edema had the strongest correlation with portal venous pressure amongst capsule endoscopy findings.
Previous studies have reported small intestinal lesions in patients with portal hypertensive disease. However, the etiology of these lesions is not clear, as portal venous pressure was not measured in any of these studies. The aim of this study is to clarify the association between small intestinal lesions and hepatic venous pressure gradient (HVPG), which correlates well with portal venous pressure. Thirty-five patients with liver cirrhosis were evaluated by capsule endoscopy for small intestinal lesions. HVPG was measured within 3 days of capsule endoscopy. Blood tests, clinical symptoms, Child-Pugh classification and HVPG were analyzed against small intestinal lesions such as edemas, red spots, angiodysplasia and varices. Lesions were categorized according to their location in the duodenum, jejunum or ileum. Edema was evaluated using a 4-grade capsule endoscopy scoring index. HVPG and edema scores increased with Child-Pugh scores. Red spots and angiodysplasia did not correlate with HVPG. Varices were detected in only 5 patients. The edema score was the factor which most strongly correlated with HVPG by multivariate analysis (p = 0.0008). There was also a strong linear relation between edema scores and HVPG (R = 0.75, p < 0.0001). Small intestinal edemas showed the strongest correlation with HVPG among all small intestinal lesions.


First clinical experience with the new Surpass Evolve flow diverter: technical and clinical considerations.
To describe the results in patients treated with the Surpass Evolve (SE) device, the new generation of Surpass flow diverters. Twenty-five consecutive patients (20 women, average age 58 years), with anterior or posterior circulation aneurysms treated with SEs in two early-user centers, were included. Device properties and related technical properties, imaging and clinical follow-up data, and intraprocedural, early (<30 days) and delayed (>30 days) neurological complications, further divided into minor (silent/non-permanent) and major (permanent) complications, were recorded and analyzed. Twenty-nine SEs were successfully implanted in all subjects to treat 26 aneurysms using an 0.027" microcatheter with an average of 1.2 stents per patient. No intraprocedural thromboembolic or hemorrhagic complications were seen. At clinical follow-up, 24/25 (96%) patients had a modified Rankin Score of 0-2. Mortality was 0%. Imaging follow-up, available in 22/25 (88%) patients (median follow-up time 4 months), showed a complete aneurysm occlusion in 13/23 (57%) imaged lesions. Minor, transitory neurological deficits were recorded in 5/25 (20%) patients. One (4%) major complication was seen in one patient (4%) with a left-sided hemispheric stroke on postprocedural day 4 due to an acute stent thrombosis. Preliminary experience in patients demonstrates a good performance of the SE. This newly designed implant maintains the engineering characteristics of Surpass flow diverters, including precise placement due to its lower foreshortening and a high mesh density, yet can be deployed through a significantly lower-profile delivery system.


[Internal fistulas of bile ducts caused by cholelithiasis].
Operative treatment of 41 patients is analysed. It is shown that internal fistulas of the bile tract are severe complications of cholelithiasis. Late detection and treatment of diseases of the biliary system is the main cause of formation of the fistulas. Removal of the internal biliary fistula as well as correction of abnormal changes in the bile ducts is the object of the operative intervention. The postoperative fatality was 12.2%.


Live-cell visualization of transmembrane protein oligomerization and membrane fusion using two-fragment haptoEGFP methodology.
Protein interactions play key roles throughout all subcellular compartments. In the present paper, we report the visualization of protein interactions throughout living mammalian cells using two oligomerizing MV (measles virus) transmembrane glycoproteins, the H (haemagglutinin) and the F (fusion) glycoproteins, which mediate MV entry into permissive cells. BiFC (bimolecular fluorescence complementation) has been used to examine the dimerization of these viral glycoproteins. The H glycoprotein is a type II membrane-receptor-binding homodimeric glycoprotein and the F glycoprotein is a type I disulfide-linked membrane glycoprotein which homotrimerizes. Together they co-operate to allow the enveloped virus to enter a cell by fusing the viral and cellular membranes. We generated a pair of chimaeric H glycoproteins linked to complementary fragments of EGFP (enhanced green fluorescent protein)--haptoEGFPs--which, on association, generate fluorescence. Homodimerization of H glycoproteins specifically drives this association, leading to the generation of a fluorescent signal in the ER (endoplasmic reticulum), the Golgi and at the plasma membrane. Similarly, the generation of a pair of corresponding F glycoprotein-haptoEGFP chimaeras also produced a comparable fluorescent signal. Co-expression of H and F glycoprotein chimaeras linked to complementary haptoEGFPs led to the formation of fluorescent fusion complexes at the cell surface which retained their biological activity as evidenced by cell-to-cell fusion.


Implementing parity for mental health and substance use treatment in Medicaid.
To estimate the association between the implementation of parity in coverage for mental health and substance use disorder (MHSUD) services within the Medicaid program and MHSUD service use. Wisconsin Medicaid enrollment and claims data from 2013 to 2015. In April 2014, Wisconsin Medicaid transitioned childless adult beneficiaries from coverage with limited MHSUD services to parity-consistent coverage. Preparity, they only had Medicaid coverage for MHSUD visits to psychiatrists and the emergency department, while parent beneficiaries had parity-consistent coverage. The study uses a difference-in-differences design to compare outcome changes for childless adult and parent beneficiaries. We identified 76, 569 childless adult and parent beneficiaries aged 18-64 who were continuously enrolled for the 2-year study period. Introducing parity-consistent coverage within Medicaid was associated with increased utilization of Medicaid-reimbursed MHSUD services: outpatient, prescription medication, ED, and inpatient. Increased MHSUD outpatient visits were driven by increased visits to nonpsychiatrists. Parity's effects on MHSUD service use have been studied in the context of private insurance, but its impact among Medicaid beneficiaries has not. Our findings suggest that parity implementation in Medicaid could increase access to effective MHSUD services in a high-need population.


Community-Based Crisis Services, Specialized Crisis Facilities, and Partnerships With Law Enforcement.
How a community responds to behavioral health emergencies is both a public health issue and a social justice issue. Individuals experiencing a behavioral health crisis often receive inadequate care in emergency departments, boarding for hours or days while awaiting treatment. Such crises also account for a quarter of police shootings and 2 million jail bookings per year, and racism and implicit bias magnify these problems for people of color. Fortunately, the new 988 mental health emergency number compounded with police reform movements have created momentum for building behavioral health crisis response systems that deliver comparable quality and consistency of care as we expect for medical emergencies. This paper provides an overview of the rapidly evolving landscape of crisis services. The authors discuss the role of law enforcement and various approaches to lessening the impact on individuals experiencing behavioral health emergencies, especially for historically marginalized populations. The authors provide an overview of the crisis continuum, including crisis hotlines, mobile teams, observation units, crisis residential programs, and peer wraparound services that can help ensure that linkage to aftercare is successful. The authors also highlight opportunities for psychiatric leadership, advocacy, and strategies for creating a well-coordinated crisis system that meets the needs of the community.


Feasibility and acceptability of undertaking postmortem studies for tuberculosis medical research in a low income country.
If we are to break new ground in difficult-to-treat or difficult-to-vaccinate diseases (such as HIV, malaria, or tuberculosis), we must have a better understanding of the immune system at the site of infection in humans. For tuberculosis (TB), the initial site of infection is the lungs, but obtaining lung tissues from subjects suffering from TB has been limited to bronchoalveolar lavage (BAL) or sputum sampling, or surgical resection of diseased lung tissue. We examined the feasibility of undertaking a postmortem study for human tuberculosis research at Mulago National Referral Hospital in Kampala, Uganda. Postmortem studies give us an opportunity to compare TB-involved and -uninvolved sites, for both diseased and non-diseased individuals. We report good acceptability of the next-of-kin to consent for their relative's tissue to be used for medical research; that postmortem and tissue processing can be undertaken within 8 hours following death; and that immune cells remain viable and functional up to 14 hours after death. Postmortem procedures remain a valuable and essential tool both to establish cause of death, and to advance our medical and scientific understanding of infectious diseases.


Astragalus Polysaccharide Improves Insulin Sensitivity via AMPK Activation in 3T3-L1 Adipocytes.
Astragalus polysaccharide (APS) is an important bioactive component of Astragalus membranaceus which is used as an anti-diabetes herb in traditional Chinese medicine. The objective of this study was to investigate the effects and mechanisms of APS on insulin-sensitizing of adipocytes. Mouse 3T3-L1 preadipocytes were used as a model. The results showed that APS increased preadipocytes proliferation in a dose dependent manner, and 0.1 μg/mL APS sufficiently increased Proliferating Cell Nuclear Antigen (PCNA) content (p < 0.01). Moreover, APS enhanced intracellular lipid accumulation and mRNA expression of proliferator-activated receptor γ (PPARγ, p < 0.01), CCAAT/enhancer binding protein α (C/EBPα, p < 0.01) and fatty acid binding protein (aP2, p < 0.01). As expected, corresponding protein contents were elevated. Importantly, APS increased 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose (2-NBDG) uptake (p < 0.01). Meanwhile, both mRNA and protein content of glucose transporter 4 (Glut4) were elevated by APS (p < 0.01). The APS treatment enhanced tyrosine phosphorylation of insulin receptor substrate 1 (IRS1, p < 0.05) and phosphor-Akt content (p < 0.01). Besides, phosphorylated AMP-activated protein kinase (AMPK) content was increased in the APS treated cells (p < 0.01). Taken together, APS improved insulin sensitivity by enhancing glucose uptake, possibly through AMPK activation. These results suggested that APS might be a therapeutic candidate for insulin resistance.


Activation of cAMP-dependent protein kinase increases the protein level of steroidogenic factor-1.
The orphan nuclear receptor steroidogenic factor 1 (SF-1) is an essential regulator of endocrine organogenesis, sexual differentiation, and steroidogenesis. SF-1 is a transcriptional regulator of cAMP responsive genes, but the exact mechanisms by which cAMP-dependent PKA modulates SF-1 dependent transcription leading to increased steroidogenic output have not been determined. In this report the effects of PKA activation on SF-1 in living cells have been examined by the use of full-length SF-1 cDNA fused to the cDNA encoding green fluorescent protein (GFP). The GFP-SF-1 fusion protein localized to the nucleus of both steroidogenic Y1 cells and nonsteroidogenic COS-1 cells, and the functional properties of wild-type SF-1 were conserved. When the catalytic subunit of PKA was coexpressed with GFP-SF-1, we observed that the fluorescence emission was markedly elevated. These findings were confirmed by Western blot analysis, showing that stimulation of PKA increased SF-1 protein levels. The PKA- induced expression of SF-1 protein was not accompanied by an increase in SF-1 mRNA levels. However, pulse-chase studies showed a decrease in SF-1 degradation rate in response to activation of PKA, indicating that PKA elevates the level of SF-1 by increasing the stability of SF-1 protein.


Nonlinear evolution of the plasma beat wave: Compressing the laser beat notes via electromagnetic cascading.
The near-resonant beat wave excitation of an electron plasma wave (EPW) can be employed for generating the trains of few-femtosecond electromagnetic (EM) pulses in rarefied plasmas. The EPW produces a comoving index grating that induces a laser phase modulation at the difference frequency. As a result, the cascade of sidebands red and blue shifted by integer multiples of the beat frequency is generated in the laser spectrum. The bandwidth of the phase-modulated laser is proportional to the product of the plasma length, laser wavelength, and amplitude of the electron density perturbation. When the beat frequency is lower than the electron plasma frequency, the redshifted spectral components are advanced in time with respect to the blueshifted ones near the center of each laser beat note. The group velocity dispersion of plasma compresses so chirped beat notes to a few-laser-cycle duration thus creating a train of sharp EM spikes with the beat periodicity. Depending on the plasma and laser parameters, chirping and compression can be implemented either concurrently in the same, or sequentially in different plasmas. Evolution of the laser beat wave and electron density perturbations is described in time and one spatial dimension in a weakly relativistic approximation. Using the compression effect, we demonstrate that the relativistic bistability regime of the EPW excitation [G. Shvets, Phys. Rev. Lett. 93, 195004 (2004)] can be achieved with the initially subthreshold beat wave pulse.


FAB: First UK feasibility trial of a future randomised controlled trial of Family focused treatment for Adolescents with Bipolar disorder.
This first mixed-methods UK trial examined the feasibility and acceptability of a future definitive randomised controlled trial (RCT) to evaluate whether Family Focussed Treatment for Adolescents with Bipolar Disorder (FFT-A) UK version can improve family functioning and well-being as part of the management of Paediatric Bipolar Disorder (PBD). The trial used a randomised, parallel group, non-blinded design where participants received FFT-A UK (16 sessions over 6 months) immediately or after 12 months (delayed arm). Measures of family functioning, well-being and quality of life of the young person and the main carer (most commonly a parent) were completed at baseline, 6 and 12-months in both arms. Primary outcome measures included rates of eligibility, consent and retention along with estimates of variability in the measures and assessment of the intervention delivery. Qualitative interviews allowed assessment of participants' views about FFT-A and the trial processes. Twenty-seven of 36 young persons with PBD and their families consented; of these, 14 families were randomised to the immediate and 13 to the delayed arm. Two families from the immediate arm withdrew consent and discontinued participation. Quantitative measures were completed by 22 families (88%) at 6-months and 21 families (84%) at 12-months. Qualitative interviews were conducted with 30 participants (9 young people, 15 parents and 6 other family members). Nine families attended 3 post-trial focus groups. It was feasible to recruit and retain to this trial. The results highlighted that trial design and measures were acceptable to participants. A benefit in family relationships was reported by participants which they attributed to the intervention in qualitative interviews. Families recommended that future modifications include definitive trial(s) recruiting participants in the age range 15-25 years as it felt this was the age range with maximum need. Trial registration ISRCTN, ISRCTN59769322. Registered 20 January 2014, http://www.isrctn.com/ISRCTN59769322.


Whole almond consumption is associated with better diet quality and cardiovascular disease risk factors in the UK adult population: National Diet and Nutrition Survey (NDNS) 2008-2017.
This work aimed to estimate whole almond consumption in a nationally representative UK survey population and examine associations with diet quality and cardiovascular disease (CVD) risk. Four-day food record data from the National Diet and Nutrition Survey (NDNS) 2008-2017 (n = 6802, age ≥ 19 year) were analyzed to investigate associations between whole almond consumption and diet quality, measured by the modified Mediterranean Diet Score (MDS) and modified Healthy Diet Score (HDS), and CVD risk markers, using survey-adjusted multivariable linear regression. Whole almond consumption was reported in 7.6% of the population. Median intake in whole almond consumers was 5.0 g/day (IQR 9.3). Consumers had higher diet quality scores relative to non-consumers; higher intakes of protein, total fat, monounsaturated, n-3 and n-6 polyunsaturated fats, fiber, folate, vitamin C, vitamin E, potassium, magnesium, phosphorus, and iron; and lower intakes of trans-fatty acids, total carbohydrate, sugar, and sodium. BMI and WC were lower in whole almond consumers compared to non-consumers: 25.5 kg/m2 (95% CI 24.9, 26.2) vs 26.3 kg/m2 (25.9, 26.7), and 88.0 cm (86.2, 89.8) vs 90.1 cm (89.1, 91.2), respectively. However, there were no dose-related fully adjusted significant associations between increasing almond intake (g per 1000 kcal energy intake) and lower CVD risk markers. Almond intake is low in the UK population, but consumption was associated with better dietary quality and lower CVD risk factors. Habitual consumption of whole almonds should be encouraged as part of a healthy diet.


Recovery of renal function in a dialysis-dependent patient following gastric bypass surgery.
There is increasing evidence that obesity, independently from other comorbidities such as diabetes and hypertension, can cause renal dysfunction. While this indolent dysfunction may be asymptomatic, it can render patients more susceptible to renal insufficiency when the kidneys are further injured by other pathological processes. Here, we present a morbidly obese patient whose type-A aortic dissection was complicated by acute renal failure that subsequently progressed into end-stage renal disease. However, his renal function improved dramatically following substantial weight reduction after gastric bypass surgery obviating the need for dialysis and transplantation. The potential mechanisms by which a patient's obesity may lead to renal dysfunction are discussed. This case and other similar reports suggest that obese patients with renal failure can safely undergo bariatric surgery and that bariatric surgery may have a role in treating chronic kidney disease in select morbidly obese patients.


Alcohol Consumption during Adolescence in a Mouse Model of Binge Drinking Alters the Intrinsic Excitability and Function of the Prefrontal Cortex through a Reduction in the Hyperpolarization-Activated Cation Current.
Periodic episodes of excessive alcohol consumption ("binge drinking") occur frequently among adolescents, and early binge drinking is associated with an increased risk of alcohol use disorders later in life. The PFC undergoes significant development during adolescence and hence may be especially susceptible to the effects of binge drinking. In humans and in animal models, adolescent alcohol exposure is known to alter PFC neuronal activity and produce deficits in PFC-dependent behaviors, such as decision making, response inhibition, and working memory. Using a voluntary intermittent access to alcohol (IA EtOH) procedure in male mice, we demonstrate that binge-level alcohol consumption during adolescence leads to altered drinking patterns and working memory deficits in young adulthood, two outcomes that suggest medial PFC dysfunction. We recorded from pyramidal neurons (PNs) in the prelimbic subregion of the medial PFC in slices obtained from mice that had IA EtOH and found that they display altered excitability, including a hyperpolarization of the resting membrane potential and reductions in the hyperpolarization-activated cation current (Ih) and in intrinsic persistent activity (a mode of neuronal firing that is dependent on Ih). Many of these effects on intrinsic excitability were sustained following abstinence and observed in mice that showed working memory deficits. In addition, we found that resting membrane potential and the Ih-dependent voltage "sag" in prelimbic PFC PNs are developmentally regulated during adolescence, suggesting that adolescent alcohol exposure may compromise PFC function by arresting the normal developmental trajectory of PN intrinsic excitability.SIGNIFICANCE STATEMENT Binge alcohol drinking during adolescence has negative consequences for the function of the developing PFC. Using a mouse model of voluntary binge drinking during adolescence, we found that this behavior leads to working memory deficits and altered drinking behavior in adulthood. In addition, we found that adolescent drinking is associated with specific changes to the intrinsic excitability of pyramidal neurons in the PFC, reducing the ability of these neurons to generate intrinsic persistent activity, a phenomenon thought to be important for working memory. These findings may help explain why human adolescent binge drinkers show performance deficits on tasks mediated by the PFC.


Changes of dimension of EEG/ECoG nonlinear dynamics predict epileptogenesis and therapy outcomes.
The lack of early biomarkers of epileptogenesis precludes a sound prediction of epilepsy development after acute brain injuries and of the natural course of the disease thus impairing the development of antiepileptogenic treatments. We investigated whether the dimensional changes of nonlinear dynamics in EEG/ECoG signals, that were recorded in the early aftermath of different epileptogenic injuries, provide a measure to be exploited as a sensitive prognostic and predictive biomarker for epilepsy. Using three different models of epilepsy in two rodent species, we report a common and significant decrease of nonlinear dynamics dimension in EEG/ECoG tracings during early epileptogenesis. In particular, the magnitude of this dimensional decrease predicts the severity of ensuing epilepsy, and this measure is modulated by disease-modifying or antiepileptogenic treatments. The broad application of EEG/ECoG monitoring in epilepsy underlines the translational value of these findings for enriching the population of patients at risk for developing epilepsy in clinical investigations.


The Drosophila Nab2 RNA binding protein inhibits m6A methylation and male-specific splicing of Sex lethal transcript in female neuronal tissue.
The Drosophila polyadenosine RNA binding protein Nab2, which is orthologous to a human protein lost in a form of inherited intellectual disability, controls adult locomotion, axon projection, dendritic arborization, and memory through a largely undefined set of target RNAs. Here, we show a specific role for Nab2 in regulating splicing of ~150 exons/introns in the head transcriptome and focus on retention of a male-specific exon in the sex determination factor Sex-lethal (Sxl) that is enriched in female neurons. Previous studies have revealed that this splicing event is regulated in females by N6-methyladenosine (m6A) modification by the Mettl3 complex. At a molecular level, Nab2 associates with Sxl pre-mRNA in neurons and limits Sxl m6A methylation at specific sites. In parallel, reducing expression of the Mettl3, Mettl3 complex components, or the m6A reader Ythdc1 rescues mutant phenotypes in Nab2 flies. Overall, these data identify Nab2 as an inhibitor of m6A methylation and imply significant overlap between Nab2 and Mettl3 regulated RNAs in neuronal tissue.


Collar pressure mapping: An evaluation of seven collar types used on working donkeys in Europe.
Working donkeys represent an important source of energy worldwide. Poor working conditions and equipment affect their ability to work. Poorly designed, ill-fitted harness causes inefficient transfer of power and leads to health and welfare issues. Using technology to assess different types of collars provides a better understanding of those that are most efficient for working donkeys. Seven different collars were tested using pressure pads. Contact area, median, maximum and peak pressures were obtained for the whole collar and critical points. Eight donkeys pulled 20% and 40% of their body weight, using each collar, under controlled conditions. Contact area and pressures vary between collars and effort, with design and expansion capacity of the collars playing a major role. Simple collars designed specifically for donkeys performed well, with full collars designed for horses also having good results. Due to reduced expansion capacity and contact in the critical points, the breast collars were the least effective. Design, appropriate padding and manufacturing materials and adjustment capacity are key features for good collars, and such parameters are of paramount importance in terms of health and welfare for working donkeys.


Pericarditis - clinical features and management.
Pericarditis is an important diagnosis to consider in a patient presenting with chest pain. It is diagnosed in 5% of patients presenting to hospital emergency departments with chest pain in the absence of a myocardial infarction. This article describes the common features and management of pericarditis in the general practice setting. Characteristic clinical findings in pericarditis include pleuritic chest pain and a pericardial friction rub on auscultation of the left lower sternal border. Electrocardiography may reveal diffuse PR depressions and diffuse ST segment elevations with upward concavity. The most common aetiologies of pericarditis are idiopathic and viral, and the most common treatment for these is nonsteroidal antiinflammatory drugs and colchicine. The complications of pericarditis include effusion, tamponade and myopericarditis. Pericardial effusion may present as a globular heart shadow on chest X-ray. The presence of effusion, constriction or tamponade can be confirmed on echocardiography. Tamponade is potentially life threatening and is diagnosed by the clinical findings of decreased blood pressure, elevated jugular venous pressure, muffled heart sounds on auscultation and pulsus paradoxus.


Patients with Neurological Illnesses and Their Experience During the Lockdown: A Teleinterview-based Study.
Governments have imposed lockdowns in the wake of the COVID-19 pandemic. Hospitals have restricted outpatient clinics and elective services meant for non-COVID illnesses. This has led to patients facing unprecedented challenges and uncertainties. This study was carried out to assess patients' concerns and apprehensions about the effect of the lockdown on their treatments. An ambispective, observational cross-sectional single centre study was conducted. Patients were contacted telephonically and requested to answer a structured questionnaire. Their responses were documented and summarized as frequency and proportions. A total of 727 patients were interviewed. Epilepsy (32%) was the most common neurological illness in our cohort followed by stroke (18%). About half the patients and/or their caregivers reported health-related concerns during the lockdown. The primary concern was how to connect with their treating neurologist if need arose. Forty-seven patients (6.4%) had drug default. Among patients on immunomodulatory treatments, only eight patients had drug default. High compliance rates were also observed in the stroke and epilepsy cohorts. Of the 71 patients who required emergency care during the lockdown, 24 could reach our hospital emergency. Fourteen patients either had a delay or could not seek emergency care. Two-thirds of our patients found the telemedicine experience satisfactory. The ongoing pandemic will continue to pose challenges to both physicians and patients. Patients in follow-up may need to be contacted regularly and counselled regarding the importance of maintaining drug compliance. Telemedicine can be used to strengthen the healthcare delivery to patients with non-COVID illnesses.


Accurate platelet counting in an insidious case of pseudothrombocytopenia.
Anticoagulant-induced aggregation of platelets leads to pseudothrombocytopenia. Blood cell counters generally trigger alarms to alert the user. We describe an insidious case of pseudothrombocytopenia, where the complete absence of Coulter counter alarms both in ethylenediaminetetraacetic acid blood and in citrate or acid citrate dextrose blood samples was compounded by the fact that the massive aggregates were exclusively found at the edges of the blood smear. Non-recognition of pseudothrombocytopenia can have serious diagnostic and therapeutic consequences. While the anti-aggregant mixture citrate-theophylline-adenosine-dipyridamole completely failed in preventing pseudothrombocytopenia, addition of iloprost to anticoagulants only partially prevented the aggregation. Only the prior addition of gentamicin to any anticoagulant used resulted in a complete prevention of pseudothrombocytopenia and enabled to count accurately the platelets.


[Functional heterogeneity of the piramidal system: corticobulbar and corticospinal tracts].
The pyramidal system is constituted by the cortical fibers reaching the bulbar pyramids at the level of the inferior Olive. Close to 75% of these fibers decussate terminating at bulbar level about half of them while the other half form the crossed corticospinal tract. The majority of the uncrossed fibers descend to the cord forming the direct corticospinal tract. This revision presents evidence demonstrating the functional heterogeneity of the pyramidal system. The corticobulbar fibers are slower conducting and branch more than the corticospinal fibers. The conduction speed of the corticospinal fibers increases as they reach more caudal segments, thus assuring that the different signals modulating the inter segmental activity reach their targets simultaneously. Those from the somatosensory cortex end in the dorsal horn while those from the primary motor cortex end primarily on interneurons of the reflex pathways to distal limb muscles although in rats, primates and humans about 10% of them terminate directly on motoneurons. The corticobulbar component of the pyramidal system selects the adequate motor synergies and modulates other descending systems to coordinate the activity of the distal musculature and the associated postural adjustments. The corticospinal component is functionally related to motor activities requiring accuracy, and to motoneuronal recruitment to adjust the contractile force. Both pyramidal subsystems modulate the processing and integration of the ascending somatosensory information generated by the movement itself.


Non-contact acoustic cell trapping in disposable glass capillaries.
Non-contact trapping using acoustic standing waves has shown promising results in cell-based research lately. However, the devices demonstrated are normally fabricated using microfabrication or precision machining methods leading to a high unit cost. In e.g. clinical or forensic applications avoiding cross-contamination, carryover or infection is of outmost importance. In these applications disposable devices are key elements, thus making the cost per unit a critical factor. A solution is presented here where low-cost off-the-shelf glass capillaries are used as resonators for standing wave trapping. Single-mode as well as multi-node trapping is demonstrated with an excellent agreement between simulated and experimentally found operation frequencies. Single particle trapping is verified at 7.53 MHz with a trapping force on a 10 microm particle of up to 1.27 nN. The non-contact trapping is proved using confocal microscopy. Finally, an application is presented where the capillary is used as a pipette for aspirating, trapping and dispensing red blood cells.


Cardiac Tamponade by Tack Fixation of a Hiatal Mesh. Should Tacks Still Be Used in the Diaphragm?
Since the first successful use of mesh in hernia surgery, the development and progress in materials, techniques, and procedures have increased exponentially; consequently, surgeons started to use meshes for hiatal hernia repair to prevent postoperative hernia recurrences and complications. Nonetheless, there are alarming reports in literature concerning cardiac tamponade as an apparently rare complication of hiatal mesh placement, especially when fixation is performed with tacks. A 50-year-old female diagnosed with gastroesophageal reflux disease undergoes an elective laparoscopic Nissen fundoplication and hiatal hernia repair with tack fixation of the mesh; on the fourth postoperative day she was readmitted with cardiac tamponade diagnosed via echocardiography, and CT scan showed proximity of the tacks to the pericardium. She underwent a failed attempt of ultrasound guided pericardiocentesis (PC), therefore, a pericardial window was performed. The ideal method for diaphragmatic mesh fixation is still controversial. Some recent articles alert of this potential risk; although the manufacturers contraindicate the use of tacks in the diaphragm, one-third of surgeons prefer this method.


Bone marrow stromal antigen 2 expressed in cancer cells promotes mammary tumor growth and metastasis.
Several innate immunity genes are overexpressed in human cancers and their roles remain controversial. Bone marrow stromal antigen 2 (BST-2) is one such gene whose role in cancer is not clear. BST-2 is a unique innate immunity gene with both antiviral and pro-tumor functions and therefore can serve as a paradigm for understanding the roles of other innate immunity genes in cancers. Meta-analysis of tumors from breast cancer patients obtained from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets were evaluated for levels of BST-2 expression and for tumor aggressiveness. In vivo, we examined the effect of knockdown of BST-2 in two different murine carcinoma cells on tumor growth, metastasis, and survival. In vitro, we assessed the effect of carcinoma cell BST-2 knockdown and/or overexpression on adhesion, anchorage-independent growth, migration, and invasion. BST-2 in breast tumors and mammary cancer cells is a strong predictor of tumor size, tumor aggressiveness, and host survival. In humans, BST-2 mRNA is elevated in metastatic and invasive breast tumors. In mice, orthotopic implantation of mammary tumor cells lacking BST-2 increased tumor latency, decreased primary tumor growth, reduced metastases to distal organs, and prolonged host survival. Furthermore, we found that the cellular basis for the role of BST-2 in promoting tumorigenesis include BST-2-directed enhancement in cancer cell adhesion, anchorage-independency, migration, and invasion. BST-2 contributes to the emergence of neoplasia and malignant progression of breast cancer. Thus, BST-2 may (1) serve as a biomarker for aggressive breast cancers, and (2) be a novel target for breast cancer therapeutics.


Determinants of Willingness to Become Organ Donors among Dialysis Patients' Family Members.
This study explores the factors affecting the willingness of dialysis patients' family members to become involved in living and deceased organ donation. We utilize cross sectional data on 350 family members of dialysis patients collected through self-administered survey from June to October 2013. The factors affecting willingness to become deceased and living organ donors among respondents were identified by running logistic regressions. The findings reveal that ethnicity, education and role in family are significant factors explaining willingness for living donation, while ethnicity, knowledge of organ donation and donor age drive willingness for deceased donation. We also find that the reasons of respondents being unwilling to donate center on the lack of information and family objections for deceased donation, while being medically unfit, scared of surgery and family objections are the reasons for unwillingness to donate living organs. In light of our findings, educational efforts are suggested to decrease the reluctance to become involved in living and deceased donation.


Crystal structure of Caulobacter crescentus polynucleotide phosphorylase reveals a mechanism of RNA substrate channelling and RNA degradosome assembly.
Polynucleotide phosphorylase (PNPase) is an exoribonuclease that cleaves single-stranded RNA substrates with 3'-5' directionality and processive behaviour. Its ring-like, trimeric architecture creates a central channel where phosphorolytic active sites reside. One face of the ring is decorated with RNA-binding K-homology (KH) and S1 domains, but exactly how these domains help to direct the 3' end of single-stranded RNA substrates towards the active sites is an unsolved puzzle. Insight into this process is provided by our crystal structures of RNA-bound and apo Caulobacter crescentus PNPase. In the RNA-free form, the S1 domains adopt a 'splayed' conformation that may facilitate capture of RNA substrates. In the RNA-bound structure, the three KH domains collectively close upon the RNA and direct the 3' end towards a constricted aperture at the entrance of the central channel. The KH domains make non-equivalent interactions with the RNA, and there is a marked asymmetry within the catalytic core of the enzyme. On the basis of these data, we propose that structural non-equivalence, induced upon RNA binding, helps to channel substrate to the active sites through mechanical ratcheting. Structural and biochemical analyses also reveal the basis for PNPase association with RNase E in the multi-enzyme RNA degradosome assembly of the α-proteobacteria.


The Effect of Memantine on Functional Recovery of the Sciatic Nerve Crush Injury in Rats.
Following severe peripheral nerve injury (PNI), regeneration is often insufficient and functional recovery is incomplete. In this regard, glutamate N-methyl-D-aspartate (NMDA) receptor antagonist such as Memantine have been shown to have neuroprotective effects. We evaluated the effects of Memantine against sciatic nerve crush injury in male Wistar Rats. Memantine or vehicle was given parenteraly to rats for 7 days postoperative. In Memantine treatment groups, a single dose of agent (5 and 10 mg/kg) was administered daily. The control group was given vehicle in the same manner. The rats were subjected to crush injury in the left sciatic nerve with non-serrated clamp for 30 seconds. Behavioural, electrophysiological and morphological alterations were evaluated during the experimental period. Results showed that Memantine has no significant effect on regeneration process rate and functional recovery quality. In the sciatic functional index (SFI) test no significant difference was observed between Memantine treatment groups (5 and 10 mg/ kg) at any week. Since the major neuroprotective effect of Memantine is due to its protective activity against NMDA receptormediated excitotoxicity, it seems that glutamate excitotoxicity is less important in motor impairment due to sciatic nerve crush injury. It is clear that more research is needed to confirm these findings.


Nonpalpable versus palpable invasive breast tumors treated with breast-conserving surgical management.
Most mammographically detected breast cancers are small, nonpalpable malignancies that should be amenable to cure by definitive breast-conserving therapy (BCT) consisting of tumor excision and postoperative radiation. We examined this hypothesis by retrospectively comparing the incidence of local recurrence and the rate of survival in breast cancer patients undergoing BCT for nonpalpable versus palpable lesions. Between 1982 and 1991, 345 patients at the John Wayne Cancer Institute, a large referral center for breast diseases, underwent BCT for invasive ductal and/or invasive lobular breast carcinomas: 120 (35%) had nonpalpable lesions detected by mammography (MG group), and 225 (65%) had palpable lesions detected by physical exam (PE group). The clinical and pathologic tumor status and the clinical outcome were recorded in each case. Median tumor size was significantly larger in PE than MG patients (2 cm versus 1 cm, P < 0.001). Only 29 percent of MG patients were premenopausal, compared with 51 percent of PE patients (P < 0.05). Axillary node involvement was more frequent in PE than MG patients (46% versus 19%, P < 0.01). Over a median follow-up of 58 months, local recurrence rates were 8 per cent for both MG and PE patients. In both groups, the incidence of local recurrence increased significantly when tumor was found in the margins of the resected breast specimen. In the MG group, the risk of local recurrence was significantly higher in premenopausal patients (P < 0.05). Survival was similar in both groups. The rate of local recurrence after BCT is the same for nonpalpable and palpable breast tumors. However, nonpalpable lesions have a lower rate of regional node metastases, which may improve survival. Both local recurrence and metastases seem to be related to tumor size. Tumor-free operative margins are the best predictor of local control.


Comparative effect of cane syrup and natural honey on abdominal viscera of growing male and female rats.
The high intake of refined sugars, mainly fructose has been implicated in the epidemiology of metabolic diseases in adults and children. With an aim to determine whether honey can substitute refined sugars without adverse effect, the long-term effects of natural honey and cane syrup have been compared on visceral morphology in growing rats fed from neonatal age. Honey increased the caecum and pancreas weights in male rats, which could enhance enzymatic activities of pancreas and digestive functions by intestinal microflora of caecum. Unlike honey, cane syrup caused fatty degenerations in the liver of both male and female rats. Honey enhanced intestinal villi growth, and did not cause pathology in the rodents' abdominal viscera, suggesting potential nutritional benefit as substitution for refined sugars in animal feed.


Coronavirus Disease 2019 Complicated by Multiple Simultaneous Intracerebral Hemorrhages.
The relationship between coronavirus disease 2019 (COVID-19) and intracerebral hemorrhage remains unclear. We herein report a case of severe COVID-19 pneumonia complicated by multiple simultaneous intracerebral hemorrhages (MSICH). The patient died eight days after the episode of MSICH. No apparent coagulopathy was observed; however, extracorporeal membrane oxygenation and anticoagulation might have caused the occurrence of MSICH. Laboratory findings showed hypercoagulability, suggesting that thrombotic etiologies, such as sinus thrombosis or cerebral infarction, might also have caused MSICH. MSICH can occur as a fatal complication of COVID-19, and this should be considered when providing treatment.


Natural variation in rosette size under salt stress conditions corresponds to developmental differences between Arabidopsis accessions and allelic variation in the LRR-KISS gene.
Natural variation among Arabidopsis accessions is an important genetic resource to identify mechanisms underlying plant development and stress tolerance. To evaluate the natural variation in salinity stress tolerance, two large-scale experiments were performed on two populations consisting of 160 Arabidopsis accessions each. Multiple traits, including projected rosette area, and fresh and dry weight were collected as an estimate for salinity tolerance. Our results reveal a correlation between rosette size under salt stress conditions and developmental differences between the accessions grown in control conditions, suggesting that in general larger plants were more salt tolerant. This correlation was less pronounced when plants were grown under severe salt stress conditions. Subsequent genome wide association study (GWAS) revealed associations with novel candidate genes for salinity tolerance such as LRR-KISS (At4g08850),flowering locus KH-domain containing protein and a DUF1639-containing protein Accessions with high LRR-KISS expression developed larger rosettes under salt stress conditions. Further characterization of allelic variation in candidate genes identified in this study will provide more insight into mechanisms of salt stress tolerance due to enhanced shoot growth.


Origin of supposedly biogenic magnetite in the Martian meteorite Allan Hills 84001.
Crystals of magnetite (Fe(3)O(4)) and periclase (MgO) in Fe-Mg-Ca carbonate in the Martian meteorite Allan Hills 84001 were studied by using transmission electron microscopy to understand their origin and evaluate claims that the magnetites were made by Martian microorganisms. In magnesian carbonate, periclase occurs as aggregates of crystals (grain size approximately equal to 3 nm) that are preferentially oriented with respect to the carbonate lattice. Larger periclase crystals approximately equal to 50 nm in size are commonly associated with voids of similar size. Periclase clearly formed by precipitation from carbonate as a result of partial decomposition and loss of CO(2). Magnetite occurs in more ferroan carbonate, and, like periclase, it is associated with voids and microfractures and the two oxides may be intermixed. Magnetite nanocrystals that are commonly euhedral and entirely embedded in carbonate are topotactically oriented with respect to the carbonate lattice, showing that they formed as solid-state precipitates. Magnetites in Fe-rich carbonate rims are not well oriented. These magnetites are generally more irregular in shape and diverse in size than the euhedral variety. All occurrences of magnetite and periclase are entirely consistent with in situ growth by solid-state diffusion as a result of carbonate decomposition during impact heating. Biogenic sources should not be invoked for any magnetites.


'Ca(2+)-induced Ca(2+) entry' or how the L-type Ca(2+) channel remodels its own signalling pathway in cardiac cells.
The adjustment of Ca(2+) entry in cardiac cells is critical to the generation of the force necessary for the myocardium to meet the physiological needs of the body. In this review, we present the concept that Ca(2+) can promote its own entry through Ca(2+) channels by different mechanisms. We refer to it under the general term of 'Ca(2+)-induced Ca(2+) entry' (CICE). We review short-term mechanisms (usually termed facilitation) that involve a stimulating effect of Ca(2+) on the L-type Ca(2+) current (I(Ca-L)) amplitude (positive staircase) or a lessening of Ca(2+)-dependent inactivation of I(Ca-L). This latter effect is related to the amount of Ca(2+) released by ryanodine receptors (RyR2) of the sarcoplasmic reticulum (SR). Both effects are involved in the control of action potential (AP) duration. We also describe a long-term mechanism based on Ca(2+)-dependent down-regulation of the Kv4.2 gene controlling functional expression of the repolarizing transient outward K(+) current (I(to)) and, thereby, AP duration. This mechanism, which might occur very early during the onset of hypertrophy, enhances Ca(2+) entry by maintaining Ca(2+) channel activation during prolonged AP. Both Ca(2+)-dependent facilitation and Ca(2+)-dependent down-regulation of I(to) expression favour AP prolongation and, thereby, promote sustained voltage-gated Ca(2+) entry used to enhance excitation-contraction (EC) coupling (with no change in the density of Ca(2+) channels per se). These self-maintaining mechanisms of Ca(2+) entry have significant functions in remodelling Ca(2+) signalling during the cardiac AP. They might support a prominent role of Ca(2+) channels in the establishment and progression of abnormal Ca(2+) signalling during cardiac hypertrophy and congestive heart failure.


Contrasting plasma free amino acid patterns in elite athletes: association with fatigue and infection.
There is little information on the plasma free amino acid patterns of elite athletes against which fatigue and nutrition can be considered. Therefore the aim was to include analysis of this pattern in the medical screening of elite athletes during both especially intense and light training periods. Plasma amino acid analysis was undertaken in three situations. (1) A medical screening service was offered to elite athletes during an intense training period before the 1992 Olympics. Screening included a blood haematological/biochemical profile and a microbial screen in athletes who presented with infection. The athletes were divided into three groups who differed in training fatigue and were considered separately. Group A (21 track and field athletes) had no lasting fatigue; group B (12 judo competitors) reported heavy fatigue at night but recovered overnight to continue training; group C (18 track and field athletes, one rower) had chronic fatigue and had been unable to train normally for at least several weeks. (2) Athletes from each group were further screened during a post-Olympic light training period. (3) Athletes who still had low amino acid levels during the light training period were reanalysed after three weeks of additional protein intake. (1) The pre-Olympics amino acid patterns were as follows. Group A had a normal amino acid pattern (glutamine 554 (25.2) micromol/l, histidine 79 (6.1) micromol/l, total amino acids 2839 (92.1) micromol/l); all results are means (SEM). By comparison, both groups B and C had decreased plasma glutamine (average 33%; p<0.001) with, especially in group B, decreased histidine, glucogenic, ketogenic, and branched chain amino acids (p<0.05 to p<0.001). None in group A, one in group B, but ten athletes in group C presented with infection: all 11 athletes had plasma glutamine levels of less than 450 micromol/l. No intergroup differences in haematological or other blood biochemical parameters, apart from a lower plasma creatine kinase activity in group C than in group B (p<0.05) and a low neutrophil to lymphocyte ratio in the athletes with viral infections (1.2 (0.17)), were found. (2) During post-Olympic light training, group A showed no significant amino acid changes. In contrast, group B recovered normal amino acid levels (glutamine 528 (41.4) micromol/l, histidine 76 (5.3) micromol/l, and total amino acids 2772 (165) micromol/l) (p<0.05 to p<0.001) to give a pattern comparable with that of group A, whereas, in group C, valine and threonine had increased (p<0.05), but glutamine (441 (24.5) micromol/l) and histidine (58 (5.3) micromol/l) remained low. Thus none in group A, two in group B, but ten (53%) in group C still had plasma glutamine levels below 450 micromol/l, including eight of the 11 athletes who had presented with infection. (3) With the additional protein intake, virtually all persisting low glutamine levels increased to above 500 micromol/l. Plasma glutamine rose to 592 (35.1) micromol/l and histidine to 86 (6.0) micromol/l. Total amino acids increased to 2761 (128) micromol/l (p<0.05 to p<0.001) and the amino acid pattern normalised. Six of the ten athletes on this protein intake returned to increased training within the three weeks. Analysis of these results provided contrasting plasma amino acid patterns: (a) a normal pattern in those without lasting fatigue; (b) marked but temporary changes in those with acute fatigue; (c) a persistent decrease in plasma amino acids, mainly glutamine, in those with chronic fatigue and infection, for which an inadequate protein intake appeared to be a factor.


Shear flow in smectic A liquid crystals.
This paper considers the onset of a shear-induced instability in a sample of smectic A liquid crystal. Unlike many previous models, the usual director n need not necessarily coincide with the local smectic layer normal a; the traditional Oseen constraint ([Formula: see text]) is not imposed when flow is present. A recent dynamic theory for smectic A (Stewart 2007 Contin. Mech. Thermodyn. 18 343-60) will be used to examine a stationary instability in a simple model when the director reorientation and smectic layer distortions are, firstly, assumed not to be coupled to the velocity and, secondly, are supposed coupled to the velocity. A critical shear rate at which the onset of the instability occurs will be identified, together with an accompanying critical director tilt angle and critical wavenumber for the associated smectic layer undulations. Despite some critical phenomena being largely unaffected by any coupling to the flow, it will be shown that the influence of some material parameters, especially the smectic layer compression constant B(0) and the coupling constant B(1), upon the critical shear rate and critical tilt angle can be greatly affected by flow.


Comparison of Dynamic Vault Changes Following Implantation of Two Different Models of Phakic Intraocular Lenses.
To compare the dynamic vault range (the difference in the central vault height from scotopic to photopic light condition) after implantation of the ICL/TICL (STAAR Surgical) and Eyecryl phakic/Eyecryl phakic toric intraocular lens (IOL) (Biotech Healthcare). This retrospective study included patients with myopia or myopic astigmatism eligible for phakic IOL implantation with either the ICL/TICL or Eyecryl phakic/Eyecryl phakic toric IOL. Vault changes in varying light conditions (scotopic, mesopic, and photopic) were assessed using an anterior segment optical coherence tomography-based tomographer and dynamic vault range (DVR) was compared between the two groups. A total of 60 eyes from 36 patients (30 eyes in each group) with a mean age of 28.63 ± 6.36 years were included. The mean postoperative follow-up at the time of assessment was 9.4 ± 5.3 and 8.9 ± 5.28 months (P = .75) in the ICL and Eyecryl groups, respectively. The mean values of scotopic, mesopic, and photopic vault were 490.56 ± 238.64, 453.56 ± 224.30, and 373.96 ± 200.24 μm in the ICL group and 515.46 ± 174.34, 490.26 ± 184.04, 450.43 ± 173.92 μm in the Eyecryl group (P = .32, .24, and .05, respectively). The DVR was 116.6 ± 59.29 μm in the ICL group versus 65.03 ± 31.78 μm in the Eyecryl group (P < .001). The Eyecryl phakic IOL showed significantly fewer light-induced changes in the central vault height (DVR) compared to the ICL, which may be attributed to the difference in the material of the two phakic IOL models. This may be clinically significant in eyes with low postoperative vaults with respect to their follow-up and risk assessment of cataractogenesis in the long term. [J Refract Surg. 2023;39(8):546-554.].


Neonatal mortality in infants of diabetic mothers.
To assess the effects of an educational program emphasizing detection and tight control of maternal glucose levels during pregnancy, the management and outcome of all pregnancies complicated by diabetes mellitus delivered at a county hospital during two time periods, 1978-1980 and 1981-1983, are compared. The prevalence of diabetes during pregnancy was 1.4% between 1978 and 1980 and 2.6% between 1981 and 1983 (P less than 0.01). The perinatal death rate decreased for infants of diabetic mothers from 100 per thousand deliveries in 1978-1980 to 32 per thousand in 1981-1983 (P less than 0.02). The perinatal death rate for infants of mothers with gestational diabetes was nearly the same as the perinatal death rate for all neonates born in the state in 1981-1983. Congenital anomalies followed by stillbirths were the most frequent causes of perinatal death.


[Correlation between symptoms and social adjustment in patients suffering from schizophrenia or major affective disorder].
With a view to examining the appropriateness of relying solely on pharmacotherapy rather than on a program of multimodal therapy, the goal of this study is to test the hypothesis that there is little relationship between psychotic and affective symptoms on the one hand, and life skills and social functioning on the other. Eighty-four male subjects presenting a diagnosis of schizophrenia, mania or severe depression were therefore recruited in hospitals in the Montreal region. The relationships previously identified were studied, while factors likely to affect them, such as the chronicity of the disorder, the level of intellectual functioning, and the presence of additional symptoms, were controlled as necessary. The results suggest poorer social functioning among the schizophrenics having a high level of negative symptoms. In addition, the relationship between negative symptoms and IQ suggests that the intellectual functioning of these individuals can potentially affect the acquisition of skills required for adequate social functioning. Among subjects with a major affective disorder, the results reveal poor social functioning even during quasi-asymptomatic periods. These results suggest that patients suffering from schizophrenia or a major affective disorder require interventions aimed at increasing their level of psychosocial functioning.


Who benefits from which activity? On the relations between personality traits, leisure activities, and well-being.
Leisure activities have been emphasized as an important predictor of well-being. However, little research has examined the effects of leisure activity enactment on well-being over time. Moreover, it is unknown which activities are most beneficial for whom. We integrate diverse theoretical accounts of person-environment relations and propose a generic Personality-Activity-Well-Being (PAW) framework, which highlights different relations between personality traits, activities, and well-being. To investigate these relations, we used 11 annual waves from the Longitudinal Internet Studies for the Social Sciences (LISS) panel (total N = 12,703 participants, N = 59,108 assessments), which included measures of the Big Five personality traits, 15 different leisure activities, and affective well-being and life satisfaction. Our preregistered multilevel models revealed three sets of findings. First, we observed on average small expected between-person associations between leisure activities and well-being (e.g., higher average levels of holidays, evening socializing, talking to close others, exercise, and cultural activities were associated with higher well-being). Annual within-person fluctuations in several leisure activities also predicted well-being in expected ways, but effect sizes were very small and varied strongly across participants. Second, personality traits were related to leisure activities in hypothesized ways, yielding on average small but also some moderate and large correlations. Third, Personality Trait × Leisure Activity interactions were only evident on the between-person level, very small in size, and in the opposite direction of our expectations. Personality traits did not moderate well-being benefits from leisure within persons. We discuss the implications of our findings and sketch an agenda for future work. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Environmental correlates of adolescent active travel to school in Asia: An ecological study.
This study aimed to examine the association between country-level environmental correlates and the prevalence of active school travel (AST) in Asia and country-level differences in AST by age and sex. This ecological study involved 31 Asian countries. Dependent variables were AST prevalence, AST prevalence difference by age, and by sex. Independent variables were country-level environmental correlates extracted using publicly available datasets, classified into physical and social environments. Association estimates of each dependent variable and each of the independent variables were calculated using univariate linear regression. All variables were standardized to have a mean of 0 and a standard deviation of 1. Results showed that 1 standard deviation (SD) difference in urban population percentage, night-time light, secondary-school enrolment, and prevalence of adult insufficient physical activity were negatively associated with AST prevalence (SD difference: -0.44 (-0.78 to -0.09), -0.40 (-0.76 to -0.04), -0.39 (-0.74 to -0.04), and -0.40 (-0.76 to -0.03), respectively). A 1 SD difference in car per people was associated with a -0.46 (-0.84 to -0.09) difference of AST prevalence by age. A 1 SD difference in PM2.5 concentration and of prevalence of adult insufficient physical activity were associated with a difference of 0.38 (0.01-0.74) and 0.42 (0.03-0.80) difference of AST prevalence by sex. This study shows that Asian countries with a greater number of people living in urban areas, lower levels of overall adult physical activity and higher levels of night-time light have a lower prevalence of adolescent AST. Country-level physical and social environmental correlates explained some of the regional variance in AST. Future policy actions and interventions for the region need to be contextually sensitive to the environmental correlates that vary between countries.


Acromegaly with empty sella syndrome.
Acromegaly is a rare, chronic progressive disorder with characteristic clinical features caused by persistent hypersecretion of growth hormone (GH), mostly from a pituitary adenoma (95%). Occasionally, ectopic production of GH or growth hormone-releasing hormone (GHRH) with resultant GH hypersecretion may lead to acromegaly. Sometimes localizing the source of GH hypersecretion may prove difficult. Rarely, acromegaly has been found in patients with an empty sella (ES) secondary to prior pituitary radiation and/or surgery. However, acromegaly in patients with primary empty sella (PES) is exceeding rarely and has only been described in a few cases. We describe a 47-year-old male who presented with overt features of acromegaly (macroglossia, prognathism, increased hand and feet size). Biochemically, both the serum GH (21.6 μg/L) and insulin-like growth factor 1 (635 μg/L) were elevated. In addition, there was a paradoxical elevation of GH following a 75 g oral glucose load. Pituitary MRI demonstrated an ES. In order to exclude an ectopic source of GH hypersecretion, further biochemical tests and imaging were done, which were unremarkable. Notably, increased uptake in the sella turcica on the 68Gallium DOTATATE PET/CT confirmed the ES as the likely source of GH secretion. As no overt lesion was noted, medical treatment (octreotide acetate) was initiated with a good clinical and biochemical response. At his 3 month follow-up, he reported an improvement in symptoms (fatigue and headache), however he still complained of low libido. Due to a persistently low testosterone level at follow-up, a long-acting testosterone was initiated. His GH level normalised, and IGF-1 has significantly reduced. The commonest cause of acromegaly is due to GH hypersecretion from pituitary adenomas (95%). Acromegaly has rarely been found in patients with ES. It is important to exclude a past history suggestive of pituitary apoplexy. Extra-pituitary source of GH such as ectopic production of GHRH with resultant GH hypersecretion needs to be excluded. In such cases, since there is no resectable mass, medical therapy is the primary treatment option.


The Physiochemical Properties and Adsorption Characteristics of Processed Pomelo Peel as a Carrier for Epigallocatechin-3-Gallate.
The NaOH-HCl- and ethanol-pretreated pomelo peel samples were prepared to apply to the batch adsorption for epigallocatechin-3-gallate (EGCG). The characteristics of peel samples were determined by Fourier transform infrared spectroscopy, scanning electron microscopy and a laser particle analyzer. The results of the physiochemical properties of the peel samples demonstrate that these peel samples have a promising adsorption capacity for EGCG, because of the increased potential binding sites on the surface compared with those of untreated peel samples. These two peel samples showed enhanced adsorption capacities of EGCG compared with that of unmodified peel in terms of the isothermal adsorption process, which could be described by both Langmuir and Freundlich models, with the theoretical maximum adsorption capacity of 77.52 and 94.34 mg g-1 for the NaOH-HCl and ethanol-treated peel samples, respectively. The adsorption kinetics demonstrated an excellent fitness to pseudo-second-order, showing that chemisorption was the rate-limiting step. The thermodynamics analysis revealed that the adsorption reaction was a spontaneous and endothermic process. This work highlights that the processed pomelo peels have outstanding adsorption capacities for EGCG, which could be promising candidates for EGCG delivering in functional food application.


Dabrafenib as a diagnostic and therapeutic strategy for the non-surgical management of papillary craniopharyngioma.
Papillary craniopharyngiomas can cause considerable morbidity due to mass effect and potential surgical complications. These tumors are known to harbor BRAF V600 mutations, which make them exquisitely sensitive to BRAF inhibitors. The patient is a 59 year old man with a progressive suprasellar lesion that was radiographically consistent with a papillary craniopharyngioma. He was consented to an Institution Review Board-approved protocol, which permits sequencing of cell free DNA in plasma and the collection and reporting of clinical data. The patient declined surgical resection and was empirically treated with dabrafenib at 150 mg twice daily. Treatment response was demonstrated after 19 days, confirming the diagnosis. After achieving a near complete response after 6.5 months on drug, a decision was made to deescalate treatment to dabrafenib 75 mg twice daily with subsequent tumor stability for 2.5 months. Patients with a suspected papillary craniopharyngioma can be challenged with dabrafenib as a potentially effective diagnostic and therapeutic strategy, given that rapid regression with dabrafenib is only observed in tumors harboring a BRAF V600 mutation. Further work is needed to explore the optimal regimen and dose of the targeted therapy.


Acyltransferase families that act on thioesters: Sequences, structures, and mechanisms.
Acyltransferases (AT) are enzymes that catalyze the transfer of acyl group to a receptor molecule. This review focuses on ATs that act on thioester-containing substrates. Although many ATs can recognize a wide variety of substrates, sequence similarity analysis allowed us to classify the ATs into fifteen distinct families. Each AT family is originated from enzymes experimentally characterized to have AT activity, classified according to sequence similarity, and confirmed with tertiary structure similarity for families that have crystallized structures available. All the sequences and structures of the AT families described here are present in the thioester-active enzyme (ThYme) database. The AT sequences and structures classified into families and available in the ThYme database could contribute to enlightening the understanding acyl transfer to thioester-containing substrates, most commonly coenzyme A, which occur in multiple metabolic pathways, mostly with fatty acids.


Possibilities and limitations of current technologies for quantification of biological extracellular vesicles and synthetic mimics.
Nano-sized extracelullar vesicles (EVs) released by various cell types play important roles in a plethora of (patho)physiological processes and are increasingly recognized as biomarkers for disease. In addition, engineered EV and EV-inspired liposomes hold great potential as drug delivery systems. Major technologies developed for high-throughput analysis of individual EV include nanoparticle tracking analysis (NTA), tunable resistive pulse sensing (tRPS) and high-resolution flow cytometry (hFC). Currently, there is a need for comparative studies on the available technologies to improve standardization of vesicle analysis in diagnostic or therapeutic settings. We investigated the possibilities, limitations and comparability of NTA, tRPS and hFC for analysis of tumor cell-derived EVs and synthetic mimics (i.e. differently sized liposomes). NTA and tRPS instrument settings were identified that significantly affected the quantification of these particles. Furthermore, we detailed the differences in absolute quantification of EVs and liposomes using the three technologies. This study increases our understanding of possibilities and pitfalls of NTA, tRPS and hFC, which will benefit standardized and large-scale clinical application of (engineered) EVs and EV-mimics in the future.


Extremely long-lived stigmas allow extended cross-pollination opportunities in a high Andean plant.
High-elevation ecosystems are traditionally viewed as environments in which predominantly autogamous breeding systems should be selected because of the limited pollinator availability. Chaetanthera renifolia (Asteraceae) is an endemic monocarpic triennial herb restricted to a narrow altitudinal range within the high Andes of central Chile (3300-3500 m a.s.l.), just below the vegetation limit. This species displays one of the larger capitulum within the genus. Under the reproductive assurance hypothesis, and considering its short longevity (monocarpic triennial), an autogamous breeding system and low levels of pollen limitation would be predicted for C. renifolia. In contrast, considering its large floral size, a xenogamous breeding system, and significant levels of pollen limitation could be expected. In addition, the increased pollination probability hypothesis predicts prolonged stigma longevity for high alpine plants. We tested these alternative predictions by performing experimental crossings in the field to establish the breeding system and to measure the magnitude of pollen limitation in two populations of C. renifolia. In addition, we measured the stigma longevity in unpollinated and open pollinated capitula, and pollinator visitation rates in the field. We found low levels of self-compatibility and significant levels of pollen limitation in C. renifolia. Pollinator visitation rates were moderate (0.047-0.079 visits per capitulum per 30 min). Although pollinator visitation rate significantly differed between populations, they were not translated into differences in achene output. Finally, C. renifolia stigma longevity of unpollinated plants was extremely long and significantly higher than that of open pollinated plants (26.3±2.8 days vs. 10.1±2.2, respectively), which gives support to the increased pollination probability hypothesis for high-elevation flowering plants. Our results add to a growing number of studies that show that xenogamous breeding systems and mechanisms to increase pollination opportunities can be selected in high-elevation ecosystems.


Reservoir Computing Properties of Neural Dynamics in Prefrontal Cortex.
Primates display a remarkable ability to adapt to novel situations. Determining what is most pertinent in these situations is not always possible based only on the current sensory inputs, and often also depends on recent inputs and behavioral outputs that contribute to internal states. Thus, one can ask how cortical dynamics generate representations of these complex situations. It has been observed that mixed selectivity in cortical neurons contributes to represent diverse situations defined by a combination of the current stimuli, and that mixed selectivity is readily obtained in randomly connected recurrent networks. In this context, these reservoir networks reproduce the highly recurrent nature of local cortical connectivity. Recombining present and past inputs, random recurrent networks from the reservoir computing framework generate mixed selectivity which provides pre-coded representations of an essentially universal set of contexts. These representations can then be selectively amplified through learning to solve the task at hand. We thus explored their representational power and dynamical properties after training a reservoir to perform a complex cognitive task initially developed for monkeys. The reservoir model inherently displayed a dynamic form of mixed selectivity, key to the representation of the behavioral context over time. The pre-coded representation of context was amplified by training a feedback neuron to explicitly represent this context, thereby reproducing the effect of learning and allowing the model to perform more robustly. This second version of the model demonstrates how a hybrid dynamical regime combining spatio-temporal processing of reservoirs, and input driven attracting dynamics generated by the feedback neuron, can be used to solve a complex cognitive task. We compared reservoir activity to neural activity of dorsal anterior cingulate cortex of monkeys which revealed similar network dynamics. We argue that reservoir computing is a pertinent framework to model local cortical dynamics and their contribution to higher cognitive function.


Protective Effects of Quercetin on Rat Pial Microvascular Changes during Transient Bilateral Common Carotid Artery Occlusion and Reperfusion.
The aim of this study was to assess the in vivo effects of quercetin on pial microvascular responses during transient bilateral common carotid artery occlusion (BCCAO) and reperfusion. Rat pial microcirculation was visualized by fluorescence microscopy through a closed cranial window. Pial arterioles were classified in five orders of branchings. Capillaries were assigned order 0, the smallest arterioles order 1, and the largest ones order 5. In ischemic rats, 30 min BCCAO and 60 min reperfusion caused arteriolar diameter decrease (by 14.5 ± 3.3% of baseline in order 2), microvascular leakage [0.47 ± 0.04, normalized gray levels (NGL)], leukocyte adhesion in venules (9 ± 2/100 μm venular length, v.l./30 s), and reduction of capillary perfusion (by 40 ± 7% of baseline). Moreover, at the end of BCCAO and reperfusion there was a significant increase in reactive oxygen species (ROS) formation when compared with baseline. Quercetin highest dose determined dilation in all arteriolar orders (by 40 ± 4% of baseline in order 2) and prevented microvascular permeability (0.15 ± 0.02 NGL), leukocyte adhesion (3 ± 1/100 μm v.l./30 s) as well as ROS formation, while capillary perfusion was protected. Inhibition of endothelial nitric oxide synthase (NOS) prior to quercetin reduced arteriolar dilation (order 2 diameter increase by 10.3 ± 2.5% of baseline) and caused permeability increase (0.29 ± 0.03 NGL); inhibition of neuronal NOS or inducible NOS did not affect quercetin-induced effects. Inhibition of guanylyl cyclase prior to quercetin reversed the quercetin's effects on pial arteriolar diameter and leakage. In conclusion, quercetin was able to protect pial microcirculation from ischemia-reperfusion damage inducing arteriolar dilation likely by nitric oxide release. Moreover, quercetin scavenger activity blunted ROS formation preserving the blood-brain barrier integrity.


Prevalence of Clinically Significant anti-HLA Antibodies in Renal Transplant Patients: Single-center Report from North India.
Solid organ transplantation is the preferred therapeutic modality of treatment in patients affected by terminal organ failures. Human leukocyte antigens (HLAs) plays an important role in graft survival. In many of the cases of rejection, antibodies are directed against HLA antigens expressed on the cells of the transplanted organ. Pre-transplant compatibility testing involves the use of different methodologies for the determination of anti-HLA antibodies. Luminex single-antigen bead (SAB) assay demonstrates higher sensitivity and specificity in detecting anti-HLA antibodies. The aim of this study was to determine the prevalence of anti-HLA antibodies in pre-transplant work up recipients, planned for renal transplant at a tertiary care center in India. 1640 patients visiting tertiary care hospital for pre-transplant compatibility testing were screened with complement-dependent micro-lymphocytotoxicity crossmatch (CDC-XM) and flow cytometric crossmatch (FC-XM). The patients positive for either or both screening tests were assayed with the Luminex SAB tests in order to establish defined antigen specificity of the alloantibodies and determining donor-specific antibody (DSA). The two most frequent antibodies identified in each A, B, C locus of HLA class I were -A*24:03 (43.9%), A*25:01 (36.6%), B*57:01 (40.3%), B*15:12 (37.1%), C*17:01 (61.9%), C*07:01 (52.4%) and in DR, DQ DP locus in HLA class II were DRB1*09:01(40.0%), DRB1*14:04(37.6%), DQA1*04:01/DQB1*03:03 (58.4%), DQA1*05:01/DQB1*03:01 (55.1%), DPA1*02:01/DPB1*17:01 (55.0%), DPA1*02:01/DPB1*05:01 (45.0%). This study has found the prevalence and specificity of anti-HLA antibodies in north India.


Extracellular matrix remodelling in myocardial hypertrophy and failure : focus on osteopontin.
Cardiac remodelling refers to molecular and cellular changes of the myocardium, as well as adapting alterations in size, shape and function of the heart in response to changing loading conditions. It represents the final common pathway of different heart diseases, and is recognized as a crucial aspect of cardiac and myocardial dysfunction and a well established determinant of the clinical course of heart failure.Osteopontin is an extracellular matrix glycoprotein secreted by osteoblasts, osteoclasts, macrophages, T cells, vascular smooth muscle cells, fibroblasts and cardiomyocytes. Osteopontin is not expressed in healthy cardiac tissue, although its expression can be triggered by pressure or volume overload, hypoxia and angiotensin II. Indeed, osteopontin has been reported in macrophages and interstitial tissues early after myocardial infarction and in cardiac macrophage-like cells of inflammatory lesions in experimental models of cardiomyopathy. Pressure overload is associated with osteopontin overexpression as well. Indeed, myocardial osteopontin messenger RNA is upregulated in rats following renovascular hypertension or aortic banding. In humans, a significant correlation exists between increased osteopontin immunoreactivity in cardiac myocytes and impaired left ventricular function or cardiomyocyte hypertrophy in patients with dilated cardiomyopathy.The present article focuses on the role of osteopontin in myocardial hypertrophy and remodelling. In general, evidence supports the concept that osteopontin plays a crucial role in extracellular matrix remodelling following myocardial adaptation to hypertrophic, inflammatory and neurohormonal stimuli in the overloaded heart.


Abstinence, occasional drinking and binge drinking in middle-aged women. The Women's Health in Lund Area (WHILA) Study.
Although drinking patterns in women have received increased attention, few studies have focused on middle-aged women. Drinking patterns were investigated in a population sample of 513 Swedish women aged 50-59, and analysed in relation to social situation, and mental and physical health. The chi-square test was used to analyse differences in proportions. Variables showing significant differences were entered into a multivariate or multinomial logistic regression model. Abstainers and occasional drinkers had lower levels of education and more often regular medical control compared with weekly drinkers. Furthermore, abstainers more often had disability pension. Among women drinking alcohol, 56.6% affirmed binge drinking within the last year and 39.4% within the last month. Binge drinkers did not differ in terms of social situation, mental or physical health, compared with other drinkers. Drinking to relieve tension was affirmed by 7.2%. These women had more mental symptoms and less contact with friends compared with other drinkers; furthermore, they were more often binge drinkers. Binge drinking was common and health and social consequences of this drinking pattern in middle-aged women need to be further explored. Women drinking to relieve tension may need intervention for both drinking habits and mental health.


The equity lens in the health care performance evaluation system.
The main objective of this paper is to describe how indicators of the equity of access to health care according to socioeconomic conditions may be included in a performance evaluation system (PES) in the regional context level and in the planning and strategic control system of healthcare organisations. In particular, the paper investigates how the PES adopted, in the experience of the Tuscany region in Italy, indicators of vertical equity over time. Studies that testify inequality of access to health services often remain just a research output and are not used as targets and measurements in planning and control systems. After a brief introduction to the concept of horizontal and vertical equity in health care systems and equity measures in PES, the paper describes the 'equity process' by which selected health indicators declined by socioeconomic conditions were shared and used in the evaluation of health care institutions and in the CEOs' rewarding system, and subsequently analyses the initial results. Results on the maternal and child path and the chronicity care path not only show improvements in addressing health care inequalities, but also verify whether the health system responds appropriately to different population groups.


Effect of irradiation in the space environment on the blood-forming system in rats.
A special experiment was carried out on board Cosmos 690 [correction of 605] in order to study the modifying influence of weightlessness on the radiobiological effect. On the tenth flight day 35 rats were exposed to irradiation using an on-board gamma-ray source. They were irradiated for 24 hours at a dose rate of 32 rads/hr with a total dose of 220 +/- 25 rads and 800 +/- 53 rads. On the 1st and 26th post-flight days haemopoiesis in bone marrow (determined from myelograms and the total count of myelo-karyocytes) was examined and the blood composition was analysed. The total count of thymocytes and spleenocytes was measured in the thymus and spleen. Identical measurements were made in the control animals exposed to irradiation on the earth. The haematological findings indicate an enhancement of the radiobiological effect in the rats irradiated in space flight.


Alpha 2-adrenoceptors and endothelium-derived relaxing factor.
The endothelium can release potent vasodilator substances, in particular prostacyclin and endothelium-derived relaxing factor. The triggers for the release of endothelium-derived relaxing factor include increases in levels of shear stress, neurotransmitters, autacoids, platelet products, and hormones. The endothelium-dependent response to catecholamines involves stimulation of alpha 2-adrenoceptors on the endothelial cells. Indeed, in a number of blood vessels, selective alpha 2-adrenergic agonists cause endothelium-dependent relaxations. These are seen most typically in blood vessels with long-term exposure to high flows and high partial pressures of oxygen. In addition to the release of endothelium-derived relaxing factor, alpha 2-adrenergic agonists can stimulate postjunctional (postsynaptic) alpha 2-adrenoceptors on vascular smooth muscles. These receptors, which are more abundant in hypertensive blood vessels, activate the contractile process. However, the alpha 2-adrenergic vasoconstrictors act as partial agonists (with a limited receptor reserve) and hence their vasoconstrictor response is very sensitive to functional antagonists such as endothelium-derived relaxing factor. Thus, the presence of endothelial cells can blunt the vasoconstrictor response to these substances not only because of an augmented release of endothelium-derived relaxing factor but also because the vasoconstriction that they induce is particularly susceptible to the inhibitory effect of the factor.


Occupational risk factors for Parkinson's disease: a case-control study in Japan.
The evidence for associations between occupational factors and the risk of Parkinson's disease (PD) is inconsistent. We assessed the risk of PD associated with various occupational factors in Japan. We examined 249 cases within 6 years of onset of PD. Control subjects were 369 inpatients and outpatients without neurodegenerative disease. Information on occupational factors was obtained from a self-administered questionnaire. Relative risks of PD were estimated using odds ratios (ORs) and 95% confidence intervals (CIs) based on logistic regression. Adjustments were made for gender, age, region of residence, educational level, and pack-years of smoking. Working in a professional or technical occupation tended to be inversely related to the risk of PD: adjusted OR was 0.59 (95% CI: 0.32-1.06, P = 0.08). According to a stratified analysis by gender, the decreased risk of PD for persons in professional or technical occupations was statistically significant only for men. Adjusted ORs for a professional or technical occupation among men and women were 0.22 (95% CI: 0.06-0.67) and 0.99 (0.47-2.07), respectively, and significant interaction was observed (P = 0.048 for homogeneity of OR). In contrast, risk estimates for protective service occupations and transport or communications were increased, although the results were not statistically significant: adjusted ORs were 2.73 (95% CI: 0.56-14.86) and 1.74 (95% CI: 0.65-4.74), respectively. No statistical significance was seen in data concerning exposure to occupational agents and the risk of PD, although roughly a 2-fold increase in OR was observed for workers exposed to stone or sand. The results of our study suggest that occupational factors do not play a substantial etiologic role in this population. However, among men, professional or technical occupations may decrease the risk of PD.


A human homologue of the Drosophila developmental gene, Notch, is expressed in CD34+ hematopoietic precursors.
Members of the Notch gene family have been shown to mediate cell-fate decisions by multipotent precursors in a number of different systems. To determine whether members of this family might play a similar role in hematopoiesis, we asked if homologues of the Notch gene are expressed in human hematopoietic precursors. Using degenerate oligonucleotides corresponding to conserved amino acid sequences in known Notch homologues as primers for the polymerase chain reaction (PCR), we demonstrated that at least one Notch homologue is expressed in human bone marrow CD34+ cells, a population enriched for hematopoietic precursors. Cloning and sequencing of the PCR products identified this Notch homologue as TAN-1, a member of the Notch family previously cloned from a T-cell leukemia with a translocation involving this gene. Subsequent evaluation of bone marrow hematopoietic cells for TAN-1 expression using a reverse transcription-PCR assay confirmed the expression of TAN-1 in CD34+ hematopoietic precursors, including the immature subset that lacks expression of lineage-associated antigens (CD34+lin-). These findings, together with the known role of Notch homologues in other systems, suggest that members of the Notch family, including TAN-1, may be involved in mediating cell-fate decisions during hematopoiesis.


Growth hormone (GH) provocative retesting of 108 young adults with childhood-onset GH deficiency and the diagnostic value of insulin-like growth factor I (IGF-I) and IGF-binding protein-3.
Serum levels of total insulin-like growth factor I (IGF-I) and IGF-binding protein-3 (IGFBP-3) reflect the endogenous GH secretion in healthy children and exhibit little diurnal variation, which makes them good diagnostic markers for screening of GH deficiency (GHD) in short children, although some controversy still exists. In adults, the diagnostic value of IGF-I and IGFBP-3 suspected of GHD has been reported in only a few studies. We performed a GH provocative test, using oral clonidine, in 108 patients who had previously been treated with GH during childhood (73 men and 35 women). Basal IGF-I and IGFBP-3 levels were compared to those in 1237 healthy controls (312 controls > 18 yr) as well as to peak GH levels. Seventy-nine patients had peak GH values below a cut-off value of 7.5 micrograms/L (34 with isolated GHD), whereas 29 patients had a normal GH response (28 with previous isolated GHD), i.e. 45% of patients treated with GH during childhood because of isolated GHD had a normal GH response when retested in adulthood. Multiple regression analysis revealed that peak GH levels were dependent on the degree of hypopituitarism, body mass index, and duration of disease. IGF-I levels were below -2 SD in 60 of 79 GHD patients and above -2 SD in 21 of 29 patients with a normal GH response. IGFBP-3 levels were below -2 SD in 54 of 79 GHD patients and above -2 SD in 23 of 29 patients with a normal GH response. Multiple linear regression analysis demonstrated that IGF-I and IGFBP-3 were significantly dependent on peak GH levels and the number of other pituitary axes affected. In this analysis, duration of disease was significantly associated with both IGF-I and IGFBP-3, whereas body mass index was significantly associated with IGFBP-3, but not with IGF-I. We conclude that IGF-I and IGFBP-3 determinations predict the outcome of a GH provocative test in adults suspected of GHD and believe that IGF-I as well as IGFBP-3 serum concentrations are valuable diagnostic parameters in the evaluation of GHD in adults with childhood-onset disease. We suggest that children who have been treated with GH should undergo reassessment of their GH secretory status as young adults by provocative testing as well as by IGF-related peptides before continued adult GH replacement therapy is considered. However, our data suggest that it is not necessary to reconfirm GH deficiency by GH provocative testing in young adults who have two or more pituitary hormone deficiencies in addition to GHD.


Molecular epidemiology of endemic and very virulent infectious bursal disease virus genogroups in backyard chickens in California, 2009-2017.
Pathogenic strains of infectious bursal disease virus (IBDV) are associated with increased morbidity, mortality, and immunosuppression in susceptible chickens. Backyard poultry is increasing in popularity in the United States, but very little is known about the prevalence and molecular epidemiology of IBDV within these flocks. We performed a retrospective study and phylogenetic analyses of IBDV detected in backyard chickens (BYCs) submitted to the California Animal Health and Food Safety (CAHFS) diagnostic laboratory system in 2009-2017. There were 17 CAHFS autopsy cases of very virulent IBDV (vvIBDV) segment A detected by RT-rtPCR in BYC flocks from 7 counties in California from 2009-2017. During this same time period, non-vvIBDV genotypes were detected by RT-rtPCR in 16 autopsy cases originating from BYC premises in 10 counties in California. Subsequent RT-PCR and phylogenetic analysis of a segment of the hvVP2 and VP1 gene identified vvIBDV, interserotypic reassortant IBDV (vvIBDV segment A and serotype 2 segment B), and non-vvIBDV (variant/subclinical IBDV and classic IBDV) strains in BYC flocks in California.


Gastric cancer. Clinico-biological updating and analysis of 400 operated cases.
Gastric cancer is a rather common disease worldwide. In Italy it still accounts for 15,000 deaths annually. A sharp drop in the incidence rate of Lauren's intestinal histotype has been reported, whereas the frequency of the diffuse histotype is relatively steady. If the histogenesis of the latter is still somewhat obscure, the intestinal type confirms the sequence: atrophic gastritis--intestinal metaplasia--dysplasia--neoplasia. These different stages of development can nowadays be singled out through a series of indicators, the most reliable of which are the pepsinogen I/pepsinogen II ratio, the presence of sulphomucins and Lewis antigens in the gastric juices and NOR (Nucleolar Organizer Regions), cell ploidy and oncogenes determination. The genes involved in the neoplastic transformation are mostly oncosuppressors, the most frequent alterations being those relative to the APC gene, p53 and c-myc. In addition to the by now indispensable pathological staging of the disease, the modern prognostic factors are arising great interest: the most significant are the immunohistochemical examination of the peritoneal washing, and cell ploidy. Surgery is still the only potentially curative treatment: the earlier surgery is performed in the course of disease, the greatest the curative potential. The Authors' experience, which includes 400 operated cases with complete follow-up records, is here reported. The resectability rate turned out to be 84%, overall operative mortality was 6.5% with that due to surgical causes along being 3.7%. Overall survival at 5 years was 36%, while that of the curative operations 47%. Good results were obtained with the association surgery + intraoperative radiotherapy which resulted in a significant decrease in local recurrences of the disease.


Is body mass index associated with lowest mortality increasing over time?
It is debatable whether the body mass index (BMI) value that is associated with the lowest all-cause mortality has increased over time. Such an increase might indicate that the WHO BMI categories for normal weight and overweight need to be revised over time. This study assessed whether the BMI associated with the lowest all-cause mortality increased over time among US adults in the National Health Interview Survey. This survey with up to 25 years of follow-up included 901 197 participants, aged 20 to 79 years with baseline BMI between 18.5 and 39.9 kg m-2 and known mortality status between the original survey dates and 31 December 2011. The BMI values associated with the lowest mortality were estimated for different survey time periods: 1986-1989, 1990-1994, 1995-1999, 2000-2004 and 2000-2009. Among 901 197 participants, 130 495 died during over 14.5 million person-years of follow-up. There was a U-shaped BMI-mortality association in all the survey periods. When we used the original follow-up durations, the BMI associated with the lowest mortality increased monotonically from 23.9 kg m-2 in 1986-1989 to 28.6 kg m-2 in 2005-2009. When using a fixed follow-up duration of 5, 10, 15 or 20 years, we found no monotonic increasing pattern in the BMI associated with the lowest mortality. With duration of 15 years, the estimates of BMI associated with lowest mortality appeared to be relatively stable over time among both the general population and never smokers free from cardiovascular disease and cancer at baseline. With a fixed long-term follow-up duration, the BMI value associated with the lowest mortality remains relatively stable over time.


Dibutyryl cyclic AMP mimics ovariectomy: nuclear protein phosphorylation in mammary tumor regression.
Growth of mammary carcinoma induced by 7,12-dimethyl-benz(a) anthracene is arrested by either ovariectomy or treatment with N6,O2-dibutyryl cyclic adenosine 3',5'-monophosphate (dibutyryl cyclic AMP). When this occurs, a new nonhistone protein species becomes the predominant endogenous substrate of cyclic AMP-dependent protein kinase in the tumor nuclei. Phosphorylation of this regression-associated protein ceases when resumption of tumor growth is induced by either the injection of 17 beta-estradiol or cessation of dibutyryl cyclic AMP treatment. Thus phosphorylation of regression-associated protein may play a role in the regression of hormone-dependent mammary tumors.


Formulation and In Vitro and In Vivo Evaluation of Lipid-Based Terbutaline Sulphate Bi-layer Tablets for Once-Daily Administration.
The objective of this study was to prepare and evaluate terbutaline sulphate (TBS) bi-layer tablets for once-daily administration. The bi-layer tablets consisted of an immediate-release layer and a sustained-release layer containing 5 and 10 mg TBS, respectively. The sustained-release layer was developed by using Compritol®888 ATO, Precirol® ATO 5, stearic acid, and tristearin, separately, as slowly eroding lipid matrices. A full 4 × 2(2) factorial design was employed for optimization of the sustained-release layer and to explore the effect of lipid type (X 1), drug-lipid ratio (X 2), and filler type (X 3) on the percentage drug released at 8, 12, and 24 h (Y 1, Y 2, and Y 3) as dependent variables. Sixteen TBS sustained-release matrices (F1-F16) were prepared by melt solid dispersion method. None of the prepared matrices achieved the targeted release profile. However, F2 that showed a relatively promising drug release was subjected to trial and error optimization for the filler composition to develop two optimized matrices (F17 and F18). F18 which consisted of drug-Compritol®888 ATO at ratio (1:6 w/w) and Avicel PH 101/dibasic calcium phosphate mixture of 2:1 (w/w) was selected as sustained-release layer. TBS bi-layer tablets were evaluated for their physical properties, in vitro drug release, effect of storage on drug content, and in vivo performance in rabbits. The bi-layer tablets showed acceptable physical properties and release characteristics. In vivo absorption in rabbits revealed initial high TBS plasma levels followed by sustained levels over 24 h compared to immediate-release tablets.