Orthostatic hypotension and paroxysmal hypertension in humans with high spinal cord injury.
The spinal cord is essential for normal autonomic nervous system regulation of the cardiovascular system as the preganglionic neurons controlling the heart and blood vessels originate in the thoracolumbar spinal segments. The site and extent of a spinal cord injury determine the degree of autonomic involvement in cardiovascular dysfunction after the injury. After complete cervical cord lesions the entire sympathetic outflow is separated from cerebral control; this may cause orthostatic hypotension. Commonly after traumatic injuries to the spinal cord, one or more segments are totally destroyed. However, the distal portion of the spinal cord often retains function and activation of spinal cord reflexes working independently of the brain can result in paroxysmal hypertension. This chapter will focus on orthostatic hypotension and paroxysmal hypertension in cord-injured people with lesions affecting the cervical and upper thoracic spinal cord. Conditions promoting these abnormalities in blood pressure will be elaborated. Possible mechanisms for the hypo- and hypertension will be discussed, as will strategies for managing these problems.


Ethanol enhances recurrent inhibition in the dentate gyrus of the hippocampus.
Intraperitoneal injection of ethanol (2 g/kg) substantially augmented recurrent inhibition in the dentate gyrus, as measured by population responses to paired-pulse stimulation of the perforant path. In contrast, this dose of ethanol had no significant effect on singly evoked (or conditioning) population spikes. These data indicate that the increased recurrent inhibition by ethanol was not due to a generalized depressant effect, and suggests that at these doses and time points ethanol can selectively alter synaptic transmission in the hippocampus.


Clinical response and tissue effects of etretinate treatment of patients with solar keratoses and basal cell carcinoma.
Patients with basal cell carcinoma and solar keratoses were treated with etretinate. Substantial and prolonged clinical improvement was seen. All patients with solar keratoses showed a decrease in the mean area and number of lesions and eight patients demonstrated complete healing clinically. Two patients experienced recurrence at 9 months after completion of treatment. Histometric and cell kinetic measurements on the epidermis of skin samples from these patients were performed. They revealed epidermal thickening and increased deoxyribonucleic acid (DNA) synthesis both in lesions and in clinically uninvolved skin following treatment. Assessments were also made of enzyme activities in lesions and uninvolved skin with the use of established quantitative cytochemical techniques. Significant reduction in levels of succinic dehydrogenase activity following etretinate treatment was detected in solar keratoses and in basal cell carcinomas. This was also the case for uninvolved skin of patients with solar keratoses. Glucose-6-phosphate dehydrogenase (G6PD) activity was significantly reduced following etretinate treatment in solar keratoses and in basal cell carcinomas, but uninvolved skin did not exhibit significant changes. These changes are in contrast to those previously reported in normal subjects, where the activity increased, but are similar to those observed in patients with ichthyotic disorders. The alterations in the cytochemical profile following administration of etretinate in the lesions of patients reported here are consistent with the view that the drug promotes a more normal pattern of epidermal differentiation. We favor the view that etretinate's antineoplastic action is exerted by preferentially allowing differentiation of normal epidermal cells and inhibiting dysplastic cells.


Persistence with hepatitis C therapy in the Department of Veterans Affairs.
Persistence with Hepatitis C therapy has been identified as a key variable for predicting treatment success. The primary purpose of this study was to assess the persistence with therapy for patients undergoing hepatitis C treatment in the VA healthcare system with two forms of combination therapies: peginterferon alfa-2a with Ribavirin (peg-IFN alpha-2a/Rib) and peginterferon alpha-2b with Ribavirin (peg-IFN alpha-2b/Rib). A retrospective cohort study design was used to analyse persistence in VA patients undergoing hepatitis C therapy during FY 2003-2004 using a large national VA data set. Stringent inclusion and exclusion criteria along with various defining variables were used to identify the inception cohort. Persistence rates were calculated for each of the two treatment groups at 3, 6, 9 and 11 months using the Kaplan-Meier method. Likelihood ratio test of equality between the two treatment groups was performed to detect any differences in persistence rates. A total of 5816 hepatitis C patients formed the inception cohort. Persistence rates for the overall duration showed significantly higher rates for patients on peg-IFN alpha-2a/Rib than peg-IFN alpha-2b/Rib. Cox regression analysis also showed favourable hazard ratio of persistence (0.88) for peg-IFN alpha-2a/Rib over peg-IFN alpha-2b/Rib. Peg alfa-2A/Rib showed slightly higher persistence rates for the overall duration of treatment as compared to Peg alfa-2B/Rib. However the differences, even though statistically significant, are small and not likely to translate into any substantial clinical advantage. Further research involving other approaches is required to confirm these findings.


Tinea mammae mimicking atopic eczema.
Tinea mammae is a dermatophyte infection of the breast. Although rarely reported in this anatomical location, it can mimic other dermatoses. In this paper we describe an 85-year-old man with an erythema at the left breast which had enlarged over the previous 3 weeks. Trichophyton rubrum was isolated. Digital 20-MHz sonography revealed a reduction in echogenicity of the corium and a widened corium. Treatment with fluconazole over 5 weeks led to clearing of the lesion at the glabrous skin. At the end of therapy no difference between the involved and uninvolved skin areas was found sonographically.


Van der Waals two-color infrared photodetector.
With the increasing demand for multispectral information acquisition, infrared multispectral imaging technology that is inexpensive and can be miniaturized and integrated into other devices has received extensive attention. However, the widespread usage of such photodetectors is still limited by the high cost of epitaxial semiconductors and complex cryogenic cooling systems. Here, we demonstrate a noncooled two-color infrared photodetector that can provide temporal-spatial coexisting spectral blackbody detection at both near-infrared and mid-infrared wavelengths. This photodetector consists of vertically stacked back-to-back diode structures. The two-color signals can be effectively separated to achieve ultralow crosstalk of ~0.05% by controlling the built-in electric field depending on the intermediate layer, which acts as an electron-collecting layer and hole-blocking barrier. The impressive performance of the two-color photodetector is verified by the specific detectivity (D*) of 6.4 × 109 cm Hz1/2 W-1 at 3.5 μm and room temperature, as well as the promising NIR/MWIR two-color infrared imaging and absolute temperature detection.


An overview of ghrelin O-acyltransferase inhibitors: a literature and patent review for 2010-2019.
The peptide hormone ghrelin regulates physiological processes associated with energy homeostasis such as appetite, insulin signaling, glucose metabolism, and adiposity. Ghrelin has also been implicated in a growing number of neurological pathways involved in stress response and addiction behavior. For ghrelin to bind the growth hormone secretagogue receptor 1a (GHS-R1a) and activate signaling, the hormone must first be octanoylated on a specific serine side chain. This key transformation is performed by the enzyme ghrelin O-acyltransferase (GOAT), and therefore GOAT inhibitors may be useful in treating disorders related to ghrelin signaling such as diabetes, obesity, and related metabolic syndromes. This report covers ghrelin and GOAT as potential therapeutic targets and summarizes work on GOAT inhibitors through the end of 2019, highlighting recent successes with both peptidomimetics and small molecule GOAT inhibitors as potent modulators of GOAT-catalyzed ghrelin octanoylation. A growing body of biochemical and structural knowledge regarding the ghrelin/GOAT system now enables multiple avenues for identifying and optimizing GOAT inhibitors. We are at the beginning of a new era with increased opportunities for leveraging ghrelin and GOAT in the understanding and treatment of multiple health conditions including diabetes, obesity, and addiction.


Are Candida albicans isolates from the oral cavity of HIV-infected patients more virulent than from non-HIV-infected patients? Systematic review and meta-analysis.
Candida albicans is the main causative agent of oral lesions in HIV-infected patients and its oral colonization is a potential source of systemic dissemination. Although the high prevalence of lesions in HIV patients can be explained by the immunosuppressive condition, several studies have reported that natural selection can make C. albicans more virulent in this group of patients. Comparisons of the activity of exoenzymes (phospholipase, proteinase and hemolysin) in C. albicans isolated from HIV-infected and uninfected patients have yielded conflicting results. This study aimed, through a systematic review and meta-analysis, to answer the question: "Is the hydrolytic enzymatic activity of C. albicans, isolated from the oral cavity, different in individuals infected and not infected with HIV?" The question was addressed using the PECO framework: P (Population): children and adults, E (Exposure): HIV infection, C (Comparator): non-HIV-infected patients; O (Outcomes): exoenzymes activity i.e. phospholipase, proteinase and hemolysin. We conducted a systematic search on Pubmed, Embase, Scopus, Livivo, Lilacs, Web of Science, and Science Direct databases, and Google Scholar. The MAStARI tool was used to evaluate the risk of bias in the selected studies. From 2259 studies, 19 were included in this review and 11 comprised the meta-analysis. The activity of phospholipase (M-H = 0.15; Z = 2,76; p = 0.0006) and hemolysin exoenzymes (M-H = 0.07; z = 1,94; p = 0.05) was higher in C. albicans isolated from the oral cavity of HIV-infected patients, whereas the levels of protease activity were not different compared with non-HIV-infected individuals. This study showed a higher phospholipase and hemolysin activity in C. albicans isolates from the oral cavity of HIV-infected patients.


Mortality Patterns of Synchronous Uterine and Ovarian Cancers: A SEER Registry Analysis.
The degree to which uterine cancer metastatic to the ovary is misdiagnosed as synchronous stage I uterine and ovarian cancers is unclear. We sought to determine whether patients with synchronous cancers had mortality patterns similar to either stage IIIA uterine, stage I uterine, or stage I ovarian cancers alone. The Surveillance, Epidemiology, and End Results database was used to compare mortality of patients with synchronous stage I uterine and stage I ovarian cancers versus those with stage IIIA uterine, stage I uterine, or stage I ovarian cancers alone. We calculated age-adjusted mortality hazard ratios (HR) and 95% confidence intervals (CI) accounting for calendar year and grade, adjuvant treatment, grade 1 endometrioid cancers, grade 3 endometrioid cancers, and stage IA cancers. Among the 9,321 patients, we observed lower age-adjusted mortality in patients with stage I synchronous cancers (n = 937) compared to those with stage IIIA uterine (n = 531; HR, 0.45 95% CI, 0.35-0.58), stage I uterine (n = 6,919; HR, 0.74; 95% CI, 0.60-0.91), and stage I ovarian cancers (n = 934; HR, 0.52; 95% CI, 0.41-0.67). Results were similar after taking into account diagnosis year and grade, and limiting to those receiving adjuvant therapy, grade 1 or grade 3 endometrioid cancers, or stage IA cancers. We observed lower mortality for synchronous stage I uterine and ovarian cancers, which was not explained by younger age, earlier stage, lower grade, histology type, or adjuvant therapy. The possible misdiagnosis associated with clinicopathologic of synchronous uterine and ovarian cancers does not appear to worsen survival on a population level.


Diagnosis and treatment of vascular damage in dementia.
This paper provides an overview of cognitive impairment due to vascular brain damage, which is referred to as vascular cognitive impairment (VCI). Over the past decades, we have seen marked progress in detecting VCI, both through maturation of diagnostic concepts and through advances in brain imaging, especially MRI. Yet in daily practice, it is often challenging to establish the diagnosis, particularly in patients where there is no evident temporal relation between a cerebrovascular event and cognitive dysfunction. Because vascular damage is such a common cause of cognitive dysfunction, it provides an obvious target for treatment. In patients whose cognitive dysfunction follows directly after a stroke, the etiological classification of this stroke will direct treatment. In many patients however, VCI develops due to so-called "silent vascular damage," without evident cerebrovascular events. In these patients, small vessel diseases (SVDs) are the most common cause. Yet no SVD-specific treatments currently exist, which is due to incomplete understanding of the pathophysiology. This review addresses developments in this field. It offers a framework to translate diagnostic criteria to daily practice, addresses treatment, and highlights some future perspectives. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia, edited by M. Paul Murphy, Roderick A. Corriveau, and Donna M. Wilcock.


Th1 and Th2 in human IVF pregnancy with allogenic fetus.
Positive obstetric outcome of allogenic in vitro fertilization (IVF) pregnancies makes interesting the subject of additional regulatory mechanisms after oocyte donation. Eighty eight women: 23 donation of oocytes (DO), 33 IVF, 32 natural conception (NC) were studied in first trimester of pregnancy. Intracellular production of cytokines and chemokine receptors expression were studied by flow cytometry. Intracellular production of interferon-gamma (IFN-gamma), interleukin (IL)-4, tumor necrosis factor-alpha by CD4 T lymphocytes in DO women was higher than in IVF and NC women. Ratio IFN-gamma/IL-4 in DO was lower than in IVF. We found higher expression of chemokine receptor CCR4 but not CXCR3 on CD4 T cells in DO compared with IVF and NC. Ratio CXCR3/CCR4 in DO was lower than in NC. Hyperactivation of T helper 1 (Th1) and T helper 2 (Th2) by allogenic fetus is specific for DO pregnancy. Preferable activation of Th2 and relative suppression of Th1 chemokine expression reflect additional regulatory counteractive mechanism(s).


Pharmacologic Approaches to Electrolyte Abnormalities in Heart Failure.
Electrolyte abnormalities are common in heart failure and can arise from a variety of etiologies. Neurohormonal activation from ventricular dysfunction, renal dysfunction, and heart failure medications can perturb electrolyte homeostasis which impact both heart failure-related morbidity and mortality. These include disturbances in serum sodium, chloride, acid-base, and potassium homeostasis. Pharmacological treatments differ for each electrolyte abnormality and vary from older, established treatments like the vaptans or acetazolamide, to experimental or theoretical treatments like hypertonic saline or urea, or to newer, novel agents like the potassium binders: patiromer and zirconium cyclosilicate. Pharmacologic approaches range from limiting electrolyte intake or directly repleting the electrolyte, to blocking or promoting their resorption, and to neurohormonal antagonism. Because of the prevalence and clinical impact of electrolyte abnormalities, understanding both the older and newer therapeutic options is and will continue to be necessity for the management of heart failure.


4-Nitro-isophthalic acid.
In the crystal structure of the title compound, C(8)H(5)NO(6), both carboxyl groups are involved in inter-molecular centrosymmetric cyclic O-H⋯O hydrogen-bonding associations, which give a zigzag chain structure extending along (2[Formula: see text]1). Weak π-π stacking inter-actions are also present [minimum ring centroid separation = 3.893 (4) Å].


FLOT and CROSS chemotherapy regimens alter the frequency of CD27+ and CD69+ T cells in oesophagogastric adenocarcinomas: implications for combination with immunotherapy.
Combining immunostimulatory chemotherapies with immunotherapy is an attractive strategy to enhance treatment responses in oesophagogastric junctional adenocarcinoma (OGJ). This study investigates the immunostimulatory properties of FLOT, CROSS and MAGIC chemotherapy regimens in the context of OGJ using in vitro and ex vivo models of the treatment-naïve and post-chemotherapy treated tumour microenvironment. FLOT and CROSS chemotherapy regimens increased surrogate markers of immunogenic cell death (HMGB1 and HLA-DR), whereas the MAGIC treatment regimen decreased HMGB1 and HLA-DR on OGJ cells (markedly for epirubicin). Tumour-infiltrating and circulating T cells had significantly lower CD27 expression and significantly higher CD69 expression post-FLOT and post-CROSS treatment. Similarly, the supernatant from FLOT- and CROSS-treated OGJ cell lines and from FLOT- and CROSS-treated OGJ biopsies cultured ex vivo also decreased CD27 and increased CD69 expression on T cells. Following 48 h treatment with post-FLOT and post-CROSS tumour conditioned media the frequency of CD69+ T cells in culture negatively correlated with the levels of soluble immunosuppressive pro-angiogenic factors in the conditioned media from ex vivo explants. Supernatant from FLOT- and CROSS-treated OGJ cell lines also increased the cytotoxic potential of healthy donor T cells ex vivo and enhanced OGJ patient-derived lymphocyte mediated-killing of OE33 cells ex vivo. Collectively, this data demonstrate that FLOT and CROSS chemotherapy regimens possess immunostimulatory properties, identifying these chemotherapy regimens as rational synergistic partners to test in combination with immunotherapy and determine if this combinatorial approach could boost anti-tumour immunity in OGJ patients and improve clinical outcomes.


[Oral appliances or maxillomandibular advancement osteotomy for severe obstructive sleep apnoea in patients refusing CPAP].
The management of patients with severe obstructive sleep apnea syndrome (OSAS) refusing or not tolerating continuous positive pressure ventilation (CPAP) remains problematic. We evaluated the effectiveness of oral appliances and of maxillomandibular advancement osteotomy. One hundred and two patients with severe OSAS were included between 2001 and 2006. Maxillo-mandibular advancement osteotomy was proposed to patients less than 60 years of age, non obese and without comorbidities. The other patients were treated with oral appliances. All patients underwent polysomnography at 3 months. Group A: 25 patients with mean apnea-hypopnea index (AHI) at 45/h were treated by maxillo-mandibular advancement. Three months after the surgery, AHI had decreased from 45 to 7. The success rate was 89% when AHI was less than 15/h and 74% when AHI was less than 10/h. Sixteen patients performed a polysomnography one year after surgery with similar results. There were no major postoperative complications. Group B: 77 patients with a mean AHI at 41/h were treated with oral appliances. Only 23 patients underwent polysomnography at 3 months. The mean AHI had decreased from 41/h to 22/h. The success rate was 56% when AHI was less than 15/h and 30% when AHI was less than 10/h. We are confronted with an increasing number of severe OSAS patients with CPAP failure or intolerance. Surgery for maxillo-mandibular advancement is an effective alternative. However, it is not always indicated or accepted by the patient. So an oral appliance remains a useful therapeutic option despite its moderate success rate.


Quantitative Measures of Right Ventricular Size and Function by Echocardiogram Correlate with Cardiac Catheterization Hemodynamics in Congenital Diaphragmatic Hernia.
To evaluate associations between cardiac catheterization (cath) hemodynamics, quantitative measures of right ventricular (RV) function by echocardiogram, and survival in patients with congenital diaphragmatic hernia (CDH). This single-center retrospective cohort study enrolled patients with CDH who underwent index cath from 2003 to 2022. Tricuspid annular plane systolic excursion z score, RV fractional area change, RV free wall and global longitudinal strain, left ventricular (LV) eccentricity index, RV/LV ratio, and pulmonary artery acceleration time were measured from preprocedure echocardiograms. Associations between hemodynamic values, echocardiographic measures, and survival were evaluated by Spearman correlation and Wilcoxon rank sum test, respectively. Fifty-three patients (68% left-sided, 74% liver herniation, 57% extracorporeal membrane oxygenation, 93% survival) underwent cath (39 during index hospitalization, 14 later) including device closure of a patent ductus arteriosus in 5. Most patients (n = 31, 58%) were on pulmonary hypertension treatment at cath, most commonly sildenafil (n = 24, 45%) and/or intravenous treprostinil (n = 16, 30%). Overall, hemodynamics were consistent with precapillary pulmonary hypertension. Pulmonary capillary wedge pressure was >15 mm Hg in 2 patients (4%). Lower fractional area change and worse ventricular strain were associated with higher pulmonary artery pressure while higher LV eccentricity index and higher RV/LV ratio were associated with both higher pulmonary artery pressure and higher pulmonary vascular resistance. Hemodynamics did not differ based on survival status. Worse RV dilation and dysfunction by echocardiogram correlate with higher pulmonary artery pressure and pulmonary vascular resistance on cath in this CDH cohort. These measures may represent novel, noninvasive clinical trial targets in this population.


[Application and Effect Evaluation of Precision Nursing Care of Enhanced Rehabilitation After Surgery in the Perioperative Period of Colorectal Cancer].
To examine the effect of perioperative precision nursing care of enhanced recovery after surgery (ERAS) on the postoperative recovery, stress response, and psychological state of colorectal cancer patients. A total of 100 patients undergoing elective laparoscopic colorectal cancer surgery were randomly assigned to an experimental group and a control group, with 50 patients in each group. The experimental group received systematic, standardized, and specialized precision nursing care in three stages, the preoperative, intraoperative, and postoperative stages, while the control group received routine nursing care. The main outcome indicators compared between the two groups included the time of the first postoperative passage of flatus and stool, ambulation, liquid-diet meal, postoperative length-of-stay, and C-reactive protein (CRP), interleukin-6 (IL-6), and homeostatic model assessment of insulin resistance (HOMR-IR) measured 1 day before surgery and 1, 3, and 5 days after surgery. Secondary outcome indicators included the anxiety and depression levels of patients measured upon admission to the hospital and 48 h after surgery by Self-rating Anxiety Scale (SAS) and Self-rating Sepression Scale (SDS), respectively. In the experimental group, the time of the first postoperative passage of flatus and stool, ambulation, and liquid-diet meal and the postoperative length-of-stay were all lower than those in the control group. The postoperative CRP and IL-6 levels of the two groups were significantly higher than the preoperative levels, and the control group had higher CRP and IL-6 levels than the experimental group did, all showing significant difference ( P<0.05). The two groups presented different stress states at different points of time after surgery, with the CRP and IL-6 levels reaching the highest 3 days after surgery and then dropping to some degree afterwards. The HOMR-IR of the patients in the experimental group was significantly lower than that of the control group and the difference was significant at both 1 d and 3 d after surgery ( P<0.05). Comparison of the difference in the anxiety and the depression scores in the two groups showed significant difference ( P<0.05). Before discharge, patient satisfaction of the experimental group was significantly higher than that of the control group ( P<0.05). The implementation of ERAS precision nursing care can effectively promote the postoperative recovery of colorectal cancer patients, reduce the perioperative stress response, alleviate anxiety and depression, improve patient satisfaction, and hence should be extensively applied in clinical practice.


UV, ozone, and COVID-19 transmission in Ontario, Canada using generalised linear models.
Quantifying the impact of environmental factors on COVID-19 transmission is crucial in preventing more cases. Ultraviolet (UV) radiation and ozone (O3) have reported antimicrobial properties but few studies have examined associations with community infectivity of COVID-19. Research suggests UV light can be preventative while the effect of O3 is contested. We sought to determine the relationship between UV, O3, and COVID-19 incidence in Ontario, Canada. In our time series analyses, we calculated daily incidence rates and reproductive number (Rt) from 34,975 cases between January and June 2020 across 34 Ontario Public Health Units. We used generalised linear models, adjusting for potential confounders, to calculate point estimates (PE) and 95% confidence intervals (CI) for UV and O3. Analyses were further stratified by age groups and outbreaks at institutions versus community. We found that 1-week averaged UV was significantly associated with a 13% decrease (95% CI: 0.80-0.96) in overall COVID-19 Rt, per unit increase. A negative association with UV was also significant among community outbreaks (PE: 0.88, 95% CI: 0.81-0.96) but not institutional outbreaks (PE: 0.94, 95% CI: 0.85-1.03). A positive association of O3 with COVID-19 incidence is strongly suggested among institutional outbreak cases (PE: 1.06, 95% CI: 1.00-1.13). Our study found evidence to support the hypothesis that higher UV reduced transmission of COVID-19 and some evidence that ground-level O3 positively influenced COVID-19 transmission. Setting of infection should be strongly considered as a factor in future research. UV and O3 may explain some of COVID-19's seasonal behaviour.


Allosteric modulation of G-protein coupled receptors.
The superfamily of G-protein coupled receptors (GPCRs) has more than 1000 members and is the largest family of proteins in the body. GPCRs mediate signalling of stimuli as diverse as light, ions, small molecules, peptides and proteins and are the targets for many pharmaceuticals. Most GPCR ligands are believed to activate (agonists) or inhibit (competitive antagonists) receptor signalling by binding the receptor at the same site as the endogenous agonist, the orthosteric site. In contrast, allosteric ligands modulate receptor function by binding to different regions in the receptor, allosteric sites. In recent years, combinatorial chemistry and high throughput screening have helped identify several allosteric GPCR modulators with novel structures, several of which already have become valuable pharmacological tools and may be candidates for clinical testing in the near future. This mini review outlines the current status and perspectives of allosteric modulation of GPCR function with emphasis on the pharmacology of endogenous and synthesised modulators, their receptor interactions and the therapeutic prospects of allosteric ligands compared to orthosteric ligands.


Identification of candidate genes for Sjögren's syndrome using MRL/lpr mouse model of Sjögren's syndrome and cDNA microarray analysis.
Sjögren's syndrome is a chronic autoimmune disease characterized by focal lymphocytic infiltration of lacrimal and salivary glands, but the precise mechanism of this syndrome is poorly understood. To clarify the mechanism of onset and progression of Sjögren's syndrome, it is necessary to identify Sjögren's syndrome-related genes. For this purpose, we used MLR/MpJ-lpr/lpr (MRL/lpr) mouse as a model of human secondary Sjögren's syndrome and analyzed specific mRNA expression pattern in MRL/lpr mouse salivary glands by in-house cDNA microarray. Among arrayed 2304 genes, 13 genes were isolated as highly expressed genes in MRL/lpr mouse salivary gland in comparison with MRL/MpJ-+/+ (MRL/+) mouse tissue. Subsequently, we performed RT-PCR analysis and confirmed the high expression level of nine genes; caspase3, Ly-6C.2, vimentin, Mel-14 antigen, cathepsin B, mpt1, Laptm5, Gnai2 and UCP2. Five of the nine genes have already been identified in patients with Sjögren's syndrome or mice models of the syndrome, but the remaining four genes; mpt1, Laptm5, Gnai2, and UCP2 have not been reported previously as Sjögren's syndrome-related genes. Although, further experiments are necessary to examine the relationship between these four genes and Sjögren's syndrome, our system of mouse model of Sjögren's syndrome combined with in-house cDNA microarray is suitable for the isolation of Sjögren's syndrome-related genes.


[Imported cases of dengue fever diagnosed in metropolitan France, from January 2001 to December 2006].
Dengue fever is the main emerging vector-borne disease worldwide. It was estimated that 40% of the world population is at risk. A potential vector (Aedes albopictus) is present in four French departments of the southeast area of metropolitan France. The authors tried to document the number of imported cases of dengue diagnosed from 2001 to 2006, inclusive, as well as their main features. Between 12 and 28 cases of imported dengue were diagnosed every month during that period (eight to 18 cases per month except for years 2001-2002 during which an important dengue epidemic was documented in the French West Indies). Nearly 40% of the cases were imported between June and September during which the vector is active in the metropolitan area. This data underlines the strong and close link between the endemic zones of the French territory (French West Indies and Guyana) and the risk of imported cases to metropolitan France. The identification of this "importation track" entails strengthening the system for detecting and managing imported dengue cases in metropolitan France when a dengue epidemic is detected in the French West Indies.


Peroneal neuropathy after liver transplantation.
The incidence of peroneal neuropathy (PN), occurring predominantly in the left leg, increases after the incorporation of intermittent pneumatic compression (IPC) devices among adult liver transplantation (OLT) recipients in our hospital. The aim of this study was to investigate the possible risk factors for PN and the reason for the left-leg predominance. We retrospectively reviewed the medical records of 501 OLT recipients. The patients were first divided into 2 groups, PN (n = 33) and non-PN (n = 468), to assess possible risk factors. The patients were then categorized into IPC (n = 262) and non-IPC (n = 239) groups according to the use of IPC devices. In a subsequent prospective study, we measured the degree and duration of the tilt of the operating table during OLT to investigate their relationship to the predominant left-leg PN. The rate of IPC device use was significantly greater among the PN than non-PN group (78.8% vs 50.4%, P < .01). The incidence of PN was significantly higher among the IPC than non-IPC group (9.9% vs 2.9%, P < .01). The degree and duration of left tilt of the operating table were greater and longer than the right tilt. The use of IPC devices during OLT increased the occurrence of PN and the left tilt of the operating table was strongly related to the predominant left-leg PN. Careful protection of the vulnerable point and minimization of the tilting of the operating table is advised during OLT, especially when IPC devices are used.


New laboratory test in flow cytometry for the combined analysis of serologic and cellular parameters in the diagnosis of heparin-induced thrombocytopenia.
Heparin-induced thrombocytopenia (HIT) is a major complication of heparin therapy. A quick and reliable laboratory assay for the combined determination of pathogenic anti-heparin and platelet factor 4 (H:PF4) antibodies in the serum and platelet activation is not currently available. We developed a new single-tube assay in flow cytometry that combines the detection of antibodies in the serum and their activatory properties on platelets. The assay was tested on 13 serum samples from patients with suspected HIT and six samples from normal donors. The presence of anti-H:PF4 antibody complexes was detected by H:PF4-coated beads, and donor platelet activation induced by HIT sera was determined by Annexin V binding. All data were compared with the patients' clinical setting, laboratory tests, and standard enzyme-linked immunosorbent assay detection of anti-H:PF4 antibodies. This flow cytometry assay allowed unequivocal, simultaneous detection of anti-H:PF4 antibodies in sera and their activatory properties on platelets. All cases for which the diagnosis of HIT was confirmed were detected by the flow assay. This assay, combining for the first time functional and nonfunctional testing on anti-H:PF4 antibodies, is likely to influence the clinical decision for the management of HIT patients.


The future of food from the sea.
Global food demand is rising, and serious questions remain about whether supply can increase sustainably1. Land-based expansion is possible but may exacerbate climate change and biodiversity loss, and compromise the delivery of other ecosystem services2-6. As food from the sea represents only 17% of the current production of edible meat, we ask how much food we can expect the ocean to sustainably produce by 2050. Here we examine the main food-producing sectors in the ocean-wild fisheries, finfish mariculture and bivalve mariculture-to estimate 'sustainable supply curves' that account for ecological, economic, regulatory and technological constraints. We overlay these supply curves with demand scenarios to estimate future seafood production. We find that under our estimated demand shifts and supply scenarios (which account for policy reform and technology improvements), edible food from the sea could increase by 21-44 million tonnes by 2050, a 36-74% increase compared to current yields. This represents 12-25% of the estimated increase in all meat needed to feed 9.8 billion people by 2050. Increases in all three sectors are likely, but are most pronounced for mariculture. Whether these production potentials are realized sustainably will depend on factors such as policy reforms, technological innovation and the extent of future shifts in demand.


A scoping review of transfer learning research on medical image analysis using ImageNet.
Employing transfer learning (TL) with convolutional neural networks (CNNs), well-trained on non-medical ImageNet dataset, has shown promising results for medical image analysis in recent years. We aimed to conduct a scoping review to identify these studies and summarize their characteristics in terms of the problem description, input, methodology, and outcome. To identify relevant studies, MEDLINE, IEEE, and ACM digital library were searched for studies published between June 1st, 2012 and January 2nd, 2020. Two investigators independently reviewed articles to determine eligibility and to extract data according to a study protocol defined a priori. After screening of 8421 articles, 102 met the inclusion criteria. Of 22 anatomical areas, eye (18%), breast (14%), and brain (12%) were the most commonly studied. Data augmentation was performed in 72% of fine-tuning TL studies versus 15% of the feature-extracting TL studies. Inception models were the most commonly used in breast related studies (50%), while VGGNet was the common in eye (44%), skin (50%) and tooth (57%) studies. AlexNet for brain (42%) and DenseNet for lung studies (38%) were the most frequently used models. Inception models were the most frequently used for studies that analyzed ultrasound (55%), endoscopy (57%), and skeletal system X-rays (57%). VGGNet was the most common for fundus (42%) and optical coherence tomography images (50%). AlexNet was the most frequent model for brain MRIs (36%) and breast X-Rays (50%). 35% of the studies compared their model with other well-trained CNN models and 33% of them provided visualization for interpretation. This study identified the most prevalent tracks of implementation in the literature for data preparation, methodology selection and output evaluation for various medical image analysis tasks. Also, we identified several critical research gaps existing in the TL studies on medical image analysis. The findings of this scoping review can be used in future TL studies to guide the selection of appropriate research approaches, as well as identify research gaps and opportunities for innovation.


Incidence and survival rates and trends of skull Base chondrosarcoma: A Population-Based study.
Chondrosarcomas are extremely rare, locally invasive, and potentially mortal malignant cartilaginous tumors. In this study, we aimed to evaluate the incidence and survival rates and trends of skull base chondrosarcomas (SBC). Data from SBC patients between 1975 and 2017 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The age-adjusted incidence rates (AAR) were calculated for the overall cases and based on gender, age, race, and histology. Furthermore, the relative survival rates for one, three, and five years, and the rates stratified to the aforementioned selected variables were computed. Besides, we conducted a joint point regression analysis to calculate the annual percent change (APC) and its associated standard error (SE) for AAR and mortality. The AAR rate of SBC was 0.019 per 100,000. Higher AAR rates were observed in patients who were in the 65-74-year-age-group, females, Caucasians, and had none mesenchymal subtype. The relative one-year, three-year and five-year-survival rates were 99.58 %, 93.67 %, and 89.10 %, respectively. Lower survival rates were noted in patients who were males, African Americans, and had a mesenchymal subtype. The trend analysis has shown a significant yearly increase (P < 0.001) in AAR of SBC (APC ± SE = 0.0005 %±0.0001), along with a significant yearly decline in mortality rates (APC ± SE= -0.0202 %±0.0029). Despite the increase in AAR over time, there has been a significant decline in mortality rates over time, which might have been due to the advancement of treatment modalities, improvement in diagnostic imaging, and modification in disease grading.


Laminin α5_CD239_Spectrin is a candidate association that compensates the linkage between the basement membrane and cytoskeleton in skeletal muscle fibers.
The linkage between the basement membrane (BM) and cytoskeleton is crucial for muscle fiber stability and signal transduction. Mutations in the linkage molecules can cause various types of muscular dystrophies. The different severities and times of onset suggest that compensatory linkages occur at the sarcolemma. Cluster of differentiation 239 (CD239) binds to the α5 subunit of laminin-511 extracellularly and is connected to spectrin intracellularly, resulting in a linkage between the BM and cytoskeleton. In this study, we explored the linkage of laminin α5_CD239_spectrin in skeletal muscles. Although laminin α5, CD239, and spectrin were present in embryonic skeletal muscles, they disappeared in adult skeletal muscle tissues, except for the soleus and diaphragm. Laminin α5_CD239_spectrin was localized in the skeletal muscle tissues of Duchenne muscular dystrophy and congenital muscular dystrophy mouse models. The experimental regeneration of skeletal muscle increased the CD239-mediated linkage, indicating that it responds to regeneration, but not to genetic influence. Furthermore, in silico analysis showed that laminin α5_CD239_spectrin was upregulated by steroid therapy for muscular dystrophy. Therefore, CD239-mediated linkage may serve as a therapeutic target to prevent the progression of muscular dystrophy.


The significance of conversion of skin reactivity to efficacy of bacillus Calmette-Guérin (BCG) vaccinations given immediately after radical surgery in stage II melanoma patients.
A group of 668 stage II melanoma patients was entered into a randomized prospective study aimed at evaluating the efficacy of adjuvant BCG, 5-(dimethyltriazeno)imidazole-4-carboxamide (DTIC), or a combination of the two, given immediately after radical lymph node dissection. Of these, 176 patients received BCG and 164 BCG plus DTIC. These 340 patients had histologically proven metastatic nodes and 156 had a negative skin reactivity to BCG at the beginning of treatment. The distribution of known prognostic factors (sex, age, number of positive nodes, extracapsular invasion) was balanced in the groups of patients either with initially negative or with positive skin reactivity. All patients who were initially non-reactive to BCG developed skin reactivity after 6.7 +/- 9 BCG vaccinations. Disease-free and overall survival of patients receiving BCG or BCG + DTIC with an initially negative skin reactivity to BCG was significantly (P = 7 x 10(-3) better than that observed in patients with an initial positive skin reactivity. This finding was still evident after adjustment for other known prognostic criteria (P = 0.02). It seems likely that the initial BCG skin reactivity as such marks the prognosis; however, some therapeutic effect of BCG treatment in patients having initially no skin reactivity to BCG, can not be ruled out.


Lamin A/C-dependent chromatin architecture safeguards naïve pluripotency to prevent aberrant cardiovascular cell fate and function.
Tight control of cell fate choices is crucial for normal development. Here we show that lamin A/C plays a key role in chromatin organization in embryonic stem cells (ESCs), which safeguards naïve pluripotency and ensures proper cell fate choices during cardiogenesis. We report changes in chromatin compaction and localization of cardiac genes in Lmna-/- ESCs resulting in precocious activation of a transcriptional program promoting cardiomyocyte versus endothelial cell fate. This is accompanied by premature cardiomyocyte differentiation, cell cycle withdrawal and abnormal contractility. Gata4 is activated by lamin A/C loss and Gata4 silencing or haploinsufficiency rescues the aberrant cardiovascular cell fate choices induced by lamin A/C deficiency. We uncover divergent functions of lamin A/C in naïve pluripotent stem cells and cardiomyocytes, which have distinct contributions to the transcriptional alterations of patients with LMNA-associated cardiomyopathy. We conclude that disruption of lamin A/C-dependent chromatin architecture in ESCs is a primary event in LMNA loss-of-function cardiomyopathy.


Toward a digital decision- and workflow-support system for initiation and control of long-term non-invasive ventilation in stable hypercapnic COPD patients.
Due to an increasing demand for the initiation and control of non-invasive ventilation (NIV), digital algorithms are suggested to support therapeutic decisions and workflows in an ambulatory setting. The DIGIVENT project established and implemented such algorithms for patients with chronic hypercapnic respiratory failure due to chronic obstructive pulmonary disease (COPD) by a predefined process. Based on long-term clinical experience and guideline recommendations as provided by the German Respiratory Society, detailed graphical descriptions of how to perform NIV in stable COPD patients were created. Subsequently, these clinical workflows were implemented in the Business Process Model and Notation (BPMN) as one tool to formalize these workflows serving as input for an executable digital implementation. We succeeded in creating an executable digital implementation that reflects clinical decision-making and workflows in digital algorithms. Furthermore, we built a user-friendly graphical interface that allows easy interaction with the DIGIVENT support algorithms. The DIGIVENT project established digital treatment algorithms and implemented a decision- and workflow-support system for NIV whose validation in a clinical cohort is planned.


Magnetic resonance imaging biomarkers of chronic obstructive pulmonary disease prior to radiation therapy for non-small cell lung cancer.
In this prospectively planned interim-analysis, the prevalence of chronic obstructive lung disease (COPD) phenotypes was determined using magnetic resonance imaging (MRI) and X-ray computed tomography (CT) in non-small-cell-lung-cancer (NSCLC) patients. Stage-III-NSCLC patients provided written informed consent for pulmonary function tests, imaging and the 6-min-walk-test. Ventilation defect percent (VDP) and CT lung density (relative-of-CT-density-histogram <-950, RA950) were measured. Patients were classified into three subgroups based on qualitative and quantitative COPD and tumour-specific imaging phenotypes: (1) tumour-specific ventilation defects (TSD), (2) tumour-specific and other ventilation defects without emphysema (TSDV), and, (3) tumour-specific and other ventilation defects with emphysema (TSDVE). Seventeen stage-III NSCLC patients were evaluated (68 ± 7 years, 7 M/10 F, mean FEV1 = 77%pred) including seven current and 10 ex-smokers and eight patients with a prior lung disease diagnosis. There was a significant difference for smoking history (p = .02) and FEV1/FVC (p = .04) for subgroups classified using quantitative imaging. Patient subgroups classified using qualitative imaging findings were significantly different for emphysema (RA950, p < .001). There were significant relationships for whole-lung VDP (p < .05), but not RECIST or tumour-lobe VDP measurements with pulmonary function and exercise measurements. Preliminary analysis for non-tumour burden ventilation abnormalities using Reader-operator-characteristic (ROC) curves reflected a 94% classification rate for smoking pack-years, 93% for FEV1/FVC and 82% for RA950. ROC sensitivity/specificity/positive/negative likelihood ratios were also generated for pack-years, (0.92/0.80/4.6/0.3), FEV1/FVC (0.92/0.80/4.6/0.3), RA950 (0.92/0.80/4.6/0.3) and RECIST (0.58/0.80/2.9/1.1). In this prospectively planned interim-analysis of a larger clinical trial, NSCLC patients were classified based on COPD imaging phenotypes. A proof-of-concept evaluation showed that FEV1/FVC and smoking history identified NSCLC patients with ventilation abnormalities appropriate for functional lung avoidance radiotherapy.


Prospective study of the Acri.LISA bifocal intraocular lens.
To assess the visual results after bilateral implantation of the bifocal Acri.LISA 366D intraocular lens (IOL) (Acri.Tec AG). Fernández-Vega Ophthalmological Institute, Oviedo, Spain. Eighty-one patients had bilateral implantation of the distance-dominant bifocal Acri.LISA 366D IOL in a prospective study. Monocular and binocular best corrected distance visual acuity and best distance-corrected near visual acuity, binocular best distance-corrected intermediate visual acuity, and distance contrast sensitivity under photopic (85 cd/m(2)) and mesopic (5 cd/m(2)) conditions were determined. At the 3-month postoperative visit, the mean binocular best corrected distance acuity was 0.048 +/- 0.111 logMAR and the mean binocular best distance-corrected near acuity, 0.012 +/- 0.0084 logMAR (both approximately 20/20). The mean binocular best distance-corrected intermediate acuity changed significantly as a function of the distance of the test, from 0.012 +/- 0.084 logMAR (approximately 20/20) at 33 cm to 0.265 +/- 0.099 logMAR (approximately 20/40) at 70 cm (P<.01). Contrast sensitivity was within normal limits under photopic and mesopic conditions. Binocular contrast sensitivity was statistically significantly better than monocular contrast sensitivity at all spatial frequencies under both illumination levels (P<.01). The Acri.LISA 366D IOL provided a satisfactory full range of vision; a high level of uncorrected and corrected distance, intermediate, and near acuity; and improved contrast sensitivity under photopic and mesopic conditions.


Sensory ecology: giant eyes for giant predators?
Mathematical models suggest the enormous eyes of giant and colossal squid evolved to see the bioluminescence induced by the approach of predatory whales.


βlinc1 encodes a long noncoding RNA that regulates islet β-cell formation and function.
Pancreatic β cells are responsible for maintaining glucose homeostasis; their absence or malfunction results in diabetes mellitus. Although there is evidence that long noncoding RNAs (lncRNAs) play important roles in development and disease, none have been investigated in vivo in the context of pancreas development. In this study, we demonstrate that βlinc1 (β-cell long intergenic noncoding RNA 1), a conserved lncRNA, is necessary for the specification and function of insulin-producing β cells through the coordinated regulation of a number of islet-specific transcription factors located in the genomic vicinity of βlinc1. Furthermore, deletion of βlinc1 results in defective islet development and disruption of glucose homeostasis in adult mice.


Functional characterization of an ACCase subunit from the diatom Phaeodactylum tricornutum expressed in Escherichia coli.
The marine diatom Phaeodactylum tricornutum, a widely used forage species, has a storage lipid content of up to 30% dry cell weight. To explore the mechanism behind the high storage lipid accumulation in this diatom, acetyl-CoA carboxylase (ACCase), which catalyzes the first committed step of the fatty acid biosynthetic pathway, was characterized in this study. A homogeneous type of ACCase (PtACC) was identified from P. tricornutum by homology searches. The first exon of the ACCase gene (PtACC-1) was cloned. PtACC-1 was fused with a Myc epitope tag and cloned into plasmid pMD18 driven by the LacZ promoter and expressed in Escherichia coli. The expression of the PtACC-1-Myc protein was verified by Western blot. The neutral lipid content in transformed E. coli increased substantially by twofold as determined by Nile red fluorescent dye staining. Concomitantly, ACCase activity increased by 1.72-fold. The fatty acid composition, analyzed by GC-MS, demonstrated a significant difference in the ratio of saturated fatty acids and monounsaturated fatty acids (MUFAs). MUFAs of PtACC-1 expressing cells increased by 13%. This study represents the first characterization of the key domains of ACCase from a diatom and demonstrates high neutral lipid accumulation in E. coli expressing PtACC-1, providing an additional genetic resource with the potential for biodiesel development.


[Cholecystitis and cholelithiasis induced by lincomycin. Microscopic and ultrastructural studies].
Gallbladder of 30 golden hamsters was evaluated after a seven days course of lincomycin (60 mg/kg/day). Fifteen animals injected with an equivalent volume of saline and 15 animals non injected at all, were used as controls. Weight, sex, age, and food were similar in all groups. Eight hamsters (23%) treated with lincomycin formed pigmented gallstones.


DNA ploidy and cell-cycle analysis in pancreatic and ampullary carcinoma: flow cytometric study of formalin-fixed paraffin-embedded tissue.
The cellular DNA content of formalin-fixed, paraffin-embedded specimens from 47 ductal adenocarcinomas of the pancreas and 5 adenocarcinomas of the ampulla of Vater was analysed using flow cytometry. Ploidy and the fraction of cells in the S and G2M phases were determined and correlated with tumour stage and grade as well as patients' survival. Cell populations with aneuploid DNA content were observed in 15% of the tumours. The S + G2M fractions ranged between 1% and 10%. Compared to non-neoplastic tissue of the pancreas the S + G2M fraction was significantly higher in the carcinomas. Cox regression analysis revealed the S + G2M fraction as an independent prognostic factor (p less than 0.05). Ploidy was of no prognostic value for survival, but correlated weakly with tumour stage and tumour grade. All patients without lymph node metastases at time of surgery had diploid tumours. Aneuploidy was restricted to tumours in advanced stages and tended to be more frequent in high-grade tumours.


Valorisation of black mulberry and grape seeds: Chemical characterization and bioactive potential.
Grape (Vitis vinifera L. var. Albariño) and mulberry (Morus nigra L.) seeds pomace were characterized in terms of tocopherols, organic acids, phenolic compounds and bioactive properties. Higher contents of tocopherols (28 ± 1 mg/100 g fw) were obtained in mulberry, whilst grape seeds were richer in organic acids (79 ± 4 mg/100 g fw). The phenolic analysis of hydroethanolic extracts characterised grape seeds by catechin oligomers (36.0 ± 0.3 mg/g) and mulberry seeds by ellagic acid derivatives (3.14 ± 0.02 mg/g). Both exhibited high antimicrobial activity against multiresistant Staphylococcus aureus MIC = 5 mg/mL) and no cytotoxicity against carcinogenic and non-tumour primary liver (PLP) cells. Mulberry seeds revealed the strongest inhibition (p < 0.05) against thiobarbituric reactive substances (IC50 = 23 ± 2 µg/mL) and oxidative haemolysis (IC50 at 60 min = 46.0 ± 0.8 µg/mL). Both seed by-products could be exploited for the developing of antioxidant-rich ingredients with health benefits for industrial application.


[Ru(pipe)(dppb)(bipy)]PF6: A novel ruthenium complex that effectively inhibits ERK activation and cyclin D1 expression in A549 cells.
Lung cancer is the most frequent type of cancer worldwide. In Brazil, only 14% of the patients diagnosed with lung cancer survived 5years in the last decades. Although improvements in the therapeutic approach, it is relevant to identify new chemotherapeutic agents. In this framework, ruthenium metal compounds emerge as a promising alternative to platinum-based compounds once they displayed lower cytotoxicity and more selectivity for tumor cells. The present study aimed to evaluate the antitumor potential of innovative ruthenium(II) complex, [Ru(pipe)(dppb)(bipy)]PF6 (PIPE) on A549 cells, which is derived from non-small cell lung cancer. Results demonstrated that PIPE effectively reduced the viability and proliferation rate of A549 cells. When PIPE was used at 9μM there was increase in G0/G1 cell population with concomitant reduction in frequency of cells in S-phase, indicating cell cycle arrest in G1/S transition. Antiproliferative activity of PIPE was associated to its ability of reducing cyclin D1 expression and ERK phosphorylation levels. Cytotoxic activity of PIPE on A549 cells was observed when PIPE was used at 18μM, which was associated to its ability of inducing apoptosis by intrinsic pathway. Taken together, the data demonstrated that PIPE is a promising antitumor agent and further in vivo studies should be performed.


Hunger or Deportation: Implications of the Trump Administration's Proposed Public Charge Rule.
Until recently, lawfully present noncitizens participating in the US Department of Agriculture Supplemental Nutrition Assistance Program (formerly Food Stamps) faced no immigration consequences. However, in September, 2018, the Trump Administration proposed a more expansive public charge rule in the Federal Register that would deny lawfully present noncitizens a path to citizenship if they had participated in certain federal safety net programs, including Supplemental Nutrition Assistance Program. This perspective discusses the proposed rule's implications, particularly for those with professional interests in promoting effective nutrition education and healthy behavior through research, policy, and practice among individuals who will potentially be affected.


Population-based epidemiology of human immunodeficiency virus infection in Western Australia. Western Australian AIDS Advisory Committee.
A total of 328 cases of infection with human immunodeficiency virus (HIV) in Western Australia in 1983-1987 was studied with respect to demographic factors, the risk profile, the clinical progression of disease, the utilization of inpatient services and trends in incidence over time. The crude incidence rates were 8.8 cases/100,000 person-years in men and 0.4 cases/100,000 person-years in women. Age-specific rates peaked at 25 to 29 years of age in men. The risk of HIV infection was associated with metropolitan residence, low socioeconomic level, and two specific occupational groups. Homosexual and bisexual men constituted 86% of all cases; the incidence rate of HIV infection in such men was approximately 1000-times higher than was the incidence rate by apparent sexual transmission in heterosexual persons. However, the proportion of cases that occurred in women or that apparently was caused by heterosexual sexual transmission increased from zero in 1983-1984 to 7.5% and 5.4%, respectively, in 1987. After two years of follow-up, 71% of preclinical (category-C) patients had developed signs, symptoms or evidence of immune dysfunction, and 12% of those patients with lymphadenopathy or with other early clinical features of disease (category-B) had progressed to the acquired immunodeficiency syndrome (AIDS). At 21 months of follow-up, the survival rate with AIDS was 9%. Patients with AIDS utilized an average of 68.9 short-stay hospital bed-days per person-year, while category-B patients used 11.5 hospital bed-days per person-year. Notifications of HIV infection increased each year from 1983 to 1986, but fell by 22% in 1987. The latter may have been as a result of chance, a screening artefact or a real reduction in the incidence rate.


[Location of the lesion and the cerebrospinal fluid findings in tuberculous meningitis: differences in the lumbar, cisternal and ventricular compartments].
Tuberculosis remains one of the most prevalent infectious diseases worldwide. In the present study, we describe a case of tuberculous meningitis that caused cerebrospinal fluid (CSF) flow block, leading to difficulties in the diagnosis. The importance of the lesion site and its influence on CSF analysis as a support for the diagnosis of tuberculous meningitis is discussed. In this case, the search for acid-fast bacilii was positive in the cisternal CSF, but not in the ventricular and lumbar CSF, demonstrating the relationship between the accuracy of the test and the location of the inflamatory lesion disease.


Characterization of channel-forming peptide nanostructures.
We have prepared fluorescent analogs of known ion-channel-forming synthetic peptide nanostructures. These analogs were designed as probes to gain insight about the mechanism by which self-assembling amphiphilic peptides interact with lipid membranes. Conformational studies demonstrated that the labeled analogs retain their propensity to adopt a strong helical conformation in 2,2,2-trifluoroethanol and lipid bilayers. Attenuated total reflectance results indicated that the fluorescent peptide nanostructures are under an incorporation equilibrium between two forms, adsorbed at the surface or incorporated within the bilayer, similar to their unlabeled counterparts. However, when using a HeLa mimicking membrane, the proportion of peptide nanostructures in the transmembrane orientation decreases significantly. Finally, we were able to show by confocal microscopy studies that fluorescent analogs internalized into HeLa cells and localized into both the membranes of inner organelles and the cell membrane.


The effect of hepatitis B antigenemia on pregnancy outcome.
Sixty patients documented to have hepatitis B antigenemia during pregnancy were identified retrospectively and compared with an equal number of matched control patients. Maternal and newborn infant parameters were examined. No statistically significant differences were noted between the two groups, except for an increase in infant birth weight in the group showing antigen-positive test results, specifically in infants born to Oriental mothers. It is concluded that infants born to women testing positive for hepatitis B surface antigen represent normal infants eminently suitable for peripartal preventive immunotherapy.


Long-term changes in social interaction and reward following repeated MDMA administration to adolescent rats without accompanying serotonergic neurotoxicity.
MDMA is a popular drug of abuse in adolescents which causes serotonergic neurotoxicity in adult but not young rodents. However, few studies have examined the long-term behavioural consequence of MDMA and it is unclear whether such changes occur in the absence of neurotoxicity. The present study examined whether treatment of young rats with MDMA produced long-term behavioural alterations without accompanying serotonergic neurotoxicity. Male Lister hooded rats ( n=36, postnatal day (PND) 39) received MDMA (7.5 mg/kg i.p., twice daily for 3 days) or saline (l ml/kg i.p.) and the acute effect on open field behaviour and body temperature was monitored. Following drug withdrawal, social interaction in pre-treatment- and weight-matched rat pairs, cortical [(3)H]paroxetine binding and hippocampal and frontal cortical serotonin and dopamine levels (PND 53, n=12) and conditioned place preference (PND 70, n=24) to cocaine (5 mg/kg IP) were analysed. MDMA elicited the expected immediate serotonin syndrome with significant hyperlocomotion, decreased rearing and hypothermia. Twelve to 29 days after the last MDMA injection social interaction was significantly attenuated (by 41%) and the sub-threshold conditioned place preference to cocaine was significantly enhanced compared with that in saline controls, although no significant side preference to cocaine occurred in the latter. MDMA pre-treatment did not alter 5-HT levels or cortical [(3)H]paroxetine binding. MDMA administration to adolescent rats reduced social interaction and enhanced the sub-threshold rewarding effect of cocaine at adulthood, despite an absence of accompanying serotonergic and dopaminergic neurotoxicity.


Stomatin-like protein 2 (SLP2) regulates the proliferation and invasion of trophoblast cells by modulating mitochondrial functions.
Stomatin-like protein 2 (SLP2) is highly expressed in human first trimester trophoblast cells, but its functions in placental morpho-physiology remain unknown. This study aimed to determine the role of SLP2 in the proliferation and invasion of human first trimester trophoblast cells. Immunofluorescence was used to determine the expression and localization of SLP2 in normal and miscarriage human first trimester placenta. Western blot was used to determine the expression of SLP2, PCNA, Cyclin D3, N-cadherin, Vimentin, PGC1α and PPARα in HTR-8/SVneo cells. SLP2 was knocked down in the HTR-8/SVneo cells by using si-Slp2. Wound healing and migration assays were used to determine the effect of SLP2 knockdown on the migration and invasion in the HTR-8/SVneo cells. Mitochondrial membrane potential, reactive oxygen species (ROS), ATP production and biogenesis were measured to assess the effects of SLP2 knockdown on mitochondrial functions. SLP2 was strongly expressed in the cytotrophoblasts (CTB), syncytiotrophoblast (STB) and extravillous trophoblasts (EVT) of normal pregnancy placenta as compared to miscarriage placenta. SLP2 was highly expressed in the invasive EVT cell lines, HTR-8/SVneo and HPT-8 compared to the CTB cell line JAR. Knockdown of SLP2 significantly inhibited the migration and invasion of HTR-8/SVneo cells and placental villous explants, and repressed mitochondrial biogenesis and functions in HTR-8/SVneo cells. Silencing of SLP2 inhibited the proliferation, migration and invasion of HTR-8/SVneo cells via the impairment of mitochondrial functions. This indicates that the downregulation of SLP2 in miscarriage placenta could be part of the pathogenesis and pathophysiology of the disease.


Management of the pediatric OSAS: what about simultaneously expand the maxilla and advance the mandible? A retrospective non-randomized controlled cohort study.
This retrospective non-randomized controlled cohort study aimed to evaluate the efficiency of simultaneous maxillary expansion and mandibular advancement for the management of pediatric OSAS. The sample was composed of 94 children treated with an innovative orthopedic device to correct a Class II malocclusion associated with an OSAS. Polysomnographic recordings were performed before and after the treatment. We also included a group of 113 age-matched control patients who had the same pathologies, but who did not receive the orthopedic treatment at the time they undergone polysomnographic exams. Statistical tests evaluated the significance of the evolution of these data, both in treated and untreated control patients. After nine months (±3 months) of treatment, respiratory OSAS symptoms significantly improved: the AHI significantly decreased as it became inferior to the pathological threshold (<1) for 53% of the treated patients' sample, with a greater proportion within the youngest age group (63%). Only two patients still presented a moderate OSAS after treatment, with an AHI slightly superior to 5. This positive evolution of OSAS respiratory symptoms was not observed within the control group, highlighting the real impact of the orthopedic treatment over the children's natural growth. However, sleep remained fragmented following the treatment. This study confirmed that simultaneous maxillary expansion and mandibular advancement induced a modification of the maxilla-mandibular anatomy, helping in the significant improvement of the respiratory OSAS symptoms. Then, considering these preliminary results, pediatric OSAS can be managed with this new orthopedic strategy, especially if it is performed early.


Cembrane diterpenoids: Chemistry and pharmacological activities.
Cembrane diterpenoids (cembranoids), characterized by a 14-membered carbon ring and wide variety of functional groups, found in marine and terrestrial organisms. Many studies have shown that cembrane diterpenoids have cytotoxic and anti-inflammatory activities and are widely used in the development of new drugs. This review covered publications from 2011 to 2022 and classified the cembrane-type diterpenoids into isopropyl (ene) type, γ-lactone or unsaturated five-membered ring, δ-lactone or unsaturated six-membered ring, ε-lactone or unsaturated seven-membered ring, and other cembrane diterpenes. In addition, the biological activity and structure-activity relationship were summarized. This will provide guidance for new cembrane-type diterpenes as lead compounds to explore their potential application for treating cancer and inflammatory diseases.


Amino acid transporter Asc-1 (SLC7A10) expression is altered in basal ganglia in experimental Parkinsonism and L-dopa-induced dyskinesia model mice.
In Parkinson's disease (PD), a decrease in dopamine levels in the striatum causes abnormal circuit activity in the basal ganglia, resulting in increased output via the substantia nigra pars reticulata (SNr). A characteristic feature of glutamatergic synaptic transmission in the basal ganglia circuitry under conditions of dopamine depletion is enhanced synaptic activity of NMDA receptors. However, the cause of this NMDA receptor hyperactivity is not fully understood. We focused on Asc-1 (SLC7A10), an alanine-serine-cysteine transporter, as one of the factors that regulate NMDA receptor activity by modulating D-serine and glycine concentration in synaptic clefts. We generated PD model mice by injection of 6-hydroxydopamine into the unilateral medial forebrain bundle and analyzed the expression level of Asc-1 mRNA in the nuclei of basal ganglia (the external segment of the globus pallidus (GPe), subthalamic nucleus (STN), and SNr) compared to control mice. Each nucleus was dissected using laser microdissection, and RNA was extracted and quantified by quantitative PCR. Asc-1 mRNA expression was significantly higher in the GPe and lower in the SNr under the PD state than that in control naïve mice. The STN showed no change in Asc-1 mRNA expression. We further modeled L-dopa-induced dyskinesia by administering L-dopa continuously for 14 days to the PD model mice and found that Asc-1 mRNA expression in the GPe and SNr became close to that of control mice, regardless of the presence of abnormal involuntary movements. The present study revealed that Asc-1 mRNA expression is differentially regulated in the basal ganglionic nuclei in response to striatal dopamine concentration (depleted or replenished) and suggests that Asc-1 can be a therapeutic target for the amelioration of motor symptoms of PD.


An EMG-based, muscle driven forward simulation of single support phase of gait.
This paper describes the process used to generate lower limb kinematics during single limb stance phase of gait, using musculoskeletal modelling, muscle driven forward simulation and gradient based optimisation techniques (including design of experiment techniques). Initial inputs to the forward simulation process were the normalised quantified muscle activation patterns of 22 muscles, and the initial segmental configuration (both angles and angular velocity) derived from Winter (The biomechanics and motor control of human gait, 1987, University of Waterloo Press, pp. 1-72). Two distinct musculoskeletal models (one including 6 DOF, the other 7 DOF) were defined and a muscle driven forward simulation was implemented.A series of optimisation sequences then were executed to modify the muscle activation patterns and initial segmental configuration, until the system output of the forward simulation approximated the angle data reported by. The accuracy and effectiveness of the analysis sequence proposed and the model response obtained using two distinct musculoskeletal models were verified and analysed with respect to the kinesiology of normal walking.


Prognostic Significance of Flail Mitral Leaflet in Transcatheter Edge-to-Edge Repair for Primary Mitral Regurgitation.
Despite the growing experience with MitraClip in the broad spectrum of mitral regurgitation (MR), limited data are available regarding the independent prognostic role on survival of different mitral regurgitation etiology subtypes. We sought to evaluate the impact of flail leaflet etiology in a large series of patients with primary MR (PMR) who underwent MitraClip treatment. The study included 588 patients with significant PMR from the multicenter GIOTTO (Italian Society of Interventional Cardiology [GIse] registry Of Transcatheter treatment of mitral valve regurgitaTiOn), stratified into 2 groups according to MR etiology: flail+ (n = 300) and flail- (n = 288). The primary end point was a composite of cardiac death and first rehospitalization for heart failure (HF). To account for the baseline differences, patients were propensity score-matched 1:1. Flail leaflet etiology was present in about a half of the patients. Acute technical success was achieved in 98% of the overall cohort, with no significant differences between the study groups (p = 0.789). At the 2-year Kaplan-Meier analysis, the primary end point occurred in 13% of flail+ patients compared with 23% in flail- (p = 0.009). The flail+ group presented lower rates of both cardiac death and rehospitalization for HF, whereas a similar overall death rate was observed between the groups. A multivariate Cox regression analysis identified flail leaflet etiology as an independent predictor of favorable outcome in terms of the primary end point (hazard ratio 0.141, 95% confidence interval 0.049 to 0.401, p <0.001). After propensity score matching, flail+ patients had confirmed lower rates of cardiac mortality and rehospitalization for HF but similar rates of overall death. In conclusion, flail leaflet-related etiology was common in patients with PMR who underwent MitraClip treatment and was an independent predictor of midterm favorable clinical outcomes.


Treatment of double carcinoma of the esophagus and lung.
We report four cases of double carcinoma of the esophagus and the lung. Case 1: a patient with synchronous double carcinoma of the esophagus and the lung underwent chemoradiotherapy (CRT) because of respiratory dysfunction. Case 2: a patient who was diagnosed with esophageal carcinoma after the surgery for lung carcinoma underwent CRT because of respiratory dysfunction. Case 3: a patient with synchronous double carcinoma underwent a two-stage operation. Case 4: a patient with synchronous double carcinoma underwent CRT at another hospital. To further treat the patients, we chose a two-stage operation. CRT is believed to be a feasible treatment in inoperable patients because patients 1 and 2 are alive 28 and 21 months after CRT, respectively. A two-stage operation is considered a suitably safe surgical procedure because no fatal postoperative complications occurred in cases 3 and 4.


The incidence and prevalence of early-onset scoliosis: a regional multicenter epidemiological study.
Despite the many advances in understanding and treating early-onset scoliosis, the incidence and prevalence of this disease in the population remains unknown. Such knowledge is important for guiding clinical practice, directing research and raising awareness. To identify the incidence and prevalence of early-onset scoliosis, including all categories, within the population. A regional multicenter retrospective cohort study PATIENT SAMPLE: All patients diagnosed with early-onset scoliosis in the region, who were followed-up between January 2000 and December 2020. Frequency distributions for early-onset scoliosis subtypes, demographics, curve patterns and progression statuses. Relevant population data, for children under 10 years old, was extracted from the official government census for the years 2000 to 2020. Identification of cases was carried out by pediatricians at mandatory government funded regular child wellness check-up visits. Outpatient records were reviewed for all included patients, with extraction of the following: Medical identifier, date of birth, date of initial visit, sex, primary diagnosis, length of follow-up, curve pattern, initial cobb angle, and final cobb angle. Incidence and prevalence values were calculated using population figures and case numbers. Kaplan-Meier survival analysis and Log-rank testing was performed on curve progression data. The regional population of children, under the age of 10 years, included a total of 2,295,929 children, 1,170,149 (51.0%) males and 1,125,780 (49.0%) females, between the years 2000 and 2020. Early-onset scoliosis cases followed within the same timeframe, totaled 469 patients, 227 (48.4%) males and 242 (51.6%) females. The annual incidence of early-onset scoliosis was found to be 0.019% (95% CI: 0.015%-0.023%), and the prevalence was 0.077% (95% CI: 0.059%-0.096%). The most common age at first presentation was 6 years old. More females (51.6%) than males (48.4%) were observed, and more left-sided curves (54.2%) than right-sided curves (45.8%) were encountered, with the majority being single thoracic curves (38.2%). Scoliosis curves did not progress in 44.3% of cases, while they progressed in 38% of them. Follow-up was inadequate to determine progression status in 17.7% of cases. Neuromuscular etiologies were the most common, at 40.1%, of which 83.5% had cerebral palsy. Based on the regional population included in this study, the annual incidence of early-onset scoliosis in children under 10 years old was calculated to be 0.019%, while the prevalence of early-onset scoliosis in children under 10 years old was found to be 0.077%.


Optimal foraging: The responses of Peromyscus leucopus to experimental changes in processing time and hunger.
Food density, degree of hunger prior to foraging, and food processing difficulty were varied in order to determine their effects on the diet diversity of captive Peromyscus leucopus foraging for buried seeds. No relationship was found between diet diversity and food density. However, diet diversity exhibited a significantly positive relationship with hunger, and a significantly negative relationship with seed processing time. These results strongly support optimal foraging theory.


Using the animal to the last bit: Consumer preferences for different beef cuts.
Meat is expensive to produce, making it is essential to understand the importance consumers pay to different meat cuts. Previous research on consumers' meat choices has mainly focused on meat species, while consumer preferences for meat cuts has so far only received limited interest. The aim of this study is to shed some light into this relatively unexplored area by answering four research questions. First, this study intends to show the relative importance meat cuts play in relation to other extrinsic product attributes. Secondly, this paper looks into differences in choice criteria between regular and special occasions. Third, consumer segments that differ in their preferences and beef purchase are identified, and, finally, the meat purchase portfolios of these segments are revealed. A stated preference methodology of a discrete choice experiment with cut-specific prices covering several meat cuts simultaneously is proposed to answer the research questions. The sample consists of 1500 respondents representative of the Italian population in terms of age, gender and geographic location The results shows that meat cut is the most important factor when choosing bovine meat followed by quality certification (origin), production technique, the type of breed and price. In terms of consumption occasions, we observe significantly lower price sensitivity for marbled steaks and cutlets for special occasions compared to normal occasions. Segmentation analysis shows that while the choices of two segments (comprising about 40% of the sample) are mostly driven by extrinsic product attributes, the remaining segments are mostly driven by meat cuts. These varying preferences are also reflected in the purchase portfolios of the different segments, while less variability is detected from a socio-demographic perspective.


Effect of failed defibrillation shocks on electrogram amplitude in a nonintegrated transvenous defibrillation lead system.
Concern has been raised regarding the ability of a nonthoracotomy integrated lead system to redetect ventricular fibrillation following failed defibrillation shocks due to diminution in postshock intracardiac electrogram amplitude. Whether such a problem could occur with other lead systems is not known, leading to uncertainty regarding a potential ongoing risk of sudden cardiac death in some patients despite implantable cardioverter-defibrillator therapy. To investigate this problem, we measured the amplitude of 10 consecutive ventricular fibrillation endocardial electrograms immediately before and immediately after failed defibrillation shocks in 15 patients at the time of implantation of a nonintegrated, transvenous, pace/sense/defibrillation lead. Overall, mean electrogram amplitude decreased 21%, from 10.7 +/- 4.6 mV before to 8.5 +/- 4.9 mV immediately after failed defibrillation shocks. The change in electrogram amplitude postshock was directly related to shock energy (r = 0.85, p < 0.0005), but shock waveform had no differential effect. Electrogram amplitude could also increase after failed shocks, particularly following those of low energy. No failures to redetect ventricular fibrillation were found. Thus, intracardiac electrogram amplitude is reduced following failed defibrillation shocks in this nonintegrated lead system, but by an amount less than that previously reported for some integrated lead systems. Our findings reveal that failed low energy defibrillation shocks are likely to result in less diminution in postshock intracardiac electrogram amplitude than high energy shocks, and that the postshock amplitude may even increase after some failed shocks.


Resampling probability values for measures of ordinal variation and consensus.
Resampling permutation procedures provide good approximations to exact permutation procedures and are therefore the preferred alternative when large samples render exact tests intractable. Resampling permutation procedures are described for three measures of variation and the three corresponding measures of consensus among ordered categories.


Development of accurate binding affinity predictions of novel renin inhibitors through molecular docking studies.
In this study, an attempt was made to explore a possible correlation between different docking scoring functions (Glide InducedFit docking score and GOLD's GoldScore and ChemScore) and binding energy values of a set of renin inhibitors, using linear regression model. The renin inhibitors under study are characterized by known bound to the receptor crystal structures possessing a great variety of pharmacophore groups and a wide range of IC₅₀ values. Linear regression models were derived to relate the docking scoring function and pIC₅₀ values of renin inhibitors under study. The developed derived models are seeking to be helpful for the rational design of new, more potent renin inhibitors.


Impact of germinal center-associated nuclear protein polymorphisms on breast cancer risk and prognosis in a Japanese population.
Germinal center-associated nuclear protein (GANP) is a phosphoprotein involved in mRNA export and regulation of DNA recombination. Although GANP expression in human breast cancer tissue is associated with breast cancer prognosis, the association between the genetic background of GANP and susceptibility and prognosis of breast cancer is unclear. We selected 694 breast cancer cases and 1376 age- and menopausal status-matched non-cancer controls from the Hospitable-based Epidemiologic Research Program, conducted at Aichi Cancer Center between 2001 and 2005. We evaluated the impact of two polymorphisms at the GANP locus (rs2839178 and rs11702450) on the susceptibility and prognosis of breast cancer. Reference alleles were defined as the A allele for rs2839178 and G allele for rs11702450. The GG genotype of rs2839178 was statistically significantly associated with breast cancer risk (odds ratio [OR] 0.48, 95% confidence interval [CI] 0.30-0.76, P = 0.002). In prognostic analysis, compared to those with AA genotype of rs2839178, patients with AG or GG genotypes had longer disease-free survival (DFS) (hazard ratio [HR] 0.71, 95% CI 0.49-1.04 and HR 0.42, 95% CI 013-1.42, respectively, P for trend = 0.04). eQTL analysis indicated that association with rs2839178 can be explained by the effect of rs2839173 on expression of GANP/MCM3AP. The G allele of rs2839178 at the GANP locus was significantly associated with reduced breast cancer risk and longer DFS in breast cancer patients, showing a consistent direction in the association between susceptibility and clinical outcome. GANP is, therefore, important for the occurrence and progression of sporadic breast cancer.


The effect of a prior eccentric lowering phase on concentric neuromechanics during multiple joint resistance exercise in older adults.
Aging involves a marked decline in physical function and especially muscle power. Thus, optimal resistance exercise (RE) to improve muscle power is required for exercise prescription. An eccentric lowering phase immediately before a concentric lift (ECC-CON) may augment concentric power production, due to various proposed mechanisms (e.g., elastic recoil, pre-activation, stretch reflex, contractile history), when compared with a concentric contraction alone (CON-Only). This study compared the effect of a prior eccentric lowering phase on older adult concentric power performance (ECC-CON vs. CON-Only) during a common multiple joint isoinertial RE (i.e., leg press) with a range of loads. Twelve healthy older adult males completed two measurement sessions, consisting of ECC-CON and CON-Only contractions, performed in a counterbalanced order using 20-80% of one repetition maximum [% 1RM] loads on an instrumented isoinertial leg press dynamometer that measured power, force, and velocity. Muscle activation was assessed with surface electromyography (sEMG). For mean power ECC-CON>CON-Only, with a pronounced effect of load on the augmentation of power by ECC-CON (+19 to +55%, 35-80% 1RM, all p < 0.032). Similarly, for mean velocity ECC-CON>CON-Only, especially as load increased (+15 to 54%, 20-80% 1RM, all p < 0.005), but mean force showed more modest benefits of ECC-CON (+9 to 14%, 50-80% 1RM, all p < 0.05). In contrast, peak power and velocity were similar for ECC-CON and CON-Only with all loads. Knee and hip extensor sEMG were similar for both types of contractions. In conclusion, ECC-CON contractions produced greater power, and velocity performance in older adults than CON-Only and may provide a superior stimulus for chronic power development.


Endothelial cell compatibility of clarithromycin for intravenous use.
Tolerance of intravenously applied clarithromycin has been tested on marginal ear veins of rabbits. Use of human umbilical venous endothelial cells (HUVEC) for testing antibiotic solutions for intravenous compatibility provides a valuable alternate model. In order to evaluate the effect of clarithromycin on intracellular purines, reflecting cell viability, energy production, signal transduction and DNA/RNA synthesis, intracellular adenosine 5' triphosphate (ATP), adenosine 5' diphosphate (ADP), guanosine 5' triphosphate (GTP), and guanosine 5' diphosphate (GDP) levels were measured by means of high performance liquid chromatography (HPLC). Incubation of cells with 2 mg/mL clarithromycin resulted in a rapid decrease of the intracellular ATP from 12.6 +/- 1.1 to 8.87 +/- 0.82 nmol/million cells or 1.5 +/- 0.6 nmol/million cells, after 20 or 60 min, respectively. In addition, ADP was extensively depleted. Purine nucleotide profiles were markedly different following exposure to 1 mg/mL clarithromycin. There was no significant decline of intracellular high energy phosphate levels after 20 min. These results show that clarithromycin has a better endothelial compatibility if diluted to a final concentration of 1 mg/mL. These data are in line with our clinical observations that the occurrence of phlebitis could be minimized by diluting the manufacturers' preparation of clarithromycin to 1 mg/mL.


Expert Recommendations on Cardiac Computed Tomography for Planning Transcatheter Left Atrial Appendage Occlusion.
Transcatheter left atrial appendage occlusion is an increasingly used alternative to oral anticoagulation in selected patients with atrial fibrillation. Pre-procedural imaging is a prerequisite to a successful intervention, with transesophageal echocardiography as the current gold standard. However, cardiac computed tomography offers improved imaging with high-quality multiplanar and 3-dimensional reconstructed images. Nevertheless, the lack of a standardized imaging protocol has slowed the adoption of cardiac computed tomography into clinical practice. On the basis of current research and expert consensus, this paper provides a protocol for the preparation, acquisition, and interpretation of cardiac computed tomographic imaging in pre-procedural planning of left atrial appendage occlusion.


Left-Sided Amyand Hernia: Case Report and Review of the Literature.
Left-sided Amyand hernia is a rare condition that requires a high degree of clinical suspicion to correctly diagnose.


Scaling of the fast-start escape response of juvenile bluegills.
Morphology, size and physiological properties change markedly across fish ontogeny. This impacts locomotor performance and organismal fitness, although the effects are unpredictable due to the complexity of phenotype-function relationships. Morphological and behavioral changes with growth are often paralleled by changes in habitat use, diet and vulnerability to predators. Our goal was to quantify the changes in external morphology and escape performance throughout post-larval development in bluegill sunfish (Lepomis macrochirus), and place these changes in context with known changes in habitat use in the field. Development into adult ecomorphs is associated with phenotypic plasticity in response to habitat-specific differences in diet. On this basis, we hypothesized that variation in morphology and performance would increase during bluegill ontogeny as diversification of adult ecomorphs occurred. However, we found that variation in phenotype and escape performance decreased during early ontogeny. Phenotypic variation expanded later in development, after fish gained access to the variety of habitats and food types that may favor phenotypic plasticity. Performance is predicted to decline with growth due to the differential scaling of inertia and cross-sectional area, a major determinant of muscle force. In contrast, acceleration increased with size, and velocity and acceleration increased more rapidly with size than predicted. Post-larval maturation in bluegill featured a shift to a deeper body shape, and an increase in the relative size of the anal and caudal fins. This was a likely factor in the deviation of escape performance scaling relationships from predictions based on geometric similarity.


A mitochondrial gene involved in cytochrome c maturation (ccmC) is expressed as a precursor with a long NH2-terminal extension in sugar beet.
Extensive genome rearrangement is one of the major mechanisms of angiosperm mitochondrial evolution. As a by-product, some angiosperm mitochondrial genes exhibit divergent organization, but not all of these genes have been fully characterized. Sugar beet ccmC, which plays an important role in cytochrome c maturation, harbors a unique extended NH(2) terminal region of 277 amino acid residues (N-extension) instead of a conserved translational initiation codon. The 5' termini of two major RNA species were determined by primer extension analysis, which revealed that the larger transcript covered the entire N-extension. Nucleotide sequencing of the cDNA revealed that a total of 31 C-to-U RNA editing events occurred in the N-extension and the ccmC-homologous region (ccmC-core region), resulting in improvement of amino acid sequence conservation. Antiserum was raised against a synthetic peptide corresponding to the ccmC-core region and was used for protein gel blot analysis of sugar beet and radish mitochondrial proteins. The detected 29.5-kDa signal band is shared by sugar beet and radish. Two additional larger signal bands are exclusively detected from sugar beet. The largest signal band is also detected by anti-N-extension antiserum. Our results indicate that sugar beet ccmC is translated as a long precursor with N-extension.


The effect of two new alpha-glucosidase inhibitors on metabolic responses to a mixed meal in normal volunteers.
1. alpha-Glucosidase inhibitors delay carbohydrate absorption and have been proposed as adjunctive therapy for diabetes mellitus. 2. To determine the effects of two new alpha-glucosidase inhibitors, Bay-m-1099 and Bay-o-1248, on meal carbohydrate and lipid tolerance, plasma glucose, insulin and triglyceride levels were measured at 15-60 min intervals over 12 h after ingestion of a standard breakfast, lunch and dinner of identical composition in 31 normal volunteers. 3. The volunteers were randomized to receive either Bay-m-1099 (50 or 25 mg) or placebo prior to each meal, or the single administration of Bay-o-1248 (20 or 10 mg) or placebo prior to breakfast. 4. Only Bay-m-1099 at the 50 mg dose reduced significantly the postprandial increase in plasma insulin levels after each meal when compared with placebo (25, 36, 54% at breakfast, lunch, and dinner, respectively; P less than 0.05). Both drugs were well tolerated, with side effects limited to complaints of flatulence. 5. Thus, with the dosage schedule employed, Bay-m-1099, but not Bay-o-1248, significantly reduced postprandial increments in plasma insulin.


Hypoxia enhances gene expression of inducible nitric oxide synthase and matrix metalloproteinase-9 in ras/myc-transformed serum-free mouse embryo cells under simulated inflammatory and infectious conditions.
Ras/myc-transformed serum-free mouse embryo (ras/myc SFME) cells were treated with interferon-gamma (IFN-gamma; 100 U/ml) and/or lipopolysaccharide (LPS; 0.5 microg/ml) for 24 h to simulate inflammatory and infectious conditions and investigate their effects on the expression of inducible nitric oxide synthase (iNOS) mRNA, nitric oxide (NO) and matrix metalloproteinase-9 (MMP-9). In addition, aminoguanidine (AG; 1 mM), a NOS inhibitor, S-nitroso-N-acetyl-DL-penicillamine (SNAP; 10-200 microM), an NO donor or (+/-)-N-[(E)-4-ethyl-2-[(Z)-hydroxyimino]-5-nitro-3-hexene-1-yl]-3-pyridine carboxamide (NOR4; 10-200 microM), an NO donor, were added to analyze possible associations of NO with MMP-9. Tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 were also measured to analyze possible relationships of NO with the MMP-9/TIMP balance. Furthermore, the cells were treated with 1% O2 under the simulated inflammatory and infectious conditions and the mRNA expressions of iNOS and MMP-9 were analyzed to investigate the possible effects of hypoxia on the expression of genes involved in tumor malignant progression and distant metastasis. Co-treatment with IFN-gamma and LPS increased the expression levels of iNOS mRNA, NO and MMP-9, but NO may not be directly associated with MMP-9 or the MMP-9/TIMP balance. Treatment with 1% O2 markedly increased the gene expression levels of iNOS and MMP-9, indicating that ras/myc SFME cells alter the expression levels of tumor-associated genes and possibly enhance their malignancy as cancer cells under inflammatory, infectious and hypoxic conditions.


Barriers to influenza vaccination among pregnant women.
Despite pregnant women's increased morbidity and mortality from influenza, vaccination rates remain low. This study intended to evaluate barriers to pregnant women's uptake of influenza vaccine. A survey was designed that assessed participant demographics, knowledge, beliefs, attitudes, and general experiences with seasonal and 2009 novel H1N1 influenza. Associations between patient characteristics and vaccine uptake were then assessed. 88 women completed the survey. Women who correctly answered >75% of knowledge questions regarding influenza were significantly more likely to accept the influenza vaccine (seasonal: p=0.04, H1N1: p<0.01). Conversely, patients who declined the vaccine were more likely to hold false beliefs, such as perceiving that the vaccine was not protective (seasonal: p<0.01, H1N1: p<.01) and that they were not at risk for influenza (seasonal: p< 0.01). The reasons for influenza vaccine declination in pregnant patients include lower levels of knowledge and unfavorable attitudes regarding the safety and efficacy of the vaccine, and suggest the importance of education as a tool to improve vaccination uptake.


8-Hy-droxy-6-meth-oxy-7-(3-methyl-but-2-en-yloxy)coumarin (capensine).
The title coumarin derivative, C15H16O5, was isolated from the roots of Sophora japonica. The coumarin (2H-chromen-2-one) fragment is almost planar, with an r.m.s. deviation of 0.0356 Å. The carbon atom of the meth-oxy substituent is coplanar with the benzo-pyran oxa-heterocycle. The 3-methyl-but-2-en-yloxy group is disordered over two sets of sites with occupation factors of 0.920 (3) and 0.080 (3). In the crystal, mol-ecules are linked by O-H⋯O and C-H⋯O hydrogen bonds into chains propagating along the [101] direction.


Body Mass Index and Risk for Mental Stress Induced Ischemia in Coronary Artery Disease.
Acute emotionally reactive mental stress (MS) can provoke prognostically relevant deficits in cardiac function and myocardial perfusion, and chronic inflammation increases risk for this ischemic phenomenon. We have described parasympathetic withdrawal and generation of inflammatory factors in MS. Adiposity is also associated with elevated markers of chronic inflammation. High body mass index (BMI) is frequently used as a surrogate for assessment of excess adiposity, and associated with traditional CAD risk factors, and CAD mortality. BMI is also associated with autonomic dysregulation, adipose tissue derived proinflammatory cytokines, which are also attendant to emotion provoked myocardial ischemia. Thus, we sought to determine if body mass index (BMI) contributes to risk of developing myocardial ischemia provoked by mental stress. We performed a prospective interventional study in a cohort of 161 patients with stable CAD. They completed an assessment of myocardial blood flow with single photon emission computed tomography (SPECT) simultaneously during 2 conditions: laboratory mental stress and at rest. Multivariate logistic regression determined the independent contribution of BMI to the occurrence of mental-stress induced ischemia. Mean age was 65.6 ±9.0 years; 87.0% had a history of hypertension, and 28.6% had diabetes. Mean BMI was 30.4 ± 4.7. Prevalence of mental stress ischemia was 39.8%. BMI was an independent predictor of mental stress ischemia, OR=1.10, 95% CI [1.01-1.18] for one-point increase in BMI and OR=1.53, 95% CI [1.06-2.21] for a 4.7 point increase in BMI (one standard deviation beyond the cohort BMI mean), p=0.025 for all. These data suggest that BMI may serve as an independent risk marker for mental stress ischemia. The factors attendant with greater BMI, which include autonomic dysregulation and inflammation, may represent pathways by which high BMI contribute to this risk and serve as a conceptual construct to replicate these findings in larger CAD populations.