Common polymorphisms in the promoter of the visfatin gene (PBEF1) influence plasma insulin levels in a French-Canadian population

The adipokine visfatin (PBEF1) exhibits insulin-mimetic effects and correlates strongly with visceral adiposity. We sequenced visfatin gene exons and 1,480 bp of the promoter in 23 individuals, including 18 individuals from the Quebec Family Study (QFS) with varying degrees of abdominal visceral fat, assessed by computed tomography, and 5 individuals from the Saguenay-Lac-Saint-Jean region of Québec. We identified a synonymous polymorphism in exon 7 (SER301SER) but no nonsynonymous mutations. We observed an additional 10 polymorphisms, including 5 intronic, 4 within the promoter, and 1 within the 3' untranslated region. Further promoter sequencing (816 bp) identified five additional single nucleotide polymorphisms (SNPs) in the QFS population. To investigate the role of visfatin gene variants in obesity-related phenotypes, we genotyped a total of 13 SNPs in the promoter region of the gene. From these, we analyzed the seven common SNPs in the QFS sample (918 participants from 208 families). A significant association was found between two SNPs (rs9770242 and rs1319501), in perfect linkage disequilibrium, and fasting insulin levels (P = 0.002). These SNPs were also associated with fasting glucose (P 相似文献   

Incidence and outcomes of spinal cord injury clinical syndromes

BACKGROUND/OBJECTIVE: To examine and compare demographics and functional outcomes for individuals with spinal cord injury (SCI) clinical syndromes, including central cord (CCS), Brown-Sequard (BSS), anterior cord (ACS), posterior cord (PCS), cauda equina (CES), and conus medullaris (CMS). DESIGN: Retrospective review. SETTING: Tertiary care, level 1 trauma center inpatient rehabilitation unit. PARTICIPANTS: Eight hundred thirty-nine consecutive admissions with acute SCIs. MAIN OUTCOMES MEASURES: Functional independence measure (FIM), FIM subgroups (motor, self-care, sphincter control), length of stay (LOS), and discharge disposition. RESULTS: One hundred seventy-five patients (20.9%) were diagnosed with SCI clinical syndromes. CCS was the most common (44.0%), followed by CES (25.1%) and BSS (17.1%). Significant differences (P < or = 0.01) were found between groups with regard to age, race, etiology, total admission FIM, motor admission FIM, self-care admission and discharge FIM, and LOS. Statistical analysis between tetraplegic BSS and CCS revealed significant differences (P < or = 0.01) with respect to age (39.7 vs 53.2 years) and a trend toward significance (P < or = 0.05) with regard to self-care admission and discharge FIM. No significant differences (P < or = 0.01) were found when comparing CMS to CES. CONCLUSIONS: SCI clinical syndromes represent a significant proportion of admissions to acute SCI rehabilitation, with CCS presenting most commonly and representing the oldest age group with the lowest admission functional level of all SCI clinical syndromes. Patients with cervical BSS seem to achieve higher functional improvement by discharge compared with patients with CCS. Patients with CMS and CES exhibit similar functional outcomes. Patients with ACS and PCS show functional gains with inpatient rehabilitation, with patients with ACS displaying the longest LOS of the SCI clinical syndromes. These findings have important implications for the overall management and outcome of patients with SCI.     

The regulation of cholecystokinin release from rat caudatoputamen in vitro

Cholecystokinin (CCK) is one of the most abundant neuropeptides in the rat caudatoputamen (cp). CCK perikarya innervating cp are thought to originate in neurons in the claustrum/piriform cortex area of the amygdala. Previous studies on the release of CCK from cp have focused on the influence of dopamine agonists. The present study has examined the influence of other neuroactive substances on the release of CCK. The release of CCK from rat cp slices in vitro stimulated by potassium was quantitated with a specific CCK radioimmunoassay. This potassium-stimulated release of CCK was Ca2+-dependent. Maximal stimulation of CCK release was observed at 55 mM potassium. Several lines of evidence indicate that the release of CCK from cp is inhibited by some other substance (or substances) released by a Ca2+-dependent mechanism from cp along with CCK. Release media from cerebral cortex or cp (called 'conditioned media' or CM) inhibits the release of CCK from fresh slices of cp but not from cerebral cortex. The release of dopamine from cp is unaffected by CM from cortex or cp. The identity of the substance in CM which inhibits CCK release from cp is still under investigation, though it appears not to be CCK, dopamine, acetylcholine, somatostatin, leucine enkephalin or gamma-aminobutyric acid.     

Stress-induced interleukin-6 release in mice is mast cell-dependent and more pronounced in Apolipoprotein E knockout mice

OBJECTIVE: Interleukin-6 (IL-6) is elevated in the serum of patients with coronary artery disease (CAD) and acute coronary syndromes (ACS). Intracoronary release of IL-6 was reported in ACS that can also be triggered by acute stress. In rats, acute restraint stress increases serum IL-6 and histamine, both of which may derive from mast cells. The current study was carried out in order to determine any possible difference in stress-induced IL-6 release in atherosclerotic mice and the contribution of mast cells, corticotropin-releasing hormone (CRH) and urocortin (Ucn). METHODS: C57BL/6J, W/W(v) mast cell-deficient, Apolipoprotein E (ApoE) and CRH knockout (k/o) mice were stressed in plexiglass restraint chambers for 15 to 120 min. Serum corticosterone and IL-6 levels were measured. Some C57BL and ApoE k/o mice were pretreated with either the mast cell stabilizer disodium cromoglycate (cromolyn) or the peptide CRH receptor (CRH-R) antagonist Astressin. Cardiac mast cell activation was studied in both C57BL and ApoE k/o mice using light microscopy. RESULTS: Acute stress increased serum IL-6 in mice, an effect much greater in ApoE k/o atherosclerotic mice. Stress-induced IL-6 release was absent in W/W(v) mast cell-deficient mice and it was partially inhibited by cromolyn in C57BL and ApoE mice. Mast cells were found adjacent to atherosclerotic vessels in ApoE k/o mice and were activated after stress. CRH k/o mice released more IL-6 in response to stress than their wild types, but Astressin significantly inhibited IL-6 release. Stress-induced IL-6 release may, therefore, be at least partly due to peripheral Ucn and/or CRH, with Ucn possibly overcompensation for CRH deficiency. CONCLUSION: The present findings indicate that acute stress leads to mast cell-dependent serum IL-6 increase that may help explain stress-related coronary inflammation.     

Immediate and early percutaneous coronary intervention in very high‐risk and high‐risk non‐ST segment elevation myocardial infarction patients

BackgroundThe European Society of Cardiology (ESC) guidelines for the management of acute coronary syndromes in patients presenting without persistent ST‐segment elevation (non‐ST‐segment elevation myocardial infarction [NSTEMI]) has recommended immediate (<2 h) percutaneous coronary intervention (PCI) in very‐high risk patients and early (<24 h) PCI in high‐risk patients.HypothesisTo examine the ESC NSTEMI guidelines adherence in a nationwide survey in Israel using the Acute Coronary Syndrome Israeli Survey (ACSIS). We hypothesized that adherence to the guidlines'' recommnded PCI timing in NSTEMI pateints will be inadequate, partly due to the inconsistent evidence regarding its effect on clinical outcomes.MethodsAll NSTEMI patients who underwent PCI during the ACSIS surveys in 2016 and 2018 were included in the analysis.ResultsOut of 1793 NSTEMI patients, 1643 (92%) patients underwent PCI, and door to balloon time was documented in 1078 of them. One hundred and fifty‐six (14.5%) patients and 922 (85.5%) patients were defined as very high‐risk and high‐risk NSTEMI patients, respectively. Of the very high‐risk NSTEMI patients, only 10 (6.4%) underwent immediate coronary angiography, and 50 (32.1%) underwent early coronary angiography. Acute heart failure 139 (89.1%) was the main reason for including NSTEMI patients in the very high‐risk category. Of the high‐risk patients, early coronary angiography was performed in only 405 (43.9%) patients. Patients in whom coronary angiography was postponed were older and had more comorbidities.ConclusionsDespite guidelines recommendations for immediate and early PCI in very high‐risk and high‐risk NSTEMI patients, respectively, most patients do not undergo immediate or early PCI according to contemporary guidelines. Further studies are needed to better understand the reasons for guidelines'' nonadherence in those high‐risk patients.     

Plasma and memory antibody responses to Gamma SARS-CoV-2 provide limited cross-protection to other variants

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a global problem in part because of the emergence of variants of concern that evade neutralization by antibodies elicited by prior infection or vaccination. Here we report on human neutralizing antibody and memory responses to the Gamma variant in a cohort of hospitalized individuals. Plasma from infected individuals potently neutralized viruses pseudotyped with Gamma SARS-CoV-2 spike protein, but neutralizing activity against Wuhan-Hu-1-1, Beta, Delta, or Omicron was significantly lower. Monoclonal antibodies from memory B cells also neutralized Gamma and Beta pseudoviruses more effectively than Wuhan-Hu-1. 69% and 34% of Gamma-neutralizing antibodies failed to neutralize Delta or Wuhan-Hu-1. Although Class 1 and 2 antibodies dominate the response to Wuhan-Hu-1 or Beta, 54% of antibodies elicited by Gamma infection recognized Class 3 epitopes. The results have implications for variant-specific vaccines and infections, suggesting that exposure to variants generally provides more limited protection to other variants.     

Early detection of pleuro‐pulmonary tuberculosis by bedside lung ultrasound: A case report and review of literature

We present a case in which lung ultrasound (LUS) was relevant to reach an early diagnosis of lung tuberculosis and to manage the patient in the right setting. Moreover, ultrasound allowed to detect and treat massive pleural effusion through an ultrasound‐guided thoracentesis.     

Clinical and socioeconomic burden of rhinoviruses/enteroviruses in the community

BackgroundThe epidemiology, clinical features, and socioeconomic burden associated with detection of rhinoviruses (RV)/enteroviruses (EV) from individuals in the community with acute respiratory infections (ARIs) are not fully understood.MethodsTo assess the clinical and socioeconomic burden associated with RV/EV, a secondary analysis of data collected during a prospective, community‐based ARI surveillance study was performed. From December 2012 to September 2017, adult and pediatric participants with ARIs had nasopharyngeal specimens obtained and tested by multiplex polymerase chain reaction assay. Characteristics and socioeconomic burden including missed school or work and/or antibiotic use among participants who did and did not seek medical care and among participants with and without co‐detection of another respiratory pathogen with RV/EV were compared.ResultsThroughout the study period, RV/EV was detected in 54.7% (885/1617) of ARIs with a respiratory pathogen detected. Most ARI episodes associated with RV/EV occurred in females (59.1%) and children ≤17 years old (64.2%). Those ≤17 years were more likely to seek medical care. Compared to those not seeking medical care (n = 686), those seeking medical care (n = 199) had a longer duration of illness (5 vs. 7 days) and were more likely to miss work/school (16.4% vs. 47.7%) and/or use antibiotics (3.6% vs. 34.2%). Co‐detection occurred in 8% of ARIs of which 81% occurred in children. Co‐detection was not associated with longer illness, more missed work/or school, or antibiotic use.ConclusionNon‐medically attended and medically attended ARIs associated with RV/EV resulted in clinical and socioeconomic burden, regardless of co‐detection of other respiratory pathogens.     

Failure of voriconazole to cure disseminated zygomycosis in an immunocompromised child

Voriconazole is increasingly used as a first-line agent for empirical antifungal therapy of prolonged febrile neutropenia in paediatric cancer patients. We describe the case of a 9-year-old patient with stage IV Burkitt lymphoma, who developed pulmonary and splenic zygomycosis while receiving voriconazole for persistent febrile neutropenia. The causative agent, Absidia corymbifera, was identified by broad-range fungal PCR in a lung biopsy sample. The patient was successfully treated with a combination of partial resection of the left upper lobe and antifungal therapy with high-dose liposomal amphotericin B followed by oral itraconazole as demonstrated by resolving pulmonary infiltrates on serial high resolution CT scans. Conclusion:This case emphasises that the lack of in vitro activity of voriconazole against zygomycetes is clinically relevant. Failure of voriconazole in suspected fungal infection should be investigated for the possibility of zygomycosis. Broad-range polymerase chain reaction may be able to identify the causative organism when cultures remain sterile.     

Hemodynamic Effect of Laser Therapy in Spontaneously Hypertensive Rats

Systemic arterial hypertension (SAH) is considered to be the greatest risk factor for the development of neuro-cardiovascular pathologies, thus constituting a severe Public Health issue in the world.The Low-Level Laser Therapy (LLLT), or laser therapy, activates components of the cellular structure, therefore converting luminous energy into photochemical energy and leading to biophysical and biochemical reactions in the mitochondrial respiratory chain. The LLLT promotes cellular and tissue photobiomodulation by means of changes in metabolism, leading to molecular, cellular and systemic changes.The objective of this study was to analyze the action of low-level laser in the hemodynamic modulation of spontaneously hypertensive rats, in the long term. Animals (n = 16) were randomly divided into the Laser Group (n = 8), which received three weekly LLLT irradiations for seven weeks, and into the Sham Group (n = 8), which received three weekly simulations of laser for seven weeks, accounting for 21 applications in each group. After seven weeks, animals were cannulated by the implantation of a catheter in the left carotid artery. On the following day, the systemic arterial pressure was recorded. The Laser Group showed reduced levels of mean blood pressure, with statistically significant reduction (169 ± 4 mmHg* vs. 182 ± 4 mmHg from the Sham Group) and reduced levels of diastolic pressure (143 ± 4 mmHg* vs. 157 ± 3 mmHg from the Sham Group), revealing a 13 and 14 mmHg decrease, respectively. Besides, there was a concomitant important decline in heart rate (312 ± 14 bpm vs. 361 ± 13 bpm from the Sham Group). Therefore, laser therapy was able to produce hemodynamic changes, thus reducing pressure levels in spontaneously hypertensive rats.