Treatment with anti-programmed cell death 1 (PD-1) antibody restored postoperative CD8+ T cell dysfunction by surgical stress.
Millions of patients benefit from surgery and are exposed to surgical stress. However, ample studies suggest that surgical stress contributes to tumor recurrence or distant metastases. Surgical stress suppresses CD8+ T cells (CTL) function which is vital for eliminating the malignant cells. Anti-programmed cell death 1 (PD-1) therapy is an effective and safe treatment that increases survival rate of patients with multiple cancers, however, whether anti-PD-1 therapy is able to reverse the immunosuppression following surgery remains largely unknown. Using a surgical stress mice model, we found that surgical stress reduced CD8+ T cell total numbers in the spleen and impaired CTLs function. Surgical induced CD8+ T cells had impaired anti-tumor effects in a tumor bearing models. Blockade of PD-1 with specific antibody restored CD8+ T cell numbers and secretion ability. PGE2 expression was dramatically upregulated in the postoperative serum, and anti-PD-1 together with PGE2 inhibitor restored CTLs dysfunction induced by surgery. Collectively, blockade of PD-1 with monoclonal antibody may be an effective treatment during the postoperative period for restoring surgery-induced immunosuppression.


Tortuosity of the internal carotid artery detected during tonsillectomy: two case reports.
Tonsillectomy is one of the most common performed surgical procedures in childhood. Tortuosity of the internal carotid artery (ICA) is an anatomical variation of the course of the ICA, and can be seen at any levels along the course of the artery, even in lateral oropharyngeal wall. In this article, we present two cases in which ICA tortuosity detected as a pulsating mass in the lateral oropharyngeal wall in an eight-year and a five-year-old girls, during tonsillectomy.


A New Surgical Paradigm for Postnatal Repair of Open Neural Tube Defects Using Intraoperative Neurophysiology Monitoring.
An open neural tube defect (ONTD) features an exposed, unclosed neural plate in the form of an expanded and frequently hefty neural placode. Traditional philosophy of ONTD repair aims at preserving the placode at any cost, which often means stuffing the entire thick and unwieldy but non-functional tissue into a tight dural sac, increasing the likelihood of future tethering of the spinal cord. The same philosophy of attempting to save the whole perimetry of the placode also sometimes leads to inadvertent inclusion of parts of the squamous epithelial membrane surrounding the placode into the reconstructed product, only to form inclusion dermoid cyst causing further injury to the neural tissues. Lastly, unsuccessful neurulation of the caudal primary neural tube almost always adversely affects junctional and secondary neurulation resulting in a defective conus, often with a locally active sacral micturition centre that is isolated from and therefore lacking suprasegmental inhibitory moderation. This frequently leads to the development of a spastic, hyperactive, low-compliance and high-pressure bladder predisposing to upstream kidney damage, without benefits of normal bladder function. We are introducing a new surgical technique designed to minimise or eliminate these three undesirable complications of conventional ONTD closure.


[Identification procedures using gas chromatography in intoxications with various solvents].
An identification system of 31 volatile organic compounds has been worked out using gas chromatography with columns of various polarity (SE-30, OV-17, Porapak Q). The efficiency of the system for identifying an unknown solvent delivered with the intoxicated one, or a toxic substance in the material from a person intoxicated (blood, exhalated air, gastric rinsings) has been proved good in numerous cases of acute intoxications hospitalized in the Clinical Division of the Institute of Occupational Medicineur Lódź.


Ecology of bacteria in the human gastrointestinal tract--identification of keystone and foundation taxa.
Determining ecological roles of community members and the impact of specific taxa on overall biodiversity in the gastrointestinal (GI) microbiota is of fundamental importance. A step towards a systems-level understanding of the GI microbiota is characterization of biotic interactions. Community time series analysis, an approach based on statistical analysis of changing population abundances within a single system over time, is needed in order to say with confidence that one population is affecting the dynamics of another. Here, we characterize biotic interaction structures and define ecological roles of major bacterial groups in four healthy individuals by analysing high-resolution, long-term (>180 days) GI bacterial community time series. Actinobacteria fit the description of a keystone taxon since they are relatively rare, but have a high degree of ecological connectedness, and are positively correlated with diversity both within and between individuals. Bacteriodetes were found to be a foundation taxon in that they are numerically dominant and interact extensively, in particular through positive interactions, with other taxa. Although community structure, diversity and biotic interaction patterns were specific to each individual, we observed a strong tendency towards more intense competition within than between phyla. This is in agreement with Darwin's limiting similarity hypothesis as well as a published biotic interaction model of the GI microbiota based on reverse ecology. Finally, we link temporal enterotype switching to a reciprocal positive interaction between two key genera. In this study, we identified ecological roles of key taxa in the human GI microbiota and compared our time series analysis results with those obtained through a reverse ecology approach, providing further evidence in favour of the limiting similarity hypothesis first put forth by Darwin. Larger longitudinal studies are warranted in order to evaluate the generality of basic ecological concepts as applied to the GI microbiota, but our results provide a starting point for achieving a more profound understanding of the GI microbiota as an ecological system.


Salt taste threshold and contributory factors of chronic kidney disease patients: a cross-sectional study.
High salt intake, correlated with high salt taste threshold, may accelerate renal injury in chronic kidney disease (CKD) patients. However, few studies have focused on factors that influence salt taste threshold. Therefore, we aimed to identify factors that influence the salt taste threshold of CKD patients, to provide more precise salt restriction recommendations in dietary therapy. Between April 2016 and March 2019, we measured the salt taste threshold of 1019 CKD patients, aged 22-78 years, from 52 hospitals across southwestern China, and then we performed a cross-sectional study. The mean salt taste threshold was 0.37 ± 0.16% NaCl. There were 115 (11.3%), 670 (65.7%), and 234 (23.0%), respectively, patients who had low (≤ 0.1% NaCl), medium (0.1-0.4% NaCl), and high (> 0.4% NaCl) salt taste thresholds. One-way ANOVA and regression results revealed that sex (male), age, decreased estimated glomerular filtration rate, and absence of salt restriction were factors that influenced CKD groups with high salt taste threshold. We found an independent correlation between contributory factors including sex, age, eGFR, and salt restriction behavior of subjects with the salt taste threshold of CKD patients. Our findings also offer insights on salt taste thresholds that could be useful for clinicians advising salt restriction to impair the salt taste sensitivity of the corresponding populations.


Analysis of clinical characteristics of Kounis syndrome induced by contrast media.
Understanding the relationship between contrast agents and Kounis syndrome (KS) is mainly based on case reports. The purpose of this research is to explore the clinical characteristics of contrast media induced KS. We searched for contrast-induced KS case reports through Chinese and English databases from 1991 to October 31, 2021. A total of 26 patients (19 men and 7 women,) were included, with a median age of 60 years (range 30-83). The contrast agents that cause KS mainly included gadolinium-based contrast agent (7 cases), iodine-containing contrast media (12 cases). KS mainly occurred within 30 min after administration and mainly manifests as chest pain and allergic reactions. Electrocardiogram (ECG) mainly showed ST elevation. Echocardiography mainly revealed normal. Coronary angiography showed normal, coronary vasospasm, stent thrombosis, occlusion and stenosis. After treatment with steroids, antihistamines and anti-ischemic therapy, 24 patients recovered completely and 2 patients died. KS is a rare adverse reaction of contrast media. Radiologists should recognize this rare but serious disease to ensure rapid diagnosis and proper management.


Acute Liver Failure.
Acute liver failure (ALF) is a life-threatening condition of heterogeneous etiology. Outcomes are better with early recognition and prompt initiation of etiology-specific therapy, intensive care protocols, and liver transplantation (LT). Prognostic scoring systems include the King's College Criteria and Model for End-stage Liver Disease score. Cerebral edema and intracranial hypertension are reasons for high morbidity and mortality; hypertonic saline is suggested for patients with a high risk for developing intracranial hypertension, and when it does, mannitol is recommended as first-line therapy. Extracorporeal liver support system may serve as a bridge to LT and may increase LT-free survival in select cases.


Identification and functional characterization of a novel bipartite nuclear localization sequence in ARID1A.
AT-rich interactive domain-containing protein 1A (ARID1A) is a recently identified nuclear tumor suppressor frequently altered in solid tumor malignancies. We have identified a bipartite-like nuclear localization sequence (NLS) that contributes to nuclear import of ARID1A not previously described. We functionally confirm activity using GFP constructs fused with wild-type or mutant NLS sequences. We further show that cyto-nuclear localized, bipartite NLS mutant ARID1A exhibits greater stability than nuclear-localized, wild-type ARID1A. Identification of this undescribed functional NLS within ARID1A contributes vital insights to rationalize the impact of ARID1A missense mutations observed in patient tumors.


Human papillomavirus genotypic characteristics of 60,685 subjects under age-expansion vaccination of the nine-valent human papillomavirus vaccine: A cross-sectional study.
Human papillomavirus (HPV) vaccination is a key initiative to promote the WHO global strategy to accelerate the elimination of cervical cancer, and this study aimed to investigate the current status of HPV infection and genotypic characteristics of the population under the impact of age-expansion of nine-valent HPV vaccination policy in China. The clinical data of 60,685 subjects who were admitted in the Renmin Hospital of Wuhan University and underwent HPV genotyping from January 2017 to October 2022 were retrospectively analyzed. The total number of positive HPV genotyping in the included population was 10,303, with a positivity rate of 17.0 %. The HPV positivity rate in the male and female populations increased slowly year by year, with a higher rate of positivity in men (32.7 %) than in women (16.7 %) (P < 0.001). HPV was predominantly single infection in all populations, with higher prevalence of high-risk HPV than low-risk HPV in females, while low-risk HPV infection was predominant in the male population. The age distribution of female subjects infected with HPV, with HPV52 as the most common type, showed a bimodal pattern. As for HPV infected male subjects, HPV6 was the main type, and there was no bimodal age distribution. The expanded age vaccination of the nine-valent HPV vaccine will result in 42.4 % efficiency of vaccine protection for 49.9 % of age-eligible women. If the nine-valent HPV vaccine were open to males in China, it would reduce HPV infections in men by 56.4 %. The HPV positivity rate in the population remains high and tends to increase, and the age-expansion of the nine-valent HPV vaccine would contribute to reducing the threat of disease caused by HPV infection for age-eligible women. Moreover, attention should be paid to enhancing HPV screening in males and opening up vaccination when appropriate.


Cardiac surgery-specific screening tool identifies preoperative undernutrition in cardiac surgery.
Loss of body tissue resulting in undernutrition can be caused by reduced food intake, altered metabolism, ageing, and physical inactivity. The predominant cause of undernutrition before cardiac operations is unknown. First, we explored the association of reduced food intake and inactivity with undernutrition in patients before elective cardiac operations. Second, we assessed if adding these reversible, cause-based items to the nutritional screening process improved diagnostic accuracy. A prospective observational study was performed. Undernutrition was defined by low fat-free mass index (LFFMI) measured by bioelectrical impedance spectroscopy and/or unintended weight loss (UWL). Reduced food intake was defined as the patient having a decreased appetite over the previous month. Patients admitted to hospital preoperatively were assumed to be less physically active than patients awaiting cardiac operations at home. Using these data, we developed a new tool and compared this with an existing cardiac surgery-specific tool (Cardiac Surgery-Specific Malnutrition Universal Screening Tool [CSSM]). A total of 325 patients who underwent open cardiac operations were included. Reduced food intake and inactivity were associated with undernutrition (odds ratio [OR], 4.2; 95% confidence interval [CI], 2.1-8.5 and OR, 2.0; 95% CI, 1.0-4.0). Reduced food intake and inactivity were integrated with body mass index (BMI) and UWL into a new scoring system: the Cardiac Surgery-Specific Undernutrition Screening Tool (CSSUST). Sensitivity in identification of undernourished patients was considerably higher with the CSSUST (90%) than with the CSSM (71%) (receiver operating characteristic [ROC] curve-based area under the curve [AUC], 0.79; 95% CI, 0.73-0.86 and ROC AUC, 0.71; 95% CI, 0.63-0.80). Results suggest that reduced food intake and inactivity partly explain undernutrition before cardiac operations. Our new cause-based CSSUST, which includes reduced food intake and inactivity, is superior to existing tools in identifying undernutrition in patients undergoing cardiac operations.


New surgical treatments for heart failure.
Medical therapy for heart failure is quickly advancing, but long-term survival unfortunately remains poor. New surgical techniques seek to halt and reverse the progression of heart failure. Positron emission tomography has refined patient selection techniques for coronary artery bypass grafting in the failing heart. Left ventricular (LV) remodeling surgery and new devices change the shape of the LV and decrease LV wall stress. Passive restraint devices improve systolic function by preventing ventricular dilatation. LV assist devices have proven to be effective and provide a significantly higher 1-year survival rate when compared with maximal medical therapy. New ideas and devices are defining a new role for surgical treatment of the aging population of the United States and may provide the answer to long-term management of heart failure.


Lack of influence of cytokeratin-positive mini micrometastases in "Negative Node" patients with colorectal cancer: findings from the national surgical adjuvant breast and bowel projects protocols R-01 and C-01.
Results of the few extant reports concerning the clinical significance of so-called "occult micrometastases" of lymph nodes of patients with Dukes A and B colorectal cancer have been variable. We examined the presumably negative nodes of a larger cohort of such patients who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trials R-01 and C-01 for the influence of what we preferably designate as nodal mini micrometastases on parameters of survival. Mini micrometastases were detected by immunohistochemical staining of the original lymph node sections with anticytokeratin A1/A3 in a total of 241 Dukes A and B patients with rectal and 158 with colonic cancers. Their frequency, as well as that of nuclear and histologic grades, and an estimation of their relationship to relative risks were correlated with overall and recurrence-free survival by univariate and multivariate analyses. Nodal mini micrometastases were detected in 73 of 399 (18.3 percent) patients of this cohort. They failed to exhibit any significant relationship to overall or recurrence-free survival. No association between the assessments of tumor differentiation and mini micrometastases was found. Nuclear and histologic grades also failed to further discriminate overall or recurrence-free survival in patients with A or B stages of colonic or rectal cancers in this cohort. The immunohistochemical demonstration of nodal mini micrometastases failed to discriminate high- and low-risk groups of patients with colorectal cancer who were designated as being node-negative after routine pathologic examination.


Ultrasonography for ureteral stone detection in patients with or without caliceal dilatation.
To evaluate the relationship between the degree of hydronephrosis and the detection rates of ureteral stones with ultrasonography (US). Of 250 consecutive patients with suspected ureterolithiasis, 214 who were diagnosed with ureterolithiasis were enrolled in this study. First, both kidneys were observed by US to evaluate the intrarenal collecting systems. Thereafter, the possible course of the ureters and the bladder were searched to find any stones. Stones were clearly observed in 80 (73%) of 109 patients with caliceal dilatation, whereas stones were clearly observed in 46 (44%) of 105 patients without dilatation (P < 0.05). Of the former 80 patients, 31 (39%) had stones in the ureterovesical junction (UVJ), whereas 51 (64%) had stones in the more proximal ureter. Of the latter 46 patients, 37 (80%) had stones in the UVJ or the bladder, whereas 9 (20%) had stones in the more proximal ureter. The US detection rate of ureteral stones was high in patients with caliceal dilatation. The whole ureter should be scanned in patients with caliceal dilatation for detection of ureteral stones. Even when patients have no caliceal dilatation, it is still considered to be useful to scan the UVJ and the bladder.


Influence of nutrients pollution on the growth and organic matter output of Ulva prolifera in the southern Yellow Sea, China.
The influence of nutrients on the growth of Ulva prolifera was studied in the SYS by field experiments. The wet weight of U. prolifera gradiently increased from 11.94% to 25.92% in proportion to contents of DIN supply, which indicated DIN content was essentially decisive for the output of U. prolifera blooms. Continuous nutrient supply could promote the growth of U. prolifera, indicated by the increase of growth rate from 10.46% of the batch culture to 42.17% of the in situ culture. The higher P utilized rate in all treatments showed P was the potential limited factor for the growth of U. prolifera. Moreover, it was calculated about 4.1×10(5)t organic matter was begot by U. prolifera in the whole Yellow Sea based on the statistical relationship between output of U. prolifera and DIN content. This work could be convenient to evaluate biomass and prepare enough tools to manage U. prolifera.


Characterization of ionic currents and electrophysiological properties of goldfish somatotropes in primary culture.
Growth hormone release in goldfish is partly dependent on voltage-sensitive Ca(2+) channels but somatotrope electrophysiological events affecting such channel activities have not been elucidated in this system. The electrophysiological properties of goldfish somatotropes in primary culture were studied using the whole-cell and amphotericin B-perforated patch-clamp techniques. Intracellular Ca(2+) concentration ([Ca(2+)]i) of identified somatotropes was measured using Fura-2/AM dye. Goldfish somatotropes had an average resting membrane potential of -78.4 ± 4.6 mV and membrane input resistance of 6.2 ± 0.2 GΩ. Voltage steps from a holding potential of -90 mV elicited a non-inactivating outward current and transient inward currents at potentials more positive than 0 and -30 mV, respectively. Isolated current recordings indicate the presence of 4-aminopyridine- and tetraethylammonium (TEA)-sensitive K(+), tetrodotoxin (TTX)-sensitive Na(+), and nifedipine (L-type)- and ω-conotoxin GVIA (N-type)-sensitive Ca(2+) channels. Goldfish somatotropes rarely fire action potentials (APs) spontaneously, but single APs can be induced at the start of a depolarizing current step; this single AP was abolished by TTX and significantly reduced by nifedipine and ω-conotoxin GVIA. TEA increased AP duration and triggered repetitive AP firing resulting in an increase in [Ca(2+)]i, whereas TTX, nifedipine and ω-conotoxin GVIA inhibited TEA-induced [Ca(2+)]i pulses. These results indicate that in goldfish somatotropes, TEA-sensitive K(+) channels regulate excitability while TTX-sensitive Na(+) channels together with N- and L-type Ca channels mediates the depolarization phase of APs. Opening of voltage-sensitive Ca(2+) channels during AP firing leads to increases in [Ca(2+)]i.


Control of expiratory duration by arterial CO2 oscillations in vagotomized dogs.
The role of respiratory oscillations of PaCO2 (CO2 oscillations) in the regulation of expiratory duration (TE) was examined in eight anesthetized dogs by measuring instantaneous changes of arterial pH during the respiratory cycle with a catheter-tip ISFET (ion-sensitive field effect transistor) pH electrode. Steady-state changes in arterial pH oscillation were induced by vagotomy, which increased the amplitude of pH oscillation from 0.014 +/- 0.002 (mean +/- SEM) to 0.058 +/- 0.006 units (P less than 0.001), and prolonged TE from 5.12 +/- 0.56 to 9.99 +/- 1.11 sec (P less than 0.005) with little change in average pH (0.021 +/- 0.011 units, P = 0.12). Vagotomy also reversed the phase relationship between arterial pH oscillation at the carotid bodies and tidal ventilation, such that pH rose during early expiration, rather than falling as occurred in the intact state. When the within-breath oscillation of arterial pH was transiently reduced by having the vagotomized dogs inspire a single breath of CO2 enriched air, TE of the same breath was shortened in proportion to the reduction in amplitude of pH oscillation (r = 0.72, P less than 0.001), rather than in proportion to changes in the average pH of the test breath (r = 0.44). The results indicate that the profile of within-breath oscillation of PaCO2 (phase relationship and amplitude) can exert an important influence on TE, and may in part account for the prolongation of TE following vagotomy.


Validation of a claims-based diagnostic code for Stevens-Johnson syndrome in a commercially insured population.
PURPOSE: To validate the administrative claims identification of a diagnosis of Stevens-Johnson syndrome (SJS) using medical records as the "gold standard" in a large, commercially insured US population. METHODS: Patients with >1 medical claim with the International Classification of Diseases, Ninth Revision, Clinical Modification code 695.1x between 1 July 2000 and 31 May 2007 were queried in the HealthCore Integrated Research Database(SM) , which contains administrative claims data for 14 commercial health insurance plans. Trained nurses and pharmacists abstracted pertinent information from the identified patients' medical records, which were then reviewed by two independent dermatologists to identify criteria to determine SJS diagnosis. Positive predictive values (PPVs) based on the claims and chart data were computed for all the cases. RESULTS: Medical charts for 200 claims-identified cases, with the International Classification of Diseases, Ninth Revision, Clinical Modification code 695.1x, were abstracted and reviewed by the dermatologists. A total of five cases (PPV = 2.50%, 95%CI = 0.8%-5.7%) were determined to be SJS with clinical certainty. PPVs varied with data stratification: PPV for inpatient claims only (PPV = 2.00%, 95%CI = 0.24%-7.04%), inpatient claims with 695.1x in first diagnosis field (PPV = 4.11%, 95%CI = 0.86%-11.54%), and final decisions of either clinical certainty or probable cases of SJS (PPV = 6.00%, 95%CI = 3.14%-10.25%). CONCLUSION: These findings demonstrate the difficulties associated with identifying rare disorders, which lack specific diagnostic criteria, within administrative claims databases. They underscore the challenges of using claims data to monitor ill-defined clinical conditions as well as the need to validate claims-identified cases with information from other sources, such as medical charts. Copyright © 2012 John Wiley & Sons, Ltd.


Linearity analysis and comparison study on the epoc(®) point-of-care blood analysis system in cardiopulmonary bypass patients.
The epoc(®) blood analysis system (Epocal Inc., Ottawa, Ontario, Canada) is a newly developed in vitro diagnostic hand-held analyzer for testing whole blood samples at point-of-care, which provides blood gas, electrolytes, ionized calcium, glucose, lactate, and hematocrit/calculated hemoglobin rapidly. The analytical performance of the epoc(®) system was evaluated in a tertiary hospital, see related research article "Analytical evaluation of the epoc(®) point-of-care blood analysis system in cardiopulmonary bypass patients" [1]. Data presented are the linearity analysis for 9 parameters and the comparison study in 40 cardiopulmonary bypass patients on 3 epoc(®) meters, Instrumentation Laboratory GEM4000, Abbott iSTAT, Nova CCX, and Roche Accu-Chek Inform II and Performa glucose meters.


Natural gas shortages during the "coal-to-gas" transition in China have caused a large redistribution of air pollution in winter 2017.
The Chinese "coal-to-gas" and "coal-to-electricity" strategies aim at reducing dispersed coal consumption and related air pollution by promoting the use of clean and low-carbon fuels in northern China. Here, we show that on top of meteorological influences, the effective emission mitigation measures achieved an average decrease of fine particulate matter (PM2.5) concentrations of ∼14% in Beijing and surrounding areas (the "2+26" pilot cities) in winter 2017 compared to the same period of 2016, where the dispersed coal control measures contributed ∼60% of the total PM2.5 reductions. However, the localized air quality improvement was accompanied by a contemporaneous ∼15% upsurge of PM2.5 concentrations over large areas in southern China. We find that the pollution transfer that resulted from a shift in emissions was of a high likelihood caused by a natural gas shortage in the south due to the coal-to-gas transition in the north. The overall shortage of natural gas greatly jeopardized the air quality benefits of the coal-to-gas strategy in winter 2017 and reflects structural challenges and potential threats in China's clean-energy transition.


Uterine junctional zone: function and disease.
The myometrium is usually thought of as a homogeneous mass of smooth muscle fibres. However, magnetic resonance studies of the uterus have revealed two distinct zones--the subendometrial myometrium or junctional zone and the outer myometrium. The junctional zone is not only structurally but also functionally different from the outer myometrium. For instance, myometrial contractions in a non-pregnant woman originate exclusively from the junctional zone, and their amplitude, frequency, and direction depend on the phase of the cycle. Irregular thickening of the junctional zone has been proposed as the magnetic resonance criterion for the diagnosis of diffuse adenomyosis. However, this magnetic resonance appearance relies on the disruption of the inner myometrial architecture secondary to smooth muscle hyperplasia but does not provide proof of mucosal invasion of the myometrium. We postulate that adenomyosis is a dichotomous disease characterised primarily by disruption of the inner myometrial architecture and function, with secondary infiltration of endometrial elements into the myometrium under certain circumstances. This hypothesis focuses on the inner myometrium and may explain the high incidence of superficial adenomyosis in dysfunctional uterine bleeding.


Persistent mild cognitive impairment in geriatric depression.
Cognitive impairment often occurs with geriatric depression and impairments may persist despite remission of depression. Although clinical definitions of mild cognitive impairment (MCI) have typically excluded depression, a neuropsychological model of MCI in depression has utility for identifying individuals whose cognitive impairments may persist or progress to dementia. At baseline and 1-year follow-up, 67 geriatric patients with depression had a comprehensive clinical examination that included depression assessment and neuropsychological testing. We defined MCI by a neuropsychological algorithm and examined the odds of MCI classification at Year 1 for remitted depressed individuals with baseline MCI, and examined clinical, functional and genetic factors associated with MCI. Fifty-four percent of the sample had MCI at baseline. Odds of MCI classification at Year 1 were four times greater among patients with baseline MCI than those without. Instrumental activities of daily living were associated with MCI at Year 1, while age and APOE genotype was not. These results confirm previous observations that MCI is highly prevalent among older depressed adults and that cognitive impairment occurring during acute depression may persist after depression remits. Self-reported decline in functional activities may be a marker for persistent cognitive impairment, which suggests that assessments of both neuropsychological and functional status are important prognostic factors in the evaluation of geriatric depression.


The vasovagal response of the rat: its relation to the vestibulosympathetic reflex and to Mayer waves.
Vasovagal responses (VVRs) are characterized by transient drops in blood pressure (BP) and heart rate (HR) and increased amplitude of low-frequency oscillations in the Mayer wave frequency range. Typical VVRs were induced in anesthetized, male, Long-Evans rats by sinusoidal galvanic vestibular stimulation (sGVS). VVRs were also produced by single sinusoids that transiently increased BP and HR, by 70-90° nose-up tilts, and by 60° tilts of the gravitoinertial acceleration vector using translation while rotating (TWR). The average power of the BP signal in the Mayer wave range increased substantially when tilts were >70° (0.91 g), i.e., when linear accelerations in the x-z plane were ≥0.9-1.0 g. The standard deviations of the wavelet-filtered BP signals during tilt and TWR overlaid when they were normalized to 1 g. Thus, the amplitudes of the Mayer waves coded the magnitude of the linear acceleration ≥1 g acting on the head and body, and the average power in this frequency range was associated with the generation of VVRs. These data show that VVRs are a natural outcome of stimulation of the vestibulosympathetic reflex and are not a disease. The results also demonstrate the usefulness of the rat as a small animal model for studying human VVRs.


Effectiveness and safety of oral anticoagulants in older patients with atrial fibrillation: a systematic review and meta-regression analysis.
the study analysed the effectiveness and safety of warfarin use compared with warfarin non-use and non-vitamin K antagonist oral anticoagulants (NOACs) in atrial fibrillation (AF) patients aged ≥65 years. after searching PubMed and the Cochrane Library, 26 studies were included, with 10 comparing warfarin with warfarin non-use and 16 comparing warfarin with NOACs, in older AF patients (≥65 years). warfarin use was superior to no antithrombotic therapy [relative risk (RR) 0.59, 95% confidence interval (CI) 0.51-0.76, I2 = 12.3%, n = 8] and aspirin (RR 0.44, 95% CI 0.24-0.64, I2 = 0.0%, n = 5) for stroke/thromboembolism (TE) prevention. Warfarin use was associated with a non-significant increase in risk of major bleeding compared with no antithrombotic therapy (RR 1.26, 95% CI 0.99-1.52, I2 = 0.0%, n = 7) and aspirin (RR 1.20, 95% CI 0.91-1.50, I2 = 0.0%, n = 5). NOACs were superior to warfarin for stroke/TE prevention [hazard ratio (HR) 0.81, 95% CI 0.73-0.89, I2 = 56.6%, n = 9], and also were associated with reduced risk of major bleeding compared to warfarin (HR 0.87, 0.77-0.97, I2 = 86.1%, n = 9). warfarin use was superior to warfarin non-use, aspirin and no antithrombotic therapy in reducing the risk of stroke/TE in older AF patients, but with a possible increase in major bleeding. NOACs were superior to warfarin for stroke/TE prevention, with reduced risk of major bleeding.


Treatment of Chronic Nonunion of a Sternal Fracture With Teriparatide.
Chronic nonunion of sternal fractures is typically treated by osteosynthesis plating with or without autologous bone grafting. Described here is a case of the successful use of teriparatide, a bone-forming drug currently used for the treatment of severe osteoporosis, in the healing of a sternal nonunion fracture occurring after blunt thoracic trauma.


Modification of the Siepser slip-knot technique.
A new modification of the Siepser sliding knot technique allows the surgeon to create a locking knot when performing iris reconstruction or intraocular lens fixation to the iris.


Epidemiology of otorhinolaryngologic emergencies in a secondary hospital: analysis of 64,054 cases.
To determine the incidence and distribution of care in relation to urgent otorhinolaryngologic pathologies by the different medical specialist units. A descriptive, observational and retrospective study was conducted of patients seen by the Emergency Service at a secondary hospital over the course of 7 years (2011-2017). A total of 546,701 patients were seen during the period in question, of which 64,054 presented with otorhinolaryngologic symptoms. The attendance rate was 450/1000 inhabitants/year. The most frequent diagnoses were upper respiratory tract infection, with 13,639 cases (21.3%), tonsillopharyngitis, with 10,150 cases (15.8%) and vertigo/dizziness with 8761 cases (13.7%). Patients seen by the Hospital Emergency Service physicians and those referred to the Otorhinolaryngology or Paediatric Units were analysed both together and separately. The Hospital Emergency Service dealt with 77.1% of the cases, and referred 15.4% to the Otorhinolaryngology Unit and 7.5% to the Paediatrics Unit. Within the subgroup of patients referred to the Otorhinolaryngology Unit, the most frequent diagnoses were problems related to inflammatory ear disease (25.6%), followed by cervicofacial trauma (15.4%) and bleeding with otorhinolaryngologic symptoms (12.5%). The percentage of hospital admissions for the entire sample was 3%, while for patients referred to the Otorhinolaryngology Unit this figure was 6.8%. A large percentage of patients presenting at the Hospital Emergency Service do so with otorhinolaryngologic symptoms, and the vast majority are treated effectively by the physicians in that service and are referred to the specialist services on the basis of sound criteria.


Prevention of cold inactivation of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase by NADPH.
Solubilized 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 184.108.40.206) from rat liver microsomes has been reported to be reversibly inactivated by temperatures below 19 degrees C. Cold inactivation has now been found to be completely prevented by NADPH and by NADP+ at a concentration of 3 mM. NADPH, however, was more active than NADP+ at lower concentrations and prevented 50% of the cold inactivation at 0.2 mM, whereas a 1.1 mM NADPH+ without effect and the substrate 3-hydroxy-3-methylglutaryl coenzyme A prevented only 30% of the cold inactivation at a concentration 50 times greater than the Km value.


Sub-toxic concentrations of volatile organic compounds inhibit extracellular respiration of Escherichia coli cells grown in anodic bioelectrochemical systems.
Low-cost and rapid detection of volatile organic compounds (VOCs) is important for the control of water quality of used water and protection of downstream used water treatment processes. In this work, the effect of sub-toxic concentration of VOCs on the current output of Escherichia coli in bioelectrochemical systems (BES) is shown, in light of environmental sensing applications for sewage and used water networks. E. coli cells were grown on carbon felt electrodes in artificial used water, to increase sensitivity and decrease response time for detection. Extracellular electron transfer was promoted by the addition of a biocompatible redox mediator, 2-hydroxy-1,4-naphthoquinone (HNQ). Among the eight VOCs investigated, toluene is the most toxic to E. coli, with a detection limit of 50±2mgL(-1) and current output of 32±1nAmg(-1)L(-1). This work offers a straightforward route to enhance the detection of organic contaminants in used water for environmental applications.


The significant relationship between platelet count and haemorrhagic complications on ECMO.
Haemorrhagic complications, which occur in up to 35% of infants during extracorporeal membrane oxygenation (ECMO), often produce devastating sequelae. Although many complex factors interact to control haemostasis, platelet number and function has significant impact on the development of primary haemostasis. The optimum platelet count on ECMO, however, has not been defined. At our institution prior to August 1987, platelet counts were maintained at greater than 100,000/mm3. After August 1987, however, platelet counts of greater than 200,000/m3 were maintained. In a retrospective study, patients were randomly chosen from these two treatment periods: group 1--March 1986 to July 1987; and group 2--June 1988 to June 1989. The average platelet count, platelets administered, hours on ECMO, and bleeding complications were compared to each other and to the July 1992 ELSO Registry. There was a significant difference in average platelet counts between group 1 and group 2. However, the amount of platelets administered per kg per day was similar. There was a significant difference in overall bleeding complications between Group 2 (12%) and the ELSO Registry (35%) (p < 0.01). There was a trend towards decreased complications in all subgroups, although sample size precluded significance. We conclude that increasing platelet counts to greater than 200,000/mm3 decreases the overall bleeding complication rate. This advantage is achieved without a continuous need for increased platelet administration once the desired level is reached and without an increase in perfusion time, mechanical complications, or mortality.


Volumetric behavior of a bolaamphiphile in different amides-water and ethylene glycol-water mixtures.
The effect of binary aqueous mixtures of ethylene glycol (EG), formamide (FA), N-methylformamide (NMF), dimethylformamide (DMF), and their pure phase on the apparent molar volume phi(V) of the bolaamphiphile decamethonium bromide (C10Me6) has been investigated at 298.15 K. The behavior of standard molar volumes V2(0) and transfer volumes Delta(t)phi(V) of C10Me6 from water to solvent/water (S/W) binary mixtures, shows different minima and maxima depending on the composition of the solvent. This behavior is influenced by the nature of the cosolvent and on the type of the solute and more or less corresponds to volumetric changes in the S/W mixture. The investigation of the transfer volumes in different fixed concentrations reveals an inversion of Delta(t)phi(V) values between the compositions, which suggests a differentiation of the effects of different volume contributions on the partial molar volume of ions. The correlation of Delta(t)phi(V) with the dielectric constant of the aqueous amide mixtures shows that the behavior of Delta(t)phi(V) vs x(amide) reflects the changes of epsilon(E) vs x(amide).


Regulation of insulin receptor substrate-2 tyrosine phosphorylation in animal models of insulin resistance.
Insulin induces a wide variety of growth and metabolic responses in many cell types. These actions are initiated by insulin binding to its receptor and involve a series of alternative and complementary pathways created by the multiple substrates of the insulin receptor (insulin receptor substrates [IRSs]). We investigated IRS-1 and IRS-2 tyrosine phosphorylation; their association with phosphatidylinositol-3-OH kinase (PI3-K); and the phosphorylation of Akt, a serine-threonine kinase situated downstream of PI3-K, in liver and muscle of two animal models of insulin resistance: epinephrine- or dexamethasone-treated rats. We used in vivo insulin infusion followed by tissue extraction, immunoprecipitation, and immunoblotting. IRS-1 and IRS-2 protein expression did not change in liver and muscle of the epinephrine- treated rats, but in dexamethasone-treated rats IRS-1 presented an increase in liver and a decrease in muscle tissue. PI3-K and Akt protein expression did not change in liver or muscle of the two animal models of insulin resistance. There was a downregulation in insulin- induced IRS-1 and IRS-2 tyrosine phosphorylation and association with PI3-K in both models of insulin resistance. In parallel, insulin-induced Akt phosphorylation was reduced in both tissues of epinephrine-treated rats, and in liver but not in muscle of dexamethasonetreated rats. The reduction in insulin-induced Akt phosphorylation may help to explain the insulin resistance in liver and muscle of epinephrine-treated rats and in the liver of dexamethasone-treated rats.


Long-term Outcome 10 Years After Free Gastroepiploic Artery Graft for Coronary Artery Bypass Surgery.
The long-term benefits of "free" gastroepiploic artery (GEA) grafts remain unclear. The aim of this study is to investigate the long-term patency and clinical results of en bloc free GEA grafts. Of the 1478 patients undergoing coronary artery bypass graft surgery at our institution between January 1997 and December 2009, 137 patients underwent en bloc free GEA grafting. Graft patency, late survival, and freedom from major adverse cardiovascular events were examined. Propensity score matching was used to compare the patency of free GEA grafts with the saphenous vein grafts, and 134 matched pairs were generated. The early patency rate of free GEA grafts was 98.6%. The long-term patency rates of the free GEA grafts was 96.5% at 5 years, 95% at 10 years, and 86.6% at 15 years. In the 134 matched pairs, the long-term patency rates of free GEA grafts anastomosed to the right coronary artery were significantly higher than those of saphenous vein grafts to the right coronary artery (97% vs 91.8% at 5 years; 95.3% vs 79.6% at 10 years; 85.9% vs 61.7% at 15 years; P < .001). Survival was 94% at 5 years, 86.6% at 10 years, and 66.8% at 15 years; and freedom from major adverse cardiovascular events was 93.2% at 5 years, 91.3% at 10 years, and 73.1% at 15 years. En bloc free GEA grafts had favorable long-term performance and can be considered as an effective option for patients who need to receive as many arterial grafts as possible.


A rare cause of ureteral injuries; simultaneous common iliac artery and ureter injury during posterior lumbar disc surgery.
Major vascular injuries during lumbar disc surgery are rare but well-recognized complications. However, vascular injuries of the branches of the aorta and ureteral injuries are very rare. Although its incidence is not known definitely, it is estimated to be 1/1000. Ureteral injuries comprise less than 1% of all genitourinary traumas. In this article, we report clinical progress of a patient who had simultaneous internal iliac artery and ureteral injury during lumbar discectomy. The patient was managed with primary ureteroureterostomy. To our knowledge, this is the first case reported with simultaneous ureter and iliac artery trauma during lumbar disc surgery.


Survey of pertussis morbidity in adults in western Sydney.
To estimate morbidity due to Bordetella pertussis infection in a representative population of Australian adults. Telephone survey using structured questionnaire. Adults (aged 20 years and over) notified with pertussis to a public health unit in western Sydney between 1 December 1997 and 31 May 1998. Duration of cough; time to improvement; symptoms and complications; time to diagnosis; health resource use; lost work days. Of 90 eligible patients, 73 (81%) completed questionnaires. Cough lasted a median of 60 days, but persisted over 90 days in 20 people (27%). Presentation was within a median of seven days of symptom onset, but diagnosis of pertussis took a median of 21 days. Participants reported a mean of 3.7 general practitioner visits and 1.2 prescription drugs. Of those employed, 17 (35%) missed more than five work days (range, 0-93 days). B. pertussis infection in adults can result in prolonged, significant disruption to social and working life. Results suggest that, in 1998, there were more than 8000 general practitioner visits and 15,000 lost work days caused by pertussis in Australian adults.


Parallel effects of arachidonic acid on insulin secretion, calmodulin-dependent protein kinase activity and protein kinase C activity in pancreatic islets.
A potential role of arachidonic acid in the modulation of insulin secretion was investigated by measuring its effects on calmodulin-dependent protein kinase and protein kinase C in islet subcellular fractions. The results were interpreted in the light of arachidonic acid effects on insulin secretion from intact islets. Arachidonic acid could replace phosphatidylserine in activation of cytosolic protein kinase C (K0.5 of 10 microM) and maximum activation was observed at 50 microM arachidonate. Arachidonic acid did not affect the Ca2+ requirement of the phosphatidylserine-stimulated activity. Arachidonic acid (200 microM) inhibited (greater than 90%) calmodulin-dependent protein kinase activity (K0.5 = 50-100 microM) but modestly increased basal phosphorylation activity (no added calcium or calmodulin). Arachidonic acid inhibited glucose-sensitive insulin secretion from islets (K0.5 = 24 microM) measured in static secretion assays. Maximum inhibition (approximately 70%) was achieved at 50-100 microM arachidonic acid. Basal insulin secretion (3 mM glucose) was modestly stimulated by 100 microM arachidonic acid but in a non-saturable manner. In perifusion secretion studies, arachidonic acid (20 microM) had no effect on the first phase of glucose-induced secretion but nearly completely suppressed second phase secretion. At basal glucose (4 mM), arachidonic acid induced a modest but reproducible biphasic insulin secretion response which mimicked glucose-sensitive secretion. However, phosphorylation of an 80 kD protein substrate of protein kinase C was not increased when intact islets were incubated with arachidonic acid, suggesting that the small increases in insulin secretion seen with arachidonic acid were not mediated by protein kinase C. These data suggest that arachidonic acid generated by exposure of islets to glucose may influence insulin secretion by inhibiting the activity of calmodulin-dependent protein kinase but probably has little effect on protein kinase C activity.


Genetic Diversity and Anti-Oxidative Potential of Streptomyces spp. Isolated from Unexplored Niches of Meghalaya, India.
Streptomyces is genetically and functionally diverse genus known to produce a wide array of phenolics and flavonoids with significant biotechnological applications. 52 isolates belonging to 26 species of Streptomyces collected from Meghalaya, India were analyzed for their genetic diversity using BOX-PCR. Significant inter- and intra- generic diversity was observed among the Streptomyces isolates especially those belonging to S. cacaoi, S. lavendulae, S. olivochromogenes, S. aureus, S. flavovirens. During bioactivity screening of the isolates, S. rectiviolaceus MJM72 recorded the highest DPPH activity (77.13 ± 0.91%) whereas S. antimycoticus MSCA162 showed excellent ABTS radical scavenging activity (99.65 ± 0.41%). On the other hand, S. novaecaesareae MJM58 had the highest (756.4 ± 7.38 μg GAE g-1 fresh weight) phenolic content while S. rectiviolaceus MJM72 was recorded with the highest flavonoid content (69.3 ± 0.12 μg QE g-1 fresh weight). As compared to total flavonoid content, total phenolic content had a stronger correlation with antioxidant activities. HPLC analysis of five selected isolates showed presence of gallic acid and pyrocatechol as predominant phenolics. In case of flavonoids, three isolates showed presence of rutin with S. rochei MSCA130 having the highest rutin content (0.95 μg g-1 fresh weight). The results of this study showed high genetic diversity and antioxidant potential among the Streptomyces isolates.


The terminal part of the QT interval (T peak to T end): a predictor of mortality after acute myocardial infarction.
The terminal part of the QT interval (T peak to T end; Tp-e)-an index for dispersion of cardiac repolarization-is often prolonged in patients experiencing malignant ventricular arrhythmias after acute myocardial infarction (AMI). We wanted to explore whether high Tp-e might predict mortality or fatal arrhythmia post-AMI. Tp-e was measured prospectively in 1359/1384 (98.2%) consecutive patients with ST elevation (n = 525) or non-ST elevation (n = 859) myocardial infarction (STEMI or NSTEMI) admitted for coronary angiography. Tp-e was significantly correlated with age, heart rate (HR), heart failure, LVEF, creatinine, three-vessel disease, previous AMI and QRS and QT duration. During a mean follow-up of 1.3 years (range 0.4-2.3),109 patients (7.9%) died; 25, 45, and 39 from cardiac arrhythmia, nonarrhythmic cardiac causes and other causes, respectively. Long Tp-e was strongly associated with increased risk of death, and Tp-e remained a significant predictor of death in multivariable Cox analyses (RR 1.5, 95% CI[1.3-1.7]). HR-corrected Tp-e (cTp-e) was the strongest predictor of death (RR 1.6 [1.4-1.9]). Tp-e and cTp-e were particularly strong predictors of fatal cardiac arrhythmia (RR 1.6 [1.2-2.1] and RR 1.8 [1.4-2.4]). Findings were similar in STEMI and NSTEMI. When comparing two methods for measuring Tp-e, one including the tail of the T wave and one not, the former had markedly higher predictive power (P < 0.001). Tp-e, and in particular cTp-e, were strong predictors of mortality during the first year post-AMI, and should be further evaluated as prognostic factors additional to established post-AMI risk factors.


Radioimmunoassay for etiocholanolone.
A sensitive and reliable radioimmunoassay for serum unconjugated etiocholanolone (3alpha-hydroxy-5beta-androstan-17-one) is reported. The antiserum was obtained from rabbits by immunization of etiocholanolone-17-(O-carboxymethyl) oxime [CMO]-bovine serum albumin [BSA]. Two ml of serum with 3H-etiocholanolone added for recovery was extracted with ether, and etiocholanolone was separated from cross-reacting steroids by Sephadex LH-20 column chromatography. The mean recovery after extraction and chromatography was 80.7 +/- 6.8 (S.D.)%. The sensitivity of the assay was less than 40 pg. The intraassay and interassay coefficients of variation were 9.2% and 10.9%, respectively. The mean of serum unconjugated etiocholanolone concentration determined by the present method was 0.39 +/- 0.10 (S.D.) ng/ml (n = 50) in normal men and 0.36 +/- 0.08 (S.D.) ng/ml (n = 20) in women in the follicular phase of the menstrual cycle.


Performance and private speech of children with attention-deficit/hyperactivity disorder while taking the Tower of Hanoi test: effects of depth of search, diagnostic subtype, and methylphenidate.
We administered the Tower of Hanoi to demographically comparable samples of control participants (n = 34) and children with the Combined (n = 22) and Inattentive subtypes (n = 19) of Attention-Deficit/Hyperactivity Disorder (ADHD). Controls excelled over children with the Inattentive subtype, who outperformed patients with the Combined subtype. These results replicated findings of greater executive deficits in the Combined than in the Inattentive type of ADHD. Double-blind administration of methylphenidate improved task performance only for patients with the Inattentive subtype. In a drug-free Baseline session, children with both subtypes of ADHD made more private verbalizations than controls, particularly when failing puzzles. In later sessions, regardless of drug condition, the inattentive sample exhibited a smaller increase in self-regulatory utterances under failure. In contrast, the combined sample decreased self-regulatory verbalizations under failure only under methylphenidate. The results support some differences between the two subtypes of ADHD in executive functioning and in their response to stimulant therapy.


Ca2+-dimethylphosphate complex formation: providing insight into Ca2+-mediated local dehydration and membrane fusion in cells.
Earlier studies using X-ray diffraction, light scattering, photon correlation spectroscopy, and atomic force microscopy, strongly suggest that SNARE-induced membrane fusion in cells proceeds as a result of calcium bridging opposing bilayers. The bridging of phospholipid heads groups in the opposing bilayers by calcium leads to the release of water from hydrated Ca(2+) ions as well as the loosely coordinated water at PO-lipid head groups. Local dehydration of phospholipid head groups and the calcium, bridging opposing bilayers, then leads to destabilization of the lipid bilayers and membrane fusion. This hypothesis was tested in the current study by atomistic molecular dynamic simulations in the isobaric-isothermal ensemble using hydrated dimethylphosphate anions (DMP(-)) and calcium cations. Results from the study demonstrate, formation of DMP-Ca(2+) complexes and the consequent removal of water, supporting the hypothesis. Our study further demonstrates that as a result of Ca(2+)-DMP self-assembly, the distance between anionic oxygens between the two DMP molecules is reduced to 2.92A, which is in close agreement with the 2.8A SNARE-induced apposition established between opposing bilayers, reported earlier from X-ray diffraction measurements.


Redetermination of the crystal structure of caesium tetra-fluorido-bromate(III) from single-crystal X-ray diffraction data.
Caesium tetra-fluorido-bromate(III), CsBrF4, was crystallized in form of small blocks by melting and recrystallization. The crystal structure of CsBrF4 was redetermined from single-crystal X-ray diffraction data. In comparison with a previous study based on powder X-ray diffraction data [Ivlev et al. (2013 ▸). Z. Anorg. Allg. Chem. 639, 2846-2850], bond lengths and angles were determined with higher precision, and all atoms were refined with anisotropic displacement parameters. It was confirmed that the structure of CsBrF4 contains two square-planar [BrF4]- anions each with point group symmetry mmm, and a caesium cation (site symmetry mm2) that is coordinated by twelve fluorine atoms, forming an anti-cubocta-hedron. CsBrF4 is isotypic with CsAuF4.


Oesophagostomum radiatum: successful vaccination of calves with high molecular weight antigens.
Extracts of adult Oesophagostomum radiatum were resolved into four fractions by gel filtration chromatography on a Superose 12 column. ELISA assays on these four fractions showed that the antibodies produced by naturally infected calves predominantly reacted with the void volume fraction (VV). Three trials were conducted in which calves were vaccinated with the VV fraction of adult extract. When compared to untreated controls, vaccination with the VV of adult extract significantly (P less than 0.05) reduced worm establishment and faecal egg output after challenge infection relative to untreated controls.


Correlations between subjective well-being, dyadic adjustment and marital satisfaction in Brazilian married people.
This study aimed to investigate the relationships between the constructs subjective well-being (SWB), dyadic adjustment (DA) and marital satisfaction (MS). Participants were 106 married Brazilians, of both sexes, with a mean age of 42 (+/- 11) years. Instruments used for the sociodemographic characterization and socioeconomic classification were the Subjective Wellbeing Scale (SWBS), the Dyadic Adjustment Scale (DAS) and the Marital Satisfaction Scale (MSS). Through the analysis of correlations and of stepwise multiple regression, it was verified that all the factors of the dyadic adjustment showed correlation with the marital satisfaction. The satisfaction with life (factor of the SWBS) and dyadic satisfaction (factor of the DAS), were positively and significantly correlated (r = .20: p = .04), which reveals that people who say they are satisfied with life in different domains also do so in relation to the marital experience,


Nicotinamide N-Methyltransferase inhibits HBV replication by suppressing NR5A1 expression invitro.
Chronic hepatitis B virus (HBV) infection can lead to fibrosis, liver cirrhosis, and primary hepatocellular carcinoma. Investigating host factors that regulate HBV replication helps to identify antiviral targets. In the current study, we identified Nicotinamide N-Methyltransferase gene (NNMT) as a novel factor that regulates HBV transcription. NNMT is up-regulated at both the mRNA and protein levels in HepG2.2.15 cells compared to HepG2 cells. Overexpression of NNMT reduces HBV replication in several cell models, while knockdown of NNMT enhances HBV DNA levels. Mechanistically, NNMT suppresses HBV DNA replication by inhibiting HBV RNA transcription. The region required for the inhibitory effect of NNMT was narrowed to nt 1672-1708 in enhancer II by luciferase assays. On the other hand, ChIP assays and EMSA results showed that NNMT does not bind to this region substantially, either directly or indirectly. Next, a collection of hepatic nuclear receptor transcription factors was screened to determine whether they were affected by NNMT overexpression. NR5A1, a positive regulator of HBV replication, decreased significantly after NNMT overexpression. Collectively, the findings of this study shed light on the regulation of HBV transcription.


Effect of common low-molecular-weight organic acid on the photodegradation of sertraline by ferrihydrite.
Sertraline is one of the most commonly used antidepressant pharmaceuticals with ubiquitous distribution in the aqueous environment. However, the environmental behavior of sertraline in the co-presence of low-molecular-weight organic acid (LMWOA) and iron oxide mineral is still poorly understood. In this study, the photodegradation of sertraline was systematically investigated in a common photosensitizing system (ferrihydrite (Fh)-LMWOA). Six LMWOAs, including citrate acid (CA), tartrate acid (TA), malate acid (MA), lactate acid (LA), succinate acid (SA) and malonic acid (MOA) were chosen as the representatives. Our results implied that the different Fe3+ dissolution rates would lead to rather different sertraline degradation patterns following the order of Fh-CA > Fh-TA > Fh-MA > Fh-LA > Fh-SA > Fh-MOA. The reaction was initiated by the interaction between LMWOA and Fh via ligand-promoted-dissolution mechanism. Furthermore, the Fe3+ dissolution rates also showed a strong correlation with the metal-organic complexation constants, indicating that the photodegradation process is strongly related to the complexation ability of LMWOA with Fe3+. •OH, O2•- and CO2•- were detected, indicating that they contributed to the photodegradation of sertraline. •OH was demonstrated to be the dominant Reactive oxygen species (ROS) for the degradation of sertraline, and the detailed transformation pathways were proposed based on the product analysis and theoretical calculation. According to the ecological structure activity relationship estimation, the photodegradation products of sertraline possessed lower toxicity compared to the parent compound. These findings contribute to a more comprehensive understanding of the environmental fate of sertraline and evaluate its potential ecotoxicity in natural systems.


Liposomal nanocarriers for statins: A pharmacokinetic and pharmacodynamics appraisal.
Statins, inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, are a well-known class of drug with beneficial therapeutic effects in cardiovascular disease and lipid disorders and have potential use against cancer. However, the bioavailability of statins is hampered due to low aqueous solubility and rapid metabolism. To improve pharmacokinetic profiles of statins, development of drug delivery systems is promising. Hence, the use of liposomes for selective delivery of statins to a selected site or for bioavailability enhancement is an effective strategy to increase statin therapeutic effects. Moreover, liposomal delivery can reduce the required dose of statins especially in terms of antitumor effects. Liposomes, because of their unique properties and biphasic and amphiphilic nature, have attracted much interest and can be considered as a suitable choice for delivery of both hydrophilic and lipophilic statins. In this review article, we focus on liposomes and evaluate the effects of different liposomal delivery systems, based on differences in size, phospholipid composition, circulation half-life, and cholesterol content, on statin function.


[Role of chemotherapy in castration-resistant prostate cancer: are there new approaches?].
Chemotherapy options for the treatment of metastatic castration-resistant prostate cancer (CRPC) have been very limited for many decades. Until 2004, only mitoxantrone was approved, providing palliation, but no survival benefit. With the introduction of docetaxel, the landscape of chemotherapy for CRPC changed substantially. Prednisone and three-weekly docetaxel showed an overall survival (OS) benefit compared to mitoxantrone plus prednisone, in addition to a significant improvement of quality of life and pain reduction. Further strategies to treat CRPC with chemotherapy include reinduction with docetaxel in responding patients and the use of cabazitaxel, a novel semi-synthetic microtubule inhibitor, in the docetaxel-refractory population. This review article is meant to guide physicians through the optimal use of chemotherapy in CRPC patients in daily clinical practice.


Percutaneous absorption of clindamycin in the pig and the rat.
Clindamycin HCl in a 3% formulation was applied twice daily to the back skin of three white (Yorkshire) and three black (Hampshire) pigs for 22 days. Partial thickness samples of skin were obtained by use of a dermatome on shaved opposite sides at 4 hours and 5 days posttreatment. More than twice the antibiotic activity (P less than or equal to .001) was found in thinner (254 micrometers epidermis) samples than in thicker (1016 micrometers epidermis and dermis, 1 to 3) samples. A significantly higher content of antibiotic (P = 0.015) was retained in the skin of black pigs at five days posttreatment. Groups of ten Upjohn Sprague-Dawley rats were treated similarly with clindamycin phosphate in a 3% formulation three times daily for 22 days. At termination of treatment antibiotic activity was widely distributed, whereas at five days posttreatment residual activity was confined largely to samples of treated skin. No cutaneous irritation due to treatment was observed in either study.


Economics of polio vaccination in the post-eradication era: should OPV-using countries adopt IPV?
The continued use of oral polio vaccine (OPV) poses a threat to polio virus eradication. Stopping all polio vaccination in the post-certification era is no longer considered to be a practical option. Policy makers agree that OPV use must stop immediately after certification. Therefore, the pragmatic alternative is for the OPV-using countries to switch to IPV. This study estimates the cost of switching to IPV, and the cost-effectiveness of this switch. Using data on the number of polio cases and the number of unvaccinated children in different countries of the world, the risks of polio and polio outbreaks have been calculated. The current cost of routine and intensive OPV immunisation is about US $2143 million in the 148 OPV-using countries. Routine use of IPV in these countries should cost US $1246 million. If the current costs of routine and intensive polio immunisation are considered, adopting IPV to replace OPV will not increase the total global cost. Even if the cost of intensive polio immunisation is ignored, cost-effectiveness ratio of adopting IPV remains less than the average GNI per capita of OPV-using countries. The incremental cost of adopting IPV to replace OPV is relatively low, about US $1 per child per year, and most countries should be able to afford this additional cost.


Clinical relevance of a newly developed endometrial receptivity test for patients with recurrent implantation failure in Japan.
To assess the clinical efficacy of personalized embryo transfer (pET) guided by a new endometrial receptivity test, ERPeakSM, in patients with recurrent implantation failure (RIF). Recurrent implantation failure patients of all ages at two private Japanese clinics from April 2019 to June 2020 were retrospectively analyzed. The intervention group (n = 244) received pET in accordance with endometrial receptivity testing results and was compared to control group (n = 306) receiving standardized timing, non-personalized embryo transfer (npET). In propensity score matching analysis, the clinical pregnancy rate (CPR) and live birth rate (LBR) were compared between groups, and a subanalysis of advanced maternal age (AMA) (≥38 years old) versus non-AMA (<38 years old) patients was also conducted. The CPR and LBR of the pET group were significantly higher than those of the npET group (37.7% vs. 20.0%, adjusted OR: 2.64; 95%CI, 1.70-4.11, p < 0.001 and 29.9% vs. 9.7%, adjusted OR: 4.13; 95%CI, 2.40-7.13, p < 0.001, respectively). Furthermore, in the subanalyses, the CPR and LBR of the pET group were significantly higher than those of the npET group in both the AMA non-AMA patients. The new ERPeakSM endometrial receptivity test is a useful alternative diagnostic tool for poor-prognosis patients, regardless of age.


Author Correction: TRAF3 regulates the oncogenic proteins Pim2 and c-Myc to restrain survival in normal and malignant B cells.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Effect of mitochondrial viability and metabolism on technetium-99m-sestamibi myocardial retention.
This study investigated the mechanism of myocardial retention of technetium-99m-sestamibi. 99mTc-sestamibi was injected intravenously into guinea pigs, and the myocardium was homogenized and fractionated by differential centrifugation. More than 90% of myocardial 99mTc-sestamibi was localized within the mitochondrial fraction. Calcium was found to release 99mTc-sestamibi from the mitochondrial fraction, with an IC50 of 2.54 +/- 0.98 mM. This effect was potentiated by NaCl, and inhibited by the mitochondrial calcium channel blocker ruthenium red. In vitro uptake of 99mTc-sestamibi was found to increase from 10.5% +/- 3.0% to 61.2% +/- 0.2% with the addition of 10 mM succinate, indicating that respiration is involved. Since irreversible ischemia results in cellular and mitochondrial calcium "overload" and loss of mitochondrial metabolic function, 99mTc-sestamibi should not be retained in necrotic or irreversibly ischemic myocardium, and could potentially act as a sensitive indicator of myocardial cell viability.


Endobronchial Ultrasound/Transbronchial Needle Aspiration-Biopsy for Systematic Mediastinal lymph Node Staging of Non-Small Cell Lung Cancer in Patients Eligible for Surgery: A Prospective Multicenter Study.
The treatment of lung cancer depends on histological and/or cytological evaluation of the mediastinal lymph nodes. Endobronchial ultrasound/transbronchial needle aspiration-biopsy (EBUS/TBNA-TBNB) is the only minimally invasive technique for a diagnostic exploration of the mediastinum. The aim of this study is to analyze the reliability of EBUS in the preoperative staging of non-small cell lung cancer (NSCLC). A prospective study was conducted from December 2019 to December 2022 on 217 NSCLC patients, who underwent preoperative mediastinal staging using EBUS/TBNA-TBNB according to the ACCP and ESTS guidelines. The following variables were analyzed in order to define the performance of the endoscopic technique-comparing the final staging of lung cancer after pulmonary resection with the operative histological findings: clinical characteristics, lymph nodes examined, number of samples, and likelihood ratio for positive and negative outcomes. No morbidity or mortality was noted. All patients were discharged from hospital on day one. In 201 patients (92.6%), the preoperative staging using EBUS and the definitive staging deriving from the evaluation of the operative specimen after lung resection were the same; the same number of patients were detected in downstaging and upstaging (8 and 8, 7.4%). The sensitivity, specificity, positive and negative predictive value, and diagnostic accuracy were 90%, 90%, 82%, 94%, and 90%, respectively. The likelihood ratio for positive and negative results was 9 and 0.9, respectively, confirming cancer when present and excluding it when absent. EBUS is the only low-invasive and easy procedure for mediastinal staging. The possibility to check the method in each of its phases-through direct visualization of the vessels regardless of their location in relation to the lymph nodes-makes it safe both for the endoscopist and for the patient. Certainly, the cytologist/histologist and/or operator must have adequate expertise in order not to negatively affect the outcome of the method, although three procedures appear to reduce the impact of the individual professional involved on performance.


Cracking the nut: geographical adjacency of sister taxa supports vicariance in a polytomic salamander clade in the absence of node support.
The urodelan genus Lyciasalamandra, which inhabits a relatively small area along the southern Turkish coast and some Aegean islands, provides an outstanding example of a diverse but phylogenetically unresolved taxon. Molecular trees contain a single basal polytomy that could be either soft or hard. We here use the information of nuclear (allozymes) and mitochondrial (fractions of the 16S rRNA and ATPase genes) datasets in combination with area relationships of lineages to resolve the phylogenetic relationships among Lyciasalamandra species in the absence of sufficient node support. We can show that neither random processes nor introgressive hybridization can be invoked to explain that the majority of pairs of sister taxa form geographically adjacent units and interpret that this pattern has been shaped by vicariant events. Topology discordance between mitochondrial and nuclear trees mainly refers to an affiliation of L. helverseni, a taxon restricted to the Karpathos archipelago, to the western-most and geographically proximate mainland taxon in the nuclear tree, while in the organelle tree it turns out to be the sister lineage to the geographically most distant eastern clade. As this discordance cannot be explained by long-branch attraction in either dataset we suppose that oversea dispersal may have accounted for a second colonization of the Karpathos archipelago. It may have initiated introgression and selection driven manifestation of alien eastern mitochondrial genomes on a western nuclear background. Our approach of testing for area relationships of sister taxa against the null hypothesis of random distribution of these taxa seems to be especially helpful in phylogenetic studies where traditional measures of phylogenetic branch support fail to reject the null hypothesis of a hard polytomy.


Automated caries detection in vivo using a 3D intraoral scanner.
The use of 3D intraoral scanners (IOS) and software that can support automated detection and objective monitoring of oral diseases such as caries, tooth wear or periodontal diseases, is increasingly receiving attention from researchers and industry. This study clinically validates an automated caries scoring system for occlusal caries detection and classification, previously defined for an IOS system featuring fluorescence (TRIOS 4, 3Shape TRIOS A/S, Denmark). Four algorithms (ALG1, ALG2, ALG3, ALG4) are assessed for the IOS; the first three are based only on fluorescence information, while ALG4 also takes into account the tooth color information. The diagnostic performance of these automated algorithms is compared with the diagnostic performance of the clinical visual examination, while histological assessment is used as reference. Additionally, possible differences between in vitro and in vivo diagnostic performance of the IOS system are investigated. The algorithms show comparable in vivo diagnostic performance to the visual examination with no significant difference in the area under the ROC curves ([Formula: see text]). Only minor differences between their in vitro and in vivo diagnostic performance are noted but no significant differences in the area under the ROC curves, ([Formula: see text]). This novel IOS system exhibits encouraging performance for clinical application on occlusal caries detection and classification. Different approaches can be investigated for possible optimization of the system.


Cellular mechanism of adrenalin stimulated chloride secretion via beta-adrenoceptor in T84 cells.
In the present study, the intracellular regulatory pathways involved in the adrenalin-stimulated chloride secretion across T84 cells were investigated. Biphasic characteristics were observed in the Isc response to the basolateral addition of adrenalin (0.25 nM-100 microM). The biphasic response was almost abolished by removing ambient Cl(-). Chloride secretion was found to depend on the activities of basolaterally located Na+-K+-2Cl(-) cotransporters and K+ channels. The alpha-adrenoceptor antagonist phentolamine did not have any effect on either phase of adrenalin-induced Isc, while after pretreatment of the beta-adrenoceptor antagonist propranolol, the adrenalin-induced Isc was substantially abolished, suggesting the biphasic response may be mediated by the beta-adrenoceptor. Under whole cell patch-clamp conditions, T84 cells responded to adrenalin with a rise in inward current. The current, which exhibited a linear I-V relationship and time- and voltage-independent characteristics, was inhibited by the chloride channel blocker DPC and the reverse potential was close to the equilibrium potential for Cl(-) (0 mV), implying that the current was Cl(-) selective. When preloaded with a Ca2+-chelating agent, BAPTA/AM did not affect the Isc response to adrenalin, whereas the Isc was destroyed by pretreating the cells with an adenyl cyclase inhibitor, MDL12330A. These observations were further supported by the intracellular [cAMP] measurement experiment, indicating that adrenalin induced chloride secretion could be mediated by a beta-adrenoceptor only involving cAMP as an intracellular second messenger.


Fluvoxamine in the treatment of menstrually related mood disorders.
Twenty women with premenstrual complaints were treated in a double-blind placebo controlled trial during two consecutive menstrual cycles with fluvoxamine, a selective serotonin uptake blocker. A beneficial effect was found on somatic and affective symptoms in both treatment groups, the effect of fluvoxamine being not different from placebo. The results of this study do not support a role for serotonin in menstrually related affective symptoms.


International Federation of Societies for Surgery of the Hand Committee report: the role of nerve transfers in the treatment of neonatal brachial plexus palsy.
Nerve transfers have gained popularity in the treatment of adult brachial plexus palsy; however, their role in the treatment of neonatal brachial plexus palsy (NBPP) remains unclear. Brachial plexus palsies in infants differ greatly from those in adults in the patterns of injury, potential for recovery, and influences of growth and development. This International Federation of Societies for Surgery of the Hand committee report on NBPP is based upon review of the current literature. We found no direct comparisons of nerve grafting to nerve transfer for primary reconstruction of NBPP. Although the results contained in individual reports that use each strategy for treatment of Erb palsy are similar, comparison of nerve transfer to nerve grafting is limited by inconsistencies in outcomes reported, by multiple confounding factors, and by small numbers of patients. Although the role of nerve transfers for primary reconstruction remains to be defined, nerve transfers have been found to be effective and useful in specific clinical circumstances including late presentation, isolated deficits, failed primary reconstruction, and multiple nerve root avulsions. In the case of NBPP more severe than Erb palsy, nerve transfers alone are inadequate to address all of the deficits and should only be considered as adjuncts if maximal re-innervation is to be achieved. Surgeons who commit to care of infants with NBPP need to avoid an over-reliance on nerve transfers and should also have the capability and inclination for brachial plexus exploration and nerve graft reconstruction.


Evaluation of Fatigue and Workload among Workers Conducting Complex Manual Assembly in Manufacturing.
OCCUPATIONAL APPLICATIONSWe conducted a study to evaluate fatigue and workload among workers performing complex assembly tasks. We investigate several predictors of fatigue, including subjective workload estimates, sleep duration, the shift being worked, and production levels. High levels of fatigue were reported in one-third of the shifts evaluated. The main predictors of high fatigue were workload estimates, working evening shifts, and baseline fatigue. Among the six dimensions of workload, only mental demand and frustration were predictors of high fatigue. Mental demand was also rated highest. Participants reported less than seven hours of sleep in 60% of the nights evaluated. These results suggest that managers and supervisors should consider cognitive workload as a key contributing factor to fatigue in complex manual assembly. Similarly, work schedule planning should consider shift duration, start times, and end times, because of the negative influence on fatigue and the potential disruptions on sleep among workers.


Blunted renal dopaminergic system activity in HgCl2-induced membranous nephropathy.
The present study evaluated the possible role of the renal dopaminergic system in the sodium retention of HgCl2-induced nephrotic syndrome. The time courses of urinary excretion of sodium, protein, dopamine and the precursor l-3,4-dihydroxyphenylalanine (L-Dopa) were evaluated in HgCl2-treated and control rats up to day 21. The renal aromatic l-amino acid decarboxylase (AADC) activity, the enzyme responsible for the synthesis of renal dopamine, was evaluated during negligible proteinuria accompanied with enhanced sodium retention (day 7), increased proteinuria accompanied with greatest sodium retention (day 14) as well as during increased proteinuria accompanied with negative sodium balance (day 21). Also, the influence of volume expansion (VE, 5% bw) and the effects of the D1-like agonist fenoldopam (10 microg kg bw(-1) min(-1)) on natriuresis and on proximal tubular Na+,K+-ATPase activity were examined on day 14. The daily urinary dopamine output and urinary dopamine/L-Dopa ratios were reduced in HgCl2-treated rats from day 2 and beyond. This was accompanied by a marked decrease in renal AADC throughout the study. During VE, the fenoldopam-induced inhibition of proximal tubular Na+,K+-ATPase activity was similar between HgCl2-treated and control rats. However, the urinary sodium excretion during fenoldopam infusion was markedly increased by 60% to 120% in control rats but was not altered in HgCl2-treated rats. It is concluded that HgCl2 nephrosis is associated with a blunted renal dopaminergic system activity. However, the lack of renal dopamine in HgCl2 nephrosis does not appear to be related with the overall renal sodium retention in a state of proteinuria.


Pulmonary venous flow and risk of cardiovascular disease in essential hypertension.
The prognostic significance of the pulmonary venous flow in essential hypertensive patients was investigated. Doppler transthoracic echocardiograms were analyzed in 705 essential hypertensive subjects with no prior cardiovascular disease. At baseline, most subjects had 'normal diastolic function' or 'mild diastolic dysfunction'. During follow-up (mean, 32 months), 56 participants developed cardiovascular disease. Sex-specific median values were used to separate the higher group from the lower group of the peak velocity ratio of the pulmonary venous systolic to diastolic wave (S/D) (male < 1.51, female < 1.66), and of the transmitral velocity ratio of early diastolic to atrial filling (E/A) (male < 0.84, female < 0.82). Kaplan-Meier curves with log-rank tests showed significantly poorer event-free survival rates in the groups with high S/D (P < 0.01) and low E/A (P < 0.01), respectively. In multivariate Cox regression analysis, the S/D ratio (HR 1.07 for each 0.1 increase, P = 0.03) or E/A ratio (P < 0.01) was an independent predictor of cardiovascular disease events. When divided into four groups based on the respective sex-specific median levels of S/D in the E/A > or = median and E/A < median groups, the group with high S/D and low E/A (S/D; male > or = 1.77, female > or = 1.81) had a significantly poorer event-free survival rate (chi2 = 28.06, P < 0.01), and the adjusted-hazard ratio by multivariate Cox regression analysis was 2.16 (95% CI; 1.40-3.07, P < 0.01). Increased S/D or decreased E/A is associated with an increased cardiovascular disease risk, and the combination of high S/D and low E/A may be a powerful predictor of cardiovascular disease in essential hypertension. Pulmonary venous flow evaluation may provide clinically important prognostic information in patients with essential hypertension.


Metabolic behavior of acetyl glyceryl ether phosphorylcholine on interaction with rabbit platelets.
The metabolic fate of 1-O-[3H]alkyl-2-acetyl-sn-glycero-3-phosphorylcholine ([3H]-AGEPC) upon interaction with rabbit platelets was investigated. [3H]AGEPC was converted to a product identified as the long-chain fatty acyl analog. The reaction was unaffected by extracellular calcium. After a lag time of 30 to 60 s the kinetics of the conversion was linear. The rate of the reaction was found to be a function of platelet and AGEPC concentrations. Of the [3H]AGEPC (10(-9) M) 85 +/- 5% was processed into the-long chain fatty acyl analog within 1 h when incubated at 37 degrees C with a 1.25 X 10(9) platelets per milliliter suspension. A maximal number of 1200 to 3600 [3H]AGEPC molecules were converted to the long-chain fatty acyl derivative per minute per platelet in the presence of 2 mM EDTA. Under similar conditions the 1-O-[3H]alkyl-2-(lyso)-sn-glycero-3-phosphorylcholine ([3H]lysoGEPC) also was transformed to a comparable long-chain fatty acyl derivative at a much slower rate and to a lower extent. No significant increase in lysoGEPC was noted in incubation mixtures containing [3H]AGEPC. The possible direct transacylation of AGEPC upon interaction with platelets is discussed as well as the possible involvement of this reaction in directly triggering the platelet response to AGEPC stimuli.


Calphostin C induces tyrosine dephosphorylation/inactivation of protein kinase FA/GSK-3 alpha in a pathway independent of tumor promoter phorbol ester-mediated down-regulation of protein kinase C.
The signal transduction mechanism of protein kinase FA/GSK-3 alpha by tyrosine phosphorylation in A431 cells was investigated using calphostin C as an inhibitor for protein kinase C (PKC). Kinase FA/GSK-3 alpha could be tyrosine-dephosphorylated and inactivated to approximately 10% of control in a concentration-dependent manner by 0.1-10 microM calphostin C (IC50, approximately 1 microM), as demonstrated by immunoprecipitation of kinase FA/GSK-3 alpha from cell extracts, followed by phosphoamino acid analysis and by immunodetection in an antikinase FA/GSK-3 alpha immunoprecipitate kinase assay. In sharp contrast, down-regulation of PKC by 0.05 microM calphostin C (IC50, approximately 0.05 microM for inhibiting PKC in cells) or by tumor promoter phorbol ester TPA was found to have stimulatory effect on the cellular activity of kinase FA/GSK-3 alpha, when processed under identical conditions. Furthermore, TPA-mediated down-regulation of PKC was found to have no effect on calphostin C-mediated tyrosine dephosphorylation/inactivation of kinase FA/GSK-3 alpha. Taken together, the results provide initial evidence that the PKC inhibitor calphostin C may induce tyrosine dephosphorylation/inactivation of kinase FA/GSK-3 alpha in a pathway independent of TPA-mediated down-regulation of PKC, representing a new mode of signal transduction for the regulation of this multisubstrate/multifunctional protein kinase by calphostin C in cells. Since kinase FA/GSK-3 alpha is a possible carcinoma dedifferentiation/progression-promoting factor, the results further suggest calphostin C as a potential anticancer drug involved in blocking carcinoma dedifferentiation/progression, possibly via inactivation of protein kinase FA/GSK-3 alpha in tumor cells.


Pancreatic volume in type 1 and type 2 diabetes mellitus.
We measured pancreatic volume (PV) using helical computed tomography (CT) in 26 patients with type 1 diabetes mellitus (DM), 29 patients with type 2 DM, and 22 healthy individuals. We also evaluated the relationship between PV and the body surface area (BSA), established the pancreatic volume index (PVI) by dividing PV by BSA to correct PV for the body build, and examined its relationships with the duration of illness, serum C-peptide immunoreactivity level (CPR), and serum immunoreactive trypsin level (IRT). BSA and PV were correlated significantly (p<0.0001, r=0.645) in healthy individuals, and they were correlated also in the diabetic patients (p=0.0023, r=0.563 in type 1 DM; p=0.0346, r=0.392 in type 2 DM). PV was significantly smaller in the type 1 DM group than in the healthy group and type 2 DM group (p<0.001 for both). PVI was also significantly smaller in the type 1 DM group than in the healthy group and type 2 DM group (p<0.001 for both). PVI and IRT were significantly correlated in both DM groups (p<0.0001, r=0.732 in type 1 DM; p=0.0469, r=0.371 in type 2 DM). PVI was not correlated with the duration of illness or CPR. Helical CT was useful for the measurement of the pancreatic volume, and the pancreatic volume was reduced particularly in the patients with type 1 DM. A strong correlation was observed between PV and exocrine pancreatic function in type 1 DM, but the correlation between PV and exocrine pancreatic function was weak in type 2 DM.


Ultrasound Assisted On-Table Management of Type III Endoleak at Endovascular Repair of Isolated Giant Common Iliac Aneurysm.
This report presents the endovascular treatment of a large isolated common iliac artery aneurysm, focusing on the use of on table ultrasonography to characterise and treat an early endoleak that could not be defined by angiography alone. A 58 year old man presented with an asymptomatic, large (13cm) left common iliac artery aneurysm (LCIAA) whilst being investigated for change in bowel habit. This was treated successfully via a percutaneous approach using left internal iliac embolisation followed by endovascular aneurysm repair (EVAR) with deployment of an aorto-uni-iliac converter system from the LCIA origin to the external iliac artery. A non-characterised endoleak at the end of the procedure was shown to be a type IIIb endoleak by application of immediate on table ultrasonography, allowing immediate supplementary targeted stent graft deployment to cover the leaking segment. The patient was discharged uneventfully and will remain on follow up. On table ultrasonography allowed both localisation and characterisation of an immediate intra-procedural endoleak and confirmed cessation of the endoleak with supplementary stent grafting and thrombosis within the sac. Isolated CIAA is rare, and endovascular therapy is appropriate for them, given that open surgery, whilst feasible, carries a high morbidity and mortality risk. Application of on-table ultrasound allows definition and targeted treatment of endoleaks, reducing the need for further intervention at a later stage, and thus also reducing the risk of continued pressurisation of the large sac post-EVAR till the next surveillance episode.


The sonographic "coffee bean" sign helps distinguish an axillary neurofibroma from a lymphadenopathy.
Axillary masses may represent various soft tissue tumors or lymphadenopathy. Neurofibromas are benign peripheral nerve sheath tumors and, while they are very uncommon, it is important to remember that neurogenic tumors arising from brachial plexus can develop in the axilla. We describe an axillary neurofibroma arising from the brachial plexus that presented with a "coffee bean sign" on sonography that distinguished it from axillary lymphadenopathy.


Improved optical detection of colony enlargement and drug cytotoxicity in primary soft agar cultures of human solid tumour cells.
The presence of cellular aggregates in cell suspensions derived from human solid tumours often complicates subsequent evaluation of colony formation in primary soft agar cultures (Agrez et al., 1982b). In the present study, performance of a conventional colony formation assay was observed to lack sufficient sensitivity to identify growth and active chemotherapeutic agents in the majority of specimen cultures. Modification of conventional methodologies to include filtration of cell suspensions, use of "proliferation control" and "cytotoxicity control" cultures as well as vital staining were found to be essential for the valid assessment of primary soft agar cultures in our laboratory. In addition, application of drugs to culture surface in place of culture incorporation appeared to facilitate culture performance and drug sensitivity testing.


Functional Imaging in the Follow-Up of Enteropancreatic Neuroendocrine Tumors: Clinical Usefulness and Indications.
Functional imaging tests (FITs) detecting somatostatin receptor expression [i.e., somatostatin receptor scintigraphy, 68Ga-DOTA positron emission tomography/computed tomography (CT)] have a pivotal role in the diagnosis of neuroendocrine tumors (NETs), although their indication during follow-up still needs to be clarified. Investigate the role of FITs after diagnosis of metastatic enteropancreatic NETs, identifying patients who might benefit from these exams. Multicenter retrospective analysis of metastatic enteropancreatic NETs. Analysis of imaging tests performed between January 1995 and December 2015 in Rome, Berlin, Milan, Marburg, or Graz. One hundred forty-three patients with metastatic pancreatic NETs and small intestine NETs, at least 2-year follow-up, and positive FITs. Patients had received CT every 6 months (unless clinical conditions and tumor behavior required shorter intervals) and FIT every 12 months. Clinical usefulness of FITs, defined as changes in patient management (indication to biopsy, medical therapy, surgery, or further imaging tests) due only to FITs. FITs affected management in 73.4% of patients, mostly when G2 vs G1 [odds ratio (OR), 2.40; 95% confidence interval (CI), 1.09 to 5.27; P = 0.03]. Changes were observed in a 12-month time frame especially with pancreatic NETs vs small intestine NETs (OR, 2.89; 95% CI, 1.09 - 7.67; P = 0.03) or metastases since diagnosis vs developed during follow-up (OR, 4.00; 95% CI, 1.43 to 11.17; P < 0.01). FITs used in addition to CT in the follow-up of stage IV enteropancreatic NETs improve patient management (especially for G2 tumors). Follow-up program should be tailored according to tumor features.


Influence of dietary linoleic acid on cardiac function and prostaglandin release and on the effects of isoprenaline in the isolated rat heart.
We studied the effects of dietary linoleate on cardiac function and on the effectiveness of isoprenaline in isolated rat heart preparations. Male Wistar rats were fed either a diet rich in linoleic acid (LA) (25% of digestible energy as sunflower oil, 5% lard) or an LA-deficient diet (30% hydrogenated palm kernel oil). Control rats received a standard lab chow. Under certain experimental conditions the LA-rich diet resulted in increased contractile force, coronary flow rate, and prostaglandin (PG) release (PG-like substances and PGI2) and in a reduction in heart rate. These effects were modified by the duration of the feeding period and/or the age of the animals. In isolated perfused hearts of rats fed on a diet rich in LA for a 10-week period the inotropic effects of isoprenaline were diminished, whereas the isoprenaline-induced increase in coronary flow rate was augmented. The PG-releasing effect of isoprenaline was antagonized by the LA-rich diet. Preliminary in vivo investigations support these in vitro results. The mechanisms by which dietary LA influences cardiac function and the effectiveness of isoprenaline remain unclear.


Fluorescence formation from hydroperoxide of phosphatidylcholine with amino compound.
The hydroperoxides of methyl linoleate, 1-palmitoyl-2-linoleoyl-phosphatidylcholine and trilinolein each produced similar fluorescent substances through reaction with amino compounds after decomposition by heme methyl ester. Fluorescent substances formed from methyl linoleate with 1-aminopentane revealed characteristic fluorescence peaks on HPLC, while those obtained from 1-palmitoyl-2-linoleoyl-phosphatidylcholine and trilinolein were not eluted under the same conditions. However, when both of these fluorescent substances were transesterified to methyl ester, the same fluorescence peaks were observed. This result suggests that fluorescent substances formed from oxidized membrane lipids with amino compounds remain attached to phospholipids without being released from their glycerol backbone.


Tuberculosis of the Spermatic Cord: Case Report.
The spermatic cord tuberculoma is uncommon, especially in its lower portion. Most cases were described in Japanese literature. We report a case of tuberculosis of the spermatic cord in a sexually active young man, revealed by a scrotal mass mimicking a tumor of the testicle and discuss the suitable diagnostic and therapeutic procedures, with preservation of the testes and the other sexual organs.


[Laser epithelial keratomileusis (LASEK) for treatment of myopia up to -6.0 D. Results from 108 eyes after 12 months].
Laser epithelial keratomileusis (LASEK) is a new keratorefractive procedure for the correction of myopia and myopic astigmatism, which may combine advantages and eliminate disadvantages of photorefractive keratectomy (e.g. pain, corneal haze) and laser in situ keratomileusis (e.g. flap and interface complications, dry eye, keratectasia). We present the results of 108 consecutively LASEK-treated eyes with a follow-up period of 12 months. LASEK was performed on 108 consecutive eyes with myopia or myopic astigmatism using a keracor 117 excimer laser. The mean preoperative refraction was -4.12+/-1.30 diopters (D) spherical equivalent range: -1.75 to -6.0 D and maximal cylinder was 3.25 D. Results of the 12 months visit are available for 101 eyes (93.5%). No serious complications were observed. After 12 months, SE was within +/-1.0 D of emmetropia in 96% and within +/-0.5 D in 86% of the eyes; 6 eyes had to be retreated. None of the eyes showed haze worse than grade 1 or lost more than one line of best-corrected visual acuity. Uncorrected visual acuity (UCVA) was > or =20/20 in 80% and > or =20/40 in 98%. Laser epithelial keratomileusis (LASEK) seems to be safe and effective in treatment of myopia and myopic astigmatism of up to -6.0 D. Preliminary results compare favourably with those after photorefractive keratectomy and laser in situ keratomileusis. Haze formation after LASEK seems to be low. Coverage of the stromal wound with a vital epithelial flap could positively influence postoperative wound healing reactions.


Intrauterine resuscitation with terbutaline: a method for the management of acute intrapartum fetal distress.
Terbutaline, a selective beta-2 adrenergic receptor stimulator, has been used to decrease myometrial activity and improve uteroplacental blood flow in 15 patients with acute intrapartum fetal distress. In all cases electronic monitoring gave evidence of partial or total fetal recovery after therapy. Thirteen of these patients were delivered by cesarean section and two were allowed to resume labor and deliver vaginally. In 10 cases the initial Apgar score was 7 or more and in all cases the score was 7 or more after 5 minutes of life. No significant maternal morbidity occurred as a consequence of the treatment. These results suggest that inhibition of uterine activity with terbutaline may be a valuable maneuver in the management of patients with severe intrapartum fetal distress.


Immunogenicity of tetanus toxoid conjugates of anti-idiotypes that mimic Pseudomonas aeruginosa surface polysaccharides.
Pseudomonas aeruginosa continues to be a serious pathogen in humans, and there is no commercially available vaccine. We have previously developed monoclonal anti-idiotypic antibodies that mimic two surface polysaccharide epitopes of pseudomonas--the high-molecular-weight polysaccharide of the O side chain of immunotype 1 lipopolysaccharide and mucoid exopolysaccharide. We now show that conjugation of the anti-idiotypes to the carrier tetanus toxoid is not necessary to induce antipolysaccharide antibodies of equal or greater titer than the native polysaccharide antigen in mice.