Systemic Inflammatory Response Syndrome Combined with Pre- and Postoperative White Blood Cell Ratio Is a Better Criterion to Identify Septic Shock Patients After Flexible Ureteroscopic Lithotripsy.
Objective: To find out a better criterion to identify septic shock patients after flexible ureteroscopic lithotripsy (FUL). Materials and Methods: In total, 2364 patients who underwent the FUL procedure were enrolled in the study. The demographics and preoperative results of laboratory tests of the patients were collected. The postoperative white blood cell (WBC), systemic inflammatory response syndrome (SIRS), and quick sequential (sepsis-related) organ failure assessment score (qSOFA) were assessed 2 hours after FUL. The predictive efficacy was measured by sensitivity, specificity, positive and negative predictive value, and area under the receiver's operating characteristic curve (AUROC). Results: A total of 15 (0.63%) patients developed septic shock. There were 86 (3.64%) patients who were SIRS positive and 69 (2.92%) patients who were qSOFA positive. The pre- and postoperative WBC ratios in septic shock patients and normal patients were 2.50 ± 1.55 and 0.69 ± 0.24, respectively (p < 0.001). For sensitivity and negative predictive value, all reached 100%. For specificity, qSOFA was 97.70%, SIRS was 96.98%, and SIRS combining pre- and postoperative WBC ratio (the new criterion) was 99.79%. The new criterion had statistically significant higher specificity than SIRS or qSOFA (p < 0.001 for both), but when comparing SIRS and qSOFA, it had statistically insignificant specificity (p = 0.142). For positive predictive value, qSOFA was 21.73%, SIRS was 17.44%, and the new criterion was 75%. qSOFA and SIRS had similar AUROC (0.989 for qSOFA and 0.985 for SIRS), both lower than the new criterion (AUROC: 0.999). Conclusions: SIRS combined with pre- and postoperative WBC ratio has a much better specificity and positive predictive value than SIRS or qSOFA alone. It has 99.79% specificity and 75% positive predictive value, and as high as 100% sensitivity and negative predictive value.


Transgenic crops for the agricultural improvement in Pakistan: a perspective of environmental stresses and the current status of genetically modified crops.
Transgenic technologies have emerged as a powerful tool for crop improvement in terms of yield, quality, and quantity in many countries of the world. However, concerns also exist about the possible risks involved in transgenic crop cultivation. In this review, literature is analyzed to gauge the real intensity of the issues caused by environmental stresses in Pakistan. In addition, the research work on genetically modified organisms (GMOs) development and their performance is analyzed to serve as a guide for the scientists to help them select useful genes for crop transformation in Pakistan. The funding of GMOs research in Pakistan shows that it does not follow the global trend. We also present socio-economic impact of GM crops and political dimensions in the seed sector and the policies of the government. We envisage that this review provides guidelines for public and private sectors as well as the policy makers in Pakistan and in other countries that face similar environmental threats posed by the changing climate.


Restoration of podosomes and chemotaxis in Wiskott-Aldrich syndrome macrophages following induced expression of WASp.
We used a direct-viewing (Dunn) chemotaxis chamber to analyse the chemotactic responses of human normal and Wiskott-Aldrich syndrome (WAS) macrophages to the cytokine colony stimulating factor-1 (CSF-1). In five patients with classic WAS, where specialised adhesion complexes called podosomes are absent, chemotaxis of macrophages was abolished. The deficient chemotactic responses of WAS macrophages following cytokine stimulation could be correlated with abnormalities in cell polarisation and actin organisation. In a series of cell microinjection studies we found that normal chemotactic responses were restored in WASp macrophages transfected with a full-length human WAS construct. Expression of exogenous WAS protein (WASp) in these cells also restored normal polarised cell morphology and the ability to form podosomes.


Dysfunctional loop ileostomy after low anterior resection for rectal cancer in the presence of Meckel's diverticulum: a case report.
A temporary protective loop ileostomy is a routine procedure to protect the anastomosis in patients who undergo low anterior resection for rectal cancer. The aim of this case report is to present a rare complication caused by Meckel's diverticulum. We describe a case of a 71-year-old white man with dysfunctional ileostomy after low anterior resection for rectal cancer due to adhesions and pressing effects of Meckel's diverticulum near the ileostomy site, which led to volvulus of his small intestine and obstruction. As a result he underwent a supplementary operation to resolve this complication by Meckel's diverticulum resection. During a low anterior resection for rectal cancer and a protective ileostomy procedure the presence of Meckel's diverticulum should not be ignored. Our proposal is the primary resection of Meckel's diverticulum as the best surgical choice; according to the limited international literature on such cases we report a possible alternative to a protective ileostomy by creating a conduit using Meckel's diverticulum as a stoma.


Cataracts and macular degeneration.
The intraocular lens restores general vision and some degree of independence and mobility to patients with dense cataracts and macular degeneration. The patient, however, must be repeatedly warned that fine central vision, particularly reading, will not be possible after the surgery. An aphakic spectacle leaves such patients a narrow band of vision when superimposed over the macular lesion, and contact lenses are too small for the patient to manage insertion without help.


Use of Taurolidine in a Patient With a Cardiac Implantable Electronic Device Protrusion.
We report the successful salvage of cardiac implantable electronic device pulse generator protrusion sealed by the surrounding skin in a frail patient presenting 5 months after the last surgical revision. (Level of Difficulty: Advanced.).


Superficial sural artery flap--a study in 40 cases.
The distally based superficial sural artery flap is an important skin flap that can be used for soft tissue defects of the distal lower limb and proximal foot. It is a versatile flap, has a wide arc of rotation and requires minimal expertise. Forty patients with soft tissue defects of the lower leg due to various causes were treated with sural flaps and the results are discussed. The flap was either used as a long pedicled flap or islanded to treat patients with ages ranging from 4 to 75 years. The arc of rotation of the flap was N 90-180 degrees with minimal flap loss in most of the cases. On this basis we would like to reintroduce the safe and reliable use of the sural flap to treat large soft tissue defects of the distal lower limb and the proximal foot.


Gating, enhanced gating, and beyond: information utilization strategies for motion management, applied to preclinical PET.
Respiratory gating and gate optimization strategies present solutions for overcoming image degradation caused by respiratory motion in PET and traditionally utilize hardware systems and/or employ complex processing algorithms. In this work, we aimed to advance recently emerging data-driven gating methods and introduce a new strategy for optimizing the four-dimensional data based on information contained in that data. These algorithms are combined to form an automated motion correction workflow. Software-based gating methods were applied to a nonspecific population of 84 small-animal rat PET scans to create respiratory gated images. The gated PET images were then optimized using an algorithm we introduce as 'gating+' to reduce noise and optimize signal; the technique was also tested using simulations. Gating+ is based on a principle of only using gated information if and where it adds a net benefit, as evaluated in temporal frequency space. Motion-corrected images were assessed quantitatively and qualitatively. Of the small-animal PET scans, 71% exhibited quantifiable motion after software gating. The mean liver displacement was 3.25 mm for gated and 3.04 mm for gating+ images. The (relative) mean percent standard deviations measured in background ROIs were 1.53, 1.05, and 1.00 for the gated, gating+, and ungated values, respectively. Simulations confirmed that gating+ image voxels had a higher probability of being accurate relative to the corresponding ungated values under varying noise and motion scenarios. Additionally, we found motion mapping and phase decoupling models that readily extend from gating+ processing. Raw PET data contain information about motion that is not currently utilized. In our work, we showed that through automated processing of standard (ungated) PET acquisitions, (motion-) information-rich images can be constructed with minimal risk of noise introduction. Such methods have the potential for implementation with current PET technology in a robust and reproducible way.


Acute gastric dilatation in a patient with anorexia nervosa.
A 43-year-old female with a history of anorexia nervosa presented to our hospital with diffuse abdominal pain and distension after a binge eating episode. Vital signs and routine laboratory test results were unremarkable, except for a slightly elevated white blood cell count (14.5 x 109/l). Abdominal radiography and computed tomography (CT) revealed a massively dilated stomach, with a craniocaudal measurement of 37 cm.


Pattern of acute poisoning in a medical unit in central Sri Lanka.
One hundred and seventy nine cases of acute poisoning constituting 1.1% of all admissions to the medical unit over 3 years were analysed. Eighty-three per cent of the patients were under 30 years of age and 72% were males. The common agents were: OP insecticides in 51%, kerosene oil in 12%, rat poison in 8% and drugs in 8%. Ingestion with suicidal intent was the common mode of poisoning. The overall mortality was 16%. The results from four other major centres in Sri Lanka are presented for comparison.


Longitudinal analysis of immune abnormalities in varying severities of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis patients.
Research has identified immunological abnormalities in Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME), a heterogeneous illness with an unknown cause and absence of diagnostic test. There have been no CFS/ME studies examining innate and adaptive immune cells longitudinally in patients with varying severities. This is the first study to investigate immune cells over 6 months while also examining CFS/ME patients of varying symptom severity. Participants were grouped into 18 healthy controls, 12 moderate and 12 severe CFS/ME patients and flow cytometry was used to examine cell parameters at 0 and 6 months. Over time, iNKT CD62L expression significantly increased in moderate CFS/ME patients and CD56(bright) NK receptors differed in severe CFS/ME. Naïve CD8(+)T cells, CD8(-)CD4(-) and CD56(-)CD16(-) iNKT phenotypes, γδ2T cells and effector memory subsets were significantly increased in severe CFS/ME patients at 6 months. Severe CFS/ME patients were significantly reduced in CD56(bright)CD16(dim) NKG2D, CD56(dim)CD16(-) KIR2DL2/DL3, CD94(-)CD11a(-) γδ1T cells and CD62L(+)CD11a(-) γδ1T cells at 6 months. Severe CFS/ME patients differed from controls and moderate CFS/ME patients over time and expressed significant alterations in iNKT cell phenotypes, CD8(+)T cell markers, NK cell receptors and γδT cells at 6 months. This highlights the importance of further assessing these potential immune biomarkers longitudinally in both moderate and severe CFS/ME patients.


Comparative Evaluation of the Efficiency of Manual and Rotary Gutta-percha Removal Techniques.
This study aimed to evaluate the efficiency of 2 manual and 2 rotary gutta-percha (GP) removal techniques in terms of both the total operating time and GP remnants left in the canal. GP was removed with manual techniques using H-files and xylene (H + X) and H-files and System B (H + SB) (SybronEndo, Orange, CA) and with rotary techniques using the ProTaper Univeral Retreatment (PTUR) (Dentsply Maillefer, Ballaigues, Switzerland) and D-RaCe Retreatment (D-RR) (FKG Dentaire, La Chaux-de-Fonds, Switzerland) systems. The total operating time was evaluated as the time taken to reach the working length and completely remove GP until no radiopaque remnants were observed in the final radiograph. Any GP remnants left in the canal were evaluated in terms of percentage in the whole canal. Rotary techniques were significantly faster and left lesser GP remnants than manual techniques (P < .05). In rotary techniques, the D-RR system was significantly faster than the PTUR system (P < .05), but there was no significant difference between them regarding GP remnants (P > .05). In manual techniques, H + X was significantly faster and left lesser GP remnants than H + SB (P < .05). Rotary techniques were more efficient than manual techniques in GP removal. Overall, the D-RaCe Retreatment system was most efficient, whereas manual use of H-files with System B was least efficient. However, because all the techniques showed GP remnants in the canal and radiographs failed to show these remnants, additional measures would be required to ensure complete GP removal and check for cleaner canals during endodontic retreatment.


Lymph node metastases in splenic flexure colon cancer: Is subtotal colectomy warranted?
Tumors of the splenic flexure (TSF) can be associated with metastatic lymph nodes (LN) along the left colic pedicle, but also along the superior mesenteric vessels. We aimed to detail the anatomical distribution of metastatic LNs in patients undergoing elective subtotal colectomy for TSF. Between 2000 and 2016, 65 patients were included. At pathological analysis, LNs were classified into two groups: locoregional LN (along the left colic artery) and distant LN (along the middle colic, right colic, and ileocolic arteries). The median number of LNs examined was 20. Eighteen patients (27%) were pN+. Among them, six (33% of pN+ patients and 9% of the series) had at least one positive distant LN. All these patients had a positive distant LN along the right colic artery. These patients had a significantly advanced stage and more positive LNs than the others (stage III-IV: 100% vs 22%, P = 0.0009 and 6 [3-15] vs 0 [0-15], P < 0.0001, respectively). The presence of synchronous metastases was predictor of metastatic distant LNs (P = 0.042). Elective subtotal colectomy for TSF allows to discover distant positive LNs in nearly 10% of patients. For those having TSF and synchronous metastatic disease enable to resection, subtotal colectomy should be recommended.


Assessing the toxicity of bisphenol A and its six alternatives on zebrafish embryo/larvae.
Bisphenol A (BPA) analogues are gradually replacing BPA in the plastics industry. Whether these alternatives are indeed safer than BPA itself, however, remains unclear. Here, we studied the toxicity of BPA and six of its alternatives-BPB, BPC, BPE, BPF, BPAF, and BPAP-using zebrafish embryos/larvae. According to their half lethal concentration (LC50) values, the acute toxicity of BPA and six alternative bisphenols to zebrafish embryos, from highest to lowest, was BPAP ≈ BPAF > BPC > BPB > BPA > BPE > BPF. Under nonlethal concentrations, the tested bisphenols had different toxic effects on development in terms of reducing the hatching rate, frequency of spontaneous movements, and heart rate in the embryo, as well as inducing yolk sac edema, pericardial edema, and spinal deformation in the larvae. The estrogenic activity of BPE, BPF, and BPAF was higher than that of BPA, as shown by vtg1 expression assays. Moreover, BPA and its alternatives increased SOD activity and cell apoptosis in embryos/larvae under nonlethal concentrations. Our findings indicate that BPA alternatives may not be safer than BPA in zebrafish, and that these BPA alternatives should be applied with caution.


Immunological studies on bovine milk lipoprotein lipase. Effects of Fab fragments on enzyme activity.
Rabbit antiserum was prepared against purified bovine mild lipoprotein lipase. Immunoelectrophoresis of lipoprotein lipase gave a single precipitin line against the antibody which was coincident with enzyme activity. The gamma-globulin fraction inhibited heparin-releasable lipoprotein lipase activity of bovine arterial intima, heart muscle and adipose tissue. The antibody also inhibited the lipoprotein lipase activity from adipose tissue of human and pig, but not that of rat and dog. Fab fragments were prepared by papain digestion of the gamma-globulin fraction. Fab fragments inhibited the lipoprotein lipase-catalyzed hydrolysis of dimyristoylphosphatidylcholine vesicles and trioleoylglycerol emulsions to the same extent. The Fab fragments also inhibited the lipolysis of human plasma very low density lipoproteins. The change of the kinetic parameters for the lipoprotein lipase-catalyzed hydrolysis of trioleoylglycerol by the Fab fragments was accompanied with a 3-fold increase in Km and a 10-fold decrease in Vmax. Preincubation of lipoprotein lipase with apolipoprotein C-II, the activator protein for lipoprotein lipase, did not prevent inhibition of enzyme activity by the Fab fragments. However, preincubation with dipalmitoylphosphatidylcholine-emulsified trioleoylglycerol or Triton X-100-emulsified trioleoylglycerol had a protective effect (remaining activity 7.0 or 25.8%, respectively, compared to 1.0 or 0.4% with no preincubation). The addition of both apolipoprotein C-II and substrate prior to the incubation with the Fab fragments was associated with an increased protective effect against inhibition of enzyme activity; remaining activity with dipalmitoylphosphatidylcholine-emulsified trioleoylglycerol was 40.6% and with Triton X-100-emulsified trioleoylglycerol, 45.4%. Human plasma very low density lipoproteins also protected against the inhibition of enzyme activity by the Fab fragments. These immunological studies suggest that the interaction of lipoprotein lipase with apolipoprotein C-II in the presence of lipids is associated with a conformational change in the structure of the enzyme such that the Fab fragments are less inhibitory. The consequence of a conformational change in lipoprotein lipase may be to facilitate the formation of an enzyme-triacylglycerol complex so as to enhance the rate of the lipoprotein lipase-catalyzed turnover of substrate to products.


Associations between schizotypal personality features, mentalizing difficulties and thought problems in a sample of community adolescents.
Schizotypal trait expression and mentalizing impairments represent key factors associated with increased vulnerability for schizophrenia. In the current study, we analysed the nature of associations linking specific schizotypal personality features to mentalizing difficulties during adolescence. Furthermore, we examined the extent to which mentalizing difficulties mediate the relationship between schizotypal trait features and self-reported thought problems. One hundred and five community adolescents (Mage = 15.72; SD = 1.91) completed a recently developed self-report measure of mentalizing (Reflective Functioning Questionnaire [RFQ]), evaluating the degree of certainty (RFQc-scale) and uncertainty (RFQu-scale) with which individuals utilize mental state information to understand their own and others' behaviour. High scores on the RFQu-scale reflect poor usage of mental state information, while high scores on the RFQc-scale capture adaptive levels of certainty about mental states. Self-report questionnaires were also used to assess schizotypal trait expression, thought problems and symptoms of anxiety/depression. Linear regression models indicated that schizotypal features of social anxiety and odd speech accounted for increased RFQu scores, while odd speech also accounted for reduced RFQc scores. RFQu partially mediated the effects of social anxiety and odd speech on the level of thought problems in the sample. Present findings suggest that schizotypal features that impede interpersonal communication during adolescence are linked to difficulties in mental state understanding. Our study also provides original data suggesting that the effects of social anxiety and odd speech on psychosis-risk may partially depend upon the level of mentalizing uncertainty. Mentalizing difficulties may constitute important clinical assessment and early prevention treatment targets in adolescents who demonstrate schizotypal features.


Under-notification of cryptosporidiosis by routine clinical and laboratory practices among non-hospitalised children with acute diarrhoea in Southern Spain.
In a prevalence study of 400 stool samples from non-hospitalised children under 7 years of age with diarrhoea, the presence of Cryptosporidium was evaluated. In addition to standard microbiological analyses used for testing for bacteria, parasites, adenoviruses and reoviruses, all samples were re-evaluated for the presence of Cryptosporidium by means of microscopy using a modified acid-fast staining technique, a rapid immunoassay for the qualitative detection of C. parvum and Giardia lamblia, the ImmunoCard STAT! test, and nested polymerase chain reaction (PCR). For identifying the genotypes of Cryptosporidium, the gene 18S ssu rRNA was amplified and sequenced. Thirty-two samples were positive by microscopy, 26 by immunoassay and 61 by nested PCR. Twenty-seven of these organisms were identified as Cryptosporidium hominis, 31 as Cryptosporidium parvum and, in four samples, it was impossible to identify the species. C. parvum was significantly more frequent in girls and C. hominis was significantly more frequent in boys (Fisher's exact test, p = 0.034). Although Cryptosporidium is only notified in a very small number of patients (1-4%) with diarrhoea in Spain, the microorganism was identified by nested PCR in 15.1% of the samples. This study, therefore, highlights the under-notification of infections caused by Cryptosporidium in Southern Spain and poses the question of whether its routine testing should be carried out in cases of gastroenteritis in children.


Expansion of antigen-specific T cells from cerebrospinal fluid of patients with multiple sclerosis.
We have expanded cerebrospinal fluid (CSF) T lymphocytes obtained from four patients with multiple sclerosis (MS). Fresh CSF cells were placed into culture with medium, interleukin-2, irradiated autologous peripheral blood mononuclear cells, and either myelin basic protein (BP) or measles virus antigen. Two CSF cell lines demonstrated a mild degree of antigen-specific proliferation to BP, a third reacted with measles virus, and the fourth demonstrated no known antigenic specificity. The percentage of HLA-DR + cells was increased in all four cell lines. The culture procedure has thus selected for a population of activated T cells, some of which demonstrate reactivity with antigens of potential relevance to the pathogenesis of MS.


Increased left prefrontal activation during staring/mutism episodes in a patient with resistant catatonic schizophrenia: a near infrared spectroscopy study.
To present the first near infrared spectroscopy (NIRS) study of a patient with resistant catatonic schizophrenia during residual episodes of catatonia-related symptoms. Functional imaging studies generally point to a decreased cortical activation in catatonic patients, with the notable exception of increased orbitofrontal/medial prefrontal activity elicited by negative stimuli. Cortical activity of the left anterior prefrontal area was recorded with a Techen 4 x 4 NIRS apparatus. Four episodes of staring/mutism were recorded and averaged. Compared with normal activity, these episodes were characterized by increased cortical activation. Within its methodologic limitations, the present observation suggests that increased anterior prefrontal activation in catatonic patients is not specific to negative stimuli. Known functions of the anterior prefrontal cortex such as self monitoring, reallocation of attention, or conflict resolution might underlie these findings. These also attest to the potential of NIRS for functional imaging of vulnerable subjects.


Effect of repetitive stimulation on the frog neuromuscular transmission.
Presynaptic and postsynaptic effects on the neuromuscular transmission were studied during 20 min of indirect stimulation at 10/s. During the 'facilitation' period, there was an increase in the quantal content, in the frequency of miniature endplate potentials and in their amplitude. All these parameters were decreased during the 'depression' period. Besides, the end-plate current (e.p.c.), recorded during this high rate of stimulation, increasingly lengthened. The falling phase of the e.p.c. was exponential during facilitation, while marked deviations from the exponential time course were observed during depression. The experiments showed that a possible change in the kinetics between the receptors and the mediator was not responsible for the lengthened time course of the e.p.c. Therefore, it is assumed that either the delayed diffusion of the transmitter from the synaptic cleft or an altered mechanism of the release of acetylcholine may be involved. The latter possibility is supported by a progressive prolongation of the synaptic delay, which was observed during a prolonged repetitive stimulation.


Deep phenotypical characterization of human CD3+ CD56+ T cells by mass cytometry.
CD56+ T cells are a group of pro-inflammatory CD3+ lymphocytes with characteristics of natural killer cells, being involved in antimicrobial immune defense. Here, we performed deep phenotypic profiling of CD3+ CD56+ cells in peripheral blood of normal human donors and individuals sensitized to birch-pollen or/and house dust mite by high-dimensional mass cytometry combined with manual and computational data analysis. A co-regulation between major conventional T-cell subsets and their respective CD3+ CD56+ cell counterparts appeared restricted to CD8+ , MAIT, and TCRγδ+ T-cell compartments. Interestingly, we find a co-regulation of several CD3+ CD56+ cell subsets in allergic but not in healthy individuals. Moreover, using FlowSOM, we distinguished a variety of CD56+ T-cell phenotypes demonstrating a hitherto underestimated heterogeneity among these cells. The novel CD3+ CD56+ subset description comprises phenotypes superimposed with naive, memory, type 1, 2, and 17 differentiation stages, in part represented by a phenotypical continuum. Frequencies of two out of 19 CD3+ CD56+ FlowSOM clusters were significantly diminished in allergic individuals, demonstrating less frequent presence of cells with cytolytic, presumably protective, capacity in these donors consistent with defective expansion or their recruitment to the affected tissue. Our results contribute to defining specific cell populations to be targeted during therapy for allergic conditions.


Trichoscopic evaluation of dental pulp stem cell conditioned media for androgenic alopecia.
Conditioned media (CM) derived from mesenchymal stem cells (MSC) is known to induce hair regrowth in androgenic alopecia. The objectives of the study were to assess the efficacy and safety of one type of MSC-CM, the CM derived from dental pulp stem cells obtained from human exfoliated deciduous teeth (SHED-CM) and to compare the efficacy of SHED-CM with and without dihydrotestosterone synthesis inhibitor (DHT-inhibitor). Eighty-eight male androgenic alopecia subjects with Hamilton-Norwood Classification (H-N C) I-VII were evaluated by trichoscopy to explore which trichoscopic factors statistically correlated with H-N C. After being screened, 33 subjects received six SHED-CM treatments at 1-month intervals. Clinical severity was assessed through global and trichoscopic images from baseline to 9th month. SHED-CM was effective for 75% of subjects regardless of disease severity, concomitant DHT-inhibitor use, and age. Adverse effects including pain and small hemorrhages were transient and mild. We also found that clinical hair status evaluated by absolute values of three quantitative trichoscopic factors (maximum hair diameter, vellus hair rate, and multi-hair follicular unit rate) showed a good correlation with H-N C stages, and what is more-a scoring system of these three factors can be a possible predictor of SHED-CM efficacy. We have shown that SHED-CM provides global and trichoscopic image improvement for androgenic alopecia, regardless of concomitant DHT-inhibitor use.


The next generation: poor compliance with risk factor guidelines in the children of parents with premature coronary heart disease.
The offspring of individuals with premature coronary heart disease are themselves at increased risk for myocardial infarction before the age of 55. Consensus panels have recommended that all such offspring undergo an evaluation of cardiovascular risk, including cholesterol testing. To examine self-reported rates of cardiovascular risk factor assessment in this population, we conducted a telephone survey of 318 Canadian adults with premature coronary heart disease and of one offspring from 298 (94%) of the 318 families. The median age of the offspring was 20 years (range 2 to 39 y). Among the 219 late adolescent and young adult offspring, only 97 (44%) reported having had a blood cholesterol measurement during the preceding 3 years. Thirty-seven percent reported being current smokers, 31% were overweight, and 30% exercised fewer than three times per week. Men were less likely than women to report having had their blood pressure measured in the preceding year (57% vs 80%). These low rates of cardiac risk factor assessment families of patients with premature coronary heart disease represent missed opportunities for primary prevention. More effective strategies to prevent atherosclerosis in this population are needed.


Bilateral Horner's syndrome in cluster type headaches.
A patient with cluster type headaches demonstrated bilateral and alternating ocular sympathetic dysfunction during a spontaneous as well as a nitroglycerin-induced attack. Biochemical evaluation revealed postganglionic pupillary dysfunction on the symptomatic side and preganglionic pupillary dysfunction contralaterally. These findings defy a simple explanation regarding a central or peripheral origin of the oculocephalic sympathetic dysfunction.


(4-Substituted-phenyl)-(5H-10,11-dihydro-pyrrolo [2,1-c][1,4] benzodiazepin-10-yl)-methanone derivatives as vasopressin receptor modulators.
Synthesis and structure-activity relationships (SAR) of arginine vasopressin (AVP) receptor modulators are described. Potent and selective compounds are prepared when the amide linkage connecting rings A and B of VPA-985 is replaced with a bond, CO, -O-, -S-, or -SO2- bond.


Confirmation of existence of a new syndrome: LAPS syndrome.
In l998, Hopkin et al. described a new disorder characterized by progressive laryngotracheal stenosis, short stature, and arthropathy. We provide extensive clinical information on two additional unrelated patients with this distinctive disorder and propose the name LAPS syndrome, to reflect the most consistently recognized features, namely, Laryngotracheal stenosis, Arthropathy, Prognathism, and Short stature.


Brow/Upper lid anatomy, aging and aesthetic analysis.
The upper eyelid serves the important anatomic function of protecting the eye and rewetting the cornea to maintain vision. The complex dynamic action of the upper eyelid explains its relatively complex anatomy. The brow has an important supportive role. Studies have revealed facial characteristics perceived as youthful and aged, and the anatomic basis of these changes is defined at many levels. Characteristic aging changes in the upper eyelid and brow create an appearance of aging and opportunities for functional and aesthetic improvement.


Esophageal Dysmotility, Gastro-esophageal Reflux Disease, and Lung Transplantation: What Is the Evidence?
Lung transplantation is an effective and life-prolonging therapy for patients with advanced lung disease (ALD). However, long-term patient survival following lung transplantation is primarily limited by development of an inflammatory and fibrotic process involving the lung allograft known as bronchiolitis obliterans syndrome (BOS). Although the precise cause of BOS remains uncertain and is likely multifactorial, chronic aspiration of gastro-duodenal contents is one possible contributing factor. Multiple small, cross-sectional studies performed over the past two decades have reported a high prevalence of gastro-esophageal reflux disease (GERD) and esophageal dysmotility in the ALD population and several investigations suggest the prevalence may increase following lung transplantation. More recent studies evaluating the direct effect of gastro-duodenal contents on airways have demonstrated a possible biologic link between GERD and BOS. Despite the recent advances in our understanding of BOS, further investigations are needed to establish GERD as a causative factor in its development. This review will discuss the existing literature that has identified an association of GERD with ALD and post-transplant populations, with a focus on recent advances in the field.


A pharmacist-led pilot program to facilitate deprescribing in a primary care clinic.
To develop and pilot-test a model in which a community-based clinical pharmacist was incorporated as part of a Medicare Annual Wellness Visit (AWV) to make deprescribing recommendations targeted at potentially inappropriate medications (PIMs) in seniors. A family medicine patient-centered medical home (PCMH) clinic in Buffalo, NY. Implementation and evaluation of a pilot program incorporating a pharmacist-provided medication review targeting PIMs in seniors as part of a Medicare AWV. A community pharmacy-based clinical pharmacist provided face-to-face medication reviews for patients older than 65 years as part of their AWV with a focus on deprescribing PIMs. No clinical pharmacy service existed at the practice when this program was implemented. Identified PIMs, pharmacist recommendations, recommendation acceptance rate, time spent on intervention, health care utilization at 6 months postvisit, and barriers to implementation. Of the 21 patients enrolled, 13 unique patients received a total of 20 deprescribing recommendations from the pharmacist. The overall acceptance rate for pharmacist recommendations was 20%. The pharmacist spent a mean (± SD) of 34 (± 6) minutes per patient encounter. One patient in the intervention group was hospitalized, and 1 was seen in the emergency department (ED) during the 6-month follow-up period compared with 1 patient in the control group who had an ED visit. We identified multiple logistical and organizational barriers to the implementation of the intervention. In this prospective pilot study, a workflow to include a pharmacist medication review to facilitate deprescribing in the primary care setting was tested. We encountered several barriers to integrating the pharmacist into the AWV workflow to deliver the intervention. Future pragmatic clinical trials are warranted to improve provider awareness and comfort with deprescribing PIMs in seniors.


Incidental detection of carcinoma gall bladder in laparoscopic cholecystectomy specimens: a thirteen year study of 23 cases and literature review.
Carcinoma of gall bladder is the most common malignancy of the biliary tract worldwide and is usually associated with poor prognosis. In this era of laparoscopic cholecystectomy, there has been increase in detection of early stage incidental gall bladder carcinoma in cholecystectomy specimens. A retrospective study was carried out in tertiary care hospital in central India. A total of 2990 patients underwent laparoscopic cholecystectomy during the year 2001-2013. Hospital records and histopathology reports of these patients were studied in detail. Twenty three cases of gall bladder carcinoma were detected incidentally accounting for an incidence of 0.76 %. It was more common in females with an M: F ratio of 1:1.9. Mean age of presentation was 57.8 years. Gall stones were present in 22 cases and one patient presented with features of acute cholecystitis. Three patients had associated xanthogranulomatous inflammation and 10 had associated intestinal metaplasia. It is not uncommon to encounter incidental malignancies of gall bladder in laparoscopic cholecystectomy specimens sent to histopathology for presumably benign disease. Histopathology reports must include comments on extent of infiltration, perineural invasion, tumor differentiation and nodal involvement for oncologist information and subsequent management of patients.


Protein-ligand binding interactions of imidazolium salts with SARS CoV-2.
The disease called severe acute respiratory syndrome (SARS) is a lifestyle intimidating viral contamination affected by a positive, single stranded novel RNA virus (COVID-2019) from the enveloped coronaviruse family. The COVID-2019 virus has affected many people, scattering promptly, and researchers are attempting to find out medicines for its effectual cure in all over the globe. Chloroquine (ChQ) and its derivatives, an older drug used for the cure of malaria, is exposed to encompass a perceptible feasibility and commendable well-being in opposition to SARS CoV-2 associated pneumonia clinical trials conducted in China. Later on, a few investigations have been directed to find and present SARS CoV-2 antiviral medications. The aim of this present work deals with the potential binding interactions of some imidazolium salts with Nsp9 (Nonstructural protein 9) RNA binding protein of SARS CoV-2.


Flightlessness affects cranial morphology in birds.
Flightless birds belonging to phylogenetically distant clades share several morphological features in the pectoral and pelvic apparatus. There are indications that skull morphology is also influenced by flightlessness. In this study we used a large number of flightless species to test whether flightlessness in modern birds does indeed affect cranial morphology. Discriminant analyses and variation partitioning show evidence for a relationship between skull morphology and the flightless condition in birds. A possible explanation for the change in cranial morphology can be linked to the reduced selective force for light-weight skulls in flightless birds. This makes an increase in muscle mass, and therefore an enlargement of muscle insertion areas on the skull, possible. We also compared the ontogenetic trajectory of Gallus with the adult morphology of a sample of flightless species to see whether the apomorphic features characterizing the skull of flightless birds share the same developmental basis, which would indicate convergent evolution by parallelism. Skull morphology (expressed as principal component scores) of palaeognathous flightless birds (ratites) is dissimilar (higher scores) to juvenile stages of the chicken and therefore seem peramorphic (overdeveloped). Principal component scores of adult neognathous flightless birds fall within the range of chicken development, so no clear conclusions about the ontogenetic trajectories leading to their sturdier skull morphology could be drawn.


Intra-arterial DSA: early experience with a 1024(2) matrix.
Twenty patients were studied with intra-arterial digital subtraction angiography (IA DSA), utilizing a 1024(2) matrix memory. Acquisition of the images was through a prototype television camera incorporating a finely focused electron beam. In five cases, comparison between a 512 X 512 (512(2)) matrix acquisition and a 1024 X 1024 (1024(2)) matrix acquisition mode was made, with injections occurring in the same vessel in the same patient. The clinical material demonstrated no significant improvement in image quality at the 4 1/2 as well as the 6 inch image intensifier (II) modes. However, the 1024(2) matrix combined with the 9 inch II mode showed foci of disease and normal anatomy with detail not always seen on the 9 inch II when a 512(2) matrix was used. In no case, however, was the basic diagnosis missed with the 512(2) matrix. Spatial resolution, as measured from lead bar test pattern images, demonstrated that the 1024(2) matrix allows a 70% or greater improvement in spatial resolution over the 512(2) for the 4 1/2, 6 and 9 inch II modes. For a given mode the radiation dose was held constant for the two matrix sizes.


Varied Presentation of Venous Ectasia Head and Neck: Case Series and Review of Literature.
Jugular venous ectasia in head and neck region is a rare entity. They may present as asymptomatic neck masses and should be considered in the differential diagnosis of cystic neck masses. Management is individualised based on the patient and includes conservative or surgical management. We hereby report three cases of venous ectasia (2-external jugular and 1-facial vein) managed at our institute.


Estrogen receptor α is the major driving factor for growth in tamoxifen-resistant breast cancer and supported by HER/ERK signaling.
Resistance to tamoxifen is a major clinical challenge in the treatment of breast cancer; however, it is still unclear which signaling pathways are the major drivers of tamoxifen-resistant growth. To characterize resistance mechanisms, we have generated different tamoxifen-resistant breast cancer cell lines from MCF-7. In this model, we investigated whether signaling from human epidermal growth factor receptors (HERs), their downstream kinases, or from the estrogen receptor α (ERα) was driving tamoxifen-resistant cell growth. Increased expression of EGFR and increased phosphorylation of HER3 were observed upon acquisition of tamoxifen resistance, and the extracellular activated kinase (ERK) signaling pathway was highly activated in the resistant cells. The EGFR inhibitor gefitinib and the ERK pathway inhibitor U0126 resulted in partial and preferential growth inhibition of tamoxifen-resistant cells. All the tamoxifen-resistant cell lines retained ERα expression but at a lower level compared to that in MCF-7. Importantly, we showed via ERα knockdown that the tamoxifen-resistant cells were dependent on functional ERα for growth and we observed a clear growth stimulation of resistant cell lines with clinically relevant concentrations of tamoxifen and 4-OH-tamoxifen, indicating that tamoxifen-resistant cells utilize agonistic ERα stimulation by tamoxifen for growth. The tamoxifen-resistant cells displayed high phosphorylation of ERα at Ser118 in the presence of tamoxifen; however, treatment with U0126 neither affected the level of Ser118 phosphorylation nor expression of the ERα target Bcl-2, suggesting that ERK contributes to cell growth independently of ERα in our cell model. In support of this, combined treatment against ERα and ERK signaling in resistant cells was superior to single-agent treatment and as effective as fulvestrant treatment of MCF-7 cells. Together, these findings demonstrate that ERα is a major driver of growth in tamoxifen-resistant cells supported by HER/ERK growth signaling, implying that combined targeting of these pathways may have a clinical potential for overcoming tamoxifen resistance.


Partner influences on young women's risky drug and sexual behavior.
Adolescent girls with a history of maltreatment are at heightened risk for health-risking behaviors, including unsafe sexual behaviors and drug use. However, few studies have examined the views of this population in regard to sexual partner choice, sexual behaviors, and decisions to use drugs with sexual partners. We conducted 15 semistructured, open-ended qualitative interviews with young women ages 18-24 with a history of maltreatment and asked them to reflect on their experiences as adolescents. We used the constant comparison method to group the qualitative coded data into themes. Analysis of the interviews suggested that adolescent girls with maltreatment histories often report that they chose partners who are promotive of risky drug and sexual behavior. The interviews also provided insight into why this population is likely to use drugs with their partner and why they might be hesitant to talk about or practice safe sex with their partner. The young women's feedback highlighted five areas where adolescent girls with maltreatment histories could benefit: (a) provision of information about partner characteristics that are promotive of both risky behavior and those that are linked to healthy relationships, (b) provision of information about how one's partner can influence one's own drug use,


[Use of the macrophage migration inhibition test in the study of relationships between mycobacterial antigens].
In this study, 3 groups of 15 rabbits each were sensitized with killed Mycobacterium tuberculosis, M. kansasii or M. avium bacteria. The sensitization was performed through the footpad. Eighteen days after sensitization, cellular immunity of the rabbits was tested with total homologous and heterologous antigens by direct and indirect migration inhibition tests using spleen macrophages. The bacteria were sonicated and centrifuged at 100,000 g for 1 h. The supernatant was used as the cytoplasmic antigen. Assayed by indirect migration, the migration index (MI) for homologous antigens was highly specific compared to heterologous antigens (MI of 0,60-0,65 compared to 0,79-0,96). The patterns obtained for rabbits sensitized with M. tuberculosis or M. kansasii when assayed by direct migration in the presence of homologous antigens (MI of 0,58 and 0,61, respectively) were similar. M. avium gave a distinct pattern. The results obtained indicate that crossed activity with heterologous antigens would be due to the presence of common components in the total antigens of the mycobacteria in question. On the other hand, the lower specificity of the direct test would result from the role played by humoral factors and antibodies, which might influence simultaneously migration of the target macrophages.


Effect of Sensory Modality on Reaction Time in Individuals with Auditory Neuropathy Spectrum Disorder.
To investigate and compare the reaction time of individuals with auditory neuropathy in three modalities, auditory, visual, and audio-visual. The reaction time of individuals with auditory neuropathy was also compared with those with normal hearing. The relationship between reaction time across modalities and the duration of hearing loss in auditory neuropathy was also investigated. The reaction time of adults with auditory neuropathy and those with normal hearing was measured in the three modalities using the Choice reaction time task. The auditory neuropathy group significantly had a longer reaction time than the normal hearing in all modalities. The trend of the mean reaction time differed across groups. Further, a significant difference in reaction time of the auditory neuropathy group was noted between auditory and visual mode, auditory and audio-visual mode. However, no significant difference between visual and audio-visual modalities was noted in reaction time. Significantly longer reaction time in auditory neuropathy is presumed to have resulted from neural conduction delay and impaired processing. The auditory neuropathy group can utilize visual cues for faster processing, and the study recommends an audio-visual mode for their management. In addition, the duration of hearing loss in auditory neuropathy had no relationship with reaction time across all modalities.


5-Lipoxygenase and leukotriene A4 hydrolase expression in primary nephrotic syndrome.
Gene expression of 5-lipoxygenase (5-LO) and leukotriene A(4) (LTA(4)) hydrolase was analyzed in the peripheral blood of 48 children with active primary nephrotic syndrome (PNS) (group I), 27 children with PNS in remission (group II), and 20 controls. Group I included 34 patients with steroid-sensitive PNS (SSNS) and 14 patients with steroid-resistant PNS (SRNS). Total RNA purified from peripheral blood mononuclear (PBMN) cells was reverse transcribed into cDNA and amplified with specific primers in the polymerase chain reaction. All group I patients and none of the controls expressed 5-LO and LTA(4 )hydrolase. Of group II children, 22.2% expressed 5-LO, while 51.9% expressed LTA(4 )hydrolase. Among group I patients there was a significant positive correlation between the degree of proteinuria and the expression of 5-LO ( r=0.27, P=0.03) and LTA(4 )hydrolase ( r=0.44, P=0.001). There was no difference in the degree of expression of both enzymes between SSNS and SRNS patients. In conclusion, leukotrienes may play a role in the pathogenesis of PNS in children, but they do not participate in the response of these patients to steroids.


Patient-directed Internet-based Medical Image Exchange: Experience from an Initial Multicenter Implementation.
Inefficient transfer of personal health records among providers negatively impacts quality of health care and increases cost. This multicenter study evaluates the implementation of the first Internet-based image-sharing system that gives patients ownership and control of their imaging exams, including assessment of patient satisfaction. Patients receiving any medical imaging exams in four academic centers were eligible to have images uploaded into an online, Internet-based personal health record. Satisfaction surveys were provided during recruitment with questions on ease of use, privacy and security, and timeliness of access to images. Responses were rated on a five-point scale and compared using logistic regression and McNemar's test. A total of 2562 patients enrolled from July 2012 to August 2013. The median number of imaging exams uploaded per patient was 5. Most commonly, exams were plain X-rays (34.7%), computed tomography (25.7%), and magnetic resonance imaging (16.1%). Of 502 (19.6%) patient surveys returned, 448 indicated the method of image sharing (Internet, compact discs [CDs], both, other). Nearly all patients (96.5%) responded favorably to having direct access to images, and 78% reported viewing their medical images independently. There was no difference between Internet and CD users in satisfaction with privacy and security and timeliness of access to medical images. A greater percentage of Internet users compared to CD users reported access without difficulty (88.3% vs. 77.5%, P < 0.0001). A patient-directed, interoperable, Internet-based image-sharing system is feasible and surpasses the use of CDs with respect to accessibility of imaging exams while generating similar satisfaction with respect to privacy.


Clinical outcomes and survival following lung transplantation in patients with Alpha-1 antitrypsin deficiency.
The primary intention of our study is to describe disease-specific outcomes in patients with alpha-1 antitrypsin deficiency (AATD) following lung transplantation (LT). We reviewed the Organ Procurement and Transplant Network database to identify AATD patients who have undergone LT in the United States. Two thousand two hundred and thirteen patients with AATD underwent LT between March 1992 and September 2019. A total of 1556 patients received LT with a median age at listing was 51 years. The median time spent on the LT waitlist was 263 days. The median ischemic time was 4.75 h. The Kaplan-Meier survival analysis following LT for AATD patients at 1-, 5-, and 10 years was 82%, 56%, and 34%, at 1-, 5-, and 10 years, respectively. The median survival time post-LT is 6.4 years (Interquartile range 5.6-6.8 years). The post-LT survival was significantly better in double LT compared to single LT (Median 7.7 vs 4.4 years, p < 0.001). Increasing age, presence of CMV mismatch, reintubation prior to discharge, and requiring treatment for rejection within one year of transplantation did impact post-LT mortality. The median survival after LT in AATD is 6.4 years and is similar to other lung diseases. When compared to usual COPD LT, AATD patients have increased post-LT mortality due to infections and liver disease. Recipients of a double lung transplant had a favorable outcome compared to single lung transplant.


Binding characteristics of fluoresceinated Lotus tetragonolobus fucolectin to macrophage populations which are either responsive or refractory to activation by lymphokine.
Fucose binding protein (FBP) from Lotus tetragonolobus seed was studied by fluorescence microscopy for its binding characteristics to various guinea pig peritoneal macrophage populations. Fluoresceinated FBP (FITC-FBP) was bound optimally at 22 degrees C in a punctate distribution and was internalized at 37 degrees C. Binding of FBP to macrophages was reversed specifically by the competitive sugar L-fucose, and not by D-fucose, L-rhamnose, or D-galactose. FBP was bound with greater frequency and intensity to 3-day oil-elicited peritoneal macrophages which are responsive to migration inhibition by FBP and migration inhibitory factor (MIF) than to resident or 7-day inflammatory macrophages which are unresponsive to activation by the same effectors. Competition for visual binding of FITC-FBP to macrophages was demonstrated by preincubation of cells with unlabeled FBP or MIF. Competition of FITC-FBP binding by MIF was reversed by L-fucose. These results indicate that FBP binds preferentially, with greater frequency and intensity, to macrophage subpopulations which are responsive to MIF than to MIF-refractory macrophages. The data further supports the existence of a common receptor site for MIF and FBP on the macrophage membrane which involves fucosyl determinants.


Pharmacokinetics of triamterene in geriatric patients--influence of piretanide and hydrochlorothiazide.
Pharmacokinetics of triamterene (single oral dose of 50 mg) and its pharmacologically active metabolite (OH-TA-ester) were determined in 20 geriatric patients with multiple diseases. Mean peak concentration of triamterene was increased in the elderly patients compared with the data of young healthy volunteers. Coadministration of piretanide seems to lower the mean plasma concentration (AUC) and the mean concentration after 24 h of triamterene as compared with the coadministration of hydrochlorothiazide.


ATP-binding cassette protein ABCF1 couples transcription and genome surveillance in embryonic stem cells through low-complexity domain.
OCT4 and SOX2 confer pluripotency by recruiting coactivators to activate stem cell–specific transcription. However, the composition of coactivator complexes and their roles in maintaining stem cell fidelity remain unclear. Here, we report the ATP-binding cassette subfamily F member 1 (ABCF1) as a coactivator for OCT4/SOX2 critical for stem cell self-renewal. The intrinsically disordered low-complexity domain (LCD) of ABCF1 contributes to phase separation in vitro and transcriptional activation of pluripotency genes by mediating multivalent interactions with SOX2 and co-dependent coactivators XPC and DKC1. These LCD-driven transcription factor–coactivator interactions critical for pluripotency gene expression are disrupted by DNA damage, likely due to LCD-dependent binding of ABCF1 to damage-generated intracellular DNA fragments instead of SOX2. This study identifies a transcriptional coactivator that uses its LCD to form selective multivalent interactions to regulate stem cell self-renewal and exit from pluripotency when genome integrity is compromised.


Thyroid function and mortality in older men: a prospective study.
Mild abnormalities of thyroid function have been associated with both beneficial and detrimental effects on mortality. Our objective was to determine the association between continuous TSH as well as categories of thyroid function with total and cause-specific mortality in a cohort of older men. Data were analyzed from the Osteoporotic Fractures in Men (MrOS) study, a cohort of community-dwelling U.S. men aged 65 yr and older. A total of 1587 participants randomly selected for thyroid function testing were included in this analysis. TSH and free T4 were measured at baseline, and four categories of thyroid function were defined. (subclinical hyperthyroid; euthyroid; subclinical hypothyroid TSH<10 mIU/liter; and subclinical hypothyroid, TSH≥10 mIU/liter.) Total mortality, cardiovascular (CV) and cancer deaths were confirmed by review of death certificates. There were 432 deaths over a mean follow-up of 8.3 yr. In fully adjusted models, there was no association between baseline TSH and any death [relative hazard (RH)=1.01 per mIU/liter, 95% confidence interval (CI)=0.95-1.06], CV death (RH=1.05 per mIU/liter, 95% CI 0.96-1.15), or cancer death (RH=0.96 per mIU/liter, 95% CI=0.85-1.07). There was also no statistically significant association between thyroid function category and total or cause-specific mortality, but few men (n=8) had subclinical hypothyroidism with TSH levels of 10 mIU/liter or higher. A single measurement of thyroid function did not predict total or cause-specific mortality in this cohort. These data support neither a beneficial nor a detrimental effect of subclinical thyroid dysfunction in older men. Subclinical thyroid dysfunction is not associated with an increased risk of all-cause or CV mortality in older men.


A new gonad-infecting species of Philometra (Nematoda: Philometridae) from the red cusk-eel Genypterus chilensis (Osteichthyes: Ophidiidae) off Chile.
A new nematode species, Philometra genypteri sp. n. (Philometridae), is described from male and female specimens found in the ovary of red cusk-eel, Genypterus chilensis (Guichenot) (Ophidiidae, Ophidiiformes), from the eastern South Pacific Ocean off the coast of northern Chile. Based on light and scanning electron microscopy examination, the new species differs from most other gonad-infecting Philometra spp. in the length of spicules (126-135 μm), a gubernaculum with dorsal lamella-like structures on its distal end, and the number and arrangement of genital papillae in the male. From a few congeneric, gonad-infecting species with unknown males, it can be distinguished by some morphological and biometrical features found in gravid female (absence of caudal projections, length of first-stage larvae or oesophagus, moderately developed anterior oesophageal inflation) and by the host type (fish family) and geographical distribution. P. genypteri is the first philometrid species reported from a fish belonging to the order Ophidiiformes and the second nominal species of Philometra recorded from marine fishes of the eastern South Pacific.


Sex differences in clinical characteristics and long-term outcomes in patients with vasospastic angina: results from the VA-Korea registry, a prospective multi-center cohort.
Sex differences in clinical characteristics and prognosis of vasospastic angina (VA) have not been well elucidated. This study was performed to investigate sex-specific characteristics and predictors for long-term clinical outcomes in patients with VA. We analyzed 1838 patients (55 years and 62% male) who were diagnosed with definite (n = 680) or intermediate (n = 1212) VA in ergonovine provocation test from a nation-wide VA registry. The primary study end-point was composite events including cardiac death, acute coronary syndrome, ventricular tachycardia or fibrillation, and atrioventricular block during clinical follow-up. Male patients were younger, and there were more smokers and alcohol drinkers in male patients than in female patients. During the median follow-up period of 760 days (interquartile range, 336-1105 days), there were 73 cases (3.97%) of composite events. There was no sex difference in the occurrence of composite events (log-rank p = 0.649). Concomitant significant (≥ 50%) organic coronary stenosis was associated with worse clinical outcomes in both male (hazard ration [HR], 1.97; 95% confidence interval [CI], 1.01-3.85; p = 0.047) and female (HR, 3.26; 95% CI, 1.07-9.89; p = 0.037) patients. Obesity (body mass index ≥ 25 kg/m2) was associated with better prognosis in female VA patients (HR, 0.22; 95% CI, 0.07-0.68; p = 0.008). Even when only patients with definite diagnosis of VA were considered, there was no significant sex difference in clinical outcomes (log-rank p = 0.876). In VA patients, there were several different clinical characteristics according to sex; however, long-term clinical outcome was similar between sexes. Significant organic coronary stenosis in both sexes and low body mass index (< 25 kg/m2) in females were associated with worse prognosis in VA patients.


Efficacy and safety of zero-fluoroscopy ablation for supraventricular tachycardias. Use of optional contact force measurement for zero-fluoroscopy ablation in a clinical routine setting.
Conventional catheter ablation of cardiac arrhythmias is associated with radiation risks for patients and laboratory personnel. Widespread use of zero-fluoroscopic catheter ablation in clinical routine is limited by safety concerns. This study investigated the feasibility of zero-fluoroscopy catheter ablation using a three-dimensional mapping system and optional catheter contact force technology for an all-comers collective. The study comprised 184 patients; 91 patients, including 29 pediatric patients, underwent a zero-fluoroscopic electrophysiology (EP) study using the EnSite NavX system with real-time visualization of all electrodes. These patients were matched to a control group, which was treated using fluoroscopy in the same period. Inclusion criteria were documented supraventricular tachycardia or a history of symptomatic paroxysmal supraventricular tachycardia. Transseptal access, if necessary, was achieved under transesophageal echocardiographic guidance for ablation of left-sided arrhythmias. Radiofrequency (using optional contact force measurement) or a cryotechnique was used for ablation. We observed no major acute complications. There were no significant differences between the two groups in the follow-up period. Zero-fluoroscopic catheter ablation is generally feasible in right-sided cardiac arrhythmias. Safety concerns regarding left atrial substrates or children can be overcome with optional real-time contact force measurement.


Groin pain syndrome: an association of different pathologies and a case presentation.
groin pain affects all types of athletes, especially soccer players. Many diseases with different etiologies may cause groin pain. offer a mini review of groin pain in soccer accompanied by the presentation of a case report highlighting the possible association of more clinical frameworks into the onset of groin pain syndrome, in order to recommend that clinical evaluations take into account possible associations between bone, muscle and tendon such as inguinal canal disease. the multifactorial etiology of groin pain syndrome needs to be examined with a comprehensive approach, with standardized clinical evaluation based on an imaging protocol in order to evaluate all possible diseases. Mini review- Case report (Level V).


Swept-Source OCT Analysis of the Margin of Choroidal Coloboma: New Insights.
To study the retinal architecture and vitreoretinal interface at the edge of choroidal coloboma using swept-source OCT. Prospective observational case series at a tertiary eye care center. Patients with choroidal coloboma treated at an ophthalmology department and fulfilling the inclusion criteria of the study. Swept-source OCT was carried out in 30 eyes of 20 patients with choroidal coloboma. The primary objective was to describe the OCT features at the margin of the coloboma. Swept-source OCT of the coloboma margin revealed new features in addition to the previously described findings. Two types of transition from normal retina into intercalary membrane (ICM) were noted: abrupt (73.33%) and gradual (26.67%). Outer retinal layers (interdigitation zone and ellipsoid zone) terminated at a variable distance before the retinal pigment epithelium in 56.67% of eyes. Cystic spaces in the ICM (46.67%), schisis-like spitting of the ICM (30%), and breaks in the ICM (6.67%) were seen as well. Subclinical retinal detachment (RD) was also noted in 1 eye. The peculiar features noted at the vitreoretinal interface included vitreous attachment at the coloboma margin (23.33%), vitreous condensation (6.67%), and hill like projections of ICM into the vitreous cavity (26.67%). In the region of the coloboma, sclera and Tenon's capsule could also be analyzed as a hyperreflective lamellar structure and an irregularly arranged less hyperreflective structure. Swept-source OCT of the coloboma margin revealed various new features in addition to those described previously. The detection of subclinical RD or early termination of outer retinal layers in selected cases may be helpful in guiding new management protocols.


[Part III: free periosteal flaps as a treatment for mandibular osteoradionecrosis].
The vascularized periosteal free flap transposes a non-irradiated soft tissue with neo-angiogenesis, bone induction, and osteogenesis qualities. Its technique and interest are studied for early osteoradionecrosis. A retrospective study was made between 1992 and 2002. Thirty-four patients were selected among the 59 cases operated for osteoradionecrosis; all patients were classified stage II and I on the Epstein scale. Twenty-six patients were reconstructed using a non-periosteum free flap (bone, muscular or cutaneous flap), and eight patients were reconstructed using a "periosteum free flap". The study was clinical, radiological, and histological. Osteoradionecrosis evolved for two of the eight patients having undergone periosteum free flap surgery. Operative morbidity and the number of reoperation were less important than for the rest of the series. The reconstruction was satisfactory on a functional and esthetic level. A bone production was noted for two patients of the "periosteum" group. Periosteum free flap surgery is an alternative for early osteoradionecrosis. The periosteum brings osteo-induction and osteogenesis, and revascularization recorded clinically, radiologically, and histologically, even on an irradiated area.


Delayed thromboxane or tumor necrosis factor-alpha, but not leukotriene inhibition, attenuates prolonged pulmonary hypertension in endotoxemia.
The early phase of endotoxin-induced acute hemodynamic disturbances and hypoxemia is mediated by various factors, including eicosanoids and tumor necrosis factor-alpha (TNF alpha). Thromboxane A2 is the major mediator of the early pulmonary hypertension associated with endotoxemia, but the mechanisms underlying the prolonged hemodynamic disturbances observed in ongoing endotoxemia are not well understood. The authors used a chronically instrumental young piglet model to determine the roles of several eicosanoids and of TNF alpha in the prolonged endotoxin-induced pulmonary hypertension and other cardiovascular derangements. Animals were given 40 micrograms/kg endotoxin intravenously per hour for 30 minutes, followed by 20 micrograms/kg per hour. In all animals, persistent pulmonary hypertension, lowered cardiac output, any hypoxemia developed during endotoxin infusion. After 3 hours of endotoxin infusion, randomly ordered infusions of 1 mg/kg dazmegrel (a thromboxane A2 synthesis inhibitor), 5mg/kg nordihydroguaiaretic acid (a 5-lipoxygenase inhibitor), and 20 mg/kg pentoxifylline (A TNF alpha inhibitor) were given intravenously at 30-to-60-minute intervals. Dazmegrel and pentoxifylline lowered pulmonary arterial pressure and resistance and raised arterial oxygen tension. Cardiac output increased significantly after pentoxifylline. These hemodynamic effects persisted for 30-60 minutes, despite continued endotoxin infusion. The elevated plasma concentrations of thromboxane B2 and TNF alpha returned toward preendotoxin baseline values after dazmegrel and pentoxifylline treatment, respectively. No beneficial effects were noted after administration of nordihydroguaiaretic acid. Based on these results, both thromboxane A2 and TNF alpha, but not 5-lipoxygenase products, play active roles in prolonged endotoxin-induced pulmonary hypertension and hypoxemia in young piglets. Combined thromboxane A2 and TNF alpha blockade may be clinically useful in treatment of advanced sepsis in neonates.


External fixators as an adjunct to wound healing.
Complex foot and ankle wounds present multiple challenges for the reconstructive surgeon. Soft tissue deficits must be closed to protect underlying structures from infection and to provide a stable environment for healing. Surgical options commonly used include healing by secondary intention, local flap closure, skin grafts, pedicled flaps, and free tissue transfer. Despite a surgeon's best operative efforts, these strategies may fail because of postoperative shear forces created by premature joint motion or pressure (either weight bearing or decubitus). In the properly selected patient population, external fixators serve as an indispensable adjunct to wound healing by providing temporary offloading or immobilization of joints.


Effects of an 1-day education program on physical functioning, activity and quality of life in community living persons with multiple sclerosis.
Persons with MS (pwMS) in the community show reduced physical activity while studies demonstrated beneficial effects of exercise therapy in supervised settings. This study investigated, in pwMS living in the community, the effects of a 1-day education program about exercises and sports, on physical activity behavior and related outcome measures as self-efficacy, perceived walking ability, fatigue, perceived impact of MS and quality of life. PwMS attended an education day with theoretical and practical sessions that was organized by the Flemish MS Society and professional exercise experts. Forty-two participants immediately completed questionnaires as well as after three and six months. Overall disability and physical activity level were measured using PDSS (patient determined disease steps) and PASIPD (Physical Activity Scale for Individuals with Physical Disabilities) respectively. Other outcomes were the ESES, MSWS-12, MFIS, MSIS-29 and SF-36. Analyses of variance were performed in groups distinguished by self-reported disability level (PDDS ≤1; n = 24 and PDSS >1; n = 18). Groups differed significantly for perceived walking ability (PDDS,MSWS-12) and physical related-domains of MSIS-29 and SF-36, but not PASIPD. A trend towards significant group*time interaction effect was found for the PASIPD indicating, at 3 and 6 months, increased physical activity in the subgroup PDDS ≤1. For the MSIS-29, a significant time effect was found with reduced impact being largest for the more disabled group at 6 months. No changes were found in other outcome measures. An one-day education program had, depending on perceived disability level, some long-standing effects on physical activity and perceived impact of MS.


Intracellular synthesis of myxovirus neuraminidase in chick embryo cell monolayer culture. I. Neuraminidase activity, hemagglutinin synthesis, and content of cellbound sialic acid in Newcastle disease virus-infected cells.
Neuraminidase (Nase) activity of chick embryo monolayer cell homogenates was determined by its rate of splitting of neuraminlactose, free neuraminic acid (NA) being determined by the thiobarbituric acid assay. Noninfected cells were found to have no detectable amount of Nase activity. Newcastle disease virus (NDV)-infected cells (multiplicity of infection, 20 to 75 plaque-forming units per cell) displayed a high level of Nase synthesis, the rate of synthesis being parallel to that of hemagglutinin (HA) synthesis (with a 1.5 hr delay in the latter). An "eclipse" of the Nase and HA activities associated with the virus that was adsorbed onto cells was observed. The data provide evidence that the Nase is not incorporated into the viral envelope from a pre-existing cell supply but that its synthesis is coded by the viral genome. The content of cell-bound sialic acid, determined simultaneously in infected-cell homogenates, showed characteristic features allowing certain conclusions concerning the renewal of NA-terminating cell receptors during the course of infection, and the intracellular action of the Nase of the virus introduced into cells by the inoculum and that of the newly synthesized Nase at different stages of infection.


Panobinostat, a histone deacetylase inhibitor, rescues the angiogenic potential of endothelial colony-forming cells in moyamoya disease.
Moyamoya disease (MMD) is one of the most common causes of pediatric stroke. We found defective angiogenic function and downregulation of retinaldehyde dehydrogenase 2 (RALDH2) in MMD endothelial colony-forming cells (ECFCs). Downregulation of RALDH2 mRNA was caused by decreased binding of acetyl-histone H3 (Ac-H3) to the RALDH2 promoter. In this study, we evaluated the feasibility of using a histone deacetylase (HDAC) inhibitor, panobinostat, to upregulate RALDH2 expression and restore the angiogenic potential of MMD ECFCs. ECFCs from healthy normal controls and patients with MMD were isolated and characterized. After panobinostat treatment, western blot, tube formation, and chromatin immunoprecipitation (ChIP) assays were conducted in vitro. A matrigel plug assay was performed in vivo. Panobinostat increased the levels of Ac-H3 and Ac-H4 in both normal and MMD ECFCs but was much more effective in MMD ECFCs. Increased expression of RALDH2 by panobinostat was observed only in MMD ECFCs. Panobinostat increased the tube formation of both normal and MMD ECFCs in vitro and in vivo, but the effect was greater with MMD ECFCs. We demonstrated that panobinostat increases the angiogenic ability of MMD ECFCs by regulating RALDH2 acetylation. Our results suggest that panobinostat might be a potent therapeutic option for MMD patients.


First-Trimester Preterm Preeclampsia Screening in Nulliparous Women: The Great Obstetrical Syndrome (GOS) Study.
To estimate the ability of a combination of first-trimester markers to predict preterm preeclampsia in nulliparous women. We conducted a prospective cohort study of nulliparous women with singleton gestations, recruited between 110 and 136 weeks gestation. Data on the following were collected: maternal age; ethnicity; chronic diseases; use of fertility treatment; body mass index; mean arterial blood pressure (MAP); serum levels of pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF), soluble fms-like tyrosine kinase-1 (sFlt-1), alpha fetoprotein (AFP), free beta human chorionic gonadotropin (ß-hCG); and mean uterine artery pulsatility index (UtA-PI). We constructed a proportional hazard model for the prediction of preterm preeclampsia selected based on the Akaike information criterion. A receiver operating characteristic curve was created with the predicted risk from the final model. Our primary outcome was preterm preeclampsia and our secondary outcome was a composite of preeclampsia, small for gestational age, intrauterine death, and preterm birth. Among 4659 nulliparous women with singleton gestations, our final model included 4 variables: MAP MoM, log10PlGF MoM, log10AFP MoM and log10UtA-PI MoM. We obtained an area under the curve of 0.84 (95% CI 0.75-0.93) with a detection rate of preterm preeclampsia of 55% (95% CI 37%-73%) and a false-positive rate of 10%. Using a risk cut-off with a false-positive rate of 10%, the positive predictive value for our composite outcome was 33% (95% CI 29%-37%). The combination of MAP, maternal serum PlGF and AFP, and UtA-PI are useful to identify nulliparous women at high risk of preterm preeclampsia but also at high risk of other great obstetrical syndromes.


Heterochromatin associated with active versus inactive centromeres of mouse replicates at different times.
A subline of mouse L-cells carries a dicentric chromosome in which one centromere always separates prematurely. This centromere is not involved in the dynamics of chromosome migration and is considered inactive. By use of anti-BRdU antibody binding to BRdU-treated chromosomes it is shown that the pericentric constitutive heterochromatin associated with the prematurely separating centromere replicates earlier than its counterpart associated with the active centromere and even before several euchromatic regions in the genome. These results point to a possible mechanism by which dicentric chromosomes segregate equationally.


Laparoscopically assisted resection of intussuscepted Meckel's diverticulum.
We report a case of a Meckel's diverticulum with pancreatic heterotopia that had intussuscepted into the distal ileum, masquerading as a small bowel tumor and presenting with acute lower gastrointestinal hemorrhage. Laparoscopically assisted resection of the diverticulum was successfully accomplished.


[Mid-term, relatively tumor-stable outcome after an initially successful interdisciplinary surgical intervention with locally achieved R0 resection status including a multimodal therapeutic concept of a metastasized leiomyosarcoma of the inferior vena cava].
Progredient tumor-growth does not mean necessarily nihilism since (because of the latest multimodal therapeutic options) it might be possible to convert the malignant disease into a chronic stage depending on tumor entity, specific tumor-associated findings and expertise of the interdisciplinary oncological/oncosurgical team to utilize available and potential therapeutic measures. The aim of this report on an unusual case (with its patient-associated, therapeutic and prognostic aspects) of a leiomyosarcoma of the inferior vena cava with advanced tumor growth (characterized initially by pulmonary and hepatic, later on by additional vertebral metastases) is to illustrate its changeful clinical course after and during multimodal treatment episodes comprising surgical (abdomino-/vascular-/cardio- and neurosurgical-locally, R0 resection status), radiological and chemotherapeutic measures. A relatively stable disease over a specific time period of 5 years and 6 months was achieved. The 54-year old female patient with metastasized leiomyosarcoma of the inferior vena cava underwent local tumor resection en bloc with inferior vena cava segmental resection (following vascular surgical interposition of a prosthesis) and hemihepatectomy as well as resection of hepatic segment I. After recovery, a multistep and -modal treatment was initiated comprising of various protocols of systemic chemotherapy, thermoablation of recurrent hepatic metastases, various brachytherapy procedures (for hepatic and pulmonary metastases) and resection of a cerebral metastasis by a neurosurgeon including subsequent radiation. The patient demonstrates impressively that even in case of advanced tumor stage with initial, novel and recurrent metastases, a relatively stable disease over an intermediate time period (of more than 5 years) with an acceptable quality of life was achieved despite several complications.


Basolateral potassium channels of rabbit colon epithelium: role in sodium absorption and chloride secretion.
In order to assess the role of different classes of K(+) channels in recirculation of K(+) across the basolateral membrane of rabbit distal colon epithelium, the effects of various K(+) channel inhibitors were tested on the activity of single K(+) channels from the basolateral membrane, on macroscopic basolateral K(+) conductance, and on the rate of Na(+) absorption and Cl(-) secretion. In single-channel measurements using the lipid bilayer reconstitution system, high-conductance (236 pS), Ca(2+)-activated K(+) (BK(Ca)) channels were most frequently detected; the second most abundant channel was a low-conductance K(+) channel (31 pS) that exhibited channel rundown. In addition to Ba(2+) and charybdotoxin (ChTX), the BK(Ca) channels were inhibited by quinidine, verapamil and tetraethylammonium (TEA), the latter only when present on the side of the channel from which K(+) flow originates. Macroscopic basolateral K(+) conductance, determined in amphotericin-permeabilised epithelia, was also markedly reduced by quinidine and verapamil, TEA inhibited only from the lumen side, and serosal ChTX was without effect. The chromanol 293B and the sulphonylurea tolbutamide did not affect BK(Ca) channels and had no or only a small inhibitory effect on macroscopic basolateral K(+) conductance. Transepithelial Na(+) absorption was partly inhibited by Ba(2+), quinidine and verapamil, suggesting that BK(Ca) channels are involved in basolateral recirculation of K(+) during Na(+) absorption in rabbit colon. The BK(Ca) channel inhibitors TEA and ChTX did not reduce Na(+) absorption, probably because TEA does not enter intact cells and ChTX is 'knocked off' its extracellular binding site by K(+) outflow from the cell interior. Transepithelial Cl(-) secretion was inhibited completely by Ba(2+) and 293B, partly by quinidine but not by the other K(+) channel blockers, indicating that the small (<3 pS) K(V)LQT1 channels are responsible for basolateral K(+) exit during Cl(-) secretion. Hence different types of K(+) channels mediate basolateral K(+) exit during transepithelial Na(+) and Cl(-) transport.


A bifunctional molecule-assisted synthesis of mimics for use in probing the ubiquitination system.
Ubiquitination regulates almost every life process of eukaryotes. The study of the ubiquitin (Ub) coupling or decoupling process and the interaction study of Ub-Ub binding protein have always been the central focus. However, such studies are challenging, owing to the transient nature of Ub-coupling enzymes and deubiquitinases in the reactions, as well as the difficulty in preparing large quantities of polyubiquitinated samples. Here we describe a recently developed strategy for the efficient preparation of analogs of Ub chains and analogs for Ub coupling and uncoupling intermediates, which facilitate the study of the ubiquitination process. The strategy includes mainly the following steps: (i) the bifunctional molecule conjugation on the only cysteine (Cys) residue of a target protein (usually a Ub or Ub-conjugating enzyme), exposing an orthogonal reactive site for native chemical ligation; (ii) covalent ligation with a Ub-derived thioester, exposing a free sulfhydryl; and (iii) (optional) a disulfide bond formation with a substrate protein (mainly with only one Cys protein) through nonactivity-based cross-linking or with a deubiquitinase (mainly with several Cys residues) through activity-based cross-linking. When the bifunctional molecule and target proteins are obtained, the final products can be prepared in milligram quantities within 2 weeks.


Sarcopenic obesity is associated with frailty among community-dwelling older adults: findings from the WCHAT study.
Uncertainties remain regarding the relationship between sarcopenic obesity and frailty. This study aimed to explore the association of these two common geriatric syndromes among community-dwelling older adults. Baseline data from the West China Health and Aging Trend (WCHAT) study was used. Sarcopenia was assessed based on the criteria established by the Asian working group for sarcopenia. Body fat percentages above the 60th percentile specified by sex were classified as obesity. Sarcopenic obesity was defined as the concurrence of obesity and sarcopenia. Frailty was assessed by Fried criteria. Multinomial logistic regression was adopted to explore associations of sarcopenic obesity with frailty. Overall, 2372 older adults (mean age 67.6 ± 5.9) were involved in this study. The prevalence of frailty and sarcopenic obesity was 6.2 and 6.28%, respectively. After adjusting for covariates, sarcopenic obesity was significantly associated with prefrailty (OR = 1.74, 95% CI = 1.15-2.64, P = 0.009) and frailty (OR = 4.42, 95% CI = 2.19-8.93, P < 0.001) compared to nonsarcopenia and nonobesity. Sarcopenic obesity was significantly correlated with prefrailty and frailty among older adults. Intervention for sarcopenic obesity may contribute to the prevention of incident frailty.


Crisis of Authority: The Truth of Post-Truth.
This article is a critique of the notion of post-truth. Drawing on the work of Hannah Arendt, I argue that the epistemological crisis suggested by the notion of post-truth is epiphenomenal to a more general crisis of authority, a crisis that is poorly understood in the literature. I also argue that revisiting Arendt's account of authority can help us elucidate the vexed dynamics of authority in modern society, as well as the dynamics behind its current crisis. The post-truth situation is a loss of authority that is political before it presents as epistemological. Effectively addressing this situation, I conclude, is a much more challenging and complex proposition than what is suggested in the literature on post-truth.


Evaluation by quantitative 99m-technetium MIBI SPECT and echocardiography of myocardial perfusion and wall motion abnormalities in patients with dobutamine-induced ST-segment elevation.
ST-segment elevation during exercise testing has been attributed to myocardial ischemia and wall motion abnormalities (WMA). However, the functional significance of ST-segment elevation during dobutamine stress testing (DST) has not been evaluated in patients referred for diagnostic evaluation of myocardial ischemia. DST (up to 40 micrograms/kg/min) with simultaneous echocardiography and technetium-99m sestamibi single-photon emission computed tomography (SPECT) was performed in 229 consecutive patients with suspected myocardial ischemia who were unable to perform an adequate exercise test; 127 (55%) had a previous acute myocardial infarction (AMI). ST elevation was defined as > or = 1 mm new or additional J point elevations with a horizontal or upsloping ST segment lasting 80 ms. Reversible perfusion defects on SPECT and new or worsening WMA during stress on echocardiography were considered diagnostic of ischemia. ST elevation occurred in 40 patients (17%) during the test; 34 of them (85%) had previous AMI. All patients with ST-segment elevation had abnormal scintigrams (fixed or reversible defects, or both) and abnormal wall motion (fixed or transient defect, or both) at peak stress. In patients who had ST elevation and no previous AMI (n = 6), ischemia was detected in all by echocardiography and in 5 (83%) by SPECT. In patients with previous AMI, the prevalence of ischemia was not different with or without ST elevation (53% vs 43% by echocardiography and 53% vs 48% by SPECT, respectively). Baseline regional wall motion score in the infarct zone was higher in patients with ST elevation.(ABSTRACT TRUNCATED AT 250 WORDS)


A Review: Cereals on Modulating the Microbiota/Metabolome for Metabolic Health.
Diet can modulate both the composition and functionality of the human gut microbiota. Cereals are rich in specific macro and functional elements that are considered important dietary components for maintaining human health; therefore, it is important to examine precise nutritional mechanism involved in exerting the health benefits via modulating gut microbiota. The purpose of this review is to summarize recent research on how different cereals in the diet can regulate the microbiota for health and disease. There is an increased interest in targeting the gut microbiome for the treatment of chronic diseases. Cereals can alter the gut microbiome and may improve energy and glucose homeostasis, interfere with host energy homeostasis, appetite, blood glucose regulation, insulin sensitivity, and regulation of host metabolism. However, more human research is necessary to confirm the beneficial health outcomes of cereals via modulating gut microbiota. Cereals play an essential role in shaping the intestinal microbiota that contributes to exerting health effects on various diseases.


Cumulative sum control charts for assessing performance in arterial surgery.
The Melbourne Vascular Surgical Association (Melbourne, Australia) undertakes surveillance of mortality following aortic aneurysm surgery, patency at discharge following infrainguinal bypass and stroke and death following carotid endarterectomy. Quality improvement protocol employing the Deming cycle requires that the system for performing surgery first be analysed and optimized. Then process and outcome data are collected and these data require careful analysis. There must be a mechanism so that the causes of unsatisfactory outcomes can be determined and a good feedback mechanism must exist so that good performance is acknowledged and unsatisfactory performance corrected. A simple method for analysing these data that detects changes in average outcome rates is available using cumulative sum statistical control charts. Data have been analysed both retrospectively from 1999 to 2001, and prospectively during 2002 using cumulative sum control methods. A pathway to deal with control chart signals has been developed. The standard of arterial surgery in Victoria, Australia, is high. In one case a safe and satisfactory outcome was achieved by following the pathway developed by the audit committee. Cumulative sum control charts are a simple and effective tool for the identification of variations in performance standards in arterial surgery. The establishment of a pathway to manage problem performance is a vital part of audit activity.


Energy Transport in Dichroic Metallo-organic Crystals: Selective Inclusion of Spatially Resolved Arrays of Donor and Acceptor Dyes in Different Nanochannels.
In this study, the precise positioning and alignment of arrays of two different guest molecules in a crystalline host matrix has been engineered and resulted in new optically active materials. Sub-nm differences in the diameters of two types of 1D channels are sufficient for size-selective inclusion of dyes. Energy transport occurs between the arrays of different dyes that are included in parallel-positioned nanochannels by Förster resonance energy transfer (FRET). The color of individual micro-sized crystals are dependent on their relative position under polarized light. This angular-dependent behavior is a result of the geometrically constrained orientation of the dyes by the crystallographic packing of the host matrix and is concentration dependent.


Risk factors related to hearing impairment and screening with the Crib-O-Gram.
A "Crib-O-Gram" was employed for an automatic screening of hearing impaired newborns. A series of 502 neonates were tested, and 57 babies were judged to be "REFER." These "REFER'd" subjects were further examined with ABR, and 4 hearing impaired subjects were found. A detailed history was available in 427 neonates, and "risk factors" related to hearing impairment were investigated. The incidence of "REFER" judgment was found to be significantly higher for the group of neonates with risk factors than for those without risk factors. The rate of "REFER" judgment was computed for each risk factor, and the phi-coefficient of association was calculated to study the statistical relationship between the "REFER" judgment and each risk factor. A significant relationship was confirmed for anatomic malformations, positive family history of deafness, and congenital perinatal infection. The relationship between the existence of hearing impairment and each risk factor was similarly studied. Congenital perinatal infection and family history of deafness were significantly associated with hearing impairment, although anatomic malformation was not significantly related. The quantification theory (Hayashi type II) was applied to calculate a relative weight of each risk factor in reference to both the REFER judgment and hearing impairment. It was pointed out that proper weighting of each risk factor may be useful in improving the efficiency of screening.


Immune response of white shrimp, Litopenaeus vannamei, after a concurrent infection with white spot syndrome virus and infectious hypodermal and hematopoietic necrosis virus.
In the present study, we investigated immunological changes in viral-infected white shrimp, Litopenaeus vannamei. White shrimp were infected with white spot syndrome virus (WSSV) or co-infected with WSSV and infectious hypodermal and hematopoietic necrosis virus (IHHNV) as detected by polymerase chain reaction (PCR). The complete (100%) mortality rate of shrimp was caused by viral infection due to immune parameters being suppressed including decreases in phenoloxidase activity, total hemocyte counts, differential hemocyte counts, and the gene expressions of prophenoloxidase and peroxinectin. In addition, increases in lipopolysaccharide and beta-1,3-glucan-binding protein of hemocytes and the hepatopancreas, and respiratory bursts per cell, and a decrease in superoxide dismutase were found in viral-infected shrimp, which may have been related to the defense against viral infection.


Bone loss in patients with inflammatory bowel disease: a prospective study.
To assess the rate of bone loss in patients with inflammatory bowel disease, we prospectively studied 35 patients (17 women) aged 36 +/- 13 (range 17-60) years, 14 of whom had Crohn's disease and 21 with ulcerative colitis (including 12 with ileoanal anastomosis). Bone mineral density was measured by dual-energy X-ray absorptiometry at the lumbar spine and femoral neck. The follow-up was 19 +/- 8 months. During this period, 14 patients received oral steroids. Lumbar bone density changes expressed as a percentage per year were -3.1 +/- 4.9%, -6.4 +/- 7.5% and +2.0 +/- 4.0% in Crohn's disease and ulcerative colitis without and with ileoanal anastomosis respectively (p = 0.007). The same pattern was observed at the femoral neck. Mean annual lumbar bone density changes were -6.2 +/- 7.0% and +0.9 +/- 3.9% in patients with and without steroids during follow-up (p = 0.002). We conclude that patients with inflammatory bowel disease are at risk of lumbar and femoral bone loss. However, bone loss is not observed in patients with ileoanal anastomosis.


Cortactin and focal adhesion kinase as predictors of cancer risk in patients with premalignant oral epithelial lesions.
There is a need for novel and accurate biomarkers based on genetic abnormalities capable of predicting the risk of malignant transformation of epithelial lesions of the oral cavity. Therefore, we investigate the role of cortactin and focal adhesion kinase (FAK) protein expression in oral dysplasias and their potential utility as cancer risk markers. Cortactin and FAK expression were immunohistochemically evaluated in 64 patients with oral epithelial dysplasia. During follow-up, 17 of 64 patients developed an oral squamous cell carcinoma (OSCC). Increased immunoexpression of cortactin and FAK was found in 52 and 27 of 64 oral dysplasias, respectively, and the expression of both proteins increased with the grade of dysplasia. Increased cortactin and FAK expression was also observed in 13 and 15 OSCC, respectively. Overall, cortactin and FAK expression was maintained or further augmented in the oral squamous cell carcinoma compared to the patient-matched preinvasive lesion. Univariate analysis showed that cortactin and FAK expression, as well as histological grading were significantly associated with oral cancer risk. Strong coexpression of both proteins reflected a significantly higher cancer risk than that of weak to moderate expression or than whenever only one of those proteins showed a strong expression. In multivariate analysis, premalignant oral lesions which exhibited a high coexpression of cortactin and FAK showed a significant risk of developing an OSCC (HR=6.298). Our results indicate that strong immunoexpression of cortactin and FAK, and not only one of them, is a predicting factor for increased cancer risk in oral premalignant lesions.


Alanyl-glutamine infusions to patients with acute pancreatitis.
In this study we infused different amounts of glutamyl-dipeptides (group 1: 1.5 g ALA-GLN + 3.5 g GLY-GLN, group 2: 20 g ALA-GLN, group 3: 40 g ALA-GLN) for a period of five days into patients with acute pancreatitis. In spite of this high amount of ALA-GLN administration we were not able to normalise the depleted glutamine pool of skeletal muscle in these catabolic patients.


Pathophysiological role of inflammatory molecules in paediatric ischaemic brain injury.
Ischaemic stroke is one of the major causes of death and lifelong disability also in the paediatric population. Strong scientific effort has been put to clarify the pathophysiology of this disease in adults. However, only few studies have been performed in children. Preliminary results indicate that pathophysiological processes might differently affect the poststroke neuronal injury in neonates as compared to children. During the neural development, selective molecular mechanisms might be differently triggered by an ischaemic insult, thus potentially resulting in defined postischaemic clinical outcomes. Basic research studies in neonatal animal models of cerebral ischaemia have recently shown a potential role of soluble inflammatory molecules (such as cytokines, chemokines and oxidants) as pivotal players of neuronal injury in both perinatal and childhood ischaemic stroke. Although larger clinical trials are still needed to confirm these preliminary results, the potential benefits of selective treatments targeting inflammation in perinatal asphyxia encephalopathy might represent a promising investigation field in the near future. In this review, we will update evidence on the pathophysiological role of soluble inflammatory mediators in neonatal and childhood ischaemic stroke. Recent evidence on potential anti-inflammatory treatments to improve paediatric stroke prognosis will be discussed.


Characterization of the phosphatase activity of a baculovirus-expressed calcineurin A isoform.
Calcineurin A was purified by calmodulin-Sepharose affinity chromatography from Sf9 cells infected with recombinant baculovirus containing the cDNA of a rat calcineurin A isoform. The Sf9-expressed calcineurin A has a low basal phosphatase activity in the presence of EDTA (0.9 nmol/min/mg) which is stimulated 3-5-fold by Mn2+. Calmodulin increased the Mn2+ stimulated activity 3-5-fold. Bovine brain calcineurin B increased the A subunit activity 10-15-fold, and calmodulin further stimulated the activity of reconstituted A and B subunits 10-15-fold (644 nmol/min/mg). The Km of calcineurin A for 32P-RII pep (a peptide substrate (DLDVPIPGRFDRRVSVAAE) for CaN), was 111 microM with or without calmodulin, and calmodulin increased the Vmax about 4-fold. The Km of reconstituted calcineurin A plus B for 32P-RII pep was 20 microM, and calmodulin increased the Vmax 18-fold without affecting the Km. CaN A467-492, a synthetic autoinhibitory peptide (ITSFEEAKGLDRINERMPPRRDAMP) from calcineurin, inhibited the Mn2+/calmodulin-stimulated activities of the reconstituted enzyme and the A subunit with IC50's of 25 microM and 90 microM, respectively. The reconstitution of the phosphatase activity of an expressed isoform of calcineurin A by purified B subunit and calmodulin may facilitate comparative studies of the regulation of calcineurin A activity by the B subunit and calmodulin.