The effects of adriamycin (doxorubicin HCl) on human red blood cells.
We have studied the effects of adriamycin (doxorubicin HCl) on human red blood cells. The peroxidizing effect of adriamycin on the thiols of red cell constituents resulted in decreased glutathione stability, and oxidation of hemoglobin and membrane protein components 1, 2, and 3, forming large molecular weight complexes. Membrane lipids were also peroxidized. Adriamycin itself did not inhibit the enzymes of the reductions system (glucose-6-phosphate dehydrogenase, 6-phosphogluconic dehydrogenase, glutathione reductase, glutathione peroxidase, catalase, superoxide dismutase) of the red cells. Because adriamycin has the potential of inhibiting ATPase, including both Na-K-dependent ATPase and ouabain insensitive ATPase, at concentrations not inhibitory to other enzymes, the net sodium content increased, and potassium content decreased after incubation of red cells with adriamycin at high concentrations. The experimental results described with adriamycin may serve as a model for the possible mechanism of cardiotoxicity observed in its clinical use, and also explain the potential hemolyzing effect on red cells. There was greater oxidizing effect on glucose-6-phosphate dehydrogenase (G-6-PD) deficient than on normal erythrocytes. It is suggested that adriamycin be used with caution in individuals with G-6-PD deficient red cells.


Fourteen Day In Vivo Testing of a Compliant Thoracic Artificial Lung.
The compliant thoracic artificial lung (cTAL) has been studied in acute in vivo and in vitro experiments. The cTAL's long-term function and potential use as a bridge to lung transplantation are assessed presently. The cTAL without anticoagulant coatings was attached to sheep (n = 5) via the pulmonary artery and left atrium for 14 days. Systemic heparin anticoagulation was used. Compliant thoracic artificial lung resistance, cTAL gas exchange, hematologic parameters, and organ function were recorded. Two sheep were euthanized for nondevice-related issues. The cTAL's resistance averaged 1.04 ± 0.05 mmHg/(L/min) with no statistically significant increases. The cTAL transferred 180 ± 8 ml/min of oxygen with 3.18 ± 0.05 L/min of blood flow. Except for transient surgical effects, organ function markers were largely unchanged. Necropsies revealed pulmonary edema and atelectasis but no other derangements. Hemoglobin levels dropped with device attachment but remained steady at 9.0 ± 0.1 g/dl thereafter. In a 14 day experiment, the cTAL without anticoagulant coatings exhibited minimal clot formation. Sheep physiology was largely unchanged except for device attachment-related hemodilution. This suggests that patients treated with the cTAL should not require multiple blood transfusions. Once tested with anticoagulant coatings and plasma resistant gas exchange fiber, the cTAL could serve as a bridge to transplantation.


Identification of Positive Chemotaxis in the Protozoan Pathogen Trypanosoma brucei.
To complete its infectious cycle, the protozoan parasite Trypanosoma brucei must navigate through diverse tissue environments in both its tsetse fly and mammalian hosts. This is hypothesized to be driven by yet unidentified chemotactic cues. Prior work has shown that parasites engaging in social motility in vitro alter their trajectory to avoid other groups of parasites, an example of negative chemotaxis. However, movement of T. brucei toward a stimulus, positive chemotaxis, has so far not been reported. Here, we show that upon encountering Escherichia coli, socially behaving T. brucei parasites exhibit positive chemotaxis, redirecting group movement toward the neighboring bacterial colony. This response occurs at a distance from the bacteria and involves active changes in parasite motility. By developing a quantitative chemotaxis assay, we show that the attractant is a soluble, diffusible signal dependent on actively growing E. coli Time-lapse and live video microscopy revealed that T. brucei chemotaxis involves changes in both group and single cell motility. Groups of parasites change direction of group movement and accelerate as they approach the source of attractant, and this correlates with increasingly constrained movement of individual cells within the group. Identification of positive chemotaxis in T. brucei opens new opportunities to study mechanisms of chemotaxis in these medically and economically important pathogens. This will lead to deeper insights into how these parasites interact with and navigate through their host environments.IMPORTANCE Almost all living things need to be able to move, whether it is toward desirable environments or away from danger. For vector-borne parasites, successful transmission and infection require that these organisms be able to sense where they are and use signals from their environment to direct where they go next, a process known as chemotaxis. Here, we show that Trypanosoma brucei, the deadly protozoan parasite that causes African sleeping sickness, can sense and move toward an attractive cue. To our knowledge, this is the first report of positive chemotaxis in these organisms. In addition to describing a new behavior in T. brucei, our findings enable future studies of how chemotaxis works in these pathogens, which will lead to deeper understanding of how they move through their hosts and may lead to new therapeutic or transmission-blocking strategies.


The Temple Scroll: Reconstructing an ancient manufacturing practice.
The miraculously preserved 2000-year-old Dead Sea Scrolls, ancient texts of invaluable historical significance, were discovered in the mid-20th century in the caves of the Judean desert. The texts were mainly written on parchment and exhibit vast diversity in their states of preservation. One particular scroll, the 8-m-long Temple Scroll is especially notable because of its exceptional thinness and bright ivory color. The parchment has a layered structure, consisting of a collagenous base material and an atypical inorganic overlayer. We analyzed the chemistry of the inorganic layer using x-ray and Raman spectroscopies and discovered a variety of evaporitic sulfate salts. This points toward a unique ancient production technology in which the parchment was modified through the addition of the inorganic layer as a writing surface. Furthermore, understanding the properties of these minerals is particularly critical for the development of suitable conservation methods for the preservation of these invaluable historical documents.


Evolution of honesty in higher-order social networks.
Sender-receiver games are simple models of information transmission that provide a formalism to study the evolution of honest signaling and deception between a sender and a receiver. In many practical scenarios, lies often affect groups of receivers, which inevitably entangles the payoffs of individuals to the payoffs of other agents in their group, and this makes the formalism of pairwise sender-receiver games inapt for where it might be useful the most. We therefore introduce group interactions among receivers and study how their interconnectedness in higher-order social networks affects the evolution of lying. We observe a number of counterintuitive results that are rooted in the complexity of the underlying evolutionary dynamics, which has thus far remained hidden in the realm of pairwise interactions. We find conditions for honesty to persist even when there is a temptation to lie, and we observe the prevalence of moral strategy profiles even when lies favor the receiver at a cost to the sender. We confirm the robustness of our results by further performing simulations on hypergraphs created from real-world data using the SocioPatterns database. Altogether, our results provide persuasive evidence that moral behavior may evolve on higher-order social networks, at least as long as individuals interact in groups that are small compared to the size of the network.


[Pathogenicity of Enterococcus spp. Characteristics of 169 hospital isolates].
To know the characteristics of Enterococcus spp. strains isolated in the hospital; to analyse the importance of this microorganism and its resistance to antimicrobial agents. Retrospective analysis of the case histories of 169 patients with Enterococcus spp. isolates, selected at random at the Infanta Cristina Hospital in Badajoz. Investigation was carried out on: age, date of admission and discharge, clinical symptoms, risk factors, previous antibiotic treatment, clinical and microbiological evolution, recommended treatment and prescribed treatment. Identification of microorganisms and antibiogram with Pos Combo 41 microScam panels, read on Baxter WalkAway-40 equipment. The most frequently found species was Enterococcus faecalis. In 75 cases the isolations were polymicrobial. The enterococci were isolated mainly from urinary infections (27%), skin infections (20%), intrabdominal infections (14%) and infections from surgical wounds (14%). The existence of peripheral catheter was the main risk factor. All the strains of E. faecalis were susceptible to the glycopeptides. Two strains of Enterococcus faecium were not susceptible to vancomycin and one of these was not susceptible to teicoplanin. Mortality was from 21-27.5%. Enterococcus spp. is frequently isolated in nosocomial infections, although in approximately half the cases it is associated with other bacteria. For this reason, it is not always possible to determine its pathogenic contribution. The isolated strains, except two strains of E. faecium, are susceptible to vancomycin. A relation exists between high resistance to aminoglucosides and resistance to fluoroquinolones.


Cutaneous Leishmaniasis.
Leishmaniasis is a parasitic infection that can involve the skin, mucosal membranes, and internal organs. Soldiers are at highrisk of leishmaniasis when conducting operations in endemic regions. Medical providers should have a low threshold to consider Leishmaniasis as the cause of persisting skin lesions.


Training in academic medicine: a way forward for the new millennium. A discussion document from the Academic Medicine Committee of the Royal College of Physicians.
Three schemes are presented for discussion whereby physicians undergoing postdoctoral training can combine a period of research training with their clinical training and so enable those who wish to follow a career in academic medicine to do so, or alternatively to revert to a clinical career. The training arrangements for those wishing to take up clinical academic medicine have hitherto been uncertain and hence unattractive to some. As well as encouraging more high-calibre trainees into academic medicine, the training programmes described are intended to bring greater clarity to those responsible for academic and clinical training and to those who fund research.


Majority of erectile dysfunction patients would have preferred earlier implantation of their penile prosthesis: validation of the recently changed EAU guidelines.
Until 2019, the European Association of Urology guidelines recommended the implantation of a penile prosthesis as a third-line therapy, which has since then changed to "if other treatments fail or depending on the patient's preference". Primary endpoint was to assess whether patients with a penile prosthesis and their partner would have preferred earlier implantation. Secondary endpoints were the reason why patient and partner wanted earlier implantation, how much earlier they wanted it, satisfaction of patient and partner and if patient and partner would have recommended the intervention. We selected patients with a virgin inflatable penile prosthesis operated between April 2013 and December 2019. We included 155 patients and 65 partners. Telephonic interview was conducted in a structured manner. Further data were collected retrospectively. The preference for earlier implantation was reported in 59.4% of patients and 46.2% of partners. Of them, respectively 53.2% and 46.6% would have wanted the prosthesis more than 5 years earlier. Satisfaction was seen in 83.2% of patients and 73.8% of partners. Respectively 82.6% and 78.4% of patients and partners would recommend the procedure. Our results indicate that a more patient-oriented approach with good counseling is desirable and that the "three-level" concept must be abandoned.


Wavelength resolved UV photodesorption and photochemistry of CO2 ice.
Over the last four years we have illustrated the potential of a novel wavelength-dependent approach in determining molecular processes at work in the photodesorption of interstellar ice analogs. This method, utilizing the unique beam characteristics of the vacuum UV beamline DESIRS at the French synchrotron facility SOLEIL has revealed an efficient indirect desorption mechanism that scales with the electronic excitations in molecular solids. This process, known as DIET--desorption induced by electronic transition--occurs efficiently in ices composed of very volatile species (CO, N2), for which photochemical processes can be neglected. In the present study, we investigate the photodesorption energy dependence of pure and pre-irradiated CO2 ices at 10-40 K and between 7 and 14 eV. The photodesorption from pure CO2 is limited to photon energies above 10.5 eV and is clearly initiated by CO2 excitation and by the contribution of dissociative and recombination channels. The photodesorption from "pre-irradiated" ices is shown to present an efficient additional desorption pathway below 10 eV, dominating the desorption depending on the UV-processing history of the ice film. This effect is identified as an indirect DIET process mediated by photoproduced CO, observed for the first time in the case of less volatile species. The results presented here pinpoint the importance of the interconnection between photodesorption and photochemical processes in interstellar ices driven by UV photons having different energies.


[Legg-Perthes-Calvé disease. Plea for an original ambulatory orthosis].
Legg-Perthes-Calvé disease is a local disease which should be treated by non-iatrogenic means. The authors have designed a new ambulatory orthosis allowing containment in abduction, flexion and medial rotation, with relief of weight-bearing on the femoral head. It was tested in thirty six hips. In only eight of them a surgical procedure had to be performed during the evolution of the disease (femoral or pelvic osteotomy) because of secondary exenteration of the hip.


Enhanced renal tubular ouabain-sensitive ATPase in streptozotocin diabetes mellitus.
The effect of streptozotocin-induced diabetes mellitus on rat renal ouabain-sensitive ATPase in six distinct nephron segments was studied. Twenty-four hours after administration of streptozotocin, blood glucose increased threefold (P less than 0.001), and glucosuria was evident. Aldosterone levels increased almost twofold (P less than 0.001). Ouabain-sensitive ATPase increased in the proximal segments PC (proximal convoluted tubule) and PS (proximal straight tubule) by 43 and 62%, respectively, (P less than 0.001) and CD (cortical collecting duct) ouabain-sensitive ATPase increased 77% (P less than 0.001). Ouabain-sensitive ATPase in the cortical (CTAL) and medullary (MTAL) thick ascending limbs of Henle's loop and in the DC (distal convoluted tubule) remained unchanged after 24 h of streptozotocin administration. Eight days after streptozotocin administration, when glomerular filtration rate (GFR) was already markedly elevated, ouabain-sensitive ATPase remained increased in the PC, PS, and CD but was significantly less compared with the activity after 24 h (P less than 0.05), whereas in the CTAL and MTAL a marked increase in ouabain-sensitive ATPase occurred by 54% in the CTAL and 65% in the MTAL (P less than 0.001). Aldosterone levels remained elevated compared with control but less than after 24 h. Pretreatment with deoxycorticosterone acetate abolished the increase in ouabain-sensitive ATPase in the CD. These findings show that streptozotocin-induced diabetes mellitus in the rat is associated with a substantial increase in ouabain-sensitive ATPase activity along most of the nephron. This increase in enzyme activity may represent a mechanism of physiological adaptation of the nephron to maintain electrolyte homeostasis in diabetes in face of the increased GFR and osmotic diuresis.


Structure of an N276-Dependent HIV-1 Neutralizing Antibody Targeting a Rare V5 Glycan Hole Adjacent to the CD4 Binding Site.
All HIV-1-infected individuals develop strain-specific neutralizing antibodies to their infecting virus, which in some cases mature into broadly neutralizing antibodies. Defining the epitopes of strain-specific antibodies that overlap conserved sites of vulnerability might provide mechanistic insights into how broadly neutralizing antibodies arise. We previously described an HIV-1 clade C-infected donor, CAP257, who developed broadly neutralizing plasma antibodies targeting an N276 glycan-dependent epitope in the CD4 binding site. The initial CD4 binding site response potently neutralized the heterologous tier 2 clade B viral strain RHPA, which was used to design resurfaced gp120 antigens for single-B-cell sorting. Here we report the isolation and structural characterization of CAP257-RH1, an N276 glycan-dependent CD4 binding site antibody representative of the early CD4 binding site plasma response in donor CAP257. The cocrystal structure of CAP257-RH1 bound to RHPA gp120 revealed critical interactions with the N276 glycan, loop D, and V5, but not with aspartic acid 368, similarly to HJ16 and 179NC75. The CAP257-RH1 monoclonal antibody was derived from the immunoglobulin-variable IGHV3-33 and IGLV3-10 genes and neutralized RHPA but not the transmitted/founder virus from donor CAP257. Its narrow neutralization breadth was attributed to a binding angle that was incompatible with glycosylated V5 loops present in almost all HIV-1 strains, including the CAP257 transmitted/founder virus. Deep sequencing of autologous CAP257 viruses, however, revealed minority variants early in infection that lacked V5 glycans. These glycan-free V5 loops are unusual holes in the glycan shield that may have been necessary for initiating this N276 glycan-dependent CD4 binding site B-cell lineage. The conserved CD4 binding site on gp120 is a major target for HIV-1 vaccine design, but key events in the elicitation and maturation of different antibody lineages to this site remain elusive. Studies have shown that strain-specific antibodies can evolve into broadly neutralizing antibodies or in some cases act as helper lineages. Therefore, characterizing the epitopes of strain-specific antibodies may help to inform the design of HIV-1 immunogens to elicit broadly neutralizing antibodies. In this study, we isolate a narrowly neutralizing N276 glycan-dependent antibody and use X-ray crystallography and viral deep sequencing to describe how gp120 lacking glycans in V5 might have elicited these early glycan-dependent CD4 binding site antibodies. These data highlight how glycan holes can play a role in the elicitation of B-cell lineages targeting the CD4 binding site.


Robot-assisted laparoscopy in gynecologic oncology.
The aim of this prospective study was to evaluate the feasibility and the outcome of gynaecological cancer surgery with the Da Vinci S surgical system (Intuitive Surgical). From February 2007 to September 2007, 28 patients underwent 32 gynaecological procedures in a single centre. Surgical procedures consisted of total hysterectomy, bilateral oophorectomy, and pelvic and/or lombo-aortic lymphadenectomy. In all cases, surgery was performed using both laparoscopic and robot-assisted laparoscopic techniques. In this heterogeneous series, a subgroup of 12 patients treated for advanced cervical cancer was compared with a retrospective series of 20 patients who underwent the same surgical procedure by laparotomy. Mean age of the entire population was 52.5 years (range 25-72 years) and mean body mass index (BMI) was 25 kg/m(2) (range 18-40 kg/m(2)). Indications for surgery were cervical cancer in 21 cases, endometrial cancer in 7 cases, ovarian cancer in 1 case and cervical dysplasia in 3 cases. Median operating time was 180 min (mean 175.25 min, range 80-360 min) and median estimated blood loss was 110 cc (range 0-400 cc); no transfusions were necessary. No perioperative complications were observed and median time of hospitalisation was 3 days (mean 3.9 days, range 2-8 days). In the subgroup of 12 advanced cervical cancer a significant difference was observed in terms of hospital stay compared with laparotomy; no difference was observed concerning operative time. Fewer complications were observed with laparotomy (33% versus 25%) but more serious complications than with robot-assisted laparoscopy. As suggested in the literature, the use of robot-assisted laparoscopy leads to less intraoperative blood loss, less post operative pain and shorter hospital stays compared with those treated by more traditional surgical approaches. Despite the need for more extensive studies, robot-assisted surgery seems to represent a similar technological evolution as the laparoscopic approach 50 years ago.


Detection of prokaryotic mRNA signifies microbial viability and promotes immunity.
Live vaccines have long been known to trigger far more vigorous immune responses than their killed counterparts. This has been attributed to the ability of live microorganisms to replicate and express specialized virulence factors that facilitate invasion and infection of their hosts. However, protective immunization can often be achieved with a single injection of live, but not dead, attenuated microorganisms stripped of their virulence factors. Pathogen-associated molecular patterns (PAMPs), which are detected by the immune system, are present in both live and killed vaccines, indicating that certain poorly characterized aspects of live microorganisms, not incorporated in dead vaccines, are particularly effective at inducing protective immunity. Here we show that the mammalian innate immune system can directly sense microbial viability through detection of a special class of viability-associated PAMPs (vita-PAMPs). We identify prokaryotic messenger RNA as a vita-PAMP present only in viable bacteria, the recognition of which elicits a unique innate response and a robust adaptive antibody response. Notably, the innate response evoked by viability and prokaryotic mRNA was thus far considered to be reserved for pathogenic bacteria, but we show that even non-pathogenic bacteria in sterile tissues can trigger similar responses, provided that they are alive. Thus, the immune system actively gauges the infectious risk by searching PAMPs for signatures of microbial life and thus infectivity. Detection of vita-PAMPs triggers a state of alert not warranted for dead bacteria. Vaccine formulations that incorporate vita-PAMPs could thus combine the superior protection of live vaccines with the safety of dead vaccines.


Patient dignity in an acute hospital setting: a case study.
Nurses have a professional duty to respect patients' dignity. There is a dearth of research about patients' dignity in acute hospital settings. The study investigated the meaning of patient dignity, threats to patients' dignity, and how patient dignity can be promoted, in acute hospital settings. A qualitative, triangulated single case study design (one acute hospital), with embedded cases (one ward and its staff, and 24 patients). The study was based on a 22-bedded surgical ward in an acute hospital in England. Twenty-four patients, aged 34-92 years were purposively selected. There were 15 men and 9 women of varied socio-economic backgrounds. They could all communicate verbally and speak English. Twelve patients, who had stayed in the ward at least 2 days, were interviewed following discharge. The other 12 patients were observed and interviewed on the ward. The ward-based staff (26 registered nurses and healthcare assistants) were observed in practice. 13 were interviewed following observation. Six senior nurses were purposively selected for interviews. The data were collected during 2005. The Local Research Ethics Committee gave approval. Unstructured interviews using topic guides were conducted with the 24 patients, 13 ward-based staff and 6 senior nurses. Twelve 4-h episodes of participant observation were conducted. The data were analysed thematically using the framework approach. Patient dignity comprised feelings (feeling comfortable, in control and valued), physical presentation and behaviour. The environment, staff behaviour and patient factors impacted on patient dignity. Lack of environmental privacy threatened dignity. A conducive physical environment, dignity-promoting culture and other patients' support promoted dignity. Staff being curt, authoritarian and breaching privacy threatened dignity. Staff promoted dignity by providing privacy and interactions which made patients feel comfortable, in control and valued. Patients' impaired health and older age rendered them vulnerable to a loss of dignity. Patients promoted their own dignity through their attitudes (rationalisation, use of humour, acceptance), developing relationships with staff and retaining ability and control. Patients are vulnerable to loss of dignity in hospital. Staff behaviour and the hospital environment can influence whether patients' dignity is lost or upheld.


Children and adolescents coping with cancer: self- and parent reports of coping and anxiety/depression.
The diagnosis and treatment of cancer present children and adolescents with significant stress. However, research on the ways that children and adolescents cope with cancer-related stress has not yielded clear findings on the efficacy of different coping strategies, and has been limited by reliance primarily on self-reports of both coping and distress. To address this gap, the current study used a control-based model of coping to examine self- and parent reports of child/adolescent coping and symptoms of anxiety and depression in a sample of children with cancer. Children and adolescents (5 to 17 years old) and their parents were recruited near the time of a child's diagnosis or relapse of cancer (M = 1.30 months postdiagnosis). Child self-reports (n = 153), mother reports (n = 297), and father reports (n = 161) of children's coping and symptoms of anxiety/depression were obtained. Bivariate correlations revealed significant associations for secondary control coping (efforts to adapt to source of stress; e.g., acceptance, cognitive reappraisal) and disengagement coping (e.g., avoidance, denial) with anxiety/depression within and across informants. Linear multiple regression analyses indicated that secondary control coping accounted for unique variance in symptoms of anxiety/depression both within and across informants. Secondary control coping appears important for children and adolescents during early phases of treatment for cancer, and it may serve as an important target for future interventions to enhance adjustment in these children.


Neural tube defect genes and maternal diabetes during pregnancy.
Maternal diabetes during pregnancy is a well-known teratogen that increases the risk for birth defects, such as neural tube defects (NTDs). We have previously shown that maternal diabetes profoundly affects gene expression in the developing embryo, in particular a suite of known NTD genes. In rodent experimental systems, NTDs present as phenotypes of incomplete penetrance in diabetic pregnancies. This property is difficult to reconcile with observations of consistently altered gene expression in exposed embryos. We here show that maternal diabetes increases the overall variability of gene expression levels in embryos. Altered gene expression and increased variability of gene expression together may constitute the molecular correlates for incomplete phenotype penetrance. Based on this model, we suggest that maternal diabetes reduces the precision of gene regulation in exposed individuals. Loss of precision in embryonic gene regulation may include changes to the epigenome via deregulated expression of chromatin-modifying factors. Unraveling the mechanisms underlying such epigenetic modifications in diabetic pregnancies will help to understand how teratogenic insults compromise embryonic development and possibly provide avenues for therapeutic intervention.


Validity of measurement of shear modulus by ultrasound shear wave elastography in human pennate muscle.
Ultrasound shear wave elastography is becoming a valuable tool for measuring mechanical properties of individual muscles. Since ultrasound shear wave elastography measures shear modulus along the principal axis of the probe (i.e., along the transverse axis of the imaging plane), the measured shear modulus most accurately represents the mechanical property of the muscle along the fascicle direction when the probe's principal axis is parallel to the fascicle direction in the plane of the ultrasound image. However, it is unclear how the measured shear modulus is affected by the probe angle relative to the fascicle direction in the same plane. The purpose of the present study was therefore to examine whether the angle between the principal axis of the probe and the fascicle direction in the same plane affects the measured shear modulus. Shear modulus in seven specially-designed tissue-mimicking phantoms, and in eleven human in-vivo biceps brachii and medial gastrocnemius were determined by using ultrasound shear wave elastography. The probe was positioned parallel or 20° obliquely to the fascicle across the B-mode images. The reproducibility of shear modulus measurements was high for both parallel and oblique conditions. Although there was a significant effect of the probe angle relative to the fascicle on the shear modulus in human experiment, the magnitude was negligibly small. These findings indicate that the ultrasound shear wave elastography is a valid tool for evaluating the mechanical property of pennate muscles along the fascicle direction.


Short-term outcomes of endoscopic sleeve gastroplasty in 1000 consecutive patients.
Questions related to the safety and long-term efficacy of endoscopic sleeve gastroplasty (ESG) are not yet answered. Here we report weight loss, morbidity, revisions, and comorbidity resolution during the first 18 months after primary ESG. This is a consecutive case series from a prospective observational study executed in a specialized center with a standardized pathway for multimodal management of obesity. The 1000 patients in this study had a baseline body mass index of 33.3 ± 4.5 kg/m2 and age of 34.4 ± 9.5 years. Eight hundred ninety-seven patients (89.7%) were women. Mean percentage of total weight loss at 6, 12, and 18 months was 13.7% ± 6.8% (n = 369; follow-up rate = 423; 87.2%), 15.0% ± 7.7% (n = 216; follow-up rate = 232; 93.1%), and 14.8% ± 8.5% (n = 54; follow-up rate = 63; 85.7%), respectively. Lost to follow-up at the 12- and 18-month visits were 6.9% and 14.3%, respectively. Thirteen of 17 cases of diabetes, all 28 cases of hypertension, and 18 of 32 cases of dyslipidemia were in complete remission by the third month. With regard to postoperative complaints, 924 patients (92.4%) complained of nausea or abdominal pain that was controlled with medications during the first week after ESG. Twenty-four patients were readmitted: 8 for severe abdominal pain, of whom 3 had ESG reversal; 7 for postprocedure bleeding, 2 of whom received 2 units of packed red blood cells each; 4 for perigastric collection with pleural effusion, 3 of whom underwent percutaneous drainage; and 5 for postprocedure fever with no sequelae. Eight patients were revised to sleeve gastrectomy, and 5 had redo-ESG. No patient required an emergency intervention, and there were no mortalities. ESG appears to be well tolerated, safe, and effective. Significant weight loss occurs during the first 18 months without mortality or significant morbidity. Some patients require revision or reversal during the first year.


Conformation-dependent blockage of activated VWF improves outcomes of traumatic brain injury in mice.
Traumatic brain injury-induced coagulopathy (TBI-IC) causes life-threatening secondary intracranial bleeding. Its pathogenesis differs mechanistically from that of coagulopathy arising from extracranial injuries and hemorrhagic shock, but it remains poorly understood. We report results of a study designed to test the hypothesis that von Willebrand factor (VWF) released during acute TBI is intrinsically hyperadhesive because its platelet-binding A1-domain is exposed and contributes to TBI-induced vascular leakage and consumptive coagulopathy. This hyperadhesive VWF can be selectively blocked by a VWF A2-domain protein to prevent TBI-IC and to improve neurological function with a minimal risk of bleeding. We demonstrated that A2 given through intraperitoneal injection or IV infusion reduced TBI-induced death by >50% and significantly improved the neurological function of C57BL/6J male mice subjected to severe lateral fluid percussion injury. A2 protected the endothelium from extracellular vesicle-induced injury, reducing TBI-induced platelet activation and microvesiculation, and preventing a TBI-induced hypercoagulable state. A2 achieved this therapeutic efficacy by specifically blocking the A1 domain exposed on the hyperadhesive VWF released during acute TBI. These results suggest that VWF plays a causal role in the development of TBI-IC and is a therapeutic target for this life-threatening complication of TBI.


NDM-2 carbapenemase-producing Acinetobacter baumannii in the United Arab Emirates.
Screening 155 carbapenem non-susceptible Acinetobacter baumannii strains recovered in Abu Dhabi hospitals identified two metallo-ß-lactamase bla(NDM) gene-carrying isolates. They were isolated 4 months apart from the urine of a cancer patient previously treated in Egypt, Lebanon and in the United Arab Emirates. They were clonally related and carried the bla(NDM-2) gene recently identified in A. baumannii in Egypt and Israel. Sequences surrounding the bla(NDM-2) gene showed significant similarities with those associated with bla(NDM-1) in Enterobacteriaceae and A. baumannii. Repeated isolation of bla(NDM-2)-positive A. baumannii in the Middle East raises the possibility of the local emergence and spread of a unique clone.


Reducing environmental impact of dairy cattle: a Czech case study.
We analyze options to reduce the future environmental impact of dairy cattle production, using an optimization model (DAIRY) applied to the Czech Republic. The DAIRY model can be used to calculate the overall environmental impact (OEI). We show that aquatic eutrophication and global warming are the 2 most important problems caused by dairy cattle. These problems are largely caused by nitrate leaching and emissions from animal housing. The DAIRY model indicates that the costs of reducing the OEI in 2020 by 20% are 12 MEuro. It is most cost effective to achieve this reduction by improving the efficiency of animal manure used as fertilizer. We tested the sensitivity of the model to assumptions about the following: 1) the relative importance of environmental problems as expressed in weighting factors, and 2) future cattle numbers and milk yield per milking cow. The first case indicates that disagreement on which problem is most urgent need not lead to disagreement about policies to be undertaken. Regardless of the weighting factors used, aquatic eutrophication and global warming are the most important problems. However, the overall costs of reducing the OEI differ with alternative sets of weighting factors, because the costs of emission reduction differ among pollutants. The second case shows that the DAIRY model results are more sensitive to changes in cattle numbers than to changes in milk yield. This study is the first integrated assessment of dairy cattle production for a Central European country and illustrates how systematic analyses may help to find optimal solutions.


Epstein-Barr virus LMP1 blocks p16INK4a-RB pathway by promoting nuclear export of E2F4/5.
The p16INK4a-RB pathway plays a critical role in preventing inappropriate cell proliferation and is often targeted by viral oncoproteins during immortalization. Latent membrane protein 1 (LMP1) of Epstein-Barr virus (EBV) is often present in EBV-associated proliferative diseases and is critical for the immortalizing and transforming activity of EBV. Unlike other DNA tumor virus oncoproteins, which possess immortalizing activity, LMP1 does not bind to retinoblastoma tumor suppressor protein, but instead blocks the expression of p16INK4a tumor suppressor gene. However, it has been unclear how LMP1 represses the p16INK4a gene expression. Here, we report that LMP1 promotes the CRM1-dependent nuclear export of Ets2, which is an important transcription factor for p16INK4a gene expression, thereby reducing the level of p16INK4a expression. We further demonstrate that LMP1 also blocks the function of E2F4 and E2F5 (E2F4/5) transcription factors through promoting their nuclear export in a CRM1-dependent manner. As E2F4/5 are essential downstream mediators for a p16INK4a-induced cell cycle arrest, these results indicate that the action of LMP1 on nuclear export has two effects on the p16INK4a-RB pathway: (1) repression of p16INK4a expression and (2) blocking the downstream mediator of the p16INK4a-RB pathway. These results reveal a novel activity of LMP1 and increase an understanding of how viral oncoproteins perturb the p16INK4a-RB pathway.


Pharmacological Agents with Antiviral Activity against Monkeypox Infection.
Monkeypox infection is caused by a virus of the genus Orthopoxvirus, a member of the Poxviridae family. Monkeypox virus is transmitted from individual to individual through contact with lesions, body fluids, and respiratory droplets. The infection caused by monkeypox is usually a self-limited disease with mild symptoms lasting 2 to 4 weeks. Monkeypox typically presents with fever, rash, and enlarged lymph nodes. New vaccines have recently been authorized for the prevention of monkeypox infection, whereas there are no specific pharmacological antiviral treatments for monkeypox infection. However, because the viruses which cause adult smallpox and monkeypox are similar, antiviral drugs developed in the past have also shown efficacy against monkeypox. In this review, we highlight the in vitro and clinical evidence found in the literature on the efficacy and safety of pharmacological agents with antiviral activity against monkeypox infection and the different regulatory aspects of countries.


Whole-Body Change-of-Direction Task Execution Asymmetries After Anterior Cruciate Ligament Reconstruction.
Cutting maneuvers can be executed at a range of angles and speeds, and these whole-body task descriptors are closely associated with lower-limb mechanical loading. Asymmetries in angle and speed when changing direction off the operated and nonoperated limbs after anterior cruciate ligament reconstruction may therefore influence the interpretation of interlimb differences in joint-level biomechanical parameters. The authors hypothesized that athletes would reduce center-of-mass heading angle deflection and body rotation during the change-of-direction stance phase when cutting from the operated limb, and would compensate for this by orienting their center-of-mass trajectory more toward the new intended direction of travel prior to touchdown. A total of 144 male athletes 8 to 10 months after anterior cruciate ligament reconstruction performed a maximum-effort sidestep cutting maneuver while kinematic, kinetic, and ground reaction force data were recorded. Peak ground reaction force and knee joint moments were lower when cutting from the operated limb. Center-of-mass heading angle deflection during stance phase was reduced for cuts performed from the operated limb and was negatively correlated with heading angle at touchdown. Between-limb differences in body orientation and horizontal velocity at touchdown were also observed. These systematic asymmetries in cut execution may require consideration when interpreting joint-level interlimb asymmetries after anterior cruciate ligament reconstruction and are suggestive of the use of anticipatory control to co-optimize task achievement and mechanical loading.


Late cardiovascular consequences of gestational diabetes mellitus.
Gestational diabetes mellitus (GDM), defined as carbohydrate intolerance of any degree first recognized during pregnancy, complicates approximately 4% of all pregnancies in the United States. Several factors can increase one's risk of developing GDM, including obesity, family history of type 2 diabetes mellitus (T2DM), and race/ethnicity. Conversely, a history of GDM can increase the risk of developing not only T2DM but also cardiovascular disease (CVD) independent of a diagnosis of T2DM. Several investigations have explored GDM relationships with CVD risk factors, CVD surrogate markers, and clinically evident CVD. These studies have included evaluations of biochemical parameters, such as inflammatory and endothelial biomarkers; endothelial dysfunction, such as that seen in impaired brachial artery flow-mediated vasodilation; and vascular dysfunction, manifest as cardiac dysfunction or in diseases such as hypertension. This article will review these studies and examine factors considered to be responsible for promoting CVD in women with a history of GDM, such as T2DM and metabolic syndrome and its components. In addition, studies evidencing CVD in women with a history of GDM will be explored.


P2Y1 receptors mediate an activation of neuronal calcium-dependent K+ channels.
Molecularly defined P2Y receptor subtypes are known to regulate the functions of neurons through an inhibition of K(V)7 K(+) and Ca(V)2 Ca(2+) channels and via an activation or inhibition of Kir3 channels. Here, we searched for additional neuronal ion channels as targets for P2Y receptors. Rat P2Y(1) receptors were expressed in PC12 cells via an inducible expression system, and the effects of nucleotides on membrane currents and intracellular Ca(2+) were investigated. At a membrane potential of 30 mV, ADP induced transient outward currents in a concentration-dependent manner with half-maximal effects at 4 μm. These currents had reversal potentials close to the K(+) equilibrium potential and changed direction when extracellular Na(+) was largely replaced by K(+), but remained unaltered when extracellular Cl() was changed. Currents were abolished by P2Y(1) antagonists and by blockade of phospholipase C. ADP also caused rises in intracellular Ca(2+), and ADP-evoked currents were abolished when inositol trisphosphate-sensitive Ca(2+) stores were depleted. Blockers of K(Ca)2, but not those of K(Ca)1.1 or K(Ca)3.1, channels largely reduced ADP-evoked currents. In hippocampal neurons, ADP also triggered outward currents at 30 mV which were attenuated by P2Y(1) antagonists, depletion of Ca(2+) stores, or a blocker of K(Ca)2 channels. These results demonstrate that activation of neuronal P2Y(1) receptors may gate Ca(2+)-dependent K(+) (K(Ca)2) channels via phospholipase C-dependent increases in intracellular Ca(2+) and thereby define an additional class of neuronal ion channels as novel effectors for P2Y receptors. This mechanism may form the basis for the control of synaptic plasticity via P2Y(1) receptors.


Autologous stem cell transplantation for malignancy: a systematic review of the literature.
A systematic review of the literature was undertaken to assess what published evidence is currently available to support the increasing use of autologous stem cell transplantation (ASCT), and to evaluate the published data with regard to the comparative cost of high-dose and conventional therapy. The review aimed to identify all published, randomized controlled trials (RCTs) comparing high-dose therapy (HDT) with ASCT versus conventional chemotherapy (CC) in acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, and breast, lung, testicular and ovarian cancer. The review also aimed to identify all studies that had compared the cost of the two treatment strategies. Reports were identified by systematic searches of Cancerlit, Embase and Medline, and handsearching of several conference proceedings. Where possible, pooled odds ratios (ORs) were calculated according to the fixed-effect model. A total of 18 randomized trials were identified in acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, and breast, lung and testicular cancer. Trials were generally small and no disease site had sufficient information to determine reliably whether high-dose therapy with autologous transplant is more effective than CC. Five studies were identified that compared the cost of the two treatments. These found the cost of HDT to be between one and four times higher than that of CC. Further randomized trials are required. Where appropriate, these should include economic assessment and assessments of long-term toxicity.


The relationship of sodium intake to calcium and sodium excretion and bone mineral density of the hip in postmenopausal African-American and Caucasian women.
During the past several decades in the United States, there has been a shift in dietary habits, with an increased consumption of processed foods that are high in sodium. It is known that calcium and sodium metabolism are linked and that higher sodium intakes may increase calcium excretion. Epidemiological studies in patients with idiopathic hypercalciuria suggest that hypercalciuria is linked to low bone mass. However, the relationship of sodium intake to bone mineral density (BMD) is controversial in Caucasians and has not been explored in African-Americans. To determine the consequences of sodium intake on bone in African-American and Caucasian postmenopausal women, sodium and calcium excretion and BMD of the total hip were measured in 50 Caucasian and 39 African-American postmenopausal women. After adjustment for race and urine volume, sodium excretion was a significant predictor of calcium excretion (P < 0.01). This relationship was modulated by calcium intake (P < 0.01), but not by race (P = 0.63). There was no significant effect of sodium excretion (P = 0.42) or calcium excretion (P = 0.90) on BMD of the total hip after adjusting for race and urine volume. Sodium excretion is a significant predictor of calcium excretion in both postmenopausal African-American and Caucasian women. The relationship between sodium and calcium excretion is modulated by calcium intake, and the relationship is strongest at low calcium intakes (< or =1000 mg/day). However, sodium excretion in the range of 53.75-283.33 mmole/g/total volume (mmole/g/TV) is not a significant predictor of total hip BMD in elderly African-American and Caucasian postmenopausal women.


Marine latitudinal diversity gradients are generally absent in intertidal ecosystems.
Current latitudinal diversity gradient (LDG) meta-analyses have failed to distinguish one of the most widespread marine habitats, the intertidal zone, as a separate system despite it having unique abiotic challenges and spatially compressed stress gradients that affect the distribution and abundance of resident species. We address this issue by revisiting published literature and datasets on LDGs since 1911 to explore LDG patterns and their strengths in intertidal benthic, subtidal benthic, and pelagic realms and discuss the importance of recognizing intertidal ecosystems as distinct. Rocky shorelines were the most studied intertidal ecosystem encompassing 64.2% of intertidal LDG studies, and 62.9% of studies focused on assemblage composition, while the remaining 37.1% of studies were taxa specific. While our analyses confirmed LDGs in subtidal benthic and pelagic realms, with a decrease in richness toward the poles, we found no consistent intertidal LDGs in any ocean or coastline across hemispheres or biodiversity unit. Analyzing intertidal and subtidal zones as separate systems increased the strength of subtidal benthic LDGs relative to analyses combining these systems. We demonstrate that in intertidal ecosystems across oceans in both hemispheres, a latitudinal decrease in species richness is not readily apparent, which stands in contrast with significant LDG patterns found in the subtidal realm. Intertidal habitat heterogeneity, regional environmental variability and biological interactions can create species-rich hot spots independent of latitude, which may functionally outweigh a typical latitudinal decline in species richness. Although previous work has shown weaker LDGs in benthic than pelagic systems, we demonstrate that this is caused by combining subtidal and intertidal benthic ecosystems into a single benthic category. Thus, we propose that subtidal and intertidal ecosystems cannot be combined into one entity as the physical and biological parameters controlling ecosystem processes are vastly different, even among intertidal ecosystems. Thus, the intertidal zone offers a unique model system in which hypotheses can be further tested to better understand the complex processes underlying LDGs.


Identification of bacteriophage virion proteins by the ANOVA feature selection and analysis.
The bacteriophage virion proteins play extremely important roles in the fate of host bacterial cells. Accurate identification of bacteriophage virion proteins is very important for understanding their functions and clarifying the lysis mechanism of bacterial cells. In this study, a new sequence-based method was developed to identify phage virion proteins. In the new method, the protein sequences were initially formulated by the g-gap dipeptide compositions. Subsequently, the analysis of variance (ANOVA) with incremental feature selection (IFS) was used to search for the optimal feature set. It was observed that, in jackknife cross-validation, the optimal feature set including 160 optimized features can produce the maximum accuracy of 85.02%. By performing feature analysis, we found that the correlation between two amino acids with one gap was more important than other correlations for phage virion protein prediction and that some of the 1-gap dipeptides were important and mainly contributed to the virion protein prediction. This analysis will provide novel insights into the function of phage virion proteins. On the basis of the proposed method, an online web-server, PVPred, was established and can be freely accessed from the website (http://lin.uestc.edu.cn/server/PVPred). We believe that the PVPred will become a powerful tool to study phage virion proteins and to guide the related experimental validations.


In-depth analyses unveil the association and possible functional involvement of novel RAD51B polymorphisms in age-related macular degeneration.
The contribution of DNA damage to the pathogenesis of age-related macular degeneration (AMD) has been reported. Recently, a genomewide association study detected the association of a single-nucleotide polymorphism (SNP) in RAD51B (rs8017304 A>G) with AMD. RAD51B is involved in recombinational repair of DNA double-strand breaks. We analyzed RAD51B influence on AMD using two cohorts from Caucasian and Han Chinese populations. The Caucasian set replicated the rs8017304 A>G association and revealed two novel AMD-associated SNPs in RAD51B, rs17105278 T>C and rs4902566 C>T. Under the dominant model, these two SNPs exhibit highly significant disease risk. SNP-SNP interaction analysis on rs17105278 T>C and rs4902566 C>T homozygous demonstrated a synergistic effect on AMD risk, reaching an odds ratio multifold higher than well-established AMD susceptibility loci in genes such as CFH, HTRA1, and ARMS2. Functional study revealed lower RAD51B mRNA expression in cultured primary human fetal retinal pigment epithelium (hfRPE) carrying rs17105278 T>C variants than in hfRPE carrying rs17105278 wild type. We concluded that the risk of developing AMD exhibits dose dependency as well as an epistatic combined effect in rs17105278 T>C and rs4902566 C>T carriers and that the elevated risk for rs17105278 T>C carriers may be due to decreased transcription of RAD51B. This study further confirms the role of DNA damage/DNA repair in AMD pathogenesis.


[Optimization of energy parameters of ultrasound and laser cataract surgery with a preliminary transcorneal endocapsular YAG-laser impact exerted on the cataract lens nuclei].
The values of the main energy and time parameters of ultrasound and laser fragmentation of different-hardness cataract-lens nuclei were analyzed in patients of various age groups after a preliminary transcorneal endocapsular YAG-laser treatment of the lens. The results show, in all cases, lower key energy and time characteristics, which primarily concerns a total energy index of the ultrasound and laser effect of no less than 20% versus the ordinarily used parameters.


Current and Emerging Technologies for the Detection of Norovirus from Shellfish.
Reports of norovirus infections associated with the consumption of contaminated bivalve molluscan shellfish negatively impact both consumers and commercial shellfish operators. Current virus recovery and PCR detection methods can be expensive and time consuming. Due to the lack of rapid, user-friendly and onsite/infield methods, it has been difficult to establish an effective virus monitoring regime that is able to identify contamination points across the production line (i.e., farm-to-plate) to ensure shellfish quality. The focus of this review is to evaluate current norovirus detection methods and discuss emerging approaches. Recent advances in omics-based detection approaches have the potential to identify novel biomarkers that can be incorporated into rapid detection kits for onsite use. Furthermore, some omics techniques have the potential to simultaneously detect multiple enteric viruses that cause human disease. Other emerging technologies discussed include microfluidic, aptamer and biosensor-based detection methods developed to detect norovirus with high sensitivity from a simple matrix. Many of these approaches have the potential to be developed as user-friendly onsite detection kits with minimal costs. However, more collaborative efforts on research and development will be required to commercialize such products. Once developed, these emerging technologies could provide a way forward that minimizes public health risks associated with shellfish consumption.


The Inhibition of Metabolic Inflammation by EPA Is Associated with Enhanced Mitochondrial Fusion and Insulin Signaling in Human Primary Myotubes.
Sustained fuel excess triggers low-grade inflammation that can drive mitochondrial dysfunction, a pivotal defect in the pathogenesis of insulin resistance in skeletal muscle. This study aimed to investigate whether inflammation in skeletal muscle can be prevented by EPA, and if this is associated with an improvement in mitochondrial fusion, membrane potential, and insulin signaling. Human primary myotubes were treated for 24 h with palmitic acid (PA, 500 μM) under hyperglycemic conditions (13 mM glucose), which represents nutrient overload, and in the presence or absence of EPA (100 μM). After the treatments, the expression of peroxisome proliferator-activated receptor γ coactivator 1-α (PPARGC1A) and IL6 was assessed by q-PCR. Western blot was used to measure the abundance of the inhibitor of NF-κB (IKBA), mitofusin-2 (MFN2), mitochondrial electron transport chain complex proteins, and insulin-dependent AKT (Ser473) and AKT substrate 160 (AS 160; Thr642) phosphorylation. Mitochondrial dynamics and membrane potential were evaluated using immunocytochemistry and the JC-1 (tetraethylbenzimidazolylcarbocyanine iodide) dye, respectively. Data were analyzed using 1-factor ANOVA followed by Tukey post hoc test. Nutrient excess activated the proinflammatory NFκB signaling marked by a decrease in IKBA (40%; P < 0.05) and the upregulation of IL6 mRNA (12-fold; P < 0.001). It also promoted mitochondrial fragmentation (53%; P < 0.001). All these effects were counteracted by EPA. Furthermore, nutrient overload-induced drop in mitochondrial membrane potential (6%; P < 0.05) was prevented by EPA. Finally, EPA inhibited fuel surplus-induced impairment in insulin-mediated phosphorylation of AKT (235%; P < 0.01) and AS160 (49%; P < 0.05). EPA inhibited NFκB signaling, which was associated with an attenuation of the deleterious effects of PA and hyperglycemia on both mitochondrial health and insulin signaling in human primary myotubes. Thus, EPA might preserve skeletal muscle metabolic health during sustained fuel excess but this requires confirmation in human clinical trials.


Serological classification and typing of Clostridium botulinum.
Serological classification of Cl. botulinum, based on the antigenic structure of the toxins produced, is distinguished by the behaviour of the toxin-antitoxin mixtures in in vivo neutralization tests. Observations on the dissimilarity between strains within types, the behaviour of antitoxins in the cross-neutralization tests, the established concepts of the antigenic structure of the toxin types and the lack of a standard methodology for typing, have led to the definition of the terms efficiency, type, subtype, intratypic serological variant (ISV), and degree of serological homology. These definitions are primarily applied to typing and to the establishment of the taxonomic serological categories of type, subtype and ISV. In the case of antitoxin standardization, the accepted standard methods must be followed.


Intrahepatic portosystemic venous shunt: diagnosis by colour/power Doppler imaging and three-dimensional ultrasound.
Intrahepatic portosystemic venous shunt, considered to be a rare disease, can lead to hepatic encephalopathy. With recent advances in diagnostic imaging techniques, the number of reports of intrahepatic portosystemic venous shunts identified incidentally in patients without symptoms are increasing. We report an intrahepatic portosystemic venous shunt that was diagnosed incidentally by real-time ultrasound and colour Doppler imaging, including the use of three-dimensional ultrasound using minimum intensity projections and power Doppler.


Effects of subretinal electrical stimulation in mer-KO mice.
Subretinal electrical stimulation (SES) from microphotodiode arrays protects photoreceptors in the RCS rat model of retinitis pigmentosa. The authors examined whether mer(kd) mice, which share a Mertk mutation with RCS rats, showed similar neuroprotective effects from SES. Mer(kd) mice were implanted with a microphotodiode array at postnatal day (P) 14. Weekly electroretinograms (ERGs) followed by retinal histology at week 4 were compared with those of age-matched controls. RT-PCR for fibroblast growth factor beta (Fgf2), ciliary nerve trophic factor (Cntf), glial-derived neurotrophic factor (Gdnf), insulin growth factor 1 (Igf1), and glial fibrillary acidic protein (Gfap) was performed on retinas at 1 week after surgery. Rates of degeneration using ERG parameters were compared between mer(kd) mice and RCS rats from P28 to P42. SES-treated mer(kd) mice showed no differences in ERG a- and b-wave amplitudes or photoreceptor numbers compared with controls. However, the expression of Fgf2 and Cntf was greater (6.5 ± 1.9- and 2.5 ± 0.5-fold, respectively; P < 0.02) in SES-treated mer(kd) retinas. Rates of degeneration were faster for dark-adapted maximal b-wave, log σ, and oscillatory potentials in mer(kd) mice than in RCS rats. Although SES upregulated Fgf2 in mer(kd) retinas, as reported previously for RCS retinas, this was not accompanied by neuroprotection of photoreceptors. Comparisons of ERG responses from mer(kd) mice and RCS rats across different ages showed inner retinal dysfunction in mer(kd) mice but not in RCS rats. This inner retinal dysfunction and the faster rate of degeneration in mer(kd) mice may produce a retinal environment that is not responsive to neuroprotection from SES.


A case of Woodhouse-Sakati syndrome with pituitary iron deposition, cardiac and intestinal anomalies, with a novel mutation in DCAF17.
Woodhouse-Sakati syndrome is a rare genetic syndrome caused by homozygous mutations of the DCAF17 gene. Several endocrine organs may be affected in the course of the disease. We present a new case with pituitary iron deposition, cardiac and intestinal anomalies, with a novel mutation in DCAF17 gene. An 18-year-old female was admitted because of delayed puberty and amenorrhea. Hormonal evaluation revealed combined hyper-hypogonadotropic hypogonadism. GH and IGF-1 levels were low without short stature. ACTH levels were high and cortisol levels were supranormal with the lack of clinical findings of cortisol excess or deficiency. Pituitary MRI indicated paramagnetic substance deposition in gland. On follow-ups, non-autoimmune, insulinopenic diabetes mellitus and secondary hypothyroidism emerged. Woodhouse-Sakati syndrome was diagnosed on the basis of consistent clinical context and subsequently a novel mutation in DCAF17 was detected.


Room Temperature Sensing Achieved by GaAs Nanowires and oCVD Polymer Coating.
Novel structures comprised of GaAs nanowire arrays conformally coated with conducting polymers (poly(3,4-ethylenedioxythiophene) (PEDOT) or poly(3,4-ethylenedioxythiophene-co-3-thiophene acetic acid) display both sensitivity and selectivity to a variety of volatile organic chemicals. A key feature is room temperature operation, so that neither a heater nor the power it would consume, is required. It is a distinct difference from traditional metal oxide sensors, which typically require elevated operational temperature. The GaAs nanowires are prepared directly via self-seeded metal-organic chemical deposition, and conducting polymers are deposited on GaAs nanowires using oxidative chemical vapor deposition (oCVD). The range of thickness for the oCVD layer is between 100 and 200 nm, which is controlled by changing the deposition time. X-ray diffraction analysis indicates an edge-on alignment of the crystalline structure of the PEDOT coating layer on GaAs nanowires. In addition, the positive correlation between the improvement of sensitivity and the increasing nanowire density is demonstrated. Furthermore, the effect of different oCVD coating materials is studied. The sensing mechanism is also discussed with studies considering both nanowire density and polymer types. Overall, the novel structure exhibits good sensitivity and selectivity in gas sensing, and provides a promising platform for future sensor design.


COVID-19 in babies: Knowledge for neonatal care.
Infection is a leading cause of death worldwide in babies under one month of age who are more susceptible to sepsis due to immature host defence mechanisms. Usually, babies may become acutely unwell from infective pathogens due to specific differences in their respiratory and immune systems. However, with the COVID-19 virus, the focus of this paper, it appears that the neonatal population is not significantly affected in the same way as adults. That said, knowledge about this novel virus is rapidly emerging. Therefore, it is vital that neonatal nurses, midwives and other healthcare professionals are adequately informed and educated about the potential impact on neonatal practice. This review paper draws upon key findings and themes from a selection of recent literature to provide an overview of current knowledge on COVID-19 and the implications for care within the neonatal field. The discussion focuses on the nature of COVID-19, its pathophysiology and transmission relevant to maternal and neonatal care. This is followed by implications for practice; namely, maternal issues, the importance of human breast milk, neonatal care relating to parenting and specific management before a final review of the current World Health Organization guidance.


Functional cortical network in alpha band correlates with social bargaining.
Solving demanding tasks requires fast and flexible coordination among different brain areas. Everyday examples of this are the social dilemmas in which goals tend to clash, requiring one to weigh alternative courses of action in limited time. In spite of this fact, there are few studies that directly address the dynamics of flexible brain network integration during social interaction. To study the preceding, we carried out EEG recordings while subjects played a repeated version of the Ultimatum Game in both human (social) and computer (non-social) conditions. We found phase synchrony (inter-site-phase-clustering) modulation in alpha band that was specific to the human condition and independent of power modulation. The strength and patterns of the inter-site-phase-clustering of the cortical networks were also modulated, and these modulations were mainly in frontal and parietal regions. Moreover, changes in the individuals' alpha network structure correlated with the risk of the offers made only in social conditions. This correlation was independent of changes in power and inter-site-phase-clustering strength. Our results indicate that, when subjects believe they are participating in a social interaction, a specific modulation of functional cortical networks in alpha band takes place, suggesting that phase synchrony of alpha oscillations could serve as a mechanism by which different brain areas flexibly interact in order to adapt ongoing behavior in socially demanding contexts.


Volatile Profile Characterization of Croatian Commercial Sparkling Wines.
Commercial sparkling wine production represents a relatively low but important part of the Croatian wine production, especially in the Zagreb county. This study presents the results of volatile aroma compounds profile and organic acid composition of commercial sparkling wine samples from three vine-growing regions in Zagreb county. In total, 174 volatile aroma compounds were identified, separated between their chemical classes (aldehydes, higher alcohols, volatile phenols, terpenes, C13-norisoprenoids, lactones, esters, fatty acids, sulfur compounds, other compounds, other alcohols). Higher alcohols such as phenylethyl and isoamyl alcohol as well as 2-methyl-1-butanol, and esters such as diethyl succinate, ethyl hydrogensuccinate, and ethyl lactate had the strongest impact on the volatile compounds profile of Zagreb county sparkling wine. The presence of diethyl glutarate and diethyl malonate, compounds whose concentrations are influenced by yeast autolysis or caused by chemical esterification during the ageing process, was also noted. The influence of every single volatile aroma compound was evaluated by discriminant analysis using forward stepwise model. The volatile profiles of traditional sparkling wines from Croatia were presented for the first time. It is hoped the results will contribute to better understanding the quality potential and to evaluate possible differences on the bases of detected aroma concentrations and multivariate analysis.


Pancreatic acinar cell carcinomas and mixed acinar-neuroendocrine carcinomas are more clinically aggressive than grade 1 pancreatic neuroendocrine tumours.
Acinar cell carcinomas (ACCs) and mixed acinar-neuroendocrine carcinomas (MAcNECs) of the pancreas are extremely rare carcinomas with a significant component with acinar differentiation. To date, the clinicopathological behaviours of these neoplasms remain unclear. In this study, we evaluated the histopathological and molecular characteristics of 20 ACCs and 13 MAcNECs and compared them to a cohort of 269 well-differentiated pancreatic neuroendocrine tumours (PanNETs). Compared to PanNETs, both ACCs and MAcNECs had an advanced pT classification (p<0.001), as well as more prevalent lymphovascular and perineural invasion (p=0.002) and lymph node and distant metastases (p<0.001). Patients with MAcNECs had worse overall (p<0.001) and recurrence-free survival (p<0.001) than those with PanNETs, but no significant difference with those with ACCs. Subgroup analyses revealed that patients with ACCs and MAcNECs had significantly worse recurrence-free survival than those with grade 1 PanNET (p<0.001), and patients with MAcNECs also had worse overall survival than those with grade 1 and 2 PanNETs (p<0.001, and p=0.001). ACCs presented more commonly with intraductal growth (p=0.014) than MAcNECs, while MAcNECs more often had lymph node metastasis (p=0.012) than ACCs. The telomere maintenance mechanism Alternative Lengthening of Telomeres (ALT) was assessed by telomere-specific FISH, and ALT was detected in 1 of 20 ACCs and in three of the 13 MAcNECs. Patients with MAcNECs and ACCs had worse survival and more aggressive behaviour than those with grade 1 PanNETs; thus, the clinicopathological behaviour of MAcNECs resembles ACCs rather than PanNETs. Combined neuroendocrine and acinar cell immunohistochemical markers are helpful for differentiating these different tumour types.


Incidence, risk factors, and outcomes of Panton-Valentine leukocidin-positive methicillin-susceptible Staphylococcus aureus infections in Auckland, New Zealand.
Panton-Valentine leukocidin (PVL) has been linked to invasive community-acquired methicillin-resistant Staphylococcus aureus infections. However, the association between disease and PVL-positive methicillin-susceptible Staphylococcus aureus (MSSA) has not been widely reported. We aimed to examine the epidemiology of PVL in clinical MSSA isolates from patients presenting to Auckland City Hospital. Four hundred eleven MSSA clinical isolates and 93 nasal carriage isolates were collected and tested for the presence of the lukSF-PV genes using PCR. The results were examined in light of host and disease factors. Multilocus sequence typing (MLST) was performed on a random subset of isolates to ensure that there was no single PVL-positive MSSA clone responsible for disease in Auckland. The prevalence of the lukSF-PV genes in MSSA isolates associated with disease (124/335; 37%) was not significantly different from the prevalence of the lukSF-PV genes in MSSA nasal carriage isolates (29/93; 31% [P = 0.33]). PVL-positive MSSA isolates in Auckland are genetically diverse and come from a number of different clonal complexes. PVL-positive infections peaked at between 10 and 20 years of age, with a subsequent decline. Pacific ethnicity, age, diagnosis of skin and soft tissue infection (SSTI), community-onset infection, and the need for surgical intervention were found by multivariate analysis to be independently associated with PVL-positive MSSA infection. More than one-third of MSSA infections in our patient population are caused by PVL-positive strains. Those patients with PVL-positive MSSA infection were more likely to be of Pacific ethnicity, be younger in age, have community-onset infection, have SSTI, and need surgical intervention.


[Present-day vascular surgery--unsolved problems].
With the establishment in the USSR of the ALL-Union Society of Cardiovascular Surgeons, a section of angiology at the All-Union Society of Cardiologists, and sections of heart and vascular surgery at the All-Union Society of Surgeons, the necessity of consolidating the efforts of all these organizations to advance and intensify the scientific and practical work in rendering adequate and effective aid to patients with vascular diseases must be recognized. Twenty-two thousand reconstructive operations were performed on the aorta and great arteries in the USSR in 1987. The main trends in vascular surgery in the USA and USSR were analysed; insufficient attention to such problems as surgery of the branches of the arch of the aorta and aneurysms of the abdominal aorta was pointed out, the need to intensify training of new angiosurgeons in the country and increase two- to threefold the number of operations performed by each one of them (to 100 reconstructive operations carried out by each surgeon annually) was substantiated. The experience of the Bakulev Institute of Cardiovascular Surgery is shown in illustration of the main organizational measures which allow the number of reconstructive operations in the cardinal branches of angiosurgery to be increased twofold. The following should be considered the main branches of angiosurgery: surgery of multifocal atherosclerosis, branches of the arch of the aorta, aneurysms of the aorta, and surgery in thromboembolism of the pulmonary arteries, reconstructive operations in injury and acute thrombosis of the great arteries, radiologically-guided surgery for recanalization of arteries and creation of new thromboresistant vascular prostheses.


Low-power slice selective imaging of broad signals.
One of the major challenges in using magnetic resonance imaging (MRI) to study immobile samples, such as solid materials or rigid tissues like bone or ligaments, is that the images appear dark due to these samples' short-lived signals. Although it is well known that narrowband signals can be excited in inhomogeneously-broadened lines, it is less well known that similar effects can be observed in dipolar-broadened systems. These long-lived signals have not been used much, mainly because their description frequently does not match intuition. While 3D imaging with these signals has previously been reported, here we focus on the demonstration of faster, 2D slice-selective imaging. The faster imaging provides more flexibility for visualizing these rigid objects. We also focus on the frequently-encountered regime wherein the maximum power achievable for rf pulses is significantly weaker than the linewidth. This regime is typically encountered in clinical MRI scans or large volume setups. When compared to UTE and conventional slice-selective spin echo methods, this technique provides better representations of the sample considered here (an eraser sample), and higher signal-to-noise ratios than spin-echo techniques in both the high and low power regimes.


Occupational therapy inpatient rehabilitation interventions with deconditioned older adults following an acute hospital admission: a Delphi study.
Older adults admitted to an acute hospital setting with an illness often experience deconditioning. Although occupational therapists frequently work with deconditioned older adults in inpatient rehabilitation programmes, limited information exists regarding the type of interventions used and how these interventions are provided. This study aimed to determine the level of consensus among Australian occupational therapists about occupational therapy service delivery and interventions commonly used during inpatient rehabilitation with older adults who have become deconditioned during acute hospital admission for a medical illness. The Delphi technique was used to reach consensus among expert occupational therapists regarding service delivery and interventions commonly used in an ideal clinical setting. Data were analysed from three rounds of surveys and the percentage of agreement between clinicians were calculated. Twenty-six participants completed round one survey, with 24 completing subsequent surveys (92% response rate). Fifteen commonly used interventions were identified, including showering/dressing, light meal preparation and home assessment. Consensus was reached on commonly used aspects of service delivery, including intervention provision, programme length, team members and follow up after discharge. Results generated may assist in guiding occupational therapists in the attributes of service delivery and the type of interventions currently considered best practice when working with deconditioned older adults in a rehabilitation setting. The information provides preliminary data for effectiveness studies.


Physiological evidence for arteriovenous anastomoses in the uterine circulation of late-pregnant ewes.
1. The objective of the present study was to determine whether arteriovenous anastomoses (AVA) are present in the uterine circulation of conscious, late-pregnant ewes. 2. Twenty late-pregnant ewes were assigned to two groups. In group 1, 15 microm coloured microspheres were injected into the uterine artery of the pregnant horn and the relative proportion of microspheres trapped in the uterus and lungs was determined. The percentage shunting of blood measured by this method was 17+/-3%, representing a blood flow of 164+/-39 mL/min (n = 12). Any contribution of ovarian, cervical, rectal and other vascular beds was specifically excluded in this group. 3. In group 2, total uterine capillary flow was measured using the reference blood flow method, by injecting 15 microm microspheres into the heart. Calibrated flow probes, placed on both main uterine arteries, concurrently measured total uterine blood flow. Total blood flow to the uterus (flow probe) was significantly greater (t = 3.415; P = 0.027) than uterine capillary flow (microspheres), indicating AVA shunting in the uterine circulation. Mean total blood flow to the uterus was 1749+/-160 mL/min, of which an average 25+/-5% (n = 5 sheep) was shunted. 4. The percentage AVA shunting for groups 1 and 2 was not significantly different (t = 1.219; P = 0.24) and, when combined, the mean percentage of uterine blood flow passing through AVA in the late-pregnant sheep was determined to be 19+/-3%. 5. The present study shows that AVA are present and patent in the uterine circulation of late-pregnant ewes and that they account for the shunting of approximately 20% of the uterine blood flow into the maternal venous circulation.


Management for Residual Ground-Glass Opacity Lesions After Resection of Main Tumor in Multifocal Lung Cancer: A Case Report and Literature Review.
There are increasing numbers of synchronous multiple primary lung cancer (SMPLC) patients in clinical practice, with most lesions presenting as ground-glass opacity (GGO). For SMPLC patients, surgical resection should be a prior option for all lesions suspected of being malignant, if medically and technically feasible. However, it is frequently a dilemma for the management of residual GGO lesions that were unresected simultaneously with the main tumor in SMPLC patients. We report a case of SMPLC, in which the patient underwent surgical resection of the major lesion with EGFR mutation and then received compelling EGFR-TKI treatment for one enlarging residual GGO lesion after 12 months since operation. Furthermore, a comprehensive literature review about the risk for the progress of GGOs unresected simultaneously with the main lesion and the management of these residual GGOs was also summarized. With the treatment of EGFR-TKI gefitinib for 3 months, the biggest residual GGO lesion (more than 10mm) achieved a complete response (CR), three lesions reduced in size, and the other three lesions remained stable in this case. Surgical resection for major lesion and EGFR-TKI treatment on unresected GGOs might bring favorable outcome for patients with EGFR-mutated multifocal lung cancer. This strategy is safe and effective, which could be a promising therapeutic approach for unresectable GGO lesions in EGFR-mutated SMPLC patients after primary surgery. Notably, folate receptor-positive circulating tumor cell (FR+-CTC) for therapeutic monitoring was more sensitive for GGO-featured lung adenocarcinoma than serum markers.


Correlating Nitrile IR Frequencies to Local Electrostatics Quantifies Noncovalent Interactions of Peptides and Proteins.
Noncovalent interactions, in particular the hydrogen bonds and nonspecific long-range electrostatic interactions are fundamental to biomolecular functions. A molecular understanding of the local electrostatic environment, consistently for both specific (hydrogen-bonding) and nonspecific electrostatic (local polarity) interactions, is essential for a detailed understanding of these processes. Vibrational Stark Effect (VSE) has proven to be an extremely useful method to measure the local electric field using infrared spectroscopy of carbonyl and nitrile based probes. The nitrile chemical group would be an ideal choice because of its absorption in an infrared spectral window transparent to biomolecules, ease of site-specific incorporation into proteins, and common occurrence as a substituent in various drug molecules. However, the inability of VSE to describe the dependence of IR frequency on electric field for hydrogen-bonded nitriles to date has severely limited nitrile's utility to probe the noncovalent interactions. In this work, using infrared spectroscopy and atomistic molecular dynamics simulations, we have reported for the first time a linear correlation between nitrile frequencies and electric fields in a wide range of hydrogen-bonding environments that may bridge the existing gap between VSE and H-bonding interactions. We have demonstrated the robustness of this field-frequency correlation for both aromatic nitriles and sulfur-based nitriles in a wide range of molecules of varying size and compactness, including small molecules in complex solvation environments, an amino acid, disordered peptides, and structured proteins. This correlation, when coupled to VSE, can be used to quantify noncovalent interactions, specific or nonspecific, in a consistent manner.


Low serum creatinine levels as risk factor of diabetes mellitus: prediabetes considerations.
It has been reported that low serum creatinine level is a risk factor of diabetes. We hypothesize that should this be true, serum creatinine levels would be lower and more prevalent in prediabetes than in normal individuals. 1017 glucose tolerance tests performed at South West Pathology Service of the New South Wales Health, Australia, in 2008 were sorted into normal (control), prediabetes and diabetes based on decisive interpretation. All cases with creatinine results in the control (n=48), diabetes (n=18) and prediabetes (n=36) groups were selected. Mean levels of serum creatinine levels in the controls (80 +/- 32 micromol/L), diabetes (82 +/- 26 micromol/L) and prediabetes (82 +/- 23 micromol/L) were not statistically significantly different. The prevalence of low levels of serum creatinine is less in prediabetes (11%) than in the control (23%). Further studies using a larger number and adjusting for confounding factors is needed to ascertain the role of low serum creatinine level as a risk factor of diabetes.


Effect of Fe nanoparticle on growth and glycolipid biosurfactant production under solid state culture by marine Nocardiopsis sp. MSA13A.
Iron is an essential element in several pathways of microbial metabolism, and therefore low iron toxicity is expected on the usage of Fe nanoparticles (NPs). This study aims to determine the effect of Fe NPs on biosurfactant production by marine actinobacterium Nocardiopsis sp. MSA13A under solid state culture. Foam method was used in the production of Fe NPs which were long and fiber shaped in nature. The SEM observation showed non toxic nature of Fe NPs as no change in the morphology of the filamentous structure of Nocardiopsis MSA13A. The production of biosurfactant by Nocardiopsis MSA13A under solid state culture supplemented with Fe NPs increased to 80% over control. The biosurfactant produced by Nocardiopsis MSA13A was characterized as glycolipid derivative which effectively disrupted the pre-formed biofilm of Vibrio pathogen. The use of metal NPs as supplement would reduce the impact of non-metallic ions of the metal salts in a fermentation process. This would ultimately useful to achieve greener production process for biosurfactants. The present results are first report on the optimization of biosurfactant production under SSC using Fe NPs.


Hospital management training in the North Eastern Region.
The article highlights the lack of training facilities for hospital management in the entire North Eastern Region, explores the quantum of need of the training in the region by identifying hospitals, other health institutions and manpower in the region which require, for their qualitative and quantitative improvement, the expertise in hospital management, and recommends suitable courses of hospital management to start with.


Modeling and inverse controller design for an unmanned aerial vehicle based on the self-organizing map.
The next generation of aircraft will have dynamics that vary considerably over the operating regime. A single controller will have difficulty to meet the design specifications. In this paper, a self-organizing map (SOM)-based local linear modeling scheme of an unmanned aerial vehicle (UAV) is developed to design a set of inverse controllers. The SOM selects the operating regime depending only on the embedded output space information and avoids normalization of the input data. Each local linear model is associated with a linear controller, which is easy to design. Switching of the controllers is done synchronously with the active local linear model that tracks the different operating conditions. The proposed multiple modeling and control strategy has been successfully tested in a simulator that models the LoFLYTE UAV.


Wasserstein Dictionaries of Persistence Diagrams.
This paper presents a computational framework for the concise encoding of an ensemble of persistence diagrams, in the form of weighted Wasserstein barycenters [100], [102] of a dictionary of atom diagrams. We introduce a multi-scale gradient descent approach for the efficient resolution of the corresponding minimization problem, which interleaves the optimization of the barycenter weights with the optimization of the atom diagrams. Our approach leverages the analytic expressions for the gradient of both sub-problems to ensure fast iterations and it additionally exploits shared-memory parallelism. Extensive experiments on public ensembles demonstrate the efficiency of our approach, with Wasserstein dictionary computations in the orders of minutes for the largest examples. We show the utility of our contributions in two applications. First, we apply Wassserstein dictionaries to data reduction and reliably compress persistence diagrams by concisely representing them with their weights in the dictionary. Second, we present a dimensionality reduction framework based on a Wasserstein dictionary defined with a small number of atoms (typically three) and encode the dictionary as a low dimensional simplex embedded in a visual space (typically in 2D). In both applications, quantitative experiments assess the relevance of our framework. Finally, we provide a C++ implementation that can be used to reproduce our results.


Affective components in promoting physical activity: A randomized controlled trial of message framing.
Although the study of the affective components involved in predicting physical activity is spreading faster and faster, there is a lack of studies testing their role when promoting physical activity through message interventions. In the present study, we considered these components by focusing on how anticipated affective reactions and emotional processing of the messages influence receivers' affective attitude toward physical activity, concurrent behavior, and future intention. A sample of 250 participants was involved in an intervention relying on prefactual (i.e., "If … then…") messages promoting physical activity. All messages were sent through a research app and were focused on the expected consequences of exercising (or not exercising). Four experimental conditions involving messages differing as to their outcome sensitivity framing (i.e., gain, non-loss, non-gain, and loss) were compared to a control condition. Results showed that reading gain and non-gain messages enhanced the positive affective attitude toward physical activity, compared to control. Enhanced affective attitude after the intervention increased, in turn, self-reported physical activity and future intention. Interestingly, gain messages were even more persuasive for people with a low level of positive anticipated affective reactions. Furthermore, their effectiveness was especially attributable to the elicitation of hope in receivers. Discussion focuses on the advantages of considering affective components and their implications when promoting physical activity.


BAS1 and SOB7 act redundantly to modulate Arabidopsis photomorphogenesis via unique brassinosteroid inactivation mechanisms.
Active brassinosteroids (BRs), such as brassinolide (BL) and castasterone (CS), are growth-promoting plant hormones. An Arabidopsis cytochrome P450 monooxygenase (CYP734A1, formerly CYP72B1), encoded by the BAS1 gene, inactivates BRs and modulates photomorphogenesis. BAS1 was identified as the overexpressed gene responsible for a dominant, BR-deficient mutant, bas1-D. This mutant was isolated in an activation-tagged screen designed to identify redundant genes that might not be identified in classic loss-of-function screens. Here we report the isolation of a second activation-tagged mutant with a BR-deficient phenotype. The mutant phenotype is caused by the overexpression of SOB7 (CYP72C1), a homolog of BAS1. We generated single and double null-mutants of BAS1 and SOB7 to test the hypothesis that these two genes act redundantly to modulate photomorphogenesis. BAS1 and SOB7 act redundantly with respect to light promotion of cotyledon expansion, repression of hypocotyl elongation and flowering time in addition to other phenotypes not regulated by light. We also provide biochemical evidence to suggest that BAS1 and SOB7 act redundantly to reduce the level of active BRs, but have unique mechanisms. Overexpression of SOB7 results in a dramatic reduction in endogenous CS levels, and although single null-mutants of BAS1 and SOB7 have the same level of CS as the wild type, the double null-mutant has twice the amount. Application of BL to overexpression lines of BAS1 or SOB7 results in enhanced metabolism of BL, though only BAS1 overexpression lines confer enhanced conversion to 26-OHBL, suggesting that SOB7 and BAS1 convert BL and CS into unique products.


CIDP diagnostic pitfalls and perception of treatment benefit.
We aimed to explore the diagnosis and misdiagnosis of chronic inflammatory demyelinating polyneuropathy (CIDP) and to identify pitfalls that erroneously lead to a misdiagnosis. A retrospective study of 59 consecutive patients referred with a diagnosis of CIDP was performed. Patients were classified as having or not having CIDP according to European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) criteria. Diagnostic and treatment data were compared in the 2 groups. Forty-seven percent of patients referred with a diagnosis of CIDP failed to meet minimal CIDP diagnostic requirements. All misdiagnosed patients who satisfied EFNS/PNS clinical criteria would be considered atypical as defined by the EFNS/PNS. CSF cytoalbuminologic dissociation was present in 50% of those without CIDP, although protein elevations were generally mild. Nerve conduction studies in patients without CIDP were heterogeneous, but generally showed demyelinating features better explained by a process other than CIDP. Patients frequently reported improvements after being treated with immunotherapy, even if the CIDP diagnosis was incorrect. CIDP misdiagnosis is common. Over-reliance on subjective patient-reported perception of treatment benefit, liberal electrophysiologic interpretation of demyelination, and placing an overstated importance on mild or moderate cytoalbuminologic dissociation are common diagnostic errors. Utilization of clear and objective indicators of treatment efficacy might improve our ability to make informed treatment decisions.


Improved health or improved decision making? The ethical goals of EBM.
Evidence-based medicine (EBM) is frequently portrayed as a value-free approach to knowing what kinds of treatment 'really work.' Since practitioners should help patients to improve their health, and EBM tells us which interventions will work, then it follows that we must practice EBM, offering only those interventions supported by evidence. The primary goal of EBM, then, is an ethical one - to improve health. More recently, EBM's authors have also committed themselves to 'shared decision making' in which evidence plays a role in the clinical encounter, but where patients, motivated by their own values, should have final decision-making authority. Envisioned this way, strengthening the informed consent process, rather than improved health per se, is viewed as the goal of EBM. In this paper, I will explore this shift in EBM's ethics from the goal of improved health towards the goal of strengthened informed consent. Drawing upon data from a qualitative enquiry of scholars involved in the development of EBM, I will argue that EBM is now committed to both of these ethical goals. Where they conflict, the aim of the intervention will determine which goal practitioners should pursue. Having increased the ethical complexity of EBM, we are left with the question of whether EBM would still be judged a success if it did not lead to much in the way of improvements in health, but primarily strengthened informed consent. This paper will conclude by arguing that this more nuanced version of EBM's ethics accurately reflects the dynamics of real clinical practice but undermines the original, perceived need for EBM.


[The use of fluorography in the diagnosis of tumors of the large intestine].
A current approach to the perfection of the diagnosis of colonic tumors is proposed in patients at risk by means of introduction into the ambulatory health care system (polyclinics, diagnostic centers) of standardized colonic fluorography followed by endoscopy in necessary cases. The main organizational and methodological principles of the use of colonic fluorography were worked out as a method of screening to reveal colonic tumors. It is suggested that such new elements as the "prescopic stage" realized outside the radiation zone, automated distant air inflation into the colon and so forth may be introduced in colonic fluorographic examination. Experience gained with over 2065 colonic fluorographies on a special fluorograph and 1120 examinations on routine x-ray diagnostic units fitted with the amplifier and a photochannel (79 cases of colonic carcinoma and 89 benign tumors were identified) evidences that the program of making colonic fluorography enables one to significantly improve the diagnosis of colonic tumors.


Congenital median clefts of the upper lip.
This is a report of 12 cases of congenital median cleft deformity of the upper lip seen in the Department of Plastic Surgery, Singapore General Hospital. This deformity is extremely rare and there are probably not more than 100 cases reported in the literature. The classification, nomenclature, pathogenesis and embryological development of median clefts are still not clearly understood. An analysis of the 12 cases is made with the view to clarify the nomenclature and classification of median clefts. An attempt is also made to explain the embryogenesis of this deformity and its common association with cranial and other facial defects.


Role of the central adrenergic system in mediating amitriptyline-induced alteration in the mammalian blood-brain barrier in vivo.
All tricyclic antidepressants increase the degree of equilibration of [3H]water across the cerebral capillary (Ew) as measured by a dual-label radioactive tracer technique. By using amitriptyline (AMI) as a prototype, a series of studies was conducted to determine the mechanism for this drug effect. The AMI-induced increase in Ew was blocked by 6-hydroxydopamine ablation of central aminergic neurons and by pretreatment with phenoxybenzamine, an alpha adrenergic antagonist. Pretreatment with propranolol, a beta adrenergic antagonist, did not block the AMI-induced increase. Central serotonergic ablation by p-chloroamphetamine had no effect on the AMI-induced increase. Treatment with atropine and hydroxyzine separately also did not alter Ew. Based on these results, the AMI-induced increase in Ew appears to be mediated by the effect of the drug on central adrenergic neurons. The serotonergic, anticholinergic and antihistaminergic actions of AMI, by themselves, do not appear to play a role in this phenomenon. The results are compatible with the concept that the central adrenergic system functions, in part, to regulate the cerebromicrocirculation.


A Prospective Study of Predictors and Consequences of Hooking Up for Sexual Minority Women.
Hooking up, which refers to a sexual encounter (ranging from kissing to penetrative sex) between individuals who are not in a committed relationship, is an increasingly normative form of sexual exploration among emerging adults. Past research has focused on hookups within a heteronormative context, and some of this work has examined hookups as a way to cope with distress. Building on this work, we examined the role of hookups as a means for lesbian and bisexual women to cope with minority stress through increasing connection and engagement with the LGBTQ (lesbian/gay/bisexual/transgender/queer or questioning) community. A nationally recruited sample of 520 lesbian and bisexual women ages 18 to 25 years completed questionnaires regarding their hookup behaviors as part of a longitudinal study. Childhood sexual abuse, posttraumatic stress symptoms, alcohol use, minority stress, and involvement and connectedness with the LGBTQ community were also assessed. First, regression analyses were used to examine baseline predictors of hookup behaviors reported at a 12-month follow-up. Findings revealed that alcohol use was associated with a greater likelihood of any subsequent hookups, and individuals reporting more minority stress subsequently hooked up with more partners. Second, hookup behaviors at 12 months were examined as predictors of outcomes at a 24-month follow-up, after controlling for baseline variables. Findings revealed that hookup behaviors were associated with reduced minority stress as well as increased involvement with and connectedness to the LGBTQ community, suggesting hookups may serve a protective function. Overall, findings support the notion that, for sexual minority women, hookups may operate as a means of coping and connection.