Stabilizing family life after gastric bypass surgery.
Weight-loss surgery requires lifelong lifestyle modifications for the maintenance of weight loss and health effects, and can affect both the individual and family. Earlier research indicates that the quality of social relationships has positive and negative influences on wellbeing and health. There is little research on family-life after a member has undergone gastric bypass (GBP) against obesity. Thus, this study aimed to develop a classic grounded theory about families with a member treated with GBP against obesity. The study design used classic grounded theory and included data from 16 interviews. Families' shared a main concern of unexpected changes after GBP, resulting in the theory Stabilizing family life, explained as a social process to decrease uncertainty and find stability and well-being in family interactions. The social process develops differently which entail families: attaining unity, returning to old patterns, or disconnecting to find stability, depending on the discrepancy in expectations and knowledge. This is affected by the overall life situation, life-stage and relationship quality. The theory highlights unexpected change as a potential challenge for the family, as well as how they resolve this. Hence, the theory can be applied in care strategies for families. Identification of families needing support to stabilize family life after GBP requires further research.


The effect of nitric oxide production by sinusoidal endothelial cells on preservation injury during cold ischemia.
Multifactorial elements are responsible for preservation and reperfusion injury in liver allografts. Sinusoidal endothelial cells (SECs) are a primary target of cold preservation injury of the liver. We examined the correlation between nitric oxide (NO) production by SECs and their injury during cold preservation. SECs were isolated from rat livers and preserved in either Euro-Collins (EC) or University of Wisconsin (UW) solution. Injury to the SECs was more severe when preserved in the EC solution than in the UW solution during cold ischemia. In addition, NO production by SECs was found to be proportionate to the cell injury. Cell viability was not improved by the addition of NO inhibitor, L-NMMA. Further, NO inhibitor was detrimental to the SECs in a 24-h preservation in UW solution. LDH release by SECs preserved in UW solution supplemented with L-NMMA was 11.10+/-2.03 IU/l, while that in UW solution alone was 3.70+/-0.70 IU/l (P<0.01). Together, our results suggest that NO protects SECs during cold preservation and that NO from SECs may have beneficial effects on the liver during cold ischemia.


Imaging genetic liability to schizophrenia: systematic review of FMRI studies of patients' nonpsychotic relatives.
There is a growing literature on brain activity in the nonpsychotic first-degree relatives of patients with schizophrenia as measured using functional imaging. This systematic review examined 20 studies in 4 domains of cognition, including cognitive control (7 samples), working memory (5 samples), long-term memory (4 samples), and language (4 samples). While the literature was widely divergent, these studies did consistently find activation differences between patients' relatives and controls. The most consistent increases in activation within hemisphere were found in right ventral prefrontal cortex (PFC) and right parietal cortex. Abnormal activity, defined as significant increases or decreases in activation relative to controls irrespective of hemisphere, was found in about two-thirds of contrasts in the cerebellum, dorsal prefrontal, lateral temporal, and parietal cortices, and thalamus, with basal ganglia and ventral PFC showing abnormalities in approximately half of those contrasts. Anterior cingulate was generally spared in patients' relatives. The diversity of findings in studies of patients' relatives may derive from differences between the cognitive demands across studies. We identify avenues for building a more accurate and cumulative literature, including symmetrical inclusion criteria for relatives and controls, recording in-scanner responses, using both a priori and whole-brain tests, explicitly reporting threshold values, reporting main effects of task, reporting effect sizes, and quantifying the risk of false negatives. While functional imaging in the relatives of schizophrenia patients remains a promising methodology for understanding the impact of the unexpressed genetic liability to schizophrenia, no single region or mechanism of abnormalities has yet emerged.


Association of Sex With Recurrence of Autism Spectrum Disorder Among Siblings.
Autism spectrum disorder (ASD) is known to be more prevalent among males than females in the general population. Although overall risk of recurrence of ASD among siblings has been estimated to be between 6.1% and 24.7%, information on sex-specific recurrence patterns is lacking. To estimate high-confidence sex-specific recurrence rates of ASD among siblings. This observational study used an administrative database to measure the incidence of ASD among children in 1 583 271 families (37 507 with at least 1 diagnosis of ASD) enrolled in commercial health care insurance plans at a large US managed health care company from January 1, 2008, through February 29, 2016. Families in the study had 2 children who were observed for at least 12 months between 4 and 18 years of age. The primary measure of ASD recurrence was defined as the diagnosis of ASD in a younger sibling of an older sibling with an ASD diagnosis. Among the 3 166 542 children (1 547 266 females and 1 619 174 males; mean [SD] age, 11.2 [4.7] years) in the study, the prevalence of ASD was 1.96% (95% CI, 1.94%-1.98%) among males and 0.50% (95% CI, 0.49%-0.51%) among females. When a male was associated with risk in the family, ASD was diagnosed in 4.2% (95% CI, 3.8%-4.7%) of female siblings and 12.9% (95% CI, 12.2%-13.6%) of male siblings. When a female was associated with risk in the family, ASD was diagnosed in 7.6% (95% CI, 6.5%-8.9%) of female siblings and 16.7% (95% CI, 15.2%-18.4%) of male siblings. These findings are in agreement with the higher rates of ASD observed among males than among females in the general population. Our study provides more specific guidance for the screening and counseling of families and may help inform future investigations into the environmental and genetic factors that confer risk of ASD.


Pregnant women's alcohol consumption and knowledge about its risks: An Israeli survey.
Alcohol consumption is found in a significant proportion of women during their pregnancies. The only study on the prevalence of alcohol consumption during pregnancy in Israel was conducted over a decade ago. Thus, our study aimed to assess alcohol consumption before and during pregnancy, associations with demographic characteristics, knowledge of possible risks of prenatal alcohol exposure, and relations among such knowledge, sociodemographic characteristics, and drinking habits. A convenience sample of 802 pregnant Israeli women completed an anonymous online questionnaire regarding their alcohol consumption during pregnancy, recommendations received, and knowledge of possible risks. Of the sample, 539 (67.2 %) women self-reported drinking alcohol in the 2 months prior to learning they were pregnant, and 96 (12 %) during their pregnancy. Twice as many (28.1 %) reported knowing other women who had consumed alcohol during pregnancy. Women with higher education, in their first pregnancies, ethnically Jewish, and secular reported the highest pre-pregnancy rates of alcohol consumption. About 40 % reported receiving no education about the dangers of alcohol consumption during pregnancy. A concerning percentage of pregnant women in Israel acknowledge drinking alcohol near and after conception. Although most participants reported discontinuing use after realizing they were pregnant, a worrying percentage continued consumption with little knowledge of the dangers. Actual rates may be higher. Information about risks of prenatal alcohol exposure is not widely disseminated, emphasizing the need to increase public awareness.


Long-term survival effect of metoprolol in dilated cardiomyopathy. The SPIC (Italian Multicentre Cardiomyopathy Study) Group.
To evaluate the additive effect of metoprolol treatment on long-term incidence of fatal and non-fatal cardiac events in idiopathic dilated cardiomyopathy. 586 patients with idiopathic dilated cardiomyopathy were prospectively enrolled in a multicentre registry and followed up for a mean (SD) of 52 (32) months. Metoprolol, carefully titrated to the maximum tolerated dose, was added to conventional heart failure treatment in 175 patients. Survival and transplant-free survival at seven years were significantly higher in the 175 metoprolol treated patients than in the remaining 411 on standard treatment (81% v 60%, p < 0.001, and 69% v 49%, p < 0.001, respectively). By multivariate analysis, metoprolol independently predicted survival and transplant-free survival (relative risk reduction values for all cause mortality and combined mortality or transplantation 51% (95% confidence interval 21% to 69%), p = 0.002, and 34% (5% to 53%), p = 0.01, respectively). New York Heart Association class, left ventricular end diastolic diameter, and pulmonary wedge pressure were also predictive. Seven year survival (80% v 62%, p = 0.004) and transplant-free survival (68% v 51%, p = 0.005) were significantly higher in 127 metoprolol treated cases than in 127 controls selected from the entire control cohort and appropriately matched. Metoprolol was associated with a 30% reduction in all cause mortality (7% to 48%, p = 0.015) and a 26% reduction in mortality or transplantation (7% to 41%, p = 0.009). The addition of metoprolol to standard heart failure treatment, including angiotensin converting enzyme inhibitors, was effective in the long-term, reducing both all cause mortality and transplantation in patients with idiopathic dilated cardiomyopathy.


Clinical features and prognosis of canine megaesophagus in Japan.
Megaesophagus (ME) is a common esophageal disease in dogs and the prognosis is generally poor, especially with aspiration pneumonia (AP). We retrospectively investigated the clinical features and prognosis of canine ME in Japan. Twenty-eight dogs were included in this study, with the Miniature Dachshund breed being significantly overrepresented (odds ratio: 4.33). Most cases (21 of 28) were diagnosed as idiopathic ME and Myasthenia gravis was the most common cause of secondary ME. The overall median survival time (MST) was not reached and the 3-month survival rate was 85.7%. Ten dogs were diagnosed with AP, at least once during the study period, and the MST of ME dogs with AP was 114 days. The survival time overall and even with AP, was notably more prolonged compared to the previous studies. We hypothesized that treatment for canine ME could prolong the survival time, even in those with both ME and AP.


The spread of state any willing provider laws.
To describe the growth of any willing provider (AWP) and freedom of choice (FOC) laws applicable to managed care firms and to explore empirically the determinants of their enactment. A 1996 compendium of state laws and state-level data from the 1991-1994 period. Pooled cross-section time-series logistic regression of the decision to enact various types of AWP and FOC laws. Analysis uses a public choice framework to examine enactment. Key variables include proxy measures of proponent and opponent strength and the political environment. The model works well for laws affecting hospitals, but performs poorly for physician and pharmacy laws. More providers are associated with the enactment of AWP and FOC laws. More large employers are associated with a reduced likelihood of enactment of some forms of the laws but not others. Conservative states are more likely to enact laws limiting selective contracting with hospitals and physicians. States with greater interparty competition are also more likely to adopt some types of legislation. The empirical results generally are consistent with the view that AWP and FOC laws are often enacted as a defensive strategy on the part of providers, but additional research is needed to provide a more definitive assessment of the determinants of these laws. Suggestions for future research are provided.


The role of hepatocyte growth factor/c-Met in chronic rhinosinusitis with nasal polyps.
Hepatocyte growth factor (HGF) is a growth factor thought to attenuate Th2-driven eosinophilic airway inflammatory responses. Increased expression of HGF and its receptor c-Met in nasal polyps suggests a role in disease pathogenesis. The effect of HGF on human sinonasal epithelial cell (SNEC) responses to Th2 inflammatory cytokines in chronic rhinosinusitis with nasal polyps (CRSwNP) has not been explored. SNECs isolated from patients with CRSwNP and control subjects were grown in cell culture at the air-liquid interface. The Th2 cytokine IL-13 was applied for 24 hours in the presence or absence of HGF. Eotaxin-3 and c-Met expression was assessed using real-time PCR, immunohistochemistry, and flow cytometry. SNECs obtained from both CRSwNP and control subjects showed markedly increased expression of eotaxin-3 after exposure to IL-13. HGF significantly blocked IL-13-induced expression of eotaxin-3 in control SNECs, but not in SNECs derived from CRSwNP subjects. SNECs are active participants in sinonasal mucosal immunity, expressing inflammatory mediators in response to potential pathogens and endogenous cytokines. Although Th2 cytokines can elicit expression of proeosinophilic mediators by SNECs, HGF appears to have a down-regulating effect on this response. In patients with CRSwNP, SNECs are resistant to this attenuation, showing continued IL-13-induced eotaxin-3 expression despite HGF treatment. Abnormalities in the regulation of epithelial cell responses to endogenous cytokines and growth factors may contribute to the persistent eosinophilic inflammatory state in CRSwNP.


First trimester prenatal diagnosis: chorionic villus sampling.
Chorionic villus sampling has been used successfully for first trimester diagnosis of genetic disorders for over 14 years. When performed between 10 and 14 weeks' gestation, it is both safe and effective in the diagnosis of fetal chromosomal, biochemical, and molecular disorders, with risks comparable to those of second trimester amniocentesis. Cytogenetic results have been confirmed to be reliable and accurate. Although confined placental mosaicism occurs in approximately 1% of cases requiring interpretation, and occasionally additional invasive testing, its finding adds additional information about perinatal outcome and can alert the practitioner to fetal genetic disorders. Earlier concerns about procedure-induced limb defects have been reduced with the accumulation of additional data, showing minimal to no risk when chorionic villus sampling is performed after 70 days of gestation. In experienced hands, it may be the procedure of choice for sampling multiple gestations. Secondary to the advantage of safe, early diagnosis, chorionic villus sampling appears to be the optimal choice for first trimester testing.


Experiences of Venous Leg Ulcer persons following an individualised nurse-led education: protocol for a qualitative study using a constructivist grounded theory approach.
Venous leg ulcers are slow-healing wounds with a high risk of recurrences. To prevent recurrences and promote healing, different nurse-led educational interventions have been developed. The impact of these interventions on self-management is ambiguous. Also, how persons with a venous leg ulcer experiences these educational sessions are poorly described. This study protocol presents the methodology to provide a comprehensive explanation of participants' journeys-of how they experience their individualised education sessions concerning self-management. A constructivist grounded theory approach according to Charmaz involving 30 participants will be used. Data will be collected through semistructured face-to-face interviews. Interviews will be transcribed verbatim and analysed with initial and focus coding using MAXQDA. Data collection and data analysis will occur iteratively, focusing on constant comparison to obtain well-developed categories. Categories will be reinforced using existent literature. This pre-results study is embedded in a clinical trial (NCT04019340) and approved by ethical committee of the canton of Geneva (CCER: 2019-01964). A theory will emerge from participants' journeys informing future education sessions for patients with venous leg ulcers. The findings will be disseminated through peer-reviewed publications and communications.


Is a guanine nucleotide-binding protein involved in excitation-contraction coupling in skeletal muscle?
Plasma membrane depolarization causes skeletal muscle contraction by triggering Ca2+ release from an intracellular membrane network, the sarcoplasmic reticulum. A specialized portion of the sarcoplasmic reticulum, the terminal cisternae, is junctionally associated with sarcolemmal invaginations called the transverse tubules, but the mechanism by which the action potential at the level of the transverse tubules is coupled to Ca2+ release from the terminal cisternae is still mysterious. Here we show that: (i) GTP gamma S, a non-hydrolyzable analog of GTP, elicits isometric force development in skinned muscle fibre; (ii) GTP gamma S is unable to release CA2+ from isolated sarcoplasmic reticulum fractions; (iii) the threshold for tension development is shifted to higher GTP gamma S concentrations by pre-incubation with pertussis toxin. These results suggest that a GTP-binding protein is involved in coupling the action potential of transverse tubules to Ca2+ release from the terminal cisternae.


Diagnostic accuracy of serum 1,3-β-D-glucan for pneumocystis jiroveci pneumonia, invasive candidiasis, and invasive aspergillosis: systematic review and meta-analysis.
Serum 1,3-β-d-glucan (BG) assay may be helpful as a marker for the diagnosis of Pneumocystis jiroveci pneumonia (PJP) and invasive fungal infection (IFI). We conducted a systematic review to assess the diagnostic accuracy of this assay. We searched MEDLINE, Web of Science, Cochrane Collaboration databases, Ichushi-Web, reference lists of retrieved studies, and review articles. Our search included studies of serum BG assay that used (i) positive cytological or direct microscopic examination of sputum or bronchoalveolar lavage fluid for PJP and (ii) European Organization for Research and Treatment of Cancer or similar criteria for IFI as a reference standard and provided data to calculate sensitivity and specificity. Only major fungal infections such as invasive candidiasis and invasive aspergillosis were included in the IFI group. Twelve studies for PJP and 31 studies for IFI were included from January 1966 to November 2010. The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (AUC-SROC) for PJP were 96% (95% confidence interval [95% CI], 92% to 98%), 84% (95% CI, 83% to 86%), 102.3 (95% CI, 59.2 to 176.6) and 0.96 (95% CI, 0.94 to 0.99), respectively. No heterogeneity was found. For IFI, the values were 80% (95% CI, 77% to 82%), 82% (95% CI, 81% to 83%), 25.7 (95% CI, 15.0 to 44.1), and 0.88 (95% CI, 0.82 to 0.93). Heterogeneity was significant. The diagnostic accuracy of the BG assay is high for PJP and moderate for IFI. Because the sensitivity for PJP is particularly high, the BG assay can be used as a screening tool for PJP.


Cortical Bone Repositioning Technique for Horizontal Alveolar Bone Augmentation: A Case Series.
The objective of this study was to present a novel procedure for cortical bone repositioning (CBR) that maintains a secure space under the periosteum by replacement of the lateral cortex via fixation, employing titanium screws. Seven systemically healthy patients presenting with horizontal alveolar bone defects in radiographs and CT images were enrolled for CBR technique for horizontal alveolar bone augmentation. A lateral cortical bone block was cut in the defects and freed from the original bony surface. A screw was inserted into the block, and the block was placed laterally to allow fixation. The block was checked for adequate stability, and the flap was closed after creation of periosteal releasing incisions to ensure tension-free closure. There were no complications, and 16 implants were placed uneventfully. Preoperative bone width in the defect area was 3.28 mm; the postoperative 4-month bone width in the same area was 6.46 mm. The mean implant stability quotient (ISQ) at placement was 68. At the secondary operation for changing to a healing abutment, the mean ISQ was 72. All patients were functionally and esthetically rehabilitated with implant-supported dentures. CBR technique is a simple procedure without the use of any biomaterials or devices. The main advantage of this technique in comparison to autogenous grafts is the lack of donor site issues. This technique has the possibility of inducing the patient's regenerative ability for bone healing.


KRAS and BRAF mutation analysis in routine molecular diagnostics: comparison of three testing methods on formalin-fixed, paraffin-embedded tumor-derived DNA.
Accurate mutation detection assays are strongly needed for use in routine molecular pathology analyses to aid in the selection of patients with cancer for targeted therapy. The high-resolution melting (HRM) assay is an ideal prescreening tool, and SNaPshot analysis offers a straightforward genotyping system. Our present study was determined to compare these mutation testing methods on formalin-fixed, paraffin-embedded (FFPE) tumor-derived DNA. We compared the performance of HRM, followed by cycle sequencing (HRM-sequencing); multiplex PCR assay, followed by SNaPshot analysis (multiplex mutation assay); and a successor assay using HRM, followed by SNaPshot (HRM-SNaPshot) for mutation analysis of both KRAS (codon 12/13/61) and BRAF (codon 600/601). In a series of 195 FFPE-derived DNA specimens, a high genotypic concordance between HRM-sequencing and multiplex mutation assay was found (κ, 0.98; 95% CI, 0.94 to 1), underlining the potential of a combined HRM-SNaPshot approach. In reconstruction experiments, the analytical sensitivity of HRM-SNaPshot was twofold to fourfold higher than HRM-sequencing and multiplex mutation assay, respectively. In addition, HRM-SNaPshot had a good performance rate (99%) on FFPE tumor-derived DNA, and mutation detection was highly concordant with the predecessor assays (κ for both, 0.98). The occurrence of BRAF and KRAS mutations is mutually exclusive. HRM-SNaPshot is an attractive method for mutation analysis in pathology, given its good performance rate on FFPE-derived DNA, high analytical sensitivity, and prescreening approach.


Cancer immunology - development of novel anti-cancer therapies.
The vast majority of tumours are characterised by high frequencies of genetic and epigenetic alterations resulting in tumour-specific antigens, which may, in principle, be recognised by cytotoxic T cells. Though early clinical immunotherapy trials have yielded mixed results with ambiguous clinical benefit, cancer immunotherapy is now attracting increasing attention as a viable therapeutic option, mainly in melanoma and lung cancer, but increasingly also in other malignancies. In particular, recent therapeutic efforts targeting inhibitory receptors on T cells to overcome tumour-induced immune dysfunction have the potential to reshape current treatment standards in oncology. The clinical development has been pioneered by the antibody ipilimumab, which blocks cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and has demonstrated survival benefit in two randomised landmark trials in melanoma. Capitalising on this success, the research on the clinical implication of T cell checkpoint inhibition has been boosted. Early clinical trials have demonstrated meaningful response rates, sustained clinical benefits with encouraging survival rates and good tolerability of next-generation checkpoint inhibitors, including programmed death-1 (PD-1) and programmed death ligand 1 (PD-L1) inhibitors, across multiple cancer types. Attractive perspectives include the concurrent blockade of immunological (non-redundant) checkpoints, which has recently been demonstrated using combinations of immune checkpoint modulators themselves or with other therapies, such as chemotherapy, targeted therapy or radiotherapy. This article summarises the mechanism of action and subsequent clinical studies of immune checkpoint antibodies in oncology with a particular focus on melanoma and lung cancer.


Vascular staging of renal and adrenal malignancies with a noncontrast enhanced steady state free precession technique.
To compare a noncontrast enhanced balanced steady state free precession (bSSFP) MRI technique with a conventional dynamic contrast-enhanced (DCE) three-dimensional (3D) spoiled gradient recalled echo (SPGR) imaging in the vascular staging of renal and adrenal malignancies. Sixty-three MRIs with both bSSFP and DCE acquisitions performed for initial staging of renal and adrenal malignancies were retrospectively evaluated for presence and extent of thrombus in the renal veins and inferior vena cava (IVC). Thrombus characterization was also evaluated. DCE imaging was used as the standard-of-reference. Histopathology was available in 46 of 63 cases as an additional external standard. There is very good agreement between bSSFP and DCE imaging for determining the presence or absence of thrombus in the renal veins (r = 0.95; P < 0.0001) and IVC (r = 0.91; P < 0.0001). BSSFP is less successful at distinguishing bland from tumor thrombus. Noncontrast enhanced bSSFP is an acceptable alternative to DCE imaging for vascular staging of locally advanced renal/adrenal malignancies, with somewhat limited ability to distinguish bland from tumor thrombus.


Zoning: focused support: a trust wide implementation project.
Applying pragmatic risk management procedures to facilitate the sharing of clinical knowledge in and across mental health teams. Abstract Zoning: focused support is pragmatic risk management support procedure that enhances adherence to operational policies, provides a forum in which staff can receive support and visually facilitates the sharing of clinical knowledge. This paper presents a 3-year multi-method management project that sought to introduce zoning principles into all teams of an inner city Mental Health NHS Trust. By changing the language and culture of the organization findings indicate that there has been a positive attitudinal shift in how the approach is perceived. It is considered to be of value to staff, service users and their families and 73% of teams are now using it routinely.


Serotonin increases calcium current in human atrial myocytes via the newly described 5-hydroxytryptamine4 receptors.
In various species, including humans, 5-hydroxytryptamine (5-HT) has been shown to exert positive chronotropic and inotropic cardiac effects through different types of receptors. The goal of the present study was to investigate the regulation by 5-HT of voltage-gated Ca2+ channels in human atrial myocytes and to characterize the receptor involved. Cardiomyocytes isolated enzymatically and mechanically were voltage-clamped using the whole-cell configuration of the patch-clamp technique. Extracellular perfusion of 5-HT increased Ca2+ current (ICa) amplitude with a EC50 (0.1 microM) similar to that observed with isoprenaline. The effects of 5-HT were blocked by the addition of protein kinase A inhibitor in the pipette. In addition, the effects of 5-HT, isoprenaline, and intracellular cAMP on ICa were not additive. These results support the hypothesis that the inotropic effect of 5-HT in human atrial myocytes is related to an increase of ICa via an elevation of intracellular cAMP levels and stimulation of cAMP-dependent protein kinase. The effects of 5-HT were not blocked by antagonists of 5-HT1 (methiothepin), 5-HT2 (ketanserin), or 5-HT3 (ICS 205-930 at a low concentration) receptors. The benzamide derivatives renzapride and zacopride and the azabicyclobenzimidazolone derivative BIMU 8 increased ICa, but less efficiently than did 5-HT or 5-methoxytryptamine. Moreover, ICS 205-930 at high concentrations (greater than 1 microM) completely antagonized the effects of 5-HT. Thus, the pharmacology of the 5-HT receptor involved in an increase of ICa in human atrial myocytes resembles that recently described for the 5-HT4 receptor. In atrial myocytes dissociated from rat, rabbit, guinea pig, or frog, 5-HT at high concentrations had no effect on Ca2+ currents, suggesting that the distribution of 5-HT4 receptors in cardiac tissues is species dependent.


How to treat the persistent perineal sinus after rectal excision.
As surgery for more advanced and complex pelvic malignancies continues to expand to include larger and more exenterative techniques, dealing with the resulting pelvic and perineal defect has become an increasingly frequent necessity. The goal is both to close the defect and to accomplish complete healing. Methodology for managing the perineal wound, which results after proctocolectomy for cancer and more recently, after exenterative resection of the rectum, sacrum, uterus, vagina, bladder and larger areas of soft tissue (i.e. perineum), varies between simple closure on one hand and creation of complex gluteal and rectus abdominus flaps on the other. We examined these methodologies in terms of indications, technical details, complications and outcomes. Finally, the newest techniques for eliminating persistent perineal sinus tracts are detailed.


Cerebral CT findings in methylmalonic acid propionic acidemias.
The cerebral computed tomographic findings in two infants with methylmalonic acidemia and one infant and one adult with propionic acidemia are presented. Pertinent metabolic, clinical, and pathologic features of these genetic disorders of vitamin B12 (cobalamin) and biotin metabolism are reviewed briefly. Computed tomographic abnormalities consist of focal or diffuse deep cerebral hemisphere lucencies and diffuse loss of brain substance. These findings correlated well with the clinical and pathologic findings. The leukoencephalopathy in these uncommon autosomal recessive conditions appears to be due to ketoacidosis, which in some cases may be managed by vitamin supplementation.


Effects of Orange Pulp Conservation Methods (Dehydrated or Ensiled Sun-Dried) on the Nutritional Value for Finishing Pigs and Implications on Potential Gaseous Emissions from Slurry.
The inclusion of orange pulp (OP) in pig diets may promote the circular economy, but drying procedures might influence its nutritional value and environmental impact. The purpose of this study was to determine the energy value and nutrient digestibility of dehydrated (DOP) and ensiled sun dried (ESDOP) orange pulp. The potential ammonia (NH3) and methane (CH4) emissions derived from slurry were also measured. Digestible energies of 14.2 and 13.2 MJ/kg DM for DOP and ESDOP, respectively, were estimated by difference after a 500 g/kg substitution of a basal diet with OPs. A high fiber digestion efficiency was observed for both OPs. Pigs fed the basal diet showed a higher intake and a greater excretion of urine N than pigs fed with OP, but fecal N excretion did not differ among diets. A higher benzoic and hippuric acid content in urine was observed in OP than in basal diet. Altogether, these findings explained a lower pH in slurry of OP diets and a reduction of potential NH3 emissions. The biochemical CH4 potential also decreased, especially with ESDOP. Overall, both OP are relevant sources of energy for pig diets. Their inclusion in feeds generate favorable changes of slurry characteristics that reduce potential NH3 and CH4 emissions.


Detection of White Sturgeon Iridovirus (WSIV) in Wild Sturgeons (Actinopterygii: Acipenseriformes: Acipenseridae) in Poland.
White sturgeon iridovirus (WSIV) disease is caused by a virus of the eponymous family and is mostly triggered by stressful environmental conditions, i.e. high rearing density, excessive handling, or temporary loss of water. The aim of this study was to develop the most effective diagnostic method for quick and efficient confirmation or exclusion of the presence of WSIV. A total of 42 samples (spleen, gills, intestine, skin, kidney, and brain) were collected from eight sturgeon (Acipenser gueldenstaedtii and A. oxyrinchus) aged ≤5+ farmed or caught between 2010 and 2014 in open waters (Dąbie Lake and Szczecin Lagoon). They were tested for WSIV presence using conventional PCR, qPCR, and in situ hybridisation (ISH). In gross examination, all fish appeared to be healthy. Neither species showed clinical signs typical of WSIV infection. In the majority of cases, fragments of iridoviral DNA were found using molecular methods in the kidneys, and also in the liver, gills, and skin. The detection rate using ISH was 47.37% and most commonly the brain and kidney tissues were positive. The most efficient of the methods used was real-time PCR, with 100% effectiveness in detection of WSIV DNA. The study demonstrates the capabilities for WSIV diagnosis available to sturgeon farmers and water administrators, indicating useful methods of adequate sensitivity as well as organs to sample in order to achieve the highest probability of viral detection.


The minimum important difference for the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form in women with stress urinary incontinence.
Minimum important difference (MID) estimates the minimum degree of change in an instrument's score that correlates with a patient's subjective sense of improvement. We aimed to determine the MID for the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI SF) using both anchor based and distribution based methods derived using data from the Trial of Midurethral Slings (TOMUS). Instruments for the anchor-based analyses included the urogenital distress inventory (UDI), incontinence impact questionnaire (IIQ), patient global impression of improvement (PGI-I), incontinence episodes (IE) on 7-day bladder diary, and satisfaction with surgical results. After confirming moderate correlation (r ≥ 0.3) of ICIQ-UI SF and each anchor, MIDs were determined by calculating the difference between the mean instrument scores for individuals with the smallest amount of improvement and with no change. The distribution-based method of MID assessment was applied using effect sizes of 0.2 and 0.5 SD (small to medium effects). Triangulation was used to examine these multiple MID values in order to converge on a small range of values. Anchor-based MIDs range from -4.5 to -5.7 at 12 months and from -3.1 to 4.3 at 24 months. Distribution-based MID values were lower. Triangulation analysis supports a MID of -5 at 12 months and -4 at 24 months. The recommended MIDs for ICIQ-UI SF are -5 at 12 months and -4 at 24 months. In surgical patients, ICIQ-UI SF score changes that meet these thresholds can be considered clinically meaningful.


In vivo regulation of beta-adrenergic receptors on human mononuclear leukocytes: assessment of receptor number, location, and function after posture change, exercise, and isoproterenol infusion.
We studied the regulation of beta-adrenergic receptors in human mononuclear leukocytes (MNL). Total receptor number was determined as specific binding at 4 C of [3H] dihydroalprenolol or [125I]iodopindolol, and redistributed receptors were defined as those binding sites to which the hydrophilic antagonist CGP-12177 did not have access. Receptor function was assessed as cAMP accumulation stimulated by isoproterenol. In in vitro experiments, high concentrations of isoproterenol desensitized receptor function and promoted redistribution of about 80% of the receptors away from the cell surface. However, three in vivo protocols (upright posture for 3 h, moderate exercise, and infusion of isoproterenol for 30 min) redistributed few beta-adrenergic receptors on MNL. The 30-min isoproterenol infusion did not alter later cAMP accumulation, but posture change and exercise increased isoproterenol-stimulated cAMP accumulation in intact MNL. Infusion of isoproterenol for 120 min redistributed 9 +/- 2% (+/- SEM) of the receptors and decreased isoproterenol-stimulated cAMP accumulation by 19 +/- 6%. Isoproterenol-stimulated adenylate cyclase activity in membranes isolated from MNL previously was found to be decreased with upright posture, and we confirmed these findings in assays that did not include exogenous GTP, but instead relied upon guanine nucleotides retained in the membrane preparation. However, when excess GTP was included, isoproterenol-stimulated adenylate cyclase activity in MNL membranes was not altered by posture change. We conclude that substantial receptor redistribution of beta-receptors on MNL does not readily occur in physiological situations.


Ultrastructural localization of cytomegalovirus DNA synthesis in infected guinea-pig cells.
Using electron microscopic autoradiographic techniques, the uptake of [methyl-3H] thymidine into uninfected and guinea-pig cytomegalovirus (GPCMV)-infected guinea-pig embryo (GPE) fibroblast cells was investigated. In GPCMV-infected GPE cells, [methyl-3H]thymidine uptake into cellular DNA was inhibited prior to the onset of virus DNA synthesis as well as during the entire period of virus replication. Virus DNA synthesis increased slowly during the period of active virus replication, which usually lasted from 18 to 48 h post-infection. Only the electron-dense amorphous matrices and fibrillar structures in the nuclear inclusions were associated with the tritiated labels and thus contained virus DNA.


Efficacy of ESHAP Regimen in Transplant Ineligible Patients With Relapsed/Refractory T-Cell Lymphoma.
Salvage chemotherapy is the mainstay for the treatment of relapsed/refractory peripheral T-cell lymphomas (R/R PTCLs). ESHAP regimen, consisting of etoposide, methylprednisolone, high-dose Ara-C, and cisplatin is considered one of the well-accepted regimens for R/R lymphoma. Though, the evidence of long-term efficacy of ESHAP on R/R PTCLs is limited. This study aims to determine the efficacy and safety of ESHAP as a first salvage regimen, not followed by autologous stem cell transplantation (ASCT), in R/R PTCLs. Patients with PTCLs, who progressed after one prior therapy and received ESHAP as a salvage treatment without subsequent ASCT, were recruited from the prospective observational study in the patients with lymphoma. From January 2005 to April 2015, 33 patients with R/R PTCLs received ESHAP as first salvage regimen at Chiang Mai University Hospital. The overall response rate was 46% (complete remission (CR) 39%). The median duration of response was 18 months. Median second progression-free survival (PFS) and overall survival (OS) were 8.0 and 11.0 months, respectively. Patients having late relapse had more favorable OS than those having early relapsed or refractory disease with a median OS of 21, 17 and 3 months, respectively (P = 0.001). Patients achieving CR after ESHAP had significantly better median OS (39, 7 and 5 months, P < 0.0001) and second PFS (33, 2 and 2 months, P < 0.0001) than those achieving PR or having progressive disease. Grade 3-4 neutropenia (45.5%) and thrombocytopenia (33.4%) were common but manageable. ESHAP offers a long-term survival in some transplant ineligible patients with PTCLs who were chemosensitive with late relapse after front-line therapy. These results require further investigation in a prospective study.


[18F]fluorodeoxyglucose positron emission tomography in refractory complex partial seizures.
Positron emission tomography with simultaneous electroencephalographic monitoring was performed with [18F]fluorodeoxyglucose in 20 patients with complex partial seizures who had normal computed tomographic scans. Seven patients had only unilateral epileptiform discharges on the electroencephalogram, 3 had predominantly unilateral discharges, and 10 had nonlocalized epileptiform abnormalities. Positron emission tomography showed a hypometabolic lesion in 16 of the 20 patients. Pathological changes in the hypometabolic region were found in postoperative specimens in 4 of 5 patients studied. Positron emission tomography was unaffected by the seizure frequency, state of alertness, or number of spike discharges during the scan. There was a tendency for patients to have higher overall metabolic rates when taking less medication. Seizures occurring during [18F]fluorodeoxyglucose uptake in 3 patients produced a hypermetabolic area at the interictal hypometabolic focus. Positron emission tomography sometimes showed more widespread hypometabolism than suspected on the basis of the scalp-recorded electroencephalogram. The frontal lobe showed a greater degree of hypometabolism than the temporal lobe in 3 patients. Focal lesions may be identified by positron emission tomography even if the electroencephalographic abnormality is not well localized.


Slaughterhouses Fungal Burden Assessment: A Contribution for the Pursuit of a Better Assessment Strategy.
In slaughterhouses, the biological risk is present not only from the direct or indirect contact with animal matter, but also from the exposure to bioaerosols. Fungal contamination was already reported from the floors and walls of slaughterhouses. This study intends to assess fungal contamination by cultural and molecular methods in poultry, swine/bovine and large animal slaughterhouses. Air samples were collected through an impaction method, while surface samples were collected by the swabbing method and subjected to further macro- and micro-scopic observations. In addition, we collected air samples using the impinger method in order to perform real-time quantitative PCR (qPCR) amplification of genes from specific fungal species, namely A. flavus, A. fumigatus and A. ochraceus complexes. Poultry and swine/bovine slaughterhouses presented each two sampling sites that surpass the guideline of 150 CFU/m³. Scopulariopsis candida was the most frequently isolated (59.5%) in poultry slaughterhouse air; Cladosporium sp. (45.7%) in the swine/bovine slaughterhouse; and Penicillium sp. (80.8%) in the large animal slaughterhouse. Molecular tools successfully amplified DNA from the A. fumigatus complex in six sampling sites where the presence of this fungal species was not identified by conventional methods. This study besides suggesting the indicators that are representative of harmful fungal contamination, also indicates a strategy as a protocol to ensure a proper characterization of fungal occupational exposure.


Interplay between CD45RA+ regulatory T cells and TNF-alpha in the regulation of human Th17 differentiation.
The balance between effector CD4(+) T cells secreting IL-17 (T(h)17) and regulatory T cells (Treg) plays an important role in autoimmune disorders that include rheumatoid arthritis (RA) and Crohn's disease. Tumor necrosis factor (TNF)-alpha is a key pro-inflammatory cytokine that contributes to disease pathogenesis. We investigated the interplay between CD45RA(+) Treg and TNF-alpha in the regulation of human T(h)17 differentiation. We found that CD45RA(+) Treg promoted while TNF-alpha inhibited naive CD4(+) T-cell differentiation into IL-17 and CCL20 co-expressing T(h)17 cells without influencing their IL-22 release. Unexpectedly, CD45RA(+) Treg depletion abrogated TNF-alpha suppressive function. Finally, dendritic cell-derived TNF-alpha suppressed the development of IL-17(+)CCL20(+) expressing T(h)17 cells. In conclusion, CD45RA(+) Treg positively governs human T(h)17 development, which is impaired by TNF-alpha. We propose that TNF-alpha may represent a negative feedback mechanism to control IL-17/CCL20- but not IL-22-associated autoimmune pathologies.


Exploitation of complement regulatory proteins by Borrelia and Francisella.
Pathogens have developed sophisticated mechanisms of complement evasion such as binding to the host complement regulatory proteins (CRPs) on their surface or expression of CRP mimicking molecules. The ability of pathogens to evade the complement system has been correlated with pathogenesis and host selectivity. Hitherto, little work has been undertaken to determine whether Borrelia and Francisella exploit various CRPs to block complement attack. Seventeen Borrelia (twelve species) and six Francisella (three subspecies) strains were used to assess their ability to bind human, sheep and cattle CRPs or mimic membrane associated complement regulators. A series of experiments including affinity ligand binding experiments, pull-down assays and mass spectrometry based protein identification, revealed an array of CRP binding proteins of Borrelia and Francisella. Unlike Francisella, Borrelia strains were able to bind multiple human CRPs. Three strains of Borrelia (SKT-4, SKT-2 and HO14) showed the presence of a human CD46-homologous motif, indicating their ability to possess putative human CD46 mimicking molecules. Similarly, five strains of Borrelia and two strains of Francisella may have surface proteins with human CD59-homologous motifs. Among ovine and bovine CRPs, the only CRP bound by Francisella (LVS, Tul4 strain) was vitronectin, while ovine C4BP, ovine factor H and bovine factor H were bound to Borrelia strains SKT-2, DN127 and Co53. This study presents an array of proteins of Borrelia and Francisella that bind CRPs or may mimic membrane-CRPs, thus enabling multiphasic complement evasion strategies of these pathogens.


Serologic prevalence of caprine arthritis-encephalitis virus in California goat dairies.
Fifty-three percent of goats in 13 California goat dairies had antibodies to caprine arthritis-encephalitis virus (CAEV), as determined by agar-gel immunodiffusion. Those goat dairies that reared kids on pasteurized milk had a lower seroprevalence than those that did not. Age, rearing kids on unpasteurized milk, and the presence of large joints were associated with antibodies to CAEV. Breed was associated with seroreactivity, but the association was confounded by other factors. Sex was not associated with antibodies to CAEV. The relationship between age and antibodies to CAEV was observed for goats reared on pasteurized or unpasteurized milk, which indicated that continued horizontal (contact) transmission may be important on these dairies and limited the effect of a pasteurized rearing program on control of CAEV infection.


Behavior of piglets after castration with or without carbon dioxide anesthesia.
Surgical castration of male piglets without anesthesia is a routine management practice conducted on commercial pig farms. For animal welfare reasons, it would be beneficial to develop methods of practical pain relief. The objective of this study was to evaluate the effect of providing CO₂ anesthesia before castration on the behavior of piglets for up to 8 d after castration in comparison with piglets castrated without anesthesia. In 3 successive replicates, the behavior of 186 male piglets castrated with (n = 95) or without (n = 91) anesthesia was observed for up to 8 d after castration. All piglets in a given replicate were castrated on the same day, before 8 d of age. Behavioral observations were carried out in accordance with a continuous focal sampling procedure that began immediately after castration and continued for a period of 1 wk. Barrows anesthetized with CO₂ before castration displayed more interactive behaviors during the overall observation period than the other barrows (P = 0.0412), which may indicate better welfare. Assessing all observation periods separately, differences in activity at the udder, lying, walking, and interactive behaviors appeared to support the beneficial effect of providing CO₂ anesthesia before castration. However, these differences varied over time between treatment groups. The most important conclusion was that piglets castrated with or without CO₂ anesthesia displayed behaviors indicative of pain and discomfort for up to 6 d after castration. Therefore, additional analgesia may be necessary to eliminate the long-term pain caused by castration even in piglets anesthetized with CO₂ before castration.


Relationships Among Peripheral and Central Electrophysiological Measures of Spatial and Spectral Selectivity and Speech Perception in Cochlear Implant Users.
The ability to perceive speech is related to the listener's ability to differentiate among frequencies (i.e., spectral resolution). Cochlear implant (CI) users exhibit variable speech-perception and spectral-resolution abilities, which can be attributed in part to the extent of electrode interactions at the periphery (i.e., spatial selectivity). However, electrophysiological measures of peripheral spatial selectivity have not been found to correlate with speech perception. The purpose of this study was to evaluate auditory processing at the periphery and cortex using both simple and spectrally complex stimuli to better understand the stages of neural processing underlying speech perception. The hypotheses were that (1) by more completely characterizing peripheral excitation patterns than in previous studies, significant correlations with measures of spectral selectivity and speech perception would be observed, (2) adding information about processing at a level central to the auditory nerve would account for additional variability in speech perception, and (3) responses elicited with spectrally complex stimuli would be more strongly correlated with speech perception than responses elicited with spectrally simple stimuli. Eleven adult CI users participated. Three experimental processor programs (MAPs) were created to vary the likelihood of electrode interactions within each participant. For each MAP, a subset of 7 of 22 intracochlear electrodes was activated: adjacent (MAP 1), every other (MAP 2), or every third (MAP 3). Peripheral spatial selectivity was assessed using the electrically evoked compound action potential (ECAP) to obtain channel-interaction functions for all activated electrodes (13 functions total). Central processing was assessed by eliciting the auditory change complex with both spatial (electrode pairs) and spectral (rippled noise) stimulus changes. Speech-perception measures included vowel discrimination and the Bamford-Kowal-Bench Speech-in-Noise test. Spatial and spectral selectivity and speech perception were expected to be poorest with MAP 1 (closest electrode spacing) and best with MAP 3 (widest electrode spacing). Relationships among the electrophysiological and speech-perception measures were evaluated using mixed-model and simple linear regression analyses. All electrophysiological measures were significantly correlated with each other and with speech scores for the mixed-model analysis, which takes into account multiple measures per person (i.e., experimental MAPs). The ECAP measures were the best predictor. In the simple linear regression analysis on MAP 3 data, only the cortical measures were significantly correlated with speech scores; spectral auditory change complex amplitude was the strongest predictor. The results suggest that both peripheral and central electrophysiological measures of spatial and spectral selectivity provide valuable information about speech perception. Clinically, it is often desirable to optimize performance for individual CI users. These results suggest that ECAP measures may be most useful for within-subject applications when multiple measures are performed to make decisions about processor options. They also suggest that if the goal is to compare performance across individuals based on a single measure, then processing central to the auditory nerve (specifically, cortical measures of discriminability) should be considered.


Stem cell and progenitor fate in the mammalian intestine: Notch and lateral inhibition in homeostasis and disease.
The control of cell fate decisions is vital to build functional organs and maintain normal tissue homeostasis, and many pathways and processes cooperate to direct cells to an appropriate final identity. Because of its continuously renewing state and its carefully organised hierarchy, the mammalian intestine has become a powerful model to dissect these pathways in health and disease. One of the signalling pathways that is key to maintaining the balance between proliferation and differentiation in the intestinal epithelium is the Notch pathway, most famous for specifying distinct cell fates in adjacent cells via the evolutionarily conserved process of lateral inhibition. Here, we will review recent discoveries that advance our understanding of how cell fate in the mammalian intestine is decided by Notch and lateral inhibition, focusing on the molecular determinants that regulate protein turnover, transcriptional control and epigenetic regulation.


Treating acute hypertensive crisis with sodium nitroprusside.
In patients with dangerously elevated diastolic blood pressures, the titrated intravenous administration of sodium nitroprusside usually reduces blood pressure to near-normal levels in less than an hour. This rapid reduction of pressure is well tolerated by hypertensive patients and probably diminishes the morbidity from renal and cardiac failure and stroke. The side effects of sodium nitroprusside treatment are minimal.


Study of trainer/trainee workload with special reference to the care of the elderly.
A study of the workload of trainers and their trainees in general practice, was undertaken throughout East Anglia. Thirty trainer/trainee pairs returned data over a two-week period and follow-up information was obtained from five pairs, eight months later. A simple encounter form was used.Trainee workloads were found to be similar to those of earlier studies, though there was considerable variation between the workloads. Trainees had little experience with elderly patients, and there was a lack of teamwork between members of the practices in providing care for the elderly.


II. Ambulatory cardiac catheterization.
The experience of the Virginia Heart Institute should encourage Virginia's hospitals, planning agencies and physicians to consider ambulatory catheterization as a cost effective method for the early identification of ischemic heart disease.


Trade-offs between sexual advertisement and immune function in the pied flycatcher (Ficedula hypoleuca).
Good genes models of sexual selection assume that sexual advertisement is costly and thus the level of advertisement honestly reveals heritable viability. Recently it has been suggested that an important cost of sexual advertisement might be impairment of the functioning of the immune system. In this field experiment we investigated the possible trade-offs between immune function and sexual advertisement by manipulating both mating effort and activity of immune defence in male pied flycatchers. Mating effort was increased in a non-arbitrary manner by removing females from mated males during nest building. Widowed males sustained higher haematocrit levels than control males and showed higher expression of forehead patch height, suggesting that manipulation succeeded in increasing mating effort. Males that were experimentally forced to increase mating effort had reduced humoral immune responsiveness compared with control males. In addition, experimental activation of immune defence by vaccination with novel antigens reduced the expression of male ornament dimensions. To conclude, our results indicate that causality behind the trade-off between immune function and sexual advertisement may work in both directions: sexual activity suppresses immune function but immune challenge also reduces sexual advertisement.


Changes in the expression of CD106, osteogenic genes, and transcription factors involved in the osteogenic differentiation of human bone marrow mesenchymal stem cells.
Mesenchymal stem cells (MSCs) are well known to possess multipotential differentiation and are becoming a good tool for clinical research. However, specific markers for their purification and the mechanism of their osteogenic differentiation remain to be elucidated. In the present study, we compared the expression of CD106, and osteogenic differentiation-related proteins and genes in human bone marrow (BM)-derived MSCs, before and after differentiation by FACS, histochemical staining, immunohistochemical staining, RT-PCR, and real-time PCR. It was found that MSCs were positive for CD13, CD29, CD44, CD73, CD90, CD105, and CD166, but negative for CD14, CD31, CD34, CD62E, CD45, and GlyA. Notably, CD106 was detected before osteogenic induction, but its expression was downregulated 10 fold after 2 weeks of osteogenic differentiation as determined by flow cytometry. The results of RT-PCR and real-time PCR revealed that the expression of CD106 mRNA in MSCs significantly decreased by 7.1-, 4.2-, and 5.1-fold, respectively after osteogenic, chondrogenic, and adipogenic differentiation. In contrast, other MSC-positive markers described above did not change significantly even after differentiation. Compared to levels in control cells, after 2 weeks of osteogenic differentiation, mRNA levels of alkaline phosphatase, bone sialoprotein, osteocalcin, and transcript factors RUNX2 and Osterix showed more than 2-fold, 5-fold, 1.5-fold, 2-fold, and 5-fold increase, respectively. Thus, we speculate that CD106 might be a useful surface marker for BMMSCs. Moreover, alkaline phosphatase, type I collagen, osteonectin, osteopontin, and biglycin were expressed in the early stages of osteogenic differentiation before bone sialoprotein and osteocalcin. The present study should help to provide a novel marker for isolating purified MSCs and characterizing osteogenic differentiation.


Review article: high stakes and high risk: a focused qualitative review of hazards during cardiac surgery.
Cardiac surgery is a high-risk procedure performed by a multidisciplinary team using complex tools and technologies. Efforts to improve cardiac surgery safety have been ongoing for more than a decade, yet the literature provides little guidance regarding best practices for identifying errors and improving patient safety. This focused review of the literature was undertaken as part of the FOCUS initiative (Flawless Operative Cardiovascular Unified Systems), a multifaceted effort supported by the Society of Cardiovascular Anesthesiologists Foundation to identify hazards and develop evidence-based protocols to improve cardiac surgery safety. Hazards were defined as anything that posed a potential or real risk to the patient, including errors, near misses, and adverse events. Of the 1438 articles identified for title review, 390 underwent full abstract screening, and 69 underwent full article review, which in turn yielded 55 meeting the inclusion criteria for this review. Two key themes emerged. First, studies were predominantly reactive (responding to an event or report) instead of proactive (using prospective designs such as self-assessments and external reviewers, etc.) and very few tested interventions. Second, minor events were predictive of major problems: multiple, often minor, deviations from normal procedures caused a cascade effect, resulting in major distractions that ultimately led to major events. This review fills an important gap in the literature on cardiac surgery safety, that of systematically identifying and categorizing known hazards according to their primary systemic contributor (or contributors). We conclude with recommendations for improving patient outcomes by building a culture of safety, promoting transparency, standardizing training, increasing teamwork, and monitoring performance. Finally, there is an urgent need for studies that evaluate interventions to mitigate the inherent risks of cardiac surgery.


The effect of maternal stress on birth outcomes: exploiting a natural experiment.
A growing body of research highlights that in utero conditions are consequential for individual outcomes throughout the life cycle, but research assessing causal processes is scarce. This article examines the effect of one such condition-prenatal maternal stress-on birth weight, an early outcome shown to affect cognitive, educational, and socioeconomic attainment later in life. Exploiting a major earthquake as a source of acute stress and using a difference-in-difference methodology, I find that maternal exposure to stress results in a significant decline in birth weight and an increase in the proportion of low birth weight. This effect is focused on the first trimester of gestation, and it is mediated by reduced gestational age rather than by factors affecting the intrauterine growth of term infants. The findings highlight the relevance of understanding the early emergence of unequal outcomes and of investing in maternal well-being since the onset of pregnancy.


Appearance of the hymen in prepubertal girls.
The recent increase in requests for genital examinations in girls who may have been sexually abused has necessitated detailed information not previously available on normal anatomy of the prepubertal girl. This study was undertaken to document the genital anatomy of 211 girls between the ages of 1 month and 7 years who presented for well child care or nongynecologic complaints and who had no history of sexual abuse. Each child's genitalia was examined and photographed, with findings reported reflecting those observed photographically. The study population consisted of 36% blacks, 33.6% white non-Hispanics, 29.9% Hispanics, and 0.5% Asians. Subjects had a mean age of 21 +/- 20.6 (SD) months. Extensive labial agglutination sufficient to obscure the hymen was noted in 5% (10/211) and partial agglutination in an additional 17% (35/211). A significant difference was noted in hymenal configuration by age, with a fimbriated hymen the most common type (46%) in infants aged 12 months or younger and a crescentic hymen the most common (51%) in girls older than 24 months (P less than or equal to .001). No significant difference was noted in hymen configuration by race. Hymenal bumps (mounds) were observed in 7%, hymenal tags in 3%, vestibular bands in 98%, longitudinal intravaginal ridges in 25%, and external ridges in 15% of subjects in whom the anatomy under study could be visualized. Hymenal notches (clefts) occurred superiorly and laterally on the hymenal rim but none were found inferiorly on the lower half of the hymen. A narrow rounded hymenal ring with a transection was observed in only 1 (0.5%) of 201 subjects and was not considered a normal finding.(ABSTRACT TRUNCATED AT 250 WORDS)


[Morphological anomalies in "tailed" lymphocyte nuclei and their connection with dicentric chromosomes in irradiated patients].
Lymphocyte nuclei with a narrow outgrowth into the cytoplasm ("tail") were detected on peripheral blood smears of patients exposed to ionizing radiation during the clean up after the Chernobyl meltdown (liquidators). On average, lymphocytes with tailed nuclei occurred at a frequency of 0.43% and 0.15% in exposed patients (n = 101) and healthy donors (n = 50), respectively; the difference between the samples was significant, P < 0.001. The coefficient of correlation between frequencies of lymphocytes with tailed nuclei and those with dicentric chromosomes was 0.74 (n = 27, P < 0.001). The frequency of lymphocytes with dicentric chromosomes was increased in 9 out of 10 patients, in which lymphocytes with tailed nuclei occurred at a frequency larger than 0.8%. A double-color FISH was used to localize centromeric (not more than two signals) and telomeric (not more than one signal) regions in nuclear tails. Abnormal tailed lymphocyte nuclei were assumed to result from breaking the chromosome bridges formed by the dicentric chromosomes.


High Systemic Type I Interferon Activity Is Associated With Active Class III/IV Lupus Nephritis.
Previous studies suggest a link between high serum type I interferon (IFN) and lupus nephritis (LN). We determined whether serum IFN activity is associated with subtypes of LN and studied renal tissues and cells to understand the effect of IFN in LN. Two hundred and twenty-one patients with systemic lupus erythematosus were studied. Serum IFN activity was measured by WISH bioassay. mRNA in situ hybridization was used in renal tissue to measure expression of the representative IFN-induced gene, IFN-induced protein with tetratricopeptide repeats-1 (IFIT1), and the plasmacytoid dendritic cell (pDC) marker gene C-type lectin domain family-4 member C (CLEC4C). Podocyte cell line gene expression was measured by real-time PCR. Class III/IV LN prevalence was significantly increased in patients with high serum IFN compared with those with low IFN (odds ratio 5.40, P = 0.009). In multivariate regression models, type I IFN was a stronger predictor of class III/IV LN than complement C3 or anti-dsDNA antibody, and could account for the association of these variables with LN. IFIT1 expression was increased in all classes of LN, but most in the glomerular areas of active class III/IV LN kidneys. IFIT1 expression was not closely colocalized with pDCs. IFN directly activated podocyte cell lines to induce chemokines and proapoptotic molecules. Systemic high IFN is involved in the pathogenesis of severe LN. We did not find colocalization of pDCs with IFN signature in renal tissue, and instead observed the greatest intensity of the IFN signature in glomerular areas, which could suggest a blood source of IFN.


[Ants in a hospital environment and its importance as vector of bacteria].
The external ant community of Hospital Municipal de Morrinhos, in Morrinhos, Goiás State, was characterized by the low rates of richness, diversity, dominance and equity of species abundance. Pheidole sp.1, a polygynic species was numerically dominant in this environment, although it coexists with potentially competitive species. This ant species prevailed within all hospital departments and its space-time distribution was a little aggregated (variance/mean ratio = 1.102, chi2 = 29.38, P < 0.01). Escherichia, Salmonella, Aeromonas, Enterococcus, Staphylococcus and Klebsiella were the bacteria associated to this ant species in nearly all hospital annexes. The unicolonialism of Pheidole sp.1 tends to increase the contamination and dissemination process of infecto-contagious agents. The control and management of this ant species must be followed by practices that reduce the colonization process by other queens and the quantity of site nidification within the hospital.


Adeno-associated virus vector for high-frequency integration, expression, and rescue of genes in mammalian cells.
We describe the construction of an adeno-associated virus (AAV) vector in which the coding sequence of the procaryotic gene neo is expressed under the control of the major AAV promoter p40. This AAV-neo vector allowed stable expression of neo as a dominant selective marker in mammalian cells by selection of cells which were resistant to the antibiotic geneticin (G418). When the vector was introduced into human (293 or HeLa) cell lines by a DNA transfection procedure, stable geneticin-resistant colonies were obtained. When the vector was first packaged into AAV particles and then introduced into cells via particle infection, geneticin-resistant cells were obtained at higher frequencies than those obtained by DNA transfection. In geneticin-resistant cells the AAV-neo vector was integrated at low copy number and could be rescued by subsequent infection with wild-type AAV and the helper adenovirus or, in some cases, by infection with adenovirus alone. The rescued AAV-neo vector could then be recovered as amplified unintegrated DNA from a Hirt lysate. These results demonstrate that AAV can be used as a transducing viral vector for stable integration and expression of a foreign gene in mammalian cells. The high frequency of integration and the ability to rescue the integrated vector suggest that this vector system may be useful for selecting genes from cDNA libraries. This vector may also be useful for introduction of genes into cells which are refractory to transfection in procedures such as those involving the use of CaPO4 or DEAE-dextran.


Synthesis and in vitro and in vivo evaluations of poly(ethylene glycol)-block-poly(4-vinylbenzylphosphonate) magnetic nanoparticles containing doxorubicin as a potential targeted drug delivery system.
The main challenge in antitumor chemotherapy is to enhance the curative effect and minimize the adverse effects of an anticancer drug. Administration of functionalized magnetic iron oxide nanoparticles is one of the strategies to improve sensitivity to cancer chemotherapy, and these nanoparticles are attractive materials that have been widely used in medicine for various applications, including diagnostic imaging and therapeutic applications. In this study, we describe the synthesis and characterization of drug-loaded iron oxide nanoparticles. Our aim was to obtain a biocompatible and injectable nanocarrier with anticancer activity. Iron oxide nanoparticles (IONs) were synthesized by alkali co-precipitation of iron salts followed by coating with our original surface modification agent, poly(ethylene glycol)-block-poly(4-vinylbenzylphosphonate) copolymer (PEG-PIONs). An anticancer drug doxorubicin (DOX), which clinical use is associated with cardiotoxicity, was loaded onto PEG-PIONs (PEG-PIONs/DOX), and to the best of our knowledge, this formulation showed higher drug encapsulation efficiency (drug loading capacity of the nanocarrier was 11.7%) than other formulations previously reported. PEG-PIONs/DOX had a hydrodynamic diameter of about 35nm and were stable in biological conditions over a period more than one month and showed stable and continuous in vitro drug release and antiproliferative effects on cancer cells. Fluorescent imaging indicated internalization of the PEG-PIONs/DOX in the cytoplasm of cancer cells. Biodistribution studies showed that PEG-PIONs/DOX preferentially accumulate in the tumor region via enhanced permeability and retention effect. In addition, analysis of the serum levels of enzymes indicated that PEG-PIONs/DOX reduced the cardiotoxicity associated with free DOX. These results indicate that PEG-PIONs/DOX have the potential for targeted delivery of antitumor drugs via systemic administration.


Tractography segmentation using a hierarchical Dirichlet processes mixture model.
In this paper, we propose a new nonparametric Bayesian framework to cluster white matter fiber tracts into bundles using a hierarchical Dirichlet processes mixture (HDPM) model. The number of clusters is automatically learned driven by data with a Dirichlet process (DP) prior instead of being manually specified. After the models of bundles have been learned from training data without supervision, they can be used as priors to cluster/classify fibers of new subjects for comparison across subjects. When clustering fibers of new subjects, new clusters can be created for structures not observed in the training data. Our approach does not require computing pairwise distances between fibers and can cluster a huge set of fibers across multiple subjects. We present results on several data sets, the largest of which has more than 120,000 fibers.


It's time to flower: the genetic control of flowering time.
In plants, successful sexual reproduction and the ensuing development of seeds and fruits depend on flowering at the right time. This involves coordinating flowering with the appropriate season and with the developmental history of the plant. Genetic and molecular analysis in the small cruciform weed, Arabidopsis, has revealed distinct but linked pathways that are responsible for detecting the major seasonal cues of day length and cold temperature, as well as other local environmental and internal signals. The balance of signals from these pathways is integrated by a common set of genes to determine when flowering occurs. Excitingly, it has been discovered that many of these same genes regulate flowering in other plants, such as rice. This review focuses on recent advances in how three of the signalling pathways (the day-length, vernalisation and autonomous pathways) function to control flowering.


Cyst-theca relationship of the arctic dinoflagellate cyst Islandinium minutum (Dinophyceae) and phylogenetic position based on SSU rDNA and LSU rDNA.
Round brown spiny cysts constitute a morphological group common in high latitude dinoflagellate cyst assemblages. The dinoflagellate cyst Islandinium minutum (Harland et Reid) Head, Harland et Matthiessen is the main paleoecological indicator of seasonal sea-ice cover in the Arctic. Despite the importance of this cyst in paleoceanographical studies, its biological affinity has so far been unknown. The biological affinity of the species I. minutum and its phylogenetic position based on the small subunit ribosomal RNA gene (SSU rDNA) and the large subunit ribosomal RNA gene (LSU rDNA) were established from cyst incubation experiments in controlled conditions, optical and scanning electron microscopy, and single-cell PCR. The thecal motile cell obtained was undescribed. Although the motile cell was similar to Archaeperidinium minutum (Kofoid) Jörgensen, the motile cell of I. minutum lacked a transitional plate in the cingular series, which is present in Archaeperidinium spp. Islandinium minutum and Archaeperidinium spp. were paraphyletic in all phylogenetic analyses. Furthermore, Protoperidinium tricingulatum, which also lacks a transitional plate, was closely related to I. minutum and transfered to the genus Islandinium. Based on available data, it is clear that Islandinium is distinct from Archaeperidinium. Therefore, we considered Islandinium Head, Harland et Matthiessen as a non-fossil genus and emend its description, as well as the species I. minutum. This is the first description of a cyst-theca relationship and the first study that reports molecular data based on SSU rDNA and LSU rDNA on a species assigned to the genus Islandinium.


Molecular evolution of the switch for progesterone and spironolactone from mineralocorticoid receptor agonist to antagonist.
The mineralocorticoid receptor (MR) is highly conserved across vertebrate evolution. In terrestrial vertebrates, the MR mediates sodium homeostasis by aldosterone and also acts as a receptor for cortisol. Although the MR is present in fish, they lack aldosterone. The MR binds progesterone and spironolactone as antagonists in human MR but as agonists in zebrafish MR. We have defined the molecular basis of these divergent responses using MR chimeras between the zebrafish and human MR coupled with reciprocal site-directed mutagenesis and molecular dynamic (MD) simulation based on the crystal structures of the MR ligand-binding domain. Substitution of a leucine by threonine in helix 8 of the ligand-binding domain of the zebrafish MR confers the antagonist response. This leucine is conserved across fish species, whereas threonine (serine in rodents) is conserved in terrestrial vertebrate MR. MD identified an interaction of the leucine in helix 8 with a highly conserved leucine in helix 1 that stabilizes the agonist conformation including the interaction between helices 3 and 5, an interaction which has previously been characterized. This switch in the MR coincides with the evolution of terrestrial vertebrates and of aldosterone synthesis. It was perhaps mandatory if the appearance of aldosterone as a specific mediator of the homeostatic salt retention was to be tolerated. The conformational changes also provide insights into the structural basis of agonism versus antagonism in steroid receptors with potential implications for drug design in this important therapeutic target.


Intensive meditation for refractory pain and symptoms.
The objective of this study was to assess patient interest in intensive meditation training for chronic symptoms. This was a cross-sectional anonymous survey among six chronic disease clinics in Baltimore including Chronic Kidney Disease, Crohn's Disease, Headache, Renal Transplant Recipients, General Rheumatology, and lupus clinic. Subjects were 1119 consecutive patients registering for their appointments at these clinics. Outcome measures were 6-month pain, global symptomatology, four-item perceived stress scale, use of complementary and alternative medicine (CAM) therapies, and attitudes toward use of meditation for managing symptoms. We then gave a scripted description of an intensive, 10-day meditation training retreat. Patient interest in attending such a retreat was assessed. Seventy-seven percent (77%) of patients approached completed the survey. Fifty-three percent (53%) of patients reported moderate to severe pain over the past 6 months. Eighty percent (80%) reported use of some CAM therapy in the past. Thirty-five percent (35%) thought that learning meditation would improve their health, and 49% thought it would reduce stress. Overall, 39% reported interest in attending the intensive 10-day meditation retreat. Among those reporting moderate to severe pain or stress, the percentages were higher (48% and 59%). In a univariate analysis, higher education, nonworking/disabled status, female gender, higher stress, higher pain, higher symptomatology, and any CAM use were all associated with a greater odds of being moderately to very interested in an intensive 10-day meditation retreat. A multivariate model that included prior use of CAM therapies as predictors of interest in the program fit the data significantly better than a model not including CAM therapies (p = 0.0013). Over 50% of patients followed in chronic disease clinics complain of moderate to severe pain. Patients with persistent pain or stress are more likely to be interested in intensive meditation.


Spontaneous liver rupture associated with hydatidiform mole pregnancy.
Spontaneous liver rupture is a rare occurrence during pregnancy. A young woman presented early in her pregnancy with severe abdominal pain, tachycardia, and hypotension. She was taken emergently to the operating room with a presumed diagnosis of ruptured ectopic pregnancy. Exploration revealed that her hemoperitoneum resulted from large fractures within her liver. During her resuscitation and treatment, a transvaginal ultrasound scan revealed a hydatidiform molar pregnancy. On resolution of postoperative complications and complete recovery, the patient was discharged home. This case illustrates that, although very unusual, hydatidiform molar pregnancies should be considered as a precipitating factor for spontaneous liver rupture.


Adjuvant therapy of colon cancer--results of a prospectively randomized trial.
After curative surgical resection, 621 patients with modified Dukes' stage B2, C1, or C2 colon carcinoma were randomly assigned to one of four treatment programs. These included chemotherapy with fluorouracil and semustine, immunotherapy with methanol extraction residue of bacillus Calmette-Guérin (BCG), combination therapy with fluorouracil, semustine, and immunotherapy, or close follow-up without adjuvant treatment. Treatment continued for 70 weeks. After a median of 51/2 years of follow-up, no significant differences were noted in either recurrence or survival rates among the four treatment programs. Leukemia developed in seven patients, all of whom had received fluorouracil and semustine. The results of this study do not support the use of chemotherapy with fluorouracil and semustine, immunotherapy with methanol extraction residue of BCG, or their combination as an adjuvant treatment program for patients at high risk for recurrent colon carcinoma. The data do, however, demonstrate the necessity for an untreated control group in a trial of adjuvant therapy for colon cancer.


[Vitreo-retinal pediatric surgery: epidemiologic factors, etiology and prognosis].
The features of pediatric vitreoretinal surgery are different from those of the adult population. In order to identify those differences, our retrospective study, dealing with a consecutive series of 2230 patients who underwent vitreoretinal surgery, analyzes several parameters for the 43 young patients (under 19 years old) (2%). Two main results can be withdrawn from the study. First, trauma is a major cause of vitreoretinal surgery in children (30% of the cases), proportionally much more frequent than in adults. Second, patient's age is the only factor that significantly influences the surgical prognosis, with a success rate of 35% under the age of 10 years, and 73% above this age (p < 0.05). We conclude that pediatric vitreoretinal surgery has a more guarded prognosis compared to the one performed in the adult population.


Progress in the surgical treatment of cardiac arrhythmias. Initial experience of 90 patients.
Between 1981 and 1985, ninety patients were treated surgically for cardiac arrhythmias and have been followed for a mean interval of 21 months (range, one to 49 months). Follow-up is 100% complete. Fifty accessory pathways were divided in 35 patients (25 male and ten female; mean age, 35.2 years; range, 10 to 72 years), with no deaths. Five females, aged 10 to 35 years, were treated for focal atrial tachycardia, three for an atrial focus alone, and two with other arrhythmia procedures; four were cured and one was improved. Two patients (one man and one woman, both aged 33 years) had ablation of the atrioventricular node. Forty-one patients (32 male and nine female; average age, 56.9 years; range, 15 to 74 years) had ablation of ventricular tachycardia. Kent bundle division and focal atrial tachycardia ablation were also performed in two of these patients. More than 80% of patients had coronary disease. Mean preoperative ejection fraction was 33.9% with a range of 14% to 65%. Aneurysmectomy, endocardial resection, cryoablation, and coronary artery bypass were the procedures used. The perioperative mortality rate was 9.8% but there were no deaths in the last 23 patients. Ventricular tachycardia was abolished in all but three survivors in whom medical treatment is now effective. The automatic implantable defibrillator was implanted in 11 patients, with no surgical deaths. These results confirm the feasibility of relieving a variety of serious arrhythmias by surgical intervention.


High temperature promotes auxin-mediated hypocotyl elongation in Arabidopsis.
Physiological studies with excised stem segments have implicated the plant hormone indole-3-acetic acid (IAA or auxin) in the regulation of cell elongation. Supporting evidence from intact plants has been somewhat more difficult to obtain, however. Here, we report the identification and characterization of an auxin-mediated cell elongation growth response in Arabidopsis thaliana. When grown in the light at high temperature (29 degreesC), Arabidopsis seedlings exhibit dramatic hypocotyl elongation compared with seedlings grown at 20 degreesC. This temperature-dependent growth response is sharply reduced by mutations in the auxin response or transport pathways and in seedlings containing reduced levels of free IAA. In contrast, mutants deficient in gibberellin and abscisic acid biosynthesis or in ethylene response are unaffected. Furthermore, we detect a corresponding increase in the level of free IAA in seedlings grown at high temperature, suggesting that temperature regulates auxin synthesis or catabolism to mediate this growth response. Consistent with this possibility, high temperature also stimulates other auxin-mediated processes including auxin-inducible gene expression. Based on these results, we propose that growth at high temperature promotes an increase in auxin levels resulting in increased hypocotyl elongation. These results strongly support the contention that endogenous auxin promotes cell elongation in intact plants.


IRS1 G972R missense polymorphism is associated with failure to oral antidiabetes drugs in white patients with type 2 diabetes from Italy.
This study tried to replicate in a large sample of white patients with type 2 diabetes (T2D) from Italy a previously reported association of the IRS1 G972R polymorphism with failure to oral antidiabetes drugs (OAD). A total of 2,409 patients from four independent studies were investigated. Case subjects (n = 1,193) were patients in whom, because of uncontrolled diabetes (i.e., HbA1c >8%), insulin therapy had been added either on, or instead of, maximal or near-maximal doses of OAD, mostly metformin and sulfonylureas; control subjects (n = 1,216) were patients with HbA1c <8% in the absence of insulin therapy. The IRS1 G972R polymorphism was typed by TaqMan allele discrimination. In all samples, individuals carrying the IRS1 R972 risk variant tended to be more frequent among case than control subjects, though reaching statistical significance only in one case. As no IRS1 G972R-by-study sample interaction was observed, data from the four samples were analyzed together; a significant association was observed (allelic odds ratio [OR] 1.30, 95% CI 1.03-1.63). When our present data were meta-analyzed with those obtained in a previous study, an overall R972 allelic OR of 1.37 (1.12-1.69) was observed. This study confirms in a large and ethnically homogeneous sample that IRS1 G972R polymorphism is associated with failure to OAD among patients with T2D.


Deep-Subwavelength-Optimized Holey-Structured Metamaterial Lens for Nonlinear Air-Coupled Ultrasonic Imaging.
Ultrasound non-destructive testing (NDT) is a common technique used for defect detection in different materials, from aluminium to carbon-fiber-reinforced polymers (CFRPs). In most cases, a liquid coupling medium/immersion of the inspected component is required to maximize impedance matching, limiting the size of the structure and materials. Air-coupled inspection methods have recently been developed for noncontact inspections to reduce contact issues in standard ultrasonic inspections. However, transmission of ultrasound in air is very inefficient because of the enormous impedance mismatch between solids and air, thus requiring a signal amplification system of high-sensitivity transducers. Hence, the captured signal amplitude may not be high enough to reveal any wave distortion due to defects or damage. This work presents a design of a holey-structured metamaterial lens with a feature size of λ/14 aiming at improvement of acousto-ultrasonic imaging using air-coupled transducers. The required effect is obtained by matching geometrical parameters of the proposed holey-structured metamaterials and the Fabry-Perot resonance modes of the structure. Transmission tests have been conducted on different fabricated metamaterial-based structures, to assess the frequency component filtering of the proposed method in both acoustic (f = 5 kHz, 20 kHz) and ultrasonic range (f = 30 kHz, 40 kHz). Results showed an improved sensitivity of damage imaging, with an increase in amplitude of the design frequencies of the lens by 11 dB. Air-coupled inspections were conducted on a stress-corrosion cracked aluminum plate and impacted CFRP plate using the holey-structured lens. Results showed an improvement in the damage-imaging resolution due to a wave-amplitude increase across the defective features, thus demonstrating its potential as an efficient and sensitive inspection tool for damage-detection improvement in geometrically complex components of different materials.


Toxic effect of sampling swabs and transportation test tubes on the formation of intracytoplasmic inclusions of Chlamydia trachomatis in McCoy cell cultures.
The ability of Chlamydia trachomatis, immunotype E, to produce intracytoplasmic inclusions in cycloheximide-treated McCoy cells after being exposed to different types of sampling swabs in experimentally infected transport medium was studied. A larger number of inclusions was obtained with cotton-tipped aluminium and rayon-tipped plastic swabs than with calcium-alginate-tipped aluminium and cotton-tipped wooden swabs (P less than 0.0001). Transport medium stored in glass tubes caused a cytopathic effect when inoculated on to McCoy cell cultures; no such effect occurred with plastic tubes. When cotton-tipped aluminium instead of calcium-alginate-tipped aluminium swabs were used to collect 50 make urethral specimens significantly more were chlamydia-positive (P less than 0.025). This was also true when cotton-tipped aluminium swabs were used instead of alginate-tipped swabs in a study of 123 cervical specimens (P less than 0.01). When the calcium-alginate-tipped aluminium and cotton-tipped wooden swabs were shaken in the transport medium after sampling from the male urethra and the cervix, instead of being left in the medium during transport to the laboratory, more specimens were chlamydia-positive and a greater number of chlamydial inclusions were found per culture-positive sample; these results were, however, not statistically significant (P greater than 0.05).


Coercion in psychiatric care - patients' and relatives' experiences from four Swedish psychiatric services.
The aim of this study was to explore possible regional differences in the use of coercion in psychiatric care as experienced by patients and relatives. At four psychiatric care settings in different parts of Sweden, 138 committed and 144 voluntarily admitted patients were interviewed at admission using the Nordic Admission Interview. At discharge or, if the care episode was still ongoing, after 3 weeks of care, a follow-up patient interview and an interview with 162 relatives of these patients took place. In one of the centers, where involuntarily admitted patients were treated without locking the doors of the wards, the patients reported less coercion at admission than in the other three centers. Regarding the patients' reports of the use of coercive measures, personal treatment and outcome of care, and concerning the relatives' experiences, few differences were found between centers among committed and voluntarily admitted patients, respectively. Coercion in psychiatric care, as reported by patients and relatives, was not always legally based, and many of the patients reported they felt violated during the admission process. Only a minority of patients and relatives reported participation in treatment and care planning, as regulated by law. Still, a majority of both committed and voluntarily admitted patients reported they had been well treated by the personnel at admission as well as during the stay at the ward, and that they had been improved in their mental health after the psychiatric care episode.


Pirfenidone treatment in a patient with IPF and possible initial hypersensitivity pulmonitis.
The diagnosis of idiopathic pulmonary fibrosis (IPF) requires exclusion of other known causes of interstitial lung disease (ILD) (e.g., domestic and occupational environmental exposures, systemic connective tissue disease, and drug toxicity), the presence of a 'usual interstitial pneumonia' (UIP) pattern on high resolution computed tomography (HRCT), and specific combinations of HRCT and histopathologic patterns in patients subjected to surgical lung biopsy (SLB). A clear diagnosis and early treatment with currently the only approved anti-fibrotic drug, pirfenidone, represents the standard of care for the treatment of mild-to-moderate IPF. This case report describes a patient with possible initial hypersensitivity pneumonitis and subsequent diagnosis of IPF with late development of pulmonary hypertension, and who was a candidate for lung transplantation. The patient showed slow progression of IPF during pirfenidone treatment in the CAPACITY and RECAP studies.


Embryonic senescence and laminopathies in a progeroid zebrafish model.
Mutations that disrupt the conversion of prelamin A to mature lamin A cause the rare genetic disorder Hutchinson-Gilford progeria syndrome and a group of laminopathies. Our understanding of how A-type lamins function in vivo during early vertebrate development through aging remains limited, and would benefit from a suitable experimental model. The zebrafish has proven to be a tractable model organism for studying both development and aging at the molecular genetic level. Zebrafish show an array of senescence symptoms resembling those in humans, which can be targeted to specific aging pathways conserved in vertebrates. However, no zebrafish models bearing human premature senescence currently exist. We describe the induction of embryonic senescence and laminopathies in zebrafish harboring disturbed expressions of the lamin A gene (LMNA). Impairments in these fish arise in the skin, muscle and adipose tissue, and sometimes in the cartilage. Reduced function of lamin A/C by translational blocking of the LMNA gene induced apoptosis, cell-cycle arrest, and craniofacial abnormalities/cartilage defects. By contrast, induced cryptic splicing of LMNA, which generates the deletion of 8 amino acid residues lamin A (zlamin A-Δ8), showed embryonic senescence and S-phase accumulation/arrest. Interestingly, the abnormal muscle and lipodystrophic phenotypes were common in both cases. Hence, both decrease-of-function of lamin A/C and gain-of-function of aberrant lamin A protein induced laminopathies that are associated with mesenchymal cell lineages during zebrafish early development. Visualization of individual cells expressing zebrafish progerin (zProgerin/zlamin A-Δ37) fused to green fluorescent protein further revealed misshapen nuclear membrane. A farnesyltransferase inhibitor reduced these nuclear abnormalities and significantly prevented embryonic senescence and muscle fiber damage induced by zProgerin. Importantly, the adult Progerin fish survived and remained fertile with relatively mild phenotypes only, but had shortened lifespan with obvious distortion of body shape. We generated new zebrafish models for a human premature aging disorder, and further demonstrated the utility for studying laminopathies. Premature aging could also be modeled in zebrafish embryos. This genetic model may thus provide a new platform for future drug screening as well as genetic analyses aimed at identifying modifier genes that influence not only progeria and laminopathies but also other age-associated human diseases common in vertebrates.


[Oral Findings in Patients With COVID-19].
The aim of this study was to describe oral lesions in a group of patients with COVID-19. We recruited 55 patients, 25 women (45.5%) and 30 men (54.5%), aged between 1 and 89 years with confirmed COVID-19 at different stages of severity. After obtaining informed consent, we examined their mouths and recorded clinical findings. Forty percent of the patients had at least 1 oral lesion. The most common lesions were candidiasis and ulcers (7 patients each); 2 patients had enanthems. Geographic tongue and caviar tongue were also observed. Altered taste, dry mouth, and painful/burning mouth were noted in 60%, 27.3%, and 36.4% of patients, respectively. Oral mucosal alterations and lesions were prevalent in this series of COVID-19 patients. Altered taste and a painful/burning mouth were common symptoms.


[Detection of antiviral activity of monoclonal antibodies, specific to Marburg virus proteins].
Monoclonal antibodies (MAbs) specific to Marburg virus (MBG), Popp strain, have been previously produced and characterized by indirect ELISA. Protein specificity of MAbs was determined by immunoblotting with SDS-PAGE proteins of MBG: one to NP, four to VP40, and protein specificity of one antibody was not detected. The effect of MAb binding to protein epitopes on viral functions was investigated in vitro and in vivo. None of antibodies neutralized the virus in the neutralization test in vitro, but MAb 5G9.G11 and 5G8.H5 specific to MBG VP40 protein were active in antibody-dependent complement mediated lysis of virus-infected cells. In vivo these antibodies (5G9.G11 and 5G8.H5) protected guinea pigs from lethal MBG infection after passive inoculation. Studies of biological activity and analysis of epitope specificity of MAb-antiVP40 by competitive ELISA showed that 2 of 7 epitopes of VP40 protein of MBG induce the production of protective antibodies. Hence, MAbs 5G9.G11 and 5G8.H5 reacting with MBG VP40 protein caused lysis of virus infected cells in the presence of the complement in vitro and protected guinea pigs from MBG infection by passive inoculation.


Postthrombotic syndrome in children.
The postthrombotic syndrome (PTS) is a clinical condition of limb pain along with physical findings that range from swelling to stasis ulcers following one or more episodes of deep vein thrombosis (DVT). While venous thromboembolism has recently gained increased recognition in children, the sequelae of limb thrombi are being recognized in a substantial proportion of affected children, and with varying degrees of severity. PTS is caused by both obstructed as well as refluxed venous blood flow, with combined effects of obstruction and reflux resulting in earlier, and more extensive symptoms. PTS can be diagnosed using an evaluation tool adapted from an international adult scale. Certain risk factors predispose children to PTS including elevations in factor VIII activity and D-dimer, clot occlusiveness, clot persistence, number of venous segments involved and duration of observation following DVT. Optimal prevention and treatment have not yet been determined, although antithrombotic therapy to facilitate rapid clot resolution, elevation, compression, moderate exercise and achievement of optimal body weight are likely to improve outcome.