Fibrovascular pigment epithelial detachment in eyes with subretinal hemorrhage secondary to neovascular AMD or PCV: a morphologic predictor associated with poor treatment outcomes.
To evaluate the influence of fibrovascular pigment epithelial detachment (FVPED) on treatment outcomes in eyes with subretinal hemorrhage secondary to neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV). This retrospective study included 83 eyes diagnosed with fovea-involving submacular hemorrhage secondary to neovascular AMD or PCV. All the patients were treated with intravitreal anti-vascular endothelial growth factor. Eyes showing definite FVPED, which involves the subfoveal region, were included in the FVPED group. Eyes without subfoveal PED, shallow irregular PEDs, or serous/hemorrhagic PED were stratified to the non-FVPED group. The best-corrected visual acuity (BCVA) at diagnosis, at 3 months, at 12 months, and lesion re-activation after initial treatment were compared between the two groups. The mean size of hemorrhage was 8.6 ± 7.6 disc diameter areas. In the FVPED group, the mean logarithm of minimal angle of resolution BCVA was 1.11 ± 0.49 at diagnosis, 0.89 ± 0.58 at 3 months, and 1.05 ± 0.63 at 12 months. In the non-FVPED group, the values were 0.97 ± 0.56, 0.56 ± 0.55, and 0.45 ± 0.50, respectively. The BCVA at 3 months (P = 0.036) and at 12 months (P < 0.001) was significantly worse in the FVPED group than in the non-FVPED group. In addition, the incidence of lesion reactivation was greater in the FVPED group (83.3%) than in the non-FVPED group (38.5%) (P < 0.001). The presence of subfoveal FVPED was associated with a high incidence of lesion re-activation and poor treatment outcomes in eyes with subretinal hemorrhage. This result suggests that different treatment strategies are needed between eyes with and without FVPED.


Timely diagnosis of early ectopic pregnancy using a single blood progesterone measurement.
We obtained a single serum P measurement in 70 subjects at risk for an EP. Retrospectively, a P less than 15 ng/ml was 100% predictive of either an EP or otherwise nonviable IUP, while P greater than 15 ng/ml would have ruled out an EP in all cases. Because of this high degree of diagnostic accuracy, we speculated on the clinical utility of an outpatient D and C for those patients in our series having a P less than 15 ng/ml. Laparoscopy would be reserved for those cases without identifiable chorionic villi on frozen section of curettings. Following this course of management could have potentially diagnosed all EPs at the first ER visit without disruption of a single normal IUP in our series. This sequence could have expedited the diagnosis of EP by up to 14 days compared with a standard hCG/US protocol. This report describes a promising new test for the early detection of EP. The findings, however, require confirmation in a prospective trial before widespread clinical implementation.


Evaluation of resection of pituitary microadenoma for the treatment of Cushing's disease in patients with radiologically normal sella turcica.
Six patients with Cushing's disease and a radiologically normal sella turcica have been treated by transsphenoidal hypophysectomy. Microadenomas were found and removed in five. One patient was in complete remission by 2 months and three by 6 months post-operatively. Two of the remaining patients (one with and the other without a surgically demonstrable tumour) were not cured after 8 and 15 months follow-up, respectively. Our data suggest that pituitary tumours are present in the majority of patients with Cushing's disease. The possibilities of incomplete adenomectomy or of a tumour buried within the gland should be considered in patients in whom pituitary surgery does not induce remission. In one patient, subsequently proven to have a pituitary adenoma, the disease remitted pre-operatively with cyproheptadine, suggesting hypothalamic regulation of the tumour and/or direct drug action at the pituitary level.


Leaf production of an overstorey rainforest tree and its effects on the temporal distribution of associated insect herbivores.
The host phenology and temporal distribution of insect herbivores associated with a rainforest canopy tree, Argyrodendron actinophyllum (Sterculiaceae), were monitored for 3 and 2 years respectively in an Australian subtropical rain forest near Brisbane. Leaf production of this evergreen species was synchronous among individuals, occurring from October to February, but differed markedly between years for some fast-growing trees. Most herbivore species fed selectively upon young leaves and, consequently, occurred only during "windows" of young foliage availability, with the exception of some mesophyll-feeders that preferred mature foliage. Fast-growing trees sustained high herbivore activity during periods of intense leaf production but some slow-growing trees, whose availability of young foliage appeared to be more constant and predictable, also supported high herbivore activity in the long term. Host suitability of particular trees during study years was dependent upon the intensity of leaf production and other unidentified factors, and was different for generalist and specialist herbiovores. Certain specialist species, such as psyllids, were able to overcome the changing availability of young foliage between years on vigorous A. actinophyllum trees by feeding upon both vegetative and reproductive meristems. Most of the data suggest that availability of young foliage is an important factor in this insect-plant system.


The metabolic clearance rate of estradiol-17 beta in rainbow trout, Salmo gairdneri R., estimated by both single injection and constant infusion methods: increase during oocyte maturation.
A dual cannulation of free-swimming rainbow trout is used to estimate the metabolic clearance rate (MCR) of Estradiol-17 beta (E2-17 beta) by both single injection and constant infusion methods. It is shown that E2-17 beta MCR changes significantly during the progress of oogenesis, mainly at the end of the sexual cycle. The same changes in MCR and very similar values are found with both single injection and constant infusion methods: MCR is stable (28.8 ml/hr/kg) from the postovulation period (throughout endogenous vitellogenesis) to early exogenous vitellogenesis. It decreases significantly during advanced exogenous vitellogenesis (18.7 ml/hr/kg) and increases clearly at the onset of oocyte maturation (40.9 ml/hr/kg). A direct relationship between MCR and plasma E2-17 beta occurs: Plasma E2-17 beta levels increase (advanced exogenous vitellogenesis) when MCR decreases. Then estradiol decline takes place at the same time that MCR reaches its highest values (oocyte maturation). An increase in MCR is probably one event required to allow the establishment of an appropriate hormonal environment for oocyte maturation.


SSVEP recognition using common feature analysis in brain-computer interface.
Canonical correlation analysis (CCA) has been successfully applied to steady-state visual evoked potential (SSVEP) recognition for brain-computer interface (BCI) application. Although the CCA method outperforms the traditional power spectral density analysis through multi-channel detection, it requires additionally pre-constructed reference signals of sine-cosine waves. It is likely to encounter overfitting in using a short time window since the reference signals include no features from training data. We consider that a group of electroencephalogram (EEG) data trials recorded at a certain stimulus frequency on a same subject should share some common features that may bear the real SSVEP characteristics. This study therefore proposes a common feature analysis (CFA)-based method to exploit the latent common features as natural reference signals in using correlation analysis for SSVEP recognition. Good performance of the CFA method for SSVEP recognition is validated with EEG data recorded from ten healthy subjects, in contrast to CCA and a multiway extension of CCA (MCCA). Experimental results indicate that the CFA method significantly outperformed the CCA and the MCCA methods for SSVEP recognition in using a short time window (i.e., less than 1s). The superiority of the proposed CFA method suggests it is promising for the development of a real-time SSVEP-based BCI.


Deaths during pregnancy, childbirth and puerperium: Exploring causes, context and evidence from Eastern India.
The study was aimed to identify the specific reasons and circumstances of maternal deaths in West Bengal. The present study is a retrospective study of 317 maternal deaths, conducted between November 2013 and October 2015 at two major referral hospitals of eastern India, West Bengal. The frequencies, proportions, measures of central tendency and dispersion were used to describe the data. The data were analyzed using the statistical software spss version 20.0. ArcGIS 10.1 was also employed to show the distributional pattern of maternal deaths. The overall maternal mortality ratio was estimated as 561 per 100 000 live births. Eclampsia or hypertensive disorders of pregnancy contributed to one-third (33.1%, n = 105/317) of maternal deaths. The maternal deaths were more common (41%) among women belonging to the age group of 20-24 years and primiparous (36.9%) group. The average distance for traveling to reach the final hospital was 47.37 km. Approximately, three-fourths (72.2%) of maternal deaths were in the post-partum period. Half of the women (50.5%) sought medical care after 12 hrs of developing complications. The majority of the cases (80.1%) were referred and about 45% of patients had a cesarean section. The result suggests there was a shift in causes of maternal deaths from hemorrhage to eclampsia. Establishment of separate eclampsia units at lower-level health facilities may be a more plausible pathway to prevent eclampsia-related maternal deaths in West Bengal.


Differential gene expression of RAW 264.7 macrophages in response to the RGD peptide lunasin with and without lipopolysaccharide stimulation.
Lunasin is a novel peptide from soybean with demonstrated chemopreventive property. We compared the effect of lunasin on gene expression of RAW 264.7 macrophages with and without lipopolysaccharide (LPS)-stimulation. Our hypothesis was that lunasin will have a differential effect in RAW 264.7 gene expression in a normal and challenged state. Analysis of the microarray data using False Discovery Rate (FDR) method resulted in the identification of 340 up-regulated and 162 down-regulated genes (FDR p-value <0.05) associated with simultaneous treatment of lunasin and LPS for 24h. Treatment of lunasin with no LPS for 24h resulted in the up-regulation of 855 genes and down-regulation of 397 genes. Pre-treatment of lunasin for 24h resulted in the up-regulation of 35 genes and down-regulation of 65 genes in LPS-stimulated RAW 264.7 macrophages. GeneVenn analysis of these three sets of genes showed that there are 66 genes common among the three groups which are mostly associated with regulation of cell death, ion binding and transcription as datamined by DAVID. Analysis of the 838 genes unique to lunasin alone by functional annotation clustering tool showed that lunasin mostly affected genes associated with RNA processing, apoptosis and protein kinase activity. Further datamining of these genes by ingenuity pathway analysis (IPA) showed that lunasin affected genes involved in cellular growth and proliferation, cellular function and maintenance, and cell to cell signaling and interaction. These findings support the potential chemopreventive and chemotherapeutic use of lunasin against cancer.


Novel inhibitors of alpha 4 beta 1 integrin receptor interactions through library synthesis and screening.
A library of 2302 small molecule beta-turn mimetics was screened for inhibition of the alpha 4 beta 1 integrin-CS1 splice variant binding interaction. Preliminary data revealed several active ligands, and validation with purified material culminated in the identification of some of the first small molecule ligands (1, IC50 = 5 microM, and 2, IC50 = 8 microM) to be reported for this class of integrins.


Renal disease in pregnancy. Three controversial areas: mesangial IgA nephropathy, focal glomerular sclerosis (focal and segmental hyalinosis and sclerosis), and reflux nephropathy.
Whether gestation has adverse effects on the course of renal disease is controversial. Three diseases regarding which conflicting opinions are especially noteworthy are IgA nephropathy, focal and segmental hyalinosis and sclerosis, and reflux nephropathy. We analyzed 102 pregnancies in 65 women with IgA nephropathy, noting hypertension in 63% of the gestations (severe in 18%), decreases in renal function in 22%, and biopsy evidence demonstrating a significantly greater amount of glomerular proliferation and crescents as well as focal and segmental hyalinosis and sclerosis when the renal histology from women who were pregnant and those who had never conceived were compared. Our experience with glomerular sclerosis is limited to 28 gestations in 15 patients, but the clinical findings resemble those of women with IgA nephropathy who conceived. Finally, we analyzed 227 pregnancies in 95 women with normal renal function and reflux nephropathy comparing results to 118 gestations in 42 patients with evidence of dysfunction (serum creatinine SCr greater than 1.25 mg/dL). Women with preserved function had good outcomes in general, whereas hypertension (36%) and an accelerated decline in function (8%) were observed in the groups that had moderate renal insufficiency in the initial stage of pregnancy. Increased proteinuria was the best predictor of progression of reflux nephropathy in both groups.


Patient response prediction with logistic regression in gastrointestinal endoscopy under midazolam-alfentanil sedation performed as well as response surface model.
Researchers have used logistic regression (LR) and non-linear response surface models (RSMs) to predict patient responses to sedation. The reduced Greco and hierarchy RSMs have proven to be more appropriate than other RSMs in gastrointestinal endoscopies using midazolam and alfentanil. In this study, we evaluate the performance of a simpler model, LR, and compared it with that of RSM. Thirty-three patients who received esophagogastroduodenoscopy (EGD) and colonoscopy sedation with midazolam and alfentanil were enrolled in the study. LR was performed for the EGD group and validated using the colonoscopy group. The two RSMs were performed using the same process, and performances and receiver operating characteristic (ROC) curves of the models were evaluated. The native EGD LR model had an ROC curve area of 0.94. For external validation, the ROC curves were 0.92, 0.94, and 0.94 for the reduced Greco, hierarchy, and LR models, respectively. Pairwise comparison between models was not significant. The LR model performed as well as RSM in generalizing the predicted sedative effect of midazolam and alfentanil during gastrointestinal endoscopies. LR may be used for generalization across patients experiencing procedures with similar stimulus intensities.


Akkermansia muciniphila and its outer membrane protein Amuc_1100 prophylactically attenuate 5-fluorouracil-induced intestinal mucositis.
5-Fluorouracil (5-FU) is a chemotherapy drug used to treat tumors. Previous studies have shown that Akkermansia muciniphila (A. muciniphila) and its outer membrane protein, Amuc_1100, alleviate dextran sodium sulfate (DSS)-induced colitis in mice. We investigated the effects of both A. muciniphila and Amuc_1100 on 5-FU-induced intestinal mucosal damage in mice. C57BL/6 mice were gavaged with A. muciniphila or Amuc_1100 daily before, during, and after 5-FU injection for a total of 14 days. By evaluating diarrheal toxicity scores, body weight changes, colonic anatomy images, and histopathology of intestinal injury in these mice, we found that A. muciniphila and Amuc_1100 alleviated 5-FU-induced intestinal mucositis. Quantitative polymerase chain reaction assays of intestinal cytokine mRNA levels demonstrated that both A. muciniphila and Amuc_1100 attenuated the upregulation of intestinal Tumor Necrosis Factor-α (TNF-α) and interleukin-6 (IL-6) induced by 5-FU treatment. In addition, they both reduced 5-FU-induced the NLR family pyrin domain containing 3 (NLRP3) inflammatory vesicle activation. Furthermore, by monitoring the mRNA expression of tight junction proteins in the intestine, we found that A. muciniphila and Amuc_1100 were capable of restoring the damaged intestinal barrier. Notably, A. muciniphila and Amuc_1100 also played a role in altering the structure of the intestinal microbial community. The present study revealed the protective role of both A. muciniphila and Amuc_1100 in the intestinal mucositis caused by 5-FU, providing new insights into treatment options.


TNF and TNF receptors as therapeutic targets for rheumatic diseases and beyond.
The cytokine TNF signals via two distinct receptors, TNF receptor 1 (TNFR1) and TNFR2, and is a central mediator of various immune-mediated diseases. Indeed, TNF-neutralizing biologic drugs have been in clinical use for the treatment of many inflammatory pathological conditions, including various rheumatic diseases, for decades. TNF has pleiotropic effects and can both promote and inhibit pro-inflammatory processes. The integrated net effect of TNF in vivo is a result of cytotoxic TNFR1 signalling and the stimulation of pro-inflammatory processes mediated by TNFR1 and TNFR2 and also TNFR2-mediated anti-inflammatory and tissue-protective activities. Inhibition of the beneficial activities of TNFR2 might explain why TNF-neutralizing drugs, although highly effective in some diseases, have limited benefit in the treatment of other TNF-associated pathological conditions (such as graft-versus-host disease) or even worsen the pathological condition (such as multiple sclerosis). Receptor-specific biologic drugs have the potential to tip the balance from TNFR1-mediated activities to TNFR2-mediated activities and enable the treatment of diseases that do not respond to current TNF inhibitors. Accordingly, a variety of reagents have been developed that either selectively inhibit TNFR1 or selectively activate TNFR2. Several of these reagents have shown promise in preclinical studies and are now in, or approaching, clinical trials.


Effect of type of definitive treatment on race-based differences in prostate cancer-specific survival.
Racial and ethnic disparities in prostate cancer (PCa) mortality are partially mediated by inequities in quality of care. Intermediate- and high-risk PCa can be treated with either surgery or radiation, therefore we designed a study to assess the magnitude of race-based differences in cancer-specific survival between these two treatment modalities. Non-Hispanic Black (NHB) and non-Hispanic White (NHW) men with localized intermediate- and high-risk PCa, treated with surgery or radiation between 2004 and 2015 in the Surveillance, Epidemiology and End Results database were included in the study and followed until December 2018. Unadjusted and adjusted survival analyses were employed to compare cancer-specific survival by race and treatment modality. A model with an interaction term between race and treatment was used to assess whether the type of treatment amplified or attenuated the effect of race/ethnicity on prostate cancer-specific mortality (PCSM). 15,178 (20.1%) NHB and 60,225 (79.9%) NHW men were included in the study. NHB men had a higher cumulative incidence of PCSM (p = 0.005) and were significantly more likely to be treated with radiation than NHW men (aOR: 1.89, 95% CI: 1.81-1.97, p < 0.001). In the adjusted models, NHB men were significantly more likely to die from PCa compared with NHW men (aHR: 1.18, 95% CI: 1.03-1.35, p = 0.014), and radiation was associated with a significantly higher odds of PCSM (aHR: 2.10, 95% CI: 1.85-2.38, p < 0.001) compared with surgery. Finally, the interaction between race and treatment on PCSM was not significant, meaning that no race-based differences in PCSM were found within each treatment modality. NHB men with intermediate- and high-risk PCa had a higher rate of PCSM than NWH men in a large national cancer registry, though NHB and NHW men managed with the same treatment achieved similar PCa survival outcomes. The higher tendency for NHB men to receive radiation was similar in magnitude to the difference in cancer survival between racial and ethnic groups.


Creating the right environment for return-to-practice candidates.
With a recognised national shortage of qualified nurses in England, a trust and university joined forces to provide a return-to-nursing course (ENB 902). This article describes how they provided clinical support and encouraged nurses to return to practice.


Lewis acid induced tandem Diels-Alder reaction/ring expansion as an equivalent of a [4 + 3] cycloaddition.
Aluminum chloride induced reaction between cyclopentadiene and alpha,beta-unsaturated aldehydes results in the stereoselective formation of the products of a formal [4 + 3] cycloaddition. The reaction proceeds by a tandem Diels-Alder reaction/ring expansion.


Attention deficit hyperactivity disorder (ADHD) and executive functioning in affected and unaffected adolescents and their parents: challenging the endophenotype construct.
The results of twin and sibling studies suggest that executive functioning is a prime candidate endophenotype in attention deficit hyperactivity disorder (ADHD). However, studies have not assessed the co-segregation of executive function (EF) deficits from parents to offspring directly, and it is unclear whether executive functioning is an ADHD endophenotype in adolescents, given the substantial changes in prefrontal lobe functioning, EF and ADHD symptoms during adolescence. We recruited 259 ADHD and 98 control families with an offspring average age of 17.3 years. All participants were assessed for ADHD and EF [inhibition, verbal (VWM) and visuospatial working memory (VsWM)]. Data were analysed using generalized estimating equations (GEEs). Parental ADHD was associated with offspring ADHD and parental EF was associated with offspring EF but there were no cross-associations (parental ADHD was not associated with offspring EF or vice versa). Similar results were found when siblings were compared. EF deficits were only found in affected adolescents and not in their unaffected siblings or (un)affected parents. The core EFs proposed to be aetiologically related to ADHD, that is working memory and inhibition, seem to be aetiologically independent of ADHD in adolescence. EF deficits documented in childhood in unaffected siblings were no longer present in adolescence, suggesting that children 'grow out' of early EF deficits. This is the first study to document ADHD and EF in a large family sample with adolescent offspring. The results suggest that, after childhood, the majority of influences on ADHD are independent from those on EF. This has potential implications for current aetiological models of causality in ADHD.


Manual deep lamellar keratoplasty: alternative methods and air-guided technique.
To describe the techniques proposed for performing deep lamellar keratoplasty (DLK) and to evaluate the efficacy of a new, modified technique. Fourteen eyes in 11 patients with keratoconus of moderate degree were included. All patients underwent a DLK with manual dissection from a limbal side port after an air bubble injection in the anterior chamber. All patients had complete ophthalmologic examination 6 months after the suture removal, evaluating best corrected visual acuity, corneal thickness, endothelial cell count, and topographic astigmatism. One case (7.1%) was converted to penetrating keratoplasty because of microperforation. In the 13 successful cases, 10 eyes (71.4%) achieved 20/30 or better 6 months after suture removal. Mean postoperative pachymetry was 628.39 micro (SD 57.34). Specular microscopy 6 months after suture removal revealed average endothelial cell count of 2261 (SD 287/mm(2)). Comparing this modified DLK technique with other methods proposed by several authors, air-guided DLK seems to be safe and effective and, after a short learning curve, can be performed with a low risk of conversion to penetrating keratoplasty.


Phosphatidylinositol 3-kinase inhibitor failed to reduce cerebral vasospasm in dog model of experimental subarachnoid hemorrhage.
Phosphatidylinositol 3-kinase (PI3-kinase) is involved in smooth muscle contraction induced by growth factors and/or G protein-coupled receptor agonists. To evaluate the role of PI3-kinase in the pathogenesis of delayed vasospasm, we applied 2 PI3-kinase inhibitors to an established canine double-hemorrhage model of experimental subarachnoid hemorrhage. Twenty-four dogs underwent double blood injections via the cisterna magna on days 0 and 2. The dogs were killed on day 7. Dogs were treated with either vehicle (dimethyl sulfoxide), wortmannin, or LY294002 once per day on day 2 through day 6. Angiography was performed before blood injection and before the dogs were killed. The basilar arteries were collected for morphology, Western blot analysis, and PI3-kinase activity. The residual diameter of the basilar arteries in the dimethyl sulfoxide treatment group, which was compared with day 0 angiogram, decreased markedly on day 7 (the percentage of the residual diameter was 47.8+/-0.8%). Wortmannin and LY294002 did not significantly change residual diameter on day 7. Both PI3-kinase inhibitors abolished PI3-kinase activity compared with the vehicle treatment group. However, both PI3-kinase inhibitors failed to significantly attenuate PI3-kinase protein expression (Western blot) (P>0.05, ANOVA). Delayed treatment, which was to mimic the clinical situation, with PI3-kinase inhibitors failed to reverse vasospasm. PI3-kinase may not play an important role in the delayed vasospasm. The possible effect of PI3-kinase inhibitors in the early stage of vasospasm was not investigated in the present study.


Total elbow joint replacement for fractures in the elderly--Functional and radiological outcomes.
The purpose of this paper was to review the literature on the treatment of intra-articular fractures of the distal humerus in the elderly in order to evaluate the place for total elbow replacement (TER) in the light of our experience over the past 15 years. A review of the records of 11 consecutive patients over the age of 60 years who underwent primary TER for comminuted fractures of the distal humerus between 1997 and 2011 were reviewed and the surviving patients were interviewed. The Scopus database was used to perform a pragmatic review of the literature published between the mid-1990s and the present-day. At the time of the most recent follow-up 3.5 years following surgery (range: 2-6 years) 7 patients assessed with the Mayo elbow performance index were classified as excellent, 4 were classified as good. There were no complications requiring further procedures encountered. Five surviving patients remain satisfied with the function of their TER. The number of papers recommending TER for treatment of these fractures continues to increase with time. TER is now the treatment of choice for unreconstructable fractures of the distal humerus in the elderly. This option should therefore be available at the time of surgery for all distal humeral fractures in this patient population. A surgical approach other than olecranon osteotomy, which would preclude TER is therefore required.


Alpinia: the gold mine of future therapeutics.
Since prehistoric era, plant-derived drugs were much preferred due to their less side effects than drugs of synthetic origin. Bioassay-guided selection of active fraction of a plant extract and further isolation and characterization of the pure bioactive compounds are in practice in both academic and industrial research. Zingiberaceae, a medicinally important, ornamental, monocotyledonous family has potential members in the tribe Alpinieae, among which the genus Alpinia is studied under this current review due to its wide range of biomedical applications. The members in the genus possess many bioactive compounds against harmful microbes to deadly diseases like cancer by regulating the different signalling pathway systems. Several compounds have been discovered and found to deliver diversified biological efficacy either in vitro or in vivo against a range of diseases. The chemical profiling of the genus and investigation of crude essential oils and individual bioactive compounds towards the therapeutic importance in various disciplines have been documented in the current review.


Microtubule dynamics: new surprises from an old MAP.
Dis1/XMAP215 family microtubule-binding proteins are essential for cell division in animals, plants and fungi, suggesting a conserved cell-division mechanism used by all eukaryotes. Two new studies, however, reveal that different family members can have very different effects on microtubule dynamics.


Unrecognized depression in community-dwelling elderly persons in Istanbul.
Depression, one of the most prevalent psychiatric disorders, causes disability and reduces quality of life. Rates of clinical depression in community samples of older adults range between 1-16%. Most studies of old age depression have been conducted in developed countries. The present study was conducted to determine the prevalence of depressive disorders among Turkish elderly in an urban community. This study was carried out in the Kadiköy district of Istanbul. The sample for the cross-sectional part of the study was 1067 individuals age 70 or older, randomly selected from population registries. Geriatric Depression Scale (GDS), Mini-mental State Examination (MMSE) scores and demographic data were obtained by face-to-face home interviews. The data were analyzed using regression analysis for each variable. The study group consisted of 623 (61%) females and 395 (39%) males. The mean age was 74.8 years, with 63% of subjects aged 70-74, 29% between 75-84 years old and 8% aged 85 and above. Sixteen percent (n = 163) of the total group scored 14 or higher on the GDS. Only 9% of the depressed group were on antidepressant medication. Logistic regression analysis indicated that significant predictors for higher scores GDS scores were: illiteracy, aged 75-79 yrs, female sex and having 4 or more children. Depression is a common but unrecognized and thus untreated problem among the elderly population in Turkey. While gender and age are unmodifiable, education level and multiparity can be altered. Education of caregivers and medical staff about old age depression may increase its rate of detection and facilitate improved treatment.


[A cephalometric study of natural head posture and spinal position in malocclusions].
The purpose of this cephalometric study was to compare the difference of NHP (natural head posture) and spinal position among malocclusions with different skeletal patterns. 79 malocclusions aged from 12 to 16 were divided to several groups according ANB and NSL-MP. The features of head posture and spinal position were examined by comparing the groups and the statistical significant correlation among NHP, spinal position and craniofacial morphology was sought. NHP and spinal position was not the same in malocclusions with different NSL-MP, while was identical in malocclusions with different ANB. It is believed that there was correlation among NHP, spinal position and vertical, sagittal development of face rather than anteroposterior relationship between maxilla and mandible.


Treatment of hereditary amyotrophic lateral sclerosis.
Currently, only four molecules can be prescribed for amyotrophic lateral sclerosis (ALS), of which only one is approved worldwide for this indication, riluzole. Although progress in the therapeutic field remains unsatisfactory, we have to notice that genetics have undergone impressive improvements over the last three decades and, by extension, our knowledge of ALS cases linked to a pathogenic mutation that accounts for 10% of all cases (either sporadic or familiar) and is currently called hereditary ALS (hALS). In many neurological diseases treatment targeting pathogenic genes have significatively improved the natural profile of the disease: this is perfectly illustrated for familial amyloid neuropathy and spinal muscular atrophy. Because of these findings and the urgent need to find a cure for ALS, many trials have focused on familial ALS targeting the four most important genes linked to the disease: C9orf72, SOD1, TARDBP and FUS. We propose in this review an update on the perspectives of treatment that may be available in mid-term in hALS and will discuss in the last part the potential consequences for asymptomatic relatives of patients with a hALS and for ALS patients.


Monolithic Materials-Based RPLC-MS for Proteoform Separation and Identification.
High-performance separation of proteoforms plays an important role in top-down proteomic ananlysis due to high complexity of the proteome. To this end, the functionalized ethylene-bridged hybrid monolithic materials have been developed for reversed-phase liquid chromatographic separation of proteoforms followed by online combination with high-resolution mass spectrometry (MS) for top-down proteomic analysis. Such monoliths have advantages of homogenously distributed functional groups in the framework, good chemical stability, and high permeability and, thus, show high resolution, good reproducibility, and low backpressure for proteoform separation. This chapter describes in detail the preparation of such monoliths and online combination with high-resolution MS for proteoform separation and identification.


Regulatory effect of various steroid hormones on the incorporation and metabolism of [14C]stearate in rat hepatoma cells in culture.
We have examined the incorporation and metabolism of [14C] stearic acid within the total lipids of HTC rat-hepatoma cells in suspension culture in presence and in absence of steroidal hormone stimulation. Both, glucocorticoids (dexamethasone, cortisol and corticosterone) and mineralocorticoids (deoxycorticosterone and aldosterone) as well as the estrogen beta-estradiol and the androgen testosterone enhanced the extent of delta 9 desaturation to oleic acid of the saturated precursors, whereas only the two mineralocorticoids affected the incorporation rate of the exogenous acid into total cellular lipids, thus promoting a little stimulation. Furthermore, all the hormones tested increased the radiolabelling of the total cellular phospholipids except deoxycorticosterone and testosterone, the former having no effect and the latter exerting a moderate inhibition. On the other hand, the incorporation of 14C into neutral lipids was stimulated by testosterone, in contrast to the inhibition of this parameter observed exclusively with either the mineralocorticoids or the estrogen. Within the phospholipid subclasses, the radiolabelling of phosphatidylcholine was augmented by means of all the steroids tested save deoxycorticosterone and testosterone, whereas phosphatidylethanolamine exhibited a decrease only in the presence of testosterone. In a similar fashion, within the neutral lipids, the predominating triglyceride fraction was preferentially labelled--at the expense of other subclasses of lesser abundance--upon treatment with the steroids except aldosterone, which exerted no effect. The results obtained were correlated with those changes observed in the mass distribution of the different lipid subclasses either with or without prior hormonal stimulation.


Comparison of unilateral versus bilateral balloon kyphoplasty for the treatment of osteoporotic vertebral compression fractures.
Thirty-one patients with osteoporotic vertebral compression fractures (OVCF) were treated with unilateral balloon kyphoplasty (BKP), and 31 patients were treated with bilateral BKP. The efficacy of unilateral and bilateral BKP was assessed by comparing operation time, X-ray exposure times, incidence of complications, vertebral height restoration, and improvement of the visual analogue scale (VAS) scores. The mean operative time and the exposure time to X-rays in the unilateral BKP group was less than that of the bilateral BKP group (p<0.05). No statistically significant differences were observed in the cement leakage rate, VAS score, or vertebral height restoration between the two groups (p>0.05). Unilateral and bilateral BKP are safe and effective treatments for OVCF. Compared with bilateral BKP, patients undergoing unilateral BKP have shorter operations and receive lower X-ray radiation doses.


Comprehensive analysis of mitophagy in HPV-related head and neck squamous cell carcinoma.
Head and neck squamous cell carcinoma (HNSCC) is a common tumour type in otorhinolaryngology, and its occurrence is related to long-term exposure to tobacco and alcohol. Recently, HPV infection has become an increasingly important contributor to HNSCC, and HPV-associated HNSCC has a different clinical course and better prognosis than non-HPV-associated HNSCC. However, the exact molecular mechanism of HNSCC is unclear. Here, we obtained data from The Cancer Genome Atlas (TCGA) and gene expression omnibus (GEO) to analyse the mitophagy process and related influencing factors of HPV-associated HNSCC via the integration of bioinformatics analysis and experimental validation. We found that in HPV-associated HNSCC, process of mitophagy affects tumour development, immune cell infiltration and prognosis. In the mitophagy process of HPV-related HNSCC: NOS2, IL17REL, TMSB15A, TUBB4A and other hub genes showed significantly higher expression levels than in non-HPV-related HNSCC. Furthermore, this was also confirmed by quantitative real-time PCR (qRT‒PCR), which was used to detect the expression of differentially expressed genes in HNSCC tissues. Furthermore, we found that the unique immunological characteristics by expressing CD8+ T cell in a high level in HPV-related HNSCC, and the scores obtained from the score model affected the prognosis of patients. In conclusion, our study revealed the unique biomolecular signature of mitophagy in HPV-associated HNSCC, which may contribute to the development of precise treatment regimens for HPV-associated HNSCC patients.


Hypertension guidelines: Evidence-based treatments for maintaining blood pressure control.
Approximately one in three adults in the United States has hypertension. This article provides an update on the latest JNC-8 guideline for treating hypertension in adults. Emphasis is placed on new and updated information and implications for primary care clinicians to help patients achieve and maintain better blood pressure control.


Neonatal jaundice in infants of diabetic mothers.
357 IDMs and 20 healthy newborns of non-diabetic mothers were examined at term for body measurements, red blood cell count, serum bilirubin, cord blood insulin and blood glucose during the first postnatal week. The stage of maternal diabetes did not influence the course of neonatal bilirubin levels, but the IDMs had prolonged and higher bilirubinaemia compared with the controls. Hyperbilirubinaemia was found to be most prominent in newborns with an increased birthweight/length ratio and was not simply related to macrosomia (LGA). These infants had significantly lower blood glucose concentrations immediately after birth, whereas cord blood insulin was found to be identical between the IDM sub-groups. Bilirubinaemia in heavy for length infants was slightly correlated to haematocrit. For the pathogenesis of hyperbilirubinaemia in IDMs induction of heme oxygenase (due to a lack of energy provision following a phosphorylation disorder) is discussed. Nutritional support (early feeding, glucose infusions) does not affect the course of bilirubinaemia.


Steroid glycosides from the roots of Marsdenia tenacissima.
Eleven undescribed glycosylated C21 steroids and nine known homologous glycosides with diverse acyl substituents, as well as their common steroid aglycone, have been obtained from the roots of Marsdenia tenacissima. Their structures were elucidated mainly by comprehensive spectroscopic analyses and comparison with previously reported analogues, with the absolute configuration assignment being supported by chemical degradation, X-ray crystallography and ECD exciton chirality method. Among them, two pairs of regioisomers were found to exist as inseparable equilibrium mixtures due to an interesting intramolecular transesterification, and nicotinoyl substitution was first reported for metabolites from the title plant. Screening of these compounds in a panel of bioassays revealed that two glycosides displayed mild inhibition against butyrylcholinesterase.


Feline hemotropic mycoplasmosis (feline hemobartonellosis).
Hemotropic mycoplasmas represent an important cause of anemia in cats worldwide. Previously known as Haemobartonella species, sequencing of the 16S rRNA genes of these organisms has led to their reclassification as mycoplasmas. Two species have been identified in cats, M haemofelis and "Candidatus M haemominutum." The latter organism alone has not been associated with disease in naturally infected cats but may cause anemia in FeLV-infected cats and accelerate development of FeLV-induced myeloproliferative disease. The mode of transmission of these organisms remains enigmatic. Nevertheless, development of sensitive DNA-based tests for these unculturable organisms has improved the understanding of the epidemiology and pathogenesis of FHM. Cats with clinical signs and laboratory abnormalities consistent with FHM should be treated with doxycycline; enrofloxacin may represent an effective alternative. Transfusion with packed red blood cells after cross-matching may be required for severely anemia cats, and addition of prednisone may be required if the diagnosis of FHM is uncertain, or response to antimicrobials alone is insufficient. Affected cats should be tested for FeLV, the most common concurrent infection in cats with FHM.


Quantitative analysis of the localization of adrenergic binding sites in chick brain.
In the present work [3H]-WB4101, [3H]-DHA, and [3H]-clonidine were used for the study of the localization of alpha 1, alpha 2, and beta adrenergic receptors in the chick brain. The highest concentration of [3H]-WB4101 was observed in the nucleus pretectalis, followed by the nucleus brachium conjunctivum descendens. The superficial layers of stratum griseum fibrosum superficiale, the nucleus mesencephalis lateralis pars dorsalis, and the locus coeruleus showed concentrations of [3H]-WB4101 binding higher than 300 fmoles/mg protein. Concentrations of [3H]-DHA binding higher than 300 fmoles/mg protein were observed in the paleostriatum, the external part of nucleus pretectalis, the nucleus isthmi parvocellularis, the nucleus mesencephalis lateralis pars dorsalis, the dorsal nucleus of oculomotor center, and the molecular layer of cerebellum. Locus coeruleus was the only area of chick brain which showed concentration of [3H]-clonidine binding higher than 300 fmoles/mg protein. With few exceptions, [3H]-clonidine binding was very low and in the telencephalon it was undetectable.


[Influence of CRX gene on development of photoreceptors in zebrafish].
To study the development and opsin expression of zebrafish photoreceptors after CRX gene knock-down. It was a experimental study. CRX-MOs was microinjected into the zygote of zebrafish. Seventy-two and 96 hours post fertilization, we prepared the eye histological slides, electron microscope samples and whole mount in-situ hybridizations to study the development and opsin expression. of photoreceptors. There were no obvious histological changes in optical microscope observation after CRX-MOs microinjection. Outer segments were developed in control and blank groups, but no obvious outer segment was found in CRX group by electron microscope observation. Opsin Rho, SWS1 and SWS2 were expressed in control and blank groups and the expression of these genes was obviously decreased in CRX group. CRX gene can influence the development and opsins expression of photoreceptors outer segments in zebrafish.


Recurrent upper eyelid trachomatous entropion repair: long-term efficacy of a five-step approach.
To describe the lid characteristics of recurrent upper eyelid trachomatous entropion and to report the long-term outcomes of a five-step surgical approach based on the principles of upper eyelid crease lamellar splitting and retractor release with redirection. Retrospective case review of adult patients with recurrent upper eyelid trachomatous entropion who had undergone surgical correction using the five-step surgical technique between March 2014 and March 2018. Cases with primary entropion and/or <2 years of follow-up were excluded from this series. Eyelid deformities (type of trichiasis, anterior lamellar laxity, lid margin abnormality, lid retraction and lagophthalmos), recurrence of entropion and trichiasis, cosmetic satisfaction, and surgical complications. Forty-two upper eyelids in 33 patients met inclusion criteria. Preoperative anterior lamellar laxity was present in 36 eyelids (85.7%), lid retraction in 31 eyelids (73.8%) with a mean preoperative MRD1 of 6.48 ± 1.1 mm, atrophic tarsus in 28 eyelids (66.7%), lid margin notching in 22 eyelids (52.4%), and lagophthalmos in 15 eyelids (35.7%). The surgical success rate was 92.9% (95% CI 0.805-0.985). There was no documented recurrence of entropion over a mean follow-up period of 31.79 months. Postoperative trichiasis without entropion occurred in three eyelids, which required repeat epilation. The five step-approach based on the principles of lamellar splitting is effective in correction of recurrent trachomatous entropion with long-term stability. The procedure addresses the fundamental changes frequently seen in recurrent cases, in particular anterior lamellar laxity, scarred shortened posterior lamella, and trichiasis.


Semen backflow after insemination and its effect on fertilisation results in sows.
The aim of the present study was to investigate the volume of and number of spermatozoa in semen backflow during and after insemination, and the effect of backflow on fertilisation results assessed at day 5 of pregnancy. Multiparous sows (n = 140) were artificially inseminated with either (1, 3 or 6) x 10(9) mixed spermatozoa from three boars in a constant volume of 80 ml. Backflow of semen was measured three times: during insemination (M1); during the first half hour after insemination (M2); and from 0.5 h until about 2.5 h after insemination (M3). Transrectal ultrasonography was performed at intervals of 4 h to determine the time of ovulation. Sows were sacrificed at 120 +/- 0.4 h after ovulation to assess the results of fertilisation. Every sow had some backflow and the variation in volume, and number of spermatozoa within the backflow was high. The average semen backflow within 2.5 h after insemination was 70 +/- 3.4% of the volume and 25 +/- 1.4% of the spermatozoa of the inseminated dosage. The concentration of the backflow (% of the inseminated dosage) decreased with time after insemination from 65% at M1 to 40% and 26% at M2 and M3, respectively. The correlations between volume and number of spermatozoa were high: r = 0.97, r = 0.73 and r = 0.81 in M1, M2 and M3, respectively. More than 5% of the inseminated spermatozoa in backflow during insemination affected fertilisation negatively in those sows inseminated with 1 x 10(9) spermatozoa (P < 0.05). Backflow after insemination had no effect on fertilisation results (P > 0.05). Timing of insemination relative to ovulation and oestrus were not related to backflow during or after insemination (P > 0.05). Of the sows which had backflow, those of parity 1 tended to have the highest proportion of sows with more than 5 ml backflow (47%; n = 8 of 17) compared with sows from parity 2 and higher (24%; n = 14 of 59) (P = 0.075). It was concluded that excessive backflow of semen during insemination had a negative effect on fertilisation results when sows where inseminated with only 1 x 10(9) spermatozoa. Causes of variation in backflow between sows were not clearly identifiable.


Phacoemulsification of dislocated lens and suture fixation of intraocular lens using a perfluorocarbon liquid.
The objective was to describe a new surgical technique to manage a posteriorly dislocated crystalline lens. Four patients with posteriorly dislocated lenses were studied. Two patients had dislocated lenses secondary to trauma, 1 had undergone retinal detachment surgery, and 1 had an idiopathic lens dislocation. Pars plana vitrectomy was carried out on all 4 eyes, followed by an injection of perfluoro-n-octane to float the lens off the retina. The lens was phacoemulsified through a limbal incision, and an intraocular lens was positioned in the ciliary sulcus with suture fixation. Perfluoro-n-octane was replaced by a balanced salt solution. Postoperative visual acuity ranged from 1.0-1.5. Transient choroidal detachment and hypotony were observed in 3 eyes in the early postoperative period. Postoperative ocular hypertension was noted in 2 eyes and was well-controlled with topical antiglaucoma agent. These results indicate that limbal lensectomy of a posteriorly dislocated lens using perfluorocarbon liquids is a beneficial and relatively safe method.


Microstress, mood, and natural killer-cell activity.
The interactions between transient minor negative and positive life events ("microstressors"), concurrent mood states, and immunological functioning were assessed by measuring levels of natural killer-cell activity (NKA), stress, and mood weekly for four weeks. No association was found between the frequency of either positive or negative microstressors and NKA, nor between concurrent mood ratings and NKA. Some individuals showed a marked and unexplained variability in NKA on a week-to-week basis. These results do not support the hypothesis that the minor stresses of everyday living affect immune function. The study does suggest that single cross-sectional determinations of NKA may not be suitable for studies of psychosocial factors and NKA.


Development of Novel Patient-Derived Preclinical Models from Malignant Effusions in Patients with Tyrosine Kinase Inhibitor-Resistant Clear Cell Renal Cell Carcinoma.
Although targeting angiogenesis with tyrosine kinase inhibitors (TKIs) has become standard of care in the treatment of clear cell renal cell carcinoma (RCC), resistance mechanism are not fully understood, and there is a need to develop new therapeutic options overcoming them. To develop a preclinical model that predicts clinical activity of novel agents in 19 RCC patients, we established patient-derived cell (PDC) and xenograft (PDX) models derived from malignant effusions or surgical specimen. Successful PDCs, defined as cells that maintained growth following two passages, were established in 5 of 15 malignant effusions and 1 of 4 surgical specimens. One PDC, clinically refractory to TKIs, was implanted and engrafted in mice, resulting in a comparable histology to the primary tumor. The PDC-PDX model also showed similar genomic features when tested using targeted sequencing of cancer-related genes. When we examined the drug effects of the PDX model, the tumor cells showed resistance to TKIs and everolimus in vitro. The results suggest that the PDC-PDX preclinical model we developed using malignant effusions can be a useful preclinical model to interrogate sensitivity to targeted agents based on genomic alterations.


Volumetric changes of the latissimus dorsi muscle after postoperative chemotherapy in cases of immediate breast reconstruction with an extended latissimus dorsi musculocutaneous flap and implant.
This study aimed to evaluate the volume reduction of latissimus dorsi muscle in patients who underwent immediate breast reconstruction using extended latissimus dorsi musculocutaneous (eLDMC) flap with implant after skin/nipple sparing mastectomy (SSM/NSM) and postoperative chemotherapy (POCTx). We retrospectively reviewed clinical records of 19 patients who underwent this surgery with POCTx, and checked chest computer tomography (CT) at 7-10 days after surgery and 6-14 months after the end of chemotherapy, from May 2015 to October 2016. The motor nerve to latissimus dorsi muscle was severed in all patient. One plastic surgeon intervened and the follow up period was at least 18 months. Author obtained the area of latissimus dorsi muscle using the Picture Archiving and Communication System (PACS) in the axial view of the chest CT and it was verified by the experienced radiologist. The statistical test was performed (P<0.05). There was statistically decrease in latissimus dorsi muscle volume after the end of POCTx, range from 51.5-77.5%, average volume decrease was 62%, compared with latissimus dorsi muscle volume of the CT taken 7-10 days postoperatively (P<0.05). After a minimum follow-up period of 18 months, 14 of the 19 cases were satisfactory for both the surgeon and the patient. In 4 patients, breast volume was symmetrical when wearing bra, but the outline of the 90 cc implant was unfavorable. One patient had a smaller size of reconstructed breast than the other. The size of the implant should be determined considering that average latissimus dorsi muscle reduction is 62%. Especially, the size of the implant should be chosen carefully if latissimus dorsi muscle is thick or it occupies a large portion of the entire flap.


Retinopretectal projections in albino and pigmented rabbits: an autoradiographic study.
The ipsilateral and contralateral retinal projection was studied in pigmented rabbits and in 3 strains of albino rabbits by anterograde transport of [3H]proline and [3H]fucose combined with autoradiographic techniques. Special attention was paid to the terminals in the pretectal area of both the pigmented and albino strains. On the contralateral side terminal labeling was found in both pigmented and albino rabbits in the nucleus of the optic tract (NOT), the anterior pretectal nucleus (PA), the posterior pretectal nucleus (PP) and the pretectal olivary nucleus (PO). Ipsilaterally labeling was found only in the pigmented strain in small patches in the PP. Ipsilateral projection was not found in the albinos in the pretectal area. The results are in agreement with the findings of Scalia in pigmented rabbits. The absence of ipsilateral labeling in the pretectal region in albinos is in contrast with earlier findings of Giolli and Takahashi et al., in pigmented rabbits but is in agreement with the observations of Takahashi and Oyster. Since no radioactively labeled fibers were found to project to the NOT in either pigmented or albino rabbits, these results do not support the hypothesis of Collewijn that the inverted optokinetic nystagmus in albinos is due to misrouting of the ipsilateral retinal fibers to the NOT.


I was being sarcastic!: The effect of foreign accent and political ideology on irony (mis)understanding.
Misunderstood ironic intents may injure the conversation and impede connecting with others. Prior research suggests that ironic compliments, a rarer type of irony, are considered less ironic when spoken with a foreign accent. Using more ecologically-valid stimuli with natural prosodic cues, we found that this effect also applied to ironic criticisms, not just to ironic compliments. English native speakers (N = 96) listened to dialogs between Canadian English speakers and their foreign-accented peers, rating targets on multiple scales (irony, certainty in the speaker's intent, appropriateness, and offensiveness). Generalized additive mixed modelling showed that 1) ironic comments were rated lower for irony when foreign-accented, whereas literal comments were unaffected by accent; 2) the listener's political orientation, but not empathy or need for cognitive closure, modulated irony detection accuracy. The results are discussed in terms of linguistic expectations, social distance, cultural stereotypes, and personality differences.


Does the presence of accompanying symptom clusters differentiate the comparative effectiveness of second-line medication strategies for treating depression?
We explored whether clinical outcomes differ by treatment strategy following initial antidepressant treatment failure among patients with and without clinically relevant symptom clusters. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial was used to examine depression remission and response in patients with coexisting anxiety, atypical features, insomnia, and low energy. We applied propensity scoring to control for selection bias that precluded comparisons between augmentation and switch strategies in the original trial. Binomial regressions compared the likelihood of remission or response among patients with and without symptom clusters for switch versus augmentation strategies (n = 269 per arm); augmentation strategy type (n = 565); and switch strategy type (n = 727). We found no statistically significant difference in remission or response rates between augmentation or switch strategies. However, symptom clusters did distinguish among augmentation and switch strategies, respectively. For patients with low energy, augmentation with buspirone was less likely to produce remission than augmentation with bupropion (remission Risk Ratio (RR): 0.54, 95% CI: 0.35-0.85, response RR: 0.67, 95% CI: 0.43, 1.03). Also, for patients with low energy, switching to venlafaxine or bupropion was less likely to produce remission than switching to sertraline (RR: 0.59, 95% CI: 0.36-0.97; RR: 0.63, 95% CI: 0.38-1.06, respectively). Remission and response rates following initial antidepressant treatment failure did not differ by treatment strategy for patients with coexisting atypical symptoms or insomnia. However, some second-step treatments for depression may be more effective than others in the presence of coexisting low energy. Subsequent prospective testing is necessary to confirm these initial findings.


Erratum: Heart rate variability as a predictor of hypotension after spinal anesthesia in hypertensive patients.
[This corrects the article on p. 317 in vol. 65, PMID: 24228144.].


Psychologic issues in bariatric surgery--the surgeon's perspective.
The consensus that obesity surgery is superior to medical intervention is growing and is supported by abundant evidence. Most patients lose a significant amount of weight, maintain their weightloss long-term, and therefore have improved quality of life with decreased comorbidities and enhanced psychosocial functioning. Despite these benefits from surgery, 5% to 30% of patients lose little weight or are unable to maintain their weight loss postoperatively. This article discusses the psychologic issues involved in bariatric surgery and particularly the absence of psychologically related positive or negative predictors of successful outcome.


Deregulated cell cycle control in lens epithelial cells by expression of inhibitors of tumor suppressor function.
Previous studies have shown that cell cycle proteins such as retinoblastoma protein (pRB) are essential for cell cycle withdrawal in differentiating lens cells. However, little is known about which factors are critical for cell cycle control in the lens epithelial cells. Here we use the K14 promoter to direct expression of E6 and E7, oncogenes from human papillomavirus type 16, which are known to bind and inactivate p53 and pRB, as molecular tools to study cell cycle regulation in the lens epithelium of transgenic mice. Expression of either gene resulted in increased proliferation and apoptosis, and in the case of E6, a unique epithelial phenotype characterized by multilayering and intercellular vacuoles was observed. Lenses from mice expressing E7 mutants, which are defective in inactivating pRB proteins, were normal and the lens phenotype in the E6 mice was p53-independent. Thus, cell proliferation in the lens epithelium is controlled by multiple factors including, but not necessarily limited to, the pRB family.


Immune Reconstitution Inflammatory Syndrome in Aids Patient After Successful Induction of Virological Suppression with Cabotegravir/Rilpivirine.
Long-acting (LA) cabotegravir/rilpivirine (CAB/RPV) is a complete regimen for the management of human immunodeficiency virus type 1 (HIV-1) infection to replace their oral antiretroviral therapy (ART) when they have been virologically suppressed. We present a case of successful achievement of undetectable HIV RNA viral load levels in an acquired immunodeficiency syndrome (AIDS) patient with long-standing virologic failure within two months of CAB/RPV LA initiation. This was later complicated by immune reconstitution inflammatory syndrome (IRIS) due to Mycobacterium avium-intracellulare (MAI) infection and hepatitis B virus (HBV) reactivation. This case highlights the efficacy of monthly CAB/RPV LA in rapidly reducing the HIV viral load level in a poorly controlled patient who lacked significant resistance to the two drugs.This is the first case of IRIS reported in the literature while using CAB/RPV LA. IRIS in the setting of occult MAI is well recognised. It would have occurred with good adherence to any regimen which rapidly suppressed the viral load and is unlikely to be due to CAB/RPV. CAB/RPV has no activity against HBV, which may have contributed to its reactivation.The patient had serologic evidence of resolution of prior HBV. However, some patients have covalently closed circular DNA (cccDNA) that may remain long term in hepatocyte nuclei.


Human papillomavirus infection is rare in nonmalignant tonsil tissue in the UK: implications for tonsil cancer precursor lesions.
The incidence of human papillomavirus (HPV)-associated tonsil cancer is increasing but the prevalence of HPV, and of premalignant precursors, in tonsil tissue is unknown. We aimed to assess prevalence of HPV infection in nonmalignant tonsillar crypt epithelia and to histopathologically characterise positive samples. Formalin-fixed paraffin-embedded (FFPE) tonsil tissue specimens were obtained from an age- and sex-stratified random sample of patients aged 0-69 years whose paired tonsils were archived following elective tonsillectomy at hospitals throughout England and Southern Scotland from 2004 to 2008. Homogenised fresh-frozen tonsil tissue was also obtained from archive for two random subsets of males aged 25-34 and over 44. HPV status was assessed in all samples for 20 mucosal HPV types by GP5+/6+ polymerase chain reaction (PCR) enzyme immunoassay and by HPV16 type-specific PCR targeting the E6 gene. In the homogenised material, HPV status was also assessed for 44 HPV types by SPF10-PCR enzyme immunoassay. Of 4,095 randomly sampled FFPE specimens, amplifiable DNA was extracted from 3,377 (82.5%) and from 511 of 524 (97.5%) homogenised tonsils. HPV DNA was identified in 0 of 3,377 (0%, 95% CI 0-0.089%) fixed samples and 0 of 511 (0%, 95% CI 0-0.58%) homogenised samples. This suggests HPV infection may be rare in tonsil reticulated crypt epithelia. Furthermore, we found no evidence of HPV-associated premalignant neoplasia. These data suggest that if HPV-associated premalignant lesions do occur, they are likely to be rare and may have a high risk of progression to carcinoma.


GILP family: a stress-responsive group of plant proteins containing a LITAF motif.
Lipopolysaccharide-induced tumor necrosis factor-α (LITAF) is a membrane protein that is highly dependent on correct location to exert transcription factor activity and protein quality control. In humans, LITAF, PIG7 (p53-inducible gene 7), and SIMPLE (small integral membrane protein of the lysosome/late endosome) refer to the same gene, which acts as a tumor suppressor. Several studies have shown that the transcription factor activity and nuclear translocation of LITAF protein are critical for the induction of several immune cells via classical pathways. In plants, LITAF protein corresponds to the plasma membrane protein AtGILP (Arabidopsis thaliana GSH-induced LITAF domain protein). The conservation of LITAF proteins across species and their putative role is still unclear. In this study, we investigate the LITAF-containing proteins, which we call GILP proteins, in Viridiplantae. We identified a total of 59 genes in 46 species, whose gene copies range from one to three. Phylogenetic analysis showed that multiple copies were originated via block duplication posteriorly to monocot and eudicot separation. Analysis of the LITAF domain of GILP proteins allowed the identification of a putative domain signature in Viridiplantae, containing a CXXCX41HXCPXC motif. The subcellular location for the majority of GILP proteins was predicted to be in the plasma membrane, based on a transmembrane domain positioned within the LITAF domain. In silico analysis showed that the GILP genes are neither tissue-specific nor ubiquitously expressed, being responsive to stress conditions. Finally, investigation of the GILP protein network resulted in the identification of genes whose families are known to be involved with biotic and/or abiotic stress responses. Together, the expression modulation of GILP genes associated with their plasma membrane location suggests that they could act in the signaling of biotic/abiotic stress response in plants.


Hydrodynamic permeability of aggregates of porous particles with an impermeable core.
A hydrodynamic permeability of membranes built up by porous cylindrical or spherical particles with impermeable core is investigated. Different versions of a cell method are used to calculate the hydrodynamic permeability of the membranes. Four known boundary conditions, namely, Happel's, Kuwabara's, Kvashnin's and Cunningham/Mehta-Morse's, are considered on the outer surface of the cell. Comparison of the resulting hydrodynamic permeability is undertaken. A possible jump of a shear stress at the fluid-membrane interface, its impact on the hydrodynamic permeability is also investigated. New results related to the calculated hydrodynamic permeability and the theoretical values of Kozeny constant are reported. Both transversal and normal flows of liquid with respect to the cylindrical fibers that compose the membrane are studied. The deduced theoretical results can be applied for the investigation of the hydrodynamic permeability of colloidal cake layers on the membrane surface, the hydrodynamic permeability of woven materials.


The basis of niche separation during terrestrial life between two species of toad (Bufo bufo and Bufo calamita): competition or specialisation?
Two congeneric anurans with highly overlapping geographical ranges, Bufo bufo and B. calamita, were investigated with respect to isolating mechanisms during the terrestrial phase of life in the three habitat types in which both species occur in Britain. Marked spatial niche separations were observed in all three habitats (coastal dunes, upper saltmarshes and lowland heaths). B. bufo was associated with complex, dense vegetation structures and had a relatively wide niche, while B. calamita had a narrower niche and occurred mostly on open, poorly-vegetated ground. Food niche overlap was high at all three study sites. Animals translocated into atypical habitats returned to their preferred type whenever possible, and suffered increased mortality or loss of condition if prevented from doing so. B. calamita operated at significantly higher body temperatures (by an average of 1.4° C) than B. bufo when hunting at night. Experiments in outdoor vivaria indicated that B. calamita survived in open habitats because individuals escaped desiccation in daytime by burrowing into the substrate, whereas B. bufo lacked this behaviour and perished on the inhospitable surface. By contrast, B. calamita individuals lost mass and became hyperactive in densely-vegetated conditions because their hunting efficiency was selectively reduced relative to that of B. bufo. Taken together, the data indicated that spatial niche separation between these species during the terrestrial phase of life was dictated primarily by behavioural and physiological factors, and not by competition.


Multimeric immobilization of alcohol oxidase on electrospun fibers for valid tests of alcoholic saliva.
An accurate quantitation of ethanol is of great importance in clinical and forensic analyses. In the current study, alcohol oxidase (AOX) from Pichia pastoris, a multimeric enzyme consisting of eight identical subunits, was immobilized on electrospun polystyrene-co-maleic anhydride (PSMA) fibers for valid tests of alcoholic saliva. Branched polyethyleneimine (PEI) was grafted on PSMA fibers with a density of 0.15 nmol/cm(2) as tethers to allow multipoint covalent binding of enzyme molecules through glutaraldehyde activation, and the secondary and tertiary amino groups of PEI could intensify the interactions with AOX subunits to stabilize the quaternary structure. PSMA-PEI-AOX fibers were less sensitive than free AOX to the incubation temperature and pH, and indicated no detectable subunit release from the immobilized AOX after boiling in the presence of sodium dodecyl sulfate (SDS) and 2-mercaptoethanol. Color strips were established on PSMA-PEI-AOX fibrous mats dyed with indigo Carmine after incubation into ethanol solutions of different concentrations. The color fading ratio remained no significant change after repeat tests for 9 cycles after immersion in 0.2 and 0.8 mg/mL of alcoholic saliva. It was indicated that multipoint immobilization of the multimeric enzyme was essential to improve the enzyme stability by stabilizing both the quaternary structure of the enzyme and the structure of each individual subunit.


A SNP uncoupling Mina expression from the TGFβ signaling pathway.
Mina is a JmjC family 2-oxoglutarate oxygenase with pleiotropic roles in cell proliferation, cancer, T cell differentiation, pulmonary inflammation, and intestinal parasite expulsion. Although Mina expression varies according to cell-type, developmental stage and activation state, its transcriptional regulation is poorly understood. Across inbred mouse strains, Mina protein level exhibits a bimodal distribution, correlating with inheritance of a biallelic haplotype block comprising 21 promoter/intron 1-region SNPs. We previously showed that heritable differences in Mina protein level are transcriptionally regulated. Accordingly, we decided to test the hypothesis that at least one of the promoter/intron 1-region SNPs perturbs a Mina cis-regulatory element (CRE). Here, we have comprehensively scanned for CREs across a Mina locus-spanning 26-kilobase genomic interval. We discovered 8 potential CREs and functionally validated 4 of these, the strongest of which (E2), residing in intron 1, contained a SNP whose BALB/c-but not C57Bl/6 allele-abolished both Smad3 binding and transforming growth factor beta (TGFβ) responsiveness. Our results demonstrate the TGFβ signaling pathway plays a critical role in regulating Mina expression and SNP rs4191790 controls heritable variation in Mina expression level, raising important questions regarding the evolution of an allele that uncouples Mina expression from the TGFβ signaling pathway.


Multichannel matching pursuit of MEG signals for discriminative oscillation pattern detection in depression.
Magnetoencephalography (MEG) power topography may be useful for obtaining discriminative brain activity patterns that can distinguish depressed patients from healthy control subjects at the individual level. However, the application is still limited due to the lack of adequate analysis strategies to remove artifacts from the MEG signals. In this study, the multichannel matching pursuit (MMP) method was designed; in this technique, a linear decomposition method that provides components by iteratively reanalysing a residual signal after removing previously found components,. Forty-four subjects, half depressed patients and half healthy subjects, were recruited for MEG scanning whilst watching a video of sad faces. MMP was implemented to manage multichannel, multi-trial MEG signals. The representative post-MMP analysis signals were utilised to calculate the power topography over the whole brain and designed as inputs for a Support Vector Machine (SVM) classifier. A statistically significant discriminative accuracy of 86% (p=0.002) after a permutation test was achieved. Comparing the system classification performance to that of the ensemble averaging method and the established Independent Component Analysis (ICA), we demonstrated the ability of MMP to represent critical MEG information and, in turn, to mark the abnormality of oscillatory activities under negative stimuli using images of sad faces.


Highly potent multivalent VHH antibodies against Chikungunya isolated from an alpaca naïve phage display library.
Chikungunya virus (CHIKV) is a re-emerged mosquito-borne alphavirus that can cause musculoskeletal diseases, imposing a substantial threat to public health globally. High-affinity antibodies are need for diagnosis and treatment of CHIKV infections. As a potential diagnostic and therapeutic agent, the multivalent VHH antibodies is a promising tookit in nanomedicine. Here, we developed potent multivalent VHH antibodies from an alpaca naïve phage display library targeting the E2 glycoprotein of the CHIKV virus. In the present study, we generated 20 VHH antibodies using a naïve phage display library for binders to the CHIKV E2 glycoprotein. Of these, multivalent VHH antibodies Nb-2E8 and Nb-3C5 had specific high-affinity binding to E2 protein within the nanomolar range. The equilibrium dissociation constant (KD) was between 2.59-20.7 nM, which was 100-fold stronger than the monovalent antibodies' affinity. Moreover, epitope mapping showed that Nb-2E8 and Nb-3C5 recognized different linear epitopes located on the E2 glycoprotein domain C and A, respectively. A facile protocol of sandwich ELISA was established using BiNb-2E8 as a capture antibody and HRP-conjugated BiNb-3C5 as a detection antibody. A good linear correlation was achieved between the OD450 value and the E2 protein concentration in the 5-1000 ng/mL range (r = 0.9864, P < 0.0001), indicating its potential for quantitative detection of the E2 protein. Compared to monovalent antibodies, multivalent VHH antibodies Nb-2E8 and Nb-3C5 showed high affinity and are potential candidates for diagnostic applications to better detect CHIKV virions in sera.


Eradication of HCV by direct antiviral agents restores mitochondrial function and energy homeostasis in peripheral blood mononuclear cells.
Hepatitis C virus (HCV) adopts several immune evasion mechanisms such as interfering with innate immunity or promoting T-cell exhaustion. However, the recent direct-antiviral agents (DAAs) rapidly eliminate the virus, and the repercussions in terms of immune system balance are unknown. Here we compared the PBMCs transcriptomic profile of patients with HCV chronic infection at baseline (T0) and 12 weeks after the end of the therapy (SVR12) with DAAs. 3862 genes were differently modulated, identifying oxidative phosphorylation as the top canonical pathway differentially activated. Therefore, we dissected PBMCs bioenergetic profile by analyzing mitochondrial respiration and glycolysis at 4 timepoints: T0, 4 weeks of therapy, end of therapy (EoT), and SVR12. Maximal and reserve respiratory capacity considerably increased at EoT, persisting until SVR12. Notably, over time a significant increase was observed in respiratory chain (RC) complexes protein levels and the enzymatic activity of complexes I, II, and IV. Mitochondrial-DNA integrity improved over time, and the expression of mitochondrial biogenesis key regulators such as TFAM, Nrf-1, and PPARGC1A significantly increased at SVR12; hence, RC complexes synthesis and mitochondrial respiration were supported after treatment. HCV clearance with DAAS profoundly changed PBMCs bioenergetic profile, suggesting the immunometabolism study as a new approach to the understanding of viral immune evasion mechanisms and host adaptations during infections and therapies.


Fatty acid composition of umbilical arteries and veins: possible implications for the fetal EFA-status.
Fatty acid compositions were determined of phospholipids, isolated from umbilical arteries and veins, obtained from Dutch neonates after vaginal delivery, terminating normal pregnancy. The fatty acid profiles of the cord vessels were characterized by the absence of eicosapentaenoic (timnodonic) acid, a low (2-3%) content of linoleic acid and reasonable amounts of arachidonic acid (10-15%) and docosahexaenoic (cervonic) acid (3-5%). Significant amounts of Mead acid (1-4%) and its direct elongation product (0.5-2%) were also observed. In each cord, the efferent blood vessels contained significantly more Mead acid and other fatty acids of the oleic acid (n-9) family and less fatty acids of the linoleic (n-6) and linolenic (n-3) families than the afferent blood vessel. This indicates that the essential fatty acid (EFA) status of 'downstream' neonatal tissue may be marginal. No signs of EFA-deficiency were observed in endothelial and smooth muscle cells in culture, or in blood vessels from adults. In all cords 22:5(n-6) was significantly higher in the artery compared to the vein, whereas for all other (n-6) fatty acids this difference was negative. Since the synthesis of 22:5(n-6) is known to be stimulated when the required amount of cervonic acid, 22:6(n-3), is too low, our observations also suggest that the cervonic acid status of the neonates investigated was not optimal. Further studies are in progress to relate these findings to maternal EFA status and complications of pregnancy.


Magnetic resonance imaging in occupational chronic solvent encephalopathy.
The aim of this study was to characterize the magnetic resonance imaging (MRI) findings in chronic solvent encephalopathy (CSE) patients and to study whether the findings are associated with solvent exposure indices. The brain MRI scans of 71 CSE patients were independently re-evaluated and rated by two experienced neuroradiologists. All the work tasks were analyzed and the chemical composition of lifetime exposure was categorized. The MRI scans of 27/71 CSE patients (38%) were classified as abnormal. Brain atrophy in any brain area was found in 17/71 CSE patients (24%). Abnormal white matter hyperintensities (WMH) were found in 20/71 CSE patients (28%). Cerebral and cerebellar brain atrophy was associated with the duration of exposure in years, and vermian atrophy was associated with alcohol consumption. Periventricular and brainstem WMH were related to age. Slight brain atrophy is associated with CSE and there is a correlation between brain atrophy and the duration of exposure in years. However, all the MRI findings in CSE are non-specific and thus MRI is useful mainly in the differential diagnosis of CSE.


Artificial feeding Rice stripe virus enables efficient virus infection of Laodelphax striatellus.
Rice stripe virus (RSV), the causative agent of rice stripe disease, is transmitted by Laodelphax striatellus in a persistent-propagative manner. Efficient virus acquisition is primary for studies of virus transmission and virus-insect vector interactions. However, under greenhouse conditions, less than 30% of the L. striatellus population, on average, become viruliferous during feeding on RSV-infected plants. Here, we explored a method for efficient RSV acquisition by feeding the insects with a virus-containing artificial diet. Virus particles were partially purified from frozen infected rice leaves. A series of RSV concentrations in a 5% sucrose solution were tested in the feed of L. striatellus nymphs. The percentage of infected insects increased along with the increasing viral concentration, and the highest infection percentage 96% was achieved using a 1200ngμL(-1) crude RSV suspension after 48h feeding. RSV particles acquired in this manner were able to spread to L. striatellus salivary glands. This improved method of obtaining viruliferous insects should assist the study of RSV transmission mechanisms in L. striatellus.


Urethral Meatus and Glanular Closure Line: Normal Biometrics and Clinical Significance.
Purpose: The aim of this study is to explore the normal external urethral meatal and glans closure line in normal boys, and to investigate the correlation between these glans biometrics and the age of the participants. 103 male children were asked to participate in the study during ritual circumcision. Par-ents of 94 of them (mean age 5.9 years, range 0.6-13) accepted while remaining 9 did not. Glans biometrics were measured using digital calipers. 100% of the study participants had a vertical slit-like meatal opening located at the tip of the glans. The length of the meatal opening was 5.3 (± 1) mm and of ventral glans closure was 4.8 (±1.1) mm. Significant cor-relation between both the external meatal opening and closure lines lengths and age was observed. Moreover, the meatal opening size was correlated to the glans closure line as well (r = 0.36, confidence interval 0.14-0.54, P < .001). The site and size of the meatus opening in normal male children is consistent, and ventral glans clo-sure is equal to or slightly less than meatal length. These findings could aid in glanular reconstruction configuration during hypospadias surgery.


Prognosis of ovarian cancer subsequent to venous thromboembolism: a nationwide Danish cohort study.
Venous thromboembolism (VTE) is associated with ovarian cancer and may impact the prognosis of ovarian cancer. Our aims were to examine the extent of disease at the time of the diagnosis of ovarian cancer and to estimate the impact of VTE on survival of ovarian cancer. We identified 12,835 ovarian cancer patients diagnosed from 1980 to 2003 in the Danish Cancer Registry and obtained information on previous primary VTE diagnosis from the Danish National Hospital Discharge Registry. Ovarian cancer patients with previous VTE related to other cancers, surgery, or pregnancy were excluded. The vital status was determined by linking data to the Civil Registration System. We identified 50 ovarian cancer patients diagnosed less than 4 months after the VTE and 78 ovarian cancer patients diagnosed more than 4 months after the VTE diagnosis. Advanced stages tended to be more common among patients with VTE. One-year survivals were 44% and 54% among the two VTE groups, compared with 63% among patients without VTE. Adjusted (for age, calendar time, comorbidity, and FIGO-stage) mortality ratios were 1.7 (95% CI = 1.2-2.5) and 1.2 (95% CI = 0.8-1.7), respectively. Ovarian cancer diagnosed less than four months before VTE is associated with an advanced stage and a poorer prognosis.


Regulation of calcium channel activity by lipid domain formation in planar lipid bilayers.
The sarcoplasmic reticulum channel (ryanodine receptor) from cardiac myocytes was reconstituted into planar lipid bilayers consisting of 1-palmitoyl-2-oleoyl-phosphatidylethanolamine (POPE) and 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) in varying ratios. The channel activity parameters, i.e., open probability and average open time and its resolved short and long components, were determined as a function of POPE mole fraction (X(PE)) at 22.4 degrees C. Interestingly, all of these parameters exhibited a narrow and pronounced peak at X(PE) approximately 0.80. Differential scanning calorimetric measurements on POPE/POPC liposomes with increasing X(PE) indicated that the lipid bilayer enters a composition-driven transition from the liquid-crystalline state to the gel state at 22.4 degrees C when X(PE) approaches 0.80. Thus, the peaking of the reconstituted channel activity at X(PE) approximately 0.80 in the planar bilayer could result from the appearance of gel/liquid-crystalline domain boundaries at this POPE content. Lipid packing at domain boundaries is known to be looser as compared to the homogenous gel or liquid-crystalline state. We propose that the attractive potential of packing defects at lipid domain boundaries and entropic excluded-volume effects could result in the direct interactions of the transmembrane region of the channel protein with the lipid-packing defects at the lipid/protein interface, which could thus provide a favorable environment for the open state of the protein. The present findings indicate that the activity of the sarcoplasmic reticulum calcium channel could be modulated by lipid domain formation upon slight changes in membrane lipid composition in vivo.


Cinnamic aldehyde in toothpaste. 1. Clinical aspects and patch tests.
Although cinnamon is known to cause dermatitis in bakers and confectioners, it has only rarely been reported as causing trouble in food or cosmetics. A newly-formulated 'spicy' toothpaste containing cinnamon as a flavouring agent was the cause of oral symptoms in eight patients referred to clinics in Buckinghamshire and in Malmö and in a further eight patients discovered subsequently. Similar symptoms and patch test results were observed independently at both centres. Positive reactions were obtained with 1% cinnamic aldehyde in 15 out of 16 patients tested. Only one patient reacted to a standard sample of balsam of Peru (25% in petrolatum).


Author's response.
I am grateful to Andrew Leaver in his role as chairman of the NSW Chapter of Musculoskeletal Physiotherapy Australia for raising issues pertinent to our paper. It is this interest that encourages debate and helps to evolve further the ideas on a topic that has not been investigated previously.


Effect of Preoperative Oral Carbohydrate Administration on Patients Undergoing Cesarean Section with Epidural Anesthesia: A Pilot Study.
The aim of this study was to evaluate the effect of preoperative oral carbohydrate administration on patients undergoing Cesarean section with epidural anesthesia. Randomized controlled clinical study. A total of 75 patients undergoing Cesarean section (American Society of Anesthesiologists physical status grade I-II) were randomized to preparation with a carbohydrate drink (CHO group), flavored water (placebo group), or to the fasting group. The CHO and placebo groups were double-blinded and given 300 mL of the drink 2 hours before surgery. Visual analog scores of the patient were assessed to evaluate thirst, hunger, and anxiety level, and the gastric antral cross-sectional areas were recorded by ultrasonography during the operative period. Insulin resistance was calculated on the basis of the blood glucose and insulin levels assessed before administration and after surgery. The CHO and placebo groups did not show an increase in gastric fluid volumes in terms of gastric antral cross-sectional area, and there were no adverse events. The visual analog scale scores at preoperative baseline were not different between groups . During the preoperative waiting period, preparation with CHO reduced not only thirst and anxiety more efficiently than water (placebo) but also hunger (P < .05), whereas water did not. No difference was observed in insulin resistance between groups before intake of the drink. Compared with the preoperative levels, insulin resistance showed a statistically significant increase in all groups (P < .05); however, the increase was significantly higher in the fasting and placebo groups than in the CHO group (P < .05). Preoperative administration of CHO decreases postoperative insulin resistance and enhances pregnant women's comfort, leading to a reduced sense of thirst, hunger, and anxiety during the preoperative period for Cesarean section.


Propeller flaps for leg reconstruction.
Leg soft tissue defects with bone or tendon exposure need to be covered with a flap. Various local and free flaps with more or less consistent donor site defects have been described in the past. After the introduction of the perforator-based flap concept, new flaps have also been described for the leg. An evolution and simplification of the perforator flap concept, together with the 'free style' flap harvesting method, are the propeller flaps, i.e. local flaps, based on a perforator vessel, which becomes the pivot point for the skin island that can, therefore, be rotated up to 180 degrees . In this prospective study, six consecutive patients, having post-traumatic soft tissue defects of the leg or knee prosthesis infection, with bone or tendon exposure, were treated with propeller flaps. Complete and stable coverage of the soft tissue losses was obtained in all cases with an inconspicuous, only cosmetic, donor site defect. No flap necrosis was observed, with the exception of a small superficial necrosis of the tip of one flap, due to the inclusion in the design of scarred tissue. In two cases, transient venous congestion was observed and resolved spontaneously. Mean operative time was 2 h (ranging from 60 min to 6 h when an orthopaedic procedure was also needed) and mean hospital stay after surgery was 10 days. Propeller flaps allow the coverage of wide defects, can be raised with a relatively simple surgical technique, have a high success rate and good cosmetic results without functional impairment. In the light of this they can be considered among the first surgical choices to resurface complex soft tissue defects of the leg.


Biochemical testing for the diagnosis of Wilson's disease: A systematic review.
Wilson's disease (WD) is a rare inherited disorder that leads to copper accumulation in the liver, brain, and other organs. WD is prevalent worldwide, with an occurrence of 1 per 30,000 live births. Currently, there is no gold standard diagnostic test for WD. The objective of this systematic review is to determine the diagnostic accuracy for WD of three biochemical tests, namely hepatic copper, 24-hour urinary copper, and ceruloplasmin using the Leipzig criteria. Adhering to PRISMA guidelines, databases including PubMed/MEDLINE, CINAHL Plus, Web of Science, and Cochrane were searched. Studies that comprised of confirmed or suspected WD along with normal populations were included with adult and pediatric group. The sensitivity, specificity, negative predictive value and positive predictive value were computed using RevMan 5.4. Nine studies were included. The best practice evidence for 24-hour urinary copper test ranged from a cutoff value of 0.64-1.6 μmol/24 h (N = 268; sensitivity = 75.6%, specificity = 98.3%). Hepatic copper test was optimally cutoff based on the ROC curve analysis at 1.2 μmol/g yielding a power of 96.4% sensitivity and 95.4% specificity (N = 1,150); however, the tried and tested 4 μmol/g cutoff, with 99.4% sensitivity and 96.1% specificity, is more widely accepted. The ceruloplasmin test cutoff value was found to be ranging from 0.14 to 0.2 g/L (N = 4,281; sensitivity = 77.1%-99%, specificity = 55.9%-82.8%). This paper provides a large-scale analysis of current evidence pertaining to the biochemical diagnosis of WD employing the Leipzig criteria. The laboratory values are typically based on specific subgroups based on age, ethnicity, and clinical subgroups. The findings of this systematic review must be used with caution, given the over- or under-estimation of the index tests.


Examining the relationship between community mobility and participation using GPS and self-report data.
Higher levels of community mobility have been shown to be associated with better physical health, mental health, and quality of life. The ability to move about one's community is also expected to facilitate community participation, which is an aspect of health functioning. This study uses Global Positioning Systems (GPS) technology to track various dimensions of community mobility, such as destinations, time outside the home, and distance traveled, and examine the relationship between these variables and community participation in a sample of individuals with serious mental illnesses (SMI). This population was selected because they are known to have diminished health functioning in terms of their community participation, and the goal is to explore the extent to which mobility limitations may account for this. A total of 103 individuals with serious mental illnesses were recruited from mental health agencies and consented to having their mobility tracked using GPS for 13 days and answering questions about their community-based activities. Greater amount of participation was associated with having more destinations and spending more time out of the house, but not with traveling larger distances and having a greater activity space. None of the mobility variables were related to the number of important participation areas or sufficiency of participation. The findings support the hypothesis that greater mobility is related to more participation, although satisfaction with the degree to which one participates does not appear to be impacted, suggesting that other factors need to be accounted for. Health policymakers and providers should pay attention to community mobility as a factor that affects health outcomes such as participation, in individuals with serious mental illnesses, and other populations. In particular, attending to access to personal transport, public transportation, and other mobility options appears to be important, as well as interventions aimed at encouraging greater community mobility.


Fast isolation of highly specific population of platelet-derived extracellular vesicles from blood plasma by affinity monolithic column, immobilized with anti-human CD61 antibody.
A new, fast and selective immunoaffinity chromatographic method including a methacrylate-based convective interaction media (CIM®) disk monolithic column, immobilized with anti-human CD61 antibody, was developed for the isolation of CD61-containing platelet-derived extracellular vesicles (EVs) from plasma. The isolated EVs were detected and size characterized by asymmetrical flow field-flow fractionation (AsFlFFF) with multi-angle light-scattering (MALS) and dynamic light-scattering (DLS) detection, and further confirmed by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM). The mean size of platelet-derived EV isolates from the anti-CD61 CIM® disk monolithic column were 174 nm (SD 60 nm) based on the NTA results. These results indicated a successful isolation of platelet-derived EVs, which was confirmed by Western blotting the isolates against the EV-specific markers CD9 and TSG101 together with transmission electron microscopy. Additional elucidation of MALS and DLS data provided detailed information of the size distribution of the isolated fractions, confirming the successful isolation of also small platelet-derived EVs ranging from 30 to 130 nm based on the hydrodynamic radii. The isolation procedure took only 19 min and the time can be even further decreased by increasing the flow rate. The same immunoaffinity chromatographic procedure, following AsFlFFF allowed also the isolation and characterization of platelet-derived EVs from plasma in under 60 min. Since it is possible to regenerate the anti-CD61 disk for multiple uses, the methodology developed in this study provides a viable substitution and addition to the conventional EV isolation procedures.


Peripheral T-cell lymphoma - are we making progress?
Peripheral T cell lymphoma (PTCL) is a rare subtype of non-Hodgkin lymphoma. PTCLs are heterogeneous in terms of biology, but generally have more aggressive features and poorer outcomes than aggressive B-cell lymphomas when treated with combination chemotherapy. While the best long-term results are still seen with intensive chemotherapeutic approaches, significant progress has been made with molecular profiling identifying genetic drivers of PTCL that could serve as therapeutic targets. Tailoring therapy to different subtypes of PTCL may lead to more individualized approaches with the hope of improved outcomes. In this paper, we review current therapies for treatment of PTCL, newly identified molecular markers, and the role of emerging therapy and novel combinations of existing agents.


From the Au nano-clusters to the nanoparticles on 4H-SiC (0001).
The control over the configuration, size, and density of Au nanoparticles (NPs) has offered a promising route to control the spatial confinement of electrons and photons, as a result, Au NPs with a various configuration, size and density are witnessed in numerous applications. In this work, we investigate the evolution of self-assembled Au nanostructures on 4H-SiC (0001) by the systematic variation of annealing temperature (AT) with several deposition amount (DA). With the relatively high DAs (8 and 15 nm), depending on the AT variation, the surface morphology drastically evolve in two distinctive phases, i.e. (I) irregular nano-mounds and (II) hexagonal nano-crystals. The thermal energy activates adatoms to aggregate resulting in the formation of self-assembled irregular Au nano-mounds based on diffusion limited agglomeration at comparatively low annealing temperature, which is also accompanied with the formations of hillocks and granules due to the dewetting of Au films and surface reordering. At high temperature, hexagonal Au nano-crystals form with facets along {111} and {100} likely due to anisotropic distribution of surface energy induced by the increased volume of NPs. With the small DA (3 nm), only dome shaped Au NPs are fabricated along with the variation of AT from low to elevated temperature.