Characterization of a recurrent poor-quality embryo morphology phenotype and zygote transfer as a rescue strategy.
Some patients in IVF programmes repeatedly display an abnormal embryonic development characterized as soon as day 2 post fertilization by a high rate (>60%) of highly fragmented embryos (⩾40% of cytoplasmic fragments) leading to recurrent IVF failures. This study postulated that, for various maternal reasons, some embryos were unable to withstand the in-vitro environment and an early pronucleate-stage transfer was proposed to these couples. Fifty-three patients with recurrent IVF failures (a mean of 2.8±1.0 previous attempts) characterized by low embryonic quality (a mean of 62.7% of the embryos with extended fragmentation) were included this transfer protocol. As in previous cycles, the mean number of oocytes retrieved and the fertilization rate were normal. The mean number of zygotes per transfer was 2.24. Fourteen clinical pregnancies were obtained, representing a pregnancy rate and a delivery rate per oocyte retrieval of 26.4% and 18.9%, respectively. Recurrent heavy and early embryo fragmentation in vitro characterizes around 3% of IVF couples and leads to lack of transfer or implantation failure. These data on fresh zygote transfers are encouraging and may provide a valid alternative solution for some of these patients. Some patients in IVF programmes repeatedly display an abnormal embryonic development characterized as soon as day 2 post fertilization by a high rate of highly fragmented embryos, leading to recurrent IVF failures. We hypothesized that, for various reasons, some embryos were unable to withstand the in-vitro environment and an early pronucleate stage transfer was proposed to these couples. Fifty-three patients with recurrent IVF failures characterized by low embryonic quality were included in this transfer protocol. As in previous cycles, the mean number of oocytes retrieved and the fertilization rate were normal. The mean number of zygotes per transfer was 2.24. Fourteen clinical pregnancies were obtained, representing a pregnancy rate and a delivery rate per oocyte retrieval of 26.4% and 18.9%, respectively. Recurrent early and heavy embryo fragmentation in vitro characterizes around 3% of IVF couples and leads to lack of transfer or implantation failure. Our data on fresh zygote transfers are encouraging and may provide a valid alternative solution for these patients.


Critical Analysis of Interventional Research Designs to Promote Coping in Pediatric Patients.
The purpose of this article is to analyze the strengths and limitations of research designs of studies implementing coping based training interventions in adolescents. Quantitative and mixed methods studies were selected and reviewed for critical analysis of strengths, limitations, and validity concerns. Methodological strengths and weaknesses were assessed. The major limitation to the studies reviewed is selection bias in both quasi-experimental studies and randomized controlled trials. Improved coping strategies and skills were found in participants of coping skill training intervention programs. Decreased depressive symptoms and less impact of individual disease burden was found in the treatment intervention groups.


Evaluation of a new monoclonal antibody reagent for the detection of herpes simplex virus from clinical specimens.
A reformulated fluorescein isothiocyanate conjugate-labeled monoclonal antibody typing reagent for herpes simplex virus (HSV) was compared for culture confirmation and typing with a similar commercially available HSV typing stain. There was complete agreement between the two stains in the confirmation of 240 cultures for HSV-50 negative specimens and 190 positive specimens (66 type 1 and 124 type 2). The stains were equivalent in brilliance and clarity for both HSV types, with no cross-reactivity or background staining. In addition, the PathoDx stains were also mixed 1:1 with each other to form a "bivalent" stain. This mixture again identified all 190 positive cultures and 50 negative cultures with fluorescence of equal caliber to each of the individual reagents.


Clinical characteristics of Kawasaki disease in Polish children: A retrospective study.
Kawasaki disease (KD), an acute, generalized vasculitis, is associated with an increased risk of coronary heart disease and is the most common cause of acquired heart disease in childhood. The incidence of KD is increasing worldwide. Our study aims to analyze KD's clinical course in children and to evaluate risk factors for persistent changes in coronary vessels after 6-8 weeks of treatment. The retrospective analysis included patients with KD hospitalized in a single tertiary carehospital. The diagnosis, as well as treatment, were based on the current worldwide treatment standards. The clinical course, selected laboratory parameters, the treatment effect, and following cardiac complications were analyzed in different age groups. In the years 2006-2019, 140 patients aged from two months to 16 years: 52 girls and 88 boys, were diagnosed with KD. Coronary artery aneurysms (CAA) at weeks 6-8 of disease were found in 16% of patients. Boys and infants were more likely to develop aneurysms at weeks 6-8 of the disease (P = 0.045; P = 0.03; respectively). The CAA frequency was related to the atypical course (P = 0.02), late diagnosis (P = 0.04), presence of changes in the coronary arteries at the time of diag nosis (P<0.001), immunoglobulin resistance (P = 0.002), a lower hemoglobin concentraction (P<0.001), and a higher platelet count (P = 0.02). There were 28% of patients resistant to first-line time treatment. In this group, we found CAA in 31% of children. We found that late diagnosis, low hemoglobin level, high platelet count, CAA presence at diagnosis, atypical course of KD, and resistance to intravenous immunoglobulins are predictors of CAA after 6-8 weeks in KD patients.


Identification of live cells for flow cytometric analysis of lymphoid subset proliferation in low viability populations.
Combined analysis of single cell DNA content and immunofluorescence by flow cytometry is complementary to tritiated thymidine analysis of cellular proliferation, allowing detailed dissection of particular cell types in a mixed population which respond proliferatively to selective stimuli. However, in vitro culture of primary immune cells (e.g., mouse spleen or lymph node) for periods of 24-72 h frequently results in a considerable fraction of non-viable cells which bind antibodies non-specifically, resulting in altered immunofluorescence distributions, inaccurate distinctions between positive and negative cells, and sometimes in misleading DNA distributions. Forward angle light scatter cannot readily be used to distinguish live from dead cells in this case because of the heterogeneous size distributions characteristic of cultured populations. We describe a method which uses treatment with DNAase prior to immunofluorescence staining to allow more accurate distinction between live and dead cells. This treatment markedly reduces the intensity of DNA staining for non-viable cells, providing complete live/dead discrimination and improved ability to analyze the proliferative status of specific cell subtypes in low viability cultures.


Assessing the effect of PRP addition to facial micro-lipofilling for patients suffering from Scleroderma: A prospective routine care analysis.
Combining fat graft with platelet derived products is now common practice in regenerative surgery. We proposed to assess the safety and efficacy of Platelet-Rich Plasma (PRP) addition to a micro-lipofilling protocol for facial treatment of patients suffering from Systemic Sclerosis (SSc). Main objective was to evaluate the improvement of the Mouth Handicap In Systemic Sclerosis (MHISS) scale score at 6 months post-therapy. Included SSc patients had a MHISS score equal or up to 20. Surgery was performed under general anesthesia. Micro-fat and PRP (CCA-NA from DEPA Classification) were mixed in a 70/30 ratio, before injection in peri-oral sites according to a specific protocol. Efficacy criteria were recorded at baseline, 3 and 6 months. Moreover, we compared this cohort (current study) to a former (2015) non-enriched micro-lipofilling cohort in the same indication, using the same protocol. Thirteen women patients with mean age of 53.2 years (±14.3) have been included. At baseline, mean MHISS score was 29.5 (±8.7) and significantly decreased to 22.5 (±7.8) at 6 months (P=0.016), corresponding to a 22.0% of improvement from baseline, with a mean decrease of 6.5 points (±7.5) at 6 months. Patients received a mean volume of 30.8ml PRP-micro-fat (±8.1ml). PRP addition appeared beneficial, however, controlled studies are required to determine its superiority to facial micro-lipofilling.


Chemoenzymatic synthesis of trans-tetrahydrofuran cores of annonaceous acetogenins from bromobenzene.
Two types of trans-THF cores, present in acetogenins, have been synthesized by an intramolecular iodoetherification reaction. The starting alkenol was obtained in a few steps from a chiral cis-diol resulting from microbial oxidation of bromobenzene. The cyclization gave complete stereoselectivity for trans-THF cores with either (S,S) or (R,R) configurations at the THF chiral carbons.


Urothelial effects of oral agents for overactive bladder.
The cholinergic system of the bladder includes muscarinic receptors distributed to detrusor myocytes and structures within mucosa including bladder afferent (sensory) nerves. The receptors have been shown to be involved in afferent signaling from the bladder, but it has not been established to what extent effects on this mucosal signaling pathway contribute to the therapeutic efficacy of the clinically used antimuscarinics. Mucosa can be influenced by antimuscarinics via the bloodstream. However, some antimuscarinics and their active metabolites are excreted in urine in amounts that may affect the mucosal muscarinic receptors from the luminal side. This has not yet been demonstrated to imply superior clinical efficacy. Nevertheless, mucosal afferent signaling pathways are therapeutically interesting targets that should be further explored.


Discovery of a novel, orally active himbacine-based thrombin receptor antagonist (SCH 530348) with potent antiplatelet activity.
The discovery of an exceptionally potent series of thrombin receptor (PAR-1) antagonists based on the natural product himbacine is described. Optimization of this series has led to the discovery of 4 (SCH 530348), a potent, oral antiplatelet agent that is currently undergoing Phase-III clinical trials for acute coronary syndrome (unstable angina/non-ST segment elevation myocardial infarction) and secondary prevention of cardiovascular events in high-risk patients.


Latin American Older people and neuropsychiatric symptoms: a mini-systematic review of effects of COVID-19 Pandemic.
Ending December 2019, the world had to face to COVID-19. Latin America and the Caribbean suffered the effects where the contiguous and the number of deaths has been significant. Studies indicate that older adults with some degree of cognitive impairment are at greater risk of worsening their cognitive status and mental health, for this reason it's exposed that social isolation and loneliness has harmful effects on the health of this population. This mini-review inquires on the effects of COVID-19 due to social isolation on neuropsychiatric symptoms (NPS) in Latin American older adults with and without dementia. A search was carried out in PubMed, SCOPUS, and ScienceDirect identifying all articles published up to July 31, 2021 using the keywords "social isolation", "lockdown", "quarantine", "COVID-19",, "neuropsychiatric symptoms ", "neurobehavioral", "dementia"," mild cognitive impairment "," Older People ", "aging", "elderly". Two independent reviewers screened and selected appropriate articles and a third researcher helped resolve disagreements. The selected articles met the following criteria: written in English, Spanish or Portuguese, original article; focused on elderly subjects, articles that provided information on the NPS effects in Latin American populations during the COVID-19 pandemic. The review was based on the PRISMA Statement and used the SIGN criteria. From 61 articles recovered from electronic databases (PubMed, Science Direct and Scopus) 10 of them were chosen for this review. The majority of the articles reported in a general way a negative impact on the mental health of the population in Latin America. They referred to a significant increase in the anxiety and depression symptoms. The majority of the articles were studies developed in Brazil, Argentina and Chile. The COVID-19 has shown a negative impact on the mental health of older adults. Latin America is a region with important socio-sanitary problems which increase the impact of the pandemic in SNP, especially in older adults. It's necessary to increase the studies in Latin America that glimpse the real situation in the region.


Sex differences in spatial task performance of patients with and without unilateral cerebral lesions.
Two visuospatial tasks, the WAIS Block Design and the Street Gestalt Completion Test, were administered to men and women with and without unilateral cerebral lesions. These two tasks represent different categories of visuospatial functions. The Street test is a visual-perceptual gestalt task, requiring the closure of fragmented pictures, whereas Block Design is an analytical, manipulospatial task requiring rotation of spatial coordinates. For the non-brain-damaged group, the men showed a nonsignificant trend toward better Block Design performance relative to the women, whereas there was no sex-related difference in Street performance. For the brain-damaged groups, patients with right hemisphere lesions performed significantly worse than patients with left hemisphere lesions on both the Street test and Block Design, indicating that both tasks were more sensitive to right hemisphere functioning. There was, however, a significant sex X side of lesion interaction on Block Design only, with the men showing a more asymmetrical pattern of scores. These results suggest that sex differences in functional lateralization may underlie sex differences in visuospatial ability, and that sex differences in functional lateralization may be present for only certain visuospatial processes.


Trends over the recent 6 years in ablation modalities and strategies, post-ablation medication, and clinical outcomes of atrial fibrillation ablation.
Ablation strategies and modalities for atrial fibrillation (AF) have transitioned over the past decade, but their impact on post-ablation medication and clinical outcomes remains to be fully investigated. We divided 682 patients who had undergone AF ablation in 2014-2019 (420 paroxysmal AFs [PAF], 262 persistent AFs [PerAF]) into three groups according to the period, that is, the 2014-2015 (n = 139), 2016-2017 (n = 244), and 2018-2019 groups (n = 299), respectively. Persistent AF became more prevalent and the left atrial (LA) diameter larger over the 6 years. Extra-pulmonary vein (PV)-LA ablation was more frequently performed in the 2014-2015 group than in the 2016-2017 and 2018-2019 groups (41.1% vs. 9.1% and 8.1%; p < .001). The 2-year freedom rate from AF/atrial tachycardias for PAF was similar among the three groups (84.0% vs. 83.1% vs. 86.7%; p = .98) but lowest in the 2014-2015 group for PerAF (63.9% vs. 82.7% and 86.3%; p = .025) despite the highest post-ablation antiarrhythmic drug use. Cardiac tamponade was significantly decreased in the 2018-2019 group (3.6% vs. 2.0% vs. 0.33%; p = 0.021). There was no difference in the 2-year clinically relevant events among the three groups. Although ablation was performed in a more diseased LA and extra-PV-LA ablation was less frequent in recent years, the complication rate decreased, and AF recurrences for PAF remained unchanged, but that for PerAF decreased. Clinically relevant events remained unchanged over the recent 6 years, suggesting that the impact of the recent ablation modalities and strategies on remote clinically relevant events may be small during this study period.


A training model for lumbar discectomy.
Training models are becoming increasingly important for gaining surgical skills. We present an easy to prepare and cheap model using cadaver sheep spine appropriate to learn and practice various discectomy procedures.


Screening of and mechanism underlying the action of serum- and glucocorticoid-regulated kinase 3-targeted drugs against estrogen receptor-positive breast cancer.
Breast cancer is the most common cancer in women. Serum and glucocorticoid-regulated kinase 3 (SGK3) promotes the progression and drug resistance of estrogen receptor-positive (ER+) breast cancer. Therefore, SGK3 is a promising therapeutic target for the treatment of ER + breast cancer. In this study, we used computer-aided drug discovery/design to perform a virtual screening of SGK3 inhibitors from the ZINC database. The results of MTT assay, real-time cell proliferation analysis, colony formation assay, transwell migration assay, and orthotopic implantation model show that Zinc-09 inhibited the proliferation and migration of ER + breast cancer cells in vivo and in vitro. Furthermore, Zinc-09 decreased SGK3 expression, and knockdown of SGK3 by siRNA reversed the inhibitory effect of Zinc-09 in MCF-7 cells. Moreover, Zinc-09 treatment induced G1 phase arrest and autophagic cell death. Taken together, Zinc-09 can suppress ER + breast cancer. This study provides an experimental and theoretical basis for the research and development of new anti-ER + breast cancer drugs.


Stepping towards highly flexible aptamers: enzymatic recognition studies of unlocked nucleic acid nucleotides.
Enzymatic recognition of unlocked nucleic acid (UNA) nucleotides was successfully accomplished. Therminator DNA polymerase was found to be an efficient enzyme in primer extension reactions. Polymerase chain reaction (PCR) amplification of a 81 mer UNA-modified DNA library was efficiently achieved by KOD DNA polymerase.


Ruptured Infantile Myofibroma of the Head Presenting in a Neonate: Case Report and Review of the Literature.
Infantile myofibroma/myofibromatosis (IM/M) is a myofibroblastic proliferative disorder often seen in infants and children. IM/M can result in congenital tumors of the head and neck and may occasionally present to the neurosurgeon. We report a case of a solitary ruptured myofibroma of the head in a newborn patient. The lesion was initially suggestive of encephalocele. We describe the presentation and management of this patient, including relevant imaging, histopathologic evaluation, and surgical technique. We subsequently review the literature of IM/M of the head and neck, highlighting the 3 forms of the condition, each requiring a distinct management strategy. Although this tumor rarely presents to the neurosurgeon, it may do so in the process of ruling out other more dangerous conditions. It is therefore important to consider this diagnosis in masses that occur in the head and neck of newborns.


Evaluation of the efficacy of animal-assisted therapy based on the reality orientation therapy protocol in Alzheimer's disease patients: a pilot study.
The aim of this study was to evaluate the efficacy of animal-assisted therapy (AAT) in elderly patients affected by Alzheimer's disease based on the formal reality orientation therapy (ROT) protocol. Our study was carried out at an Alzheimer's centre for 6 months. A homogeneous sample (age, Mini-Mental State Examination (MMSE), 15-item Geriatric Depression Scale (GDS)) of 50 patients was selected at random and successively. Patients were divided into three groups: (i) 20 patients received a course of AAT (AAT group) based on the ROT protocol; (ii) 20 patients were engaged exclusively in activities based on the ROT group; and (iii) 10 patients (control group) participated in no stimulations. MMSE and GDS were administered at time 0 (T0 ) and time 1 (T1 ) to all three groups. Differences within groups between T0 and T1 for GDS and MMSE scores were analyzed by Student's t-test. Differences between group means were analyzed using an anova test with the Bonferroni-Dunn test for post-hoc comparisons. Both the AAT group and ROT group had improved GDS scores and showed a slight improvement in terms of mood. On the GDS, the AAT group improved from 11.5 (T0 ) to 9.5 (T1 ), and the ROT group improved from 11.6 (T0 ) to 10.5 (T1 ). At the same time, a slight improvement in cognitive function, as measured by the MMSE, was observed. In the AAT group, mean MMSE was 20.2 at T0 and 21.5 at T1 , and in the ROT group, it was 19.9 at T0 and 20.0 at T1 . In the control group, the average values of both the GDS and MMSE remained unchanged. The Bonferroni-Dunn results showed statistically significant differences between groups, particularly between the AAT group and the other two (P < 0.001). Pet therapy interventions based on the formal ROT protocol were effective and, compared to the ROT, provided encouraging and statistically significant results.


Identification of a novel cathelicidin antimicrobial peptide from ducks and determination of its functional activity and antibacterial mechanism.
The family of antimicrobial peptide, cathelicidins, which plays important roles against infections in animals, has been identified from many species. Here, we identified a novel avian cathelicidin ortholog from ducks and named dCATH. The cDNA sequence of dCATH encodes a predicted 146-amino-acid polypeptide composed of a 17-residue signal peptide, a 109-residue conserved cathelin domain and a 20-residue mature peptide. Phylogenetic analysis demonstrated that dCATH is highly divergent from other avian peptides. The α-helical structure of the peptide exerted strong antimicrobial activity against a broad range of bacteria in vitro, with most minimum inhibitory concentrations in the range of 2 to 4 μM. Moreover, dCATH also showed cytotoxicity, lysing 50% of mammalian erythrocytes in the presence or absence of 10% fetal calf serum at concentrations of 32 μM or 20 μM and killing 50% HaCaT cells at a concentration of 10 μM. The effects on bacterial outer and inner membranes, as examined by scanning electron microscope and transmission electron microscopy, indicate that dCATH kills microbial cells by increasing permeability, causing a loss of membrane integrity.


Synthesis, structure, and emissive properties of copper(I) complexes [CuI2(micro-X)2(micro-1,8-naphthyridine)(PPh3)2] (X=I, Br) with a butterfly-shaped dinuclear core having a short Cu-Cu distance.
New dinuclear copper(I) complexes [Cu2(micro-X)2(micro-1,8-naphthyridine)(PPh3)2] (X=I, Br) having the butterfly-shaped {Cu2(micro-X)2} unit show red phosphorescence at room temperature in the solid state. Molecular orbital calculations show that the emissions of the new complexes are not directly related to their short Cu...Cu separations [2.6123(5) and 2.6271(4) A] and are assignable to the triplet charge-transfer excited states from the {Cu2(micro-X)2} core to 1,8-naphthyridine.


Clinical features of the paranasal sinus fungus ball.
The goal of this study was to delineate the clinical features of the paranasal sinus fungus ball and to evaluate the effectiveness of transnasal endoscopic sinus surgery as a primary surgical method for treating the paranasal sinus fungus ball. A tertiary medical centre. Eighty-five patients (86 cases) who were treated for paranasal sinus fungus ball with transnasal endoscopic sinus surgery between 1995 and 2004 in our Department of Otorhinolaryngology-Head and Neck Surgery. Clinical features, surgical techniques, operative findings, postoperative results, and complications were analyzed retrospectively. All cases were treated successfully by transnasal endoscopic sinus surgery. No recurrences or postoperative complications were observed. However, in 18 cases, fungal debris was observed when sinus irrigation was carried out at the first follow-up visit. In these cases, no additional fungal debris was found by 1.7 weeks (average) postoperatively, and no recurrences were observed. Transnasal endoscopic sinus surgery, followed by postoperative nasal cavity and paranasal sinus irrigation, is effective as a primary treatment method for paranasal sinus fungus ball.


Mitomycin and fluorouracil in combination with concomitant radiotherapy: a potentially curable approach for locally advanced head and neck squamous cell carcinoma.
The purpose of this study was to evaluate the efficacy of radiotherapy and concurrent mitomycin-C (MC) plus 5-fluorouracil (5FU) infusion in locally advanced squamous cell carcinoma of the head and neck (SCCHN). Sixty-nine patients with SCCHN (6 Stage III and 63 Stage IV patients) were treated with external beam radiotherapy (70 Gy) and simultaneous intravenous chemotherapy with 5FU (600 mg/m(2)/day, Days 1-5) and MC (10 mg/m(2), Days 5 and 36). After a mean follow-up of 28.5 months, 59.4% of patients were alive without disease. Complete response was seen in 76.8% of patients. The 3 years overall survival, locoregional relapse-free survival and disease-free survival was 62.3, 63.1[corrected] and 49.5%, respectively. Treatment was well tolerated (Grade III mucositis in 43.5% and Grade II leukopenia in 5.8%). This concurrent chemoradiotherapy regimen offers a curative option for our patients where primary and nodal disease is fairly large resulting in hypoxic radioresistant tumors.


The active metabolite hydroxytamoxifen of the anticancer drug tamoxifen induces structural changes in membranes.
The effects of hydroxytamoxifen (OHTAM) on lipid organization of pure phospholipid liposomes, native sarcoplasmic reticulum (SR) membranes and liposomes of SR lipids were evaluated by intramolecular excimer formation of 1,3-di(1-pyrenyl)propane (Py(3)Py) and by fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) and its derivative 3-[p-(6-phenyl)-1,3,5-hexatrienyl]phenylpropionic acid (DPH-PA). OHTAM promotes alterations in the thermotropic profiles of DMPC, DPPC and DSPC. As detected by Py(3)Py and DPH-PA, OHTAM induces an ordering effect in the fluid phase and a fluidizing effect in the temperature range of the cooperative phase transition. In the gel phase, no significant effects are noticed, except for DSPC bilayers, where Py(3)Py and DPH-PA detect a disordering effect. In the hydrophobic region of the above membrane systems probed by DPH, OHTAM induces only a slight fluidizing effect in the range of the phase transition and a small ordering effect in the fluid phase. As detected by all probes, the drug broadens the transition profile of DMPC and shifts the main transition temperature to lower values. However, these effects, and so those observed for the fluid phase, decrease as the fatty acyl chain length increases. Moreover, the drug removes the pre-transitions of DPPC and DSPC bilayers, as probed by Py(3)Py. In fluid SR native membranes and liposomes of SR lipids, OHTAM induces a moderate ordering effect in the outer regions of the lipid bilayer, as monitored by Py(3)Py and by DPH-PA, DPH failing to detect any apparent effect, as observed for the fluid phase of pure phospholipids. Apparently, OHTAM distributes preferentially in the outer region of the lipid bilayer, without significant effect in the bulk lipid organization of the bilayer interior. The changes of OHTAM in the bilayer dynamic properties and the different location across the bilayer thickness relative to its drug promoter (Custódio et al. (1993) Biochim. Biophys. Acta 1150, 123-129) may be involved in the cytostatic activity of tamoxifen.


Successful treatment of interstitial cystitis with sodium pentosanpolysulfate.
The surface of the bladder is lined by a layer of sulfonated glycosaminoglycans, of which the nonspecific anti-adherence effect is reproduced by synthetic sulfonated glycosaminoglycans. This mucous layer appears to be the most important line of defense between the transitional cells and all harmful substances in the urine. Many disease states may be associated with a deficiency in the anti-adherence activity of the glycosaminoglycan layer and may benefit from treatment with synthetic glycosaminoglycans. One such disease is interstitial cystitis. We administered oral sodium pentosanpolysulfate (Elmiron), a synthetic analogue of a sulfonated glycosaminoglycan, to 24 patients with interstitial cystitis. Within 4 to 8 weeks of initiation of treatment 20 patients experienced a decrease of at least 80 per cent in pain, urgency and nocturia, and 2 experienced a 50 to 80 per cent decrease in these symptoms. The 22 patients who responded continue to experience progressive improvement with time.


Advanced microbial fuel cell for waste water treatment-a review.
Petroleum, coal, and natural gas reservoir were depleting continuously due to an increase in industrialization, which enforced study to identify alternative sources. The next option is the renewable resources which are most important for energy purpose coupled with environmental problem reduction. Microbial fuel cells (MFCs) have become a promising approach to generate cleaner and more sustainable electrical energy. The involvement of various disciplines had been contributing to enhancing the performance of the MFCs. This review covers the performance of MFC along with different wastewater as a substrate in terms of treatment efficiencies as well as for energy generation. Apart from this, effect of various parameters and use of different nanomaterials for performance of MFC were also studied. From the current study, it proves that the use of microbial fuel cell along with the use of nanomaterials could be the waste and energy-related problem-solving approach. MFC could be better in performances based on optimized process parameters for handling any wastewater from industrial process.


The role of interactions in defining the structure of mixed protein-surfactant interfaces.
The behaviour of dispersed systems is often controlled by the composition of the interface between the different phases. Because of the inherent differences between proteins and surfactants, when both are present at the interface complex pseudo two-dimensional structures can be formed. This review brings together work that allows these structures to be explained in terms of the interactions involved. The significance of both the interactions and the structures is discussed in terms of the effect on bulk properties in colloidal systems.


Oncologic Emergencies in the Head and Neck.
Patients with head and neck cancers are susceptible to emergencies related to tumor infiltration, systemic disorders, or treatment. Computed tomography plays a major role in imaging assessment and MRI provides further characterization. Hematologic disorders may lead to hemorrhage, thrombosis, or ischemia. Patients are susceptible to metabolic derangements that are often not recognized. Complications in the neck are threatening due to compromise of vascular structures and airway.


New approaches to reverse resistance to hormonal therapy in human breast cancer.
Breast cancer is now the most common malignancy diagnosed in women. Growth factor and estrogen receptors elicit tight regulation of breast tumor progression. Estrogen receptors occur in about two-thirds of breast tumors, and endocrine therapy targeted to these receptors is effective in a large proportion of tumors that express both estrogen and progesterone receptors. However, after an initial period of response to hormonal therapy, such as tamoxifen, most tumors develop resistance leading to disease relapse. Emerging data suggest that previously unsuspected interactions between growth factor and estrogen signaling pathways contribute to growth promotion in breast cancer. Targeting different components of this signaling axis may allow development of more effective and less toxic anti-hormone treatments for breast cancer. In recent clinical studies, anastrozole, letrozole and exemestane, inhibitors of the estrogen synthase, aromatase, have shown advantages over tamoxifen as treatment for advanced disease. Fulvestrant is a new type of estrogen receptor antagonist that down-regulates cellular levels of estrogen receptor and has no agonist activity. Due to its unique mode of action, fulvestrant may be an ideal candidate for combination treatment with inhibitors targeted to growth factor receptor signaling pathways. New understanding of estrogen receptor genes, gene transcripts and variants, post-translational modifications of receptor protein products and interactions with other signaling networks in tumor cells are leading us to unique targeted approaches in the hormonal therapy of breast cancer.


Proteome response of Corynebacterium glutamicum to high concentration of industrially relevant C₄ and C₅ dicarboxylic acids.
More than fifty years of industrial and scientific developments on the amino acid-producer strain Corynebacterium glutamicum has generated an extremely huge knowledge highly applicable to the development of new products. Despite the production of dicarboxylic acids has already been engineered in C. glutamicum, the effect caused by these acids at competitive industrial levels has not yet been described. Thus, aspartic, fumaric, itaconic, malic and succinic acids have been tested on the growth of C. glutamicum to obtain their minimal inhibitory concentrations and their intracellular effects analyzed by 2D-DIGE. This analysis showed the modification of the central metabolism of C. glutamicum, the cross-regulation between malic acid and glucose as well as the aspartic acid utilization as nitrogen source. The analysis of the transcriptional regulators involved in the control of the detected proteins pointed to the ramB gene as a candidate for strain improvement. The analysis of the ΔramB mutant demonstrated its function as an enhancer of the growth speed or resistance level against aspartic, fumaric, itaconic and malic acids in C. glutamicum. The effect of dicarboxylic acids addition to the C. glutamicum culture broth has been described. This proteome response is detailed and the deletion of a global regulator (ramB) has been described as a possible improving method for industrial strains. In addition, the consumption of aspartic acid as nitrogen source has been described for the first time in C. glutamicum, as well as, the cross-regulation between malic acid and glucose through the F0F1 respiratory system.


Speed regulation of genetic cascades allows for evolvability in the body plan specification of insects.
During the anterior-posterior fate specification of insects, anterior fates arise in a nonelongating tissue (called the "blastoderm"), and posterior fates arise in an elongating tissue (called the "germband"). However, insects differ widely in the extent to which anterior-posterior fates are specified in the blastoderm versus the germband. Here we present a model in which patterning in both the blastoderm and germband of the beetle Tribolium castaneum is based on the same flexible mechanism: a gradient that modulates the speed of a genetic cascade of gap genes, resulting in the induction of sequential kinematic waves of gap gene expression. The mechanism is flexible and capable of patterning both elongating and nonelongating tissues, and hence converting blastodermal to germband fates and vice versa. Using RNAi perturbations, we found that blastodermal fates could be shifted to the germband, and germband fates could be generated in a blastoderm-like morphology. We also suggest a molecular mechanism underlying our model, in which gradient levels regulate the switch between two enhancers: One enhancer is responsible for sequential gene activation, and the other is responsible for freezing temporal rhythms into spatial patterns. This model is consistent with findings in Drosophila melanogaster, where gap genes were found to be regulated by two nonredundant "shadow" enhancers.


Manganese peroxidase-catalyzed oxidative degradation of vanillylacetone.
When 4-(4-hydroxy-3-methoxy-phenyl)-2-butanone (vanillylacetone) was tested for manganese peroxidase (MnP)-catalyzed oxidation, it was found to be degraded with the cleavage of an aromatic ring. Among numerous products of vanillylacetone oxidation, four major ones were purified by thin-layer chromatography and identified using mass spectroscopy (MS) and nuclear magnetic resonance (NMR) analysis. Three of them maintained the aromatic ring structure and were identified as 4-[6,2'-dihydroxy-5,3'-dimethoxy-5'-(3-oxo-butyl)-biphenyl]-butan-2-one, 4-(4-hydroxy-3-methoxyphenyl)-3-buten-2-one, and 4-[6,2'-dihydroxy-5,3'-dimethoxy-5'-(3-oxo-butyl)-biphenyl]-3-buten-2-one. Even though the fourth product could not be purified to a single compound, data from infrared spectroscopy showed that it did not have a benzene ring. From MS and NMR analysis, 3-(3-oxo-butyl)-hexa-2,4-dienedioic acid-1-methyl ester was tentatively suggested as the dominant species. The reaction mechanism was suggested on the basis of the structural information of these products. To our knowledge, this paper is the first report on aromatic ring cleavage of the phenolic compound by MnP.


Engineering Catalytic CoSe-ZnSe Heterojunctions Anchored on Graphene Aerogels for Bidirectional Sulfur Conversion Reactions.
Sluggish sulfur reduction and lithium sulfide (Li2 S) oxidation prevent the widespread use of lithium-sulfur (Li-S) batteries, which are attractive alternatives to Li-ion batteries. The authors propose that a transition metal selenide heterojunction (CoSe-ZnSe) catalytically accelerates bidirectional sulfur conversion reactions. A combination of synchrotron X-ray absorption spectroscopy and density functional theory calculations show that a highly active heterointerface with charge redistribution and structure distortion effectively immobilizes sulfur species, facilitates Li ion diffusion, and decreases the sulfur reduction and Li2 S oxidation energy barriers. The CoSe-ZnSe catalytic cathode exhibits high areal capacities, good rate capability, and superior cycling stability with capacity fading rate of 0.027% per cycle over 1700 cycles. Furthermore, CoSe-ZnSe heterojunctions anchored on graphene aerogels (CoSe-ZnSe@G) enhance ionic transport and catalytic activity under high sulfur loading and lean electrolyte conditions. A high areal capacity of 8.0 mAh cm-2 is achieved at an electrolyte/sulfur ratio of 3 µL mg-1 . This study demonstrates the importance of bidirectional catalytic heterojunctions and structure engineering in boosting Li-S battery performances.


Is Day Care Tonsillectomy a Safe Procedure?
Tonsillectomy with or without adenoidectomy is the commonest procedure performed by an otolaryngologist. It has been performed as an in-patient procedure. To present our experience of 15 years of day care tonsillectomy with or without adenoidectomy and to assess the safety of tonsillectomy as a day care procedure. Design: retrospective study. A retrospective study of all day care tonsillectomies with or without adenoidectomies operated at a Secondary care ENT Hospital from 2002 to 2016 has been carried out. In last 15 years, we have operated 1207 tonsillectomies with or without adenoidectomies as a day care procedure. Postoperatively, the patients were discharged after observing for 6 to 8 h. Out of 1207 patients, 3 patients required readmission due to bleeding and 5 due to pain. Hence the overall readmission rate following tonsillectomy was 8/1027, which equals to 0.778 percent. Two patients with postoperative bleeding within 6 h were taken up for exploration and control of hemostasis. One patient of secondary haemorrhage was managed conservatively. None of the patients required blood transfusion. Day care tonsillectomy with or without adenoidectomy is a safe procedure as long as the patients are carefully selected. It is also cost effective. Level of evidence: Level 4.


The cost utility of bisphosphonate treatment in established osteoporosis.
Hip fracture is an important and costly problem. Bisphosphonate therapy prevents hip and other fractures among women with established osteoporosis, but there are few published economic evaluations of this treatment. To assess the cost-effectiveness of risedronate, a recently launched bisphosphonate for the prevention of fractures among women with established osteoporosis. A state transition Markov model of established post-menopausal osteoporosis based upon randomized clinical trial data was developed. Uncertainty underlying model parameters and outcomes was dealt with using traditional sensitivity analysis and stochastic sensitivity analysis to produce quasi-95%CIs. We focussed on patients aged approximately 75 years, since this population most closely matches the randomized controlled trial, and is typical of osteoporosis patients in the UK. The baseline model of treating a cohort of 1000 75-year-old women for 3 years with risedronate and then modelling the costs and benefits over their expected lifetimes, produced net savings of pound sterling 786 000 for the treatment group per 1000 treated women, (95%CI pound sterling 1.55m savings to pound sterling 47000 extra costs). Restricting the horizon of the analysis to only three years led to a small net cost of pound sterling 138 000 per 1000 treated women (95%CI pound sterling 196 000 savings to pound sterling 477 000 extra costs) with a net increment in Quality Adjusted Life years (QALYs) of 16 per 1000 treated women. This resulted in a cost per QALY of pound sterling 8625 per treated woman. In this example, the use of risedronate therapy in 75-year-old women at high risk of hip fracture leads to an improvement in quality of life with possible cost savings. Restricting the analysis to a time horizon of only three years leads to a QALY gain at a modest net cost.


['My daughter eats my mattress!'--a patient with pica].
For the third time a 17-year-old adolescent is presented to a child and adolescent ambulatory mental health clinic, because of eating foam rubber. In this case study pica is being discussed and its possible connection with a somatic disease (sickle cell anaemia). The importance of alertness to unknown symptoms in diagnosing is being underlined, as well as the value of searching for a biological explanation in order to prevent interpreting all strange behaviour as psychosocial of origin.


Mycoplasma genitalium and Bacterial Vaginosis-Associated Bacteria in a Non-Clinic-Based Sample of African American Women.
Mycoplasma genitalium is associated with adverse reproductive problems. However, prevalence estimates from studies that screen women not seeking care are rare. Studies have reported co-occurrence of M. genitalium with bacterial vaginosis (BV), but no prior study of specific BV-associated bacteria has been conducted in African Americans whose reproductive tract infection burden is high. Using quantitative polymerase chain reaction, we screened vaginal swabs for M. genitalium, 9 BV-associated bacteria, and 4 Lactobacillus species from 200 participants drawn from a cohort of African Americans 23 to 35 years old. Sexual history, herpes serostatus, and Nugent score had been assessed. Prevalence of M. genitalium was computed. The associations of other vaginal bacteria with M. genitalium were examined with binomial regression. M. genitalium prevalence was 18%. Detection and quantity of 2 BV-associated bacteria were significantly associated with a higher prevalence of M. genitalium (Leptotrichia/Sneathia: detection prevalence ratio (PR) of 2.9 [95% confidence interval {CI}, 1.1-7.7] and quantity PR of 1.2 [95% CI, 1.0-1.3]; Megasphaera phylotype 1: detection PR of 2.2 [95% CI, 1.2-4.2] and quantity PR of 1.1 [95% CI, 1.0-1.2]). Increased quantity of L. iners was also positively associated with M. genitalium (PR, 1.3 [95% CI, 1.0-1.8]). Nugent ≥7, herpes serostatus, and lifetime number of sex partners were not associated with M. genitalium. Specific BV-associated microbes and L. iners were associated with M. genitalium, but Nugent ≥7 was not. Studies are needed to confirm a high prevalence of M. genitalium in African Americans and to understand its interactions with other vaginal bacteria.


TRPV1 inactivation alters core body temperature and serum corticosterone levels: Impacts on clock genes expression in the liver and adrenal glands.
TRPV1 desensitization or blockade promotes hyperthermia in rodents. Daily changes in core body temperature (Tc), spontaneous locomotor activity (SLA), and glucocorticoids are temporal cues for peripheral clocks. Thus, this study aimed to evaluate the effects of both desensitization and blockade of TRPV1 on Tc, SLA, blood corticosterone, and the clock genes Per1 and Bmal1 in the liver and adrenal. Resiniferatoxin (RTX, 20 μg kg-1) known to desensitize the intra-abdominal TRPV1 channels was i. p. administered in adult male rats. One day after, RTX rats displayed higher Tc than vehicle rats (control) in the light and dark phases. RTX rats showed higher corticosterone at zeitgeber time (ZT) 6 and ZT12 compared to ZT0. Control rats showed a rise in corticosterone at ZT12. RTX abolished the Per1 peak in both the liver and adrenal glands, whereas it enhanced the peak of Bmal1 expression in the liver and decreased it in adrenal glands. Circadian variation in Tc and SLA was unaffected despite higher Tc being found along the light phase up to 5 days after RTX injection. Acute blockade of TRPV1 with the antagonist AMG-517 injected at ZT0 increased Tc and reduced corticosterone without affecting SLA. In the liver, while AMG-517 did not affect Per1, it increased Bmal1 mRNA. In adrenal glands, AMG-517 increased Per1 and did not affect Bmal1 expression. Although rats exposed to a 60-min 34 °C environment showed similar hyperthermia to that observed in AMG-517 rats, neither corticosterone nor liver nor adrenal clock genes changed. Inactivation of TRPV1 by abdominal desensitization or by antagonism alters the time-of-day changes of clock genes expression in the liver and adrenal, as well as corticosterone. TRPV1 may be necessary for signaling cyclical temporal cues for clock genes in the periphery but less critical for the circadian profile of Tc and SLA.


Accuracy of positron emission tomography/computed tomography in the diagnosis and restaging for recurrent ovarian cancer: a meta-analysis.
A meta-analysis was performed to estimate the diagnostic accuracy of positron emission tomography/computed tomography (PET/CT) in suspected recurrent ovarian cancer. PubMed, The Cochrane Library, Embase, and Web of Science were systematically searched. Studies that compared PET/CT and reference standards within patients for diagnosis of suspected recurrent ovarian cancer were included. Twenty-nine studies involving 1651 patients with ovarian cancer were analyzed. For recurrent versus nonrecurrent ovarian cancer, the pooled sensitivity, specificity, positive likelihood (LH) ratio, negative LH ratio, and diagnostic odds ratio of ovarian carcinoma were 88.6% (95% confidence interval [CI], 86.6%-90.3%), 90.3% (95% CI, 87.6%-92.7%), 6.104 (95% CI, 3.904-9.543), 0.122 (95% CI, 0.077%-0.192%), and 57.032 (95% CI, 30.764-105.73), respectively, for recurrence in the PET/CT. Because sensitivity, specificity, positive LH ratio, and negative LH ratio were all heterogeneous, random effects model was used, and a summary receiver operating characteristic curve was generated. The area under the curve was 0.9445 for recurrent versus nonrecurrent ovarian cancer. Positron emission tomography/computed tomography is a useful tool for predicting the diagnosis and restaging of suspected recurrent ovarian carcinoma.


Advanced water splitting for green hydrogen gas production through complete oxidation of starch by in vitro metabolic engineering.
Starch is a natural energy storage compound and is hypothesized to be a high-energy density chemical compound or solar fuel. In contrast to industrial hydrolysis of starch to glucose, an alternative ATP-free phosphorylation of starch was designed to generate cost-effective glucose 6-phosphate by using five thermophilic enzymes (i.e., isoamylase, alpha-glucan phosphorylase, 4-α-glucanotransferase, phosphoglucomutase, and polyphosphate glucokinase). This enzymatic phosphorolysis is energetically advantageous because the energy of α-1,4-glycosidic bonds among anhydroglucose units is conserved in the form of phosphorylated glucose. Furthermore, we demonstrated an in vitro 17-thermophilic enzyme pathway that can convert all glucose units of starch, regardless of branched and linear contents, with water to hydrogen at a theoretic yield (i.e., 12 H2 per glucose), three times of the theoretical yield from dark microbial fermentation. The use of a biomimetic electron transport chain enabled to achieve a maximum volumetric productivity of 90.2mmol of H2/L/h at 20g/L starch. The complete oxidation of starch to hydrogen by this in vitro synthetic (enzymatic) biosystem suggests that starch as a natural solar fuel becomes a high-density hydrogen storage compound with a gravimetric density of more than 14% H2-based mass and an electricity density of more than 3000Wh/kg of starch.


Molecular characterization of nineteen cytokine receptor family B (CRFB) members, CRFB1, CRFB2, CRFB4-17, with three CRFB9 and two CRFB14 in a cyprinid fish, the blunt snout bream Megalobrama amblycephala.
The class II cytokine receptor family members are receptors of class 2 helical cytokines in mammals, and are named cytokine receptor family B (CRFB) in fish. In zebrafish, sixteen members, including CRFB1, CRFB2 and CRFB4-17 were reported. With the availability of genome sequence, a total of nineteen CRFBs was identified in the blunt snout bream (Megalobrama amblycephala), including CRFB1, CRFB2, CRFB4-17 with the presence of three CRFB9 isoforms, and two CRFB14 isoforms. These CRFB molecules contain well conserved features, such as fibronectin type III (FNIII) domain, transmembrane and intracellular domains as other class II cytokine receptors, and are phylogenetically grouped into thirteen clades with their homologues from other species of fish. The CRFB genes were constitutively expressed in organs/tissues examined in the fish. The finding of more CRFB members in the bream may provide clues to understand possible receptor-ligand interaction and their diversity from an evolutionary point of view.


Thermal activation of Ti(1-x)Au(x) thin films with enhanced hardness and biocompatibility.
The lifetime of orthopaedic implants can be extended by coating the softer Ti6Al4V alloy with harder biocompatible thin films. In this work, thin films of Ti(1-x)Au(x) are grown on Ti6Al4V and glass substrates by magnetron sputtering in the entire x = 0-1 range, before their key biomechanical properties are performance tuned by thermal activation. For the first time, we explore the effect of in-situ substrate heating versus ex-situ post-deposition heat-treatment, on development of mechanical and biocompatibility performance in Ti-Au films. A ∼250% increase in hardness is achieved for Ti-Au films compared to bulk Ti6Al4V and a ∼40% improvement from 8.8 GPa as-grown to 11.9 and 12.3 GPa with in-situ and ex-situ heat-treatment respectively, is corelated to changes in structural, morphological and chemical properties, providing insights into the origins of super-hardness in the Ti rich regions of these materials. X-ray diffraction reveals that as-grown films are in nanocrystalline states of Ti-Au intermetallic phases and thermal activation leads to emergence of mechanically hard Ti-Au intermetallics, with films prepared by in-situ substrate heating having enhanced crystalline quality. Surface morphology images show clear changes in grain size, shape and surface roughness following thermal activation, while elemental analysis reveals that in-situ substrate heating is better for development of oxide free Ti3Au β-phases. All tested Ti-Au films are non-cytotoxic against L929 mouse fibroblast cells, while extremely low leached ion concentrations confirm their biocompatibility. With peak hardness performance tuned to >12 GPa and excellent biocompatibility, Ti-Au films have potential as a future coating technology for load bearing medical implants.


Application of holography and augmented reality based technology to visualize the internal structure of the dental root - a proof of concept.
The Augmented Reality (AR) blends digital information with the real world. Thanks to cameras, sensors, and displays it can supplement the physical world with holographic images. Nowadays, the applications of AR range from navigated surgery to vehicle navigation. The purpose of this feasibility study was to develop an AR holographic system implementing Vertucci's classification of dental root morphology to facilitate the study of tooth anatomy. It was tailored to run on the AR HoloLens 2 (Microsoft) glasses. The 3D tooth models were created in Autodesk Maya and exported to Unity software. The holograms of dental roots can be projected in a natural setting of the dental office. The application allowed to display 3D objects in such a way that they could be rotated, zoomed in/out, and penetrated. The advantage of the proposed approach was that students could learn a 3D internal anatomy of the teeth without environmental visual restrictions. It is feasible to visualize internal dental root anatomy with AR holographic system. AR holograms seem to be attractive adjunct for learning of root anatomy.


Prevalence of antibodies to soluble antigen of Epstein-Barr virus-producing cells (P3HR-1) in the sera of hamadryas baboons of the high lymphoma incidence stock.
Soluble antigen of P3HR-1 cells (SA-P3HR-1) was identified in indirect double immunodiffusion enhanced with tannic acid using serum of a nasopharyngeal carcinoma patient containing high-titer antibodies to Epstein-Barr virus (EBV) antigens. SA-P3HR-1 was nonidentical to soluble antigen of Raji cells. Human and baboon sera containing antibodies to all the known antigen of EBV and HVP respectively were anti-SA-3HR-1-positive. Human and baboon sera containing antibodies to all the known antigens of EBV and herpesvirus Papio (HVP) were also anti-SA-P3HR-1-negative. Prevalence of anti-SA-P3HR-1 was very high in two groups of the high-lymphoma incidence stock of hamadryas baboons of the Sukhumi monkey colony. 54% (15 of 28) and 38% (13 of 34) of clinically lymphomatous and clinical normal monkeys, respectively, were anti-SA-P3HR-1-positive.. Only 1 of 30 normal baboons studied, living in the forest and having no contacts with the baboons in the main stock of the Sukhumi monkey colony, was anti-SA-P3HR-1-positive (3%).


Ball milling pretreatment facilitating α-amylase hydrolysis for production of starch-based bio-latex with high performance.
Starch based bio-latex has been widely researched in the coating paper area for the purpose of partial replacement of petroleum-based binders. In this paper, a green and facile ball milling pretreatment was proposed to modify the starch granules before α-amylase hydrolysis by breaking up their crystalline structure, thus improving the accessibility and susceptibility of amylase into starch structure. It was found that the improved hydrolysis process after 8 h ball milling can generate suitable degree of polymerization of polysaccharides or oligosaccharides, which further facilitated the following H2O2 oxidation and SHMP crosslinking processes. In addition, a mechanism was also demonstrated to illustrate the improvement induced by ball milling pretreatment. The prepared bio-latex with crosslinking-structure performed excellent adhesive properties when substituted 25 % of petroleum-based latex during paper coating application, which showed great potential in improving the economic, cost, and environment benefits of traditional production of coated paper.


Evaluation of magnifying endoscopy using narrow band imaging using ex vivo bile duct (with video).
Detailed endoscopic findings of the bile duct mucosa, even of the non-neoplastic mucosa, have not yet been established. The aim of the present study was to compare a currently used video cholangioscope (CCS) with a magnifying endoscope (ME) that is commonly used for the gastrointestinal tract, for visualization of the bile duct mucosa. Ten freshly resected common bile ducts were used in this study. We observed the non-neoplastic bile duct mucosa with CCS and ME, and carried out both conventional white light imaging and narrow band imaging. After histological diagnosis, the 10 specimens were classified into three categories according to the degree of histological inflammation: normal to mild, moderate, and severe. Then, we examined the relationship between the magnifying endoscopic findings and the histopathological findings. In eight of the 10 cases, the visualization obtained with CCS was inferior to that obtained by ME. Five specimens were classified as normal to mild inflammation, and many oval-shaped, depressed areas and a fine, regular network of the microvessels were observed by ME on the mucosal surfaces of these specimens. The remaining specimens were classified as moderate or severe inflammation, and the aforementioned findings could not be clearly visualized. CCS does not allow visualization of the bile duct mucosa with high sensitivity. Oval-shaped depressed areas and a fine, regular network of microvessels are characteristic endoscopic features of non-neoplastic bile duct mucosa without inflammation.


Evaluation of appropriate conditions for Oncomine DxTT testing of FFPE specimens for driver gene alterations in non-small cell lung cancer.
The Oncomine Dx Target Test Multi-CDx System (ODxTT) is a next-generation sequencing panel approved as a companion diagnostic for drugs targeted to corresponding gene alterations in non-small cell lung cancer. However, appropriate slide conditions for ODxTT have remained unclear. We focused on the production of the number of tumor cells on a formalin-fixed paraffin-embedded (FFPE) section and the number of prepared slides, designated the TS value, and determined a TS value of ≥4000 as a target slide condition for ODxTT. We evaluated the impact of this condition on ODxTT testing with tumor specimens found to have a TS of <4000 (n = 23) or a TS of ≥4000 (n = 142). A positive correlation was apparent between the TS value and the concentrations of both DNA and RNA. Among the 142 samples with a TS of ≥4000, a sufficient concentration of DNA or RNA for ODxTT analysis was achieved in 100% and 98% samples, respectively. Among samples explored for driver gene alterations after determination of the target slide condition (TS ≥4000), most (84.9%) had a TS of ≥4000 and were submitted for ODxTT analysis. Our findings indicate that a TS of ≥4000 is a feasible and relevant criterion for ODxTT testing, and its adoption should help to improve the success rate of such testing in clinical practice.


Evidence of multisystem disorder in whole-brain map of pathological TDP-43 in amyotrophic lateral sclerosis.
Pathological 43-kDa transactivating responsive sequence DNA-binding protein (TDP-43) has been identified recently as the major disease protein in amyotrophic lateral sclerosis (ALS), and in frontotemporal lobar degeneration with ubiquitinated inclusions, with or without motor neuron disease, but the distribution of TDP-43 pathology in ALS may be more widespread than previously described. To determine the extent of TDP-43 pathology in the central nervous systems of patients with clinically confirmed and autopsy confirmed diagnoses of ALS. Performance of an immunohistochemical whole-central nervous system scan for evidence of pathological TDP-43 in ALS patients. An academic medical center. We included 31 patients with clinically and pathologically confirmed ALS and 8 control participants. Immunohistochemistry and double-labeling immunofluorescence to assess the frequency and severity of TDP-43 pathology. In addition to the stereotypical involvement of upper and lower motor neurons, neuronal and glial TDP-43 pathology was present in multiple areas of the central nervous systems of ALS patients, including in the nigro-striatal system, the neocortical and allocortical areas, and the cerebellum, but not in those of the controls. These findings suggest that ALS does not selectively affect only the pyramidal motor system, but rather is a multisystem neurodegenerative TDP-43 proteinopathy.


[Paranasal sinus diseases--potentials and limitations of radiology].
The indications for conventional plain x-ray films, computed tomography in axial and/or coronary projection and magnetic resonance tomography are discussed on the basis of case reports on inflammatory, tumorous and tumour-like diseases of the paranasal sinuses.


Value of positron emission tomography/computed tomography in diagnosis and staging of primary ocular and orbital tumors.
Accurate and reliable staging methods are crucial for optimal care of patients with ocular and orbital malignancies. Positron emission tomography/computed tomography (PET/CT) has recently emerged as a staging tool in the field of ophthalmic oncology. For detecting primary ocular or orbital lesions, PET/CT does not seem to provide an advantage over clinical ophthalmologic examination or conventional imaging studies such as CT or magnetic resonance imaging of the orbit. However, PET/CT may detect distant metastatic lesions that conventional imaging studies miss. For orbital and ocular adnexal lymphoma, use of PET/CT has been proven to be feasible and is now accepted both as a standard part of the initial staging work-up and for the assessment of response to therapy. For other ophthalmic tumors, PET/CT seems most appropriate for advanced metastatic tumors of the orbit, eyelid, and eye, for which the detection of distant metastasis with 1 comprehensive study may be preferable to performing multiple CT scans with contrast.


A Single-Cell Transcriptional Atlas of the Developing Murine Cerebellum.
The cerebellum develops from a restricted number of cell types that precisely organize to form the circuitry that controls sensory-motor coordination and some higher-order cognitive processes. To acquire an enhanced understanding of the molecular processes that mediate cerebellar development, we performed single-cell RNA-sequencing of 39,245 murine cerebellar cells at twelve critical developmental time points. Using recognized lineage markers, we confirmed that the single-cell data accurately recapitulate cerebellar development. We then followed distinct populations from emergence through migration and differentiation, and determined the associated transcriptional cascades. After identifying key lineage commitment decisions, focused analyses uncovered waves of transcription factor expression at those branching points. Finally, we created Cell Seek, a flexible online interface that facilitates exploration of the dataset. Our study provides a transcriptional summarization of cerebellar development at single-cell resolution that will serve as a valuable resource for future investigations of cerebellar development, neurobiology, and disease.


Primary squamous cell carcinoma of the vagina treated by radiotherapy: a failures analysis--the M. D. Anderson Hospital experience 1955-1982.
The retrospective study concerns 167 patients with primary squamous cell carcinoma of the vagina treated at The University of Texas M. D. Anderson Hospital and Tumor Institute between January 1955 and December 1982. Of these 167 patients, 162 were evaluable and 5 were lost to follow-up. For small tumors, localized treatment by brachytherapy alone, transvaginal irradiation with 125 to 250 kV alone or in combination with brachytherapy, was mainly used, with emphasis on use of colpostats and transvaginal irradiation for tumors of the upper half of the vagina and interstitial (with radium needles or, later, afterloaded stainless-steel guides with iridium wires) for the lower half. For medium-size tumors, local treatment was combined with external irradiation, mainly using conservative-size fields. For the majority of larger tumors or when the anatomy was distorted, external irradiation alone was used, also with portals of conservative size. Failures were analyzed in relation to FIGO (International Federation of Obstetrics and Gynecology) staging, tumor location, and modality of treatment. As expected, central failures were higher in Stage III disease (9 of 38 patients, 24%) but also uncomfortably high for Stage I patients (13 of 71 patients, 18%) treated locally or with external and local irradiation. The incidence of central treatment failures in tumors of the lower vagina (13/51 patients, 25%) was somewhat higher than for tumors located in the upper vagina (13/85 patients, 15%), but the percentage of large tumors in the lower vagina was 53% compared with 31% in the upper vagina. Severe complications were related to high doses of irradiation alone or in combination with aggressive surgery, and to pelvic inflammatory disease.


Design, synthesis and biological evaluation of 7-methylimidazo[1,5-a]pyrazin-8(7H)-one derivatives as BRD4 inhibitors.
BRD4 is an attractive target for antitumor due to its important role in regulation of gene transcription. In this paper, we synthesized a series of 7-methylimidazo[1,5-a]pyrazin-8(7H)-one derivatives as potent BRD4 inhibitors and evaluated their BRD4 inhibitory activities in vitro and anti-proliferation effects on tumor cells. Gratifyingly, compound 10j exhibited robust potency of BRD4(1) and BRD4(2) inhibition with IC50 values of 130 and 76nM respectively. Docking studies were performed to explain the structure-activity relationship. Furthermore, compound 10j potently inhibited cell proliferation in BRD4-sensitive cell lines HL-60 and MV4-11 with IC50 value of 0.57 and 0.18μM respectively. Activity on BRD4-independent K562 cell was weaker than on BRD4-sensitive lines. Overall, these results suggest that compound 10j is a potential BRD4 inhibitor deserving further investigation for cancer treatment.


Critical assessment of how to study addiction and its treatment: human and non-human animal models.
Laboratory models, both animal and human, have made enormous contributions to our understanding of addiction. For addictive disorders, animal models have the great advantage of possessing both face validity and a significant degree of predictive validity, already demonstrated. Another important advantage to this field is the ability of reciprocal interplay between preclinical and clinical experiments. These models have made important contributions to the development of medications to treat addictive disorders and will likely result in even more advances in the future. Human laboratory models have gone beyond data obtained from patient histories and enabled investigators to make direct observations of human drug self-administration and test the effects of putative medications on this behavior. This review examines in detail some animal and human models that have led not only to important theories of addiction mechanisms but also to medications shown to be effective in the clinic.


Hypospadias With Severe Chordee: Effect of Urethral Plate Transection on Penile Length.
To present our experience with urethral plate (UP) transection to treat hypospadias with severe chordee and examined the effects of this procedure on penile length. The technique involved transecting the UP to correct curvature, facilitating elongation of penile length and reconstruction of the urethra. We prospectively studied a cohort of patients with hypospadias with severe chordee who underwent UP transection and urethroplasty at our institution between February 2012 and March 2020. The length of the UP defect (length of penile elongation), complications, and patient and urologist satisfaction with penile length were analyzed. A total of 510 children were included in our study: 78 cases of distal hypospadias and 432 cases of proximal hypospadias. The mean age at initial surgery was 34.84 ± 20.10 months. The length of the UP defect after transection was 2.51 ± 0.92 cm (1.6-8.0 cm). The length of the UP defect gradually increased with age (P < .05). Seven patients were "poorly satisfied" with their penile length after urethroplasty. The median follow-up duration was 32 months. Of the 510 patients, 108 (21.1%) had complications after urethroplasty, including urethral fistulas in 86 cases, urethral strictures in 9 cases, urethral diverticulum in 8 cases and glans dehiscence in 5 cases. During the follow-up period, 7 patients had mild chordee. Transecting the UP for hypospadias with severe chordee can elongate penile length, reduce the recurrence of curvature, and improve patient satisfaction.


Characterisation of a functional allatotropin receptor in the bumblebee, Bombus terrestris (Hymenoptera, Apidae).
Allatotropins (ATs) are multifunctional neuropeptides initially isolated from the tobacco hornworm, Manduca sexta, where they were found to stimulate juvenile hormone synthesis and release from the corpora allata. ATs have been found in a wide range of insects, but appear to be absent in Drosophila. The first AT receptor (ATR) was characterised in 2008 in the lepidopteran Bombyx mori. Since then ATRs have been characterised in Coleoptera and Diptera and in 2012, an AT precursor gene was identified in hymenopteran species. ATRs show large sequence and structural similarity to vertebrate orexin receptors (OXR). Also, AT in insects and orexin in vertebrates show some overlap in functions, including modulation of feeding behaviour and reproduction. The goal of this study was to identify a functional ATR in a hymenopteran species. We used ATRs (insect sequences) and OXRs (vertebrate sequences) to search the genome of the bumblebee, Bombus terrestris. Two receptors (XP_003402490 and XP_003394933) with resemblance to ATRs and OXRs were found. Phylogenetic analysis provided the first indication that XP_003402490 was more closely related to ATRs than XP_003394933. We investigated the transcript level distribution of both receptors and the AT precursor gene by means of quantitative real-time reverse transcriptase PCR. XP_003402490 displayed a tissue distribution comparable with ATRs in other species, with high transcript levels in the male accessory glands. After pharmacological characterisation, it appeared that XP_003402490 is indeed a functional ATR. Activation of the receptor causes an increase in intracellular calcium and cyclic AMP levels with an EC50 value in the low nanomolar to picomolar range. XP_003394933 remains an orphan receptor.


Systemic evaluation of lymphocyte-bound C4d and immunoglobulins for diagnosis and activity monitoring of systemic lupus erythematosus.
To investigate the role of lymphocyte-bound C4d (LB-C4d: T-C4d, B-C4d) and immunoglobulins (LB-Igs: T-IgG, T-IgM, B-κ and B-λ) in the diagnosis and monitoring of SLE. The levels of C4d and Igs on peripheral lymphocytes were measured in 172 patients with SLE, 174 patients with other non-SLE inflammatory diseases and 100 healthy individuals. Immunobinding and blocking experiments were performed to characterize Igs from SLE patients to generate LB-C4d/Igs in vitro. Sixty-five patients with SLE were followed up longitudinally. Disease activity was assessed for each SLE patient. Patients with SLE had the highest median LB-C4d/Igs levels. LB-C4d had a significant but weak positive association with LB-Igs, with correlation coefficients ranging from 0.008 to 0.316. Anti-cardiolipin IgG and anti-β2GP1 IgG, but not C3 and C4, were found to be closely associated with LB-C4d/Igs formation, with correlations as high as 0.337. Compared to anti-dsDNA, LB-C4d performed better in SLE diagnosis, while B-κ and B-λ performed better in disease activity monitoring. Both autoantibodies and receptors on lymphocytes contribute to LB-C4d/Igs formation. LB-C4d/Igs could be used as reliable indicators for SLE diagnosis and activity monitoring.


Dynamic integration of land use changes in a hydrologic assessment of a rapidly developing Indian catchment.
Rapid land use and land-cover changes strongly affect water resources. Particularly in regions that experience seasonal water scarcity, land use scenario assessments provide a valuable basis for the evaluation of possible future water shortages. The objective of this study is to dynamically integrate land use model projections with a hydrologic model to analyze potential future impacts of land use change on the water resources of a rapidly developing catchment upstream of Pune, India. For the first time projections from the urban growth and land use change model SLEUTH are employed as a dynamic input to the hydrologic model SWAT. By this means, impacts of land use changes on the water balance components are assessed for the near future (2009-2028) employing four different climate conditions (baseline, IPCC A1B, dry, wet). The land use change modeling results in an increase of urban area by +23.1% at the fringes of Pune and by +12.2% in the upper catchment, whereas agricultural land (-14.0% and -0.3%, respectively) and semi-natural area (-9.1% and -11.9%, respectively) decrease between 2009 and 2028. Under baseline climate conditions, these land use changes induce seasonal changes in the water balance components. Water yield particularly increases at the onset of monsoon (up to +11.0mm per month) due to increased impervious area, whereas evapotranspiration decreases in the dry season (up to -15.1mm per month) as a result of the loss of irrigated agricultural area. As the projections are made for the near future (2009-2028) land use change impacts are similar under IPCC A1B climate conditions. Only if more extreme dry years occur, an exacerbation of the land use change impacts can be expected. Particularly in rapidly changing environments an implementation of both dynamic land use change and climate change seems favorable to assess seasonal and gradual changes in the water balance.


Treatment-resistant schizophrenia.
This article opens with a brief history of pharmacologic treatment of schizophrenia. It then discusses the definition and treatment of treatment-resistant schizophrenia, with particular attention to clinical, biological and neuroimaging correlates, as well as the best treatment options, including the use of clozapine in patients who meet the definition of treatment-resistant schizophrenia.


Record-based, stepwise screening for type 2 diabetes integrated into an annual cardiovascular care review system: Findings from a UK general practice.
Screening high-risk individuals for type 2 diabetes (T2DM) is recommended by many organisations. We report results from a pragmatic stepwise T2DM screening programme integrated into an annual review system in a UK general practice. Patients with hypertension, cardiovascular disease or chronic kidney disease attending an annual review were screened for dysglycaemia by random blood glucose (RBG) measurement. At the discretion of the usual doctor, individuals with an RBG≥6.1 mmol/l were invited to return for fasting blood glucose (FBG) or HbA(1C) measurement, allowing diagnosis of T2DM. 786 eligible patients were invited for T2DM screening as part of their annual review. 544 attended screening, of whom 120 had an RBG≥6.1 mmol/l. 40 individuals attended FBG measurement and 8 individuals attended HbA(1C) measurement, leading to 9 T2DM diagnoses. The positive predictive value of the test for T2DM was 19% and the laboratory cost was £91 per patient diagnosed with T2DM. It is feasible to integrate a simple T2DM screening programme within an annual review system in a UK general practice. Different strategies may be required to increase initial attendance and ensure completion of the screening programme.


Development and pilot-testing of a decision aid for women with a breech-presenting baby.
To develop a decision aid for pregnant women with a breech presentation at term, and to assess its acceptability. The external cephalic version (ECV) decision aid was developed using the Ottawa Decision Support Framework and a systematic review of the evidence to provide probabilistic information about the benefits and risks of options. It incorporates a workbook supplemented by a CD and worksheet, and these were evaluated in a pilot study using self-administered questionnaires. 19 women with a breech presentation attending antenatal clinics at a local obstetric hospital and 11 recently pregnant women. Of 30 women surveyed, nearly all found the decision aid clear and easy to understand, and thought that enough information was provided for them to make a decision. Women experienced increased knowledge, reduced decisional conflict, increased satisfaction and participation in decision making without increased anxiety. Participants also found the tool helpful and would recommend it to others. The ECV decision aid was well accepted and helpful for pregnant women with a breech presenting baby. We are currently evaluating the decision aid in a randomised trial to assess cognitive, affective and health outcomes.


The developmental trajectories of racial and gender intergroup bias in 5- to 10-year-old children: The impact of general psychological tendencies, contextual factors, and individual propensities.
Racism and intergroup discrimination are pervasive problems in human societies. Whereas several studies have shown that children show bias in the context of many kinds of groups, much less is known about how and when general psychological tendencies and contextual factors contribute to the manifestation of intergroup bias across development, and whether individual differences play a role. In the present study, we pursue these questions by investigating and comparing the developmental trajectories of intergroup bias in 5- to 10-year-old (mostly) White children (n = 100). We assessed children's liking and preferences towards 4 racial groups (White, East Asian, Black, and Middle Eastern) and towards 2 gender groups (male and female) in a within-subject design. We found that the young children in our sample showed a significant racial and gender ingroup bias, speaking to an early and strong manifestation of intergroup bias on the basic ingroup-outgroup distinction. This bias decreased with age. At the same time, we found considerable differences between the different types of outgroups from early on. Furthermore, there were remarkable differences between the developmental trajectories of gender and racial intergroup bias, highlighting the role of both social and contextual influences. Finally, our results did not reveal consistent evidence for the influence of individual differences on children's intergroup bias.


Synthesis of Functionalized Cyclopropanes from Carboxylic Acids by a Radical Addition-Polar Cyclization Cascade.
Herein, we describe the development of a photoredox-catalyzed decarboxylative radical addition-polar cyclization cascade approach to functionalized cyclopropanes. Reductive termination of radical-polar crossover reactions between aliphatic carboxylic acids and electron-deficient alkenes yielded carbanion intermediates that were intercepted in intramolecular alkylations with alkyl chlorides appended to the alkene substrate. The mild conditions, which make use of a readily available organic photocatalyst and visible light, were demonstrated to be amenable to a broad range of structurally complex carboxylic acids and a wide variety of chloroalkyl alkenes, demonstrating exquisite functional group tolerance.


Tectonic influence on Cenozoic mammal richness and sedimentation history of the Basin and Range, western North America.
Tectonic activity can drive speciation and sedimentation, potentially causing the fossil and rock records to share common patterns through time. The Basin and Range of western North America arose through widespread extension and collapse of topographic highlands in the Miocene, creating numerous basins with rich mammalian fossil records. We analyzed patterns of mammalian species richness from 36 to 0 million years ago in relation to the history of sediment accumulation to test whether intervals of high species richness corresponded with elevated sediment accumulation and fossil burial in response to tectonic deformation. We found that the sedimentary record of the Basin and Range tracks the tectonic evolution of landscapes, whereas species-richness trends reflect actual increased richness in the Miocene rather than increased fossil burial. The sedimentary record of the region broadly determines the preservation of the fossil record but does not drive the Miocene peak in mammalian species richness.


Recovery of midcycle human follicular oocytes: correlation of their morphology with endomethrial and follicular histology.
The ovarian follicles of 23 of 33 women undergoing elective pelvic laparotomy during menstrual cycle days 11 to 17 were aspirated by a low-vacuum device. The study compared the ovulatory status of women in midcycle with the health of the oocytes obtained, and determined the frequency of recovery of mature oocytes without the preadministration of exogenous hormones. Maturing or mature oocytes were obtained from 22% and nonmature oocytes from 48% of the 23 women. Sixty per cent of the women in each of the maturing or mature and nonmature groups were postovulatory as judged by evaluation of the endometrial and ovarian tissue recovered. Furthermore, 20% of the maturing or mature oocytes and 65% of the nonmature oocytes showed a moderately heavy amount of cytoplasmic degeneration, which was independent of ovulatory status. Therefore, it is concluded that, because of the relatively low rate of return of oocytes, the frequent postovulatory status of patients in midcycle, and uncertainty about the viability of the oocytes so obtained, women not stimulated by exogenous hormones are ill-suited for recovery of maturing or mature follicular oocytes for in vitro fertilization studies.


Statistical comparisons of blood alcohol samples from 6-mL and 10-mL grey-top tubes.
Historically, blood alcohol concentration (BAC) studies utilized a 1% concentration of the preservative sodium fluoride (NaF), leaving an information gap supporting usage of lower concentrations of NaF to preserve ethanol. As many forensic laboratories utilize Becton, Dickinson and Company 6-mL gray-top tubes (0.25% NaF), statistical comparisons were conducted to determine whether significant differences exist between BAC values obtained from 6-mL tubes versus 10-mL tubes (1% NaF). Whole blood was spiked at three concentrations, (0.04, 0.08, and 0.15 g/100 mL) and aliquoted into tubes at "low," "medium," and "high" fill volumes. Tubes were split into refrigerated or ambient storage and analyzed after 1, 3, 5, 7, and 30 days, using headspace gas chromatography. Each 6-mL and 10-mL tube pair, prepared, stored, and analyzed under identical conditions, was compared by t-test (95% confidence level). For refrigerated tubes, 32 of 45-tube pairs did not reject the null hypothesis (that 6-mL and 10-mL tubes yield equivalent BACs), and 31 of 45 ambient stored tube pairs did not reject the null hypothesis. Analysis of variance (ANOVA) found no significant differences between 6-mL and 10-mL gray-top tubes for 0.04 and 0.15 g/100 mL concentrations over 30 days; significant differences were observed for 0.08 g/100 mL concentration tubes, which warrants further study. Paired t-tests of grouped samples found no significant differences between 6-mL and 10-mL tubes at any concentration.


The inhibitory effect of CD46, CD55, and CD59 on complement activation after immunotherapeutic treatment of cervical carcinoma cells with monoclonal antibodies or bispecific monoclonal antibodies.
The role of membrane-bound complement regulatory proteins (mCRP) in the protection of tumor cells in vivo against elimination by the immune system is still unknown. In this study the effect of expression of these mCRP by cervical cancer cells was investigated. In situ expression of mCRP was observed on cervical carcinomas, normal cervical epithelial cells, and the surrounding stroma. Deposition of C3 and C5b-9 was sporadically found on the tumor cells and the surrounding stroma. A low expression of CD46 was statistically significantly associated with deposition of C3. Comparable expression patterns were shown on primary cervical tumor cell suspensions. A relatively high deposition of C4c was found on these tumor cells, indicating classical pathway activation. Furthermore, it was demonstrated that CD55 and CD59 were the most potent inhibitors of C3 deposition and classical pathway-mediated lysis, respectively, on cervical cancer cell lines. The feasibility of increasing complement activation at the tumor cell membrane surface was demonstrated with an anti-HLA Class I*anti-CD55 bispecific mAb. The potential immunotherapeutic applicability was investigated with both anti-G250*anti-CD55 and anti-Ep-CAM*anti-CD55 bispecific mAbs. An approximate 2-fold increase in C3 deposition, compared with the parental anti-Ep-CAM mAb, was attained with an anti-Ep-CAM*anti-CD55 bispecific mAb when the tumor-associated antigen was expressed in sufficient amounts. These results demonstrate that when tumor-associated antigens are expressed in adequate amounts, bispecific mAbs in vivo may be potent immunotherapeutic agents to enhance an inflammatory reaction at the tumor site.


A comparison of resident and program director views on the effects of subspecialty fellowships on residency training in obstetrics and gynecology.
In separate nationwide surveys, chief administrative residents and residency program directors reported their views on the impact of subspecialty fellowships on residency training. The residents expressed a less positive view of the fellowships, but like the directors, considered them beneficial to their training. The directors underestimated the degree residents regret the loss of operative experiences to the fellows, particularly in laser surgery, infertility surgery, and radical pelvic surgery. Within a given residency program, resident and program director opinions of the fellowships appear unrelated or contradictory. The implications of these findings for a discussion between residents and program directors are presented.


The Effect of Uterine Contractions on Fertility Outcomes in Frozen Embryo Transfer Cycles: A Cohort Study.
The relationship between uterine peristalsis before embryo transfer and the success of assisted reproductive techniques (ARTs) has not been properly investigated. In this study, the effect of uterine contractions on embryo implantation in frozen embryo transfer (FET) cycles was investigated to determine whether the frequency of uterine contractions can be used as a quantitative marker to assess endometrial receptivity. In this cohort study of 68 eligible FET candidates, one hour before embryo transfer (ET), frequency of uterine contractions was assessed with transvaginal ultrasonography. Patients were followed up for 20 weeks. The association between FET outcomes including clinical pregnancy, abortion, and ectopic pregnancy with uterine contractions was evaluated. Binary logistic regression was conducted to test the association between clinical pregnancy outcomes in different groups. The p<0.05 were considered statistically significant. Of 68 patients, 25 (36.8%) experienced clinical pregnancy. Multiple logistic regression for omitted confounders (age, BMI, duration, type and cause of infertility) revealed that patients with uterine peristaltic wave frequency less than 2≤ wave/min had higher chance of successful pregnancy compared to those with ≥4 wave/min (odds ratio: 10.8; 95% confidence interval: 1.5-79.4, p=0.019). The Pearson's correlation showed a statistically significant relationship between the frequency of uterine contraction and endometrial thickness (r= 0.42, p=0.002). Patients with uterine peristalsis of <4.0 wave/min before embryo transfer had a higher chance of successful implantation and pregnancy compared with those with higher contraction frequencies. It seems that measuring uterine contraction frequency before embryo transfer might help to predict pregnancy outcomes.


Recent advances in understanding the genetic basis of systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a polygenic chronic autoimmune disease leading to multiple organ damage. A large heritability of up to 66% is estimated in SLE, with roughly 180 reported susceptibility loci that have been identified mostly by genome-wide association studies (GWASs) and account for approximately 30% of genetic heritability. A vast majority of risk variants reside in non-coding regions, which makes it quite challenging to interpret their functional implications in the SLE-affected immune system, suggesting the importance of understanding cell type-specific epigenetic regulation around SLE GWAS variants. The latest genetic studies have been highly fruitful as several dozens of SLE loci were newly discovered in the last few years and many loci have come to be understood in systemic approaches integrating GWAS signals with other biological resources. In this review, we summarize SLE-associated genetic variants in both the major histocompatibility complex (MHC) and non-MHC loci, examining polygenetic risk scores for SLE and their associations with clinical features. Finally, variant-driven pathogenetic functions underlying genetic associations are described, coupled with discussion about challenges and future directions in genetic studies on SLE.


Interactions of free-living amoebae with the rice fungal pathogen, Rhizoctonia solani.
Rhizoctonia solani is a soil-borne fungal pathogen of many important crop plants. In rice, R. solani causes sheath blight disease, which results in devastating grain yield and quality losses. Few methods are available to control this pathogen and classic single gene resistance mechanisms in rice plants have not been identified. We hypothesize that alternate means of control are available in the environment including free-living amoebae. Amoebae are soil-, water- and air-borne microorganisms that are predominantly heterotrophic. Many amoeba species are mycophagous, and several harm their prey using mechanisms other than phagocytosis. Here, we used light and scanning electron microscopy to survey the interactions of R. solani with four amoeba species, with the goal of identifying amoebae species with potential for biocontrol. We observed a wide range of responses during interactions of R. solani with four different free-living amoebae. Two Acanthamoeba species encyst in co-cultures with R. solani at higher rates than medium without R. solani. Vermamoeba vermiformis (formerly Hartmanella vermiformis) attach to R. solani mycelium and are associated with mycelial shriveling and perforations of fungal cell walls, indicating an antagonistic interaction. No phenotypic changes were observed in co-cultures of Dictyostelium discoideum and R. solani.


Genital Cortex: Development of the Genital Homunculus.
The cortical representation of male and female genitals, unlike that of the rest of the body, undergoes late expansion during puberty and is modulated by sexual experience. Using chronic imaging, a recent study has shed light on the cellular changes that accompany the sex-hormone- and experience-dependent expansion of the genital cortex.


Cloning, sequencing, and characterization of CYP1A1 cDNA from leaping mullet (Liza Saliens) liver and implications for the potential functions of its conserved amino acids.
A 2,037 bp CYP1A1 cDNA (GenBank AF072899) was cloned through screening of a lambdaZipLox cDNA library constructed from the liver of a leaping mullet (Liza saliens) fish captured from Izmir Bay on the Aegean coast of Turkey using rainbow trout CYP1A1 cDNA as a probe. This clone has a 130 bp 5'-flanking region, a 1,563 bp open reading frame (ORF) encoding a 521-amino acid protein (58,972 Da), and a 344 bp 3'-untranslated region without a poly (A) tail. Alignment of the deduced amino acids of CYP1A1 cDNAs showed 58% and 69-96% identities with human and 12 other fish species, respectively. Southern blot analysis suggested that this CYP1A1 cDNA was from a single-copy gene. Based on the comparison with CYP1A1 genes reported for fish and mammals, the leaping mullet CYP1A1 gene is probably split into 7 exons. The intron insertion sites were predicted. Alignment of the CYP1A1 cDNA encoded amino acids from 13 fish and 7 mammalian species disclosed differences in highly conserved amino acids between aquatic and land vertebrates. The possible associated secondary structure; conserved motifs and substrate-binding sites were discussed. The phylogenetic relationships of CYP1A1s among 13 fish species were analyzed by a distance method.


Denaturation of mouse satellite and ribosomal DNA during hydroxyapatite thermal chromatography of chromatin.
Mouse DNA and chromatin were melted on hydroxyapatite and the denaturation profiles of ribosomal and satellite DNAs were followed by hybridization with their complementary RNAs. Neither ribosomal nor bulk DNA had significantly different melting profiles in chromatin as compared to DNA. However, most of satellite DNA eluted at higher temperature from chromatin than from purified DNA. One explaination for the higher melting temperature of mouse satellite DNA in chromatin suggests that the complex between this particular DNA component and at least some proteins in chromatin is more stable than the average DNA-protein interaction.


Thrombotic risk assessment in patients with systemic lupus erythematosus: Validation of the adjusted-Global Antiphospholipid Syndrome Score (aGAPSS) in Thai patients.
The adjusted-Global Antiphospholipid Syndrome Score (aGAPSS) has been validated and used to predict antiphospholipid antibodies (aPL) related to vascular thrombosis (VT). To validate aGAPSS for predicted aPL-related VT and pregnancy complications (PC) in Thai systemic lupus erythematosus (SLE) patients. A cross-sectional study was performed among Thai SLE patients with clinical manifestations; history of VT and PC, cardiovascular risk factors, and aPL profiles were collected. The aGAPSS was calculated from the sum of the risk factors (hyperlipidemia = 3.0, arterial hypertension = 1.0, anti-cardiolipin antibody = 5.0, anti-b2 glycoprotein I antibody = 4.0, and lupus anticoagulant = 4.0). Of 132 SLE patients, 12 (9.1%) had VT and 5 (4.1%) had PC. When comparing the aGAPSS (median; interquartile range [IQR]) of patients with events (VT and/or PC) (6.5; IQR 3.3-9.0), VT (8.0; IQR 4.0-9.0), arterial thrombosis (3.5; IQR 1.0-5.8), and PC (9.0; IQR 8.0-11.5), and the aGAPSS of patients without an event (3.0; IQR 0-4.0), aGAPSS of patients with events was significantly higher, except in patients with arterial thrombosis. An aGAPSS of 4.5 or more was associated with risk of aPL-related VT (sensitivity 71.4%, specificity 76.7%), and an aGAPSS of 6.0 or more was associated with risk of aPL-PC (sensitivity 100%, specificity 84.0%). The aGAPSS could predict the risk of aPL-PC and aPL-related VT in Thai SLE patients.


Some erythromycin derivatives are strong inducers in rats of a cytochrome P-450 very similar to that induced by 16 alpha-pregnenolone carbonitrile.
Erythromycin derivatives having lost the cladinose moiety, erythralosamine and its mono- and diacetate, are strong inducers of liver cytochrome P-450, better than troleandomycin, in rats. The major cytochrome P-450 form induced by all these macrolides is electrophoretically and immunologically indistinguishable from the major form induced in rats by pregnenolone carbonitrile. This form is particularly able to metabolize the macrolides and to lead to the corresponding 456 nm absorbing cytochrome P-450 metabolite complexes in vivo and in vitro.


Endothelial prostacyclin (PGI-2) production of human and porcine valve allografts related to ischemic history.
The significance of cellular viability in human valve allografts for functional clinical longevity continues to be debated. Meaningful tests for this biological entity are therefore in demand to quantify the relative merits of graft origin and procurement techniques. The valve leaflet endothelium is recognized as a particularly sensitive target to noxes and its continued ability to produce prostacyclin (PGI-2) after explantation has been suggested as indicating viability. Graft ischemic history and species differences were therefore studied in human and porcine valve leaflets by the measurement of endothelial prostacyclin production, post-explantational, basal and after stimulation with bradykinin. Four groups of aortic valve donors were established. Fresh human heart-beating donors (h-HBD), cadaveric human donors (h-NHBD) processed within 24 h, fresh porcine donors (p-HBD) and cadaveric porcine donors (p-NHBD) also processed within 24 h. Leaflets were separately incubated at 37 degrees C for successive periods of 30 min up to 5 h in Earle's Medium 199. After 240 min PGI-2 production was stimulated by 10 microM bradykinin. Postincubational release was stopped with indomethacin 10 microg/ml. Prostacyclin production was measured as 6-kPGF1a using an ELISA. Initial PGI-2 production is significantly higher in porcine than in human grafts and in both species enhanced by previous warm ischemia. While baseline species differences disappear during progressive incubation, differences resulting from graft history are maintained. After PGI-2 stimulation species differences dominate again while ischemic history has no effect. Ischemia and surgical manipulation are stimulators of endothelial PGI-2 production in both human and porcine allografts and, therefore, a correlation of this metabolic activity with cellular integrity may be misleading. Valid data are obtained only if the natural time-course and reaction to stimulation of PGI-2 production are duely recognized and species differences in the response to mechanical and ischemic stress are considered.


Relationship between cardiovascular resting state and visual attention.
Cardiovascular features seem to modulate performance in attention tasks. We investigated the relationship between blood pressure, resting heart rate and heart rate variability (HRV) and performance in a visuospatial attention task comparing normotensive and hypotensive young adults. We found an association between resting HRV and visual attention performance only in the normotensive group. In addition, we provided a further evidence of attention impairment in hypotensive individuals.


Radiation-induced changes in liver and kidney alkaline phosphatase and esterase of mice.
Whole-body exposure of mice to 2 Gy gamma radiation results in an increase in the specific and total activities of esterase and alkaline phosphatase found in the supernatant of liver and kidney. This increase developed at 1 h, reached a maximum at 24 h, and then declined at 48 h after irradiation. The increase in the activity of these enzymes was not accompanied by an increase in protein content. Electrophoretic analysis on acrylamide gel confirmed the results obtained by the quantitative biochemical analysis. An increase in the level and/or number of bands was observed postirradiation.