Role of calpain in the formation of human papillomavirus type 16 E1^E4 amyloid fibers and reorganization of the keratin network.
The human papillomavirus (HPV) type 16 E1^E4 (16E1^E4) protein is expressed in the middle to upper layers of infected epithelium and has several roles within the virus life cycle. It is apparent that within the epithelium there are multiple species of 16E1^E4 that differ in length and/or degree of phosphorylation and that some or all of these can associate with the cellular keratin networks, leading to network disruption. We show here that the cellular cysteine protease calpain cleaves the 16E1^E4 protein after amino acid 17 to generate species that lack the N terminus. These C-terminal fragments are able to multimerize and form amyloid-like fibers. This can lead to accumulation of 16E1^E4 and disruption of the normal dynamics of the keratin networks. The cleavage of E1^E4 proteins by calpain may be a common strategy used by α-group viruses, since we show that cleavage of type 18 E1^E4 in raft culture is also dependent on calpain. Interestingly, the cleavage of 16E1^E4 by calpain appears to be highly regulated as differentiation of HPV genome-containing cells by methylcellulose is insufficient to induce cleavage. We hypothesize that this is important since it ensures that the formation of the amyloid fibers is not prematurely triggered in the lower layers and is restricted to the upper layers, where calpain is active and where disruption of the keratin networks may aid virus release.


[Malignant degeneration in women operated on for endometriosis].
The endometriosis can undergo estrogen-dependent changes similar to endometrium and may carry a risk for developing hyperplasia and carcinoma during unopposed estrogen stimulation. We reviewed the existing literature to analyze the potential of malignancy arising from extraovarian endometriosis by estrogen stimulation. Our two cases are also discussed. According to our study there are 21 cases published in the literature of malignant transformation of endometriosis after estrogen stimulation. The most common place for malignant trans formation is the vagina. The most common hystological type is adenocarcinoma in 13 cases. Our two cases were with adenocarcinoma and adenosquamous carcinoma. The incidence of malignant transformation of the endometriosis can not be estimated based upon these cases. There is a need for randomised clinical trials. The estrogen stimulation may lead to premalignant or malignant transformations of the residual foci of endometriosis. That is why addition of progestins to the estrogen substitutional therapy should be considered in women with endometriosis after total hysterectomy with oophorectomy, especially if a residual foci are present or suspected. With our study we think we can make more clear the way an endometriosis is transformed into a malignancy.


Joint Corticosteroid Injection Associated With Higher Physical Therapy Compliance in Knee Osteoarthritis.
Background Knee corticosteroid injection (KCSI) and physical therapy (PT) are two efficacious treatments for knee osteoarthritis (KOA). However, poor adherence to PT in resource-limited communities might limit its effectiveness. KCSI prior to PT might improve adherence in this population. Methodology This was a retrospective cohort analysis of patients referred to PT for KOA from January 01, 2018 to December 31, 2019 from an adult primary care resident clinic in Hartford, Connecticut, USA. Patients were divided into two groups, namely, those who had a KCSI around the time of the referral versus those who did not. PT adherence was evaluated in both groups. Results A total of 143 patients referred to PT were selected, and 11 patients were excluded. In total, 38/132 patients had a KCSI within a four-month window of the PT referral. Patients were mostly Hispanic (no injection 79.8% vs. injection 78.9%) females (80.9% vs. 71.1%), the average age was in the 60s, and over 90% were insured by either Medicaid or Medicare. In the injection group, 18/38 patients completed at least one PT visit (47.4%) versus 21/94 patients (22.3%) in the noninjection group. The odds ratio of undergoing PT was 1.38 (95% confidence interval [CI] = 1.14-1.69; p = 0.002), and the rate ratio of PT visits was 2.50 (95% CI = 1.82-3.42; p = 1.36 × 10-8), both adjusted for age, sex, and severity. Among those who attended at least one session, the mean number of PT visits was 5.4 in both injection and noninjection groups (median 5 versus 4). Conclusions In a predominantly Hispanic patient population, those who underwent KCSI were more likely to undergo PT and, as a group, attend more sessions.


Isolation, Culture, and Differentiation of Bone Marrow Stromal Cells and Osteoclast Progenitors from Mice.
Bone marrow stromal cells (BMSCs) constitute a cell population routinely used as a representation of mesenchymal stem cells in vitro. They reside within the bone marrow cavity alongside hematopoietic stem cells (HSCs), which can give rise to red blood cells, immune progenitors, and osteoclasts. Thus, extractions of cell populations from the bone marrow results in a very heterogeneous mix of various cell populations, which can present challenges in experimental design and confound data interpretation. Several isolation and culture techniques have been developed in laboratories in order to obtain more or less homogeneous populations of BMSCs and HSCs invitro. Here, we present two methods for isolation of BMSCs and HSCs from mouse long bones: one method that yields a mixed population of BMSCs and HSCs and one method that attempts to separate the two cell populations based on adherence. Both methods provide cells suitable for osteogenic and adipogenic differentiation experiments as well as functional assays.


RGC-32 and diseases: the first 20 years.
The response gene to complement (RGC)-32 acts as a cell cycle regulator and mediator of TGF-β effects. However, recent studies have revealed other functions for RGC-32 in diverse processes such as cellular migration, differentiation, and fibrosis. In addition to its induction by complement activation and the C5b-9 terminal complement complex, RGC-32 expression is also stimulated by growth factors, hormones, and cytokines. RGC-32 is induced by TGF-β through Smad3 and RhoA signaling and plays an important role in cell differentiation. In particular, RGC-32 is essential for the differentiation of Th17 cells. RGC-32-/- mice display an attenuated experimental autoimmune encephalomyelitis phenotype that is accompanied by decreased central nervous system inflammation and reductions in IL-17- and GM-CSF-producing CD4+ T cells. Accumulating evidence has drawn attention to the deregulated expression of RGC-32 in human cancers, atherogenesis, metabolic disorders, and autoimmune disease. Furthermore, RGC-32 is a potential therapeutic target in multiple sclerosis and other Th17-mediated autoimmune diseases. A better understanding of the mechanism(s) by which RGC-32 contributes to the pathogenesis of all these diseases will provide new insights into its therapeutic potential.


Selective and adaptable access to N,N'-asymmetrically substituted imidazol-2-ylidene bis-NHC ligands: Pd(II) complexes featuring wide variation in N-alkyl and aryl steric bulk.
N,N'-Asymmetrically substituted, methylene-linked bis(imidazol-2-ylidene) complexes have been prepared subsequent to a selective synthesis of the bis(imidazolium) salt precursors involving the quarternisation of N-alkyl and -aryl imidazoles with N-halomethyl imidazolium salts. The adaptability of the ligand precursor synthesis is illustrated through access to the N-Me/N'-Mes and N-Mes/N'-2,6-(i-Pr)2Ph systems, leading to the Pd(II) complexes [{(MeIm)(MesIm)CH2}Pd(L)2](n+), L = Cl/I (n = 0) and NCMe (n = 2), and [{(MesIm)[2,6-(i-Pr)2PhIm]CH2}Pd(L)2], L = Cl/I. The dicationic hybrid N,N'-alkyl/aryl complex was inactive in the copolymerisation of ethylene/carbon monoxide, displaying reactivity akin to N,N'-dialkyl analogues.


Effects of intravenous contrast media on cortical and medullary blood flow in the rat kidney.
The effect of slow intravenous infusion of contrast medium (CM) (1600 mg I/kg body weight) on cortical blood flow (BF) and medullary BF in rat kidneys was investigated by laser-Doppler flowmetry on either renal cortex or exposed renal papillas (inner medulla). The effect on cortical BF was evaluated after infusion of either ioxaglate, iohexol, or ioxithalamate. Mannitol and Ringer's solution were used as control substances. The effect on medullary BF was examined after infusion of either ioxaglate, iohexol, iopamidol, ioxithalamate, or mannitol. BF was measured continuously during a 30-minute control period and a 60-minute experimental period, starting with the CM infusion. Cortical BF was unchanged in the ioxaglate group and significantly increased in the iohexol, ioxithalamate, and mannitol groups (P less than .05). Medullary BF was moderately increased in the ioxaglate group (P less than .05) but moderately decreased in the groups that received iohexol, iopamidol, ioxithalamate, or mannitol (P less than .05). The reduction in medullary BF following infusion of the ratio 3.0 nonionic CM and of the ratio 1.5 ionic CM might be one contributory mechanism to the pathogenesis of CM nephropathy, especially in the presence of microangiopathy in the kidney.


Personalized Smart Clothing Design Based on Multimodal Visual Data Detection.
In the traditional clothing customization system, only the designer participates in the clothing design, and the style is single. In the face of numerous styles, the user just repeatedly arranges and combines the styles, but does not realize the user's innovative design. In this paper, we propose a novel multitask deep convolutional neural network training method for task-by-task transfer learning, and learn deep image features for image retrieval tasks on noisy user click data. Image retrieval model based on image-text multimodal correlation features: this paper uses image-text multimodal correlation features to calculate the correlation between query keywords and images, and calculates the correlation between images and images. In this paper, the method of automatic generation of clothing style is researched, and parameterized coding is designed for it. Taking the typical style of suits as the initial population, through the human-computer interaction interface, the scoring value is assigned to the fitness value to carry out the evolution process. The binary string of the suit style generated by the genetic algorithm is decoded through the decoding algorithm and rules, decoded into a visual style diagram of the style of the suit style, and the style diagram of the suit style is automatically drawn. From the perspective of clothing design, this paper summarizes the general design methods of outdoor sports smart clothing, follows the integration of people-clothing-environment, and proposes a wearer-centered design concept to deeply explore the rationality of outdoor sports smart clothing design methods. This paper further solves the key problems in the design process, and takes the fashion of clothing as the core principle to design the structure of clothing modeling. The fabric selection of suits is based on the principle of clothing comfort. The key is to realize the outdoor sports monitoring function of suits through sensing technology. The design uses Arduino as an electronic prototype platform, so as to detect the heart rate of the human body during exercise and the microclimate temperature under the clothes. This kind of suit with monitoring function is ultimately a combination of sensing device and clothing. It not only has monitoring function, but also has the aesthetic concept of clothing design and conforms to the performance of human body structure, which will provide reference and reference for the design of outdoor sports smart clothing.


Non-pharmacological treatments of insomnia.
Insomnia is a prevalent and complex disorder to treat. This article reviews the prevalence, etiology, diagnosis and treatment of insomnia. With regard to treatment, there now exists an extensive literature demonstrating that compared with pharmacological treatments a range of non-pharmacological therapies are of proven clinical efficacy and durability. These include, for example, stimulus control therapy, bedtime restriction therapy, relaxation therapy, cognitive therapy and bright light therapy. These therapies are summarized and evaluated. It is recommended that therapists consider non-drug treatments based on cognitive-behavioral principles when managing a patient with insomnia.


The deposition of immunoglobulins and complement in stratum corneum in microscopic lesions in patients with active psoriasis: the relationship to hyperproliferation.
The morphology of the horny layer was utilized to determine the age distribution of corneocytes in early psoriatic lesions and in their vicinity. By using the age distribution the number of corneocyte layers found in any time interval could be obtained and expressed as the rate of corneocyte layers formed. Deposits if immunoglobulins G, M and A and C3 were also age-distributed in a similar way. In the period during which the horny layer was formed, variation in the rate of corneocyte formation could be related to the appearance of immunodeposits. Hyperproliferation was found to precede deposits of immunoglobulins G, M and A and C3 by one to several days. Deposits were examined both visually and by means of microfluorometry, with the same result. The specificity of the deposits was established in two ways. A Fab2-anti-immunoglobulin conjugate was used to detect a possible Fc receptor binding. This was not demonstrated. Albumin was used as a plasma filtrate marker. Albumin was not found in the horny layer but was abundant in the intercellular spaces in the rest of the epidermis. It was concluded that the immunodeposits found in the early lesions of psoriasis are a secondary phenomenon during the initiation of a psoriatic lesion.


Leigh's subacute necrotizing encephalomyelopathy manifesting as spasmus nutans.
Subacute necrotizing encephalomyelopathy (SNE), or Leigh's disease, is an unusual neurologic disorder that is associated with nystagmus, strabismus, and optic atrophy in the majority of cases, and is most often described in infants. The defect currently thought to account for SNE is the presence of an inhibitor factor in the thiamine pathway. We saw a patient whose eye findings initially were believed to represent spasmus nutans, but whose clinical course, computed tomographic findings, and autopsy findings were typical of SNE.


Short-term improvements in the body schema can modulate pain perception in fibromyalgia syndrome.
This study aimed to evaluate the pain perception and several aspects of disrupted body schema, in a sample of patients suffering from fibromyalgia (FM) syndrome. Twenty-six patients were organised into two groups: the tactile discrimination group and control group (exposed to tactile stimulation alone). Outcome measures were the pain intensity in body regions commonly described as painful (visual analogue scale) and clinical status, body esteem scale (BES), interoceptive awareness. Tactile acuity was measured by the two-point discrimination test (TPD), hits in the location of the stimulus, the probe size discrimination and the graphesthesia task. The group exposed to tactile discrimination experienced a significant improvement in all tactile acuity outcome measures. The decrease of the Fibromyalgia Impact Questionnaire variable was relevant (81.58, SEM 3.29 vs. 72.91, SEM 6.43; p=0.07). Likewise, pain perception was lower in all of the body regions evaluated (reduction of 12.2% in the stimulated body region (cervical VAS) with a large effect size, a pain reduction of 11.3% in the wrists and 9.2% in the knees. The correlation index showed association between the cervical VAS and TPD (ρ=0.53; p<0.05). There was no improvement in pain scores in the control group but the TPD was decreased also. The BES scores did not show differences between groups. However, interoceptive awareness showed a slight reduction in the group exposed to tactile discrimination (3.68, SEM 0.15 vs. 3.35, SEM 0.19; p=0.01). After short-term tactile discrimination protocol, the group exposed to tactile discrimination experienced a significant improvement in all tactile acuity outcome measures: pain perception, tactile acuity and body perception, compatible with adjustments in the body schema. The tactile stimulation alone group did not show the same improvement.


The venocutaneous fistula: a new technique for reducing venous congestion in replanted fingertips.
The venocutaneous fistula technique, which involves the construction of a temporary venous return bypass using a venous graft, was devised to prevent venous congestion after fingertip replantation surgery. The proximal side of the venous graft is anastomosed to a vein at the dorsum of the finger. The distal side of the graft is sutured to the skin around a punch wound on the volar side of the replanted fingertip. This procedure was applied successfully to four fingertips in two patients without any anastomosis of the proper vein or the application of bleeding wound techniques or medicinal leeches. This method provides an excellent alternative in the treatment of venous congestion.


1,6-Naphthyridin-7(6H)-ones: synthesis and optical properties.
Efficient synthesis of original 1,6-naphthyridin-7(6H)-ones and their optical properties are described. Their powerful fluorescence properties including dual fluorescence, solvatochromism, acidochromism, large Stokes shifts and high quantum yields, suitable for biological applications or as luminescent devices in materials science, are evidenced.


Conservative management of squamous cell carcinoma of the anal canal.
The treatment of anal carcinoma with concurrent chemo/radiotherapy has largely replaced abdominoperineal resection as the primary management. This report details the outcome of 62 patients with anal carcinoma treated at a single institution over a 10 year period, during which this approach has become the mainstay of therapy. Of the 34 patients treated with combination radiotherapy and chemotherapy (5-fluorouracil and mitomycin-C), 31 were evaluable and a complete response was achieved in 77%. The estimated 5 year failure-free survival was 67% and the overall survival was 81%. The overall survival was superior to that in patients treated with radiotherapy alone. Eighty-four per cent of patients received the treatment as planned, while the remainder had a reduction in the dose of radiation or chemotherapy due to acute toxicity. The use of combination therapy for primary management of anal carcinoma is generally well tolerated, appears to provide a treatment outcome at least equivalent to surgery, and allows preservation of anal function. Concurrent chemo/radiotherapy should be considered in the initial management of patients with anal carcinoma.


Missing Aspirated Impacted Denture Requiring Tracheotomy for Removal.
Aspirated foreign bodies continue to present challenges to otorhinolaryngologists. Removal of impacted airway foreign bodies via conventional methods can at times pose difficulty. This may be related to the location and type of foreign body, experience of the surgeon and anesthetist, and the availability of appropriate instruments. In adults, especially in edentulous patients, a swallowed denture usually gets lodged in the esophagus and entrance into the airway is uncommon. We report a case of an uncommon foreign body (3-toothed artificial denture plate) impacted in the trachea of a 40-year-old male following an acute episode of an epileptic attack in which conventional methods of foreign body removal had failed. It was eventually removed via a direct laryngoscopy and tracheotomy technique. This type of impaction of a large denture in the trachea is uncommon and late presentation after aspiration is even more rare. This unusual case of a foreign body in the airway is interesting due to its rarity, mode of entry, site of impaction, variable clinical presentation, and method of removal; and hence, prompted the authors to report this case.


Cortical quantitative MRI parameters are related to the cognitive status in patients with relapsing-remitting multiple sclerosis.
We aimed to assess cortical damage in patients with relapsing-remitting multiple sclerosis (RRMS)/clinically isolated syndrome (CIS) with a multiparametric, surface-based quantitative MRI (qMRI) approach and to evaluate the correlation of imaging-derived parameters with cognitive scores, hypothesizing that qMRI parameters are correlated with cognitive abilities. Multiparametric qMRI-data (T1, T2 and T2* relaxation times and proton density (PD)) were obtained from 34 patients/24 matched healthy control subjects. Cortical qMRI values were analyzed on the reconstructed cortical surface with Freesurfer. We tested for group differences of cortical microstructural parameters between the healthy and patient collectives and for partial Pearson correlations of qMRI parameters with cognitive scores, correcting for age. Cortical T2-/T2*-/PD values and four cognitive parameters differed between groups (p ≤ 0.046). These cognitive scores, reflecting information processing speed, verbal memory, visuospatial abilities, and attention, were correlated with cortical T2 (p ≤ 0.02) and T2* (p ≤ 0.03). Cortical changes appeared heterogeneous across the cortex and their distribution differed between the parameters. Vertex-wise correlation of T2 with neuropsychological parameters revealed specific patterns of cortical damage being related to distinct cognitive deficits. Microstructural changes are distributed heterogeneously across the cortex in RRMS/CIS. QMRI has the potential to provide surrogate parameters for the assessment of cognitive impairment in these patients for clinical studies. The characteristics of cognitive impairment in RRMS might depend on the distribution of cortical changes. • The goal of the presented study was to investigate cortical changes in RRMS/CIS and their relation to the cognitive status, using multiparametric quantitative MRI. • Cortical T2, T2*, and PD increases observed in patients appeared heterogeneous across the cortex and their distribution differed between the parameters. • Vertex-wise correlation of T2 with neuropsychological scores revealed specific patterns of cortical changes being related to distinct cognitive deficits.


Vortex lattice structural transitions: a Ginzburg-Landau model approach.
We analyze the rhombic to square vortex lattice phase transition in anisotropic superconductors using a variant of Ginzburg-Landau theory. The mean-field phase diagram is determined to second order in the anisotropy parameter, and shows a reorientation transition of the square vortex lattice with respect to the crystal lattice. We then derive the long-wavelength elastic moduli of the lattices, and use them to show that thermal fluctuations produce a reentrant rhombic to square lattice transition line, similar to recent studies which used a nonlocal London model.


Influence of matrix type on surface roughness of three resins for provisional crowns and fixed partial dentures.
This study evaluated the effect of matrix type on the surface roughness of resins for provisional crowns and fixed partial dentures. Ninety specimens of two acrylic resins (Trim II, Tab2000) and one bis-acryl composite (Protemp II Garant) were fabricated using one of three matrices: irreversible hydrocolloid (Cavex CA37), poly(vinyl siloxane) (Aquasil) or vacuum-formed matrix (Bio-flow Hard). The sample size for each resin-matrix combination was 10. The vestibular face of one natural maxillary central incisor was used as a model to fabricate all the specimens, following the custom fabrication technique. The average roughness measurements, Ra (mum), were obtained using a profilometer, and the data were analyzed using Kruskal-Wallis and Mann-Whitney U-tests. The results were contrasted against the surface roughness of the tooth using a one-sample t-test. Aquasil and vacuum-formed matrix had a smoother surface than Cavex CA37 regardless of the resin tested (p < 0.05). Protemp II Garant had the smoothest surface regardless of the matrix used, with no significant differences when polymerized against the three different matrices. Trim II polymerized against Cavex CA37 had a rougher (p < 0.05) surface than Aquasil or vacuum-formed matrix. Tab2000 had the smoothest surface (p < 0.05) when polymerized against a vacuum-formed matrix. There is no universal matrix that produces the smoothest surface: this depends on the compatibility between the resin and the matrix. Protemp II Garant polymerized against Cavex CA37 matrix yields a surface that is smooth enough not to require polishing unless this surface is adjusted.


A case report on a rare anatomic variant of cystic duct insertion.
We report a case a 70-year-old female presenting with abdominal pain who has a cystic duct coursing medial to the common bile duct before anastomosing just proximal to the ampulla. Low medial insertion of the cystic duct is a rare anatomic variant that is easily misidentified on imaging studies and may complicate surgical and percutaneous intervention. It can be identified by pre-operative imaging modalities such as magnetic resonance cholangiopancreatography.


Intravital two-photon imaging of T-cell priming and tolerance in the lymph node.
Two-photon microscopy makes it possible to image in real-time fluorescently labeled cells located in deep tissue environments. We describe a procedure to visualize the behavior of lymph node T cells during either priming or tolerance, in live, anesthetized mice. Intravital imaging of T lymphocytes is a powerful tool to study the cellular orchestration of adaptive immune responses in physiological settings. This method should provide new insights into the regulation of lymphocyte migration and cell-cell interactions in various immunological contexts.


Queer(y)ing aging-potentialities and problems in applying Queer Theory to studies of aging and later life.
Queer Theory is a radically deconstructionist perspective within the humanities and social sciences. Since its initial emergence in the late 1980s and early 1990s in the field of sexualities studies, Queer Theory has increasingly been used to challenges normative notions of self, identity, temporality and the nature of being, more broadly. Whilst Queer Theory has been utilized, to some extent, in gerontology and aging studies, this article makes an original contribution to this endeavor, assessing the potentiality and problems with queer(y)ing three aspects of aging: chronology; cognition; and frailty and vulnerability. To achieve this, the article draws on ideas from some key Queer theorical writers, existing studies of queer aging and illustrates theoretical points with qualitative data collected from two LGBTQ+ projects to illustrate. The article also considers problems with Queer Theory in challenging normativities associated with aging. It is concluded that despite problems, Queer Theory remains an important and valuable theoretical approach for disturbing and challenging many of the norms and understandings that shape and constrain older LGBTQ+ people's lives, in particular, and therefore have importance for how we think and understand aging and later life sociologically.


DNA repair and susceptibility to basal cell carcinoma: a case-control study.
This study investigated the role of DNA repair in susceptibility to sunlight-induced basal cell carcinoma using a host cell reactivation assay in peripheral lymphocytes. The study included Maryland basal cell carcinoma patients and cancer-free dermatologic controls who had had noncancerous skin disorders diagnosed between 1987 and 1990. Logistic regression models were used to assess the independent effect of the selected variables stratified by DNA repair level, with adjustment for age and family history. Skin type, lifetime number of severe sunburns, and actinic elastosis were also selected as risk factors for basal cell carcinoma. Cryopreserved lymphocytes from 88 cases and 135 controls were used for the DNA repair assay. When data were stratified by DNA repair level and adjusted for age and family history of skin cancer, significantly increased odds ratios associated with lighter skin (odds ratio (OR) = 3.2, 95% confidence interval (CI) 1.5-7.3), six or more severe sunburns in a lifetime (OR = 4.2, 95% CI 1.6-10.7), and moderate or severe actinic elastosis (OR = 4.4, 95% CI 1.5-12.8) were observed in persons with low DNA repair but not in those with high DNA repair. These findings suggest that impaired DNA repair may be a susceptibility factor for sunlight-induced skin cancer in the general public, as it is in patients with xeroderma pigmentosum.


[Anesthetic management for cases of placenta accreta presented for cesarean section: a 7-year single-center experience].
Anesthetic management of cesarean section for placenta accreta is very challenging. The aim of our retrospective study was to review past placenta accreta cases in our hospital to suggest a strategy for anesthetic management for placenta accreta. Placenta accreta cases were identified in our obstetric anesthesia data base. Their diagnosis, surgical procedure, amount of blood loss and anesthetic management were reviewed. Twenty-two cases of placenta accreta were identified. Of them 16 cases underwent cesarean hysterectomy. The amount of blood loss in the 22 cases ranged from 590 to 10500 ml. Neuraxial anesthesia alone was planned in 11 cases, 6 of which were converted to general anesthesia due to massive bleeding. In most of the cases, more than 2 large-bore intravenous lines and arterial line were placed prior to the beginning of surgery. All cases were well managed. We suggest the minimum requirements for anesthetic management in patients with placenta accreta as follows: (1) discussion with obstetricians to formulate a cesarean section plan, (2) early evaluation to formulate an anesthetic plan and to obtain informed consent, (3) two experienced anesthesiologists, (4) general anesthesia, (5) 2 large-bore intravenous lines, (6) an arterial line and (7) 10 units of both fresh frozen plasma and crossmatched packed red blood cells.


Collapse transitions in a flexible homopolymer chain: application of the Wang-Landau algorithm.
The thermodynamic behavior of a continuous homopolymer is described using the Wang-Landau algorithm for chain lengths up to N=561. The coil-globule and liquid-solid transitions are analyzed in detail with traditional thermodynamic and structural quantities. The behavior of the coil-globule transition is well within theoretical and computational predictions for all chain lengths, while the behavior of the liquid-solid transition is much more susceptible to finite-size effects. Certain "magic number" lengths (N=13,55,147,309,561) , whose minimal energy states offer unique icosahedral geometries, are discussed along with chains residing between these special cases. The low temperature behavior near the liquid-solid transition is rich in structural transformations for certain chain lengths, showing many similarities to the behavior of classical clusters with similar interaction potentials. General comments are made on this size dependent behavior and how it affects transition behavior in this model.


Eosinophilic esophagitis in children: immunopathological analysis and response to fluticasone propionate.
Eosinophilic esophagitis (EE) shares symptoms with gastroesophageal reflux disease but has distinctive pathologic features and unknown immunopathology. Treatments with antigen restriction or systemic immunosuppression pose problems with compliance and side effects. Topically applied steroids offer an attractive alternative treatment. The aims of this study were to determine the immunopathologic features of EE and the effectiveness of antigen-specific diet restriction (DR) and topical immunosuppression. A prospective trial was conducted examining the impact of DR and swallowed fluticasone propionate (FP) on pediatric patients with EE. Clinicopathologic features, including immunohistochemical analysis of the esophageal mucosa, were measured before and after treatment. Immunohistochemical analysis of 11 prospectively identified children showed a significantly greater number of mucosal CD3 and CD8 lymphocytes, as well as CD1a antigen-presenting cells compared with normal controls. DR did not induce clinical improvement in any patients, whereas all children who completed treatment with FP had resolution of symptoms. Posttreatment analysis of proximal and distal esophageal mucosa showed a significant reduction in the number of eosinophils, as well as CD3(+) and CD8(+) lymphocytes compared with pretreatment sections. EE is characterized by immunologically active esophageal mucosa. FP, not DR, effectively relieves symptoms. FP significantly reduces mucosal inflammation associated with EE.


Hashimoto's thyroiditis might increase polycystic ovary syndrome and associated comorbidities risks in Asia.
To investigate whether increased the comorbidities such as coronary artery disease (CAD) and risks between Hashimoto's thyroiditis (HT) and polycystic ovary syndrome (PCOS) in Taiwanese women. Patients newly diagnosed as having HT during 2000-2012 were assigned to the case group. Cases and controls were matched for age and comorbidities at a 1:2 ratio using propensity score matching. Incidence was calculated in the unit of 1000 person-year. Univariate and multivariate Cox proportional hazard regression, multivariate Cox, logistic regression, and Kaplan-Meier analyses were performed. Among 3,996 participants, 2,664 constituted the control group and 1,332 constituted the case group. The PCOS risk in patients with HT increased by 2.37 times [95% confidence interval (CI): 1.22-4.62] compared with the controls. Hypertension (HTN) [adjusted odds ratio (OR): 1.31, 95% CI: 1.03-1.66] and hyperlipidemia (adjusted OR: 1.55, 95% CI: 1.2-1.9) were more common in HT patients without PCOS than in other patients. The adjusted OR for CAD in patients with HT was 1.51 (95% CI: 1.11-2.06), whereas that in patients with HT and PCOS was 5.92 (95% CI: 1.32-26.53). In our study, the PCOS risk in patients with HT increased by 2.37 times, which is lower than the increase in HT risk in Asian patients with PCOS (4.56 times). The proportion of CAD increased significantly by 5.92 times in patients with HT and PCOS compared with patients with HT only.


Astrocytes take the stage in a tale of signaling-metabolism coupling.
Astrocytes are crucial cells in the brain that are intimately coupled with neuronal metabolism. A new paper from San Martín et al. provides evidence that physiological levels of the gaseous signal molecule NO can rapidly and reversibly increase astrocyte metabolism of glucose and production of lactate. A proposed neurological coupling-from the potential source of NO, endothelial cells, to the potential beneficiary from the lactate, neurons-prompts new questions regarding the controversial role of lactate in the brain.


Flat detectors and their clinical applications.
Diagnostic and interventional flat detector X-ray systems are penetrating the market in all application segments. First introduced in radiography and mammography, they have conquered cardiac and general angiography and are getting increasing attention in fluoroscopy. Two flat detector technologies prevail. The dominating method is based on an indirect X-ray conversion process, using cesium iodide scintillators. It offers considerable advantages in radiography, angiography and fluoroscopy. The other method employs a direct converter such as selenium which is particularly suitable for mammography. Both flat detector technologies are based on amorphous silicon active pixel matrices. Flat detectors facilitate the clinical workflow in radiographic rooms, foster improved image quality and provide the potential to reduce dose. This added value is based on their large dynamic range, their high sensitivity to X-rays and the instant availability of the image. Advanced image processing is instrumental in these improvements and expand the range of conventional diagnostic methods. In angiography and fluoroscopy the transition from image intensifiers to flat detectors is facilitated by ample advantages they offer, such as distortion-free images, excellent coarse contrast, large dynamic range and high X-ray sensitivity. These characteristics and their compatibility with strong magnetic fields are the basis for improved diagnostic methods and innovative interventional applications.


Acute myocardial infarction in an American traveler in China.
While traveling in a rural province of the People's Republic of China, an American scientist had an acute myocardial infarction that was complicated by ventricular tachycardia and congestive heart failure. Medical personnel were rapidly mobilized, and an improvised coronary care unit was created around the patient. He survived due to the organization, training, and skill of the Chinese medical staff.


[Clinical experience in using isoflurane, sevoflurane, and total intravenous anesthesia during visceral transplantation].
Based on 256 anesthesias, the authors comparatively studied the results of total intravenous anesthesia (TIVA) with neuroleptic analgesics and inhalational low- and minimal flow anesthesia with isoflurane in the anesthestic support of major operations on the liver. Both sevoflurane and isoflurane may be widely used during long and traumatic operations on the liver since the agents are distinguished by a low hepatotoxicity, the absence of pharmacological activity of their metabolism, a rapid elimination from the body in a virtually unchanged form. The use of sevoflurane and isoflurane in the low and minimal flow modes can substantially reduce the pharmacological load with opiates and myorelaxants, which is particularly important in patients with liver diseases and these modes have some advantage over TIVA during which the consumption of myorelaxants and neuroleptic analgesics has proved to be significantly higher. The minimal flow (0.4-0.5 l/min) mode uses mostly few inhalation anesthetics. The use of seroflurane reduces the period of spontaneous breathing recovery to a greater extent, activates the patient more rapidly, and substantially reduces the risk of iatrogenic complications after long and traumatic operations associated with visceral transplantation.


Conformationally locked nucleoside analogues. Synthesis of dideoxycarbocyclic nucleoside analogues structurally related to neplanocin C.
The glycon moiety of nucleosides in solution is known to exist in a rapid dynamic equilibrium between extreme northern and southern conformations as defined by the pseudorotation cycle. The concept of preparing rigid nucleoside analogues with the glycon conformation locked in one of these two extremes was tested with the synthesis of some cyclopropane-fused dideoxycarbocyclic nucleosides, similar to the well-known class of anti-HIV active dideoxynucleosides. The new compounds described here are dideoxynucleoside analogues of the fermentation product neplanocin C (6) which exhibits a typical northern geometry for its 6-oxabicyclo[3.1.0]hexane pseudosugar moiety. However, in view of the lability of the epoxide ring in this system, the equivalent cyclopropane-fused bicyclo[3.1.0]hexane system was used instead to prepare the corresponding dideoxynucleoside analogues bearing all the common bases [(+/-)-9-13]. Due to the well-documented preference of unrestricted bicyclo[3.1.0]hexane systems to exist exclusively in a boat conformation, the resulting nucleosides are structurally locked in a typical northern conformation similar to that of neplanocin C. The locked northern conformation in these nucleosides remained unchanged in solution in the 20-80 degrees C temperature range according to variable temperature 1H NMR studies. For the synthesis of these compounds, racemic trans-1-[(benzyloxy)methyl]-4-hydroxybicyclo[3.1.0]hexane [(+/-)-18] was prepared by a samarium-promoted cyclopropanation reaction with the antecedent cyclopentenol. All of the bases were incorporated under Mitsunobu conditions and converted to the desired final products following a standard methodology. Anti-HIV evaluation revealed that only the adenosine analogue (+/-)-9 possessed enough activity to warrant resolution into its optical antipodes. This was realized by chiral HPLC chromatography to give the individual enantiomers (-)-32 and (+)-33. Adenosine deaminase was used to identify isomer (+)-33 as the enantiomer with the "natural" configuration which was solely responsible for the observed biological activity and toxicity of (+/-)-9. It is possible that the exclusive northern conformation adopted by these nucleosides reduces their substrate affinity for the various activating kinases, except in the case of the adenosine analogue.


Survival study and factors associated with mortality in Chilean patients on peritoneal dialysis infected with SARS-CoV-2.
The Covid-19 pandemic has been responsible for millions of deaths worldwide. Patients with comorbidities- such as those on peritoneal dialysis (PD)- present higher morbidity and mortality than the general population. We prospectively evaluated all Chilean patients on PD (48 centres) and followed those who had Covid-19 from the beginning of the Covid-19 pandemic in Chile (March 2020) to January 2021 (start of vaccination campaign). We described demographic history, comorbidities, factors related to infection, need for hospitalisation and death due to Covid-19. During the study period, 106 adults on PD were infected by SARS-CoV-2, with a mean age of 53.1 (±16.3) and of which 53.9% were female. From that group, 54.8% required hospitalisation and 24.5% (n = 26) died due to Covid-19. Most of the patients (63.4%) were infected at home and 22.8% during hospitalisation for other reasons. There was a significant association for Covid-19 mortality with: being ≥60 years old, diabetes, time on PD ≥5 years, need for hospitalisation and hospital-acquired infection. At 90 days of follow-up, all deaths associated to Covid-19 occurred before 40 days. We conclude that patients on PD without Covid-19 vaccination have a high mortality and need for hospitalisation associated to Covid-19. To avoid this negative outcome, it is necessary to intensify strategies to avoid contagion, especially in those ≥60 years old, with diabetes and/or ≥5 years spent on PD.


Respecifying social change: the obsolescence of practices and the transience of technology.
This article proposes that social change, a fundamental topic in sociological theory, can be productively revisited by attending to studies in ethnomethodology and conversation analysis (EM/CA). We argue that the corpus of EM/CA research, from the 1960s until the present day, provides details of the constitutive and identifying aspects of practices and activities that gradually transform into descriptions of obsolescent practices and activities, and that this corpus can be revisited to learn about the ways people used to do things. Taking landline and mobile telephony as a case in point, we show that the subtle details of conversational practices are anchored in the technology used as part of the contemporary lifeworld, and that they stand for the particularities of routine social structures of their time period. We also discuss the temporal aspects of the competences required on the part of members and analysts to make sense of encountered practices in terms of their ordinary recognizability and interactional consequentiality, pointing to the anchoring of social life in its historical time. Finally, we conclude by considering different ways of respecifying social change by attending to various kinds of historicity and obsolescence of social praxis.


Hypericin induced death receptor-mediated apoptosis in photoactivated tumor cells.
Nasopharyngeal carcinoma (NPC) is a malignant disease of the head/neck region with a 5-year survival level of approximately 65%. To explore the novel therapeutic strategies in the management of this disease, the potential effects of photodynamic therapy (PDT) in NPC cells were investigated. PDT, a new mode of treatment, is based on the combined use of light-absorbing compounds and light irradiation. Two human NPC cells such as, poorly differentiated (NPC/CNE2) and moderately differentiated (NPC/TW0-1) and other types of tumor cells like colon (CCL-220.1) and bladder (SD) undergo rapid apoptosis when treated with PDT sensitized with hypericin (HY). It has been shown that this compound has a strong photodynamic effect on tumors and viruses. However, the initiating events of PDT sensitized HY-induced apoptosis are not identified completely. In this study, we sought to determine whether Fas/FasL upregulation and involvement of mitochondrial events are an early event in HY-treated PDT induced apoptosis. Loss of mitochondrial transmembrane potential, release of cytochrome c, involvement of caspases 8 and 3 and the status caspase-3 specific substrate PARP, were evaluated in PDT treated tumor cells. Photosensitization of HY enhanced both CD95/CD95L expression and induced CD95-signaling dependent cell death in all tumor cell lines studied. CD95/CD95L expression appeared within 2 h following light irradiation and appeared to be a principal event in PDT induced apoptosis. Furthermore, these results indicate that release of mitochondrial cytochrome c into the cytoplasm within 2-3 h post PDT is a secondary event following the activation of initiator caspase-8 preceding Apaf-1, caspase-9 and caspase-3 activation, cleavage of PARP and DNA fragmentation.


A double-pointed wooden throwing stick from Schöningen, Germany: Results and new insights from a multianalytical study.
The site of Schöningen (Germany), dated to ca. 300,000 years ago, yielded the earliest large-scale record of humanly-made wooden tools. These include wooden spears and shorter double-pointed sticks, discovered in association with herbivores that were hunted and butchered along a lakeshore. Wooden tools have not been systematically analysed to the same standard as other Palaeolithic technologies, such as lithic or bone tools. Our multianalytical study includes micro-CT scanning, 3-dimensional microscopy, and Fourier transform infrared spectroscopy, supporting a systematic technological and taphonomic analysis, thus setting a new standard for wooden tool analysis. In illustrating the biography of one of Schöningen's double-pointed sticks, we demonstrate new human behaviours for this time period, including sophisticated woodworking techniques. The hominins selected a spruce branch which they then debarked and shaped into an aerodynamic and ergonomic tool. They likely seasoned the wood to avoid cracking and warping. After a long period of use, it was probably lost while hunting, and was then rapidly buried in mud. Taphonomic alterations include damage from trampling, fungal attack, root damage and compression. Through our detailed analysis we show that Middle Pleistocene humans had a rich awareness of raw material properties, and possessed sophisticated woodworking skills. Alongside new detailed morphometrics of the object, an ethnographic review supports a primary function as a throwing stick for hunting, indicating potential hunting strategies and social contexts including for communal hunts involving children. The Schöningen throwing sticks may have been used to strategically disadvantage larger ungulates, potentially from distances of up to 30 metres. They also demonstrate that the hominins were technologically capable of capturing smaller fast prey and avian fauna, a behaviour evidenced at contemporaneous Middle Pleistocene archaeological sites.


Cu(II)-catalyzed oxidation of beta-amyloid peptide targets His13 and His14 over His6: Detection of 2-Oxo-histidine by HPLC-MS/MS.
The interaction of beta-amyloid peptide (betaAP) with Cu(II) leads to the formation of reactive oxygen species, neurotoxicity, and the chemical modification of the peptide. To study product formation and the potential selectivity of oxidation, we have exposed specific betaAP congeners, betaAP1-16, betaAP1-28, and betaAP1-40, to ascorbate/Cu(II)-induced metal-catalyzed oxidation and electrospray ionization-time-of-flight (ESI-TOF) MS/MS analysis. Incubation of 30 microM betaAP with 15-150 microM Cu(II) and (physiologically relevant) 720 microM ascorbate in 20 mM phosphate buffer, pH 7.4, leads to significant oxidation of the peptides within remarkably short reaction times of as low as 6 min. Initial oxidation targets are His13 and His14, which are converted to 2-oxo-His, whereas the other two metal-binding residues, His6 and Tyr10, remain intact. Longer oxidation times then also target His6. Even in betaAP1-40 the oxidation of His13 and His14 precedes the oxidation of Met35. Especially, the insensitivity of Tyr10 is noteworthy and may be explained by electron withdrawal from the Tyr side chain through complexation of Cu(II). The insensitivity of His6 to initial oxidation may be rationalized by a proposed bridging of two Cu(II)-betaAP congeners, lowering the electron density on His6, comparable to similar results on a Cu(II)- and Zn(II)-bridging His61 residue of bovine Cu,Zn superoxide dismutase.


New human V beta genes and polymorphic variants.
To extend the characterization of the human V beta gene repertoire, we utilized anchored or V beta-specific polymerase chain reaction to generate a large (approximately 200 clones) beta-chain library from the thymus of a single individual. Nine new V beta genes were identified, including single members for two new subfamilies (V beta 22 and 23), two new members of the V beta 5 subfamily, and one new member each for V beta 2, 6, 7, 9, and 12. Full-length sequences were also obtained for the published partial sequences of V beta 3, 5.3, 9.1, and 13.4, and additional nucleotides for V beta 7.1 and V beta 7.2. Based on consensus sequences from multiple clones, apparent allelic variants for six V beta genes (V beta 2.1, 5.3, 7.2, 8.2, 13.4, and 16) were also tentatively identified. Population and family studies for two of these (V beta 2.1 and 16) further confirmed that these V beta were alleles and not separate genes. Nonconservative substitutions in some of these alleles, as well as in previously identified alleles, are located at the hypervariable loops or the framework region. These findings indicate that V beta gene polymorphism appears to be significant in humans and might be the result of selective pressure imposed by conventional Ag (hypervariable loops) or superantigens (framework regions).


Relationship between soluble CD40 ligand and gamma-glutamyltransferase concentrations in non-drinking, young Type 1 diabetic individuals.
To assess the association between circulating levels of soluble CD40 ligand (sCD40L), an emerging cardiovascular risk factor, and gamma-glutamyltransferase (GGT) activity concentrations in Type 1 diabetic subjects. Plasma concentrations of sCD40L and GGT activity, a marker of liver dysfunction, were measured in 54 non-smoking, non-drinking, young Type 1 diabetic patients, who were free of diagnosed cardiovascular disease. When participants were grouped according to tertiles of GGT, plasma sCD40L concentrations steadily increased across GGT tertiles (P = 0.007 for trend). Similarly, plasma sCD40L concentrations were positively correlated with plasma GGT levels in the whole group of participants (r = 0.532; P < 0.0001). In multivariate linear regression analysis, plasma GGT activity levels were positively associated with sCD40L (standardized beta coefficient = 0.342; P = 0.027) independently of age, gender, diabetes duration, glycated haemoglobin, total cholesterol and systolic blood pressure. Further adjustment for the presence of diabetic retinopathy and microalbuminuria did not appreciably attenuate this association. Our findings suggest that there is a strong, graded, relationship between plasma GGT activity and sCD40L concentrations in non-smoking, non-drinking, young Type 1 diabetic individuals. This association appears to be independent of numerous confounding factors. Further studies are required to confirm the reproducibility of these results.


[Nailfold capillaroscopy in the evaluation of Raynaud's phenomenon and undifferentiated connective tissue disease].
Microvascular abnormalities involved in the pathogenic mechanism of several connective tissue disorders can be detected by nailfold capillaroscopy. Evaluation of the interest of nailfold capillaroscopy results in patients with Raynaud s phenomenon or undifferentiated connective tissue disease and their correlation with diagnostic and therapeutical evolution. Selection of capillaroscopic and laboratory results of patients with the diagnosis of Raynaud s phenomenon (without defined connective tissue disease) or undifferentiated connective tissue disease. Evaluation of the present diagnosis and treatment comparing with the ones existed at the time of capillaroscopy performance. 80 patients were enrolled with an age of 51.4+/-14.3 years (mean+/-SD) 78 females (97.5%) with Raynaud s phenomenon and undifferentiated connective tissue disease 27 patients (33.8%); Raynaud s Phenomenon 46 patients (57.5%); undifferentiated connective tissue disease 7 patients (8.7%). The capillaroscopic results were normal 30 patients (37.5%); minor changes tortuosity enlargement 16 patients (20.0%) major changes 34 patients (42.5%) hemorrhages 25 patients (31.3%) megacapillaries 26 patients (32.5%) avascular areas 3 patients (3.8%). The introduction of new treatments after the capillaroscopy occurred in 32 patients (40.0%) and a new diagnosis was done in 39 patients (48.8%). Major changes in capillaroscopy correlated with the change of diagnosis and the introduction of a new treatment (p<0.0001). Nailfold capillaroscopy performed in patients with isolated Raynaud s phenomenon or undifferentiated connective tissue disease has a role in the prognostic evaluation related to the possibility of an evolution of the diagnosis or to the need of the introduction of new treatments.


Audiometric testing and hearing protection training through multimedia technology.
The purpose of this paper is to present the development process of a computer-based audiometric testing and tailored intervention program, and assess its feasibility by obtaining users' feedback. The program was implemented for 397 operating engineers at their union training center, and its feasibility was evaluated by obtaining quantitative and qualitative feedback from the participants through a survey and focus group. Over 96% of the participants indicated they liked receiving a hearing test by computer; the computer-based test worked smoothly; and the computer-based training was well organized, effective and held their interests. Almost all (more than 99%) said they would recommend this program to other workers. This project is considered as one of the first ones incorporating multimedia computer technology with self-administered audiometric testing and tailored training. Participants' favorable feedback strongly supported the continued utilization of this approach for designing and developing health screening and intervention to promote healthy behaviors.


[Research progress on urban green space].
Nature, diversity, and openness are what we demand from urban green space in the 21st century. Based on the summary of urban green space connotation, types and significance, this paper reviewed the research hotspots of urban green space, i.e., conservation and planning of urban-rural fringe, restoration and preservation of natural areas and indigenous vegetation, ecological restoration and planning of green way, biodiversity conservation, ecosystem structure and services, and management policy. The difference between foreign and domestic urban green space researches and practices were summarized, and some preferential urban green space research aspects in the future were proposed. It was suggested that in China, urban green space strategy should be integrated into urban planning and land use planning.


Initial Experience with the Transapical Access for TEVAR.
Background The endovascular approach has become a mainstay in the treatment of aortic aneurysms. While the transfemoral approach is most commonly used, it is often inaccessible due to a vascular pathology, such as occlusion, tortuosity or heavy calcifications. The transapical access provides an alternative approach. The goal of this study is to report the feasibility of the transapical approach for total endovascular repair of thoracic aortic aneurysms (TEVAR). Methods Three patients with thoracic aortic aneurysms with inaccessible femoral arteries underwent TEVAR via the transapical approach. For access, the apex of the left ventricle was exposed by a mini-thoracotomy. After left ventricular puncture, a stiff guidewire was placed through the aortic valve into the descending thoracic aorta. All stent grafts were delivered under fluoroscopic guidance. Results All three procedures were technically successful with complete exclusion of the aneurysm without endoleak. One patient suffered spinal ischemia with subsequent paraplegia on day 4 after the procedure. The same patient died on day 43 after the procedure due to esophageal rupture. The two remaining patients did not present procedure-related problems. Conclusion The transapical access is a feasible and safe alternative to the transfemoral route in selected cases scheduled for TEVAR. Key Points · Transapical TEVAR is a feasible option if the transfemoral route is not accessible.. · Reversed orientation of the stent graft has to be taken into account for procedure planning and graft deployment.. · Care has to be taken in the case of aortic valve vegetation in order to avoid stroke due to downstream embolism.. Citation Format · Mahnken AH, Irqsusi M, Hundt W et al. Initial Experience with the Transapical Access for TEVAR. Fortschr Röntgenstr 2017; 189: 760 - 764.


Effective contraceptive use: an exploration of theory-based influences.
The purpose of this study was to explore factors that influence oral contraceptive (OC) use among women in Iran using the Theory of Planned Behavior (TPB) and concept of self-efficacy (SE). The study sample consisted of 360 married OC users, aged 18-49 years recruited at public health centers of Mashhad, 900 km east of Tehran. SE had the strongest association with the intent to use after the clinic visit (r = 0.784) and with actual use (r = 0.452). Family planning self-efficacy combined with TPB variables accounted for 65% of the variance for intent and 27% of the variance in behavior. The results provide support for a theory-based approach to improved family planning care that specifically addresses more effective use. Development and evaluation of culturally appropriate public education and changes in clinical efforts designed to enhance the sense of SE are discussed.


Developing professionalism: dental students' perspective.
To explore the undergraduate dental students' insight of their professionalism development through Focus Group Discussions (FGD). Constructivist approach using qualitative phenomenological design. Fatima Memorial Hospital, College of Dentistry, Lahore, from April to June 2011. Four FGDs of 1st year (8 students), 2nd year (6 students), 3rd year (6 students) and 4th year (6 students) enrolled in Bachelor of Dental Surgery (BDS) program were conducted to explore how they have developed various elements of professionalism namely altruism, accountability, excellence, duty and service, honor and integrity, and respect for all; and how professionalism can be further developed in them. The FGDs were audio taped, transcribed and analyzed through thematic analysis. Triangulation of themes and trends were done through content analysis by relating to their respective frequency of quotes. Data verification was done through audit by second author. Role models and social responsibility were the main reasons in the students' professionalism development thus far with personal virtues and reasons; religion; and punishment and reward contributing to a lesser degree. Training contributed least but was deemed most in furthering professionalism. Excessive workload (quota) and uncongenial educational environment were considered detrimental to the cause. Formal planning and implementation of professionalism curriculum; selection of students with appropriate attributes; control of hidden curriculum, including effective role models, good educational and working environments will foster professionalism among dental students maximally.


High-Content Imaging Platform to Discover Chemical Modulators of Plasma Membrane Rafts.
Plasma membrane organization profoundly impacts cellular functionality. A well-known mechanism underlying this organization is through nanoscopic clustering of distinct lipids and proteins in membrane rafts. Despite their physiological importance, rafts remain a difficult-to-study aspect of membrane organization, in part because of the paucity of chemical tools to experimentally modulate their properties. Methods to selectively target rafts for therapeutic purposes are also currently lacking. To tackle these problems, we developed a high-throughput screen and an accompanying image analysis pipeline to identify small molecules that enhance or inhibit raft formation. Cell-derived giant plasma membrane vesicles were used as the experimental platform. A proof-of-principle screen using a bioactive lipid library demonstrates that this method is robust and capable of validating established raft modulators including C6- and C8-ceramide, miltefosine, and epigallocatechin gallate as well as identifying new ones. The platform we describe here represents a powerful tool to discover new chemical approaches to manipulate rafts and their components.


Label-Free Fluorescent DNA Dendrimers for microRNA Detection Based On Nonlinear Hybridization Chain Reaction-Mediated Multiple G-Quadruplex with Low Background Signal.
Various fluorescent sensing systems for miRNA detection have been developed, but they mostly contain enzymatic amplification reactions and label procedures. The strict reaction conditions of tool enzymes and the high cost of labeling limit their potential applications, especially in complex biological matrices. Here, we have addressed the difficult problems and report a strategy for label-free fluorescent DNA dendrimers based on enzyme-free nonlinear hybridization chain reaction (HCR)-mediated multiple G-quadruplex for simple, sensitive, and selective detection of miRNAs with low-background signal. In the strategy, a split G-quadruplex (3:1) sequence is ingeniously designed at both ends of two double-stranded DNAs, which is exploited as building blocks for nonlinear HCR assembly, thereby acquiring a low background signal. A hairpin switch probe (HSP) was employed as recognition and transduction element. Upon sensing the target miRNA, the nonlinear HCR assembly of two blocks (blocks-A and blocks-B) was initiated with the help of two single-stranded DNA assistants, resulting in chain-branching growth of DNA dendrimers with multiple G-quadruplex incorporation. With the zinc(II)-protoporphyrin IX (ZnPPIX) selectively intercalated into the multiple G-quadruplexes, fluorescent DNA dendrimers were obtained, leading to an exponential fluorescence intensity increase. Benefiting from excellent performances of nonlinear HCR and low background signal, this strategy possesses the characteristics of a simplified reaction operation process, as well as high sensitivity. Moreover, the proposed fluorescent sensing strategy also shows preferable selectivity, and can be implemented without modified DNA blocks. Importantly, the strategy has also been tested for miRNA quantification with high confidence in breast cancer cells. Thus, this proposed strategy for label-free fluorescent DNA dendrimers based on a nonlinear HCR-mediated multiple G-quadruplex will be turned into an alternative approach for simple, sensitive, and selective miRNA quantification.


Status epilepticus associated with platinum chemotherapy in a patient with cervical cancer: a case report.
While peripheral neuropathy is a common side effect of platinum-based chemotherapy, central nervous system (CNS) toxicity, such as encephalopathy or seizures, appears to be rare. This manuscript describes the only reported case of nonconvulsive status epilepticus associated with cisplatin in a cervical cancer patient who does not have other underlying medical conditions. The patient is a 54-year-old Chinese female with recurrent stage IIIB moderately differentiated squamous cell carcinoma of the cervix who was being treated with cisplatin and topotecan. During the sixth cycle of this regimen, the patient presented with mental status changes. While imaging and laboratory values were within normal limits, the patient's EEG revealed nonconvulsive status epilepticus. After appropriate intervention, she made a complete recovery with no further seizures. The patient currently remains on antiepileptic therapy, but is no longer receiving cisplatin. Patients who present with new onset seizures should primarily be evaluated for underlying medical conditions. Among patients who are suspected to have CNS side effects associated with platinum use, we recommend avoidance of platinum agents in future chemotherapeutic regimens. Although rare, providers should be aware of the potential for CNS toxicity associated with this drug class.


[Immunotherapy and long-term chemoprophylaxis in prevention of recurrent urinary infections in women].
In clinical practice, management of urinary infections is a frequent task. Long-term prophylactic administration of small-dose chemotherapy had been shown to prevent recurrent urinary infections. Recently, an interest increases in applying immunotherapy in this indication. The authors compare immunomodulators Urovaxom and Luivac as part ofa combined immunotherapy and chemoprophylaxis regimens with small doses of fluorochinolones over 12 months in women with recurrent urinary infections. This treatment statistically significantly decreases occurrence of relapses and has been relatively well-tolerated. Unlike previous studies, we managed to isolate resistant strains producing the so-called extended-spectrum beta-lactamases (ESBL) and this may provide a signal for revision of some therapeutic approaches. In line with international recommendations, we prefer immunotherapy as comparably effective but safer treatment modality than the long-term chemoprophylaxis with fluorochinolones.


Stimulation by calcium and barium of somatostatin release. Evidence for lower sensitivity of D- vis-à-vis B- and A-cells.
To address the question whether a "second messenger" function of calcium differs between D-cells and other cells of the endocrine pancreas, we compared effects of calcium and barium (a calcium substitute) on somatostatin secretion to effects on insulin and glucagon secretion from the perfused pancreas of the rat. 6.5 mmol/l of calcium, when administered early during perfusion, failed to stimulate somatostatin release. 0.05 mmol/l of barium, when added to calcium-deprived media failed to affect somatostatin secretion while 0.5 induced a slight and 2.0 mmol/l a marked and sustained response. Barium-induced insulin release was left-shifted in relation to the somatostatin response, since 0.05 mmol/l of barium stimulated and 0.5 mmol/l evoked a near-maximal insulin response. All concentrations of barium evoked diphasic glucagon responses, i.e. a small (1 min) stimulation followed by sustained inhibition. Addition of 0.5 mmol/l of EGTA to calcium-deprived media abolished D- as well as B- and A-cell secretion. Reintroduction of 0.5-6.5 mmol/l of calcium stimulated somatostatin release; the secretory response was proportionate to the calcium concentration. In contrast, addition of calcium stimulated insulin and glucagon secretion maximally already at 0.5 mmol/l of calcium. We conclude that the D-cell is less sensitive than B- and A-cells to a regulatory effect on secretion exerted by extracellular calcium or barium.


A case of sarcoidosis with interstitial lung disease mimicking clinically amyopathic dermatomyositis and rapidly progressive interstitial lung disease.
Here, we report a patient with sarcoidosis who developed edematous erythema and interstitial lung disease. At the initial visit, clinically amyopathic dermatomyositis (CADM) with rapidly progressive interstitial lung disease (RP-ILD) was suspected because he had progressive dyspnea but no muscle weakness. The presence of anti-CADM-140/MDA5 autoantibodies was immediately assessed to facilitate a precise diagnosis, with negative results. Thereafter, skin and transbronchial lung biopsies revealed noncaseating granuloma with Langhans giant cells in both specimens, leading to a diagnosis of sarcoidosis. In this case, clinical features of skin and lung were unable to distinguish DM (including CADM) from sarcoidosis, but the lack of anti-CADM-140/MDA5 antibody was useful for differentiating CADM with RP-ILD mimicking sarcoidosis from bona fide sarcoidosis.


G-protein-coupled receptor Mas is a physiological antagonist of the angiotensin II type 1 receptor.
We previously identified the G-protein-coupled receptor Mas, encoded by the Mas proto-oncogene, as an endogenous receptor for the heptapeptide angiotensin-(1-7); however, the receptor is also suggested to be involved in actions of angiotensin II. We therefore tested whether this could be mediated indirectly through an interaction with the angiotensin II type 1 receptor, AT1. In transfected mammalian cells, Mas was not activated by angiotensin II; however, AT1 receptor-mediated, angiotensin II-induced production of inositol phosphates and mobilization of intracellular Ca2+ was diminished by 50% after coexpression of Mas, despite a concomitant increase in angiotensin II binding capacity. Mas and the AT1 receptor formed a constitutive hetero-oligomeric complex that was unaffected by the presence of agonists or antagonists of the 2 receptors. In vivo, Mas acts as an antagonist of the AT1 receptor; mice lacking the Mas gene show enhanced angiotensin II-mediated vasoconstriction in mesenteric microvessels. These results demonstrate that Mas can hetero-oligomerize with the AT1 receptor and by so doing inhibit the actions of angiotensin II. This is a novel demonstration that a G-protein-coupled receptor acts as a physiological antagonist of a previously characterized receptor. Consequently, the AT1-Mas complex could be of great importance as a target for pharmacological intervention in cardiovascular diseases.


Effect of nitrogen management in cultivation on the stability and microbial community of post-harvest Monoraphidium sp. algae biomass.
Long-term storage is necessary to mitigate for seasonal variation in algae productivity, to preserve biomass quality and to guarantee a constant biomass supply to a conversion facility. While ensiling has shown promise as a solution, biomass attributes for successful storage are poorly understood. Storage studies of Monoraphidium sp. biomass indicate a strong correlation between nitrogen management in algae cultivation and stability of post-harvest algae biomass. Algae cultivated with periodic nitrogen addition were stored poorly (>20% loss, dry basis) compared to biomass from nitrogen depleted cultivation (8% loss, dry basis). A follow-up study compared the post-harvest stability of Monoraphidium biomass cultivated in nitrogen-deplete or nitrogen-replete conditions. Replete biomass experienced the largest degradation (24%, dry basis), while deplete biomass experienced the least (10%, dry basis). Dry matter loss experienced among blends of each correlated positively with nitrogen-replete biomass content. The composition of the post-storage algae microbial community was also affected by cultivation conditions, with Clostridia species being more prevalent in stored biomass obtained from nitrogen-replete cultivations. Nitrogen management has long been known to influence algae biomass productivity and biochemical composition; here, we demonstrate that it also strongly influences the stability of post-harvest algae biomass in anaerobic storage.


The Feasibility and Effectiveness of PASS Plus, A Lay Health Worker Delivered Comprehensive Intervention for Autism Spectrum Disorders: Pilot RCT in a Rural Low and Middle Income Country Setting.
The treatment gap for autism globally is high. Our previous PASS intervention, delivered by community based lay health workers, showed effectiveness. This article reports the development and evaluation of a new "PASS 'Plus'" intervention in a rural population in India. Using formative research methods, we supplemented the PASS intervention with additional (Plus) modules to address autism comorbidities. This is the first time that a rigorous methodology has been used to evaluate autism symptom outcomes in a low and middle-income country setting. 40 parent-child dyads were recruited in a pilot randomized controlled trial against usual care (mean age 65 months (34 boys); n = 19 PASS Plus, n = 21 UC). 89% of intervention families partially or entirely completed the 12-session intervention. Intention to treat analysis showed a reduction in mean scores of autism symptom severity, though the confidence interval contains zero, (adjusted mean difference AMD -2.42 95% CI -7.75, 2.92; ES 0.22); large treatment effects on proximal outcomes of proportion of parent synchronous responses (AMD 0.35; 95% CI 0.18, 0.52; effect size ES 3.97) and proportion of child communication initiations with parent (AMD 0·17; 95% CI 0.03, 0.32; ES 1.02). Confidence intervals for effects on mutual shared attention (AMD 0.10; 95% CI -0.07, 0.27; ES 0.5) and co-morbid symptoms (AMD -9.0; 95% CI -24.26, 6.26; ES 0.32) contained zero. There were significant effects to improve parental mental health. PASS Plus shows good feasibility and adds to the evidence of the effectiveness of task sharing complex autism interventions to lay health workers in India. Autism Res 2019, 12: 328-339 © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This article describes the development of a comprehensive, community-delivered, intervention for young children with autism, which combines a previously developed parent-mediated communication intervention with support for co-morbid problems like challenging behaviors and sensory sensitivities. The unique aspect of this intervention is that it can be delivered by community health workers, addressing the lack of specialists in low resource settings. Our study reports the encouraging findings of a pilot trial evaluating its feasibility and effectiveness.


[Apoptosis of hypertrophic cardiomyocytes stimulated by hypoxia-reoxygenation is partially mediated by apoptosis-inducing factor].
Cardiomyocyte apoptosis leads to the functional incapacitation of myocardial plasmodium and plays an important role in the pathogenesis of heart failure transformed from compensable cardiac hypertrophy. Mitochondria are the main source of apoptosis-inducing molecule of various cells, and the role of caspartate-specific cysteinyl proteinase (caspase)-dependent mechanism has generally been accepted in the cardiomyocyte apoptosis. However, the significance of caspase-independent apoptosis-inducing factor (AIF) mechanism is not yet understood. The purpose of this study was to evaluate hypoxia-reperfusion-induced alterations of AIF mRNA and protein expressions in hypertrophic cardiomyocytes. Cardiomyocyte hypertrophy was produced by angiotensin II (0.1 mumol/L). The cells were cultured under the condition of hypoxia (95% N2 and 5% CO2; the O2 partial pressure was lower than 5 mmHg) for 8 h or 12 h (named as H8h and H12h groups, respectively), and then exposed to normal culture environment (named as H8h/R and H12h/R groups, respectively). Apoptosis was detected with Hoechst 33258 staining. The AIF mRNA and protein expressions were detected by RT-PCR and Western blot and quantified by gel scanning. The results were as follows: (1) The level of AIF mRNA expression was 0.29+/-0.08 (optical density, relative value) in the control group (hypertrophic cardiomyocytes cultured in normal environment). Compared with that in the control group, the levels of AIF mRNA expression were significantly higher in the groups of H8h and H12h (0.52+/-0.04 and 0.85+/-0.10), indicating that this effect was time-dependent. A further increase of AIF mRNA expression was observed in the groups of H8h/R (1.09+/-0.12) and H12h/R (1.41+/-0.23). (2) The level of AIF protein expression was 0.29+/-0.04 in the control group. Compared with that in the control group, the levels of AIF protein expression were significantly higher in the groups of H8h and H12h (2.07+/-0.15 and 3.12+/-0.19). The AIF protein expression was increased further in the groups of H8h/R (4.57+/-0.25) and H12h/R (5.71+/-0.27). The nuclear translocation of AIF protein was obvious only in the groups of H8h/R and H12h/R. (3) The expressions of AIF mRNA and protein were almost completely inhibited by AIF siRNA transfection. The siRNA transfection also reduced the apoptosis of hypertrophic cardiomyocytes in the groups of H8h/R and H12h/R but not in the groups of H8h and H12h. The apoptosis rate was significantly reduced by both AIF siRNA transfection and Ac-DEVD-cmk, an inhibitor of caspase-3. This reduction induced by two factors was more evident than that by one factor. (4) AIF nuclear translocation induced by hypoxia-reperfusion was not affected by inhibition of the activity of caspase-3. These data suggest that AIF plays a pivotal role in the apoptosis of hypertrophic cardiomyocytes induced by hypoxia-reperfusion.


Photoconversion Mechanisms and the Origin of Second-Harmonic Generation in Metal Iodates with Wide Transparency, NaLn(IO3)4 (Ln = La, Ce, Sm, and Eu) and NaLa(IO3)4:Ln3+ (Ln = Sm and Eu).
Four new metal iodates, namely, NaLn(IO3)4 (Ln = La, Ce, Sm, and Eu), and a series of NaLa(IO3)4:Ln3+ (Ln = Sm and Eu) solid solutions were synthesized through hydrothermal reactions. The structures of the title compounds are similar to that of NaY(IO3)4 crystallizing in the acentric monoclinic space group Cc. The iodate materials reveal layered structures composed of LnO8 square antiprisms and IO3 polyhedra, in which each layer is connected by the I···O interactions. NaLa(IO3)4 suggests a great potential as a matrix for optical source attributed to its acentricity and broad transparency from visible to mid-IR region. The photoluminescence properties depending on the concentration of Sm3+ reveal that NaLa(IO3)4:Sm3+ undergoes a self-quenching relaxation over 7 mol % of Sm3+ by dipole-quadrupole interactions. Attributable to the asymmetric coordination environment of Ln3+, stronger electric dipole transitions compared to magnetic dipole transitions were observed for both compounds. In addition, the materials exhibit strong second-harmonic generation (SHG) responses and are type I phase-matchable. The structural origin of the SHG properties for the reported iodates is elucidated.


[Occupational damage of the sense of smell].
Workers occupationally exposed to synthetic lacquers vapours and wood dust underwent olfactometric and laryngological examinations. The findings indicated that the synthetic lacquers vapours induced neurotoxic lesions of the smell sense. The wood dust causes only nasal cavity mucous membrane lesions inhibiting smell stimuli access to the smelling area. It was suggested olfactometric tests should be included into the preemployment examinations.


[Nutrition behavior of poor families].
The aim of this study was analysis of nutrition behaviour of families with low income living in village and town. The interviews concerning socio-economical conditions, actual nutrition behaviour and selected health indicator of respondents were carried in 13 rural and 14 Warsaw families. Respondents were for the most part women 34-44 years old with elementary education. Rural families were mainly numerous families, half of Warsaw families consists of mother lonely bringing children up. The main sources of living were allowances from social welfare and rents. One can observe in both kinds of families pro-healthy nutrition behavior: daily drinking milk by children, frequent consumption of poultry, using margarine and vegetables oil, and in rural families eating breakfast and several meals everyday. Negative aspects of nutrition were: small consumption of vegetables and fruits, fishes, and in town also dairy products and insufficient number of daily meals. Half of respondents both in village and town has proper BMI index. One can observe in rural families more tendency toward healthy nutrition behavior than in Warsaw families. Modeling healthy nutrition behavior in poor families (especially in town) can be realised by centers of social welfare.


The TP0796 lipoprotein of Treponema pallidum is a bimetal-dependent FAD pyrophosphatase with a potential role in flavin homeostasis.
Treponema pallidum, an obligate parasite of humans and the causative agent of syphilis, has evolved the capacity to exploit host-derived metabolites for its survival. Flavin-containing compounds are essential cofactors that are required for metabolic processes in all living organisms, and riboflavin is a direct precursor of the cofactors FMN and FAD. Unlike many pathogenic bacteria, Treponema pallidum cannot synthesize riboflavin; we recently described a flavin-uptake mechanism composed of an ABC-type transporter. However, there is a paucity of information about flavin utilization in bacterial periplasms. Using a discovery-driven approach, we have identified the TP0796 lipoprotein as a previously uncharacterized Mg(2+)-dependent FAD pyrophosphatase within the ApbE superfamily. TP0796 probably plays a central role in flavin turnover by hydrolyzing exogenously acquired FAD, yielding AMP and FMN. Biochemical and structural investigations revealed that the enzyme has a unique bimetal Mg(2+) catalytic center. Furthermore, the pyrophosphatase activity is product-inhibited by AMP, indicating a possible role for this molecule in modulating FMN and FAD levels in the treponemal periplasm. The ApbE superfamily was previously thought to be involved in thiamine biosynthesis, but our characterization of TP0796 prompts a renaming of this superfamily as a periplasmic flavin-trafficking protein (Ftp). TP0796 is the first structurally and biochemically characterized FAD pyrophosphate enzyme in bacteria. This new paradigm for a bacterial flavin utilization pathway may prove to be useful for future inhibitor design.


Carbohydrate-based N-heterocyclic carbenes for enantioselective catalysis.
Versatile syntheses of C2-linked and C2-symmetric carbohydrate-based imidazol(in)ium salts from functionalised amino-carbohydrate derivatives are reported. The novel NHCs were ligated to [Rh(COD)Cl]2 and evaluated in Rh-catalysed asymmetric hydrosilylation of ketones with good yields and promising enantioselectivities.


Two cases of Stenotrophomonas maltophilia endophthalmitis.
Two cases of Stenotrophomonas maltophilia endophthalmitis, a rare cause of postoperative endophthalmitis, are reported in this study. Both of the patients underwent vitreus tap and intravitreal antibiotic injection. The therapy was augmented with systemic and subconjunctival injections. The response to this therapy protocol was excellent and the final visual acuity in both of the patients was 10/10. The results are discussed and the literature, which consists of only 8 reported cases of Stenotrophomonas maltophilia endophthalmitis, is reviewed. Although endophthalmitis caused by this pathogen is a rare but important cataract surgery complication, with appropriate therapy, this clinical presentation can be cured without risk of reoccurrence.


The ubiquitous chromatin protein DEK alters the structure of DNA by introducing positive supercoils.
We have investigated the molecular mechanism by which the proto-oncogene protein DEK, an abundant chromatin-associated protein, changes the topology of DNA in chromatin in vitro. Band-shift assays and electron microscopy revealed that DEK induces both intra- and intermolecular interactions between DNA molecules. Binding of the DEK protein introduces constrained positive supercoils both into protein-free DNA and into DNA in chromatin. The induced change in topology is reversible after removal of the DEK protein. As shown by sedimentation analysis and electron microscopy, the DEK-induced positive supercoiling causes distinct structural changes of DNA and chromatin. The observed direct effects of DEK on chromatin folding help to understand the function that this major chromatin protein performs in the nucleus.


A National Voter Registration Campaign.
Research suggests that increased voting among adults is associated with improved child health. Despite the benefits of voting, the United States has low voter turnout compared with peer nations. Turnout is especially low among marginalized people in the United States. Voter registration is essential for increasing voter turnout, and registration efforts have been successfully carried out in clinical settings. Working with a nonprofit called Vot-ER, we advocated for nonpartisan voter registration efforts in pediatric settings nationwide preceding the November 2020 US elections. We describe lessons learned from these efforts. Using data obtained from Vot-ER, we also provide the first estimates of participation in a national voter registration campaign in pediatric settings. There was widespread engagement in voter registration efforts among pediatricians in 2020. Many lessons were learned from these efforts, including the benefits of advanced planning because registration deadlines can be up to 1 month in advance of Election Day. Obtaining buy-in from numerous stakeholders (e.g., health center leadership, public relations teams) supports widespread staff participation. Also important is to consider the tradeoffs between active voter registration (in which staff can broach the topic of voting with patients and families) and passive efforts (in which voting is discussed only if patients or families inquire about it). These and other lessons can inform future voter registration efforts in diverse pediatric settings across the country.


Nasal immunotherapy at constant dosage: a double-blind, placebo-controlled study in grass-allergic rhinoconjunctivitis.
A preliminary open study showed that intranasal immunotherapy can be administered with a constant dosage scheduling, with good safety and efficacy. In the present study the efficacy of constant dosage intranasal immunotherapy has been evaluated on 43 grass-allergic rhinitis patients according to a double-blind placebo-controlled design. The product employed for the study had a formulation in powder, and was administrated by a nasal insufflator. Clinical efficacy was evaluated for each symptom, taking into consideration the severity of the symptom in relation to its frequency. Sneezing, rhinorrea, nasal blockage, eyes itching, and drug consumption were significantly improved in active-treated patients compared to placebo-treated. The safety of this treatment was good, the only adverse events observed being some local and mild symptoms. This immunotherapy was well-tolerated and easy to handle by the patients by self-administration.


Differential expression of mRNA encoding interleukin-12 p35 and p40 subunits in situ.
Interleukin-12 (IL-12) is a heterodimeric cytokine that plays an important role in the regulation of the immune response. For biological activity the expression of both subunits of IL-12, p35 and p40, is required. Moreover, in the mouse the p40 chain of IL-12 specifically inhibits the effects of the IL-12 heterodimer. In the present study we have analyzed by in situ hybridization the expression of the p35 and p40 mRNA in the spleens of BALB/c and mutant (SCID, nude, beige) mice, unstimulated and after in vivo stimulation with lipopolysaccharide (LPS) and with staphylococcal enterotoxin B (SEB). In unstimulated spleens of BALB/c mice p35 and p40 mRNA were only detectable in a few strongly stained single cells, p35 mRNA was expressed in addition weakly in the B cell areas. After injection of LPS or SEB, p40 mRNA was strongly induced in the T cell areas all over the spleen, whereas expression of p35 mRNA and its distribution pattern did not change. Surprisingly, most of the mRNA for p35 and p40 was localized in different areas of the spleen and was apparently produced by different cells. In macrophage-depleted spleens the increased expression of p40 mRNA in response to LPS was reduced but still detectable, demonstrating that other cells besides macrophages can up-regulate IL-12 p40 mRNA. Nude mice showed a stronger expression of p35 mRNA, SCID mice lacked the weak p35 staining of the B cell areas but showed a strong basal expression of both p35 and p40 mRNA and a focal response to LPS. The pattern of IL-12 mRNA expression in beige mice was the same as in normal mice. These data demonstrate a spatial dissociation of expression of the two chains of IL-12 and are compatible with a regulatory role of the isolated IL-12 p40 chain in vivo. In addition, they indicate that the demonstration of mRNA for both chains of IL-12 in whole tissues or cell mixtures is not necessarily indicative of functional IL-12.


Contribution of the World Health Organization/ the special program for research and training in tropical disease (WHO/TDR's) in institution building: lessons from Ethiopia.
World Health Organization/Tropical Disease Research (WHO/TDR) has enduring investment in transfers of skills critical to sustaining resilient health research systems through postgraduate training, clinical research and development fellowship (CRDF), bioethics, and grants to neglected tropical disease research. TDR has a long history of partnership with Armauer Hansen Research Institute (AHRI) in Ethiopia. The collaboration started with individuals and lead to institution survival and success. Therefore, the purpose of this study was to explore the impact and lessons learned of TDR initiatives in Ethiopia. This study was guided by the 'TDR Impact Pathways'. A total of thirteen in-depth, and five key informant interviews were conducted with individuals who are currently working in Addis Ababa, Gondar, Jimma Universities and AHRI. In addition to the interviews, reports, written communications and publications were reviewed. Interviews were audio recorded, transcribed verbatim, inductively coded, and analyzed thematically. The results were presented following the themes with supportive verbatim quotes. TDR's seed grants, training opportunities and technical support catalyzed individual, institutional and national research capacity in Ethiopia. This is a useful indication of how long-term collaboration between individuals could have broader institutional implication as evidenced from the TDR-AHRI complementary partnership.


Structural Ensembles of Membrane-bound α-Synuclein Reveal the Molecular Determinants of Synaptic Vesicle Affinity.
A detailed characterisation of the molecular determinants of membrane binding by α-synuclein (αS), a 140-residue protein whose aggregation is associated with Parkinson's disease, is of fundamental significance to clarify the manner in which the balance between functional and dysfunctional processes are regulated for this protein. Despite its biological relevance, the structural nature of the membrane-bound state αS remains elusive, in part because of the intrinsically dynamic nature of the protein and also because of the difficulties in studying this state in a physiologically relevant environment. In the present study we have used solid-state NMR and restrained MD simulations to refine structure and topology of the N-terminal region of αS bound to the surface of synaptic-like membranes. This region has fundamental importance in the binding mechanism of αS as it acts as to anchor the protein to lipid bilayers. The results enabled the identification of the key elements for the biological properties of αS in its membrane-bound state.


Experience with specially designed pored polyacetal mold dressing method used in McIndoe-style vaginoplasty.
Appropriate postoperative care and prolonged use of the mold are prerequisites for achieving successful results in McIndoe-style vaginoplasty. We introduce a specially designed pored polyacetal mold to maintain the reconstructed vagina, with favorable long-term results allowing drainage of the serous and bloody discharge without removal of the mold, and reduction of infection rate and the chance of skin graft shearing in McIndoe vaginoplasty. We retrospectively reviewed data of 10 consecutive patients with Mayer-Rokitansky-Kuster-Hauser syndrome who underwent McIndoe vaginoplasty between March 2010 and January 2014. We used a specially designed pored polyacetal mold (Figure) in all reconstructed vaginal wounds. The anatomical surgical success was evaluated by physical examination and functional success, which was defined as satisfaction with sex evaluated by patient self-assessed questionnaire. The follow-up period ranged from 1 to 3.5 years. The postoperative mean vaginal length was 9.5 cm in nine patients who used the mold regularly. In all cases in which a pored polyacetal mold was used, skin engraftment was successfully maintained without partial skin graft loss or infection. The subjective patient self-assessed satisfaction evaluation reported a high satisfaction rate. The multi-holed polyacetal vaginal mold was designed to perform vaginal irrigation without removal of the mold, allowing drainage of the serous and bloody discharge. This makes it possible to reduce infection rate and maintain successful skin engraftment by reducing the chance of skin graft shearing. The characteristics of polyacetal make it useful as a vaginal mold material as it is lightweight to use, easy to manufacture in accordance with the dimensions of the neovaginal space, and cost-effective. Although a constant follow-up evaluation is required, the pored polyacetal mold is an attractive vaginal mold dressing material to maximize the initial graft uptake, and it can be individually tailored in patients undergoing McIndoe-style vaginoplasty. The specially designed vaginal mold made up of pored polyacetal is a proper vaginal mold, which could maximize the initial graft uptake, decrease the risk of wound infection, and, therefore, decrease contracture of the neovagina in patients undergoing McIndoe vaginoplasty.


Solvation effects are responsible for the reduced inhibitor affinity of some HIV-1 PR mutants.
The formulation of HIV-1 PR inhibitors as anti-viral drugs has been hindered by the appearance of protease strains that present drug resistance to these compounds. The mechanism by which the HIV-1 PR mutants lower their affinity for the inhibitor is not yet fully understood. We have applied a modified Poisson-Boltzmann method to the evaluation of the molecular interactions that contribute to the lowering of the inhibitor affinity to some polar mutants at position 82. These strains present drug resistance behavior and hence are ideally suited for these studies. Our results indicate that the reduction in binding affinity is due to the solvation effects that penalize the binding to the more polar mutants. The inhibitor binding ranking of the different mutants can be explained from the analysis of the different components of our free energy scoring function.


Electrical Conductivity and Strong Luminescence in Copper Iodide Double Chains with Isonicotinato Derivatives.
Direct reactions between CuI and isonicotinic acid (HIN) or the corresponding esters, ethyl isonicotinate (EtIN) or methyl isonicotinate (MeIN), give rise to the formation of the coordination polymers [CuI(L)]n with L=EtIN (1), MeIN (2) and HIN (3). Polymers 1-3 show similar structures based on a CuI double chain in which ethyl-, methyl isonicotinate or isonicotinic acid are coordinated as terminal ligands. Albeit, their supramolecular architecture differs considerably, affecting the distances and angles of the central CuI double chains and thereby their physical properties. Hence, the photoluminescence shows remarkable differences; 1 and 2 show a strong yellow emission, whereas 3 displays a weak emission; and 1 and 2 are semiconductors with moderate room temperature conductivities, whereas 3 has increased electrical conductivity up to 3×10(-3) S cm(-1) . Additionally, 1 and 2 present an irreversible transition to a highly conducting phase with a conductivity almost 4 orders of magnitude higher and a quasi-metallic behaviour. Thermogravimetric analysis (TGA) coupled to a mass spectrometer and magnetic measurements point to a partial thermally induced oxidation of the carboxylate groups of the ligands with Cu(I) to Cu(0) reduction. DFT calculations have been carried out to rationalise these observations.


Dielectric microwave resonators in TE(011) cavities for electron paramagnetic resonance spectroscopy.
The coupled system of the microwave cylindrical TE(011) cavity and the TE(01delta) dielectric modes has been analyzed in order to determine the maximum achievable resonator efficiency parameter of a dielectric inserted into a cavity, and whether this value can exceed that of a dedicated TE(01delta) mode dielectric resonator. The frequency, Q value, and resonator efficiency parameter Lambda for each mode of the coupled system were calculated as the size of the dielectric was varied. Other output parameters include the relative field magnitudes and phases. Two modes are found: one with fields in the dielectric parallel to the fields in the cavity center and the other with antiparallel fields. Results closely match those from a computer program that solves Maxwell's equations by finite element methods. Depending on the relative natural resonance frequencies of the cavity and dielectric, one mode has a higher Q value and correspondingly lower Lambda than the other. The mode with the higher Q value is preferentially excited by a coupling iris or loop in or near the cavity wall. However, depending on the frequency separation between modes, either can be excited in this way. A relatively narrow optimum is found for the size of the insert that produces maximum signal for both modes simultaneously. It occurs when the self-resonance frequencies of the two resonators are nearly equal. The maximum signal is almost the same as that of the dedicated TE(01delta) mode dielectric resonator alone, Lambda congruent with40 G/W(1/2) at X-band for a KTaO(3) crystal. The cavity is analogous to the second stage of a two-stage coupler. In general, there is no electron paramagnetic resonance (EPR) signal benefit by use of a second stage. However, there is a benefit of convenience. A properly designed sample-mounted resonator inserted into a cavity can give EPR signals as large as what one would expect from the dielectric resonator alone.