Acceptability of self-collection sampling for HPV-DNA testing in low-resource settings: a mixed methods approach.
Vaginal self-sampling with HPV-DNA tests is a promising primary screening method for cervical cancer. However, women's experiences, concerns and the acceptability of such tests in low-resource settings remain unknown. In India, Nicaragua, and Uganda, a mixed-method design was used to collect data from surveys (N = 3,863), qualitative interviews (N = 72; 20 providers and 52 women) and focus groups (N = 30 women) on women's and providers' experiences with self-sampling, women's opinions of sampling at home, and their future needs. Among surveyed women, 90% provided a self- collected sample. Of these, 75% reported it was easy, although 52% were initially concerned about hurting themselves and 24% were worried about not getting a good sample. Most surveyed women preferred self-sampling (78%). However it was not clear if they responded to the privacy of self-sampling or the convenience of avoiding a pelvic examination, or both. In follow-up interviews, most women reported that they didn't mind self-sampling, but many preferred to have a provider collect the vaginal sample. Most women also preferred clinic-based screening (as opposed to home-based self-sampling), because the sample could be collected by a provider, women could receive treatment if needed, and the clinic was sanitary and provided privacy. Self-sampling acceptability was higher when providers prepared women through education, allowed women to examine the collection brush, and were present during the self-collection process. Among survey respondents, aids that would facilitate self-sampling in the future were: staff help (53%), additional images in the illustrated instructions (31%), and a chance to practice beforehand with a doll/model (26%). Self-and vaginal-sampling are widely acceptable among women in low-resource settings. Providers have a unique opportunity to educate and prepare women for self-sampling and be flexible in accommodating women's preference for self-sampling.


Microgravity inhibits decidualization via decreasing Akt activity and FOXO3a expression in human endometrial stromal cells.
Decidualization is characterized by the differentiation of endometrial stromal cells (eSCs), which is critical for embryo implantation and maintenance of pregnancy. In the present study, we investigated the possible effect of simulated microgravity (SM) on the process of proliferation and in vitro decidualization using primary human eSCs. Exposure to SM for 36 h decreased the proliferation and migration of eSCs significantly, without inducing cell death and changes in cell cycle progression. The phosphorylation of Akt decreased under SM conditions in human eSCs, accompanied by a simultaneous decrease in the level of matrix metalloproteinase (MMP)-2 and FOXO3a. Treatment with Akti, an Akt inhibitor, decreased MMP-2 expression, but not FOXO3a expression. The decreased level of FOXO3a under SM conditions impeded autophagic flux by reducing the levels of autophagy-related genes. In addition, pre-exposure of eSCs to SM significantly inhibited 8-Br-cAMP induced decidualization, whereas restoration of the growth status under SM conditions by removing 8-Br-cAMP remained unchanged. Treatment of human eSCs with SC-79, an Akt activator, restored the reduced migration of eSCs and decidualization under SM conditions. In conclusion, exposure to SM inhibited decidualization in eSCs by decreasing proliferation and migration through Akt/MMP and FOXO3a/autophagic flux.


Laparoscopic radiofrequency ablation of unresectable hepatic malignancies: indication, limitation and results.
Radiofrequency-ablation (RFA) is an effective therapeutic option for destruction of irresectable primary and secondary liver tumors and has been successfully performed transcutaneously using sonographic or computer tomographic guidance or by laparotomy. The laparoscopic approach combines a minimal invasiveness with optimal diagnosis. Between 02/2003 and 10/2005, 14 patients with a total of 45 unresectable liver tumors were treated with laparoscopic radiofrequency-ablation in our hospital. Laparoscopic RFA was primarily performed in patients' superficial lesions adjacent to neighboring organs that could be displaced by laparoscopic maneuvers, deep-sited lesions with a very difficult or impossible percutaneous approach and in combination with other laparoscopic operations. All intrahepatic tumors could be detected safely by laparoscopic intraoperative ultrasound. Additional liver lesions were identified in 5 (35.7%) of the 14 patients. All 45 tumors of the 14 patients were able to be completely ablated. Laparoscopic RFA yielded no mortality and only one case of postoperative bleeding. During a mean follow-up period of 23.2 months one patient locally recurred, three patients had new malignant nodules and two patients died with disease. Laparoscopic RFA is safe and provides a minimally invasive procedure with the option of simultaneous inflow-occlusion during thermoablation. Even more, neighboring organs can be protected, simultaneous resections can be performed and intraoperative ultrasound is used to gain further diagnosis.


[Application of modified microbubble test in peripherally inserted central venous catheters tip positioning].
To analyze the specificity and sensitivity of the modified microbubble test in identifying the peripherally inserted central venous catheters (PICC) tip based on the chest X-ray location as the "gold standard", and to find out an accurate and noninvasive PICC tip positioning method that can save time and cost. Convenient sampling method was conducted. The patients under PICC guided by ultrasound in intensive care unit (ICU) or PICC clinic of the First Affiliated Hospital of Nanchang University from August 2017 to February 2018 were enrolled. All patients were followed up by ultrasound guided PICC catheter placement, modified microbubble test and chest X-ray localization. The relationship between the density of microbubbles in modified microbubble test and the location of PICC tip in chest X-ray localization was analyzed. Using chest X-ray localization as the "gold standard", the diagnostic evaluation indexes such as specificity and sensitivity of PICC tip identification by modified microbubble test were calculated. A total of 120 patients were enrolled during the study period, excluding those who refused to participate in the study, unclear right atrial ultrasound, conscious intolerance, unclear chest X-ray, and finally 108 patients completed the modified microbubble test and chest X-ray tip localization. According to the chest X-ray localization results of 108 patients, 69 patients (63.9%) were in ideal locations, 33 (30.6%) were in dissatisfactory position, and 6 (5.5%) were in malposition. There was no significant difference in gender, age, tube placement, depth of catheterization, placement of catheterization room, and catheterization among the three groups. In the modified microbubble test, there were 74 patients (68.5%) with grade I microbubble, 25 (23.2%) with grade II microbubble, and 9 (8.3%) with grade III microbubble. There was a correlation between microbubble density and the tip position of the catheter, showing a moderate intensity correlation, and the contingency coefficient was 0.662. The sensitivity of the modified microbubble test for PICC tip positioning was 95.7% (66/69), the specificity was 89.7% (35/39), the rate of missed diagnosis was 4.4% (3/69), the misdiagnosis rate was 10.3% (4/39), the positive predictive value was 94.3% (66/70), the negative predictive value was 92.1% (35/38), and the Youden index was 0.85. The consistency between the two methods was good, and the Kappa value was 0.86. Compared with the chest X-ray localization method, the modified microbubble test method has high sensitivity and specificity in identifying PICC in the position, and the operation is simple, noninvasive, with less time and low cost. The modified microbubble test can be used as a screening test for PICC tip position, especially in ICU. When there are technical limitations or suspicious patient, further chest X-ray is necessary.


[Genetic study of sensorineural hearing loss].
Genealogical and genetico-statistical analysis of 639 Moscow families with 696 children suffering from sensorineural deafness was carried out. The patients examined constituted 40% of all the registered cases of hearing loss in children under 16. The study showed that monosymptomatic sensorineural deafness in children was more often of a genetic (62,2%), than of an exogenous (37,8%) origin. 54,2% of children with the disease were born from normal parents and 50,9% of all sporadic cases of sensorineural deafness were caused by genetic factors. In 80,8% of cases, inherited sensorineural hearing loss was transmitted, as an autosomal recessive trait, in 18% - as an autosomal dominant trait and in 1,2% - as a recessive X-linked character. The incidence of recessive sensorineural deafness in children of moscow is 1: 2000, that of dominant hearing loss being 1: 10 000. The total frequency of recessive genes is 0,022; the total frequency of heterozygotes of recessive genes is 0,043.


Recruiting Latina families in a study of infant iron deficiency: a description of barriers, study adjustments and review of the literature.
Maternal minority status is a risk factor for iron deficiency in infancy and pregnancy. Because language and cultural differences may limit research participation, a prospective study examining iron deficiency included maternal minority status as an inclusionary criterion. Cognizant of potential barriers to recruitment, goals were to quantify eligible Latina enrollees and refusals, examine participation barriers, and devise possible solutions. Mothers and their full-term newborns were eligible if the women were anemic, diabetic during pregnancy, of minority and/or lower socioeconomic status, and/or delivered an infant outside the average weight range for gestational age. Self-reported ethnicity and reasons for participation refusal were documented. During the first 18 months, 255 mothers and their infants were enrolled. Based on inclusionary criteria and the percentage of minority women admitted to the birthing center in a year, we anticipated 25% minority enrollees, with 16.3% Latina. Although 27% minority enrollment was obtained, only 8% were Latina (P < 0.01). System barriers, researcher perception barriers, and participant perception barriers were encountered. Over the next 8 months, addressing these recruitment barriers improved Latina enrollment. Enrollment barriers are significant hurdles to overcome, but with increased understanding and effort, more successful inclusion of Latina families can be achieved.


Fibulin-6 expression and anoikis in human salivary gland epithelial cells: implications in Sjogren's syndrome.
Important changes in acinar and ductal morphology and function, together with pronounced extracellular matrix (ECM) remodelling, are detectable in the labial salivary glands of Sjögren's syndrome (SS) patients. The objective of this work was to determine the effect of treatment with the anti-Ro/SSA auto-antibodies, characterizing SS, on the expression of fibulin-6, a member of the fibulins family of the ECM, in primary human salivary gland epithelial cell (SGEC) cultures established from biopsies of labial minor salivary glands obtained from healthy donors. The induction of cell detachment and anoikis in SGECs treated with anti-Ro/SSA auto-antibodies were also investigated. Changes in fibulin-6 mRNA expression were measured by semi-quantitative reverse transcriptase-PCR and real-time PCR. Fibulin-6 expression in cells treated with anti-Ro/SSA auto-antibodies was evaluated by flow cytometric analysis and confocal laser scanning microscopy. SGECs undergoing death by anoikis were identified and quantified using Calcein blue/YOPRO-1 dyes. Herein, we present the first evidence of fibulin-6 expression in SGEC that results distributed in the cytoplasm surrounding the inner side of the plasma membrane. Fibulin-6 was down-regulated in SGECs treated with anti-Ro/SSA auto-antibodies in which a marked cell detachment and a reduction of cell viability were observed. Notably, a reduction of fibulin-6 expression in SGECs treated with anti-Ro/SSA auto-antibodies corresponds to an increase of anoikis cell death. Our observations demonstrate a dysregulation of fibulin-6 in the pathological processes observed in SS and provide new evidence that disorganization of the ECM environment could damage the architecture and function of the salivary glands.


Immunocytoma: a retrospective analysis from St Bartholomew's Hospital-1972 to 1996.
To analyze the presentation features and outcome for patients with immunocytoma (IMC) managed at St Bartholomew's Hospital (SBH), London, United Kingdom, between 1972 and 1996. Outcome was compared with that of patients with small lymphocytic lymphoma (SLL)/B-cell chronic lymphocytic leukemia (B-CLL) treated at SBH during the same period. One hundred twenty-six patients with newly diagnosed IMC were identified. Patients were subclassified (using the Kiel classification) as having lymphoplasmacytoid (n =92), lymphoplasmacytic (n = 24), polymorphous (n = 9), or undetermined (n = 1) IMC. Six patients (5%) had stage I to IIE disease; the rest had advanced disease. Treatment was given according to disease stage. Seven patients were managed expectantly. Eighty-two (69%) of 119 patients responded to treatment, but complete remission was seen in only 15 (13%) of 119. Treatment failed in 29 (24%) of 119 patients. There were three treatment-related deaths; five patients were not assessable for response. When survival of patients with IMC was compared with that of patients with B-CLL/SLL, a significant difference was found (P <. 01); this difference was maintained when only patients in whom the diagnosis was based on lymph node biopsy were considered (P =.01). A comparison of the three IMC subgroups showed that there was a trend (P =.06) toward a difference between B-CLL/SLL and the lymphoplasmacytoid subtype. Patients diagnosed with IMC are generally older and present with advanced disease. Conventional therapies usually result in incomplete responses of short duration. Overall, these results support the proposed World Health Organization reclassification of IMC to include lymphoplasmacytoid lymphoma (Kiel classification) as a variant of B-CLL/SLL.


The in vivo three-dimensional motion of the human lumbar spine during gait.
Lumbar spine pathology accounts for billions of dollars in societal costs each year. Although the symptomatology of these conditions is relatively well understood, the mechanical changes in the spine are not. Previous direct measurements of lumbar spine mechanics have mostly been performed on cadavers. The methods for in vivo studies have included imaging, electrogoniometry, and motion capture. Few studies have directly measured in vivo lumbar spine kinematics with in-dwelling bone pins. This study tracked the in vivo three-dimensional motion of the entire lumbar spine (L1 [corrected] to S1) in 10 healthy, young-adult subjects. Two 1.55 mm (0.062 in.) diameter Kirshner wires were inserted into each vertebra's spinous process under anesthesia. Motion capture cameras were used to track a triad of passive markers attached to the wires. Offsets between anatomical landmarks and tracking markers were established with a CT scan for each individual vertebra. Subjects were asked to perform various exercises including walking and voluntary range of motion. Subjects were able to complete all of the exercises. All subjects reported being adequately informed of all of the procedures and there were no neurological or orthopaedic complications. The range of the average inter-segmental range of motion was 4.26 degrees -4.38 degrees in the sagittal plane, 2.61 degrees -4.00 degrees in the coronal plane, and 4.11 degrees -5.24 degrees in the transverse plane. Using a direct (pin-based) in vivo measurement method, the motion of the human lumbar spine during gait was found to be triaxial. This appears to be the first three-dimensional motion analysis of the entire lumbar spine using indwelling pins. The results were similar to previously published data derived from a variety of experimental methods.


Cholesterol transport, peripheral benzodiazepine receptor, and steroidogenesis in aging Leydig cells.
The cellular mechanisms responsible for age-related decline in the ability of Leydig cells to produce testosterone are not yet fully understood. The decline in testosterone production could result from a reduction in the Leydig cell enzymatic activities mediating testosterone synthesis, the amount of substrate available for these enzymes, or both. In the present study, we examined the effect of age on a critical early step in the steroidogenic pathway, the transport of cholesterol into mitochondria. Leydig cells were isolated from the testes of young and old Brown Norway rats and incubated with human chorionic gonadotropin (hCG) and the side-chain cleavage cytochrome P450scc inhibitor aminoglutethimide (AMG). Mitochondria were isolated from these cells in the presence of AMG. Upon removal of AMG, the mitochondria from old cells produced 80% less steroid than those from young cells, only a fraction of which could be accounted for by a decrease in P450scc activity. These results suggest that the accumulation of hormonally recruited cholesterol into mitochondria is defective in old Leydig cells. With this in mind, we turned our attention to peripheral benzodiazepine receptor (PBR), a mitochondrial cholesterol-binding protein known to be involved in mediating cholesterol transport. PBR messenger RNA (mRNA) and protein expression were decreased in old cells. Moreover, both the dissociation constant (Kd) and the number of binding sites (Bmax) of the PBR were decreased in the old cells by 50% and 30%, respectively. Taken together, these results suggest that alterations in cholesterol transport and in PBR may play critical roles in age-related decreases in testosterone production in Brown Norway rat Leydig cells.


Synergistic multi-contrast cardiac magnetic resonance image reconstruction.
Cardiac magnetic resonance imaging (CMR) is an important tool for the non-invasive diagnosis of a variety of cardiovascular diseases. Parametric mapping with multi-contrast CMR is able to quantify tissue alterations in myocardial disease and promises to improve patient care. However, magnetic resonance imaging is an inherently slow imaging modality, resulting in long acquisition times for parametric mapping which acquires a series of cardiac images with different contrasts for signal fitting or dictionary matching. Furthermore, extra efforts to deal with respiratory and cardiac motion by triggering and gating further increase the scan time. Several techniques have been developed to speed up CMR acquisitions, which usually acquire less data than that required by the Nyquist-Shannon sampling theorem, followed by regularized reconstruction to mitigate undersampling artefacts. Recent advances in CMR parametric mapping speed up CMR by synergistically exploiting spatial-temporal and contrast redundancies. In this article, we will review the recent developments in multi-contrast CMR image reconstruction for parametric mapping with special focus on low-rank and model-based reconstructions. Deep learning-based multi-contrast reconstruction has recently been proposed in other magnetic resonance applications. These developments will be covered to introduce the general methodology. Current technical limitations and potential future directions are discussed. This article is part of the theme issue 'Synergistic tomographic image reconstruction: part 1'.


The Role of Nitric Oxide Synthase Uncoupling in Tumor Progression.
Here, evidence suggests that nitric oxide synthases (NOS) of tumor cells, in contrast with normal tissues, synthesize predominantly superoxide and peroxynitrite. Based on high-performance liquid chromatography analysis, the underlying mechanism for this uncoupling is a reduced tetrahydrobiopterin:dihydrobiopterin ratio (BH4:BH2) found in breast, colorectal, epidermoid, and head and neck tumors compared with normal tissues. Increasing BH4:BH2 and reconstitution of coupled NOS activity in breast cancer cells with the BH4 salvage pathway precursor, sepiapterin, causes significant shifts in downstream signaling, including increased cGMP-dependent protein kinase (PKG) activity, decreased β-catenin expression, and TCF4 promoter activity, and reduced NF-κB promoter activity. Sepiapterin inhibited breast tumor cell growth in vitro and in vivo as measured by a clonogenic assay, Ki67 staining, and 2[18F]fluoro-2-deoxy-D-glucose-deoxyglucose positron emission tomography (FDG-PET). In summary, using diverse tumor types, it is demonstrated that the BH4:BH2 ratio is lower in tumor tissues and, as a consequence, NOS activity generates more peroxynitrite and superoxide anion than nitric oxide, resulting in important tumor growth-promoting and antiapoptotic signaling properties. The synthetic BH4, Kuvan, is used to elevate BH4:BH2 in some phenylketonuria patients and to treat diseases associated with endothelial dysfunction, suggesting a novel, testable approach for correcting an abnormality of tumor metabolism to control tumor growth.


Sarcoma Immunotherapy: Confronting Present Hurdles and Unveiling Upcoming Opportunities.
Sarcomas are rare and heterogeneous mesenchymal neoplasms originating from the bone or soft tissues, which pose significant treatment challenges. The current standard treatment for sarcomas consists of surgical resection, often combined with chemo- and radiotherapy; however, local recurrence and metastasis remain significant concerns. Although immunotherapy has demonstrated promise in improving long-term survival rates for certain cancers, sarcomas are generally considered to be relatively less immunogenic than other tumors, presenting substantial challenges for effective immunotherapy. In this review, we examine the possible opportunities for sarcoma immunotherapy, noting cancer testis antigens expressed in sarcomas. We then cover the current status of immunotherapies in sarcomas, including progress in cancer vaccines, immune checkpoint inhibitors, and adoptive cellular therapy and their potential in combating these tumors. Furthermore, we discuss the limitations of immunotherapies in sarcomas, including a low tumor mutation burden and immunosuppressive tumor microenvironment, and explore potential strategies to tackle the immunosuppressive barriers in therapeutic interventions, shedding light on the development of effective and personalized treatments for sarcomas. Overall, this review provides a comprehensive overview of the current status and potential of immunotherapies in sarcoma treatment, highlighting the challenges and opportunities for developing effective therapies to improve the outcomes of patients with these rare malignancies.


Shotgun DNA sequencing using cloned DNase I-generated fragments.
A method for DNA sequencing has been developed that utilises libraries of cloned randomly-fragmented DNA. The DNA to be sequenced is first subjected to limit attach by a non-specific endonuclease (DNase I in the presence of Mn++), fractionated by size and cloned in a single-stranded phage vector. Clones are then picked at random and used to provide a template for sequencing by the dideoxynucleotide chain termination method. This technique was used to sequence completely a 4257 bp EcoRI fragment of bovine mitochondrial DNA. The cloned fragments were evenly distributed with respect to the EcoRI fragment, and completion of the entire sequence required the construction of only a single library. In general, once a clone library has been prepared, the speed of this approach (greater than 1000 nucleotides of randomly selected sequence per day) is limited mainly by the rate at which the data can be processed. Because the clones are selected randomly, however, the average amount of new sequence information per clone is substantially diminished as the sequence near completion.


Neuromuscular Evaluation of Trunk-Training Exercises.
OBJECTIVE: To evaluate the neuromuscular activation profiles of trunk muscles in commonly used gymnastic strength exercises with a polymyographic set-up and to describe the training effects of each exercise. DESIGN AND SETTING: Subjects performed 9 repetitions of each of 12 gymnastic exercises. Variations of 5 trunk flexions, 5 extensions, and 2 lateral-flexion movements were performed under standardized test conditions. SUBJECTS: Ten healthy subjects (men and women) who were familiar with the exercises participated in the study. MEASUREMENTS: We recorded surface electromyograms (EMGs) from the rectus abdominis, external oblique, rectus femoris, middle trapezius, erector spinae at T12 and L3, gluteus maximus, and semitendinosus and semimembranosus muscles. Recording of each repetition cycle was triggered by a flexible electronic goniometer attached to the trunk. The raw EMG signals were rectified, smoothed, amplitude normalized to maximal voluntary contraction (MVC), and averaged for the last 8 repetitions. RESULTS: Pure spine-flexion exercises, such as a curl-up, produced sufficient and isolated activation (greater than 50% MVC) of the abdominal muscles. When flexion of the spine was combined with hip flexion (sit-up), the peak activation was increased. Lateral-flexion tasks targeted primarily the external oblique muscle, which demonstrated high activity in side-lying flexion tasks. Back- and hip-extension exercises, such as bridging and diagonal hip and shoulder extension, produced only moderate mean activities (less than 35% MVC) in the trunk-extensor muscles. Trunk-extension exercises with combined hip extension increased the EMG activity to 50% MVC but only at the end of the extension. CONCLUSIONS: Individual responses to each exercise varied markedly, which complicated the classification of exercise effects. However, within the limitations of the study, we found that the chosen abdominal exercises provided an effective training stimulus for the trunk-flexor muscles, whereas in the back- and hip-extension exercises, the neuromuscular activation tended to be too low or unspecific to qualify as muscle-specific training.


Undernutrition and Hypoleptinemia Modulate Alloimmunity and CMV-specific Viral Immunity in Transplantation.
Immunological mechanisms linking undernutrition to infection and the alloimmune response are poorly understood in transplantation. We aimed to determine how undernutrition and hypoleptinemia impact T-cell allospecific and cytomegalovirus (CMV) viral-specific immunity in a murine model. Fed, fasted for 48 h (model of undernutrition), and fasted with leptin injections (leptin rescue), C57BL/6 mice received skin grafts from either C57BL/6 (syngeneic) or BALB/c (allogeneic) mice donors. Allograft rejection and survival were monitored. Fed, fasted, and leptin rescue C57BL/6 mice were inoculated with murine cytomegalovirus (mCMV). Mouse spleens were retrieved for T-cell flow cytometry analysis, mCMV DNA extraction, and quantitative polymerase chain reaction. Serum leptin levels were measured with ELISA. Fasted mice had prolonged rejection-free and graft survival compared with fed mice (P = 0.0002 and P = 0.043). Leptin administration did not alter rejection-free survival or allograft failure. CD8+ central memory T cell and CD8+ effector T cell proportions were significantly lower in fasted mice receiving allogeneic skin transplants compared with fed mice (P = 0.0009 and P = 0.0015). Fasted mice had higher viral loads (P = 0.0028) and impaired mCMV-specific interferon-gamma-producing CD8+ T cells (P = 0.0007), which improved with leptin rescue (P = 0.032). Undernutrition and its associated hypoleptinemia correlated with impaired allospecific and viral-specific immunities. Leptin administration decreased mCMV viral burden and increased mCMV-specific T-cell immunity, however, it did not increase rejection or worsen graft survival in complete major histocompatibility complex-mismatched skin allografts. Leptin may be a potential adjunctive therapy for CMV viremia in undernourished transplant recipients.


Community structures and distribution of anaerobic ammonium oxidizing and nirS-encoding nitrite-reducing bacteria in surface sediments of the South China Sea.
Anaerobic ammonium oxidation (anammox) and denitrification are two important processes responsible for nitrogen loss; monitoring of microbial communities carrying out these two processes offers a unique opportunity to understand the microbial nitrogen cycle. The aim of the current study was to characterize community structures and distribution of anammox and nirS-encoding nitrite-reducing bacteria in surface sediments of the northern South China Sea (SCS). The consistent phylogenetic results of three biomarkers of anammox bacteria, including 16S rRNA, hzo, and Scalindua-nirS genes, showed that Scalindua-like bacteria were the only anammox group presenting in surface sediments of the SCS. However, a relatively high micro-diversity was found within this group, including several SCS habitat-specific phylotypes, Candidatus "Scalindua zhenghei". Comparing to 16S rRNA gene, hzo and Scalindua-nirS genes provided a relatively higher resolution to elucidate anammox bacteria. For the nirS-encoding nitrite-reducing bacteria, the detected nirS gene sequences were closely related to various marine nirS denitrifiers, especially those which originated from coastal and estuarine sediments with a much higher diversity than anammox bacteria. Anammox bacterial communities shifted along with the seawater depth, while nirS-encoding nitrite-reducing bacteria did not. Although nirS-encoding nitrite-reducing bacteria have a much higher abundance and diversity than anammox bacteria, they showed similar abundance variation patterns in research sites, suggesting the two microbial groups might be affected by the similar environmental factors. The significant correlations among the abundance of the two microbial groups with the molar ratio of NH4 (+) to (NO2 (-) + NO3 (-)), pH, and organic matters of sediments strongly supported this hypothesis.


Homophilic synaptic target recognition mediated by immunoglobulin-like cell adhesion molecule Fasciclin III.
We demonstrate that the cell adhesion molecule Fasciclin III (FAS3) mediates synaptic target recognition through homophilic interaction. FAS3 is expressed by the RP3 motoneuron and its target muscles during synaptic target recognition. The RP3 growth cone can form synapses on muscles that ectopically express FAS3. This mistargeting is dependent on FAS3 expression in the motoneurons. In addition, when the FAS3-negative aCC and SNa motoneuron growth cones ectopically express FAS3, they gain the ability to recognize FAS3-expressing muscles as alternative targets. We propose that homophilic synaptic target recognition serves as a basic mechanism of neural network formation.


Asthma predicts cardiovascular disease events: the multi-ethnic study of atherosclerosis.
To identify and characterize an association between persistent asthma and cardiovascular disease (CVD) risk in the Multi-Ethnic Study of Atherosclerosis (MESA). MESA is a longitudinal prospective study of an ethnically diverse cohort of individuals free of known CVD at its inception. The presence and severity of asthma were assessed in the MESA at examination 1. Persistent asthma was defined as asthmatics using controller medications (inhaled corticosteroids, leukotriene inhibitors, and oral corticosteroids) and intermittent asthma as asthmatics not using controller medications. Participants were followed up for a mean (SD) of 9.1 (2.8) years for development of incident CVD (coronary death, myocardial infarction, angina, stroke, and CVD death). Multivariable Cox regression models were used to assess associations of asthma and CVD. The 6792 participants were 62.2 (SD, 10.2) years old: 47% men (28% black, 22% Hispanic, and 12% Chinese). Persistent asthmatics (n=156), compared with intermittent (n=511) and nonasthmatics (n=6125), respectively, had higher C-reactive protein (1.2 [1.2] versus 0.9 [1.2] versus 0.6 [1.2] mg/L) and fibrinogen (379 [88] versus 356 [80] versus 345 [73] mg/dL) levels. Persistent asthmatics had the lowest unadjusted CVD-free survival rate of 84.1%, 95% confidence interval (78.9%-90.3%) compared with intermittent asthmatics 91.1% (88.5%-93.8%) and nonasthmatics 90.2% (89.4%-91%). Persistent asthmatics had greater risk of CVD events than nonasthmatics (hazard ratio [95% confidence interval], 1.6 [1.01-2.5]; P=0.040]), even after adjustment for age, sex, race, CVD risk factors, and antihypertensive and lipid medication use. In this large multiethnic cohort, persistent asthmatics had a higher CVD event rate than nonasthmatics.


Successful prevention of oral self-mutilation using a lip guard: a case report.
Self-injurious behavior (SIB) is causing deliberate harm to the body without suicidal intent; this problem occurs in a number of psychiatric, behavioral, and developmental disorders. This report describes the case of a girl, aged 19 months, whose lower lip injuries due to SIB were successfully treated through the use a combination of extraoral and intraoral prostheses. A custom-made lip guard with a custom-made adjustable head strap was effective in the management of the lip trauma. SIB was prevented and there was no recurrence even at the 17-month follow-up appointment.


Digital radiography of the chest: detector techniques and performance parameters.
Substantial advances in detector technology characterize digital chest radiography. This article compares the various systems from a radiologist's point of view. Computed radiography (CR) is a well-established system that is robust, has good reproducibility, and is relatively inexpensive. Image quality has been continuously improved in recent years while the physical size of the readout units has been reduced and the throughput increased. CR is the only digital system that can be used for bedside chest radiographs. Improved detector properties and dual reading have made it a dose-efficient system. Although now widely available, a 4K image matrix does not appear to offer a general diagnostic improvement for imaging the chest. New developments with respect to detector composition and readout process can be expected in the future. Direct radiography (DR) is the common name for different technologies that are characterized by a direct readout matrix that covers the whole exposure area. Conversion of x-ray intensity into electric signals can either be direct (selenium-based systems) or indirect (scintillator/photodiode systems). Advantages of DR systems are a high image quality and the potential for dose reduction. The role of selenium radiography (Thoravision) has decreased after the advent of DR systems although this dedicated chest unit offers high image quality at 400 speed acquisition dose. Especially in a PACS environment, CR and DR systems will increasingly substitute for conventional radiography with advantages for CR for bedside chest radiographs and for DR for high-end chest stands.


Parental anxiety and depression are associated with adverse mental health in children with special needs during the COVID-19 pandemic.
The coronavirus disease 2019 (COVID-19) pandemic has led to restrictions in various areas of life, including social life, work, leisure, health, and education. Vulnerable groups, such as children with special needs and their parents, may be at increased risk of experiencing exacerbated mental health problems during stressful periods such as the COVID-19 lockdowns. Telephone interviews were conducted with 954 parents of children with special needs. We assessed parental levels of generalized anxiety and depression using the validated GAD-7 and PHQ-8 scales. Parents were asked to rate family burden and their worry about the COVID-19 crisis, as well as their children's adverse mental health symptoms and health behaviors. Parents also reported their children's worries about the COVID-19 crisis. We conducted regressions to examine the relationship between parents' mental health problems and their children's adverse mental health symptoms and health behaviors. Qualitative data from open-ended questions were coded thematically and major themes of parental worry about the COVID-19 crisis were identified. Parental anxiety and depression symptoms predicted adverse mental health symptoms and behaviors in children with special needs. Criteria for current depression were met by 7.9% of parents of children with special needs, whereas 4.7% of the general population in Vorarlberg met the criteria for current depression according to data from the Austrian Health Interview Survey in 2019. Parental self-ratings of both depression and anxiety were highly correlated. The majority of parents reported being burdened (79.1%) or worried (67.8%) about the COVID-19 crisis. The main themes of parental worry about the COVID-19 crisis included COVID-19 infection (40.6%), economic situation (13.1%), uncertainty (8.4%), lack of social contact with family and friends (8.1%), family health status (7.5%), and school life (7.5%). Mental health symptoms in parents of children with special needs were strongly associated with increased adverse mental health symptoms and health behaviors in their children. Parents of children with special needs were more likely to be depressed during the COVID-19 pandemic than adults in 2019. We call for additional mental health support to reduce the mental health burden in families with children with special needs.


Hydrazone-sulfonate hybrids as potential cholinesterase inhibitors: design, synthesis and molecular modeling simulation.
Aim: Design and synthesis of a series of hydrazone-sulfonate hybrids, 5a-r. Methodology: The inhibitory properties of the synthesized compounds against acetylcholinesterase and butyrylcholinesterase were evaluated using donepezil as the reference standard. Results & conclusion: Compound 5e was identified as the most potent inhibitor of acetylcholinesterase (IC50 = 9.30 μM), and compound 5i was the most potent inhibitor of butyrylcholinesterase (IC50 = 11.82 μM). To confirm the safety of the most potent hits at the used doses, toxicological bioassays were conducted. Molecular docking was performed and the tested derivatives were found to fit well in the active sites of both enzymes. This study provides valuable insights into the potential of hydrazone-sulfonate hybrids as drug candidates.


Baseball players diagnosed with ulnar collateral ligament tears demonstrate decreased balance compared to healthy controls.
Cross-sectional. To compare lower extremity balance and shoulder range of motion in baseball players with ulnar collateral ligament (UCL) tears to a healthy cohort. Background Throwing is a complex motion that requires balance and coordination to effectively transfer energy through the kinetic chain. In theory, poorer balance could negatively affect throwing mechanics and lead to injury. Thirty baseball players (mean ± SD age, 18.5 ± 1.9 years) with a diagnosis of a UCL tear of their throwing arm were compared to 30 players (age, 19.0 ± 1.1 years) without a UCL tear. All participants were competing at either the high school or collegiate level and reported an average ± SD of 13.5 ± 1.7 years of playing experience. The Y Balance Test composite scores were calculated for the stance and lead lower extremities of all players. Shoulder range of motion was used to calculate glenohumeral internal rotation deficit and side-to-side differences in total rotational motion. Group comparisons were made between participants with and without UCL tears using independent t tests. Baseball players with UCL tears scored significantly lower on the Y Balance Test for both the stance (P<.001) and lead (P<.001) lower extremities compared to the noninjured cohort. No between-group differences were noted in glenohumeral internal rotation deficit (P = .453), whereas the mean ± SD side-to-side difference in total rotational motion was -6.0° ± 9.6° for the injured group, compared to -0.4° ± 9.6° for the control group (P = .028). Participants with a UCL tear demonstrated decreased performance for their stance and lead lower extremities during the Y Balance Test. These data are consistent with a clinical hypothesis of a potential association between impaired balance and UCL tears in high school and collegiate baseball players. The lower total rotational motion of the dominant shoulder in participants with UCL tears needs to be considered in the interpretation of those results.


Symmetry breaking and pattern selection in far-from-equilibrium systems.
A mechanism enabling nonequilibrium systems to select spatially asymmetric solutions is outlined. It operates when a macroscopic mode undergoing a symmetry-breaking bifurcation can interact with a polar or a chiral field not explicitly involved in the bifurcation. The perturbation of the bifurcation induced by the field allows the system to capture the external asymmetry and build patterns of preferred polarity or preferred chirality. The chemical and biological implications of forming such an asymmetric medium are discussed.


DIAGNOSIS OF ENDOCRINE DISEASE: Evaluation of bone fragility in endocrine disorders.
An underlying disease affecting bone health is present in up to 40% and 60% of osteoporotic post-menopausal women and men respectively. Among the disorders leading to a secondary form of osteoporosis, the endocrine diseases are highly represented. A frequent finding in patients affected with an endocrine-related forms of bone disease is that the skeletal fragility is partially independent of the bone density, since the fracture risk in these patients is related more to a reduction of bone quality than to a decrease of bone mass. As a consequence, bone mineral density evaluation by dual-X-ray Absorptiometry may be inadequate for establishing the risk of fracture in the setting of the endocrine-related forms of osteoporosis. In the recent years several attempts to non-invasively estimating bone quality have been done. Nowadys, some new tools are available in the clinical practice for optimizing the fracture risk estimation in patients with endocrine disorders. The aim of this review is to summarise the evidences regarding the role of the different imaging tools for evaluating bone density and bone quality in the most frequent forms of endocrine-related osteoporosis, such as obesity, diabetes, acromegaly, thyrotoxicosis, primary hyperparathyroidism, hypercortisolism and hypogonadism. For each of these disorders, data regarding both the current available tools and the future possible new techniques for assessing bone fragility in patients with endocrine diseases are reported.


Relevance of Single-Transmetalated Resting States in Iron-Mediated Cross-Couplings: Unexpected Role of σ-Donating Additives.
Control of the transmetalation degree of organoiron(II) species is a critical parameter in numerous Fe-catalyzed cross-couplings to ensure the success of the process. In this report, we however demonstrate that the selective formation of a monotransmetalated FeII species during the catalytic regime counterintuitively does not alone ensure an efficient suppression of the nucleophile homocoupling side reaction. It is conversely shown that a fine control of the transmetalation degree of the transient FeIII intermediates obtained after the activation of alkyl electrophiles by a single-electron transfer (SET), achievable using σ-donating additives, accounts for the selectivity of the cross-coupling pathway. This report shows for the first time that both coordination spheres of FeII resting states and FeIII short-lived intermediates must be efficiently tuned during the catalytic regime to ensure high coupling selectivities.


Soluble tumor necrosis factor receptors and heart failure risk in older adults: Health, Aging, and Body Composition (Health ABC) Study.
Tumor necrosis factor (TNF) levels are associated with risk for heart failure (HF). The soluble TNF type 1 (sTNF-R1) and type 2 (sTNF-R2) receptors are elevated in patients with manifest HF, but whether they are associated with risk for incident HF is unclear. Using Cox proportional hazard models, we examined the association between baseline levels of sTNF-R1 and sTNF-R2 with incident HF risk among 1285 participants of the Health, Aging, and Body Composition Study (age, 74.0±2.9 years; 51.4% women; 41.1% black). At baseline, median (interquartile range) of TNF, sTNF-R1, and sTNF-R2 levels was 3.14 (2.42-4.06), 1.46 (1.25-1.76), and 3.43 (2.95-4.02) ng/mL, respectively. During a median follow-up of 11.4 (6.9-11.7) years, 233 (18.1%) participants developed HF. In models controlling for other HF risk factors, TNF (hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.02-1.61 per log2 increase) and sTNF-R1 (HR, 1.68; 95% CI, 1.15-2.46 per log2 increase), but not sTNF-R2 (HR, 1.15; 95% CI, 0.80-1.63 per log2 increase), were associated with a higher risk for HF. These associations were consistent across whites and blacks (TNF, sTNF-R1, sTNF-R2; interaction P=0.531, 0.091, and 0.795, respectively) and in both sexes (TNF, sTNF-R1, sTNF-R2; interaction P=0.491, 0.672, and 0.999, respectively). TNF-R1 was associated with a higher risk for HF with preserved versus reduced ejection fraction (HR, 1.81; 95% CI, 1.03-3.18; P=0.038 for preserved versus HR, 0.90; 95% CI, 0.56-1.44; P=0.667 for reduced ejection fraction; interaction P=0.05). In older adults, elevated levels of sTNF-R1 are associated with increased risk for incident HF. However, addition of TNF-R1 to the previously validated Health ABC HF risk model did not demonstrate material improvement in net discrimination or reclassification.


Thyroid function, sex hormones and sexual function: a Mendelian randomization study.
Hypothyroidism and hyperthyroidism are observationally associated with sex hormone concentrations and sexual dysfunction, but causality is unclear. We investigated whether TSH, fT4, hypo- and hyperthyroidism are causally associated with sex hormones and sexual function. We used publicly available summary statistics from genome-wide association studies on TSH and fT4 and hypo- and hyperthyroidism from the ThyroidOmics Consortium (N ≤ 54,288). Outcomes from UK Biobank (women ≤ 194,174/men ≤ 167,020) and ReproGen (women ≤ 252,514) were sex hormones (sex hormone binding globulin [SHBG], testosterone, estradiol, free androgen index [FAI]) and sexual function (ovulatory function in women: duration of menstrual period, age at menarche and menopause, reproductive lifespan, and erectile dysfunction in men). We performed two-sample Mendelian randomization (MR) analyses on summary level, and unweighted genetic risk score (GRS) analysis on individual level data. One SD increase in TSH was associated with a 1.332 nmol/L lower (95% CI: - 0.717,- 1.946; p = 2 × 10-5) SHBG and a 0.103 nmol/l lower (- 0.051,V0.154; p = 9 × 10-5) testosterone in two-sample MR, supported by the GRS approach. Genetic predisposition to hypothyroidism was associated with decreased and genetic predisposition to hyperthyroidism with increased SHBG and testosterone in both approaches. The GRS for fT4 was associated with increased testosterone and estradiol in women only. The GRS for TSH and hypothyroidism were associated with increased and the GRS for hyperthyroidism with decreased FAI in men only. While genetically predicted thyroid function was associated with sex hormones, we found no association with sexual function.


Five-year outcomes of staged percutaneous coronary intervention in the SYNTAX study.
The SYNTAX study compared PCI with TAXUS Express stents to CABG for the treatment of de novo 3-vessel and/or left main coronary disease. This study aimed to determine patient characteristics and five-year outcomes after a staged PCI strategy compared to single-session PCI. In the SYNTAX trial, staged procedures were discouraged but were allowed within 72 hours or, if renal insufficiency or contrast-induced nephropathy occurred, within 14 days (mean 9.8±18.1 days post initial procedure). A total of 125 (14%) patients underwent staged PCI. These patients had greater disease severity and/or required a more complex procedure. MACCE was significantly increased in staged patients (48.1% vs. 35.5%, p=0.004), as was the composite of death/stroke/MI (32.2% vs. 19%, p=0.0007). Individually, cardiac death and stroke occurred more frequently in the staged PCI group (p=0.03). Repeat revascularisation was significantly higher in staged patients (32.8% vs 24.8%, p=0.035), as was stent thrombosis (10.9% vs. 4.7%, p=0.005). There is a higher incidence of MACCE in patients undergoing staged compared to single-session PCI for 3-vessel and/or left main disease over the first five years of follow-up. However, these patients had more comorbidities and more diffuse disease.


Chronic Lower Back Pain in Weight Lifters: Epidemiology, Evaluation, and Management.
» Chronic lower back pain (LBP) is common in both nonathletes and weight lifters, but the diagnosis and treatment should be approached differently in these 2 populations based on the unique movement patterns causing the pain.» Injury rates of weight lifters are far less than those of contact sports, ranging from 1.0 to 4.4 injuries per 1,000 workout hours. However, the lower back was consistently one of the top 2 injury sites for weight lifters, accounting for anywhere from 23% to 59% of all injuries. LBP was most often associated with the squat or deadlift.» Guidelines for evaluating general LBP are applicable to weight lifters, including a thorough history and physical examination. However, the differential diagnosis will change based on the patient's lifting history. Of the many etiologies of back pain, weight lifters are most likely to be diagnosed with muscle strain or ligamentous sprain, degenerative disk disease, disk herniation, spondylolysis, spondylolisthesis, or lumbar facet syndrome.» Traditional recommended therapies include nonsteroidal anti-inflammatory drugs, physical therapy, and activity modification, which are often insufficient to resolve pain and prevent injury recurrence. Because most athletes will want to continue to lift weights, lifting-specific behavior modifications focused on improved technique and correcting mobility and muscular imbalances are important aspects of management in this patient population.


Case Report: Isolated Lingual Dystonia.
Oromandibular dystonia is defined as a focal dystonia that manifests as forceful contractions of the face, jaw, and/or tongue. Lingual dystonia is a rare subtype of oromandibular dystonia that specifically affects the tongue. Multiple etiologies are thought to attribute to oromandibular dystonia, including brain damage, the use of neuroleptic medications, neurodegenerative disorders, metabolic disorders, neurodevelopmental disorders, and viral infections. Idiopathic cases of isolated lingual dystonia are rare and seldom reported in the literature. This report describes a 35-year-old female patient with lingual dystonia that was present at rest and aggravated during speech. Despite detailed history taking and a thorough examination, along with multiple imaging and laboratory studies, no cause could be established and her case was classified as being that of an idiopathic etiology.


Characterization of a membrane antigen from rabbit testis and sperm isolated by using monoclonal antibodies and effect of its antiserum on fertility.
An antigen was isolated from deoxycholate-solubilized rabbit testis and sperm by using an immunosorbent column containing IgG from a monoclonal antibody (8C10.5) that inhibits fertility. Elution was by stepwise increases in pH (8.0, 10.0, and 11.4), with the pH 11.4 fraction after recycling through the column showing a single band at 63 kilodaltons in slab NaDodSO4/PAGE with a silver stain. The antigen molecule was composed of two subunits, which on two-dimensional PAGE showed many spots within the same molecular size range (50-70 kilodaltons) but differing in charge. The antigen isolated either from testis or sperm showed mainly the same spots. The antigen is periodic acid/Schiff positive and contained 21% carbohydrate. An asialo-derivative of the antigen did not change its characteristics on NaDodSO4/PAGE. This glycoprotein resolved into two types of polypeptides, those binding and those not binding to a lens culinaris lectin column; some of the polypeptides appeared common to both fractions. Murine antiserum against the antigen neither agglutinated nor immobilized rabbit sperm but in immunofluorescence reacted with the plasma membrane of viable rabbit sperm as well as with murine and human sperm. Fertilization of female rabbits inseminated with treated sperm was not affected, but, by 9 days, fertility was significantly reduced (21% of controls). The postfertilization antifertility effect was not due to parthenogenic activation or to polyspermy. The antiserum reacted with one specific band in the one- and two-dimensional gel electrophoretic transfer blot procedure and was unaffected by absorption with different somatic tissues.


Toll-like receptors: Significance, ligands, signaling pathways, and functions in mammals.
This review attempts to cover the implication of the toll-like receptors (TLRs) in controlling immune functions with emphasis on their significance, function, regulation and expression patterns. The tripartite TLRs are type I integral transmembrane receptors that are involved in recognition and conveying of pathogens to the immune system. These paralogs are located on cell surfaces or within endosomes. The TLRs are found to be functionally involved in the recognition of self and non-self-antigens, maturation of DCs and initiation of antigen-specific adaptive immune responses as they bridge the innate and adaptive immunity. Interestingly, they also have a significant role in immunotherapy and vaccination. Signals generated by TLRs are transduced through NFκB signaling and MAP kinases pathway to recruit pro-inflammatory cytokines and co-stimulatory molecules, which promote inflammatory responses. The excess production of these cytokines leads to grave systemic disorders like tumor growth and autoimmune disorders. Hence, regulation of the TLR signaling pathway is necessary to keep the host system safe. Many molecules like LPS, SOCS1, IRAK1, NFκB, and TRAF3 are involved in modulating the TLR pathways to induce appropriate response. Though quantification of these TLRs helps in correlating the magnitude of immune response exhibited by the animal, there are several internal, external, genetic and animal factors that affect their expression patterns. So it can be concluded that any identification based on those expression profiles may lead to improper diagnosis during certain conditions.


Role of oceanic air bubbles in atmospheric correction of ocean color imagery.
Ocean color is the radiance that emanates from the ocean because of scattering by chlorophyll pigments and particles of organic and inorganic origin. Air bubbles in the ocean also scatter light and thus contribute to the water-leaving radiance. This additional water-leaving radiance that is due to oceanic air bubbles could violate the black pixel assumption at near-infrared wavelengths and be attributed to chlorophyll in the visible. Hence, the accuracy of the atmospheric correction required for the retrieval of ocean color from satellite measurements is impaired. A comprehensive radiative transfer code for the coupled atmosphere--ocean system is employed to assess the effect of oceanic air bubbles on atmospheric correction of ocean color imagery. This effect is found to depend on the wavelength-dependent optical properties of oceanic air bubbles as well as atmospheric aerosols.


Cadmium sulphide quantum dots with tunable electronic properties by bacterial precipitation.
We present a new method to fabricate semiconducting, transition metal nanoparticles (NPs) with tunable bandgap energies using engineered Escherichia coli. These bacteria overexpress the Treponema denticola cysteine desulfhydrase gene to facilitate precipitation of cadmium sulphide (CdS) NPs. Analysis with transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectroscopy reveal that the bacterially precipitated NPs are agglomerates of mostly quantum dots, with diameters that can range from 3 to 15 nm, embedded in a carbon-rich matrix. Additionally, conditions for bacterial CdS precipitation can be tuned to produce NPs with bandgap energies that range from quantum-confined to bulk CdS. Furthermore, inducing precipitation at different stages of bacterial growth allows for control over whether the precipitation occurs intra- or extracellularly. This control can be critically important in utilizing bacterial precipitation for the environmentally-friendly fabrication of functional, electronic and catalytic materials. Notably, the measured photoelectrochemical current generated by these NPs is comparable to values reported in the literature and higher than that of synthesized chemical bath deposited CdS NPs. This suggests that bacterially precipitated CdS NPs have potential for applications ranging from photovoltaics to photocatalysis in hydrogen evolution.


Patients with lower extremity dialysis access have poor primary patency and survival.
Lower extremity arteriovenous (AV) access is an alternative when upper extremity access options have been exhausted. Our goal was to assess short- and medium-term outcomes of lower extremity hemodialysis access. The Vascular Quality Initiative was reviewed for all lower extremity AV hemodialysis cases. Patient and case details were recorded. Multivariable analysis was used to analyze outcomes. We identified 463 lower extremity AV access cases in the VQI registry. There were 56 AVF (12.1%) and 407 AVG (87.9%). The mean age was 56 ± 15 years, 46.9% were male, and 40.7% were Caucasian. The majority (90%) had a previous upper extremity AV access and 25.4% had a prior lower extremity access. More than one-half (57.9%) had a tunneled line at the time of the procedure. Patients undergoing an AVF vs AVG creation were younger, more often ambulatory, and less often with peripheral arterial disease. For AVF, the superficial femoral artery was more often used for access inflow (76.8% vs 49.4%; P < .001), compared with AVG, and there was no difference in using femoral vein as the main outflow (78.6% vs 82.6%; P = .466). For AVF, compared with AVG, there was no difference in wound infection (12.5% vs 9.6%; P = .571), ischemic steal (5% vs 2.2%; P = .273), or leg swelling (2.5% vs 3.3%; P = .99) at 6 months. Kaplan-Meier analysis of the overall cohort showed that freedom from loss of primary patency at 6 months was 52.9%, freedom from any reintervention at 6 months was 75.3%, and the 1-year survival was 81.9%. Survival at 5 years was 65.5%. Multivariable analysis showed no significant association of access type (AVF vs AVG) with primary patency loss or death (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.36-1.5; P = .4), any reintervention or death (HR, 1.65; 95% CI, 0.82-3.33; P = .163), or mortality (HR, 1.94; 95% CI, 0.71-5.33; P = .197). Factors independently associated with primary patency loss or death included peripheral arterial disease (HR, 1.6; 95% CI, 1.06-2.42; P = .03) and obesity (HR, 1.5; 95% CI, 1.1-2.05; P = .01). Any reintervention or death was associated with obesity (HR, 1.67; 95% CI, 1.09-2.56; P = .015). Mortality was associated with congestive heart failure (HR, 1.82; 95% CI, 1.13-2.94; P = .015) and white race (HR, 1.71; 95% CI, 1.08-2.73; P = .023). In our contemporary multicenter analysis, patients undergoing lower extremity AV access creation have low primary access patency and almost 20% mortality at 1 year. These results should be considered when suggesting a lower extremity dialysis access, as well as other dialysis alternatives when available.


Evaluation of the API 20E system for identification of nonfermentative Gram-negative bacteria.
The API 20E system for Enterobacteriaceae, recently broadened to include identification of nonfermentative gram-negative bacteria, was evaluated and compared with the conventional method for complete identification of 221 nonfermenters, which were well distributed into 48 species or biotypes and included organisms not listed in the API 20E data base. The results of 16 tests common to both systems were in close agreement. The API 20E system correctly identified 71 (43%) of the 165 organisms included in the API 20E data base. However, almost 90% of Acinetobacter calcoaceticus, three species of Pseudomonas, and Bordetella bronchiseptica were correctly identified to species.


Assessment of long-term neurodevelopmental outcome following trials of medicinal products in newborn infants.
There is significant uncertainty over the role of assessment of long-term neurodevelopmental outcome (LTO) in neonatal clinical trials. A multidisciplinary working group was established to identify key issues in this area and to make recommendations about optimal approaches to evaluate LTO in therapeutic trials in newborns, which can be developed by sponsors and investigators with other key stakeholders. A key consideration for neonatal trials is the potential for the investigational product to cause widespread effects and drives the need to assess outcome in multiple organs. Thus investigators must assess whether the product has an impact on the brain and the potential for it to cause potential effects on LTO. Critically, is assessment of LTO an important direct therapeutic target or a safety outcome? Such decisions and outcomes need to be specific to the product being studied and use published data, only considering expert opinion when prior evidence does not exist. In designing the trial, the balance of benefits, costs, and burdens of assessments to the researcher and families need to be considered. Families and parent advocates should be involved in design and execution of the study. A framework is presented for use by all key stakeholders to determine the need, nature, and duration of LTO assessments in regulatory trials involving newborn infants.


A technique for isolation of bovine hepatocytes.
A technique for preparing viable and functional isolated hepatocytes from cattle liver is described. The basic procedure, which was adapted from published methods established for laboratory species, employed a two-step in vitro vascular perfusion of the caudate lobe: (1) perfusion with a calcium-free buffer containing ethylene bis(oxyethylenenitrilo)tetraacetic acid (EGTA) for removal of blood cells and extracellular calcium and (2) perfusion with calcium-fortified buffer containing collagenase for cell dissociation. Hepatocyte suspensions prepared from the caudate lobes of 20 cattle possessed a mean viability of 81.3% as determined by trypan blue exclusion. Mean yield was 2.2 X 10(7) viable hepatocytes/g of liver (wet wt). Viable hepatocytes utilized O2 at a rate 2.82 times greater than nonviable hepatocytes. Biochemical function of the hepatocyte suspensions was assessed by rates of gluconeogenesis and fatty acid oxidation. Glucose production from added lactate ranged from .88 to 1.47 mumol X min-1 X g-1 of liver tissue (dry wt). Both gluconeogenic and fatty acid oxidation rates were substantially greater in isolated hepatocytes when compared with liver slices. Isolated hepatocyte contained .398 +/- .033 (SE) nmol cytochromes P-450/mg microsomal protein and .285 +/- .025 nmol cytochrome bs/mg microsomal protein, which was comparable with amounts in liver tissue from the same animals (.568 +/- .056 and .298 +/- .033 nmol/mg protein, respectively). No significant decline of either cytochrome was detectable for isolated hepatocytes for up to 5.5 h after euthanasia. The potential usefulness of isolated bovine hepatocytes in xenobiotic metabolism studies is illustrated by the epoxidation of aldrin.


Adverse Event Trends Associated with OTC Analgesic and Antipyretic Drug: Data Mining of the Japanese Adverse Drug Event Report Database.
OTC drugs play an important role in self-medication. OTC analgesic and antipyretic drugs are widely used in Japan. The present study aimed to survey the components of OTC drug package inserts for analgesic and antipyretic drugs and to evaluate the adverse event profiles using the Japanese Adverse Drug Event Report database (JADER). The JADER contains 430587 reports from between April 2004 and November 2016; a total of 750 reports of adverse events resulted from the use of OTC analgesic and antipyretic drugs. The safety signals were detected by the reporting odds ratio (ROR). The ROR values for "Skin & subcutaneous tissue disorders", "Immune system disorders", and "Hepatobiliary disorders" stratified by system organ class of the Medical Dictionary for Regulatory Activities (MedDRA) were 7.58 (6.56-8.76), 4.25 (3.51-5.14), and 2.35 (1.93-2.85), respectively. OTC analgesic and antipyretic drugs containing allylisopropylacetylurea (AIAU) exhibited a significantly high reporting ratio of "Skin & subcutaneous tissue disorders" compared with the drugs without AIAU. No difference in the reported incidence of "Hepatobiliary disorders" was found between the drugs with or without acetaminophen. Our results suggested that it was important to monitor patients who use OTC analgesic and antipyretic drug containing AIAU; in particular, careful attention should be paid to skin and subcutaneous tissue disorders.


The World Health Organization's Response to Emerging Human Immunodeficiency Virus Drug Resistance and a Call for Global Action.
The global community, including the World Health Organization (WHO), has committed to ending the AIDS epidemic and to ensuring that 90% of people living with human immunodeficiency virus (HIV) are diagnosed, 90% start treatment, and 90% achieve and maintain virological suppression. The emergence of HIV drug resistance (HIVDR) as antiretroviral treatment programs expand could preclude the 90-90-90 targets adopted by the United Nations General Assembly at the High-Level Meeting on Ending AIDS from being achieved. The Global Action Plan on HIVDR is a call for collective action grounded on normative guidance providing a standardized and robust approach to monitoring, preventing, and responding to HIVDR over the next 5 years (2017-2021). WHO is committed to supporting country, global, regional, and national partners to implement and monitor the progress of the Global Action Plan. This article outlines the key components of WHO's strategy to tackle HIVDR and the role the organization takes in leading the global response to HIVDR.


The Genetics of Mating Song Evolution Underlying Rapid Speciation: Linking Quantitative Variation to Candidate Genes for Behavioral Isolation.
Differences in mating behaviors evolve early during speciation, eventually contributing to reproductive barriers between species. Knowledge of the genetic and genomic basis of these behaviors is therefore integral to a causal understanding of speciation. Acoustic behaviors are often part of the mating ritual in animal species. The temporal rhythms of mating songs are notably species-specific in many vertebrates and arthropods and often underlie assortative mating. Despite discoveries of mutations that disrupt the temporal rhythm of these songs, we know surprisingly little about genes affecting naturally occurring variation in the temporal pattern of singing behavior. In the rapidly speciating Hawaiian cricket genus Laupala, the striking species variation in song rhythms constitutes a behavioral barrier to reproduction between species. Here, we mapped the largest-effect locus underlying interspecific variation in song rhythm between two Laupala species to a narrow genomic region, wherein we find no known candidate genes affecting song temporal rhythm in Drosophila Whole-genome sequencing, gene prediction, and functional annotation of this region reveal an exciting and promising candidate gene, the putative cyclic nucleotide-gated ion channel-like gene, for natural variation in mating behavior. Identification and molecular characterization of the candidate gene reveals a nonsynonymous mutation in a conserved binding domain, suggesting that ion channels are important targets of selection on rhythmic signaling during establishment of behavioral isolation and rapid speciation.


On Random Subspace Optimization-Based Hybrid Computing Models Predicting the California Bearing Ratio of Soils.
The California Bearing Ratio (CBR) is an important index for evaluating the bearing capacity of pavement subgrade materials. In this research, random subspace optimization-based hybrid computing models were trained and developed for the prediction of the CBR of soil. Three models were developed, namely reduced error pruning trees (REPTs), random subsurface-based REPT (RSS-REPT), and RSS-based extra tree (RSS-ET). An experimental database was compiled from a total of 214 soil samples, which were classified according to AASHTO M 145, and included 26 samples of A-2-6 (clayey gravel and sand soil), 3 samples of A-4 (silty soil), 89 samples of A-6 (clayey soil), and 96 samples of A-7-6 (clayey soil). All CBR tests were performed in soaked conditions. The input parameters of the models included the particle size distribution, gravel content (G), coarse sand content (CS), fine sand content (FS), silt clay content (SC), organic content (O), liquid limit (LL), plastic limit (PL), plasticity index (PI), optimum moisture content (OMC), and maximum dry density (MDD). The accuracy of the developed models was assessed using numerous performance indexes, such as the coefficient of determination, relative error, MAE, and RMSE. The results show that the highest prediction accuracy was obtained using the RSS-based extra tree optimization technique.


Myomectomy: technique and current indications.
Uterine fibroids are the commonest benign tumor of the female genital tract. They affect a significant proportion of reproductive aged women and may cause excessive menstrual bleeding, pelvic pain or pressure, and adversely affect reproductive outcomes. However, many women remain asymptomatic. Fibroids are the first indication for hysterectomy, but myomectomy is the most suitable surgical option for women who desire preservation of their fertility potential. Only a selected group of women of childbearing age will benefit from a myomectomy, as the consequences of myomectomy on reproductive function have remained controversial. The purpose of this paper was to review the main surgical approaches for myomectomy, and discuss evidence-based indications for myomectomy in women with fibroids, especially with regards to its impact on fertility and reproductive outcomes. A critical review of the literature pertaining to the surgical approaches of myomectomy and the indications for myomectomy was performed, focusing on their impact on fertility and reproductive outcomes. Myomectomy is useful for the treatment of symptomatic fibroids and in selected women with infertility. Symptomatic submucosal fibroids are classically treated by hysteroscopic resection. Symptomatic intramural and subserosal fibroids may be treated by myomectomy, either by laparotomy or laparoscopy depending on their number and size. Prophylactic myomectomy is not recommended for preventing obstetrical complications or the risk of leiomyosarcoma. Although fibroids may have a negative effect on fertility, only the removal of submucosal fibroids has been consistently shown to improve spontaneous fertility or outcomes of assisted reproduction technology.


Determination of the genotoxic effects of sweeteners, mannitol and lactitol.
The changes in dietary habit around the world have led to an increased use of additives in the food. The safety of food additives has been a main focus of research for many years due to the ongoing debate on their potential effects on health. In this study, the in vitro genotoxic effects of mannitol and lactitol, polyols used as sweetener food additives, were evaluated using chromosomal aberrations (CAs) and micronucleus (MN) assays in human peripheral lymphocytes. Additionally, the effects of these sweeteners on the mitotic index (MI) and nuclear division index (NDI) were investigated. Concentrations of 500, 1000, 2000, 4000, and 8000 μg/mL for mannitol and 250, 500, 1000, 2000, and 4000 μg/mL for lactitol were used. The results indicated that both polyols did not affect CA and MN frequency, and did not cause a significant change in NDI at all treatment concentratoins. However, mannitol (except at concentrations of 500 and 1000 μg/mL) and lactitol (except at 250 μg/mL) significantly decreased the MI compared to the control at almost all concentrations and treatment times. In conclusion, it was observed that mannitol and lactitol did not have a significant genotoxic effect at the concentrations used in human lymphocytes in vitro.


The Work Experience Survey - Rheumatic conditions (United Kingdom): Psychometric properties and identifying the workplace barriers of employed people with inflammatory arthritis receiving vocational rehabilitation.
The aims were to: revise the Work Experience Survey-Rheumatic Conditions (WES-RC- UK), a work assessment listing 142 workplace barriers; investigate content validity, reliability, and concurrent validity; update the accompanying WES-RC and WORKWELL Solutions Manuals; and investigate workplace barriers of people with inflammatory arthritis. Rheumatology therapists, following vocational rehabilitation (VR) training, assessed participants in the WORKWELL VR trial using the WES-RC. Data were extracted from the WES-RC to identify the frequency of workplace barriers, and from trial baseline questionnaires (e.g., Work Limitations Questionnaire-25 (WLQ-25). Barriers reported by ≤5 participants were considered for removal. WES-RC content validity was assessed by linking to the International Classification of Functioning, Health, and Disability Core Set for VR (ICF-VR). Reliability was assessed using Cronbach's α and concurrent validity by correlating the total number of workplace barriers reported with WLQ-25 scores. WES-RCs were completed with 116 employed participants: 79% women, age 48.72 (SD 9.49) years, and 57% working full-time. The WES-RC was reduced to 121 barriers. Content validity was good, with 73/90 ICF-VR items linked. Cronbach's α = 0.92, that is, suitable for individual use. Concurrent validity was moderate: WLQ-25 (rs = 0.40). The three most common barriers were Physical Job Demands (100%: e.g., mobility 99%; hand use 74%), Mental, Time, Energy, Emotional Job Demands (91%, e.g., concentration 47%, remembering 41%); Getting Ready for and Travel to Work (87%, e.g., driving 60%). The WES-RC (UK) has good content validity, reliability, and concurrent validity. The wide range of barriers emphasises the need for biopsychosocial work rehabilitation.


Influence of Host Plant on Thaumetopoea pityocampa Gut Bacterial Community.
Microbial communities associated to the gut of insects are attracting an increasing interest, mainly because of their role in influencing several host life-traits. The characterization of the gut microbial community is pivotal for understanding insect ecology and, thus, to develop novel pest management strategies. The pine processionary moth, Thaumetopoea pytiocampa (Denis & Schiff.) (Lepidoptera: Thaumetopoeidae), is a severe defoliator of pine forests, able to feed on several pine species. In this work, we performed a metabarcoding analysis to investigate, for the first time, the diversity of the gut bacterial community of pine processionary larvae associated with three different host pine species (Pinus halepensis, Pinus nigra subsp. laricio, and Pinus pinaster). We found that the gut microbial community of T. pityocampa larvae collected on P. halapensis was different from that associated with larvae collected from P. nigra and P. pinaster. Moreover, the high presence of bacteria belonging to the genera Modestobacter, Delftia, and unidentified Methylobacteriaceae retrieved in larvae feeding on P. halapensis suggested that specific interactions can occur. Our results provide the evidence that different host plant differently impact on the microbiota diversity of T. pityocampa larvae, contributing to the general knowledge of this pest with information that could be useful in shaping the next generation of pest control strategies.


Depression and experience of vision loss in group of adults in rehabilitation setting: mixed-methods pilot study.
There is a paucity of literature regarding the relationship between the experience of vision loss and depression. Therefore, the current pilot study aimed to explore whether significant differences existed in levels of depression between adults with different vision loss experiences. A group of adults aged between 20 and 65 yr old with irreversible vision loss in a rehabilitation setting was interviewed. Semistructured interviews were conducted in order to explore patients' experience of vision loss. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depressive levels; 39.5% (n = 15) of patients met CES-D criteria for depression. In addition, higher levels of depression (p < 0.05) were identified in patients whose interviews revealed greater self-awareness of impairment, inadequate social support, and longer rehabilitation stay. Current findings draw attention to variables such as self-awareness of impairment and perceived social support and suggest that depression following vision loss may be related to patients' emotional experiences of impairment and adjustment processes.


Custom-designed arrays of anodic alumina nanochannels with individually tunable pore sizes.
We demonstrate a process to selectively tune the pore size of an individual nanochannel in an array of high-aspect-ratio anodic aluminum oxide (AAO) nanochannels in which the pore sizes were originally uniform. This novel process enables us to fabricate arrays of AAO nanochannels of variable sizes arranged in any custom-designed geometry. The process is based on our ability to selectively close an individual nanochannel in an array by using focused ion beam (FIB) sputtering, which leads to redeposition of the sputtered material and closure of the nanochannel with a capping layer of a thickness depending on the energy of the FIB. When such a partially capped array is etched in acid, the capping layers are dissolved after different time delays due to their different thicknesses, which results in differences in the time required for the following pore-widening etching processes and therefore creates an array of nanochannels with variable pore sizes. The ability to fabricate such AAO templates with high-aspect-ratio nanochannels of tunable sizes arranged in a custom-designed geometry paves the way for the creation of nanophotonic and nanoelectronic devices.


Contrasted patterns of age-specific reproduction in long-lived seabirds.
While the number of studies providing evidence of actuarial senescence is increasing, and covers a wide range of taxa, the process of reproductive senescence remains poorly understood. In fact, quite high reproductive output until the last years of life has been reported in several vertebrate species, so that whether or not reproductive senescence is widespread remains unknown. We compared age-specific changes of reproductive parameters between two closely related species of long-lived seabirds: the small-sized snow petrel Pagodroma nivea, and the medium-sized southern fulmar Fulmarus glacialoides. Both are sympatric in Antarctica. We used an exceptional dataset collected over more than 40 years to assess age-specific variations of both breeding probability and breeding success. We found contrasted age-specific reproductive patterns between the two species. Reproductive senescence clearly occurred from 21 years of age onwards in the southern fulmar, in both breeding probability and success, whereas we did not report any decline in the breeding success of the snow petrel, although a very late decrease in the proportion of breeders occurred at 34 years. Such a contrasted age-specific reproductive pattern was rather unexpected. Differences in life history including size or migratory behaviour are the most likely candidates to account for the difference we reported in reproductive senescence between these sympatric seabird species.


The current role of contrast-enhanced ultrasound (CEUS) imaging in the evaluation of renal pathology.
By using a microbubble contrast agent and contrast-specific imaging software, the contrast-enhanced ultrasound (CEUS) is able to depict the micro and macrocirculation of the target organ. A review of the peer reviewed literature was done regarding the current role of ultrasound CEUS imaging in the evaluation of renal pathology with reference to the diagnosis of renal ischaemia, in the characterization of complex cystic lesions and in those with equivocal enhancement at CT. CEUS provides information on tissue perfusion and may play a role in kidney mass characterization similar to the role of contrast-enhanced CT and MRI. In this context, the characterization of cystic lesions is probably the most consolidated field of application of contrast agents on kidney ultrasound imaging. Finally, CEUS provides a good alternative to CT, especially in patients with contraindications to iodinated contrast agents. The usefulness of CEUS in these applications is confirmed by extensive literature production and this article focuses on the potential clinical applications of recent advances in CEUS technology in urology.


Conflict on interprofessional primary health care teams--can it be resolved?
Increasingly, primary health care teams (PHCTs) depend on the contributions of multiple professionals. However, conflict is inevitable on teams. This article examines PHCTs members' experiences with conflict and responses to conflict. This phenomenological study was conducted using in-depth interviews with 121 participants from 16 PHCTs (10 urban and 6 rural) including a wide range of health care professionals. An iterative analysis process was used to examine the verbatim transcripts. The analysis revealed three main themes: sources of team conflict; barriers to conflict resolution; and strategies for conflict resolution. Sources of team conflict included: role boundary issues; scope of practice; and accountability. Barriers to conflict resolution were: lack of time and workload; people in less powerful positions; lack of recognition or motivation to address conflict; and avoiding confrontation for fear of causing emotional discomfort. Team strategies for conflict resolution included interventions by team leaders and the development of conflict management protocols. Individual strategies included: open and direct communication; a willingness to find solutions; showing respect; and humility. Conflict is inherent in teamwork. However, understanding the potential barriers to conflict resolution can assist PHCTs in developing strategies to resolve conflict in a timely fashion.


Fine needle aspiration study of metastatic mixed adenosquamous carcinoma of the renal pelvis. A case report.
The findings in a fine needle aspirate of a psoas area metastasis from a mixed adenosquamous carcinoma of the renal pelvis are presented. The primary renal tumor is apparently the fourth such case reported in the literature; the pathogenesis of such tumors is briefly reviewed. The value of fine needle aspiration in excluding a clinically suspected abscess and in allowing a specific diagnosis of malignancy is emphasized.


[Private Prescriptions In East And West Germany - A Secondary Data Analysis].
Benzodiazepines and Z-drugs are prescribed to a considerable extent as private prescription also for persons insured by a statutory health insurance (SHI), with formerly large differences between East and West Germany. The aim of the present study was to investigate whether these differences still exist today. This secondary data analysis used anonymized prescription data from general practitioners (GPs), community neurologists, and psychiatrists. SHI-insured patients with at least one prescription for a benzodiazepine or Z-substance between 2014 and 2020 were included. Differences between East and West Germany in the proportion of private prescriptions were the central outcome. Multiple regression analyses were performed to test whether the factors region (eastern vs. western Germany) and specialist group (GPs vs. neurologists/psychiatrists) were statistically significant predictors of the proportion of private prescriptions - taking into account the age and gender composition of patients in a practice. From 867 practices, 2,200,446 prescriptions for Z-substances, benzodiazepine anxiolytics, and benzodiazepine hypnotics/sedatives were evaluated. More than 38% of these prescriptions were issued as private prescriptions: 53.6% in eastern Germany and 34.8% in western Germany. For Z-substances, the proportion of private prescriptions was particularly high (70.7% in eastern and 43.0% in western Germany). GPs issued private prescriptions far more frequently than neurologists and psychiatrists. The proportion of private prescriptions increased during the study period, comparatively strongly in the western states (from 33% to 39%) and slightly in the eastern states (from 53% to 54%). In the multivariate model, practice area (east/west) and specialist group were similarly strong predictors of the extent of private prescriptions, especially for Z-substances. Contrary to a general alignment in life expectancy, morbidity risks, and health behaviour in East and West Germany, there is, despite convergence, still a significant difference in the proportion of private prescriptions for benzodiazepines and especially for Z-substances between the two regions. The groups of physicians who mainly prescribe these substances, namely neurologists and psychiatrists, on the one hand, and GPs, on the other, also differ considerably in the proportion of their private prescriptions for these substances.


Roles of alpha1A- and alpha1B-adrenoceptors in heart: insights from studies of genetically modified mice.
1. Several mouse strains have been prepared in which different subtypes of the alpha1-adrenoceptor (AR) are overexpressed or deleted. The phenotypes of the animals generated vary depending on whether the receptors are expressed specifically in heart or generally throughout the animal, but some overall conclusions can be drawn. 2. Heightened activity of alpha1B-AR by overexpressing the receptors leads to depressed contractile responses to beta-AR activation, which may be related to activation of the inhibitory G-protein Gi. In contrast, alpha1A-AR cause substantially heightened contractility when overexpressed in heart. 3. Overexpressed alpha1B-AR predispose hearts to hypertrophy and worsen heart failure caused by pressure overload, whereas increased alpha1A-AR expression does not influence hypertrophic responses and, furthermore, improves outcomes after pressure overload or myocardial infarction. 4. Alpha1A-adrenoceptors mediate a preconditioning action to improve functional recovery after acute ischaemic insult, whereas alpha1B-AR are ineffective. Both subtypes appear to protect from inositol 1,4,5-trisphosphate generation and arrhythmogenesis in early postischaemic reperfusion. 5. Although some of the protective effects of heightened alpha1A-AR drive may be related to the enhanced contractility, it is also possible that alpha1A-AR protect from cardiomyocyte apoptotic responses.


Acute Necrotizing Encephalopathy in an Infant: Observations by CT, Contrast-Enhanced MRI and Diffusion MRI. A Case Report.
Acute necrotizing encephalopathy is characterized by bilateral necrotic, hemorrhagic lesions which occur symmetrically in the thalami, dorsal brainstem and dentate nuclei. Development of an extensive breakdown of the blood-brain barrier in the prominent lesions of acute necrotizing encephalopathy was demonstrated in a seven-month-old boy with the disorder, within 14 h after hospitalization by an initially negative post-contrast CT scan, and subsequently positive post-contrast T1-weighted MRI. Diffusion MRI demonstrated concomitant cytotoxic and vasogenic edema in the lesions. By the fortieth day, the lesions apparently regressed with remaining hemorrhagic material in the thalami.


A Quality Analysis of the Last Decade's Most Heavily Cited Data Relative to Outcomes After Penile Prosthesis Placement.
The penile prosthesis has been used for men with erectile dysfunction for nearly 5 decades. Although many articles examine various outcome measures, wide variability exists in the quality of these studies. We sought to critically evaluate the most referenced literature related to penile prosthesis outcomes over the last 10 years. A PubMed search of the indexed English literature was performed using the search terms "prospective," "penile prosthesis," and "outcomes", and all relevant publications from 2009 to 2019 were reviewed. In addition, we performed a Google Scholar search for the same interval using the search term "penile prosthesis outcomes" to evaluate manuscripts which have been most commonly cited. The most heavily cited manuscripts were sorted for relevancy using Google's internal algorithm, and then, the articles were reviewed by the authorship team for appropriateness of the subject matter. Articles with less than 10 citations were excluded. We used the Oxford Center for Evidence-Based Medicine Criteria as part of our evaluation of the published data involving independent research, as opposed to review articles summarizing previously published findings. We evaluated the most-cited literature of the past decade relevant to penile prosthesis outcomes and reported the major findings in regards to infection, erosion, extrusion, device reliability, and satisfaction (both the patient and partner). The majority of these studies are retrospective in nature. From our review of the most commonly cited studies, there was no high-level evidence published in this area within the last 10 years. There are multiple barriers to producing these types of studies in the evaluation of penile prosthesis outcomes. Using the most commonly cited articles allows us to understand the data that are being cited in other new publications. Focusing on the most cited articles on penile prosthesis outcomes in the last 10 years is a limitation as there have been many more studies published in this area. While many studies have examined penile prosthesis outcomes, most of the heavily cited literature consists of low-level evidence. Higher quality research is necessary to better assess penile prosthesis outcomes. Chouhan JD, Pearlman AM, Kovell RC, et al. A Quality Analysis of the Last Decade's Most Heavily Cited Data Relative to Outcomes After Penile Prosthesis Placement. J Sex Med 2020;17:861-869.


Serous cystadenoma of the pancreas: tumor growth rates and recommendations for treatment.
To define the natural history and optimal management of serous cystadenoma of the pancreas. Serous cystadenoma of the pancreas is the most common benign pancreatic neoplasm. Diagnostic criteria, potential for growth or malignancy, and outcomes are not well defined. As a result, management for patients with serous cystadenomas varies widely in current practice. A total of 106 patients presenting with serous cystadenoma of the pancreas from 1976-2004 were identified. Hospital records were evaluated for patient and tumor characteristics, diagnostic workup, treatment, and outcome. Twenty-four patients with serial radiographic imaging were identified, and tumor growth curves calculated. Mean age at presentation was 61.5 years and 75% of patients were female. The most common symptoms were abdominal pain (25%), fullness/mass (10%), and jaundice (7%); 47% were asymptomatic. Mean tumor diameter was 4.9 +/- 3.1 cm, which did not vary by location. Tumors <4 cm were less likely to be symptomatic than were tumors > or =4 cm (22% vs. 72%, P < 0.001). The median growth rate in the patients who had serial radiography was 0.60 cm/y. For tumors <4 cm at presentation (n = 15), the rate was 0.12 cm/y, whereas for tumors > or =4 cm (n = 9), the rate was 1.98 cm/y (P = 0.0002). Overall, 86 patients underwent surgery, with one perioperative death. Large (>4 cm) serous cystadenomas are more likely to be symptomatic. Although the median growth rate for this neoplasm is only 0.6 cm/y, it is significantly greater in large tumors. Whereas expectant management is reasonable in small asymptomatic tumors, we recommend resection for large serous cystadenomas regardless of the presence or absence of symptoms.


Acute heat-evoked temperature sensation is impaired but not abolished in mice lacking TRPV1 and TRPV3 channels.
The discovery of heat-sensitive Transient Receptor Potential Vanilloid ion channels (ThermoTRPVs) greatly advanced our molecular understanding of acute and injury-evoked heat temperature sensation. ThermoTRPV channels are activated by partially overlapping temperatures ranging from warm to supra-threshold noxious heat. TRPV1 is activated by noxious heat temperature whereas TRPV3 can be activated by warm as well as noxious heat temperatures. Loss-of-function studies in single TRPV1 and TRPV3 knock-out mice have shown that heat temperature sensation is not completely abolished suggesting functional redundancies among these two channels and highlighting the need of a detailed analysis of TRPV1::TRPV3 double knock-out mice (V1V3dKO) which is hampered by the close proximity of the loci expressing the two channels. Here we describe the generation of a novel mouse model in which trpv1 and trpv3 genes have been inactivated using bacterial artificial chromosome (BAC)-based homologous recombination in embryonic stem cells. In these mice, using classical thermosensory tests such hot plate, tail flick and the thermotaxis gradient paradigms, we confirm that TRPV1 is the master channel for sensing noxious heat temperatures and identify a cooperative role of TRPV1 and TRPV3 for sensing a well-defined window of acute moderate heat temperature. Using the dynamic hot plate assay, we unravel an intriguing and unexpected pronounced escape behavior in TRPV1 knock-out mice that was attenuated in the V1V3dKO. Together, and in agreement with the temperature activation overlap between TRPV1 and TRPV3 channels, our data provide in vivo evidence of a cooperative role between skin-derived TRPV3 and primary sensory neurons-enriched TRPV1 in modulation of moderate and noxious heat temperature sensation and suggest that other mechanisms are required for heat temperature sensation.


Auditory Hair Cells and Spiral Ganglion Neurons Regenerate Synapses with Refined Release Properties In Vitro.
Ribbon synapses between inner hair cells (IHCs) and type I spiral ganglion neurons (SGNs) in the inner ear are damaged by noise trauma and with aging, causing 'synaptopathy' and hearing loss. Co-cultures of neonatal denervated organs of Corti and newly introduced SGNs have been developed to find strategies for improving IHC synapse regeneration, but evidence of the physiological normality of regenerated synapses is missing. This study utilizes IHC optogenetic stimulation and SGN recordings, showing that newly formed IHC synapses are indeed functional, exhibiting glutamatergic excitatory postsynaptic currents. When older organs of Corti were plated, synaptic activity probed by deconvolution, showed more mature release properties, closer to the highly specialized mode of IHC synaptic transmission that is crucial for coding the sound signal. This newly developed functional assessment of regenerated IHC synapses provides a powerful tool for testing approaches to improve synapse regeneration.


Hepatitis delta in HIV-infected individuals in Europe.
Hepatitis delta virus (HDV) infection results in the most aggressive form of chronic viral hepatitis. There is scarce information about the prevalence, epidemiology, virological profile and natural history of hepatitis delta in HIV patients. From 16,597 HIV patients enrolled in EuroSIDA, 1319 (7.9%) have ever reported serum hepatitis B virus (HBV) surface antigen (HBsAg)-positive. At last follow-up, 1084 (6.5%) patients were HBsAg-positive. The HDV substudy was carried out in 422 individuals for whom stored sera were available at the time they were HBsAg-positive. Anti-HDV immunoglobulin G was assessed using a commercial enzyme immunoassay (EIA) and serum HDV-RNA was quantified using a real-time PCR method. A total of 61 of 422 HBsAg-positive carriers were anti-HDV-positive (prevalence: 14.5%). Hepatitis delta predominated in intravenous drug users and for this reason in south and/or east Europe. Serum HDV-RNA was detectable in 87% of tested anti-HDV-positive patients, with a median titer of 1.76×10(7) copies/ml. Overall, delta hepatitis patients showed lower serum HBV-DNA than the rest of HBsAg-positive carriers, although the inhibitory effect of HDV on HBV replication was not recognized in HBV genotype D patients. Whereas HDV was not associated with progression to AIDS, it significantly influenced the risk of death. The prevalence of anti-HDV in chronic HBsAg-positive/HIV carriers in EuroSIDA is 14.5%. Most of these patients exhibit detectable HDV viraemia. Viral interference between HBV and HDV is manifested in all but HBV genotype D carriers in whom overt coreplication of both viruses occurs which might result in enhanced liver damage. Overall, delta hepatitis increases the risk of liver-related deaths and overall mortality in HIV patients.


Natural human interferon alpha may act differently when given parenterally or orally to patients chronically infected with hepatitis B virus.
A literature review of patients chronically infected with hepatitis B virus (HBV) treated with natural human interferon alpha (nHuIFN-alpha) given parenterally every day for 28 days revelated that even the daily dose of (5 x 10(6)IU) of IFN-alpha inhibits cellular metabolism. As a result of metabolic block, the number of blood elements were diminished. Furthermore treated patients recorded several different adverse reactions. In contrast, among patients treated with the oral form of nHuIFN-alpha non metabolic block occurred and no adverse reactions were seen, even though the therapy lasted much longer. Two years after initiation of parenteral IFN-alpha therapy, the loss of HBV-BeAg was 53.8% and 28.8% of the patients had undergone seroconversion. In contrast, 77% of patients on oral interferon lost HBV-BeAg and 74% serconverted and normalized their biochemical liver function. The results suggest that the nHuIFN-alpha given orally and parenterally activate two different mechanisms responsible for virus elimination.