Ashworthvalentin9838

HA fillers are safe and effective with minimal recovery time and complications. Future studies with longer follow-up period and use of this 20 mg/ml HA dermal filler on areas other than midface may provide additional efficacy and safety outcomes.

HA fillers are safe and effective with minimal recovery time and complications. Future studies with longer follow-up period and use of this 20 mg/ml HA dermal filler on areas other than midface may provide additional efficacy and safety outcomes.

To report the causes, clinical features, and outcomes of infectious uveitis in patients managed in a mid-Atlantic tertiary care center.

Retrospective, observational study of infectious uveitis patients seen at the University of Virginia from 1984 to 2014.

Seventy-seven of 491 patients (15.7%) were diagnosed with infectious uveitis (mean age 58 years, 71.4% female, 76.6% Caucasian). The mean follow-up was 5 years. Anterior uveitis was the most common anatomic classification (39 patients, 50.6%) followed by panuveitis (20 patients, 26.0%) and posterior uveitis (18 patients, 23.4%). The most common infectious etiology was herpetic anterior uveitis (37 patients, 48.1%) followed by toxoplasma uveitis (14 patients, 18.2%). The most prevalent viral pathogen was varicella-zoster virus (21 patients, 27.3%) followed by herpes simplex virus (20 patients, 26.0%). Acute retinal necrosis (ARN) was diagnosed in 14 patients (18.2%). Aqueous humor yielded an etiologic diagnosis in seven (50%) of ARN patients, four of wh appropriate treatment.

The most common type of infectious uveitis seen over the study period was herpetic anterior uveitis secondary to varicella-zoster virus or herpes simplex virus, found to be most prevalent in patients over 60 years of age. This finding is comparable to other American epidemiologic studies. Ocular toxoplasmosis and ARN were also common causes of infectious uveitis. In all, 50.6% of patients had a VA better than 20/40 at the final follow-up visit, indicating the importance of prompt referral and appropriate treatment.Several features of the tendon-to-bone attachment were examined allometrically to determine load transfer mechanisms. The humeral head diameter increased geometrically with animal mass. Area of the attachment site exhibited a near isometric increase with muscle physiological cross section. In contrast, the interfacial roughness as well as the mineral gradient width demonstrated a hypoallometric relationship with physiologic cross-sectional area (PCSA). The isometric increase in attachment area indicates that as muscle forces increase, the attachment area increases accordingly, thus maintaining a constant interfacial stress. Due to the presence of constant stresses at the attachment, the micrometer-scale features may not need to vary with increasing load.Directed co-assembly of polymer-conjugated cyclic peptide nanotubes (CPNs) and block copolymers in thin films is a viable approach to fabricate sub-nanometer porous membranes without synthesizing nanotubes with identical length and vertical alignment. Here we show that the process is pathway dependent and successful co-assembly requires eliminating CPNs larger than 100 nm in solution. Optimizing polymer-solvent interactions can improve conjugate dispersion to a certain extent, but this limits thin film fabrication. Introduction of a trace amount of hydrogen-bond blockers, such as trifluoroacetic acid by vapor absorption, is more effective to reduce CPN aggregation in solution and circumvents issues of solvent immiscibility. This study provides critical insights into guided assemblies within nanoscopic frameworks toward sub-nanometer porous membranes.Although menthol, a common flavoring additive to cigarettes, has been found to impact the addictive properties of nicotine cigarettes in smokers little is known about its pharmacological and molecular actions in the brain. Studies were undertaken to examine whether the systemic administration of menthol would modulate nicotine pharmacokinetics, acute pharmacological effects (antinociception and hypothermia) and withdrawal in male ICR mice. In addition, we examined changes in the brain levels of nicotinic receptors of rodents exposed to nicotine and menthol. Administration of i.p. menthol significantly decreased nicotine's clearance (2-fold decrease) and increased its AUC compared to i.p. vehicle treatment. In addition, menthol pretreatment prolonged the duration of nicotine-induced antinociception and hypothermia (2.5 mg/kg, s.c.) for periods up to 180 min post-nicotine administration. Repeated administration of menthol with nicotine increased the intensity of mecamylamine-precipitated withdrawal signs in mice exposed chronically to nicotine. The potentiation of withdrawal intensity by menthol was accompanied by a significant increase in nicotine plasma levels in these mice. Western blot analyses of α4 and β2 nAChR subunit expression suggests that chronic menthol impacts the levels and distribution of these nicotinic subunits in various brain regions. In particular, co-administration of menthol and nicotine appears to promote significant increase in β2 and α4 nAChR subunit expression in the hippocampus, prefrontal cortex and striatum of mice. Surprisingly, chronic injections of menthol alone to mice caused an upregulation of β2 and α4 nAChR subunit levels in these brain regions. Because the addition of menthol to tobacco products has been suggested to augment their addictive potential, the current findings reveal several new pharmacological molecular adaptations that may contribute to its unique addictive profile.Systematic review aims to systematically identify, critically appraise, and summarize all relevant studies that match predefined criteria and answer predefined questions. The most common type of systematic review is that assessing the effectiveness of an intervention or therapy. In this article, we discuss some of the common methodological issues that arise when conducting systematic reviews and meta-analyses of effectiveness data, including issues related to study designs, meta-analysis, and the use and interpretation of effect sizes.Systematic reviews are carried out to provide an answer to a clinical question based on all available evidence (published and unpublished), to critically appraise the quality of studies, and account for and explain variations between the results of studies. The Joanna Briggs Institute specializes in providing methodological guidance for the conduct of systematic reviews and has developed methods and guidance for reviewers conducting systematic reviews of studies of diagnostic test accuracy. Diagnostic tests are used to identify the presence or absence of a condition for the purpose of developing an appropriate treatment plan. Owing to demands for improvements in speed, cost, ease of performance, patient safety, and accuracy, new diagnostic tests are continuously developed, and there are often several tests available for the diagnosis of a particular condition. In order to provide the evidence necessary for clinicians and other healthcare professionals to make informed decisions regarding the optimum test to use, primary studies need to be carried out on the accuracy of diagnostic tests and the results of these studies synthesized through systematic review. The Joanna Briggs Institute and its international collaboration have updated, revised, and developed new guidance for systematic reviews, including systematic reviews of diagnostic test accuracy. This methodological article summarizes that guidance and provides detailed advice on the effective conduct of systematic reviews of diagnostic test accuracy.Rhodium complexes derived from conformationally transformable α,ω-bisphosphite ligands combined with a suitable alkali metal BArF salt as a regulation agent (RA) provide high regio- and enantioselectivities in the asymmetric hydroformylation (AHF) of three heterocyclic olefins. The outcome of the AHF could be exquisitely regulated by choosing the appropriate RA with an increase in the ee, the reversal of the regioselectivity, or the complete suppression of one byproduct.Although there is evidence of a distinct profile of executive dysfunction in Williams syndrome (WS), a rare genetically based neurodevelopmental disorder, the utility of informant reports of everyday executive function (EF) impairments and their relation to intelligence is not yet clear. Here we aimed to evaluate the functional impact of executive dysfunction in adults with WS and to establish the validity of child and adult versions of the most commonly used rating scale for EF assessment, the Behaviour Rating Inventory of Executive Function (BRIEF). We were also interested in whether distinct components of everyday EF relate to intelligence in WS. Parent report child (BRIEF-C) and adult (BRIEF-A) ratings were collected on 20 adults with WS (aged 18.5 to 53 years), with a mean IQ of 60.95 (SD = 17.67). Neuropsychological measures of EF included The Shape School Test (Espy, 2007); select subdomains of EF from the Woodcock-Johnson III Tests of Cognitive Abilities, Australian Adaptation (WJ III COG); and select subdomains from the Vineland Adaptive Behaviour Scales, Second Edition-Parent Survey (Vineland-II). Results showed that the BRIEF-A, but not the BRIEF-C, was the most highly correlated with neuropsychological measures of EF, suggesting that it was a valid measure of the profile of EF impairments in adults with WS. The profile of everyday EF dysfunction revealed relative impairments in monitoring, working memory, planning and organisation in WS. In addition, both neuropsychological and rating scale measures showed an association between the shifting component of EF and intelligence. These findings indicate that the BRIEF-A is a valid measure of the multidimensional nature of real-world impairments in EF, and highlight its utility as a less labor intensive and low-cost screening tool for measuring specific EF impairments that could become the focus of targeted intervention in adults with WS.Here, we present evidence of a novel microtubule-disrupting agent, N-deacetyl-N-(chromone-2-carbonyl)-thiocolchicine (TCD), exhibiting potent antitumor activity (with IC50 values in the nanomolar range) against hepatocellular carcinoma cell lines. Cell cycle analysis revealed that TCD induced G2/M cell-cycle arrest in a dose- and time-dependent manner in both Hep-J5 and Mahlavu HCC cell lines. TCD also induced a decrease in mitochondrial membrane potential (ΔΨm) and caused DNA damage. Mechanistically, TCD activated protein kinase RNA-like endoplasmic reticular kinase and several transcription factors, including activating transcription factor (ATF) 6, ATF4, ATF3, and the CCAAT-enhancer binding protein homologous protein. These data clearly demonstrate that the antitumor activity of TCD is mechanistically linked to its capacity to trigger both intrinsic and extrinsic apoptotic cell death via endoplasmic reticular stress pathway. The potent antitumor activity of TCD was similarly demonstrated in a hepatocellular carcinoma xenograft model, where 5 and 10 mg/kg doses of TCD significantly arrested Hep-J5 and Mahlavu tumor growth. Our finding suggests that TCD is a promising therapeutic agent against hepatocellular carcinoma; further translational assessment of its clinical usage is warranted.

The use of peripheral nerve blocks for anesthesia and postoperative analgesia has increased significantly in recent years. Adjuvants are frequently added to local anesthetics to prolong analgesia following peripheral nerve blockade. Numerous randomized controlled trials and meta-analyses have examined the pros and cons of the use of various individual adjuvants.

To systematically review adjuvant-related randomized controlled trials and meta-analyses and provide clinical recommendations for the use of adjuvants in peripheral nerve blocks.

Randomized controlled trials and meta-analyses that were published between 1990 and 2014 were included in the initial bibliographic search, which was conducted using Medline/PubMed, Cochrane Central Register of Controlled Trials, and EMBASE. Only studies that were published in English and listed block analgesic duration as an outcome were included. Trials that had already been published in the identified meta-analyses and included adjuvants not in widespread use and pubhasone, magnesium, and dexmedetomidine are promising agents for use in prolongation of local anesthetic peripheral nerve blocks, and further studies of safety and efficacy are merited. However, caution is recommended with use of any perineural adjuvant, as none have Food and Drug Administration approval, and concerns for side effects and potential toxicity persist.Arsenic toxicity is a serious public health problem worldwide that brings more than 100 million people into the risk of arsenic exposure from groundwater and food contamination. Although there is accumulating evidence linking arsenic exposure with aberrant cytosine methylation in the global genome or at specific genomic loci, very few have investigated the impact of arsenic on the oxidation of 5-methylcytosine (5-mC) mediated by the Ten-eleven translocation (Tet) family of proteins. Owing to the high binding affinity of As(III) toward cysteine residues, we reasoned that the highly conserved C3H-type zinc fingers situated in Tet proteins may constitute potential targets for arsenic binding. Herein, we found that arsenite could bind directly to the zinc fingers of Tet proteins in vitro and in cells, and this interaction substantially impaired the catalytic efficiency of Tet proteins in oxidizing 5-mC to 5-hydroxymethylcytosine (5-hmC), 5-formylcytosine (5-foC), and 5-carboxylcytosine (5-caC). Treatments with arsenite also led to a dose-dependent decrease in the level of 5-hmC, but not 5-mC, in DNA isolated from HEK293T cells overexpressing the catalytic domain of any of the three Tet proteins and from mouse embryonic stem cells. Together, our study unveiled, for the first time, that arsenite could alter epigenetic signaling by targeting the zinc fingers of Tet proteins and perturbing the Tet-mediated oxidation of 5-mC in vitro and in cells. Our results offer important mechanistic understanding of arsenic epigenotoxicity and carcinogenesis in mammalian systems and may lead to novel approaches for the chemoprevention of arsenic toxicity.Corylus mandshurica, also known as pilose hazelnut, is an economically and ecologically important species in China. In this study, ten polymorphic simple sequence repeat (SSR) markers were applied to evaluate the genetic diversity and population structure of 348 C. mandshurica individuals among 12 populations in China. The SSR markers expressed a relatively high level of genetic diversity (Na = 15.3, Ne = 5.6604, I = 1.8853, Ho = 0.6668, and He = 0.7777). According to the coefficient of genetic differentiation (Fst = 0.1215), genetic variation within the populations (87.85%) were remarkably higher than among populations (12.15%). The average gene flow (Nm = 1.8080) significantly impacts the genetic structure of C. mandshurica populations. The relatively high gene flow (Nm = 1.8080) among wild C. mandshurica may be caused by wind-pollinated flowers, highly nutritious seeds and self-incompatible mating system. The UPGMA (unweighted pair group method of arithmetic averages) dendrogram was divided into two main cvelopment of conservation strategies of these valuable hazelnut resources.

Psoriasis is a chronic inflammatory skin disease and topical therapy remains a key role for treatment. The aim of this study is to evaluate the influence of psoriasis-like lesions on the cutaneous permeation of anti-psoriatic drugs.

We first set up imiquimod-induced dermatitis in mice that closely resembles human psoriasis lesions. The development of the lesions is based on the IL-23/IL17A axis for phenotypical and histological characteristics. Four drugs, 5-aminolevulinic acid (ALA), tacrolimus, calcipotriol, and retinoic acid, were used to evaluate percutaneous absorption.

The most hydrophilic molecule, ALA, revealed the greatest enhancement on skin absorption after imiquimod treatment. Imiquimod increased the skin deposition and flux of ALA by 5.6 to 14.4-fold, respectively, compared to normal skin. The follicular accumulation of ALA was also increased 3.8-fold. The extremely lipophilic drug retinoic acid showed a 1.7- and 3.8-fold increase in skin deposition and flux, respectively. Tacrolimus flux was enhanced from 2 to 21 μg/cm2/h by imiquimod intervention. However, imiquimod did not promote skin deposition of this macrolide. The lipophilicity, but not the molecular size, dominated drug permeation enhancement by psoriatic lesions. The in vivo percutaneous absorption of ALA and rhodamine B examined by confocal microscopy confirmed the deficient resistance of epidermal barrier for facilitating cutaneous delivery of drugs via psoriasis-like skin.

We established the topical delivery profiles of anti-psoriatic drugs via imiquimod-treated psoriasis-like skin.

We established the topical delivery profiles of anti-psoriatic drugs via imiquimod-treated psoriasis-like skin.Regulation of gene expression is central to many biological processes. Although reconstruction of regulatory circuits from genomic data alone is therefore desirable, this remains a major computational challenge. Comparative approaches that examine the conservation and divergence of circuits and their components across strains and species can help reconstruct circuits as well as provide insights into the evolution of gene regulatory processes and their adaptive contribution. In recent years, advances in genomic and computational tools have led to a wealth of methods for such analysis at the sequence, expression, pathway, module, and entire network level. Here, we review computational methods developed to study transcriptional regulatory networks using comparative genomics, from sequence to functional data. We highlight how these methods use evolutionary conservation and divergence to reliably detect regulatory components as well as estimate the extent and rate of divergence. Finally, we discuss the promise and open challenges in linking regulatory divergence to phenotypic divergence and adaptation.Stem cells are necessary for the maintenance of many adult tissues. Signals within the stem cell microenvironment, or niche, regulate the self-renewal and differentiation capability of these cells. Misregulation of these signals through mutation or damage can lead to overgrowth or depletion of different stem cell pools. In this review, we focus on the Drosophila testis and ovary, both of which contain well-defined niches, as well as the mouse testis, which has become a more approachable stem cell system with recent technical advances. We discuss the signals that regulate gonadal stem cells in their niches, how these signals mediate self-renewal and differentiation under homeostatic conditions, and how stress, whether from mutations or damage, can cause changes in cell fate and drive stem cell competition.Silicon (Si) particles have emerged as a promising active material for next-generation lithium-ion battery anodes. However, the large volume changes during lithiation/delithiation cycles result in fracture and pulverization of Si, leading to rapid fading of performance. Here, we report a simple, all-aqueous, directed assembly-based strategy to fabricate Si-based anodes that show capacity and capacity retention that are comparable or better than other more complex methods for forming anodes. We use a cationic surfactant, cetyltrimethylammonium bromide (CTAB), to stabilize Si nanoparticles (SiNPs) in water. This suspension is added to an aqueous suspension of para-amino benzoic acid-terminated carbon black (CB), pH 7. Charge interactions cause the well-dispersed SiNP to bind to the CB, allowing most of the SiNP to be available for lithiation and charge transfer. The CB forms a conducting network when the suspension pH is lowered. The dried SiNP/CTAB/CB anode exhibits a capacity of 1580 mAh g(-1) and efficiency of 97.3% after 50 cycles at a rate of 0.1C, and stable performance at cycling rates up to 5C. The directed spatial organization of the SiNP and CB using straightforward colloidal principles allows good contact between the well-dispersed active material and the electrically conducting network. The pore space in the CB network accommodates volume changes in the SiNPs. When CTAB is not used, the SiNPs form aggregates in the suspension, and do not contact the CB effectively. Therefore, the electrochemical performance of the SiNP/CB anode is inferior to that of the SiNP/CTAB/CB anode. This aqueous-based, room temperature, directed assembly technique is a new, but simple, low-cost scalable method to fabricate stable Si-based anodes for lithium-ion batteries with performance characteristics that match those made by other more sophisticated techniques.We study the mesoscopic effects which modify phase-segregation in LixFePO4 nanoparticles using a multiphysics phase-field model implement on a high performance cluster. We simulate 3D spherical particles of radii from 3 to 40 nm and examine the equilibrium microstructure and voltage profiles as they depend on size and overall lithiation. The model includes anisotropic, concentration-dependent elastic moduli, misfit strain, and facet dependent surface wetting within a Cahn-Hilliard formulation. We find that the miscibility gap vanishes for particles of radius ∼5 nm, and the solubility limits change with overall particle lithiation. Surface wetting stabilizes minority phases by aligning them with energetically beneficial facets. The equilibrium voltage profile is modified by these effects in magnitude, and the length and slope of the voltage plateau during two-phase coexistence.This study describes a spontaneous case of Pierre Robin sequence in a nonhuman animal species. A miniature dachshund with micrognathia developed glossoptosis, respiratory distress, dysphagia, temporomandibular ankylosis, and a misaligned upper jaw. The severity of this condition resulted in death by obstructive apnea at the age of 8 mo. Dogs with Pierre Robin sequence can provide further knowledge and a greater understanding of this abnormality, leading to better management of affected individuals and improvement of therapeutic methods.A 6 yr old castrated male English springer spaniel was evaluated with a 1 mo history of progressive right forelimb lameness with recent swelling around the elbow joint. Physical examination findings included lameness of the right forelimb, muscle atrophy around the right shoulder, grade 2/6 heart murmur, and moderate dental disease. Results of a complete blood cell count and serum biochemical analysis were unremarkable with the exception of a mildly increased alkaline phosphatase (368 U/L; reference range, 128-328 U/L). Radiographs of the right elbow revealed a mixed lytic and proliferative osseous lesion most consistent with either neoplasia or infection. Thoracic radiographs and the echocardiogram were unremarkable. Fine-needle aspiration of the bone lesion was performed. The cytological diagnosis was chondrosarcoma. The right forelimb was amputated and the axillary lymph nodes were collected. Histopathological examination of the bone lesion and axillary lymph nodes revealed chondrosarcoma with metastasis to the lymph nodes. Lymph node metastasis of chondrosarcoma is rare and needs to be further evaluated as a prognostic indicator.A 6 yr old male Yorkshire terrier was presented for an ~6 yr history of progressive cough and dyspnea. Thoracic radiographs revealed a 6 cm diameter mass within the right caudal thorax. Thoracic ultrasound identified an intrathoracic mass ultrasonographically consistent with liver tissue and a chronic diaphragmatic hernia was suspected. Exploratory laparotomy was performed, but no evidence of a diaphragmatic hernia was identified. Thoracic exploration identified abnormal lung parenchyma. The accessory lung lobe was removed using a stapling devise near its base. The consolidated mass had the gross appearance of liver and was histologically identified as ectopic hepatic tissue. Ectopic hepatic tissue, unlike ectopic splenic and pancreatic tissue, is rare and generally has a subdiaphragmatic distribution. This solitary case report demonstrates that ectopic intrathoracic hepatic tissue should be considered a differential diagnosis for a caudal mediastinal mass.A 9 yr old cat was presented with clinical signs and laboratory abnormalities attributed to arterial hypertension (mean systolic arterial pressure, 290 mm Hg). Plasma aldosterone concentration was increased at the time of admission (651 pmol/L), but serum creatinine and potassium concentrations were within the reference range. A second increased aldosterone (879 pmol/L) and normal plasma renin activity (1.85 ng/mL/hr) resulted in an increased aldosterone/renin ratio, which was suggestive of primary hyperaldosteronism (PHA). To further support the diagnosis of PHA, the urinary aldosterone/creatinine ratio was calculated both before and after oral administration of fludrocortisone acetate (0.05 mg/kg q 12 hr for 4 consecutive days). The urinary aldosterone/creatinine ratio was 92.6 × 10(-9) before fludrocortisone administration and 155.8 × 10(-9) 4 days later. Absence of suppression was typical of PHA. The cat had a limited response to antihypertensive medication and died before treatment for PHA could be instituted. A necropsy was not permitted by the owner.This manuscript describes the extended clinical abnormalities that can occur in severe snake envenomation and the clinical signs associated with antivenom hypersensitivity in a 3 yr old dog. Treatment consisted of IV fluid therapy, analgesics, a vasopressor, cardiac antiarrhythmia drugs, and polyvalent pit viper antivenom. Following initial response to treatment, relapse of clinical signs occurred. Most interesting was the recrudescence of clinical signs on day 7 that may have been caused by the release of deposited venom during surgical debridement of necrotic skin. The resulting extensive clinical signs required multiple vials of antivenom (22 vials over a 7 day period). Both F(ab')2 antivenom and antivenin (Crotalidae) polyvalent were used in this dog because of availability logistics. It is thought that this large amount of antivenom resulted in type I (anaphylaxis) and type III hypersensitivity (serum sickness) reactions. The dog made a complete clinical recovery. This description of extended, fluctuating clinical abnormalities that were associated with envenomation together with the development of hypersensitivity reactions that were presumably secondary to antivenom administration is information that can be useful for the management of patients afflicted with severe pit viper envenomation.A Silky terrier weighing 4.7 kg was presented with an airway foreign body after having aspirated a fragment of an orotracheal tube that was identified on radiological examination. Due to the small size of the patient, flexible endoscopy could not be performed through the lumen of a tracheal tube. Following IV induction of general anesthesia, the airway was instrumented with a laryngeal mask airway that was attached via a three-way connector to an anesthesia breathing circuit. A flexible endoscope was passed through the free port of the connector. That arrangement allowed for the passage of an endoscope through the lumen of the laryngeal mask airway and into the trachea without interrupting the continuous supply of O2 and sevoflurane.A 14 mo old female Jack Russell terrier presented with a 12 hr history of vomiting and inappetence. She was subsequently diagnosed with multiple acquired portosystemic shunts during an exploratory celiotomy. Gross and histopathological hepatic abnormalities were consistent with chronic disease, including features suggestive of portal hypertension that was potentially caused by migrating and resident Angiostrongylus vasorum larvae. Fecal analysis and polymerase chain reaction of hepatic tissue confirmed the presence of Angiostrongylus vasorum . The dog recovered clinically following empirical treatment and supportive care. A lack of parasite burden was confirmed 9 wk postdiagnosis; however, serum biochemical analysis at that time was suggestive of ongoing hepatic dysfunction.An 8 yr old spayed female Italian greyhound was presented with a mass in the cranial abdomen. Preliminary evaluation of the dog revealed a large, cavitary, irregularly shaped mass with no definitive association with any abdominal organs. During an exploratory celiotomy, a 16 cm × 12 cm × 6 cm mass was removed. On subsequent histopathology, extraskeletal osteosarcoma induced by a foreign body granuloma was diagnosed. The foreign body granuloma, based on histopathological findings, was suspected to be secondary to a retained surgical sponge from her routine ovariohysterectomy performed 7 yr prior to presentation. Animals with granulomas induced by foreign bodies can remain asymptomatic for years; however, those granulomas can progress to extraskeletal osteosarcomas, which carry a poor prognosis.An 11 yr old castrated male greyhound presented to the Washington State University's Veterinary Teaching Hospital (WSU VTH) for evaluation of a 4 day history of pleural effusion. The pleural effusion had a gelatinous appearance, suggestive of mucus, and was characterized cytologically as a pyogranulomatous exudate with some features suggestive of a carcinoma. Postmortem examination identified a pulmonary mass with evidence of carcinomatosis. Pulmonary papillary adenocarcinoma with carcinomatosis was the histologic diagnosis. Abundant mucin production was present, consistent with a mucinous pulmonary adenocarcinoma. To the authors' knowledge, this is the first report of a mucinous pulmonary adenocarcinoma with mucus pleural effusion in a dog.The objective of this study was to evaluate the sensitivity and specificity of an antigen enzyme immunoassay (EIA) on urine samples for the diagnosis of histoplasmosis in dogs. This retrospective medical records review included canine cases with urine samples submitted for Histoplasma EIA antigen assay between 2007 and 2011 from three veterinary institutions. Cases for which urine samples were submitted for Histoplasma antigen testing were reviewed and compared to the gold standard of finding Histoplasma organisms or an alternative diagnosis on cytology or histopathology. Sensitivity, specificity, negative predictive value, positive predictive value, and the kappa coefficient and associated confidence interval were calculated for the EIA-based Histoplasma antigen assay. Sixty cases met the inclusion criteria. Seventeen cases were considered true positives based on identification of the organism, and 41 cases were considered true negatives with an alternative definitive diagnosis. Two cases were considered false negatives, and there were no false positives. Sensitivity was 89.47% and the negative predictive value was 95.35%. Specificity and the positive predictive value were both 100%. The kappa coefficient was 0.9207 (95% confidence interval, 0.8131-1). The Histoplasma antigen EIA test demonstrated high specificity and sensitivity for the diagnosis of histoplasmosis in dogs.The objectives of this study were to determine if Doppler (DOP) blood pressure measurements more closely estimate either invasive systolic or invasive mean arterial blood pressures (ISAP or IMAP, respectively) in small dogs under general anesthesia and to assess the ability of DOP to detect anesthesia-related hypotension in small dogs. Blood pressure measurements (n = 203) were obtained from 10 client-owned dogs. DOP, ISAP, and IMAP were recorded simultaneously, and the data were categorized into two groups hypotensive (ISAP less then 90 mm Hg) and normotensive (ISAP ≥90 mm Hg and ≤160 mm Hg). DOP overestimated ISAP and IMAP in both the normotensive and hypotensive groups. The DOP was highly specific (97%) but poorly sensitive (56%) for detecting hypotension. The smallest bias was achieved when using DOP as an estimate of systolic arterial blood pressure in both normotensive and hypotensive dogs, suggesting that DOP measures systolic arterial blood pressure in dogs less then 5 kg. For dogs with hypotension, DOP met all of the performance criteria for noninvasive blood pressure monitors recommended by the American College of Veterinary Internal Medicine. DOP is an acceptably accurate and highly specific means of detecting hypotension in small dogs under general anesthesia.Hypercalcemia is uncommonly encountered in veterinary patients. When it does occur, the effects can be severe, resulting in significant morbidity and mortality if not recognized and addressed in a timely manner. Causes of hypercalcemia are varied and include pituitary-dependent and pituitary-independent causes. A diagnosis of hypercalcemia should be made based on documentation of ionized hypercalcemia. The mainstay of emergency treatment usually involves aggressive IV fluid diuresis, the use of diuretics, and, often, glucocorticoids. The use of bisphosphonates has become increasingly more common in veterinary medicine.[Purpose] To report the effects of consecutive application of stretching, Schroth, and strengthening exercises in an adult with idiopathic scoliosis. [Subject] A 26-year-old woman with idiopathic scoliosis, Cobb's angle of 20.51°, and back pain. [Methods] The exercise program consisted of 3 sessions 10 minutes of stretching exercises, 20 minutes of Schroth exercises, and 10 minutes of strengthening exercises. This program was implemented 3 times a week, for 8 weeks. [Results] The thoracic Cobb's angle decreased from 20.51° to 16.35°, and the rib hump decreased from 15° to 9°. [Conclusion] Consecutive application of stretching, Schroth, and strengthening exercises may help reduce Cobb's angle and the rib hump in adults with idiopathic scoliosis.Comparing the results of HIV trials using different endpoints and scale is a difficult task. The two main primary endpoints are the proportion of patients with HIV-1 RNA less than 50 copies/ml at week 48 and the time to virologic failure. In the A5202 study, the use of the risk difference scale instead of the risk ratio scale would have led to equivalence in the comparisons between efavirenz and atazanavir/ritonavir. We discuss these results and their impact on the design of the A5257, as well as alternative approaches.

Surveillance drug resistance mutations (SDRMs) in drug-naive patients are typically used to survey HIV-1-transmitted drug resistance (TDR). We test here how SDRMs in patients failing treatment, the original source of TDR, contribute to assessing TDR, transmissibility and transmission source of SDRMs.

This is a retrospective observational study analyzing a Portuguese cohort of HIV-1-infected patients.

The prevalence of SDRMs to protease inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs) and nonnucleoside reverse transcriptase inhibitors (NNRTIs) in drug-naive and treatment-failing patients was measured for 3554 HIV-1 subtype B patients. Transmission ratio (prevalence in drug-naive/prevalence in treatment-failing patients), average viral load and robust linear regression with outlier detection (prevalence in drug-naive versus in treatment-failing patients) were analyzed and used to interpret transmissibility.

Prevalence of SDRMs in drug-naive and treatment-failing patients were linearly cor SDRMs in drug-naive and in treatment-failing patients indicates that the prevalence in treatment-failing patients can be useful to predict levels of TDR. The slope is a cohort-dependent estimate of rate of TDR per drug class and outlier detection reveals comparative persistence of SDRMs. Outlier SDRMs with higher transmissibility are more persistent and more likely to have been acquired from drug-naive patients. Those with lower transmissibility have faster reversion dynamics after transmission and are associated with acquisition from treatment-failing patients.

To estimate the impact and cost-effectiveness of treatment as prevention (TasP), pre-exposure prophylaxis (PrEP) and condom promotion for serodiscordant couples in Nigeria.

Mathematical and cost modelling.

A deterministic model of HIV-1 transmission within a cohort of serodiscordant couples and to/from external partners was parameterized using data from Nigeria and other African settings. The impact and cost-effectiveness were estimated for condom promotion, PrEP and/or TasP, compared with a baseline where antiretroviral therapy (ART) was offered according to 2010 national guidelines (CD4 <350 cells/μl) to all HIV-positive partners. The impact was additionally compared with a baseline of current ART coverage (35% of those with CD4 <350 cells/μl). Full costs (in US $2012) of programme introduction and implementation were estimated from a provider perspective.

Substantial benefits came from scaling up ART to all HIV-positive partners according to 2010 national guidelines, with additional smaller bositive partners. Subsequent incremental benefits are greatest with condom promotion and TasP, followed by PrEP.

As antiretroviral therapy (ART) expands for HIV-infected children, it is important to determine its impact on growth. We quantified growth and its determinants following ART in resource-limited (RLS) and developed settings.

Systematic review and meta-analysis.

We searched publications reporting growth [weight-for-age (WAZ), height-for-age (HAZ), and weight-for-height (WHZ) z scores] in HIV-infected children following ART through August 2014. Inclusion criteria were as follows younger than 18 years; ART; at least 20 patients; growth at ART; and post-ART growth. Standardized and overall weighted mean differences were calculated using random-effects models.

A total of 67 articles were eligible (RLS = 54; developed settings = 13). Mean age was 5.8 years, and comparable between settings (P = 0.90). Baseline growth was substantially lower in RLS vs. developed settings (WAZ -2.1 vs. -0.5; HAZ -2.2 vs. -0.9; both P < 0.01). Rate of weight but not height reconstitution during 12 and 24 months was higher in ounterparts at ART; growth shortfalls in RLS persisted despite reconstitution. Earlier age and nutritional supplementation at ART may improve growth outcomes. Scant data on supplementation limit evaluation of impact and underscores need for systematic data collection regarding supplementation in pediatric ART programmes/cohorts.

The main aim of this study was to determine whether HIV replication can be controlled following interruption of treatment started early in the course of infection (CD4 >350 cells/μl and viral load <50 000 copies/ml), but not during the primary infection.

Patients enrolled in a multicenter trial of treatment interruption (ANRS 116 SALTO) with CD4 above 450 cells/μl and viral load below 400 copies/ml at treatment interruption were selected for this second analysis. We determined the proportion of patients whose plasma HIV-RNA load remained below 400 copies/ml during the first 12 months of treatment interruption, and baseline factors predictive of time to loss of viral control. Viral load rebound was defined as two successive values above 400 copies/ml, or as one value above 400 copies/ml, followed by treatment resumption.

We studied 95 patients with a median CD4 nadir of 382 cells/μl (340-492). At treatment interruption, the median CD4 cell count and HIV-DNA load were 813/μl (695-988) and 206 copies/10 peripheral blood mononuclear cells (PBMCs) (53-556). Twelve months after treatment interruption, seven patients still had viral load below 400 copies/ml (Kaplan-Meier estimate 7.5%, 95% confidence interval 3.7-14.6), and four of them still had viral load below 400 copies/ml at 36 months. A multivariable Cox proportional-hazards model showed that time to loss of viral control was more shorter in patients with HIV-DNA at least 150 copies/10 PBMCs at treatment interruption (hazard ratio 2.1, 95% confidence interval 1.3-3.3, P = 0.002) than in those with HIV-DNA below 150 copies/10 PBMCs.

Patients who have low HIV-DNA levels at antiretroviral treatment interruption are more likely to maintain viral control for long periods.

Patients who have low HIV-DNA levels at antiretroviral treatment interruption are more likely to maintain viral control for long periods.

Understanding tumor microenvironment and its impact on prognosis of HIV-related lymphomas may provide insight into novel therapeutic strategies.

We characterized the relationship between infiltrating immune cells with tumor characteristics, HIV disease history and survival in 80 patients with HIV-related diffuse large B-cell lymphoma (DLBCL) diagnosed in the era of combined antiretroviral therapy (1996-2007) at Kaiser Permanente California. Eighty patients with HIV-unrelated DLBCL were included for comparison.

Data on patients' clinical history were obtained from Kaiser Permanente's electronic health records. The density of stromal CD4, CD8 and FOXP3 T cells and CD68 macrophages, as well as tumor molecular characteristics were examined using immunohistochemistry. The associations between stromal immune infiltration and patient's clinical history or tumor characteristics were examined using Kruskal-Wallis tests or Pearson's correlation coefficient. The effect of stromal immune infiltration on 2-year mortality was evaluated in multivariable logistic regression.

Compared with HIV-unrelated DLBCL, patients with HIV-related DLBCL had significantly reduced stromal CD4 and FOXP3 T cells, but increased density of macrophages. Increased density of stromal macrophages was correlated with lower circulating CD4 cell count at DLBCL diagnosis. Tumor molecular characteristics, including BCL6, p53 and cMYC expression, but not Epstein-Barr virus infection status, were significantly correlated with stromal immune infiltration, particularly FOXP3 T cells. A higher density of infiltrating CD8 T cell was significantly associated with reduced mortality in patients with HIV-related DLBCL (odds ratio = 0.30 [0.09-0.97] for ≥25 vs. <10%).

These data provide evidence for the prognostic significance of cytotoxic T cells in determining outcomes of HIV-related lymphoma.

These data provide evidence for the prognostic significance of cytotoxic T cells in determining outcomes of HIV-related lymphoma.

Antiretroviral-naive HIV-positive individuals contribute to the transmission of drug-resistant viruses, compromising first-line therapy. Using phylogenetic inference, we quantified the proportion of transmitted drug-resistance originating from a treatment-naive source.

Using a novel phylotype-based approach, 24 550 HIV-1 subtype B partial pol gene sequences from the UK HIV Drug Resistance database were analysed. Ongoing transmission of drug resistance amongst HIV-positive individuals was identified as phylotypes of at least three sequences with at least one shared drug resistance mutation, a maximum intra-clade genetic distance of 4.0% and a basal branch support at least 90%. The time of persistence of the transmission chains was estimated using a fast least-squares molecular clock inference approach.

Around 70% of transmitted drug-resistance had a treatment-naive source. The most commonly transmitted mutations were L90M in the protease gene and K103N, T215D and T215S in reverse transcriptase. Reversionstance data are available.Engineering cells with active-ingredient-loaded micro/nanoparticles is becoming increasingly popular for imaging and therapeutic applications. A critical yet inadequately addressed issue during its implementation concerns the significant number of particles that remain unbound following the engineering process, which inadvertently generate signals and impart transformative effects onto neighboring nontarget cells. Here we demonstrate that those unbound micro/nanoparticles remaining in solution can be efficiently separated from the particle-labeled cells by implementing a fast, continuous, and high-throughput Dean flow fractionation (DFF) microfluidic device. As proof-of-concept, we applied the DFF microfluidic device for buffer exchange to sort labeled suspension cells (THP-1) from unbound fluorescent dye and dye-loaded micro/nanoparticles. Compared to conventional centrifugation, the depletion efficiency of free dyes or particles was improved 20-fold and the mislabeling of nontarget bystander cells by free particles was minimized. The microfluidic device was adapted to further accommodate heterogeneous-sized mesenchymal stem cells (MSCs). Complete removal of unbound nanoparticles using DFF led to the usage of engineered MSCs without exerting off-target transformative effects on the functional properties of neighboring endothelial cells. Apart from its effectiveness in removing free particles, this strategy is also efficient and scalable. It could continuously process cell solutions with concentrations up to 10(7) cells·mL(-1) (cell densities commonly encountered during cell therapy) without observable loss of performance. Successful implementation of this technology is expected to pave the way for interference-free clinical application of micro/nanoparticle engineered cells.Lipid droplets (LDs), reservoirs of cholesterols and fats, are organelles that hydrolyse lipids in the cell. In zebrafish embryos, the actomyosin complex and filamentous microtubules control the periodic regulation of the LD geometry. Contrary to the existing hypothesis that LD transport involves the kinesin-microtubule system, we find that their recruitment to the blastodisc depends on the actomyosin turnover and is independent of the microtubules. For the first time we report the existence of two distinct states of LDs, an inactive and an active state, that occur periodically, coupled weakly to the cleavage cycles. LDs are bigger, more circular and more stable in the inactive state in which the geometry of the LDs is maintained by actomyosin as well as microtubules. The active state has smaller and irregularly shaped LDs that show shape fluctuations that are linked to actin depolymerization. Because most functions of LDs employ surface interactions, our findings on the LD geometry and its regulation bring new insights to the mechanisms associated with specific functions of LDs, such as their storage capacity for fats or proteins, lipolysis etc.The luteinizing hormone beta subunit (LH-beta) gene plays a critical role in reproduction. In order to characterize and analyze the promoter region of LH-beta in sheep, a genomic library was constructed in phage lambda gt 10 and screened. A novel region of 1,224 bp upstream from the targeted LH-beta gene was identified. Blasting this sequence showed a perfect homology for the first 721 bp sequence with an upstream ovine LH-beta sequence in the database. However, the remaining 5'-503 bp showed no sequence matching. DNA from Moroccan breeds was isolated and the whole region was amplified and confirmed by sequencing. To further confirm the promoter activity of this region, an in vitro analysis using a luciferase assay was carried out. An increase in the promoter activity of the whole region was demonstrated compared to the empty vector. More interestingly, the unpublished region significantly enhanced the promoter activity compared to the known region alone. To predict putative transcription factor binding-sites (TFBSs), an in silico analysis was performed using the TFSEARCH program. The region features many TFBSs and contains two palindrome sequences of 17- and 18-bp. Taken together, a novel region was identified and confirmed in sheep which contained a promoter activity rich with binding sites for a putative regulatory element as shown in silico.Genome-wide association studies have identified and repeatedly confirmed the association of rs3197999 in MST1 with inflammatory bowel disease (IBD). However, the underlying pathophysiology remains unclear. rs3197999 is a non-synonymous single-nucleotide polymorphism which modifies the function of macrophage stimulating protein-1 (MST1). We show by haplotyping that rs3197999 is in linkage disequilibrium with rs1050450 in GPX1, with almost complete cosegregation of the minor alleles. As shown by immunoassay, rs3197999 influences the MST-1 level in serum. But also rs1050450 causes an amino acid exchange in glutathione peroxidase 1 (GPx-1) and reduced activity of this antioxidant enzyme. The association of GPx deficiency and IBD in mice was already shown. We propose that GPx-1 is a better candidate than MST1 for the pathophysiologic link between IBD locus 12 and IBD.Disorders in regulatory T-cell (T(reg)) function can result in the breakdown of immunological self-tolerance. Thus, the identification of mechanisms controlling the activity of T(reg) is of great relevance. We used T(reg) from individuals carrying the C77G polymorphism as models to study the role of CD45 molecules in humans. C77G prevents splicing of CD45 exon A thereby leading to an aberrant expression pattern of CD45 isoforms in affected individuals. Resting and in vitro expanded/activated CD4(+)CD25(high)Foxp3(+) T(reg) from carriers of C77G strongly expressed CD45RA isoforms whereas these isoforms were almost absent in cells from individuals with wild-type CD45. C77G T(reg) showed diminished upregulation of activation markers, lower phosphorylation of p56(lck)(Y505) and a reduced proliferative potential when stimulated with anti-TcR or anti-TcR plus CD28 mAb suggesting decreased responsiveness to activating stimuli. In addition, the capacity to suppress proliferation of conventional CD4(+) T cells was impaired in C77G T(reg). Furthermore, microarray studies revealed distinct gene expression patterns in T(reg) from C77G carriers. These data suggest that the changes in CD45 isoform combination resulting from the C77G mutation alter the responsiveness of T(reg) to TcR-mediated signaling. Targeting CD45 isoform expression might be a useful approach to modulate T(reg) function.There is a need to develop new and innovative polymer carriers to be used as drug delivery systems and/or imaging agents owing to the fact that there is no universal polymeric system that can be used in the treatment of all diseases. Additionally, limitations with existing systems, such as a lack of biodegradability and biocompatibility, inevitably lead to side effects and poor patient compliance. New polymer therapeutics based on amino acids are excellent candidates for drug delivery, as they do not suffer from these limitations. This article reports on a simple yet powerful methodology for the synthesis of 3-arm star-shaped polyglutamic acid with well-defined structures, precise molecular weights (MW), and low polydispersity (Đ = less then 1.3). These were synthesized by ring-opening polymerization (ROP) of N-carboxyanhydrides (NCA) in a divergent method from novel multifunctional initiators. Herein, their exhaustive physicochemical characterization is presented. Furthermore, preliminary in vitro evaluation in selected cell models, and exhaustive in vivo biodistribution and pharmacokinetics, highlighted the advantages of these branched systems when compared with their linear counterparts in terms of cell uptake enhancement and prolonged plasma half-life.