Prevalence of select infectious agents in inflammatory aural and nasopharyngeal polyps from client-owned cats.
Benign, inflammatory polyps may affect the nasopharynx and auditory canal of cats. It has been proposed that inflammation induced by infectious disease agents could trigger polyp formation. The objective of this pilot study was to determine the prevalence of feline herpesvirus-1 (FHV-1), feline calicivirus (FCV), Mycoplasma species, Bartonella species and Chlamydophila felis nucleic acids in polyp tissues collected from 30 clinically affected cats. Samples collected from the tympanic bulla from 12 clinically normal cats were also assayed. DNA or RNA of some of the target agents were amplified from samples from 25% of normal cats and 33% of affected cats; however, statistical associations were not detected for individual agent results or grouped results. The study documents that common oropharyngeal or blood borne agents can be detected in the tympanic bullae of normal cats. Failure to consistently amplify RNA or DNA of the select agents from polyp tissues suggests the agents studied were not directly associated with the pathogenesis of this syndrome in the cats tested. Alternately, the inflammatory response may have cleared microbial nucleic acids to undetectable levels by the time of sample collection.


Resident surgical experience with lens and corneal refractive surgery: survey of the ASCRS Young Physicians and Residents Membership.
A 43-question survey was e-mailed to all resident members of the American Society of Cataract and Refractive Surgery (ASCRS), ASCRS members in practice for 5 or fewer years, and residency program directors of 118 U.S. Accreditation Council for Graduate Medical Education-accredited ophthalmology programs (for distribution to their residents) in June 2010. Two hundred eighty-five of 2279 surveys sent were completed and returned, for a response rate of 12.5%. Most respondents (88.7%) had served as primary surgeon in more than 100 cataract surgeries. Fifty-two percent of respondents had not performed corneal relaxing incisions; 60% had no experience implanting a toric IOL. Twenty-two percent had experience implanting a presbyopia-correcting IOL. Over 75% had not performed any corneal refractive surgical procedures. Although basic cataract case numbers appear adequate, there are significant perceived deficiencies in current resident training models for surgical astigmatism management, implanting presbyopia-correcting IOLs, and corneal refractive surgery. No author has a financial or proprietary interest in any material or method mentioned.


The International Congress on Toxoplasmosis.
Toxoplasma gondii is an important pathogen in both veterinary and human medicine. Infection during pregnancy can result in fetal transmission and a congenital infection syndrome. In immune-compromised hosts reactivation of latent infection can result in encephalitis. It has been estimated that as many as one-third of the human population harbours this zoonosis. The Seventh International Congress on Toxoplasmosis, organised by Louis M. Weiss and Kami Kim (Albert Einstein College of Medicine, Bronx, NY) was held on 23-27 May 2003 in Tarrytown, New York. At this meeting 133 investigators from 14 countries presented 102 papers on research involving this model Apicomplexan parasite. The presented research covered the epidemiology, immunology, cellular biology and molecular biology of this pathogen.


Advances in cancer therapy through the use of carbon nanotube-mediated targeted hyperthermia.
Carbon nanotubes (CNTs) are emerging versatile tools in nanomedicine applications, particularly in the field of cancer targeting. Due to diverse surface chemistry and unique thermal properties, CNTs can act as strong optical absorbers in near infrared light where biological systems prove to be highly transparent. The process of laser-mediated ablation of cancer cells marked with biofunctionalized CNTs is frequently termed "nanophotothermolysis." This paper illustrates the potential of engineered CNTs as laser-activated photothermal agents for the selective nanophotothermolysis of cancer cells.


Dissociable visual and spatial impairments following right posterior cerebral lesions: clinical, neuropsychological and anatomical evidence.
A double dissociation of visual and spatial performance is reported in two men with chronic focal missile injuries of the right cerebral hemisphere. The clinical, neuropsychological and post-mortem anatomical data are considered in relation to evidence from physiological research of two major cortico-cortical pathways for object-recognition and spatial perception.


[Central anticholinergic syndrome and apnea after general anaesthesia. A rare manifestation of the central anticholinergic syndrome].
The central anticholinergic syndrome (CAS) is a rarely observed condition after general anaesthesia. There are no definitive criteria to set the diagnosis of CAS. The syndrome may manifest in clinical neurological signs, such as hyperactive states or a depressed CNS state. The diagnosis usually depends on a process of exclusion of other conditions and is confirmed after rapid recovery following administration of physostigmine. We report on a 34-year-old patient who suddenly lost consciousness and developed respiratory arrest 1 h after general anesthesia and normal postoperative recovery. CAS was considered, although apnea has not been reported as a clinical symptom of this disease up to now and no peripheral signs of CAS were observed. After the administration of 1 mg physostigmine the symptoms resolved immediately and the patient started sufficient spontaneous breathing. However, corresponding to the plasma elimination half-life of the drug, further comatose episodes with apnea occurred. Therefore, the patient was admitted to the ICU and an infusion of physostigmin at a rate of up to 5 mg/h was started. Due to this therapy the patient's state became stable and 15 h after the first manifestation of CAS the infusion of physostigmin was discontinued. The following postoperative course was uneventful. In case of reduced vigilance with apnea after general anaesthesia, central anticholinergic syndrome should be considered. For diagnostic and therapeutic purposes the administration of physostigmine should be attempted.


Relationship between hip abductor rate of force development and mediolateral stability in older adults.
To examine the relationship between hip abductor rate of force development (RFD) and performance of reactive and voluntary balance tasks in older adults. Descriptive study using correlation and regression analyses. University research laboratory. A volunteer sample of 30 community-dwelling men and women over the age of 65 years. Not applicable. Measures of hip abductor RFD, center of pressure (COP) displacement during compensatory stepping, and scores on 1-leg standing (OLS), and tandem gait tests. Hip abductor RFD was defined as the time required to go from 10% of maximum force to 60% of maximum force (10%-60% RFD) or to 90% of maximum force (10%-90% RFD). Hip abductor RFD did not correlate with COP displacement during compensatory stepping, but did correlate significantly with OLS and tandem gait variables (P<.05). In predicting OLS scores, age (beta=-.485, P<.05) and 10% to 60% RFD (beta=-.354, P<.05) were significant predictors. In predicting tandem gait scores, 10% to 90% RFD (beta=.384, P<.05) was the only significant predictor in the final regression model. Hip abductor RFD, tested under voluntary conditions, correlated with performance of clinical tests that challenge lateral stability. Our results support the idea that voluntary and reactive balance tasks involve different types of neuromuscular control.


Incidence of venous thromboembolic events not related to vascular catheters in a prospective cohort of critically ill children.
The risk for venous thromboembolism (VTE) is considered to be low in the general paediatric intensive care unit (PICU) population, and pharmacological thromboprophylaxis is not routinely used. PICU patients considered at high-risk of VTE could possibly benefit from pharmacological thromboprophylaxis, but the incidence of VTE in this group of patients is unclear. This was an observational, prospective study at a tertiary multi-disciplinary paediatric hospital. We used comprehensive ultrasonography screening for VTE in critically ill children with multiple risk factors for VTE. Patients admitted to PICU ≥ 72 h and with ≥ two risk factors for VTE were included. Patients receiving pharmacological thromboprophylaxis during their entire PICU stay were excluded. The primary outcome of the study was VTEs not related to the use of a CVC. Ultrasonography screening of the great veins was performed at PICU discharge. Seventy patients with median (interquartile range) 3 (2-4) risk factors for VTE were evaluated. Median age was 0.3 years (0.03-4.3) and median PICU length of stay 9 days (5-17). Regarding the primary outcome, no symptomatic VTEs occurred and no asymptomatic VTEs were found on ultrasonography screening, resulting in an incidence of VTEs not related to a vascular catheter of 0% (95% CI: 0-5.1%). Our results indicate that VTEs not related to a vascular catheter are a rare event even in a selected group of severely ill small children considered to be at high risk of VTE. • Children in the PICU often have several risk factors for venous thromboembolism (VTE). • The incidence of VTE in PICU patients is highly uncertain, and there are no evidence-based guidelines regarding VTE prophylaxis. • This study found an incidence of VTEs not related to a vascular catheter of 0% (95% CI: 0-5.1%). • This indicates that such VTE events are rare even in PICU patients with multiple risk factors for VTE.


Follow-up study of isolated calf muscular vein thrombosis for anticoagulant therapy after primary hip and knee arthroplasty.
Although isolated calf muscular vein thrombosis (ICMVT) is commonly seen after hip and knee arthroplasty, no treatment guidelines for ICMVT after joint replacement are available. The purpose of this study was to evaluate the outcomes of patients with ICMVT for anticoagulant therapy at different time points after primary hip and knee arthroplasty. Patients with ICMVT after primary hip and knee arthroplasty were included in the study. Diagnosis was established with Doppler ultrasound. Patients were followed up clinically and with Doppler ultrasound at 1, 2, and 3 months. The outcomes were efficacy (complete resolution) and acceptability (hemorrhagic events). Anticoagulant therapy at curative dosage was prescribed for 1 month and was extended for 2 additional months in case of incomplete resolution at 1 month or if propagation was present. The chi-square test was used to compare the outcomes at different time points. 302 patients were taken hip and knee arthroplasty from January 2021 to May 2022, in which 51 patients presented with 51 ICMVTs postoperatively. The incidence of ICMVT was about 16.89%. Resolution of ICMVT was considered complete at 1, 2, and 3 months at 36.73%, 61.22%, and 91.84%, respectively, with significant differences among the time points (P < 0.05). All patients with ICMVT receiving anticoagulant therapy remained free of propagations and hemorrhagic events within 3 months. Our findings provide new insights into the anticoagulant therapy for ICMVT after primary hip and knee arthroplasty, taking oral Rivaroxaban for 3 months is effective and safe, which contributes to provide the reference for clinical practice.


Solid lipid based nanocarriers: an overview.
In the era of nanoparticulate controlled and site specific drug delivery systems, use of solid lipids to produce first generation lipid nanoparticles, solid lipid nanoparticles (SLN), became a revolutionary approach in the early nineties. The present review is designed to provide an insight into how SLN are finding a niche as promising nanovectors and forms a sound basis to troubleshoot the existing problems associated with traditional systems. Herein, authors had tried to highlight the frontline aspects prominent to SLN. An updated list of lipids, advanced forms of SLN, methods of preparation, characterization parameters, and various routes of administration of SLN are explored in-depth. Stability, toxicity, stealthing, targeting efficiency and other prospectives of SLN are also discussed in detail. The present discussion embodies the potential of SLN, now being looked up by various research groups around the world for their utility in the core areas of pharmaceutical sciences, thereby urging pharmaceutical industries to foster their scale-up.


Enhancing the thermostability of carboxypeptidase A by a multiple computer-aided rational design based on amino acids preferences at β-turns.
Carboxypeptidase A (CPA) with efficient hydrolysis ability has shown vital potential in food and biological fields. In addition, it is also the earliest discovered enzyme with Ochratoxin A (OTA) degradation activity. Thermostability plays an imperative role to catalyze the reactions at high temperatures in industry, but the poor thermostability of CPA restricts its industrial application. In order to improve the thermostability of CPA, flexible loops were predicted through molecular dynamics (MD) simulation. Based on the amino acid preferences at β-turns, three ΔΔG-based computational programs (Rosetta, FoldX and PoPMuSiC) were employed to screen three variants from plentiful candidates and MD simulations were then used to verify two potential variants with enhanced thermostability (R124K and S134P). Results showed that compared to the wild-type CPA, the variants S134P and R124K exhibited rise of 4.2 min and 7.4 min in half-life (t1/2) at 45 °C, 3 °C and 4.1 °C in the half inactivation temperature (T5010), in addition to increase by 1.9 °C and 1.2 °C in the melting temperature (Tm), respectively. The mechanism responsible for the enhanced thermostability was elucidated through the comprehensive analysis of molecular structure. This study shows that the thermostability of CPA can be improved by the multiple computer-aided rational design based on amino acid preferences at β-turns, broadening its industrial applicability of OTA degradation and providing a valuable strategy for the protein engineering of mycotoxin degrading enzymes.


Feasibility of self-gated isotropic radial late-phase MR imaging of the liver.
To evaluate feasibility of a 3D-isotropic self-gated radial volumetric interpolated breath-hold examination (VIBE) for late-phase MRI of the liver. 70 patients were included and underwent liver MRI at 1.5 T. Depending on the diagnosis, either Gd-EOB-DTPA (35 patients) or gadobutrol (35 patients) were administered. During late (gadobutrol) or hepatocyte-specific phase (Gd-EOB-DTPA), a radial prototype sequence was acquired and reconstructed using (1) self-gating with 40 % acceptance (rVIBE40); (2) with 100 % acceptance of the data (rVIBE100) and compared to Cartesian VIBE (cVIBE). Images were assessed qualitatively (image quality, lesion conspicuity, artefacts; 5-point Likert-scale: 5 = excellent; two independent readers) and quantitatively (coefficient-of-variation (CV); contrast-ratio) in axial and coronal reformations. In eight cases only rVIBE provided diagnostic image quality. Image quality of rVIBE40 was rated significantly superior (p < 0.05) in Gd-EOB-DTPA-enhanced and coronal reformatted examinations as compared to cVIBE. Lesion conspicuity was significantly improved (p < 0.05) in coronal reformatted Gd-EOB-DTPA-enhanced rVIBE40 in comparison to cVIBE. CV was higher in rVIBE40 as compared to rVIBE100/cVIBE (p < 0.01). Gadobutrol-enhanced rVIBE40 and cVIBE showed higher contrast-ratios than rVIBE100 (p < 0.001), whereas no differences were found in Gd-EOB-DTPA-enhanced examinations. Self-gated 3D-isotropic rVIBE provides significantly superior image quality compared to cVIBE, especially in multiplanar reformatted and Gd-EOB-DTPA-enhanced examinations. • Radial VIBE acquisition reduces motion artefacts. • Gd-EOB-DTPA-enhanced scans provide improved image quality. • Non-diagnostic liver MRI examinations may be reduced by radial k-spaces sampling.


Age-related macular degeneration: epidemiology and optimal treatment.
Age-related macular degeneration (AMD) is a common macular disease affecting elderly people in the Western world. It is characterised by the appearance of drusen in the macula, accompanied by choroidal neovascularisation (CNV) or geographic atrophy. The disease is more common in Caucasian individuals than in pigmented races. In predominantly Caucasian populations, the age-standardised prevalence of AMD in at least one eye is 7760 cases per million. The age-standardised cumulated 1-year incidence of AMD in at least one eye is 1051 cases per million individuals. AMD is the most important single cause of blindness among Caucasian individuals in developed countries. Blindness resulting from AMD rarely occurs before age 70, and most cases occur after age 80. The age-standardised 1-year incidence of legal blindness resulting from AMD is 212 cases per million. Two-thirds of AMD cases have CNV (exudative cases); the remainder has only geographic atrophy. In cross-sectional population-based studies about 45% of eyes with AMD have visual acuity reduced to 20/200 or worse. This is true both for exudative AMD and pure geographic atrophy. Age and genetic predisposition are known risk factors for AMD. Smoking is probably also a risk factor. Preventive strategies using macular laser photocoagulation are under investigation, but their efficacy in preventing visual loss is as yet unproven. There is no treatment with proven efficacy for geographic atrophy. Optimal treatment for exudative AMD requires a fluorescein angiographic study and a physician capable of interpreting it. For CNV not involving the foveal centre, the only evidence-based treatment is laser photocoagulation. For AMD cases with subfoveal CNV, good visual acuity, and predominantly classic fluorescence pattern on fluorescein angiography, photodynamic therapy with verteporfin is the treatment of choice. Photodynamic therapy is also effective in eyes with pure occult CNV and evidence of recent disease progression. For new subfoveal CNV with poor vision and recurrent CNV, laser photocoagulation can be considered.


Built to last: Theta and delta changes in resting-state EEG activity after regulating emotions.
Over the past years, electroencephalography (EEG) studies focused on task-related activity to characterize cortical responses associated with emotion regulation (ER), without exploring the possibility that regulating emotions can leave a trace in the brain by affecting its oscillatory activity. Demonstrating whether the effect of regulation alters the brain activity after the session and whether this reflects an increased cognitive regulatory ability has great relevance. To address this issue, 5 min of electrical brain activity at rest were recorded before and after (1) one session in which participants perceived and regulated (through distancing) their emotions (regulation session, ReS), and (2) another session in which they only perceived emotions (attend session, AtS). One hundred and sixty visual stimuli were presented, and subjective ratings of valence and arousal of stimuli were recorded. Behavioral results showed the efficacy of the regulation strategy in modulating both arousal and valence. A cluster-based permutation test on EEG data at rest revealed a significant increase in theta and delta activity after the ReS compared to the AtS, suggesting that regulating emotions can alter brain activity after the session. These results allowed us to outline a comprehensive view of the neurophysiological mechanisms associated with ER, as well as some possible implications in psychotherapy.


Key challenges to voluntary medical male circumcision uptake in traditionally circumcising settings of Machinga district in Malawi.
Voluntary medical male circumcision (VMMC) is becoming more popular as an important HIV prevention strategy. Malawi, with a high HIV and AIDS prevalence rate of 8.8% and a low male circumcision prevalence rate of 28% in 2016, is one of the priority countries recommended for VMMC scale-up. This paper investigates the attitudes and key challenges to VMMC adoption in a traditionally circumcising community in Malawi where male circumcision is culturally significant. A mixed design study using quantitative and qualitative data collection methods was carried out to determine the attitudes of 262 randomly selected males towards VMMC in a culturally circumcising community in Malawi. Statistical Package for the Social Sciences (SPSS) version 20 was used to analyse the quantitative data. To identify predictors of VMMC uptake, we used logistic regression analysis. To identify the themes, qualitative data were analysed using content analysis. The findings indicate that, while more males in this community prefer medical circumcision, traditional circumcision is still practised. Panic (63%) perceived surgical complications (31%), and cost (27%) in accessing VMMC services were some of the barriers to VMMC uptake. Age and culture were found to be statistically significant predictors of voluntary medical male circumcision in the logistic analysis. According to qualitative data analysis, the key challenges to VMMC uptake were the involvement of female health workers in the circumcision team and the incentives provided to traditional circumcisers. According to the findings of this study, VMMC services should be provided in a culturally competent manner that respects and considers existing cultural beliefs and practices in the community. Coordination between local leaders and health workers should be encouraged so that VMMC services are provided in traditional settings, allowing for safe outcomes, and increasing VMMC uptake.


Acidity of vapor plume from cooling tower mixed with flue gases emitted from coal-fired power plant.
Acidity of products resulting from the reaction of flue gas components emitted from a coal-fired power plant with water contained in a vapor plume from a wet cooling tower was analyzed in a close vicinity of a power plant (710 m from the stack and 315 m from the cooling tower). Samples of this mixture were collected using a precipitation funnel where components of the mixed plumes were discharged from the atmosphere with the rainfall. To identify situations when the precipitation occurred at the same time as the wind directed the mixed vapor and flue gas plumes above the precipitation funnel, an ultrasound anemometer designed for 3D measurements of the wind field located near the funnel was used. Precipitation samples of extremely high acidity were identified - about 5% of samples collected during 12 months showed the acidity below pH=3 and the lowest recorded pH was 1.4. During the measurement period the value of pH characterizing the background acidity of the precipitation was about 6. The main outcome of this study was to demonstrate a very high, and so far completely underestimated, potential of occurrence of episodes of extremely acid depositions in the immediate vicinity of a coal-fired power plant.


TaxKB: a knowledge base for new taxane-related drug discovery.
Taxanes are naturally occurring compounds which belong to a powerful group of chemotherapeutic drugs with anticancer properties. Their current use, clinical efficacy, and unique mechanism of action indicate their potentiality for cancer drug discovery and development thereby promising to reduce the high economy associated with cancer worldwide. Extensive research has been carried out on taxanes with the aim to combat issues of drug resistance, side effects, limited natural supply, and also to increase the therapeutic index of these molecules. These efforts have led to the isolation of many naturally occurring compounds belonging to this family (more than 350 different kinds), and the synthesis of semisynthetic analogs of the naturally existing molecules (>500), and has also led to the characterization of many (>1000) of them. A web-based database system on clinically exploitable taxanes, providing a link between the structure and the pharmacological property of these molecules could help to reduce the druggability gap for these molecules. Taxane knowledge base (TaxKB, http://bioinfo.au-kbc.org.in/taxane/Taxkb/), is an online multi-tier relational database that currently holds data on 42 parameters of 250 natural and 503 semisynthetic analogs of taxanes. This database provides researchers with much-needed information necessary for drug development. TaxKB enables the user to search data on the structure, drug-likeness, and physicochemical properties of both natural and synthetic taxanes with a "General Search" option in addition to a "Parameter Specific Search." It displays 2D structure and allows the user to download the 3D structure (a PDB file) of taxanes that can be viewed with any molecular visualization tool. The ultimate aim of TaxKB is to provide information on Absorption, Distribution, Metabolism, and Excretion/Toxicity (ADME/T) as well as data on bioavailability and target interaction properties of candidate anticancer taxanes, ahead of expensive clinical trials. This first web-based single-information portal will play a central role and help researchers to move forward in taxane-based cancer drug research.


Miniature endplate potential frequency and amplitude determined by an extension of Campbell's theorem.
A method based upon an extension of Campbell's theorem is used to measure the amplitude, waveform, and frequency of occurrence of miniature endplate potentials (mepps) at rapidly secreting neuromuscular junctions of frog cutaneous pectoris muscles. Measurements of the variance, skew, and power spectrum of the fluctuations in membrane potential are used to deduce the mepp parameters. These estimates of mepp amplitude and frequency are insensitive to slow drifts in membrane potential that preclude the conventional application of Campbell's theorem, which uses the mean and variance. The new method becomes unreliable at high mepp frequencies because the distribution of the values of membrane potential approaches a Gaussian thereby reducing the accuracy of skew measurements. Frequencies approaching 10(4) s-1 can be measured, however, if the data are high-pass filtered. The method has been tested with computer simulated data and applied to junctions exposed to La3+; the effects of Ca2+ on the La3+-induced secretion have been explored. Some muscles were fixed after treatment with La3+, and changes in nerve terminal ultrastructure were assessed by morphometric analysis of electron micrographs. Horseradish peroxidase was used to obtain information about vesicle recycling.


Lipid lymphocyte chemoattractants in psoriasis.
In view of the evidence that lymphocyte infiltrates are a constant feature of the skin lesions of psoriasis and the demonstration that certain hydroxylated metabolites of arachidonic acid are present in lesional psoriatic skin and possess lymphocyte chemoattractant properties, lipid extracts of samples from lesional and normal skin were assayed to determine which are the predominant lipid lymphocyte chemoattractants in psoriasis. Dilution-related lymphocyte chemoattractant activity was found in lipid extracts of stratum corneum samples from psoriatic lesions, but not in similar extracts of stratum corneum from the heels of normal volunteers, whereas aqueous extracts of the samples from both sources contained equivalent amounts of this activity. Subsequent purification of lesional stratum corneum lipid extracts by straight and reversed phase high performance liquid chromatography (HPLC) revealed the presence of at least two different lipid chemoattractants, one major component being identified as 12-(R)-hydroxy-5,8,10,14-eicosatetraenoic acid (12[R]-HETE) by its biological and chromatographic properties. These compounds may play a role in the pathogenesis of the lymphocyte infiltrates in psoriatic lesions.


Lymphopenia during treatment with dimethyl fumarate in patients with multiple sclerosis: Prevalence, predicting factors and clinical outcomes.
Lymphopenia is a common side effect of treatment with dimethyl fumarate (DMF) in patients with multiple sclerosis (PwMS). Prevalence and predictive factors of this side effect are still uncertain, because literature has provided discrepant results and it is still a matter of debate if lymphopenia is associated with a better treatment outcome. We retrospectively recruited PwMS treated for at least one month with DMF and collected clinical, demographic data and absolute lymphocyte count (ALC) during follow-up. Lymphopenia was graded according to CTCAE. Patients according to the grade in lymphopenia (all grades) and severe lymphopenia (grade II-IV). To evaluate predictors of lymphopenia, we compared characteristics of patients with/without lymphopenia and patients with/without severe lymphopenia. A logistic binary regression was performed to elucidate any predictive factor of lymphopenia and severe lymphopenia. Area under the curve (AUC) was calculated to evaluate sensibility and specificity of predictors. We analyzed treatment outcome with NEDA-3 status at 1- and 2-years. 98 of 105 patients treated with DMF were included. 46.9% developed lymphopenia, 27.6% severe lymphopenia. Lymphopenia was associated with basal ALC (p<0.001, AUC=0.786), treatment duration (p = 0.01, AUC=0.685),% of reduction at third month (p = 0.001, AUC=0.616) Severe lymphopenia was associated with basal ALC (p = 0.003, AUC=0.750).NEDA-3 status at 1-year (n = 66) and at 2-year (n = 44) did not differ in patients with/without lymphopenia (p = 0.059; p = 0.583) or with/without severe lymphopenia (p = 1.02; p = 0.169). Lymphopenia is a common side effect of DMF and basal ALC predicts its development. Lymphopenia is not associated with the achievement of NEDA-3 status.


Supportive oncology care at home interventions: protocols for clinical trials to shift the paradigm of care for patients with cancer.
Patients with cancer often endure substantial symptoms and treatment toxicities leading to high healthcare utilization, including hospitalizations and emergency department visits, throughout the continuum of their illness. Innovative oncology care models are needed to improve patient outcomes and reduce their healthcare utilization. Using a novel hospital at home care platform, we developed a Supportive Oncology Care at Home intervention to address the needs of patients with cancer. We are conducting three trials to delineate the role of Supportive Oncology Care at Home for patients with cancer. The Supportive Oncology Care at Home intervention includes: (1) a hospital at home care model for symptom assessment and management; (2) remote monitoring of daily patient-reported symptoms, vital signs, and body weight; and (3) structured communication with the oncology team. Our first study is a randomized controlled trial to test the efficacy of Supportive Oncology Care at Home versus standard oncology care for improving healthcare utilization, cancer treatment interruptions, and patient-reported outcomes in patients with cancer receiving definitive treatment of their cancer. Participants include adult patients with gastrointestinal and head and neck cancer, as well as lymphoma, receiving definitive treatment (e.g., treatment with curative intent). The second study is a single-arm trial assessing the feasibility and acceptability of the Supportive Oncology Care at Home intervention for hospitalized patients with advanced cancer. Eligible participants include adult patients with incurable cancer who are admitted with an unplanned hospitalization. The third study is a single-arm trial assessing the feasibility and acceptability of the Supportive Oncology Care at Home intervention to enhance the end-of-life care for patients with advanced hematologic malignancies. Eligible participants include adult patients with relapsed or refractory hematologic malignancy receiving palliative therapy or supportive care alone. These studies are approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board and are being conducted in accordance with the Consolidated Standards of Reporting Trials statement for non-pharmacological trials. This work has the potential to transform the paradigm of care for patients with cancer by providing them with the necessary support at home to improve their health outcomes and care delivery. NCT04544046, NCT04637035, NCT04690205.


Effects of melatonin on ovarian reserve in cigarette smoking: an experimental study.
The aim of the study was to investigate whether melatonin has a protective effect against diminished ovarian reserve induced by smoking. Seventy-two female Wistar-Albino rats were divided into 6 groups: group I (room air), group II (chronic cigarette smoking), group III (room air + 10 mg/kg subcutaneous melatonin), group IV (room air + 20 mg/kg subcutaneous melatonin), group V (chronic cigarette smoking + 10 mg/kg subcutaneous melatonin), group VI (chronic cigarette smoking + 20 mg/kg subcutaneous melatonin). For 45 days, rats were exposed to cigarette smoke through a smoking machine, then subcutaneous melatonin was administered. Apoptotic index, immunohistochemical scoring, ovarian follicle counting, ovarian tissue and serum malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) analyses were carried out. All of the primordial, primary, secondary and mature follicle numbers were found to be significantly lowered in study groups. Increased HSCORE with anti-caspase-3 staining and a high follicular apoptotic index were demonstrated in the smoking group. Serum and ovarian tissue levels of MDA were found to be elevated with smoke exposure whereas lower MDA levels were determined in melatonin treated groups. Serum and tissue levels of SOD, GPx and CAT were shown to be reduced in the smoking group in comparison with melatonin treated and control groups. 20 mg/kg melatonin administration in the smoking group revealed significantly decreased HSCOREs and apoptotic indices. Cigarette smoking has been definitely shown to be associated with impaired ovarian reserve with respect to significantly diminished numbers of primordial, primary, secondary and mature follicles. Dose-related treatment of melatonin in smokers may provide an evidently reduced apoptotic index and improved antioxidant activity in tissue.


Ablative therapy in pancreatic cystic lesions.
The growing incidence of cystic pancreatic tumours has become a major problem in daily clinical practice. These patients usually undergo follow-up programmes of questionable clinical efficacy that put significant strain on endoscopy units. Safe and effective alternatives to surgery are desperately needed in these cases. The aim of this study was to critically review the utility of ablative therapies in cystic pancreatic tumours.


A twelve-year survey of cervicothoracic vascular injuries.
This study of a large series of victims of trauma to the cervicothoracic great vessels confirms the lethal potential of these injuries: more than half of victims of such injuries died. The optimal management of patients potentially harboring such vascular damage appears to include skilled prehospital resuscitation and rapid transport to a trauma center, a high index of diagnostic suspicion, a low threshold for the performance of contrast arteriography, aggressive surveillance for associated neurologic and aerodigestive tract injuries, and timely technical repair, including liberal indications for sternotomy or thoracotomy to assure vascular control.


Association between gestational age at threatened preterm birth diagnosis and incidence of preterm birth: the Japan Environment and Children's Study.
We evaluated the association between gestational age at threatened preterm birth (TPTB) diagnosis and preterm birth (PTB) incidence using a nationwide birth cohort. Data of 94,236 women with singleton deliveries from the Japan Environment and Children's Study (enrolled between 2011 and 2014) were analysed. Participants were divided based on parity and gestational age at TPTB diagnosis (22-24, 25-27, 28-30, 31-33, and 34-36 weeks). Multivariable logistic regression models were used to calculate the odds ratios (ORs) for PTB before 37 and 34 weeks in women from all groups, using participants without TPTB as the reference. The adjusted ORs for PTB before 37 weeks were the highest in the latest gestational age group in nulliparous and multiparous women without previous PTB, while those before 34 weeks were the highest in the earliest and latest gestational age group in multiparous women without previous PTB and in the earliest gestational age group in multiparous women with previous PTB. The association between gestational age at TPTB diagnosis and PTB incidence varies based on maternal parity and PTB before 37 or 34 weeks. Further studies with detailed clinical data and a unified TPTB diagnosis protocol are necessary to clarify this association.


Recent Advances in β2-Agonists for Treatment of Chronic Respiratory Diseases and Heart Failure.
β2-Adrenoceptor (β2-AR) agonists are widely used as bronchodilators. The emerge of ultralong acting β2-agonists is an important breakthrough in pulmonary medicine. In this review, we will provide mechanistic insights into the application of β2-agonists in asthma, chronic obstructive pulmonary disease (COPD), and heart failure (HF). Recent studies in β-AR signal transduction have revealed opposing functions of the β1-AR and the β2-AR on cardiomyocyte survival. Thus, β2-agonists and β-blockers in combination may represent a novel strategy for HF management. Allosteric modulation and biased agonism at the β2-AR also provide a theoretical basis for developing drugs with novel mechanisms of action and pharmacological profiles. Overlap of COPD and HF presents a substantial clinical challenge but also a unique opportunity for evaluation of the cardiovascular safety of β2-agonists. Further basic and clinical research along these lines can help us develop better drugs and innovative strategies for the management of these difficult-to-treat diseases.


Deconstruction of GCN4/GCRE into a monomeric peptide-DNA complex.
Here we describe a system that enables short peptides to bind DNA sequence-specifically. Linking the peptide covalently to DNA through a disulphide bond eliminates the unfavourable energetic cost of diffusion and thus potentiates the peptide-DNA interaction. By this approach we have deconstructed the GCN4/DNA complex into its elemental DNA recognition units. We find that the GCN4 basic region contacts the two half-sites with very different affinities and propose that this thermodynamic asymmetry plays a role in differential regulation of gene expression. Specific binding of the peptide to DNA stabilizes the disulphide bond toward reduction suggesting a novel approach to the discovery of new DNA-binding specificities.


GABAergic Neurons and Their Modulatory Effects on GnRH3 in Zebrafish.
γ-Aminobutyric acid (GABA) is a major amino acid neurotransmitter in the vertebrate brain. To provide detailed information on the distribution of the GABA in zebrafish (Danio rerio), neurons were labeled with mCherry driven by the glutamic acid decarboxylase 67 (gad67) promoter. In the transgenic line Tg(gad67:mCherry), mCherry-positive gad67 cell bodies were predominantly localized to the olfactory bulb, pallial zones, subpallium zones, parvocellular preoptic nucleus, periventricular gray zone of optic tectum, torus semicircularis, posterior tuberculum, medial longitudinal fascicle, caudal zone of periventricular hypothalamus, and oculomotor nucleus. mCherry-positive fibers were widely distributed in the olfactory bulbs, subpallium, thalamus, ventral hypothalamic zone, tectum opticum, mesencephalon, and rhombencephalon. mCherry-positive neurons were also observed in the retina and the spinal cord. The anatomical relationships between GABAergic and gonadotrophin-releasing hormone 3 (GnRH3) neurons were investigated by crossing Tg(gad67:mCherry) fish with the previously established Tg(gnrh3:EGFP) transgenic line. GnRH3 cell bodies and fibers were contacted by GABAergic fibers directly in the ventral telencephalon and anterior tuberal nucleus. A subpopulation of GnRH3 neurons in the ventral telencephalic area was also labeled with mCherry, so some GnRH3 neurons are also GABAergic. GABAB receptor agonist (baclofen) and antagonist (CGP55845) treatments indicated that GABAB receptor signaling inhibited gnrh3 expression in larval fish but was stimulatory in adult fish. The expression of pituitary lhβ and fshβ was stimulated by intraperitoneal injection of baclofen in adult fish. We conclude that GABA via GABAB receptors regulates GnRH3 neurons in a developmentally dependent manner in zebrafish.


Clozapine v. conventional antipsychotic drugs for treatment-resistant schizophrenia: a re-examination.
Although there is a consensus that clozapine is more effective than conventional antipsychotic drugs for treatment-resistant schizophrenia, there is great heterogeneity among results of relevant trials. To re-evaluate the evidence comparing clozapine with conventional antipsychotics and to investigate sources of heterogeneity. Individual studies were inspected with assessment of clinical relevance of results. Meta-regression analysis was performed to investigate sources of heterogeneity. Ten trials were examined. Recent large-scale studies have not found a substantial advantage for clozapine, especially in terms of a clinically relevant effect. Meta-regression showed that shorter study duration, financial support from a drug company and higher baseline symptom score consistently predicted greater advantage of clozapine. It may be inappropriate to combine studies in meta-analysis, given the degree of heterogeneity between their findings. The benefits of clozapine compared with conventional treatment may not be substantial.


Microbiome-metabolomics insights into the feces of high-fat diet mice to reveal the anti-obesity effects of yak (Bos grunniens) bone collagen hydrolysates.
In this study, a twelve-week intervention was conducted to investigate the anti-obesity effects of yak bone collagen hydrolysates (YBCH) on mice with a high-fat diet. The obesity-associated phenotypes of mice were detected and the feces of mice were jointly analyzed by 16S rRNA gene sequencing and untargeted metabolomics. Results indicated that supplementation with YBCH could ameliorate the obesity-associated phenotypes of mice, especially with the medium dose (MD) and high dose (HD) of YBCH. Compared with the high-fat diet control (HC) group, the ratio of Firmicutes and Bacteroidetes in the fecal microbiota of the low dose (LD), MD, and HD groups was separately decreased by 29.83 %, 70.85 %, and 75.70 %. Lachnospiraceae and Muribaculaceae were the key bacteria for the YBCH intervention, which might be attributed to their different substrate preferences. The joint analysis of the 16S rRNA gene sequencing and untargeted metabolomics suggested that the anti-obesity effects of YBCH might be achieved by up-regulating the arginine and proline metabolism and down-regulating the aromatic amino acids metabolism via the gut microbiota.


Homologous pairing and ring and filament structure formation activities of the human Xrcc2*Rad51D complex.
The Xrcc2 and Rad51D/Rad51L3 proteins, which belong to the Rad51 paralogs, are required for homologous recombinational repair (HRR) in vertebrates. The Xrcc2 and Rad51D/Rad51L3 genes, whose products interact with each other, have essential roles in ensuring normal embryonic development. In the present study, we coexpressed the human Xrcc2 and Rad51D/Rad51L3 proteins (Xrcc2 and Rad51D, respectively) in Escherichia coli, and purified the Xrcc2*Rad51D complex to homogeneity. The Xrcc2 small middle dotRad51D complex catalyzed homologous pairing between single-stranded and double-stranded DNA, similar to the function of the Xrcc3*Rad51C complex, which is another complex of the Rad51 paralogs. An electron microscopic analysis showed that Xrcc2*Rad51D formed a multimeric ring structure in the absence of DNA. In the presence of ssDNA, Xrcc2*Rad51D formed a filamentous structure, which is commonly observed among the human homologous pairing proteins, Rad51, Rad52, and Xrcc3*Rad51C.


Sacral orientation and Scheuermann's kyphosis.
To examine whether the association between spinal alignment and sacral anatomical orientation (SAO) can be detected in skeletal populations, by comparing SAO values in individuals with a typical SD to individuals with normal spinal alignment. 2025 skeletons were screened for Scheuermann's disease. Scheuermann's kyphosis was established by the presence of apophyseal abnormalities associated with more than 5° of anterior wedging in each of three adjacent vertebrae. SAO was measured as the angle created between the intersection of a line running parallel to the superior surface of the sacrum and a line running between the anterior superior iliac spine and the anterior-superior edge of the symphysis pubis (PUBIS). SAO was measured on 185 individuals with normal spines and 183 individuals with Scheuermann's kyphosis. Out of 2025 skeletons, 183 (9 %) were diagnosed with Scheuermann's kyphosis. The sacrum was significantly more horizontally oriented in individuals with Scheuermann's kyphosis compared with the control (SAO: 44.44 ± 9.7° vs. 50 ± 9.9°, p < 0.001). Alteration in spinal biomechanics due to a horizontally orientated sacrum may be an important contributing factor for the development of Scheuermann's kyphosis.


Calcium in lymphotoxin-mediated cytolysis: cellular pools, fluxes, and role of extracellular concentration.
This study explores, by kinetic analysis, the movement of calcium among cellular pools of target cells in which cytotoxicity is induced by human lymphotoxin, and evaluates the requirement for calcium in this reaction. We employed the kinetic model of Borle to quantitate flux rates and pool sizes. It was found that the rate of flux between the surface (plasma membrane-glycocalyx) compartment and the intracellular compartment was greatly increased. The size of the total exchangeable intracellular calcium pool was not altered, but there was an apparent decrease in the size of the surface calcium pool. This latter phenomenon may be related to the blebbing and exfoliation of plasma membranes under the influence of the lymphokine. Lymphotoxin-induced cytotoxicity is observed in calcium-free medium and over a range of calcium concentrations. These results argue against cell death due to a massive in rush of calcium into the cell under these circumstances.


Optimal designing of beta-conglycinin to genetically incorporate RPLKPW, a potent anti-hypertensive peptide.
Previously, we introduced the RPLKPW sequence, a highly potent hypotensive peptide designed based on ovokinin (2-7), into three homologous sites in the soybean beta-conglycinin alpha' subunit by site-directed mutagenesis. The modified protein expressed in Escherichia coli reduced blood pressure of spontaneously hypertensive rats (SHRs) after oral administration at a dose of 10 mg/kg, which suggested about 30% of the introduced peptide was released in vivo. In this study amino acid residues around the RPLKPW sequence were optimized with a use of synthetic peptides to facilitate release of RPLKPW by gastrointestinal proteases. Then, fourth RPLKPW was also introduced into the extension domain of the protein. The newly modified protein, which was produced in E. coli, significantly lowered blood pressure in SHRs at a dose of 2.5 mg/kg 4 h after oral administration. Furthermore, we produced an extension domain that corresponds to residues 1-143 of the modified alpha' subunit containing four RPLKPW sequences by introducing a termination codon. The minimum effective dose of the modified extension domain was 1.0 mg/kg, which is 1/2000 that of ovalbumin.


Ca2+/calmodulin-dependent modulation of cell cycle elements pRb and p27kip1 involved in the enhanced proliferation of lymphoblasts from patients with Alzheimer dementia.
Failure of cell cycle regulation in neurons might be critically involved in the process of neurodegeneration in Alzheimer's disease (AD). We present here evidence to support the hypothesis that cell cycle alterations occur in cells other than neurons in AD sufferers. Lymphocytes from AD patients immortalized with Epstein-Barr virus showed an enhanced rate of proliferation and increased phosphorylation of the retinoblastoma protein (pRb) and other members of the family of pocket proteins compared with cell lines derived from normal age-matched controls. The calmodulin antagonist calmidazolium, as well as W-7 and W-13, abrogated the enhanced activity of AD cells without altering the normal basal rate of proliferation. The effect of calmidazolium was accompanied by partially dephosphorylation of pRb. No changes were found in the expression levels of the G1 cyclin/Cdks complexes. However, lymphoblasts derived from AD patients showed reduced levels of the Cdk inhibitor p27(kip1), which were restored after anti-calmodulin treatment of the cultures. These observations suggest that in AD cells the enhanced rates of cell proliferation and phosphorylation of pRb and the intracellular content of p27(kip1) may be interrelated events controlled by a mechanism dependent on the Ca(2+)/calmodulin signaling pathway. The distinct functional features of lymphoblastoid cells from AD patients offer an invaluable, noninvasive tool to investigate the etiopathogenesis, and eventually, for the early diagnosis and prognosis of this devastating disease.


The effects and mechanism of flavonoid-rePON1 interactions. Structure-activity relationship study.
Flavonoids are plant phenolic secondary metabolites that are widely distributed in the human diet. These antioxidants have received much attention because of their neuroprotective, cardioprotective, and chemopreventive actions. While a major focus has been on the flavonoids' antioxidant properties, there is an emerging view that many of the potential health benefits of flavonoids and their in vivo metabolites are due to modulatory actions in cells through direct interactions with proteins, and not necessarily due to their antioxidant function. This view relies on the observations that flavonoids are present in the circulation at very low concentrations, which are not sufficient to exert effective antioxidant effects. The enzyme paraoxonase 1 (PON1) is associated with high-density lipoprotein (HDL), and is responsible for many of HDLs' antiatherogenic properties. We previously showed that the flavonoid glabridin binds to rePON1 and affects the enzyme's 3D structure. This interaction protects the enzyme from inhibition by an atherogenic component of the human carotid plaque. Here, we broadened our study to an investigation of the structure-activity relationships (SARs) of 12 flavonoids from different subclasses with rePON1 using Trp-fluorescence quenching, modeling calculations and Cu(2+)-induced low-density lipoprotein (LDL) oxidation methods. Our findings emphasize the 'protein-binding' mechanism by which flavonoids exert their beneficial biological role toward rePON1. Flavonoids' capacity to interact with the enzyme's rePON1 hydrophobic groove mostly dictates their pro/antioxidant behavior.


Electrical Stimulation for Cerebral Vasospasm After Subarachnoid Hemorrhage: A Systematic Review.
Cerebral vasospasm is a severe and potentially lethal complication in patients with subarachnoid hemorrhage (SAH). Its pathogenesis is still not completely understood. The efficacy of current treatments, such as triple-H therapy or calcium channel blockers, is unsatisfactory, and a new therapy model would therefore be valuable. Electrical stimulation may have a considerable influence on cerebrovascular innervation. This systematic review gives an overview of the studies that have applied electrical stimulation in models of cerebral vasospasm. We performed a systematic review of the literature, searching PubMed and Ovid Embase with the keywords "electric stimulation," "cerebral vasospasm," "subarachnoid hemorrhage," "sympathetic," and "parasympathetic." Additional papers were identified from the reference lists of the articles identified in the literature search. Increased cerebral blood flow (CBF) is a widely observed effect of spinal cord stimulation and sphenopalatine ganglion stimulation in models of physiological conditions or experimental cerebral vasospasm. Most studies were conducted in animals, 15 under physiological conditions and 11 in animals with SAH. Eight studies in humans were identified that examined the stimulation effect on CBF under physiological conditions. Only two studies looked at patients after SAH: one applied spinal cord stimulation (SCS) and the other transcutaneous electrical neurostimulation. Different mechanisms leading to stimulation-induced CBF increase that were discussed included "reversible functional sympathectomy," activation of brainstem vasomotor centers, involvement of central ascending pathways, release of neurohumoral factors, and interaction with sympathetic, parasympathetic, and trigeminal innervation. The results indicate that electrical stimulation is a promising procedure for prevention and treatment of cerebral vasospasm. Electrical stimulation, especially SCS and sphenopalatine ganglion stimulation, is a promising adjunct for existing therapies for vasospasm after SAH. Further experiments and prospective clinical studies are needed to establish its potential usefulness as a therapy or prevention option.


Natural regulation of herbivorous forest insect populations.
From basic principles of positive/negative feedback control and classical density-dependent/independent population theory we outline a general explanation for the regulation of herbivore populations in forested ecosystems. We identify three fundamental patterns of behavior; (i) populations regulated close to equilibrium ("tight" regulation) by fast-acting negative feedback processes, (ii) populations regulated by delayed negative feedback processes ("loose" regulation) which often exhibit wide-amplitude density cycles, and (iii) populations characterized by positive feedback processes over certain density ranges that may exhibit divergent (metastable) behavior. We then discuss the effects of these different kinds of herbivore population behavior on the dynamics of forest ecosystems and explore some elemental models of herbivore/forest interactions. Finally, using the spruce bark beetle, Ips typographus, as an example, we demonstrate how the theory can be used to explain the dynamics of specific herbivore populations and to develop general strategies for managing destructive herbivore outbreaks.


Traumatic tricuspid valve regurgitation and cerebral emboli.
We report a case of traumatic tricuspid valve regurgitation and late presentation with transient ischemic attacks caused by the presence of a right-to-left shunt through a small atrial septal defect.


Patient Perspective on Post-Breast Reconstruction Exercise and Physical Therapy.
Breast reconstruction may result in significant functional compromise and pain. Postoperative exercise and physical therapy can mitigate these morbidities, but it is infrequently recommended by healthcare providers. This study asked how many breast reconstruction patients are instructed to perform postoperative at-home exercises or physical therapy, how many reported following through with these instructions, and what timeline they were given for these activities. A 16-question multiple-choice anonymous online survey was distributed to a private breast cancer survivor Facebook group (Diep C. Foundation). A total of 150 breast reconstruction patients responded to our survey. The majority of respondents in our sample were not provided with specific instructions regarding postoperative at-home exercises (N = 70, 54.3%) or physical therapy (N = 77, 63.6%). Approximately 13 of 59 respondents (22%) who had been instructed to participate in postoperative at-home exercises were directed to begin at 2-3 weeks. Approximately 15 of 44 respondents (34.1%) who had been instructed to participate in physical therapy were directed to begin these at 4-5 weeks. To the best of our knowledge, this is the first study of how often postoperative at-home exercises and physical therapy are recommended to breast reconstruction patients. Despite robust evidence of these activities' benefits, most women are not instructed to participate in postoperative at-home exercises or physical therapy. This is likely to impede breast reconstruction patients' recovery and delay their return to activities of daily living. More studies are needed of how to actively engage breast reconstruction patients in postoperative at-home exercises and physical therapy.


Primary Cutaneous Anaplastic Large Cell Lymphoma-A Review of Clinical, Morphological, Immunohistochemical, and Molecular Features.
Primary cutaneous anaplastic large cell lymphoma (ALCL) is the second most common cutaneous T-cell lymphoma after mycosis fungoides and belongs to the spectrum of cutaneous CD30+ T-cell lymphoproliferative disorders. Although primary cutaneous ALCL usually presents as a localized nodule or papule with or without ulceration, multifocal lesions may occur in up to 20% of cases. Histologically, primary cutaneous ALCL consists of a diffuse dermal infiltrate of medium to large anaplastic/pleomorphic cells with abundant amphophilic-to-eosinophilic cytoplasm, horseshoe-shaped nuclei, strong and diffuse expression of CD30, and with focal or no epidermotropism. The neoplastic infiltrate may show angiocentric distribution and may extend to the subcutis. Patients with localized or multifocal disease have a similar prognosis with a 10-year overall survival rate of 90%. Approximately 30% of primary cutaneous ALCLs harbor a DUSP22 (6p25.3) gene rearrangement that results in decreased expression of this dual-specific phosphatase, decreased STAT3 activation, and decreased activity of immune and autoimmune-mediated mechanisms regulated by T-cells.


Gonorrhea and syphilis in incarcerated urban adolescents: prevalence and physical signs.
During a 1-year period from July 1983 to June 1984, 285 adolescent girls and 2,236 adolescent boys, ranging in age from 9 to 18 years (89% were 14 to 16 years of age), were screened for gonorrhea and syphilis on entry into a detention facility in New York City. The prevalence rate for gonorrhea was 3% for boys and 18.3% for girls, and the prevalence rate for syphilis was 0.63% for boys and 2.5% for girls. The rates of gonorrhea without penile or cervical discharge on physical examination were 2.1% for boys and 10.9% for girls. This high prevalence of syphilis and gonorrhea and the high frequency of disease without physical signs of illness indicate the desirability of screening high-risk adolescents for these and other sexually transmitted diseases. Our data support the need for programs in detention facilities and, we believe, schools, to encourage use of barrier contraceptives to control gonorrhea, syphilis, Chlamydia, human papillomavirus, human immunodeficiency virus, and unwanted pregnancy.


In vivo metabolism of nasally instilled benzo[a]pyrene in dogs and monkeys.
Metabolism of inhaled materials deposited in the nasal cavity potentially influences their biological fate and toxicity. Metabolic enzymes, including cytochrome P-450-dependent monooxygenases, are not evenly distributed throughout the nasal cavity. The purpose of this study was to determine whether benzo[a]pyrene (BaP) deposited in the nasal cavity could be metabolized and cleared by the nasal tissue in the ethmoid and maxillary turbinate regions of Beagle dogs and cynomolgus monkeys. Nasopharyngeal mucus was collected at frequent intervals during periodic nasal instillations of BaP (and for dogs 24 h after instillation) for analysis of BaP and its metabolites. During and up to 48 h after nasal instillation of [14C]BaP, blood, urine and feces were collected to determine BaP clearance from the nose. High pressure liquid chromatographic analysis of organic phase extracts of nasopharyngeal mucus demonstrated that [14C]BaP instilled in either turbinate region was metabolized to dihydrodiols, quinones, phenols and tetrols in both species. Phenols were the major metabolic product, although all treated animals produced trans-7,8-dihydrobenzo[a]pyrene-7,8-diol. The dog mucus sampled at 24 h had no detectable radioactivity. The excreta from both species contained only small amounts of the instilled radioactivity. There was no distinctive pattern of metabolite production based on instillation site.


Conservation of the Down syndrome critical region in humans and great apes.
A quarter century ago, a chimpanzee with trisomy 22 was reported to have the clinical manifestation of Down syndrome. The features of Down syndrome in human have been associated with chromosome 21 band q22.3. The recent availability of chromosome and loci specific probes has prompted us to utilize the human cosmid probe (D21S65) for the trisomy 21 region in the chromosomes of the chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla) and orangutan (Pongo pygmeus). Interestingly, the hybridization site for the Down syndrome region was found on the equivalent ape chromosome 22 in all three primates (the human equivalent of chromosome 21). Apparently, these results support the notion that the Down syndrome critical region of human chromosome 21 band q22.3 is conserved in great apes, which has displayed mongolism in a chimpanzee when present in triplicate conditions. Furthermore, other probes can be used as phylogenetic signals to enhance the understanding of human descent.


Lipofibroma of the superficial branch of the radial nerve.
Lipofibromas of nerve are rare hamartomatous lesions almost exclusively involving the median nerve. To our knowledge, this is the first reported case of a lipofibroma involving a branch of the radial nerve.


Fungal contamination of raw materials of some herbal drugs and recommendation of Cinnamomum camphora oil as herbal fungitoxicant.
The paper explores fungal infection and aflatoxin B1 contamination of six medicinal plant samples viz. Adhatoda vasica Nees, Asparagus racemosus Linn., Evolvulus alsinoides Linn., Glycyrrhiza glabra Linn., Plumbago zeylanica Linn. and Terminalia chebula Retz. A total of 858 fungal isolates were detected from the raw materials. Maximum number of fungal isolates was detected from A. racemosus (228). The genus Aspergillus was found to be the most dominant genus causing infection to most of the raw materials. Among the 32 isolates of A. flavus tested, 13 isolates were found to be toxigenic elaborating aflatoxin B1. The highest elaboration of aflatoxin B1 was 394.95 ppb by the isolates of A. flavus from G. glabra. The essential oil of Cinnamomum camphora (L.) Presl showed efficacy in arresting aflatoxin B1 by the toxigenic strain. The growth of a toxigenic strain of A. flavus decreased progressively with increasing concentration of essential oil from leaves of C. camphora. The oil completely inhibited aflatoxin B1 production even at 750 ppm. Hence, the oil of C. camphora is recommended as herbal fungitoxicant against the fungal contamination of the raw materials.


Deficiency of DNA ligase activity in Fanconi's anemia.
A significant decrease in DNA ligase activity was observed in lymphocytes and fibroblasts of a patient with Fanconi's anemia (FA). This decrease is related to the observed DNA repair deficiency indicated by the delayed closing of repair DNA strands following UV irradiation. Other steps of DNA repair were analyzed in the FA fibroblasts, including endonucleolytic incision of DNA, repair DNA synthesis, and exonucleolytic removal of the photoproducts. No differences were found against control cells. The action of DNA ligase is delayed during replication in the FA cells, as seen by an accumulation of replicative intermediates.


Heterogeneity in cell proliferation and expression of p53 and bcl-2 during the indolent phase of germinal centre cell lymphoma: an explanation for clinical variability.
Germinal centre cell lymphomas (GCCL) show a wide range of clinical outcomes from persistent indolent disease to large cell transformation. To investigate possible mechanisms of this heterogeneity, a combined morphometric and immunohistological study of p53, bcl-2 and cell proliferation was carried out. There was wide variation in p53 expression between biopsies and between individual follicles in the same tumour. A similar pattern of variation was seen using the cell-cycle marker MIB1, but this did not correlate with p53 expression. Even in cases in which a t(14;18) was demonstrated by PCR, variation occurred in the number of cells expressing bcl-2. On the basis of these results, we suggest that the probability of the clonal expansion of GCCL tumour cells carrying additional genetic abnormalities depends on a complex interaction of cell proliferation with p53 and bcl-2 expression, and that this may account for variation seen in the clinical behaviour seen in this group of tumours.


Convincing the "Herd" of immunity: Lessons from smallpox vaccination in 19th century Germany.
Although vaccination is a cost-effective way to control infectious diseases, it is often met with popular resistance. Studying smallpox in 19th century Germany, this paper explores how economic incentives contribute to this phenomenon. The paper adds to the literature by combining mathematical epidemiology and unpublished archival evidence from two German states - Baden and Wurttemberg. The two states are an intriguing case because their initial conditions and vaccination laws were similar. Despite this, Baden experienced lower smallpox prevalence and higher vaccination uptake than Wurttemberg. The epidemiological model predicts that incentives to vaccinate decline rapidly when immunization reduces prevalence. The archival evidence reveals that Baden offset this decline by creating a public vaccination system which reduced costs for vaccinees and vaccinators alike. This suggests that the high fixed costs of centralized immunization policies can be compensated by economies of scale and popular acceptance.


Cardiovascular abnormalities in the relatives of patients operated upon for annulo-aortic ectasia. A clinical and echocardiographic study of 40 families.
This study is based on 40 consecutive patients operated on for annuloaortic ectasia at the Turku University Central Hospital between March 1970 and April 1983. Supracoronary graft insertion was used in the first nine patients, while the remaining patients were treated by radical repair using a composite graft and reimplantation of the coronary ostia. The mean age of the patients was 40.3 years (10 to 66 years). The patients were examined postoperatively for their physical, radiological, and ophthalmological parameters. Eight had the classic Marfan syndrome. The patients had 230 first-degree relatives, and 200 of them were alive. Three of the 30 deceased relatives had died due to rupture of an ascending aortic aneurysm; 187 of the living relatives were examined as above. In addition, echocardiography was performed. Twenty-six of the surviving relatives had dilatation of the aortic root; 24 were siblings, and two were children of the operated patients. Echocardiography of the relatives revealed an increased incidence of mitral valve prolapse and enlargement of the left ventricle and left atrium. None of the relatives examined had the classic Marfan syndrome, although the incidence of some Marfan features occurred more frequently in the Marfan families. It seems clear that annuloaortic ectasia, even without the Marfan syndrome, is a hereditary disease. To detect annuloaortic ectasia at an early stage, examination of the first-degree relatives of patients operated upon is recommended.


Goal-setting in multidisciplinary team care for patients with rheumatoid arthritis: an international multi-center evaluation of the contents using the International Classification of Functioning, Disability and Health as a reference.
To make a cross-cultural comparison of the contents of rehabilitation goals of patients admitted for rehabilitation and to compare the contents with the comprehensive International Classification of Functioning, Disability and Health (ICF) Core Set for rheumatoid arthritis, by linking their contents to the ICF. A random sample of 80 patients with rheumatoid arthritis was retrieved from rehabilitation clinics in 4 countries. Rehabilitation goals were extracted from the medical records and linked to the ICF using standardized linking rules. A total of 495 rehabilitation goals were identified and linked to 952 ICF codes, resulting in 151 unique ICF codes. Two-hundred and seventy-five (29%) of the 952 ICF codes were related to "Body Functions" (b-codes), 80 (8%) to "Body Structures" (s-codes), 419 (44%) to "Activities and Participation" (d-codes) and 178 (19%) to "Environmental Factors" (e-codes). Thirty-five of the 151 unique ICF codes (23%) were not in the comprehensive ICF Core Set for RA, whereas 23 of the ICF codes in this Core Set (24%) were not in the rehabilitation goals. The goals set in a team rehabilitation setting for patients with rheumatoid arthritis are related to all ICF components, with "Activities and Participation" being the most frequently addressed. The contents of the goals are, to a considerable extent, covered by the comprehensive ICF Core Set for RA, but additional evaluation is required before the ICF Core Set is used as a rehabilitation tool in rheumatoid arthritis.


Oncocytic Schneiderian papillomas: Clinical behavior and outcomes of the endoscopic endonasal approach in 33 cases.
The purpose of this study was to evaluate the clinical behavior of oncocytic Schneiderian papillomas in relation to the rate of malignant transformation and recurrences and to report the long-term results of the endoscopic endonasal treatment. A retrospective analysis was carried out on patients with oncocytic papilloma, endoscopically managed over the past 20 years, at 2 university centers following a uniform policy. Thirty-three patients were treated between November 1991 and December 2010. The mean follow-up period was 62 months. We observed 2 cases of persistence (6%) at the maxillary sinus level. Both of these patients underwent endoscopic surgical revision. Squamous cell carcinoma (SCC) was observed in 1 patient (3%). The endonasal endoscopic technique proved to be a safe and effective approach for the treatment of oncocytic papillomas. An oncocytic papilloma is not to be considered a negative prognostic factor in terms of malignant transformation or recurrence.


The influence of history on interobserver agreement for diagnosing actinic keratoses and malignant skin lesions.
Quantifying interobserver diagnostic agreement is necessary to evaluate skin cancer screening programs, but estimates of variability are incomplete. We sought to measure agreement between dermatologists for diagnosing actinic keratoses (AKs) and malignant skin lesions and to determine the way in which blinding examiners to patient history affects agreement. We varied the amount of historical information available to examiners in two consecutive patient series (n = 50) presenting to a Veterans Affairs Medical Center dermatology clinic. Two dermatologists examined each patient independently. Assessing historical features increased the kappa statistic for malignancy recognition from -0.04 to 0.76. kappa Statistics for diagnosing single AKs were 0.17 and 0.15, respectively, and 0.62 and 0.55 for multiple AKs. Agreement was high for diagnosing malignant skin lesions when history was included in the evaluation. Agreement for multiple AKs was higher than for single AKs, although neither was influenced by inclusion of historical features.


Gastric subepithelial tumor: long-term natural history and risk factors for progression.
Subepithelial tumors are often detected incidentally during upper gastrointestinal endoscopy. However, their natural history and clinical management have yet to be clearly established. The aim of this study was to evaluate the natural history and risk factors for progression of gastric SETs. The study retrospectively reviewed the medical records of patients who were diagnosed with gastric SET using upper gastrointestinal endoscopy between January 2005 and December 2017. Tumor progression was defined by a ≥ 25% increase in diameter. Among 3237 patients, 1859 underwent serial upper gastrointestinal endoscopy for more than six months. Endoscopic ultrasonography was further performed in 733 (39.43%) patients. Resection was performed in 73 (3.93%) patients. Tumor progressed in 138 (7.42%) patients over a mean follow-up period of 59.41 months (range, 5-215 months). In progressed tumors, the mean initial size was 15.01 mm (range, 2-50 mm) and the mean size increment was 12.86 mm (range, 3-50 mm). Large initial tumor size (OR: 1.03, 95% CI: 1.01-1.05), surface ulcer or erosion (OR: 2.47, 95% CI: 1.21-5.06), lobulated shape (OR: 3.76, 95% CI: 2.00-7.06), and middle-third location (OR: 1.65, 95% CI: 1.08-2.52) were significant risk factors for tumor progression. Large SETs had higher rates of progression and tended to grow faster than smaller tumors (r = 0.44, p < 0.001). The majority of gastric SETs did not increase in size during the long-term follow-up. Serial endoscopy may be sufficient as a follow-up tool for small SETs with intact overlying mucosa without lobulated shape.


Study of Animal Mixing and the Dynamics of Hepatitis E Virus Infection on a Farrow-to-Finish Pig Farm.
In Europe, swine are a livestock reservoir for Hepatitis E virus genotype 3 (HEV-3). Consumption of food containing HEV-3 can cause zoonotic human infection, though risk is reduced by heat treatment. Implementing controls that limit infection in slaughter pigs may further reduce foodborne transmission risk but knowledge of infection dynamics on commercial farms is limited. This study addressed this knowledge gap and in particular investigated the influence of group mixing. Faeces were collected from grower (n = 212) and fattener (n = 262) pigs on a farrow-to-finish farm on four occasions. HEV RNA was detected on all occasions, and prevalence was higher in growers (85.8%) than fatteners (26.0%; p < 0.001). HEV-positive samples were also collected from the wider farm environment (n = 67; 64.7% prevalence), indicating potential sources for HEV re-circulation within the herd. Timing of infection in a cohort was also investigated. HEV was absent from all piglet faeces (n = 98) and first detected at weaner stage (25.7% prevalence), but only in groups weaned earlier or comprising pigs from many different litters. Farrowing sow faeces (n = 75) were HEV-negative but antibodies were detected in blood from two sows. Results suggest that multiple factors influence HEV infection dynamics on pig farms, and potential foci for further study into practical control solutions are highlighted.


Effect of intrathecal capsaicin analogues on the immunofluorescence of peptides and serotonin in the dorsal horn in rats.
The intrathecal administration of capsaicin, a homovanillylamide derivative, has been demonstrated to cause analgesia in response to thermal stimuli. This analgesia has been correlated with a profound depletion of spinal substance P, a putative primary afferent transmitter. We studied the effects of capsaicin, a series of capsaicin analogues, piperine and kainic acid on the immunohistochemical staining of substance P, cholecystokinin, somatostatin, methionine-enkephalin and serotonin. Capsaicin and an analogue 1-nonenoyl-vanillylamide significantly elevated the tail flick latency and when the spinal cords of the rats were analyzed immunohistochemically, a profound depletion of substance P and cholecystokinin was observed. The spinal somatostatin-immunoreactivity of these rats was slightly reduced. Piperine also depleted substance P and reduced somatostatin staining but did not alter the staining intensity or density of cholecystokinin, methionine-enkephalin or serotonin. Kainate-depleted methionine-enkephalin but did not alter any other neuropeptides studied or serotonin. These results may indicate a link between capsaicin-induced analgesia and the concomitant depletion of cholecystokinin and substance P.


The fate, acute, and subchronic risks of dinotefuran in the water-sediment system: A systematic analysis at the enantiomer level.
Environmental risks associated with neonicotinoid insecticides have attracted considerable attention. This study systematically investigated the stereoselective behavior of dinotefuran in a water-sediment system. The results showed that S-dinotefuran accumulated more easily in sediment and zebrafish. Although dinotefuran enantiomers and metabolites present a low risk to aquatic organisms, the risk of dinotefuran enantiomers to sediment organisms should be considered. Additionally, S-dinotefuran induced more remarkable oxidative damage in zebrafish than that of R-dinotefuran. Nevertheless, R-dinotefuran remarkably activated antioxidant and detoxifying enzymes. Multi-omics analyses revealed that S-dinotefuran induced more differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) in zebrafish. In particular, S-dinotefuran inhibited the expression of ribosome- and proteasome-related genes and proteins, affecting the synthesis and degradation of proteins in zebrafish. R-dinotefuran remarkably activated peroxisome-related genes and proteins, thereby enhancing antioxidant and detoxification abilities of zebrafish. The stereoselective interactions between dinotefuran enantiomers and key DEPs were elucidated using AlphaFold2 modeling and molecular docking techniques, which may serve as the main reason for stereoselective subchronic toxicity. The present study is beneficial for the correct use of dinotefuran and provides an effective means for elucidating the mechanism of the stereoselective behavior of chiral compounds.


Simple in vitro assay of Arf GAPs and preparation of Arf proteins as substrates.
Defining the interaction of Arf GAPs with specific Arfs is important for understanding their functions in the endocytic system. Cell-based approaches have been valuable for identifying Arfs and Arf GAPs active in the endocytic compartment; however, the cell-based assays have some limitations in establishing relationships among the Arfs and ArfGAPs. Here we describe a simple in vitro assay that will provide a means for comparing Arfs as substrates and serve to complement cell-based studies.


[Relationship between perceived emotional intelligence and professional quality of life with the achievement of occupational objectives in the costa del sol primary health care district].
To examine the relationship between "Quality of Professional Life" and "Perceived Emotional Intelligence" and the relationship of both of these with the level of achievement of occupational objectives in the Costa del Sol Primary Health Care District. Multicentre descriptive cross-sectional observational study. The Costa del Sol Primary Health Care District in the province of Málaga. Sample of Employees of all categories in fixed and contracted employment in the Management Units of the Costa del Sol District. (N=303). Respondents 247 (81.5%) The data collected was that of the percentage of achievement of objectives in 2010 and the socio-demographic data of the participants, using ad hoc designed self-report questionnaires. The TMMS -24 questionnaire was used to measure the "Perceived Emotional Intelligence", with the following dimensions: Perception, comprehension, and emotional control, and the CVP-35 measuring: management support, work demands, and intrinsic motivation. Significant correlationas were observed between Quality of Professional Life and Emotional Intelligence in the Regulation (p<.01) and Comprehension categories (p<0.05). There were also significant correlations between the profession and the type of contract in the achievement of objectives (p<.005), and quality of professional life and type of contract (p<.05). The perceived quality of professional life is related to perception and regulation dimensions of Emotional Intelligence. Knowledge of emotion management methods should be promoted by management organisations for all employees.


No evidence for visual context-dependency of olfactory learning in Drosophila.
How is behaviour organised across sensory modalities? Specifically, we ask concerning the fruit fly Drosophila melanogaster how visual context affects olfactory learning and recall and whether information about visual context is getting integrated into olfactory memory. We find that changing visual context between training and test does not deteriorate olfactory memory scores, suggesting that these olfactory memories can drive behaviour despite a mismatch of visual context between training and test. Rather, both the establishment and the recall of olfactory memory are generally facilitated by light. In a follow-up experiment, we find no evidence for learning about combinations of odours and visual context as predictors for reinforcement even after explicit training in a so-called biconditional discrimination task. Thus, a 'true' interaction between visual and olfactory modalities is not evident; instead, light seems to influence olfactory learning and recall unspecifically, for example by altering motor activity, alertness or olfactory acuity.


Chemiluminescence assay of mucosal reactive oxygen metabolites in inflammatory bowel disease.
Previous studies suggesting increased reactive oxygen metabolite (ROM) production in inflammatory bowel disease have been restricted to peripheral blood and isolated intestinal phagocytes. In the current study, chemiluminescence and the effect of various scavengers, enzymes, and enzyme inhibitors were used to show that ROMs account for the increased production of oxidants by colorectal mucosal biopsy specimens in inflammatory bowel disease. Luminol-amplified chemiluminescence was increased in active ulcerative colitis [macroscopic grade 1: 25 photons.mg-1.min.10(-3) (median), 8-47 (95% confidence intervals), n = 40; grade 2: 89, 65-156, n = 30; grade 3: 247, 133-562, n = 13] and Crohn's disease [mild: 9, 3-84, n = 6; severe: 105, 25-789 (range), n = 5] compared with normal-looking mucosa (ulcerative colitis: 0.8, 0.4-1.4, n = 22, P less than 0.01; Crohn's disease: 0.8, 0.1-2, n = 6, P less than 0.05) and controls (0.6, 0.04-1.4, n = 52, P less than 0.01). In ulcerative colitis, luminol chemiluminescence correlated with microscopic inflammation (Spearman's p = 0.74, P = 0.0001) and was decreased by sodium azide (-89%, P less than 0.05), taurine (-31%, P less than 0.05), catalase (-23%, P less than 0.05), and dimethyl sulfoxide (-29%, P less than 0.05). Superoxide dismutase and oxypurinol decreased lucigenin chemiluminescence in ulcerative colitis by -63% (P less than 0.05) and -27% (P less than 0.05), respectively. Luminol chemiluminescence correlated with lucigenin chemiluminescence (Spearman's rho = 0.72, P = 0.003). These results suggest that neutrophil-derived oxidants (superoxide, hydrogen peroxide, hydroxyl radical, and hypochlorite) are generated in colorectal mucosa in active inflammatory bowel disease and support the hypothesis that production of such metabolites by neutrophils is of major pathogenetic importance.


Analysis of the Reasons for Non-Uptake of Predictive Testing for Huntington's Disease in Spain: A Qualitative Study.
Children of persons affected by Huntington's disease (HD) have a 50% chance of inheriting the disease. Genetic testing in Spain is offered to individuals (presymptomatic test) or mothers of fetuses (prenatal) who run the risk of suffering from HD. The objective of this study is to analyze the factors that influence the decisions of adult children of persons affected with HD regarding predictive testing. A qualitative research methodology was used involving 4 focus groups (FGs) made up of adult children of persons with HD in different cities in Spain. The results of the study showed that over half of the focus group participants were inclined to decline genetic testing. The main explanatory determinants for taking or not taking the predictive test are: Maturity of the individual at risk, which was directly related to age; Ability to cope with a positive test result; Experience of living with HD sufferers; Information about testing and psychological support; Attitude of the family; Social visibility of genetic testing; Personality and temperament of each subject at risk of HD. These results imply that these factors should be analyzed in more detail in quantitative studies in order to help the Spanish Department of Health understand why some children of parents with HD decline genetic testing, so that they may and apply these data when creating specific policy regarding this issue.


The reproductive rates of Australian rodents.
The reproductive rates of about 50 species of Australian rodents were studied by calculating allometric equations for the relationships between female body weight, litter size, length of gestation and weaning periods as well as age of sexual maturity.Members of the subfamily Hydromyinae, which invaded Australia 5-10 million years ago, are characterised by small litters, long gestation and weaning periods and late maturity. The opposite is true for the Murinae (Rattus and Mus) which invaded Australia during the Pleistocene. Among the species of this latter group, those which invaded earlier have reproductive rates closer to the old invaders, while those which arrived with the Europeans during the last 200 years have the highest reproductive rates.Possible reasons for the low reproductive rates of Australian rodents are discussed. It is concluded that the rain forest origin of the hydromyinids is one of the factors responsible for their low reproductive rate. They maintained this rate to the present time because of the unpredictability of the climate and the low productivity of many Australian habitats.


[Early peroral feeding of patients after gastric resection].
A scheme of peroral nutrition of patients beginning on the 1st day after gastric resection is presented. Continuous clinical observations have confirmed the expediency of early nutrition without using a tube.


Correction: Protein 4.1N acts as a potential tumor suppressor linking PP1 to JNK-c-Jun pathway regulation in NSCLC.
[This corrects the article DOI: 10.18632/oncotarget.6312.].


Fluorescence wavelength shifts combined with light scattering for ratiometric sensing of chloride in the serum based on CsPbBr3@SiO2 perovskite nanocrystal composite halide exchanges.
A traditional fluorescence-scattering intensity based ratiometric sensing system utilizes both inherent scattering and fluorescence intensity and has drawn extensive attention owing to its simplicity and self-calibration properties. In this work, we propose a novel ratiometric fluorescence sensing system that combines a fluorescence wavelength shift and scattering in a single window, using second-order scattering (SOS) as the representative scattering signal based on the halide exchange of CsPbBr3@SiO2 perovskite nanocrystal composites. We observe a fast halide exchange within 10 seconds, resulting in an identifiable fluorescence wavelength blue shift, while the scattering wavelength remains relatively constant for self-correction. This system could be applied for ratiometric sensing of Cl- in the serum without any sample treatment. The established wavelength-based ratiometric system demonstrates high reliability and reproducibility, paving a new way for fluorescence sensing.


Ultrastructural identification of neurohaemal sites in a tick: evidence that the dorsal complex may be a true endocrine gland.
A fine structural study has been made of the 'paraganglionic plates' associated with the perineurium and of the 'retrocerebral organ' associated with the periganglionic sheath of the tick Boophilus microplus; these structures have been postulated, from descriptions by light microscopy, to be tick neurohaemal organs. Neurosecretory terminals are observed frequently in the neural lamella/perineurial sheath, particularly in a dorso-lateral area which may correspond to the 'paraganglionic plates'. No evidence was found of a discrete peripheral neurohaemal organ such as the corpus cardiacum of insects. The 'retrocerebral organ' is comprised of periganglionic sheath cells, which appear to be glandular rather than neurohaemal, and peripheral ganglionic cells.


Neuropsychiatric manifestations and their attribution to systemic lupus erythematosus: a retrospective single-center study in a Polish population.
Neuropsychiatric (NP) manifestations occur in patients with systemic lupus erythematosus (SLE), and it is challenging to distinguish these manifestations from other neuropsychiatric conditions. We aimed to assess the prevalence of primary neuropsychiatric SLE (NPSLE) in a Polish cohort of SLE patients. This retrospective, cross‑sectional study evaluated 164 patients with SLE. NP manifestations were attributed to SLE using the Italian model. Demographic and clinical data, including disease activity (measured by the Systemic Lupus Erythematosus Disease Activity Index version 2000 [SLEDAI‑2K] and the Physician Global Assessment) and organ damage (measured by the Systemic Lupus International Collaborating Clinics / American College of Rheumatology Damage Index), were obtained in patients with and without NP manifestations attributed to SLE. The final analysis set included 143 patients, 34 of whom (23.8%) had NP manifestations attributed to SLE. The age of the patients with NPSLE and the age of disease onset were significantly lower in comparison with those without NP symptoms attributed to SLE (median [interquartile range], 38 [29-45] vs 45 [32-55] years; P = 0.009, and 35 [24-38] vs 40 [25-48] years; P = 0.03, respectively). The disease activity and proportion of patients with active disease (SLEDAI‑2K ≥6) was significantly higher in the NPSLE patients than in those without NP symptoms attributed to SLE (P <0.005; 100% vs 85.3%; P = 0.01, respectively). NP manifestations in the central nervous system were the most frequent (91.5%). In the patients with NPSLE, cerebrovascular disease, seizures, cognitive dysfunction, psychosis, and cranial neuropathy occurred most often. NP manifestations occurred mainly in young patients with high disease activity. Cerebrovascular disease, seizures, psychosis, cognitive dysfunction, and cranial neuropathy were the most frequent manifestations of NPSLE.


Cystadenoma of the liver without mesenchymal stroma in a female following hormonal therapy for acne.
Liver cystadenomas are relatively rare tumours that can be difficult to diagnose; treatment entails complete surgical extirpation either by either anatomical resection or enucleation. A 19-year-old woman presented with acute onset of abdominal pain and was found to have a multilocular giant liver cyst.The cyst was percutaneously drained; CEA and CA 19-9 tumour markers were elevated in this cyst fluid: CEA 96 microg/L, CAI9-9 37 550 kU/L. The cyst was completely enucleated and has not recurred. Pathological examination confirmed a cystadenoma without mesenchymal stroma, and tumour oestrogen and progesterone receptors were negative. This is the fourth report of a liver cystadenoma without mesenchymal stroma in a female and the first to document elevated cyst fluid tumour markers. This case also illustrates the possible relationship between hormonal therapy and tumour growth.


Carotid artery plaque characteristics: current reporting practices on CT angiography.
Extracranial ICA imaging has largely focused on the degree of luminal stenosis, but recent advances suggest specific plaque features are crucial in stroke risk assessment. We evaluated the current state of reporting carotid plaque features on neck CTAs at an academic institution. In this retrospective observational study, we included neck CTAs performed on patients over age 50 with any reported carotid plaque. We evaluated reports for mention of the following: degree of luminal stenosis, soft plaque, calcified plaque, plaque thickness, quantification of soft and calcified plaque, plaque ulceration, and increased risk associated with specific features. We used Fisher's exact test to compare how often each feature was mentioned. We included a total of 651 reports from unique patients (mean age, 68.1 ± 13.3 years). A total of 639 reports (98.1%) explicitly mentioned degree of stenosis per NASCET criteria. Specific plaque features were less frequently characterized: soft plaque in 116 (17.8%); calcified plaque in 166 (25.5%); quantification of the amount of soft plaque and calcified plaque in 24 (3.7%) and 16 (2.5%) reports, respectively; plaque thickness in 12 (1.8%); plaque ulceration in 476 (73.1%); and increased risk associated with plaque in 2 (0.3%). Degree of stenosis was statistically more likely to be mentioned than any other plaque feature (p < 0.001). Currently, nearly all reports mention the degree of luminal stenosis on neck CTAs while a significant minority mention specific plaque features. Despite mounting evidence of the importance of carotid plaque features in stroke risk assessment, radiology reports do not routinely report these findings.


Association between the number of home injury hazards and home injury.
Although the home is a major setting for injury morbidity and mortality, there are few proven effective interventions for reducing home injury risk. To inform future research or interventions, this study measures associations between home injury hazards and home injury from a sample of New Zealand households. Logistic regression was used to assess the association between injury hazards identified by a building inspection and injuries requiring medical or associated services that occurred to household members prior to the inspection. There was an estimated increase of 22% in the odds of injury occurrence associated with each additional injury hazard found in the home (with 95% CI: 6-41%). This research suggests that addressing injury hazards in the home may be effective in reducing home injury. There are a number of potentially confounding factors that may affect relationships found between the existence of home hazards and injury occurrence. These need to be taken into account when future evaluations are planned.


Periodontal disease and spontaneous preterm birth: a case control study.
Several studies have suggested an association between periodontal disease and prematurity but this finding has not been consistently observed. Case control study. Cases (n = 50) were women who had delivered after spontaneous preterm labor at <35 weeks gestation. Two groups of controls (n = 101) were recruited: women who were undelivered but at a preterm gestation and women who delivered at term. A standard, clinical, periodontal examination was performed and gingival crevicular fluid was obtained from standardized locations and tested for neutrophil elastase along with the bacterial enzymes gingipain and dipeptidylpeptidase. Data were analyzed with Fisher's exact tests, ANOVA and multivariate logistic regression. There was no difference in the proportion of sites with significant attachment loss (> or =3 mm): Cases-3.2%, Controls-2.2% p = 0.21. The gingival crevicular fluid concentrations of elastase and gingipain were elevated in cases vs. controls 238.8 uU/ul vs. 159.6 uU/ul p = .007 and 2.70 uU/ul vs. 1.56 uU/ul p = .001. On multivariate analysis, the mean log concentration of elastase, but not of gingipain, remained a significant predictor of preterm labor p = .0.015. We found no evidence that clinical periodontal disease is associated with spontaneous preterm birth. Elevated gingival crevicular fluid levels of elastase were associated with preterm birth but further research is needed before this can be assumed to be a causal relationship.


R-(-)-gossypol (AT-101) activates programmed cell death in multiple myeloma cells.
Bcl-2 family proteins play a critical role in malignancies by regulating the balance between cell survival and apoptosis. R-(-)-gossypol (AT-101) is a small molecule that mimics the BH3 domain of cellular Bcl-2 inhibitors and interferes with the function of prosurvival Bcl-2 proteins. We examined the cytotoxicity of AT-101 in the context of multiple myeloma, a fatal hematological malignancy. Multiple myeloma cell lines and primary cells obtained from multiple myeloma patients were used to investigate the effects of AT-101. Cell viability, apoptosis, and apoptosis pathways were examined using conventional viability assays, flow cytometry, and immunoblots. AT-101 was not only cytotoxic to conventional multiple myeloma cell lines, but was also effective against drug-resistant cell lines and primary multiple myeloma patient cells. Furthermore, AT-101 decreased proliferation of multiple myeloma cell lines in the presence of marrow stromal cells, indicating that this drug may overcome the protective effect of the microenvironment that is important for multiple myeloma cell proliferation and survival. Apoptosis was activated via the mitochondrial pathway in multiple myeloma cell lines treated with AT-101 as demonstrated by an increased Bax to Bcl-2 ratio, mitochondrial membrane depolarization, and caspase activation. Finally, our studies demonstrated that AT-101 exhibits potent synergy with dexamethasone, a valuable therapeutic for multiple myeloma. These data suggest that the activity of AT-101 may be highly relevant to multiple myeloma disease biology and may represent an option for treatment of patients with this disease.