Heart rate variability following youth concussion: how do autonomic regulation and concussion symptoms differ over time postinjury?
Following youth concussion, objective physiological indicators are needed to corroborate changes in subjective clinical measures. The objectives of the current study were to: (1) explore the effect of concussion on heart rate variability (HRV) across days postinjury in youth athletes aged 13-18 years old, compared with healthy age-matched and sex-matched controls and (2) examine the relationship between postconcussion symptom domains (physical, cognitive, fatigue and emotional) and HRV. Prospective, longitudinal, case-control study (N=44). This study comprised 29 concussed athletes between the ages of 13 and 18 years old (21 females, 8 males) and 15 age-matched and sex-matched controls). All participants completed baseline testing, which included demographic information (age, sex, concussion history), self-reported concussion symptoms (Post-Concussion Symptom Inventory [PCSI]) and a 24-hour heart rate recording via the Polar RS800CX system. The PCSI and HRV were collected weekly while the participant was symptomatic and then 1, 3 and 6 months following symptom resolution. HRV variables included time and frequency domain measures. Data visualisations and mixed effects modelling were used to derive parsimonious models. HRV increased across days postinjury. Concussion symptom domains (physical, cognitive, fatigue and emotional) all had a significant main effect on HRV; concussed participants who reported more symptoms had higher HRV compared with those who reported fewer symptoms. Visualisations of HRV depict the recovery trajectory as non-linear across time. No significant differences on HRV measures were found between concussed and control participants. These preliminary findings provide the foundation to understand the varied trajectory and relationship between objective physiological measures and subjective symptom reporting.


Synergetic SERS Enhancement in a Metal-Like/Metal Double-Shell Structure for Sensitive and Stable Application.
Because of either thermal/chemical instability or high optical loss in noble metal nanostructures, searching for alternative plasmonic materials is becoming more and more urgent, considering the practical biosensing applications under various extreme conditions. In this work, titanium nitride (TiN), a low-loss metal-like material with both excellent thermal and excellent chemical stabilities, was proposed to composite with Ag hollow nanosphere (HNS) nanostructures as an effective surface-enhanced Raman scattering (SERS) substrate to realize both highly sensitive and highly stable molecular detection. Because of the multiple-mode local surface plasmon resonance around the spherical composite nanospheres and the "gap effect" derived from the ultrasmall nanogaps within the precisely controlled plasmonic arrays, an intensively enhanced local field was successfully induced on this SERS substrate. Combined with the unique charge transferring process between Ag and TiN, a synergistically enhanced SERS sensitivity involving both physical and chemical mechanisms was achieved. Especially, with the isolation of TiN, a time-durable Raman detection on these TiN-Ag HNS arrays was accomplished, showing great potential for practical applications.


The Prevalence of Psychiatric Disorders Distribution of Subjects Gender and its Relationship with Psychiatric Help-Seeking.
The aim of this study was to investigate the prevalance of psychiatric disorders and psychiatric help-seeking behaviours in central Eskisehir according to sociodemographic variables. In this study, for the purpose of revealing the psychiatric disorder profile of Eskisehir city and evaluating the prevalance of psychiatric disorders according to gender differences and psychiatric help-seeking behaviours; The Primary Care Evaluation of Mental Disorders (PRIME-MD) scale and psychiatric help questionnaire were administered to 1475 subjects who were randomly selected from 24 primary health care centers in Eskisehir. The prevalence of psychiatric disorders was as follows: at least one mood disorder 37%, anxiety disorders 29%, somatoform disorders - 8.6% and, possible alcohol abuse 7.7%. All diagnoses except possible alcohol abuse were found to be more frequent in women than men. Also It was found that in subjects who were thougth to have a psychiatric disorder, 64% of mood disorder patients, 67% of anxiety disorder patients, 70% of somatoform disorder patients and, 61% of possible alcohol abuse patients can receive appropriate treatment. Since psychiatric disorders are common, it is important to direct such patients to appropriate treatment. Therefore, new studies are necessary to find out the prevalance of psychiatric disorders and risky groups as well as to identify the reasons that why such people do not seek for help in different regions of our country.


[A case of renal malignant lymphoma].
Malignant lymphoma affects any organ of the body, but is rarely found in a urological organ. We found a case of renal malignant lymphoma. A 45-year-old male, who had been operated on for primary hepatic malignant lymphoma 9 months previously, was admitted to our clinic, complaining of high fever. X-ray and ultrasonographic examinations suggested a metastatic tumor in the right kidney. Right nephrectomy was performed, and pathohistological examination revealed primary hepatic malignant lymphoma in the right kidney.


[Vitamin E status in mothers of children with cleft lip].
It had been suspected for many years that mother's periconceptional diet may have a role in the causation of birth defects. Over the past 10 years, many studies have reported that women who used multivitamins periconceptionally had a reduction in risk for offspring with orofacial cleft. This study was aimed to establish vitamin E status in Polish mothers of children with isolated cleft lip. 37 mothers of children with cleft lip (CL) and 67 women who gave birth to healthy children were studied. All participants were healthy women without symptoms of malabsorption. Levels of alpha-tocopherol in plasma and erythrocytes were determined by high-performance liquid chromatography. There was no differences between mean plasma alpha-tocopherol level in mothers of children with birth defect and mothers of healthy children (17.81 +/- 4.81 micromol/l vs 19.44 +/- 5.01 micromol/l; p>0.05). It is believed that the ratio of alpha-tocopherol to total cholesterol is more useful as a measure of vitamin status than the a-tocopherol level alone. In mothers of children with CL plasma alpha-tocopherol to total serum cholesterol ratio was statistically lower compared to those in the control group (3.35 +/- 0.88 micromol/mmol vs 3.89 +/- 0.79 micromol/mmol; p<0.02). Ratio of alpha-tocopherol level in erythrocytes to total serum cholesterol was also lower in mothers of children with CL (0.38 +/- 0.06 micromol/mmol vs 0.48 +/- 0.10 micromol/mmol; p<0.05). Our results suggested that vitamin E may play a role in prevention of orofacial clefts.


Cytomegalovirus disease occurring before engraftment in marrow transplant recipients.
Little information is available regarding the incidence, clinical course, and response to treatment of cytomegalovirus (CMV) disease that occurs before engraftment in marrow transplant recipients. We identified 25 patients over a 12.5 year period who developed CMV disease before achieving engraftment. Twelve cases were diagnosed during life, and 13 cases were diagnosed at autopsy. The lung was the site most commonly involved (92% of patients), and most of the patients (92%) were CMV seropositive. Significant copathogens were identified in 45% of the patients. All nine patients with CMV pneumonia died within 6 weeks after the diagnosis was made, and one of two patients with gastrointestinal disease also died 6 weeks after the diagnosis was made despite the administration of antiviral therapy. Surveillance cultures were not helpful in identifying patients at risk for disease. Histopathological examination of the lungs of patients with early CMV pneumonia only infrequently showed typical CMV lesions. In conclusion, CMV disease occurring before engraftment in CMV-seropositive recipients was uncommon, was frequently associated with the presence of other opportunistic pathogens, and was associated with a high fatality rate. Better diagnostic methods to identify patients at risk are required in the preengraftment period.


Comparison of forced-air and water-circulating warming for prevention of hypothermia during transcatheter aortic valve replacement.
Transcatheter Aortic Valve Replacement (TAVR) procedures at our institution were complicated by perioperative hypothermia despite use of the standard of care forced-air convective warming device (the BairHugger, Augustine Medical Inc, Eden Prairie, MN, USA). To remedy this problem, we initiated a quality improvement process that investigated the use of a conductive warm water-circulating device (the Allon ThermoWrap, Menen Medical Corporation, Trevose, PA, USA), and hypothesized that it would decrease the incidence of perioperative hypothermia. We compared two different intraoperative warming devices using a historic control. We retrospectively reviewed intraoperative records of 80 TAVRs between 6/2013 and 6/2015, 46 and 34 of which were done with the forced-air and water-circulating devices, respectively. Continuous temperature data obtained from pulmonary artery catheter, temperature upon arrival to cardiothoracic ICU (CTU), age, BSA, height, and BMI were compared. Patients warmed with both devices were similar in terms of demographic characteristics. First recorded intraoperative temperature (mean 36.26 ± SD 0.61 vs. 35.95 ± 0.46°C, p = 0.02), lowest intraoperative temperature (36.01 ± 0.58 vs. 34.89 ± 0.76°C, p<0.001), temperature at the end of the procedure (36.47 ± 0.51 vs. 35.17 ± 0.75°C, p<0.001), and temperature upon arrival to the CTU (36.35 ± 0.44 vs. 35.07 ± 0.78°C, p<0.001) were significantly higher in the water-circulating group as compared to the forced-air group. A quality improvement process led to selection of a new warming device that virtually eliminated perioperative hypothermia at our institution. Patients warmed with the new device were significantly less likely to experience intraoperative hypothermia and were significantly more likely to be normothermic upon arrival to the CTU.


Probable Nonconvulsive Status Epilepticus With the Use of High-Dose Continuous Infusion Ceftazidime.
Multidrug resistant (MDR) bacterial infections are a major concern of health care providers due to their increasing incidence and associated mortality. In some cases, few or no antibiotics have preserved activity. Beta-lactam administration via continuous infusion can optimize time over minimum inhibitory concentration (MIC). In some cases, use of high-dose continuous infusion (HDCI) may be necessary to achieve serum levels in excess of nonsusceptible MIC values. The use of HDCI beta-lactams is not without risk, specifically neurotoxic adverse effects, which appear dose related. We describe a 64-year-old male who experienced myoclonus and nonconvulsive status epilepticus while receiving HDCI ceftazidime for treatment of multidrug resistant Pseudomonas aeruginosa bacteremia. This report serves as a cautionary example of the potential toxicities associated with HDCI beta-lactams and supports the importance of risk-benefit analysis prior to and during treatment. Additionally, the use of serum drug level monitoring may be necessary to better prevent or predict toxicity.


Methylene blue facilitates the extinction of fear in an animal model of susceptibility to learned helplessness.
The objectives were to (1) extend previous findings on fear extinction deficits in male congenitally helpless rats (a model for susceptibility to learned helplessness) to female congenitally helpless rats, and (2) attempt a therapeutic intervention with methylene blue, a metabolic enhancer that improves memory retention, to alleviate the predicted extinction deficits. In the first experiment, fear acquisition (four tone-shock pairings in operant chamber) was followed by extinction training (60 tones in open field). Congenitally helpless rats showed fear acquisition similar to controls but had dramatic extinction deficits, and did not display the gradual extinction curves observed in controls. Congenitally helpless rats demonstrated greater tone-evoked freezing as compared to controls in both the acquisition and extinction contexts one week after extinction training, and also in the extinction probe conducted one month later. In the second experiment (which began one month after the first experiment) congenitally helpless subjects were further exposed to tones for 5 days, each followed by 4 mg/kg methylene blue or saline IP, and had a fear renewal test in the acquisition context. Methylene blue administration improved retention of the extinction memory as demonstrated by significant decreases in fear renewal as compared to saline-administered congenitally helpless subjects. The impaired ability to extinguish fear to a traumatic memory in congenitally helpless rats supports the validity of this strain as an animal model for vulnerability to post-traumatic stress disorder, and this study further suggests that methylene blue may facilitate fear extinction as an adjunct to exposure therapy.


Activation of TNF-α/NF-κB axis enhances CRL4BDCAF11 E3 ligase activity and regulates cell cycle progression in human osteosarcoma cells.
Cullin 4B, a member of the Cullins, which serve as scaffolds to facilitate the assembly of E3 ligase complexes, is aberrantly expressed in many cancers, including osteosarcoma. Recently, we observed that CUL4B forms the CRL4BDCAF11 E3 ligase, which specifically ubiquitinates and degrades the cyclin-dependent kinase (CDK) inhibitor p21Cip1 in human osteosarcoma cells. However, the underlying mechanisms regarding the aberrant expression of CUL4B and the upstream members of this signaling pathway are mostly unknown. In this study, we demonstrate that nuclear factor kappaB (NF-κB) is a direct modulator of CUL4B expression. The CUL4B promoter is responsive to several NF-κB subunits, including RelA, RelB, and c-Rel, but not to p50 or p52. Additional studies reveal that the tumor necrosis factor alpha (TNF-α)/NF-κB axis pathway is activated in human osteosarcoma cells. This activation causes both CUL4B and NF-κB subunits to become abundant in the nucleus of human osteosarcoma cells. The down-regulation of individual genes, including TNFR1, RelA, RelB, c-Rel, and CUL4B, or pairs of them, including TNFR1 + RelA, TNFR1 + RelB, TNFR1 + c-Rel, and RelA+CUL4B, has similar effects on cell growth inhibition, colony formation, cell invasion, and in vivo tumor formation, whereas the overexpression of CUL4B in these knockdown cells significantly reverses their phenotypes. The inhibition of the TNF-α/NF-κB pathway greatly attenuates CRL4BDCAF11 E3 ligase activity and causes the accumulation of p21Cip1 , thereby leading to cell cycle arrest at the S phase. Taken together, our results support a model in which the activation of the TNF-α/NF-κB axis contributes to an increase in CRL4BDCAF11 activity and a decrease in p21Cip1 protein levels, thereby controlling cell cycle progression in human osteosarcoma cells.


FDP/fibrinogen ratio reflects the requirement of packed red blood cell transfusion in patients with blunt trauma.
To find factors that predict the requirement of packed red blood cells (pRBC) transfusion in patients with blunt trauma on arrival at the hospital. We conducted blood tests in trauma patients whose trauma severity was suspected as being 3 and over in the Abbreviated Injury Scale. Patients were divided into the blood transfusion (BT) and control groups according to the requirement of pRBC transfusion within 24h after arrival. We analyzed 347 patients (BT group, n=14; control group, n=333). On univariate analysis, there were significant differences in Glasgow Coma Scale (GCS), rate of positive FAST (focused assessment with sonography for trauma) finding, hematocrit, international normalized ratio of prothrombin time, activated partial thromboplastin time, fibrinogen (Fib), and level of fibrin degradation products (FDP). On multivariable analysis, positive FAST finding, GCS, Fib, and FDP influenced the requirement of pRBC transfusion. In the area under the receiver operating characteristic curve analysis, Fib and FDP were markers that predicted the requirement of pRBC transfusion. The FDP/Fib ratio had a better correlation with the requirement of pRBC transfusion than FDP or Fib. The FDP/Fib ratio can be easily measured and may be a predictor of the need for pRBC transfusion.


A systematic approach to diabetic foot infections.
Foot infection is the most common reason for hospitalization and subsequent lower extremity amputation among persons with diabetes. Foot ulceration caused by diabetic neuropathy, trauma, and peripheral vascular disease can lead to a limbor life-threatening infection. The optimum treatment of these potentially devastating conditions depends on a multidisciplinary approach that addresses the related or underlying disorders and thus ensures proper wound healing and a positive outcome. In addition to antibiotic therapy, severe soft-tissue or bone infections may necessitate surgical treatment, including drainage, débridement, and vascular reconstruction. Initial (empiric) antibiotic therapy should provide coverage against staphylococci and streptococci and should be revised according culture results. Antibiotic therapy is not indicated in clinically noninfected wounds. The duration of antibiotic treatment can range from 1 week for mild infections to 6 weeks or more for residual osteomyelitis and severe deep tissue infections. Aggressive (and sometimes repeated or staged) surgical intervention and appropriate antibiotic therapy can reduce the likelihood of a major amputation and the duration of hospitalization.


Reliability and clinical usefulness of psychometric measures in a self-referred population of odontophobics.
Questionnaire responses of 155 self-referred subjects with extreme dental fear were used to evaluate the reliability and clinical usefulness of some psychometric tests used in diagnosis and treatment. The Corah Dental Anxiety Scale (DAS), State-Trait Anxiety Inventory (STAI), and a general Geer Fear Scale (GFS) were filled out by all subjects, while 80 patients with highest dental fear scores were also tested before and after dental fear treatment with the following scales; a Getz Dental Belief Survey (DBS), Dental Fear Survey (DFS), and a Mood Adjective Checklist (MACL). Cronbach's alpha measured internal consistency reliability. SPSS data analyses calculated item-remainder and test-retest correlations. Clinical usefulness of scales was judged by Spearman correlations of initial scores and test score changes after dental fear treatment. All total test scores showed high internal consistency and test-retest reliability. DFS was judged the preferred clinical measure of threatening perceptions of pain or unpleasantness specific to dental procedures. DBS and STAI-State measured confidence in relating with the dentist and situational fear associated with that relationship. GFS, STAI-Trait, and MACL discriminated levels of general fearfulness, anxiety and mood fluctuations that can impact on dental fear.


Toll-like receptors and CD40 modulate each other's expression affecting Leishmania major infection.
Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and results in innate immune system activation that results in elicitation of the adaptive immune response. One crucial modulator of the adaptive immune response is CD40. However, whether these molecules influence each other's expression and functions is not known. Therefore, we examined the effects of TLRs on CD40 expression on macrophages, the host cell for the protozoan parasite Leishmania major. While polyinosinic-polycytidylic acid [poly (I:C)], a TLR-3 ligand, lipopolysaccharide (LPS), a TLR-4 ligand, imiquimod, a TLR-7/8 ligand and cytosine-phosphate-guanosine (CpG), a TLR-9 ligand, were shown to enhance CD40 expression, CD40 stimulation enhanced only TLR-9 expression. Therefore, we tested the synergism between CD40 and CpG in anti-leishmanial immune response. In Leishmania-infected macrophages, CpG was found to reduce CD40-induced extracellular stress-regulated kinase (ERK)1/2 activation; with the exception of interleukin (IL)-10, these ligands had differential effects on CD40-induced IL-1α, IL-6 and IL-12 production. CpG significantly enhanced the anti-leishmanial function of CD40 with differential effects on IL-4, IL-10 and interferon (IFN)-γ production in susceptible BALB/c mice. Thus, we report the first systematic study on CD40-TLR cross-talk that regulated the experimental L. major infection.


An analysis of the etiology of cervical artery dissections: 1994 to 2003.
To provide a literature review of the etiologic breakdown of cervical artery dissections. A literature search of the MEDLINE database was conducted for English-language articles published from 1994 to 2003 using the search terms cervical artery dissection (CAD), vertebral artery dissection, and internal carotid artery dissection. Articles were selected for inclusion only if they incorporated a minimum of 5 case reports of CAD and contained sufficient information to ascertain a plausible etiology. One thousand fourteen citations were identified; 20 met the selection criteria. There were 606 CAD cases reported in these studies; 321 (54%) were internal carotid artery dissection and 253 (46%) were vertebral artery dissection, not including cases with both. Three hundred seventy-one (61%) were classified as spontaneous, 178 (30%) were associated with trauma/trivial trauma, and 53 (9%) were associated with cervical spinal manipulation. If one apparently biased study is dropped from the data pool, the percentage of CADs related to cervical spinal manipulation drops to approximately 6%. The case series that were reviewed in this article indicated that most CADs reported in the previous decade were spontaneous but that some were associated with trauma/trivial trauma, and a minority with cervical spine manipulation. This etiologic breakdown of CAD does not differ significantly from what has been portrayed by most other authors.


Changes in sevoflurane plasma concentration with delivery through the oxygenator during on-pump cardiac surgery.
It is unclear what factors affect the uptake of sevoflurane administered through the membrane oxygenator during cardiopulmonary bypass (CPB) and whether this can be monitored via the oxygenator exhaust gas. Stable delivery of sevoflurane was administered to 30 elective cardiac surgery patients at 1.8 vol% (inspiratory) via the anaesthetic circuit and ventilator. During CPB, sevoflurane was administered in the oxygenator fresh gas supply (Compactflo Evolution™; Sorin Group, Milano, Italy). Sevoflurane plasma concentration (SPC) was measured using gas chromatography. Changes were correlated with bispectral index (BIS), patient temperature, haematocrit, plasma albumin concentration, oxygenator fresh gas flow, and the sevoflurane concentration in the oxygenator exhaust at predefined time points. The mean SPC pre-bypass was 54.9 µg ml(-1) [95% confidence interval (CI): 50.6-59.1]. SPC decreased to 43.2 µg ml(-1) (95% CI: 40.3-46.1; P<0.001) after initiation of CPB, and was lower still during rewarming and weaning from bypass, 39.4 µg ml(-1) (95% CI: 36.6-42.3; P<0.001). BIS did not exceed a value of 55. SPCs were higher during hypothermia (P<0.001) and with an increase in oxygenator fresh gas flow (P=0.015), and lower with haemodilution (P=0.027). No correlation was found between SPC and the concentration of sevoflurane in the oxygenator exhaust gas (r=-0.04; 95% CI: -0.18 to 0.09; P=0.53). The uptake of sevoflurane delivered via the membrane oxygenator during CPB seems to be affected by hypothermia, haemodilution, and changes in the oxygenator fresh gas supply flow. Measuring the concentration of sevoflurane in the exhaust from the oxygenator is not useful for monitoring sevoflurane administration during bypass.


An Investigation into a Gear-Based Knee Joint Designed for Lower Limb Prosthesis.
A gear-based knee joint is designed to improve the performance of mechanical-type above-knee prostheses. The gear set with the help of some bracing, and bracket arrangement, is used to enable the prosthesis to follow the residual limb movement. The motion analysis and finite-element analysis (FEA) of knee joint components are carried out to assess the feasibility of the design. The maximum stress of 29.74 MPa and maximum strain of 2.393e-004 are obtained in the gear, whereas the maximum displacement of 7.975 mm occurred in the stopper of the knee arrangement. The factor of safety of 3.5 obtained from the FE analysis indicated no possibility of design failure. The results obtained from the FE analysis are then compared with the real data obtained from the literature for a similar subject. The pattern of motion analysis results has shown a great resemblance with the gait cycle of a healthy biological limb.


[Axillary hyperhidrosis: successful treatment with botulinum toxin A].
Severe hyperhidrosis may present as a vexing condition for the patient and a therapeutic challenge for the physician. As botulinum toxin-A (BT-A) can potently block cholinergic sympathic innervation of sweat glands it was used in an open trial for controlling severe axillary hyperhidrosis. After visualization of hyperhidrosis using the iodine-starch-test BT-A (Dysport, 400 Units) was injected intradermally in one axilla. One week later gravimetric quantification of sweat secretion revealed a reduction of sweating to 4-9% of initial values. In order to rule out daily variations as well as other factors interfering with sweat production BT-A treatment was restricted to only one axilla in each individual clearly demonstrating extensive anhidrotic efficacy on the treated side only. The treatment was well tolerated without side-effects and was assessed as 'completely satisfying' by all patients. BT-A may offer a fast, safe and highly effective therapeutic option for severe hyperhidrosis.


Detecting Coherent Groups in Crowd Scenes by Multiview Clustering.
Detecting coherent groups is fundamentally important for crowd behavior analysis. In the past few decades, plenty of works have been conducted on this topic, but most of them have limitations due to the insufficient utilization of crowd properties and the arbitrary processing of individuals. In this study, a Multiview-based Parameter Free framework (MPF) is proposed. Based on the L1-norm and L2-norm, we design two versions of the multiview clustering method, which is the main part of the proposed framework. This paper presents the contributions on three aspects: (1) a new structural context descriptor is designed to characterize the structural properties of individuals in crowd scenes; (2) a self-weighted multiview clustering method is proposed to cluster feature points by incorporating their orientation and context similarities; and (3) a novel framework is introduced for group detection, which is able to determine the group number automatically without any parameter or threshold to be tuned. The effectiveness of the proposed framework is evaluated on real-world crowd videos, and the experimental results show its promising performance on group detection. In addition, the proposed multiview clustering method is also evaluated on a synthetic dataset and several standard benchmarks, and its superiority over the state-of-the-art competitors is demonstrated.


Single-Cell RNA-Seq Reveals the Promoting Role of Ferroptosis Tendency During Lung Adenocarcinoma EMT Progression.
Epithelial-mesenchymal transition (EMT) and ferroptosis are two important processes in biology. In tumor cells, they are intimately linked. We used single-cell RNA sequencing to investigate the regulatory connection between EMT and ferroptosis tendency in LUAD epithelial cells. We used Seurat to construct the expression matrix using the GEO dataset GSE131907 and extract epithelial cells. We found a positive correlation between the trends of EMT and ferroptosis tendency. Then we used SCENIC to analyze differentially activated transcription factors and constructed a molecular regulatory directed network by causal inference. Some ferroptosis markers (GPX4, SCP2, CAV1) were found to have strong regulatory effects on EMT. Cell communication networks were constructed by iTALK and implied that Ferro_High_EMT_High cells have a higher expression of SDC1, SDC4, and activation of LGALS9-HARVCR2 pathways. By deconvolution of bulk sequencing, the results of CIBERSORTx showed that the co-occurrence of ferroptosis tendency and EMT may lead to tumor metastasis and non-response to immunotherapy. Our findings showed there is a strong correlation between ferroptosis tendency and EMT. Ferroptosis may have a promotive effect on EMT. High propensities of ferroptosis and EMT may lead to poor prognosis and non-response to immunotherapy.


Cervical ectopic pregnancy after in vitro fertilization: case report successfully treated with cervical electric aspiration.
Cervical ectopic gestation is a serious and potentially lethal condition considered exceptional in in vitro fertilization. Early diagnosis is critical to successful treatment and preservation of fertility. We report a rare case of cervical pregnancy after in vitro fertilization and embryo transfer, successfully treated exclusively with electrical aspiration. Case report: A 36-year-old patient attended the Department of Human Reproduction at Pérola Byington Hospital in 2015 due to primary infertility with no apparent cause for seven years. Subjected to ovulation induction with recombinant depot FSH and GnRh analogue, triggered with chorionic gonadotropin. It evolved with the collection of ten oocytes and transfer of two embryos, with cryopreservation of the remaining ones. The control with serial ultrasound showed a gestational sac in uterine cervix topography, indicating gestation of six weeks, confirmed after 24 hours by a second operator. The treatment was successfully performed by electric aspiration with an EasyGrip® cannula of 6 mm in diameter, without the occurrence of hemorrhage or the need for other procedures. Early diagnosis allowed successful conservative treatment with only cervical aspiration. The literature review confirms the rarity of the case, but does not indicate consensus on the best treatment of cervical ectopic pregnancy.


Assessing avian leukosis virus proviral load and lesion correlates in fowl glioma-inducing virus-infected Japanese bantam chickens.
The fowl glioma-inducing virus prototype (FGVp) and its variants, which belong to avian leukosis virus subgroup A (ALV-A), induce cardiomyocyte abnormalities and gliomas in chickens. However, the molecular mechanisms underlying these myocardial changes remain unclear, and ALV-induced tumorigenesis, which is caused by proviral insertional mutagenesis, does not explain the early development of cardiac changes in infected chickens. We established a quantitative PCR (qPCR) assay to measure ALV-A proviral loads in the brains and hearts of FGV-infected Japanese bantam chickens and compared these results with morphologic lesions. Four of 22 bantams had both gliomas and cardiac lesions. Hearts with cardiac lesions had a higher proviral load (10.3 ± 2.7 proviral copies/nucleus) than those without cardiac lesions (0.4 ± 0.4), suggesting that the proviral load in hearts is correlated with the frequency of myocardial changes. Our qPCR method may be useful in the study of ALV-induced cardiomyocyte abnormalities.


Synthesis of Novel Baicalein Amino Acid Derivatives and Biological Evaluation as Neuroprotective Agents.
Baicalein, a famously effective component of the traditional Chinese medicine Rhizoma Huang Qin (Scutellaria altissima L.), has been proved to have potent neuroprotection and anti-platelet aggregation effects with few side effects. Meanwhile, recent studies have revealed that the introduction of amino acid to baicalein could improve its neuroprotective activity. In the present study, a series of novel baicalein amino acid derivatives were designed, synthesized, and screened for their neuroprotective effect against tert-butyl, hydroperoxide-induced, SH-SY5Y neurotoxicity cells and toxicity on the normal H9C2 cell line by standard methylthiazol tetrazolium (MTT) assay. In addition, all of the newly synthesized compounds were characterized by 1H-NMR, 13C-NMR, and high resolution mass spectrometry (HR-MS). The results showed that most of the compounds provided more potent neuroprotection than baicalein, and were equivalent to the positive drug edaravin. They showed no obvious cytotoxicity on normal H9C2 cells. Notably, the most active compound 8 displayed the highest protective effect (50% effective concentration (EC50) = 4.31 μM) against tert-butyl, hydroperoxide-induced, SH-SY5Y neurotoxicity cells, which was much better than the baicalein (EC50 = 24.77 μM) and edaravin (EC50 = 5.62 μM). Further research on the chick chorioallantoic membrane (CAM) model indicated that compound 8 could significantly increase angiogenesis, which might promote neurovascular proliferation. The detection of apoptosis analysis showed that compound 8 could dramatically alleviate morphological manifestations of cell damage. Moreover, the benzyloxycarbonyl (cbz)-protected baicalein amino acid derivatives showed better neuroprotective activity than the t-Butyloxy carbonyl (boc)-protected derivatives.


Descriptive analysis and spatial epidemiology of porcine reproductive and respiratory syndrome (PRRS) for swine sites participating in area regional control and elimination programs from 3 regions of Ontario.
The objectives of this study were to describe demographics, basic biosecurity practices, ownership structure, and prevalence of porcine reproductive and respiratory syndrome (PRRS) in swine sites located in 3 regions in Ontario, and investigate the presence of spatial clustering and clusters of PRRS positive sites in the 3 regions. A total of 370 swine sites were enrolled in Area Regional Control and Elimination projects in Niagara, Watford, and Perth from 2010 to 2013. Demographics, biosecurity, and site ownership data were collected using a standardized questionnaire and site locations were obtained from an industry organization. Status was assigned on the basis of available diagnostic tests and/or assessment by site veterinarians. Spatial dependence was investigated using the D-function, the spatial scan statistic test and the spatial relative risk method. Results showed that the use of strict all-in all-out (AIAO) pig flow and shower before entry are uncommon biosecurity practices in swine sites, but a larger proportion of sites reported having a Danish entry. The prevalence of PRRS in the 3 regions ranged from 17% to 48% and localized high and low risk clusters were detected. Sites enrolled in the PRRS control projects were characterized by membership in multiple and overlapping ownership structures and networks, which complicates the way the results of monitoring and disease management measures are communicated to the target population.


Note: A dual-channel sensor for dew point measurement based on quartz crystal microbalance.
A new sensor with dual-channel was designed for eliminating the temperature effect on the frequency measurement of the quartz crystal microbalance (QCM) in dew point detection. The sensor uses active temperature control, produces condensation on the surface of QCM, and then detects the dew point. Both the single-channel and the dual-channel methods were conducted based on the device. The measurement error of the single-channel method was less than 0.5 °C at the dew point range of -2 °C-10 °C while the dual-channel was 0.3 °C. The results showed that the dual-channel method was able to eliminate the temperature effect and yield better measurement accuracy.


Multiple Hydrogen-Bonding Catalysts Enhance the Asymmetric Cyanation of Ketimines and Aldimines.
A highly enantioselective cyanation of imines (up to >99 % ee) has been developed using well-designed C2 -symmetric hydrogen bonding catalysts. The catalytic strategy was characterized with low catalyst loading (0.1-1 mol %), easily accessible catalysts with diverse functional groups, and catalytic base additives. A wide range of imines, including the challenging N-Boc and N-Cbz protected ketimines and aldimines, as well as fluoroalkylated ketimines, were investigated under mild conditions to afford the products with good to excellent yields (up to 99 % yield) and high enantioselectivity (up to >99 % ee). Control experiments revealed that the multiple hydrogen bonding catalysts enhanced the reactivity and enantioselectivity of the Strecker reaction initiated by the base.


Preparation and characterization of monoclonal antibodies specific for human transforming growth factor alpha.
A series of monoclonal antibodies (mAbs) against transforming growth factor alpha (TGF alpha) have been produced. The generation of these reagents, as well as their biochemical and immunochemical characterization is described. TGF alpha peptides, mutant recombinant TGF alpha proteins and two-site immunoradiometric assays were used to identify the epitopes recognized by each antibody. This approach has allowed the specific localization of immunodominant domains on the molecule. Certain mAbs were found to be useful for selected procedures. mAb 134A-2B3 was used for immunoblotting both the precursor and mature forms of TGF alpha from conditioned media of tumor cells. One mAb 189-2130.1, which reacted with the carboxyl terminal seventeen amino acids, was able to block TGF alpha binding to the EGF receptor. mAb 213-4.4 was used for immunohistochemical detection of TGF alpha in fixed tumor cells. mAbs 137-178 and 134A-2B3 were used to develop a two-site immunoradiometric immunoassay which was sensitive to 1 ng ml-1 and detected TGF alpha from a variety of tumor cells. A series of mAbs such as these could prove useful in studying the biochemical properties as well as the immunochemical localization of TGF alpha in normal tissues and tumors.


Distinct Aeromonas Populations in Water Column and Associated with Copepods from Estuarine Environment (Seine, France).
Aeromonas spp. are ubiquitous bacteria primarily recovered from aquatic ecosystems. They are found in fresh water as well as estuarine and marine waters, and in association with numerous autochthonous aquatic organisms in these environments. However, aeromonads are also etiologic agents of fish diseases and are now recognized as emerging pathogens in humans. The estuary is therefore a key environment, harboring autochthonous aeromonads, and aeromonads originating from humans and animals, mainly released by treated WWTP effluent or watershed run-off via tributaries. The present study compares the abundance and the diversity of Aeromonas populations. Over 2 years of monitoring (eight campaigns from February 2013 to November 2015), the occurrence of Aeromonas was investigated within the water column (water and fluid mud) and in association with copepods. Moreover, the diversity of Aeromonas populations was ascertained by analyzing gyrB and radA sequences, and the antibiotic-resistance phenotypes were determined using the disk diffusion method. This study shows, for the first time, the presence of Aeromonas spp. in water (1.1 × 102 to 1.2 ± 0.3 × 103 CFU.100 mL-1), fluid mud (2.6 ± 2.6 × 102 to 9.8 ± 0.9 × 103 CFU.g-1) and in association with living copepods (1.9 ± 0.7 × 102 to >1.1 × 104 CFU.g-1) in the Seine estuary. Moreover, the diversity study, conducted on 36 strains isolated from the water column and 47 strains isolated from copepods, indicates distinct populations within these two compartments. Strains distributed in five clusters corresponding to A. bestiarum (n = 6; 5.45%), A. encheleia (n = 1; 0.91%), A. media (n = 22; 20.0%), A. rivipollensis (n = 34; 30.91%) and A. salmonicida (n = 47; 42.73%). A. salmonicida is the most abundant species associated with Eurytemora affinis (n = 35; 74.47%). In contrast, A. salmonicida accounts for only 30.56% (n = 11) of isolates in the water column. This study shows the coexistence of distinct populations of Aeromonas in the oligohaline area of an anthropized estuary. Moreover, A. media, a putative human pathogen, present in the water column and abundant in the WWTP samples, was not detected in association with living copepods.


Anthocyanin identification and composition of wild Vitis spp. accessions by using LC-MS and LC-NMR.
The composition and concentration of anthocyanins of grape berry skins were analyzed in order to assess phenotypic variation between four grape wine varieties belonging to 4 different species: Vitis vinifera, Vitis amurensis, Vitis cinerea and Vitis X champinii. High-performance liquid chromatography coupled to mass spectrometry (LC-MS) and NMR spectroscopy (LC-NMR) were used to separate and identify the structure of anthocyanins present in these species. Combination of LC-MS and LC-NMR data resulted in the identification of 33 anthocyanins. In particular, newly reported cis isomers of p-coumaric-derivatives were identified (petunidin-, peonidin- and malvidin-3-(6-p-coumaroyl)-5-diglucoside). In V. cinerea and V. vinifera, anthocyanins were monoglucoside derivatives whereas in V. amurensis and V. X champinii, both mono- and diglucoside derivatives were identified. Malvidin-, delphinidin- and petunidin-derivatives were, respectively, the most abundant components in V. cinerea and V. vinifera, V. amurensis and V. X champinii.


Operationalizing a frailty index using routine blood and urine tests.
Uncomplicated frailty instruments are desirable for use in a busy clinical setting. The aim of this study was to operationalize a frailty index (FI) from routine blood and urine tests, and to evaluate the properties of this FI compared to other frailty instruments. We conducted a secondary analysis of a prospective cohort study on 306 patients aged ≥65 years hospitalized on geriatric wards. An FI comprising 22 routine blood parameters and one standard urine parameter (FI-Lab), a 50-item FI based on a comprehensive geriatric assessment (FI-CGA), a combined FI (FI-combined [items from the FI-Lab + others from the FI-CGA]), the Clinical Frailty Scale, rule-based frailty definition, and frailty phenotype were operationalized from data obtained during patients' hospital stays (ie, before discharge [baseline examination]). Follow-up data were obtained up to 1 year after the baseline examination. The mean FI-Lab score was 0.34±15, with an upper limit of 0.74. The FI-Lab was correlated with all the other frailty instruments (all P<0.001). The FI-Lab revealed an area under the receiver-operating characteristic curve (AUC) for 6-month and 1-year mortality of 0.765 (0.694-0.836) and 0.769 (0.706-0.833), respectively (all P<0.001). Each 0.01 increment in FI-Lab increased the risk (adjusted for age and sex) for 6-month and 1-year mortality by 7.2% and 7.1%, respectively (all adjusted P<0.001). When any of the other FIs (except the FI-combined) were also included in the models, each 0.01 increment in FI-Lab score was associated with an increase in the risk of 6-month and 1-year mortality by 4.1%-5.4% (all adjusted P<0.001). The FI-Lab showed key characteristics of an FI. The FI-Lab can be applied as a single frailty measure or in combination with/in addition to other frailty instruments.


A Novel Scoring System Approach to Assess Patients with Lyme Disease (Nutech Functional Score).
A bacterial infection by Borrelia burgdorferi referred to as Lyme disease (LD) or borreliosis is transmitted mostly by a bite of the tick Ixodes scapularis in the USA and Ixodes ricinus in Europe. Various tests are used for the diagnosis of LD, but their results are often unreliable. We compiled a list of clinically visible and patient-reported symptoms that are associated with LD. Based on this list, we developed a novel scoring system. Nutech functional Score (NFS), which is a 43 point positional (every symptom is subgraded and each alternative gets some points according to its position) and directional (moves in direction bad to good) scoring system that assesses the patient's condition. The grades of the scoring system have been converted into numeric values for conducting probability based studies. Each symptom is graded from 1 to 5 that runs in direction BAD → GOOD. NFS is a unique tool that can be used universally to assess the condition of patients with LD.


Semilobar holoprosencephaly seen with diffusion tensor imaging and fiber tracking.
A neonate with semilobar holoprosencephaly was studied with diffusion tensor imaging and fiber tracking. Fiber tracking showed that the frontooccipital fasciculi were in continuity across the ventral midline, interposed between fused caudate and dysplastic fornices. Tractography of the posterior limbs of the internal capsules showed fibers arching ventrally toward the expected location of the motor cortex; some fibers also coursed dorsally, presumably to the sensory cortex. There was a posterior commissural white matter bundle representing a callosal splenium. Diffusion tensor imaging and fiber tracking revealed white matter structures not apparent on routine imaging sequences, which are in agreement with pathologic descriptions of the holoprosencephalic brain.


Spinal subdural hematoma.
The authors report a case of subacute spinal subdural hematoma in a patient with ankylosing spondylitis. Only 18 such cases have been reported in the nonradiological literature. Early diagnosis is imperative in order to minimize neurological sequelae.


Histogram and Fourier analysis of electrocardiographic data. Possible interpretations.
Small changes of normal electrocardiographic lines are simulated and analysed by programs of Fourier analysis and histograms. The importance of these methods for a diagnosis of the disease evolution in the case of apparently masked cardiographic changes is discussed.


Impaired coordination of nutrient intake and substrate oxidation in melanocortin-4 receptor knockout mice.
Mutations in the melanocortin-4 receptor (MC4R) are associated with obesity. The obesity syndrome observed in humans with MC4R haploinsufficiency is similar to that observed in MC4R knockout mice, including increased longitudinal growth, hyperphagia, and fasting hyperinsulinemia. For comparison with other commonly investigated models of obesity and insulin resistance, we have backcrossed Mc4r-/- mice into the C57BL/6J (B6) background. Female obese Mc4r-/- mice exhibit reduced energy expenditure and an attenuated increase in fatty acid (FA) oxidation after exposure to high-fat diets compared with obese Lepob/Lepob mice. The reduced energy expenditure and FA oxidation correlates with changes in hepatic gene expression. The expression of genes involved in FA oxidation increased in obese Lepob/Lepob mice compared with wild-type and obese Mc4r-/- mice. In contrast, a key lipogenic enzyme, FA synthase (FAS), is increased in obese Mc4r-/- mice compared with obese Lepob/Lepob mice. Hyperinsulinemia, increased FAS mRNA expression and hepatic steatosis appear to be secondary to obesity in B6 Mc4r-/- mice. However, Mc4r-/- mice in a mixed genetic background develop severe hepatic steatosis at an early age. This might suggest an important role of the MC4R in regulating liver FA metabolism that is masked on the B6 background. Interestingly, the 10- to 20-fold increase in liver triglyceride in the outbred strain of Mc4r-/- mice is not always associated with fasting hyperinsulinemia or increased FAS mRNA expression. This observation suggests that changes in liver secondary to triglyceride accumulation lead to hyperinsulinemia and increased hepatic FAS expression in Mc4r-/- mice.


Laparoscopic splenectomy for non-traumatic diseases.
At present, laparoscopic splenectomy (LS) is mostly indicated in hematologic benign diseases, and in case of normal size spleen it is considered the gold standard. The technique is under a continuous evolution and several studies have demonstrated feasibility and safety of laparoscopic approach also in case of massive splenomegaly, malignant diseases and even in the treatment of selected cases traumatic lesions. LS is an advanced surgical procedure that requires a management of a full trained team involved in the preoperative preparation, surgical strategy and postoperative care. A fully comprehension of the impact of the surgical strategy is needed to plan the treatment of diseases that often are managed in a multidisciplinary setting. Indications and contraindications to surgery does not differ significantly from open traditional splenectomy, but the nature of the disease and the volume of the spleen can greatly influence the operation. A preoperative study with definition of these parameters along with a standard preparation to surgery is required. Over the years the technique has been developed and adapted to respond to emergent necessities related to those parameters. Anterior, semilateral, later and hand assisted approaches offer advantages and drawbacks that should be weighed in each case. They depend on surgeons preferences but most of the time are related to the preoperative studies, even when new surgical tools (i.e. harmonic scalpel and radiofrequency). No randomized, prospective trials have been conducted, however several studies with strong evidence have shown that less surgical trauma, intraoperative blood loss, early hospital discharge, rapid return to normal activities and better cosmesis can be obtained with a laparoscopic approach.


Nanoparticle patterning for biomedicine.
Nanoparticles are being used for construction of complex and higher-order functional structures and metamaterials with applications in nanophotonics, information storage and biomedicine, to name a few. These innovations are briefly discussed within the context of future diagnostic and nanomedicine platform technologies and their possible self-assembly in vivo.


Hybrid bioartificial liver support in cynomolgus monkeys with D-galactosamine-induced acute liver failure.
To evaluate a hybrid bioartificial liver support system (HBALSS) in cynomolgus monkeys with acute liver failure. To establish a model of acute liver failure, 0.3 g/kg of D-galactosamine was injected intravenously into cynomolgus monkeys. Chinese human liver cells were introduced into a perfusion bioreactor to carry out hybrid bioartificial liver support treatment. Forty-eight hours after the injection, one group of cynomolgus monkeys received HBALSS care, and a second experimental group received no treatment. Clinical manifestations of all animals, survival time, liver and kidney functions and serum biochemistry changes were recorded. Simultaneous detection of the number, viability and function of hepatocytes in the hybrid bioartificial liver were also performed. Forty-eight hours after the injection of D-galactosamine, serum biochemistry levels were significantly increased, whereas albumin levels and the Fischer index were significantly reduced compared to baseline (all Ps < 0.05). Of the ten monkeys in the HBALSS treatment group, five survived, with an average duration of survival of 128 ± 3 h. All cynomolgus monkeys in the control group died, with a duration of survival of 112 ± 2 h. Survival time was significantly longer with HBALSS treatment (P < 0.05). Moreover, the number, viability and function of hepatocytes were maintained at a high level with HBALSS. The novel hybrid bioartificial liver plays a significant role in liver support by significantly reducing serum biochemistry levels and extending animal survival time.


Analysis using national databases reveals a positive association between dietary polyunsaturated fatty acids with TV watching and diabetes in European females.
In recent years, dietary polyunsaturated fatty acids (PUFA) have increased in parallel to sedentary behavior and diabetes across the world. To test any putative association between dietary PUFA and sedentary behavior or diabetes in females, we obtained country-specific, cross-sectional data on sedentary activity and diabetes prevalence from European Cardiovascular Statistics 2012. Age and gender-specific, nutritional data from each country were obtained from nutritional surveys as well. Socioeconomic (GDP), physical environment (urbanization index) and climatic confounders were accounted for each country. Upon analysis, we found a strong, positive association between sedentary lifestyle in 11-yr old girls (> = 2 hours of TV/ weekday) and dietary PUFA across 21 European countries. Further, a weak association of dietary PUFA and a strong relationship of per-capita GDP was established with elevated fasting blood glucose [(> = 7.0 mmol/L; or on medication] among 25+ year old adult females across 23 countries in Europe. In summary, we present novel ecological evidence that dietary PUFA is strongly associated with sedentary behavior among pre-teen girls and weakly associated with diabetes among adult women across Europe. In the latter group, per-capita GDP was a significant predictor for diabetes as well. Therefore, we recommend that prospective randomized controlled trials (RCTs) be implemented to evaluate if ubiquitous presence of dietary PUFA and low socioeconomic status are possible confounders when intervening to treat/prevent sedentary lifestyle or diabetes in female subjects in Western nations.


A novel diffusion cell model for the in vitro assessment of transcutaneous breast cancer therapeutics: effect of permeants on MCF-7 cells cultured within the receptor compartment.
A novel model is described for investigating the potential efficacy of topically delivered anti-breast cancer agents. Using all-glass Franz diffusion cells, the permeation of 4-hydroxytamoxifen, two EGFR inhibitors (PD98059 and LY294002) and eicosapentaenoic acid (EPA) were determined from a fish oil vehicle across Cyclopore track etched membrane (CTEM) alone, full-thickness porcine ear skin alone and CTEM plus full-thickness porcine ear skin. Finally, the effect of the simultaneous permeation of these compounds was determined on the breast cancer cell line, MCF-7, cultured directly into the diffusion cell receptor compartments. The CTEM was found to be not rate limiting, and all compounds permeated the skin, with a large excess of EPA. The applied combined dose reduced the growth of MCF-7 cells by 66% after 7days. The following conclusions were obtained: (1) MCF-7 breast cancer cells can be successfully cultured within glass Franz diffusion cells. (2) A composite diffusion cell/cell culture model can indicate the potential efficacy of topically delivered anti-breast cancer therapeutic agents. (3) The levels of LY294002, PD98059, 4-hydroxytamoxifen and EPA delivered across full-thickness skin have a major inhibitory effect on the growth of MCF-7 breast cancer cells.


Clinical Implications of Oscillatory Lung Function during Methacholine Bronchoprovocation Testing of Preschool Children.
To investigate the repeatability and safety of measuring impulse oscillation system (IOS) parameters and the point of wheezing during bronchoprovocation testing of preschool children. Two sets of methacholine challenge were conducted in 36 asthma children. The test was discontinued if there was a significant change in reactance (Xrs5) and resistance (Rrs5) at 5 Hz (Condition 1) or respiratory distress due to airway obstruction (Condition 2). The repeatability of PC80_Xrs5, PC30_Rrs5, and wheezing (PCw) was assessed. The changes in Z-scores and SD-indexes from prebaseline (before testing) to postbaseline (after bronchodilator) were determined. For PC30_Rrs5, PC80_Xrs5, and PCw for subjects, PC80_Xrs5 showed the highest repeatability. Fifteen of 70 tests met Condition 2. The changes from pre- and postbaseline values varied significantly for Rrs5 and Xrs5. Excluding subjects with Z-scores higher than 2SD, we were able to detect 97.1% of bronchial hyperresponsiveness during methacholine challenge based on the change in Rrs5 or Xrs5. A change in IOS parameters was associated with wheezing at all frequencies. Xrs5 and Rrs5 have repeatability comparable with FEV1, and Xrs5 is more reliable than Rrs5. Clinicians can safely perform a challenge test by measuring the changes in Rrs5, Xrs5, and Z-scores from the prebaseline values.


In Obese Patients With Type 2 Diabetes, Mast Cells in Omental Adipose Tissue Decrease the Surface Expression of CD45, CD117, CD203c, and FcϵRI.
The paradigm of mast cells in type 2 diabetes is changing. Although they were first considered deleterious inflammatory cells, now they seem to be important players driving adipose tissue homeostasis. Here we have employed a flow cytometry-based approach for measuring the surface expression of 4 proteins (CD45, CD117, CD203c, and FcϵRI) on mast cells of omental (o-WAT) and subcutaneous white adipose tissue (s-WAT) in a cohort of 96 patients with morbid obesity. The cohort was split into three groups: non-T2D, pre-T2D, and T2D. Noteworthy, patients with T2D have a mild condition (HbA1c <7%). In o-WAT, mast cells of patients with T2D have a decrease in the surface expression of CD45 (p=0.0013), CD117 (p=0.0066), CD203c (p=0.0025), and FcϵRI (p=0.043). Besides, in s-WAT, the decrease was seen only in CD117 (p=0.046). These results indicate that T2D affects more to mast cells in o-WAT than in s-WAT. The decrease in these four proteins has serious effects on mast cell function. CD117 is critical for mast cell survival, while CD45 and FcϵRI are important for mast cell activation. Additionally, CD203c is only present on the cell surface after granule release. Taking together these observations, we suggest that mast cells in o-WAT of patients with T2D have a decreased survival, activation capacity, and secretory function.


Biomarkers--the new frontier in the pathology of invasive and preinvasive neoplasias.
The papers in this symposium were presented at the 1996 Annual Meeting of the Biological Stain Commission. The authors hope that the discussion of biomarkers in the papers included in this issue and the literature reviewed in them will be useful to diagnostic pathologists as well as to investigators studying neoplastic processes in general.


Functional recovery of the parathyroid glands after surgery for primary hyperparathyroidism.
The immediate postoperative function of the parathyroid glands after surgery for primary hyperparathyroidism (pHPT) has not been established. We therefore examined the influences of hypercalcemia and hypocalcemia on serum parathyroid hormone (PTH) levels in the immediate postoperative period in patients with pHPT. Ethylenediaminetetraacetic acid was infused in patients on the first (n = 5) and fourth (n = 6) postoperative days, and in patients at 1 year after surgery (n = 6), and in healthy subjects (n = 7). Calcium was given orally before operation and on the second and fifth postoperative days in six patients and in seven healthy subjects. The increased set point seen in pHPT was normalized on the first postoperative day, and the decreased PTH suppressibility by calcium was normal on the second postoperative day. However, on the fifth postoperative day an increased suppressibility of PTH was evident. During the ethylenediaminetetraacetic acid infusion test the secretory reserve for PTH increased after operation with increasing hypocalcemia-induced levels of intact PTH between the first and fourth postoperative days (p < 0.001), and between the fourth postoperative day and the test at 1 year (p < 0.05). In the immediate postoperative period after surgery for pHPT, baseline serum levels of PTH are rapidly normalized; this is followed by an increase in the secretory reserve for PTH secretion and the development of an increased sensitivity to calcium.


Comparison of Ethanedinitrile (C2N2) and Metam Sodium for Control of Bursaphelenchus xylophilus (Nematoda: Aphelenchidae) and Monochamus alternatus (Coleoptera: Cerambycidae) in Naturally Infested Logs at Low Temperatures.
The Bursaphelenchus xylophilus, commonly known as pinewood nematode in Japan, is a quarantine pest and is most often associated with beetles of the genus Monochamus, the pine sawyers, particularly Monochamus alternatus. Long-distance dispersal of the nematode and its vectors led to widespread losses in pine forests. Two fumigation trials were conducted for treatment of logs naturally infested with both M. alternatus and B. xylophilus. The logs were treated with ethanedinitrile or metam sodium at low temperature (-7-25.7°C and -3.7-23.1°C) for 3-d exposure in winter and early spring. Fumigation with ethanedinitrile at concentrations of 48, 68, 97 and 158 g/m(3) resulted in 34.6-58.3, 91.5-97.2, 100, and 100% mortality for M. alternatus and 88.4, 77.9, 96.4, and 98.0% mortality for B. xylophilus, respectively. With Metam sodium fumigation at a dose rate of 1162 g/m(3), 100% M. alternatus and 97.4% B. xylophilus were killed. These results suggest that 97 g/m(3) of ethanedinitrile is adequate for complete control of M. alternatus in pine wood and >158 g/m(3) is required for eradication of B. xylophilus at low temperature fumigation. These results suggest that 97 g/m(3) of ethanedinitrile offers complete control of M. alternatus in pine wood and control of >98% B. xylophilus in winter or spring fumigation at a dosage rate of 158 g/m(3). Therefore, ethanedinitrile has great potential for treatment of fresh pine wooden logs to manage the nematodes and the vector insects at low temperature.


An evaluation of different saliva collection methods for detection of antibodies against hepatitis C virus (anti-HCV).
Saliva samples can be used as an alternative fluid for against hepatitis C virus (anti-HCV) detection owing to the ease of collection and excellent acceptability. This study was conducted to optimize a commercial enzyme immunoassay (EIA) to detect anti-HCV in saliva samples. Ninety-six individuals donated paired serum and saliva samples that were obtained, using a commercial device (Salivette) and spitting into a sterile container. Initially, elution buffer for the Salivette samples, sample volume, incubation time and temperature, and two different anti-HCV EIAs were evaluated. Using the optimized assay, three methods for cut-off calculation were also evaluated. A 20-fold increase in the sample volume for both collection methods was needed. Moreover, the Radim assay was the most appropriate assay for anti-HCV detection in saliva samples, and the quality parameters were increased when a ROC curve was used to determine the cut-off value. Using this optimized assay, the sensitivities, specificities, accuracies, positive and negative predictive values were above 90% for saliva obtained using both the Salivette and spitting methods. Using this assay, discordant false-negative results were obtained for only two Salivette samples and five spitting samples. The concordance kappa was 93% for the Salivette method and 86.1% for the spitting method, demonstrating excellent performance. Saliva samples obtained for both methods can be employed for anti-HCV detection among HCV-infected or HCV-suspected cases, but several modifications must be performed on commercial EIAs to obtain good results. Moreover, samples obtained with commercial devices are more appropriate for anti-HCV detection in saliva samples.


Asbestos-induced peribronchiolar cell proliferation and cytokine production are attenuated in lungs of protein kinase C-delta knockout mice.
The signaling pathways leading to the development of asbestos-associated diseases are poorly understood. Here we used normal and protein kinase C (PKC)-delta knockout (PKCdelta-/-) mice to demonstrate multiple roles of PKC-delta in the development of cell proliferation and inflammation after inhalation of chrysotile asbestos. At 3 days, asbestos-induced peribronchiolar cell proliferation in wild-type mice was attenuated in PKCdelta-/- mice. Cytokine profiles in bronchoalveolar lavage fluids showed increases in interleukin (IL)-1beta, IL-4, IL-6, and IL-13 that were decreased in PKCdelta-/- mice. At 9 days, microarray and quantitative reverse transcriptase-polymerase chain reaction analysis of lung tissues revealed increased mRNA levels of the profibrotic cytokine, IL-4, in asbestos-exposed wild-type mice but not PKCdelta-/- mice. PKCdelta-/- mice also exhibited decreased lung infiltration of polymorphonuclear cells, natural killer cells, and macrophages in bronchoalveolar lavage fluid and lung, as well as increased numbers of B lymphocytes and plasma cells. These changes were accompanied by elevated mRNA levels of immunoglobulin chains. These data show that modulation of PKC-delta has multiple effects on peribronchiolar cell proliferation, proinflammatory and profibrotic cytokine expression, and immune cell profiles in lung. These results also implicate targeted interruption of PKC-delta as a potential therapeutic option in asbestos-induced lung diseases.


Reliability of range-separated hybrid functionals for describing magnetic coupling in molecular systems.
The performance of the Heyd-Scuseria-Ernzerhorf (HSE) and single parameter long-range corrected Perdew-Burke-Ernzerhorf (LC-omegaPBE) range-separated hybrids for predicting magnetic coupling constants has been investigated for a broad set of magnetic molecular systems for which accurate experimental data exist. The set includes the H-He-H model system, two organic diradicals with different magnetic behaviors, and a series of Cu dinuclear complexes with a broad range of magnetic coupling values. Both HSE and LC-omegaPBE provide a significant improvement to standard hybrids such as the well-known hybrid Becke-3-parameters exchange with Lee-Yang-Parr correlation (B3LYP) functional. Nevertheless, the performance of these two range-separated hybrid functionals is different: HSE overestimates antiferromagnetic and ferromagnetic interactions in Cu dinuclear complexes (although significantly less than B3LYP), whereas LC-omegaPBE treats ferro- and antiferromagnetic couplings on a much more balanced way. The increased accuracy of LC-omegaPBE suggests that the inclusion of 100% Hartree-Fock exchange considered in the definition of this long-range corrected hybrid functional has important consequences for an accurate description of exchange and correlation effects on the electronic structure of open shell systems. On the other hand, HSE, which was developed with periodic systems in mind, also performs quite well (and better than B3LYP) thus opening the possibility of magnetic coupling studies in metal oxides and other challenging solids.


Combined effects of pioglitazone and doxorubicin on migration and invasion of MDA-MB-231 breast cancer cells.
Despite antitumor properties, chemotherapy medication can create conditions in tumor cells that work in favor of the tumor. Doxorubicin, commonly prescribed chemotherapy agents, can increase the risk of migration and invasion of tumor cells through overexpression of the CXCR4 gene by affecting downstream signaling pathways. The regulatory role of CXCR7 on CXCR4 function has been demonstrated. Therefore, it is hypothesized that combining doxorubicin with another anticancer drug could be a promising approach. In this research, we evaluated the anti-invasive property of pioglitazone along with antitumor effects of doxorubicin on MDA-MB-231 breast cancer cell lines. There was no significant difference between two treatment groups in neither the expression nor changes in the expression of CXCR7 and CXCR4 genes (P < 0.05). Pioglitazone-doxorubicin combination reduced cell migration in tumor cells to a significantly higher extent compared to doxorubicin alone (P < 0.05). Co-administration of pioglitazone and doxorubicin might reduce cell migration in breast cancer tumor cells, and that cell migration function is independent of some specific proteins.


Group psychological treatment for chest pain with normal coronary arteries.
We used a psychological treatment package (education, relaxation, breathing training, graded exposure to activity and exercise, and challenging automatic thoughts about heart disease) to treat 60 patients who had continuing chest pain despite cardiological reassurance following haemodynamically normal angiography. The treatment was delivered in six sessions over eight weeks to groups of up to six patients. The patients kept daily records of chest pain episode frequency and nitrate use. Questionnaires were used to assess anxiety, depression and disability. Exercise tolerance was tested by treadmill electrocardiography, with capnographic assessment of hyperventilation. The results were compared with waiting-list controls. Treatment significantly reduced chest pain episodes (p < 0.01) from median 6.5 to 2.5 per week. There were significant improvements in anxiety and depression scores (p < 0.05), disability rating (p < 0.0001) and exercise tolerance (p < 0.05), and these were maintained at six month follow-up. Treatment reduced the prevalence of hyperventilation from 54% to 34% (p < 0.01) but not the prevalence of ECG-positive exercise tests. Patients continuing to attribute their pain to heart disease had poorer outcomes. Group psychological treatment for non-cardiac chest pain is feasible, reduces pain, psychological morbidity and disability, and improves exercise tolerance.


Engaging fathers to improve complementary feeding is acceptable and feasible in the Lake Zone, Tanzania.
In Tanzania, suboptimal complementary feeding practices contribute to high stunting rates. Fathers influence complementary feeding practices, and effective strategies are needed to engage them. The objectives of this research were to examine the acceptability and feasibility of (1) tailored complementary feeding recommendations and (2) engaging fathers in complementary feeding. We conducted trials of improved practices with 50 mothers and 40 fathers with children 6-18 months. At visit 1, mothers reported current feeding practices and fathers participated in focus group discussions. At visit 2, mothers and fathers received individual, tailored counselling and chose new practices to try. After 2 weeks, at visit 3, parents were interviewed individually about their experiences. Interview transcripts were analysed thematically. The most frequent feeding issues at visit 1 were the need to thicken porridge, increase dietary diversity, replace sugary snacks and drinks and feed responsively. After counselling, most mothers agreed to try practices to improve diets and fathers agreed to provide informational and instrumental support for complementary feeding, but few agreed to try feeding the child. At follow-up, mothers reported improved child feeding and confirmed fathers' reports of increased involvement. Most fathers purchased or provided funds for recommended foods; some helped with domestic tasks or fed children. Many participants reported improved spousal communication and cooperation. Families were able to practice recommendations to feed family foods, but high food costs and seasonal unavailability were challenges. It was feasible and acceptable to engage fathers in complementary feeding, but additional strategies are needed to address economic and environmental barriers.


[Classification criteria and clinical picture of juvenile idiopathic arthritis].
In recent years a new nomenclature and classification childhood chronic arthritis has been introduced. The terms juvenile chronic arthritis and juvenile rheumatoid arthritis--have been replaced by juvenile idiopathic arthritis (JIA). The term JIA was adapted to indicate a childhood onset (before the 16th. birthday) characterized primarily by arthritis lasting for at least 6 weeks, and the cause haven't been found so far. In this paper the diagnosis and clinical course systemic arthritis, polyarthritis and oligoarthritis were characterized. The current therapeutic approach to JIA consists a complex management as the administration of antiinflammatory, immunosuppressive and immunomodulatory drugs--as well as rehabilitation.


Enhancement of the Bioactive Compound Content and Antibacterial Activities in Curcuma Longa Using Zinc Oxide Nanoparticles.
Incorporating nanoparticles into plant cultivation has been shown to improve growth parameters and alter the bioactive component compositions of many plant species, including Curcumin longa. The aim of the current study was to investigate the effects of foliar application of zinc oxide nanoparticles on the content of bioactive compounds and their antibacterial activities against potential bacterial pathogens. To this end, C. longa leaves were treated with different doses of ZnO NPs to see how this affected their bioactive component composition. The effect of different doses of ZnO NPs on the accumulation of bisdemethoxycurcumin, demethoxycurcumin, and curcumin in ethanolic extracts of C. longa rhizomes was evaluated using high-performance liquid chromatography (HPLC). When compared to the control treatment, foliar spraying with (5 and 40 mgL-1) of ZnO NPs increased bisdemethoxycurcumin, demethoxycurcumin, and curcumin levels approximately (2.69 and 2.84)-, (2.61 and 3.22)-, and (2.90 and 3.45)-fold, respectively. We then checked whether the ethanolic extracts produced from the plantlets changed in terms of their phytochemical makeup and antibacterial properties. Furthermore, the results revealed that C. long-ZnO NPs displayed antibacterial activity against the tested S. aureus and P. aeruginosa bacterium strains, but had a few effect against E. coli. The MIC for P. aeruginosa was 100 g/mL. The time-kill studies also revealed that ZnO NPs at 4 MIC killed P. aeruginosa, Actinobacteria baumannii, and Bacillus sp. after 2 h, while S. aureus did not grow when treated with 4 × MIC of the extract for 6 h. The strongest antibacterial activity was seen in the extract from plantlets grown without nanoparticles for P. aeruginosa, whereas it was seen in the extract from plantlets grown in the presence of 5 mg/L ZnO NPs for E. coli, S. aureus, and P. aeruginosa. These findings show that ZnO NPs are powerful enhancers of bioactive compound production in C. longa, a trait that can be used to combat antibiotic resistance in pathogenic bacterial species.


Collaborative study for the establishment of replacement batches of heparin low- molecular-mass for assay biological reference preparations.
A collaborative study was run by the European Directorate for the Quality of Medicines & HealthCare (EDQM) in the context of the Biological Standardisation Programme (BSP), under the aegis of the Council of Europe and the European Commission, to establish replacement batches for the dwindling stocks of the Heparin low-molecular-mass for assay European Pharmacopoeia Biological Reference Preparation (BRP). The replacement batches of BRP are intended to be used in the assays for anti-Xa and anti-IIa activities, as described in the European Pharmacopoeia (Ph. Eur.) monograph Heparins, low-molecular-mass (0828). Three freeze-dried candidate batches were calibrated against the current International Standard (IS) for Heparin, lowmolecular- weight (2nd IS, 01/608). For the purpose of the continuity check between subsequent BRP batches, the current Heparin low-molecular-mass for assay BRP (batch 5) was also included in the test panel. Thirteen official medicines control and manufacturers laboratories from European and non-European countries contributed data. A central statistical analysis of the datasets was performed at the EDQM. On the basis of the results, the 3 candidate materials were assigned a potency of 104 IU/vial for the anti-Xa activity and 31 IU/vial for the anti-IIa activity. Taken into account the preliminary stability data and the results of this collaborative study, the 3 batches of candidate BRP were adopted in June 2010 by the Commission of the Ph. Eur. as Heparin low-molecular-mass for assay BRP batches 6, 7 and 8.


[Bilateral pulmonary nodules in an HIV-infected patient].
Although infectious causes are the most common source of pulmonary nodules in HIV-infected patients, malignant diseases such as Kaposi sarcoma and lymphoma must also be considered. A 40 year-old man, diagnosed with HIV infection 16 years earlier and with a satisfactory viro-immunological control, was hospitalized for bilateral pulmonary nodules and a dorsal lytic mass. Bone and pleural biopsies showed a malignant epithelioid hemangioendothelioma. Epithelioid hemangioendothelioma is an uncommon low grade vascular tumor. We report the first case in an HIV-infected patient. Bilateral pulmonary nodules are common in this malignant disease but are not specific. In a HIV-infected patient, such clinical presentation is associated with numerous differential diagnoses and must be interpreted in relation to the immune status. In HIV-patients without immunosuppression, pulmonary nodules are often malignant. With the increased survival of these patients, these etiologies closer to those of non-infected patients.


Multi-echo length and offset VARied saturation (MeLOVARS) method for improved CEST imaging.
The aim of this study was to develop a technique for rapid collection of chemical exchange saturation transfer images with the saturation varied to modulate signal loss transfer and enhance contrast. Multi-echo Length and Offset VARied Saturation (MeLOVARS) divides the saturation pulse of length Tsat into N = 3-8 submodules, each consisting of a saturation pulse with length of Tsat /N (∼0.3-1 s), one or more low flip-angle gradient-echo readout(s) and a flip back pulse. This results in N readouts with increasing saturation time from Tsat /N to Tsat without extra scan time. For phantoms, eight images with Tsat incremented every 0.5 s from 0.5-4 s were collected simultaneously using MeLOVARS, which allows rapid determination of exchange rates for agent protons. For live mice bearing glioblastomas, the Z-spectra for five different Tsat values from 0.5 to 2.5 s were acquired in a time normally used for one Tsat . With the additional Tsat -dependence information, LOVARS phase maps were produced with a more clearly defined tumor boundary and an estimated 4.3-fold enhanced contrast-to-noise ratio (CNR). We also show that enhancing CNR is achievable by simply averaging the collected images or transforming them using the principal component analysis. MeLOVARS enables collection of multiple saturation-time-weighted images without extra time, producing a LOVARS phase map with increased CNR.


Assessment of Lifestyle, Eating Habits and the Effect of Nutritional Education among Undergraduate Students in Southern Italy.
The years spent at university represent a critical period that can influence both the quality of lifestyle and the eating habits of subsequent adulthood, and also, in the long term, the health of the individual. The aim of this study was to investigate the lifestyle of university students living away from home. Each subject recruited for the study was given a questionnaire to obtain general information, eating habits and physical activity levels before (T0) and after six month of training seminars (T1). Blood pressure, body composition and questionnaire responses were investigated. The main findings of this study are a significant decrement in blood pressure; an increment in physical activity practice; an increased number of subjects who pay attention to the calorific value of food and also an improvement in BIA parameters. In conclusion, this study demonstrated the challenges that university students face in leading a healthy lifestyle and caring for their nutritional needs, particularly when they are away from their families. No intervention specifically targets young adults, even though much emphasis is placed on the promotion of a healthy lifestyle based on a varied and balanced diet and sufficient exercise. Our study showed that it is possible to improve lifestyle through educational events aimed at making students aware of the health risks deriving from unhealthy lifestyles.


Revealing Transition States during the Hydration of Clay Minerals.
A molecular-scale understanding of the transition between hydration states in clay minerals remains a challenging problem because of the very fast stepwise swelling process observed from X-ray diffraction (XRD) experiments. XRD profile modeling assumes the coexistence of multiple hydration states in a clay sample to fit the experimental XRD pattern obtained under humid conditions. While XRD profile modeling provides a macroscopic understanding of the heterogeneous hydration structure of clay minerals, a microscopic model of the transition between hydration states is still missing. Here, for the first time, we use molecular dynamics simulation to investigate the transition states between a dry interlayer, one-layer hydrate, and two-layer hydrate. We find that the hydrogen bonds that form across the interlayer at the clay particle edge make an important contribution to the energy barrier to interlayer hydration, especially for initial hydration.


alpha-Amino acids derived from ornithine as building blocks for peptide synthesis.
Recently great interest has arisen in the synthesis of combinatorial libraries, and this technology provides a significant partner to contemporary strategies in rational design and lead discovery. By simple combination of a given set of building blocks, high numbers of different molecules are produced simultaneously, increasing the possibility of discovery of a lead compound in a limited time. One direction of research in this field focuses on the synthesis of libraries composed of modified amino acids. Here, the synthesis and characteristics of some building blocks derived from ornithine are described. The synthesis is based on the acylation/sulfonation of the copper complex of ornithine by aroyl and arylsulfonyl chlorides exemplified by 2-thiophenecarbonyl chloride, p-toluenesulfonyl chloride and 8-quinolinesulfonyl chloride. To evaluate the potential use of these modified alpha-amino acids as component in an oligopeptide library, all three derivatives were incorporated in a hexapeptide with a random sequence using a standard coupling procedure (DIC/HOBt/DIEA). Depending upon the acidity of the amido hydrogen on the delta-nitrogen, competition between intramolecular cyclization and peptide bond formation was observed. The higher the acidity, the more pronounced is this side reaction. Coupling conditions for peptide formation were optimized so that the newly described amino acid based building blocks are suitable for incorporation into libraries consisting of unnatural amino acids. The outlined procedures open up a broad avenue of possibilities for creation of diversity into peptidic libraries.


Limosilactobacillus fermentum HF06-derived paraprobiotic and postbiotic alleviate intestinal barrier damage and gut microbiota disruption in mice with ulcerative colitis.
Paraprobiotics and postbiotics have shown potential in the treatment of ulcerative colitis (UC). However, their in vivo application is still in its infancy and their mechanisms of action are not well understood. Here, we investigated the mitigation effects of Limosilactobacillus fermentum HF06-derived paraprobiotic (6-PA) and postbiotic (6-PS) on dextran sulfate sodium induced UC and the potential mechanisms. Results indicated that the administration of 6-PA and 6-PS resulted in the inhibition of weight loss and colon shortening in mice with UC. Furthermore, they led to a significant reduction in both fecal moisture content and the levels of proinflammatory cytokines and oxidative stress in the intestine of the mice. 6-PA and 6-PS treatment strengthened the intestinal mucosal barrier by dramatically upregulating the levels of zonula occludens-1 and occludin proteins. In addition, 6-PA and 6-PS restored intestinal dysbiosis by regulating abundances of certain bacteria, such as Bifidobacterium, Faecalibaculum, Muribaculaceae, Corynebacterium, Escherichia-Shigella and Clostridium_sensu_stricto_1, and regulated the level of short-chain fatty acids. These findings illustrated for the first time that L. fermentum HF06-derived paraprobiotic and postbiotic enhanced the intestinal barrier function, and restored gut microbiota alterations. © 2023 Society of Chemical Industry.


Effect of oxidation on amine-based pharmaceutical degradation and N-Nitrosodimethylamine formation.
Four pharmaceuticals (ranitidine, nizatidine, doxylamine, and carbinoxamine) were selected as model compounds to assess the efficiency of four oxidants (ozone (O3), chlorine (Cl2), chlorine dioxide (ClO2) and potassium permanganate (KMnO4)) on the removal of amine-based pharmaceutical and personal care products (PPCPs), as well as the reduction of their N-Nitrosodimethylamine formation potentials (NDMAFPs). The changes in PPCPs and their NDMAFPs during oxidation were quantified using various oxidants and dosages. The relationship between oxidation product structures and NDMAFP changes was also analyzed. The results showed that oxidation with O3, Cl2 and ClO2 were effective in removing the selected PPCPs. However, only ozonation was effective in reducing their NDMAFPs. Ozonation at 6 mg/L removed approximately 90% PPCPs and 90% NDMAFPs for all PPCPs. In addition, the results indicated that ozonation products made little contribution to NDMAFPs. In contrast, some PPCP products had higher NDMAFPs than PPCPs after oxidation with Cl2, ClO2 and KMnO4. There were two possible reaction pathways that led to decrease in NDMAFPs after oxidation. One was oxygen transfer to nitrogen at the tertiary amine site and the other was N-dealkylation from the tertiary amine site.


Left Ventricular Assist Device: What the Internist Needs to Know. A Review of the Literature.
Left ventricular assist devices (LVADs) have revolutionized therapy for patients with Stage D heart failure (HF) with reduced systolic function providing not only improved survival benefits but also meaningful changes in quality of life and functional capacity. With technological advances and improved durability of devices, length of survival has significantly improved. With continued organ donor shortage, LVADs are frequently serving as a substitute for cardiac transplant as destination therapy, particularly among the elderly. Internists not only face the important challenge of identifying the patients in need referral for these advanced therapies, they are also faced with the challenges of taking care of these patients. This review will help the internists to better understand the present status, indications and advances in LVADs and also understand the complications and adverse effects associated with these devices.


A global transcriptomic pipeline decoding core network of genes involved in stages leading to acquisition of drug-resistance to cisplatin in osteosarcoma cells.
Traditional cancer therapy is focused on eradicating fast proliferating population of tumor cells. However, existing evidences suggest survival of sub-population of cancer cells that can resist chemotherapy by entering a 'persister' state of minimal growth. These cells eventually survive to produce cells resistant to drugs. The identifying of appropriate targets that can eliminate the drug-tolerant 'persisters' remains a challenge. Hence, a deeper understanding of the distinctive genetic signatures that lead to resistance is of utmost importance to design an appropriate therapy. In this study, deep-sequencing of mRNA was performed in osteosarcoma (OS) cells, exposed to the widely used drug, cisplatin which is an integral part of current treatment regime for OS. Transcriptomic analysis was performed in (i) untreated OS; (ii) persister sub-population of cells post-drug shock; (iii) cells which evade growth bottleneck and (iv) drug-resistant cells obtained after several rounds of drug shock and revival. The transcriptomic signatures and pathways regulated in each group were compared; the transcriptomic pipeline to the acquisition of resistance was analyzed and the core network of genes altered during the process was delineated. Additionally, our transcriptomic data were compared with OS patient data obtained from Gene Ontology Omnibus. We observed a sub-set of genes to be commonly expressed in both data sets with a high correlation (0.81) in expression pattern. To the best of our knowledge, this study is uniquely designed to understand the series of genetic changes leading to the emergence of drug-resistant cells, and implications from this study have a potential therapeutic impact. All raw data can be accessed from GEO database (https://www.ncbi.nlm.nih.gov/geo/) under the GEO accession number GSE86053. Supplementary data are available at Bioinformatics online.


Infrared optical coatings for the EarthCARE Multispectral Imager.
The Earth Cloud, Aerosol and Radiation Explorer mission (EarthCARE) Multispectral Imager (MSI) is a radiometric instrument designed to provide the imaging of the atmospheric cloud cover and the cloud top surface temperature from a sun-synchronous low Earth orbit. The MSI forms part of a suite of four instruments destined to support the European Space Agency Living Planet mission on-board the EarthCARE satellite payload to be launched in 2016, whose synergy will be used to construct three-dimensional scenes, textures, and temperatures of atmospheric clouds and aerosols. The MSI instrument contains seven channels: four solar channels to measure visible and short-wave infrared wavelengths, and three channels to measure infrared thermal emission. In this paper, we describe the optical layout of the infrared instrument channels, thin-film multilayer designs, the coating deposition method, and the spectral system throughput for the bandpass interference filters, dichroic beam splitters, lenses, and mirror coatings to discriminate wavelengths at 8.8, 10.8, and 12.0 μm. The rationale for the selection of thin-film materials, spectral measurement technique, and environmental testing performance are also presented.


A step-defined sedentary lifestyle index: <5000 steps/day.
Step counting (using pedometers or accelerometers) is widely accepted by researchers, practitioners, and the general public. Given the mounting evidence of the link between low steps/day and time spent in sedentary behaviours, how few steps/day some populations actually perform, and the growing interest in the potentially deleterious effects of excessive sedentary behaviours on health, an emerging question is "How many steps/day are too few?" This review examines the utility, appropriateness, and limitations of using a reoccurring candidate for a step-defined sedentary lifestyle index: <5000 steps/day. Adults taking <5000 steps/day are more likely to have a lower household income and be female, older, of African-American vs. European-American heritage, a current vs. never smoker, and (or) living with chronic disease and (or) disability. Little is known about how contextual factors (e.g., built environment) foster such low levels of step-defined physical activity. Unfavorable indicators of body composition and cardiometabolic risk have been consistently associated with taking <5000 steps/day. The acute transition (3-14 days) of healthy active young people from higher (>10 000) to lower (<5000 or as low as 1500) daily step counts induces reduced insulin sensitivity and glycemic control, increased adiposity, and other negative changes in health parameters. Although few alternative values have been considered, the continued use of <5000 steps/day as a step-defined sedentary lifestyle index for adults is appropriate for researchers and practitioners and for communicating with the general public. There is little evidence to advocate any specific value indicative of a step-defined sedentary lifestyle index in children and adolescents.


Mediastinal perigraft seroma after thoracic aortic surgery.
We investigated pertinent factors associated with mediastinal perigraft seroma (PGS) after thoracic aortic surgery. In addition, we provided a clinical review of this entity, as reports reviewing abundant mediastinal PGS cases are rare. Eighty-two patients who underwent either ascending aortic replacement or aortic arch replacement between 2016 and 2022 in our institution were enrolled in the present study. Postoperative computed tomography scans were performed to detect fluid capsules with a diameter ≥3.0 cm and radiodensity ≤25 Hounsfield units. Patients who did and who did not develop PGS formation were compared. Variables with a statistically significant difference between these groups were included in a multiple logistic regression analysis along with other factors associated with PGS in the literature. The incidence rate of PGS was 14.6% (12/82). The average radiodensity of the mass was 16.6 ± 6.3 Hounsfield units. The average onset of PGS was 8.5 months post-surgery. Multivariate logistic regression analysis revealed that ejection fraction [odds ratio (OR): 1.25, 95% confidence interval (CI): 1.03-1.50, P = 0.021], aortic dissection (versus degenerative aortic aneurysm) (OR: 6.61, 95% CI: 1.35-32.4, P = 0.02) and warfarin use (OR: 6.67, 95% CI: 1.19-37.1, P = 0.03) significantly contributed to mediastinal PGS after thoracic aortic surgery. High ejection fraction, warfarin use and aortic dissection (versus degenerative aortic aneurysm) contributed significantly to mediastinal PGS formation after thoracic aortic surgery. Careful serial postoperative imaging studies and fluid analysis can be used to guide treatment plans. UMIN-CTR (University hospital Medical Information Network-Clinical Trial Registry) Registration number: UMIN000050764.


Fish embryos on land: terrestrial embryo deposition lowers oxygen uptake without altering growth or survival in the amphibious fish Kryptolebias marmoratus.
Few teleost fishes incubate embryos out of water, but the oxygen-rich terrestrial environment could provide advantages for early growth and development. We tested the hypothesis that embryonic oxygen uptake is limited in aquatic environments relative to air using the self-fertilizing amphibious mangrove rivulus, Kryptolebias marmoratus, which typically inhabits hypoxic, water-filled crab burrows. We found that adult mangrove rivulus released twice as many embryos in terrestrial versus aquatic environments and that air-reared embryos had accelerated developmental rates. Surprisingly, air-reared embryos consumed 44% less oxygen and possessed larger yolk reserves, but attained the same mass, length and chorion thickness. Water-reared embryos moved their opercula ∼2.5 more times per minute compared with air-reared embryos at 7 days post-release, which probably contributed to the higher rates of oxygen uptake and yolk utilization we observed. Genetically identical air- and water-reared embryos from the same parent were raised to maturity, but the embryonic environment did not affect growth, reproduction or emersion ability in adults. Therefore, although aspects of early development were plastic, these early differences were not sustained into adulthood. Kryptolebias marmoratus embryos hatched out of water when exposed to aerial hypoxia. We conclude that exposure to a terrestrial environment reduces the energetic costs of development partly by reducing the necessity of embryonic movements to dispel stagnant boundary layers. Terrestrial incubation of young would be especially beneficial to amphibious fishes that occupy aquatic habitats of poor water quality, assuming low terrestrial predation and desiccation risks.


Climate change jeopardizes the persistence of freshwater zooplankton by reducing both habitat suitability and demographic resilience.
Higher temperatures and increased environmental variability under climate change could jeopardize the persistence of species. Organisms that rely on short windows of rainfall to complete their life-cycles, like desert annual plants or temporary pool animals, may be particularly at risk. Although some could tolerate environmental changes by building-up banks of propagules (seeds or eggs) that buffer against catastrophes, climate change will threaten this resilience mechanism if higher temperatures reduce propagule survival. Using a crustacean model species from temporary waters, we quantified experimentally the survival and dormancy of propagules under anticipated climate change and used these demographic parameters to simulate long term population dynamics. By exposing propagules to present-day and projected daily temperature cycles in an 8 month laboratory experiment, we showed how increased temperatures reduce survival rates in the propagule bank. Integrating these reduced survival rates into population models demonstrated the inability of the bank to maintain populations; thereby exacerbating extinction risk caused by shortened growing seasons. Overall, our study demonstrates that climate change could threaten the persistence of populations by both reducing habitat suitability and eroding life-history strategies that support demographic resilience.


APOBEC3G and APOBEC3F require an endogenous cofactor to block HIV-1 replication.
APOBEC3G (A3G)/APOBEC3F (A3F) are two members of APOBEC3 cytidine deaminase subfamily. Although they potently inhibit the replication of vif-deficient HIV-1, this mechanism is still poorly understood. Initially, A3G/A3F were thought to catalyze C-to-U transitions on the minus-strand viral cDNAs during reverse transcription to disrupt the viral life cycle. Recently, it was found more likely that A3G/A3F directly interrupts viral reverse transcription or integration. In addition, A3G/A3F are both found in the high-molecular-mass complex in immortalized cell lines, where they interact with a number of different cellular proteins. However, there has been no evidence to prove that these interactions are required for A3G/A3F function. Here, we studied A3G/A3F-restricted HIV-1 replication in six different human T cell lines by infecting them with wild-type or vif-deficient HIV-1. Interestingly, in a CEM-derived cell line CEM-T4, which expresses high levels of A3G/A3F proteins, the vif-deficient virus replicated as equally well as the wild-type virus, suggesting that these endogenous antiretroviral genes lost anti-HIV activities. It was confirmed that these A3G/A3F genes do not contain any mutation and are functionally normal. Consistently, overexpression of exogenous A3G/A3F in CEM-T4 cells still failed to restore their anti-HIV activities. However, this activity could be restored if CEM-T4 cells were fused to 293T cells to form heterokaryons. These results demonstrate that CEM-T4 cells lack a cellular cofactor, which is critical for A3G/A3F anti-HIV activity. We propose that a further study of this novel factor will provide another strategy for a complete understanding of the A3G/A3F antiretroviral mechanism.