Laser vibrometer based on optical-feedback-induced frequency modulation of a single-mode laser diode.
We describe a sensitive and inexpensive vibrometer based on optical feedback by diffuse scattering to a single-mode diode laser. Fluctuations in the diode laser's operating frequency that are due to scattered light from a vibrating surface are used to detect the amplitude and frequency of surface vibrations. An additional physical vibration of the laser provides an absolute amplitude calibration. The fundamental bandwidth is determined by the laser response time of roughly 10(-9)s. A noise floor of 0.23 nm/Hz(1/2) at 30 kHz with 5 × 10(-5) of the incident light returning is demonstrated. This instrument provides an inexpensive and sensitive method of noncontact measurement in solid materials with low or uneven reflectivity. It can be used as a vibration or velocity sensor.


IgG induction of IL-1 receptor antagonist production by human monocytes.
In summary, IL-1ra is a unique cytokine that binds avidly to cell surface receptors for IL-1 without inducing any detectable intracellular responses. Adherent IgG and LPS induce IL-1ra production in human monocytes through different mechanisms. IL-1ra has been shown to be an effective competitive inhibitor of IL-1 both in vitro and in vivo (Arend 1993). The possibility exists that stimulation or enhancement of endogenous IL-1ra production may be an efficacious therapeutic approach in human diseases where local IL-1 may play an important role in pathophysiology. Our studies have demonstrated that IL-1ra production is induced in human monocytes in vitro by either culture on adherent IgG or culture with i.v.Ig preparations. Our initial studies failed to show increased IL-1ra levels in the peripheral circulation of patients with Kawasaki's Disease after i.v.Ig administration. However, our preliminary approaches may not have been sufficiently complete and a more extensive examination of the effects of i.v.Ig on IL-1ra production in vivo is warranted.


Characterization and Oral Delivery of Proinsulin-Transferrin Fusion Protein Expressed Using ExpressTec.
Proinsulin-transferrin fusion protein (ProINS-Tf) has been designed and successfully expressed from the mammalian HEK293 cells (HEK-ProINS-Tf). It was found that HEK-ProINS-Tf could be converted into an activated form in the liver. Furthermore, HEK-ProINS-Tf was demonstrated as an extra-long acting insulin analogue with liver-specific insulin action in streptozotocin (STZ)-induced type 1 diabetic mice. However, due to the low production yield from transfected HEK293 cells, there are other interesting features, including the oral bioavailability, which have not been fully explored and characterized. To improve the protein production yield, an alternative protein expression system, ExpressTec using transgenic rice (Oryza sativa L.), was used. The intact and active rice-derived ProINS-Tf (ExpressTec-ProINS-Tf) was successfully expressed from the transgenic rice expression system. Our results suggested that, although the insulin-like bioactivity of ExpressTec-ProINS-Tf was slightly lower in vitro, its potency of in vivo blood glucose control was considerably stronger than that of HEK-ProINS-Tf. The oral delivery studies in type 1 diabetic mice demonstrated a prolonged control of blood glucose to near-normal levels after oral administration of ExpressTec-ProINS-Tf. Results in this report suggest that ExpressTec-ProINS-Tf is a promising insulin analog with advantages including low cost, prolonged and liver targeting effects, and most importantly, oral bioactivity.


Schedules of Controlled Substances: Placement of FDA-Approved Products of Oral Solutions Containing Dronabinol [(-)-delta-9-transtetrahydrocannabinol (delta-9-THC)] in Schedule II. Interim final rule, with request for comments.
On July 1, 2016, the U.S. Food and Drug Administration (FDA) approved a new drug application for Syndros, a drug product consisting of dronabinol [(-)-delta-9-trans-tetrahydrocannabinol (delta-9-THC)] oral solution. Thereafter, the Department of Health and Human Services (HHS) provided the Drug Enforcement Administration (DEA) with a scheduling recommendation that would result in Syndros (and other oral solutions containing dronabinol) being placed in schedule II of the Controlled Substances Act (CSA). In accordance with the CSA, as revised by the Improving Regulatory Transparency for New Medical Therapies Act, DEA is hereby issuing an interim final rule placing FDA-approved products of oral solutions containing dronabinol in schedule II of the CSA.


Fetal cells and DNA in maternal blood.
Although fetal cells have been known to escape to the maternal circulation for a number of years, research attempts to use them for prenatal diagnosis have not had any consistent success. This review attempts to trace the history of such attempts and to document their progress and reasons for success or failure. The opinions of recent conferences including that of the US National Institute of Child Health and Human Development, a sponsor of major US research in the field, are reported and discussed. It is concluded that although basic work has demonstrated the biologic availability of both fetal cells and their free DNA representatives in the maternal circulation at gestational ages relevant to prenatal diagnosis, much work remains to develop practical technology for their consistent recovery and assay.


Reproducibility, fidelity, and discriminant validity of linear RNA amplification for microarray-based identification of major human enteric viruses.
Human enteric viruses are inherently a group of viruses that confer similar or overlapping clinical symptoms and pose a challenge for correct etiological diagnosis. DNA microarray technology has emerged to be of major interest to detect broad range of viral pathogens including enteric viruses. However, this approach requires a relative large amount of target nucleic acid for hybridization analysis. This feature limits its further applicability. To address this challenge, we evaluated a novel single primer linear isothermal amplification (Ribo-SPIA) procedure for preparation of single-stranded cDNA (sscDNA) from minute amount of starting RNA for microarray-based simultaneous detection and identification of three major human enteric viruses including hepatitis A virus, norovirus, and coxsachievirus B2. We performed a series of tests using different amounts of input RNA ranging from 30 ng to 55 pg to assess amplification yield, reproducibility, analytical sensitivity, and fidelity. We demonstrated that as little as 55 pg of viral RNA could produce adequate material by Ribo-SPIA to enable successful identification by microarray analysis without compromising detection specificity. Pairwise comparison of technical replicates hybridized to the microarrays by regression analysis showed excellent reproducibility in the appropriate sensitivity range. We also showed that the use of sscDNA as labeled targets offered increased microarray detection accuracy over complementary RNA generated by traditional T7 in vitro transcription amplification method.


Evidence that spinal interneurons undergo programmed cell death postnatally in the rat.
Programmed cell death has been demonstrated in several specific neuronal populations as a mechanism for modulating the population size following differentiation, but its applicability to all neuronal types is unclear. Evidence for programmed cell death in some populations such as the numerous spinal interneurons has been lacking. We have studied the incidence of apoptosis in the rat spinal cord with three different methods and found a previously undocumented wave of apoptosis occurring in spinal grey matter shortly after birth. The apoptotic morphology was confirmed ultrastructurally. Dying cells were identified as neurons by immunocytochemical labelling for neuronal markers and had an anatomical distribution which indicated that most of the apoptotic cells were interneurons not motoneurons. This wave of apoptosis has the characteristics of a discrete developmental process and occurs later than that of either ventral horn motoneurons or dorsal root ganglion cells, to which most spinal interneurons are connected. These findings indicate that interneurons do undergo programmed cell death, and we suggest that this occurs in response to the earlier reduction in size of their main synaptic targets.


WITHDRAWN: Therapeutic ultrasound for treating patellofemoral pain syndrome.
Therapeutic ultrasound is one of several rehabilitation interventions suggested for the management of pain due to patellofemoral knee pain syndrome. To assess the effectiveness and side effects of ultrasound therapy for treating patellofemoral knee pain syndrome. We searched the Cochrane Musculoskeletal Review Group register, Cochrane Field of Physical and Related Therapies register, Cochrane Controlled Trials Register, MEDLINE, EMBASE, HealthSTAR, Sports Discus, CINAHL,and PEDro databases (to December 2000) according to the sensitive search strategy for RCTs designed for the Cochrane Collaboration. The search was complemented with handsearching of the reference lists. Key experts in the area were contacted for any further articles. All randomized controlled trials (RCTs), controlled clinical trials (CCTs), case-control and cohort studies comparing therapeutic ultrasound against placebo or another active intervention in people with patellofemoral pain syndrome were selected according to an a priori protocol. Two reviewers determined the studies to be included based on a priori inclusion criteria. Data were independently extracted by the same two reviewers and checked by a third reviewer (BS) using a previously developed form. The same two reviewers independently assessed the methodological quality of the RCTs and CCTs using a validated scale. The data analysis was performed using Peto odds ratios. The search retrieved 85 articles. Of the eight that were potentially relevant, only one RCT, including 53 participants with patellofemoral pain syndrome, was identified for this review. All participants received an exercise program as concurrent therapy. Ultrasound combined with ice massage contrast (n of 13), where n equals the number of participants, was not statistically different from ice massage alone (n = 16) in terms of participant-rated pain relief or quadriceps and hamstring strengthening. In the ultrasound and ice massage group, 46% (6 of 13) reported improved pain relief compared to 31% (4 of 13) in the ice massage alone group. This difference of 15% does not meet international standards for clinically important improvements in osteoarthritis, which is 20%. Side effects were not reported. Ultrasound therapy was not shown to have a clinically important effect on pain relief for people with patellofemoral pain syndrome. These conclusions are limited by the poor reporting of the therapeutic application of the ultrasound and low methodological quality of the one trial included. No conclusions can be drawn concerning the use, or non-use, of ultrasound for treating patellofemoral pain syndrome. More well-designed studies are needed.


Analgesia for thoracic surgery: the role of paravertebral block.
An appropriate post operative analgesia after thoracotomies is mandatory to improve the patient's outcome, reduce complications rate, morbidity, hospital cost and length of stay. In this paper we review the evidences regarding the use of paravertebral block for thoracic surgery. In particular we examine the effect of paravertebral block compared to the other technique in four major issues: analgesia, complications rate, postoperative pulmonary function and transition from acute to chronic pain. We conclude that paravertebral block is superior to intravenous analgesia in providing pain control and preserving postoperative pulmonary function while it is equal to thoracic epidural analgesia regarding this two issues. Paravertebral block has a better safety profile when compared to intravenous and thoracic epidural analgesia. Its effect on chronic pain incidence still needs further studies.


Des-aspartate-angiotensin I exerts hypoglycemic action via glucose transporter-4 translocation in type 2 diabetic KKAy mice and GK rats.
The present study investigated the hypoglycemic action of des-aspartate-angiotensin I (DAA-I), a metabolite of angiotensin I, in two animal models of type 2 diabetes. The rationale was based on our earlier studies demonstrating that DAA-I acts on the angiotensin AT(1) receptor and exerts responses opposing those of angiotensin II and on recent reports that curtailment of angiotensin II formation by angiotensin converting enzyme inhibitors and blockade of the AT(1) receptor attenuate hyperglycemia in type 2 diabetics and diabetic animals. Diabetic KKAy mice and GK rats were administered orally (by gavage) one of the following doses of DAA-I: 400, 600, or 800 nmol/kg.d for 4 and 6 wk, respectively. Control diabetic animals were similarly administered water. Blood glucose of each animal was determined fortnightly by oral glucose tolerance test and blood insulin on the last day of treatment. Animals were killed, and the levels of plasma membrane glucose transporter-4 and cytosolic tyrosine-phosphorylated insulin receptor substrate-1 in hind limb skeletal muscles were determined by Western blot in insulin-challenged and nonchallenged animals. Orally administered DAA-I had no effect on blood insulin level but exerted dose-dependent hypoglycemic action in KKAy mice and GK rats after 4 and 6 wk of treatment, respectively. At the maximal effective dose of 600 nmol/kg, insulin induced a significant increase in plasma membrane glucose transporter-4 and cytosolic tyrosine-phosphorylated insulin receptor substrate-1. These findings show that DAA-I is not an insulin secretagogue and exerts hypoglycemic action by attenuating insulin resistance, the first such demonstration indicating that the nonapeptide is involved in glycemic regulation.


Reassessment of transillumination light scanning for the diagnosis of breast cancer.
Transillumination light scanning is a non-x-ray, noninvasive modality that uses low-intensity emissions of red and near infrared light to visualize the tissues of the breast. The absorption characteristics of the emitted light from the breast tissues are fed into a computer that transforms the analog signals into varying degrees of color saturation hues, ranging from blue to red. The basic premise for the use of transillumination is that breast cancer, because of its increased blood supply, absorbs more near infrared radiation than benign tissue. Thus, abnormal or malignant breast tissues appear blue on the light scan, while normal breast tissues appear red. The safety and lack of risk of radiation exposure of this technique have been demonstrated.


Periodontal plastic surgical technique for gingival fenestration closure.
Gingival fenestration is an opening through oral keratinized tissue, usually unattached, that is observed in thin gingiva with usually thick subgingival calculus deposits. This lesion is seen infrequently but may be more common than has been reported; lack of symptoms may inhibit patient awareness. Because surgical correction usually is not required, there are very few reports in the literature concerning this lesion. The following report describes a case of gingival fenestration and surgical treatment with a connective tissue/periosteal graft.


Genitourinary physicians and vulval clinics: a UK survey.
Our objectives are to examine the extent to which genitourinary physicians participate in vulval clinics in the UK; to determine the geographic distribution of such clinics and to study aspects of clinical practice and staffing of the vulval clinics identified in the survey. In February/March 1998 a questionnaire on vulval clinics was distributed via regional representatives of the British Co-operative Clinical Group to all the 174 consultants in charge of genitourinary medicine clinics in the UK. One hundred and sixty-four replies were received which identified a total of 61 vulval clinics in the UK. All former health regions had at least one vulval clinic or equivalent. Three former regions had 7 vulval clinics each. Forty-six vulval clinics had a dermatologist, 38 a genitourinary physician, and 30 had a gynaecologist. Only 7 vulval clinics claimed to have a counsellor or health adviser present. Ninety-four per cent took biopsies but only half this proportion met with a pathologist to discuss the histology. Eighty per cent had colposcopes and cameras available but rather fewer actually used them. Twenty-nine per cent had performed research in the past 5 years and 24% had either published or presented this. The majority of vulval clinics would accept direct referrals from all the agencies. This survey has demonstrated an increased number of genitourinary physicians participating in vulval clinics. Other studies have demonstrated the value of such clinics in improving diagnosis and management. It is to be hoped that further such clinics will be set up, particularly in parts of the country which are poorly served at present.


Clinical Outcomes of Radiofrequency Ablation Combined with Transarterial Chemoembolization Using Degradable Starch Microsphere Mixed with Mitomycin C for the Treatment of Non-hepatocellular Carcinoma Malignant Liver Tumors.
To retrospectively evaluate the outcomes of radiofrequency ablation combined with transarterial chemoembolization using degradable starch microspheres for non-hepatocellular carcinoma malignant liver tumors. A total of 15 patients (13 men, 2 women; median age, 67 years) who underwent radiofrequency ablation immediately after transarterial chemoembolization using degradable starch microspheres for liver tumors between July 2011 and September 2020 were included in this study. Thirteen patients had liver metastases from colorectal cancer (n = 6), esophageal cancer (n = 2), lung cancer (n = 2), and other tumors (n = 3), and 2 patients had primary liver tumor of cholangiocellular carcinoma (n = 1) and gastrinoma (n = 1). Twenty tumors (median size, 16 mm) were treated in 17 sessions. Technical success, safety, local tumor progression, and overall survival were evaluated. Safety was assessed according to the clinical practice guideline of the Society of Interventional Radiology. All treatment procedures were successfully completed. There were no major complications. Grade-B complications of self-limiting pneumothorax (n = 1), vomiting (n = 1), and fever (n = 1) occurred in 1 session each. Local tumor progression developed in two tumors (local tumor progression rate, 10%, 2/20). The local tumor progression rates were 5% and 11% at 1 year and at 3 and 5 years, respectively. Tumor size of more than 20 mm (P = 0.0003) and contact with major vessels (P = 0.03) were significant risk factors for local tumor progression. The patients were treated with repeat radiofrequency ablation combined with transarterial chemoembolization using degradable starch microspheres. During median follow-up of 48 months (range, 4-77 months), 5 patients died (33%, 5/15). The overall survival rates were 100%, 85%, and 57% at 1, 3, and 5 years, respectively. The median overall survival time was 69 months. Radiofrequency ablation combined with transarterial chemoembolization using degradable starch microspheres was safe and showed favorable local control for non-hepatocellular carcinoma malignant liver tumors.


Analysis of ancestral and functionally relevant CD5 variants in systemic lupus erythematosus patients.
CD5 plays a crucial role in autoimmunity and is a well-established genetic risk factor of developing RA. Recently, evidence of positive selection has been provided for the CD5 Pro224-Val471 haplotype in East Asian populations. The aim of the present work was to further analyze the functional relevance of non-synonymous CD5 polymorphisms conforming the ancestral and the newly derived haplotypes (Pro224-Ala471 and Pro224-Val471, respectively) as well as to investigate the potential role of CD5 on the development of SLE and/or SLE nephritis. The CD5 SNPs rs2241002 (C/T; Pro224Leu) and rs2229177 (C/T; Ala471Val) were genotyped using TaqMan allelic discrimination assays in a total of 1,324 controls and 681 SLE patients of Spanish origin. In vitro analysis of CD3-mediated T cell proliferative and cytokine response profiles of healthy volunteers homozygous for the above mentioned CD5 haplotypes were also analyzed. T-cell proliferation and cytokine release were significantly increased showing a bias towards to a Th2 profile after CD3 cross-linking of peripheral mononuclear cells from healthy individuals homozygous for the ancestral Pro224-Ala471 (CC) haplotype, compared to the more recently derived Pro224-Val471 (CT). The same allelic combination was statistically associated with Lupus nephritis. The ancestral Ala471 CD5 allele confers lymphocyte hyper-responsiveness to TCR/CD3 cross-linking and is associated with nephritis in SLE patients.


Autoantibody to human c-myc oncogene product in autoimmune patients' sera.
Sera from autoimmune diseases including systemic lupus erythematosus, dermatomyositis, progressive systemic sclerosis and Sjögren's disease, were examined for reactivity against human c-myc oncogene product. We first found the presence of the autoantibody to human c-myc oncogene product in sera from autoimmune diseases. No significant correlation between the presence of the anti-c-myc product antibody and disease activity, clinical disease types and other autoantibodies such as antinuclear factor, anti-DNA antibody, anti-RNP antibody and anti-Sm antibody were shown in this study.


Phase transformations in bulk nanostructured potassium niobiosilicate glasses.
In potassium niobiosilicate (KNS) glasses, nanostructuring can be driven and controlled by thermal treatments at the glass transition temperature and/or by modulation of the chemical composition. The tight relationship between nanostructure and nonlinear optical properties suggests these bulk nanomaterials as an appealing route to nanophotonics. The focus of this paper is placed on assessing the phase transformations which occur in these materials upon annealing at the glass transition temperature and subsequent heating. High-temperature resolved X-ray diffraction (HTXRD) and high-resolution transmission electron microscopy (HRTEM) experiments are integrated with previously published results for in-depth insight. It will be shown that nanostructuring evolves from nucleation of niobium-rich nanocrystals, which are up to 20 nm large, uniformly distributed in the matrix bulk, and metastable. Formation kinetics as well as phase transformation of the nanocrystals are determined by the glass composition. Depending on it, nanocrystal nucleation can be preceded or not by phase separation, and the nanocrystals' phase transition can be of first or second order.


Effects of lower fluence pulsed dye laser irradiation on production of collagen and the mRNA expression of collagen relative gene in cultured fibroblasts in vitro.
Lower fluence of 585-nm flashlamp-pumped pulsed dye laser has been successfully used as a nonablative technique in the treatment of wrinkles. The objective of this study was to evaluate the effect of the pulsed dye laser (585 nm) on the production of collagen and the mRNA expression of collagen related gene in fibroblasts in vitro. Cultured fibroblasts were treated with a 585-nm flashlamp-pumped pulsed dye laser (fluence 3 J/cm(2), 4 J/cm(2), spot size 7 mm, pulse duration 450 micros). The production of collagen and the mRNA expression of transforming growth factor (TGF)-beta1, SMAD2, SMAD3, SMAD4, SMAD7 and type I procollagen alpha1, alpha2 in fibroblasts were investigated by colorimetry or real time polymerase chain reaction. The production of collagen was significantly up-regulated after treatment with a 585-nm flashlamp-pumped pulsed dye laser with a fluence of 3 J/cm(2) (P < 0.001). The mRNA expression of TGF-beta1, SMAD2, SMAD3, SMAD4, SMAD7 and procollagen I was significantly up-regulated after treatment with a 585-nm flashlamp-pumped pulsed dye laser with a fluence of 3 J/cm(2) (P < 0.001). No significant difference of mRNA expression of SMAD2, SMAD3, SMAD4, SMAD7 and type I procollagen was found between controls and fibroblasts treated with pulsed dye laser with a fluence of 4 J/cm(2) (P > 0.05). Lower fluence (3 J/cm(2)) pulsed dye laser increased the collagen production in fibroblasts by up-regulating TGF-beta1, SMAD2, SMAD3, SMAD4, SMAD7 and type I procollagen mRNA expression. These may be the reason it can be effectively used in the treatment of wrinkles.


Effect of Headgroup Variation on the Self-Assembly of Cationic Surfactants with Sulfonatocalix[6]arene.
The effect of headgroup variation on the association of supramolecular amphiphiles composed of 4-sulfonatocalix[6]arene (SCX6) and cationic surfactant possessing tetradecyl substituent was studied in aqueous solutions at pH 7. When the surfactant contained hydrophilic trimethylammonium, pyridinium, or 1-methylimidazolium headgroup, highly reversible temperature-responsive nanoparticle-supramolecular micelle transformation could be attained at appropriately chosen component mixing ratios and NaCl concentrations. In these cases, the substantial negative molar heat capacity change (ΔCp) rendered nanoparticle formation strongly endothermic at low temperature, whereas the assembly to supramolecular micelle was always accompanied by enthalpy gain. The ΔCp values became less negative when the charge density and the hydrophilic character of the surfactant headgroup diminished. The association of the more hydrophobic 6-methoxyquinolinium and quinolinium surfactants with SCX6 did not lead to supramolecular micelle formation because the self-assembly into nanoparticles was highly exothermic.


Factors associated with measles complications in Gweru, Zimbabwe.
To investigate factors associated with complications or death among measles cases. A cross-sectional study. Health facilities in the city of Gweru, Zimbabwe. Six hundred and thirty seven measles cases randomly selected from measles surveillance data. (a) Associations of respiratory complications and diarrhoea with death among complicated cases; (b) associations of age at infection, gender of cases and vaccination status of cases with occurrence of either respiratory complications or diarrhoea or death among measles cases. Among cases with respiratory complications, twenty two (29%) had died, while five (5%) had died among those with diarrhoea (OR=7.06,95% CI=2.55-22.35, p<0.001). On rates of respiratory complications among cases, age groups 24-59 and 60+ months were protective by 57% (95% CI=11-79%) and 76% (95% CI=52-88%) respectively compared to the age group <24 months, and vaccination was protective by 42% (95% CI=2-65%) compared to those unvaccinated. Concerning rates of diarrhoea among cases, the age group 60+ months was protective by 80% (95% CI=62-89%) compared to age group <60 months, while vaccination was protective by 64% (95% CI=42-77%) compared to those unvaccinated. With respect to rates of mortality among cases, age was protective by six per cent (95% CI=3-9 %) for every year older. It was concluded that: (a) the risk of death was higher in cases with respiratory complications than diarrhoea; (b) the risk of complications and death was inversely related to age at infection and older age groups were protective against occurrence of complications or death; (c) the risk of complications was higher in unvaccinated cases and vaccination was protective against occurrence of complications.


[Experiences of prevention and treatment of infectious diseases in Chinese Soviet Republic].
Many kinds of infectious diseases had been prevalent during the Chinese Soviet Republic period. Experiences were accumulated during the fighting against these diseases, and high attention paid by the government including the party, the military and the administration, and strengthening of legislation for prevention and treatment works, with the Red Army as the main task force for the work, and the great mass actively involved in this work, with active propaganda for its prevention and treatment.


Toxic Epidermal Necrolysis Induced by Sintilimab: A Case Report.
Sintilimab is an anti-programmed cell death receptor-1 antibody. The phase III clinical trial ORIENT-12 confirmed the safety of sintilimab combined with pemetrexed/platinum in the treatment of advanced squamous non-small cell lung cancer. Skin reactions are the most commonly reported adverse events of immune checkpoint inhibitors and are rarely severe. We describe a case of toxic epidermal necrolysis related to sintilimab in an elderly oncologic patient. 3 weeks after immunotherapy, the patient developed an extensive rash and diffuse itching, rapidly evolving into macules, blisters, bullae and erosions. Causal evaluation was performed based on the algorithm of drug causality for epidermal necrolysis and national Food and Drug Administration qualitative analysis. The patient responded to high-dose glucocorticosteroid and supportive therapy, alongside with local wound care. If immune checkpoint inhibitors need to be extrapolated clinically, strictly following evidence-based research, promptly detecting and treating adverse reactions is crucial.


Fast Dynamic Visualizations in Microfluidics Enabled by Fluorescent Carbon Nanodots.
Microfluidic systems have become a superior platform for explorations of fascinating fluidic physics at microscale as well as applications in biomedical devices, chemical reactions, drug delivery, etc. Exploitations of this platform are built upon the fundamental techniques of flow visualizations. However, the currently employed fluorescent materials for microfluidic visualization are far from satisfaction, which severely hinders their widespread applications. Here fluorescent carbon nanodots are documented as a game-changer, applicable in versatile fluidic environment for the visualization in microfluidics with unprecedented advantages. One of the fastest fluorescent imaging speeds up to 2500 frames per second under a normal contionous wave (CW) laser line is achieved by adopting carbon nanodots in microfluidics. Besides better visualizations of the fluid or interface, fluorescent carbon nanodots-based microparticles enable quantitative studies of high speed dynamics in fluids at microscale with a more than 90% lower cost, which is inaccessible by traditionally adopted fluorescent dye based seeding particles. The findings hold profound influences to microfluidic investigations and may even lead to revolutionary changes to the relevant industries.


Great imitator with exclusive oral manifestations.
Oral manifestations in syphilis are frequent through the different stages of the disease. Exclusive oral localization in secondary syphilis (SS) is yet uncommon. Delays in diagnosis are frequent in these patients. We describe a case of SS limited to the buccal mucosa with both serological and histological confirmation.


Effect of anaesthetizing the region of the paraventricular hypothalamic nuclei on energy metabolism during exercise in the rat.
The ventromedial and posterior hypothalamic nuclei are known to influence glucoregulation during exercise. The extensive projections of the paraventricular hypothalamic nucleus (PVN) to the sympathetic nervous system suggest that the PVN also may be involved in glucoregulation during exercise. The region of the PVN was anaesthetized with bupivacaine before running (26 m min-1) or continued rest, via previously implanted bilateral brain cannulas aimed at the dorsal aspect of the PVN. Control rats were treated identically to PVN-anaesthetized rats, but were not infused. Blood, for determination of plasma concentrations of metabolites and hormones, was drawn from a tail artery, and 3H-glucose was infused in a tail vein for glucose turnover determinations. At rest, no significant changes in plasma concentrations of metabolites or hormones were induced by anaesthesia of the region of the PVN. During exercise, glucose production and utilization and plasma concentrations of glucose, lactate, glycerol, noradrenaline, adrenaline, corticosterone, and glucagon increased (P < 0.02) and plasma insulin decreased (P < 0.02) in all rats. However, initially in exercise, adrenaline (4.3 +/- 0.8 vs. 7.9 +/- 1.0 nmol l-1 in controls, P < 0.05, t = 6 min) and later corticosterone levels (1.37 +/- 0.06 vs. 1.69 +/- 0.10 nmol l-1 in controls, P < 0.05, t = 20 min) were attenuated by PVN anaesthesia. Initially during exercise, glucose utilization was higher and plasma glucose lower in PVN-anaesthetized rats compared to controls (16.6 +/- 0.8 vs. 12.7 +/- 0.6 mumol min-1 100 g-1 and 7.1 +/- 0.2 vs. 8.1 +/- 0.2 mmol l-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)


Assessing Competence in Critical Care Echocardiography: Development and Initial Results of an Examination and Certification Processes.
To describe the development and initial results of an examination and certification process assessing competence in critical care echocardiography. A test writing committee of content experts from eight professional societies invested in critical care echocardiography was convened, with the Executive Director representing the National Board of Echocardiography. Using an examination content outline, the writing committee was assigned topics relevant to their areas of expertise. The examination items underwent extensive review, editing, and discussion in several face-to-face meetings supervised by National Board of Medical Examiners editors and psychometricians. A separate certification committee was tasked with establishing criteria required to achieve National Board of Echocardiography certification in critical care echocardiography through detailed review of required supporting material submitted by candidates seeking to fulfill these criteria. The writing committee met twice a year in person at the National Board of Medical Examiner office in Philadelphia, PA. Physicians enrolled in the examination of Special Competence in Critical Care Electrocardiography (CCEeXAM). A total of 524 physicians sat for the examination, and 426 (81.3%) achieved a passing score. Of the examinees, 41% were anesthesiology trained, 33.2% had pulmonary/critical care background, and the majority had graduated training within the 10 years (91.6%). Most candidates work full-time at an academic hospital (46.9%). The CCEeXAM is designed to assess a knowledge base that is shared with echocardiologists in addition to that which is unique to critical care. The National Board of Echocardiography certification establishes that the physician has achieved the ability to independently perform and interpret critical care echocardiography at a standard recognized by critical care professional societies encompassing a wide spectrum of backgrounds. The interest shown and the success achieved on the CCEeXAM by practitioners of critical care echocardiography support the standards set by the National Board of Echocardiography for testamur status and certification in this imaging specialty area.


Hypothermia associated with autonomic dysreflexia after traumatic spinal cord injury.
Individuals with traumatic upper thoracic and cervical spinal cord injuries are at increased risk for the development of both thermoregulatory dysfunction and autonomic dysreflexia. It is unclear, however, what effect reflex autonomic sympathetic outflow has on thermoregulatory dysfunction during episodes of autonomic dysreflexia. The following case of an individual with C5 tetraplegia and both thermoregulatory dysfunction and autonomic dysreflexia illustrates the profound effects that the autonomic nervous system may have on body temperature in individuals at risk for this complication.


Reporting Military Sexual Trauma: A Mixed-Methods Study of Women Veterans' Experiences Who Served From World War II to the War in Afghanistan.
Since 2004, there has been increased effort to reduce military sexual trauma (MST) in the U.S. military. Although MST covers a range of inappropriate behaviors, the majority of research, treatment, and outreach are focused on sexual assault and the experiences of individuals serving in Afghanistan and Iraq. During a study on veterans' involvement in a national peace organization, participants were asked about their military experiences. Veterans served from World War II to current conflicts in Iraq and Afghanistan. Emerging out of the responses were descriptions of women's experiences with MST, barriers to reporting incidents of sexual misconduct and sexual assault, and the challenges they faced when seeking care. Data were gathered using anonymous questionnaires and semi-structured interviews. Out of 52 female veterans, the majority (90%) was subjected to at least one form of MST, and 15% (8) attempted to report the incident(s). Over half of the assailants were of a higher rank than the survivors. The majority of veterans remained silent due to lack of options to report, the status of perpetrators, and fear of retaliation. These data provide a glimpse into the challenges many women veterans faced when seeking assistance reporting incidents or obtaining health care for their MST.


Investigation of biomass concentration, lipid production, and cellulose content in Chlorella vulgaris cultures using response surface methodology.
The microalgae Chlorella vulgaris produce lipids that after extraction from cells can be converted into biodiesel. However, these lipids cannot be efficiently extracted from cells due to the presence of the microalgae cell wall, which acts as a barrier for lipid removal when traditional extraction methods are employed. Therefore, a microalgae system with high lipid productivity and thinner cell walls could be more suitable for lipid production from microalgae. This study addresses the effect of culture conditions, specifically carbon dioxide and sodium nitrate concentrations, on biomass concentration and the ratio of lipid productivity/cellulose content. Optimization of culture conditions was done by response surface methodology. The empirical model for biomass concentration (R(2) = 96.0%) led to a predicted maximum of 1123.2 mg dw L(-1) when carbon dioxide and sodium nitrate concentrations were 2.33% (v/v) and 5.77 mM, respectively. For lipid productivity/cellulose content ratio (R(2) = 95.2%) the maximum predicted value was 0.46 (mg lipid L(-1) day(-1) )(mg cellulose mg biomass(-1) )(-1) when carbon dioxide concentration was 4.02% (v/v) and sodium nitrate concentration was 3.21 mM. A common optimum point for both variables (biomass concentration and lipid productivity/cellulose content ratio) was also found, predicting a biomass concentration of 1119.7 mg dw L(-1) and lipid productivity/cellulose content ratio of 0.44 (mg lipid L(-1) day(-1) )(mg cellulose mg biomass(-1) )(-1) for culture conditions of 3.77% (v/v) carbon dioxide and 4.01 mM sodium nitrate. The models were experimentally validated and results supported their accuracy. This study shows that it is possible to improve lipid productivity/cellulose content by manipulation of culture conditions, which may be applicable to any scale of bioreactors.


Antibodies against oxidized low-density lipoprotein for the treatment of vulnerable plaques.
Inflammation caused by the accumulation of oxidized low-density lipoprotein (oxLDL) in the arterial wall is a key factor in the development of atherosclerosis. Accumulating evidence suggests that adaptive immune responses to oxLDL are of major importance in regulating the inflammatory response, and that humoral immunity largely has a protective effect in this process. This concept is supported by animal studies demonstrating that treatment with antibodies against oxLDL inhibits atherosclerosis. Human antibodies with high affinity and specificity for epitopes on oxLDL have been developed and are now, after appropriate safety testing and non-clinical toxicology, ready to be tested in humans. Patients that may benefit front antibody treatment are most likely to be high-risk individuals in which conventional treatments, including lipid-lowering statins, do not provide sufficient protection.


The sesquiterpene beta-caryophyllene oxide attenuates ethanol drinking and place conditioning in mice.
Approximately 20 million adults in the United States have an alcohol use disorder. In recent years, modulation of the behavioral effects of ethanol by phytochemicals has been explored. In this study, we used the ethanol-induced loss of righting reflex (LORR) assay to assess potency differences between the sesquiterpene phytochemical beta-caryophyllene (BCP) and its derivative caryophyllene oxide (BCPO). We also investigated the effects of BCPO on two bottle-choice ethanol drinking and the ethanol-induced conditioned place preference (CPP). We then determined whether there are any pharmacokinetic or pharmacodynamic interactions between BCPO and ethanol, using blood ethanol analysis and pretreatments with the selective cannabinoid receptor 2 (CB2) antagonist AM630, respectively. BCPO augmented the ethanol-induced LORR at a dose (30 mg/kg) tenfold lower than BCP (300 mg/kg). Swiss-Webster mice were found to split into stable high and low drinking groups. This same dose (30 mg/kg) of BCPO significantly decreased ethanol intake and preference for ethanol over water in mice that consumed high amounts of ethanol, without any effect on total fluid intake. BCPO had limited effects in mice that consumed low amounts of ethanol. BCPO also significantly attenuated the ethanol-induced CPP. Blood ethanol analysis showed no significant effect of ethanol on the pharmacokinetics of ethanol. Furthermore, the enhancement of the ethanol-induced LORR by BCPO was reversed by AM630. These findings demonstrate that BCPO more potently modulates the behavioral effects of ethanol than the parent compound BCP. Moreover, they suggest that BCPO modulates the behavioral effects of ethanol through pharmacodynamic rather than pharmacokinetic mechanisms.


Genomic profile of a patient with triple negative essential thrombocythemia, unresponsive to therapy: A case report and literature review.
Clonal analysis of patients with triple negative myeloproliferative neoplasm (MPN) has provided evidence of additional aberrations, including epigenetic alterations. To discover such novel genetic aberrations, patients were screened through next-generation sequencing using a myeloid sequencing panel of 54 genes using a genetic analyser. Genetic variants in 28 genes, including TET2, BCOR, BCR, and ABL1 were identified in a triple negative essential thrombocythemia (ET) patient. The individual role of some of these variants in disease pathogenesis has yet to be studied. Somatic mutations in the same genes have been reported with variable frequencies in myeloid malignancies. However, no pathogenic impact of these variants could be found; therefore, long-term follow up of patients with genetic analysis of a large cohort and the use of whole genome sequencing is required to assess the effects of these variants.


[Synthesis and experimental study of a novel polymer/gene compound drug controlled release system for the treatment of erectile dysfunction].
To overcome the deficiency in the current therapies for erectile dysfunction (ED), we designed and synthesized a novel high-efficiency polymer/gene compound drug controlled release system and discussed the feasibility of pH and temperature dually sensitive injectable hydrogel in ED gene therapy. We synthesized optimal siRNA gene nanoparticles by characterizing the zeta potential of polylysine (PLL)/siRNA gene compounds, and established a pH and temperature dually sensitive injectable gene compound drug controlled release system via Schiffs reaction between glycol chitosan (GC) and benzaldehyde capped OHC-PEO-PPO-PEO-CHO. Then we demonstrated the sustained release of the system at different temperatures. When the mass ratio of PLL to siRNA was 20:1, the zeta potential of the PLL/siRNA gene compound reached the peak (+23.5 mV) and the siRNA was encapsulated by PLL in the maximal degree. GC and OHC-PEO-PPO-PEO-CHO was crosslinked via benzoicimine reaction when environmental pH was changed from 5.5 to 7.4. The reslease of the siRNA encapsulated in this system kept at a low rate at 37 degrees C, significantly enhanced with the increase of the temperature to 60 degrees C, rising to (122.5 +/- 5.3) microg at 1 000 minutes as compared with (23.8 +/- 6.0) microg at 37 degrees C (P < 0.05). The polymer/gene compound drug controlled release system was successfully synthesized, which improved the stability and capacity of gene carriers and achieved siRNA release at different temperatures, promising to be a new approach to the gene therapy of ED.


Discovering functionally important sites in proteins.
Proteins play important roles in biology, biotechnology and pharmacology, and missense variants are a common cause of disease. Discovering functionally important sites in proteins is a central but difficult problem because of the lack of large, systematic data sets. Sequence conservation can highlight residues that are functionally important but is often convoluted with a signal for preserving structural stability. We here present a machine learning method to predict functional sites by combining statistical models for protein sequences with biophysical models of stability. We train the model using multiplexed experimental data on variant effects and validate it broadly. We show how the model can be used to discover active sites, as well as regulatory and binding sites. We illustrate the utility of the model by prospective prediction and subsequent experimental validation on the functional consequences of missense variants in HPRT1 which may cause Lesch-Nyhan syndrome, and pinpoint the molecular mechanisms by which they cause disease.


Activation of the inflammasome and enhanced migration of microparticle-stimulated dendritic cells to the draining lymph node.
Porous silicon microparticles presenting pathogen-associated molecular patterns mimic pathogens, enhancing internalization of the microparticles and activation of antigen presenting dendritic cells. We demonstrate abundant uptake of microparticles bound by the TLR-4 ligands LPS and MPL by murine bone marrow-derived dendritic cells (BMDC). Labeled microparticles induce concentration-dependent production of IL-1β, with inhibition by the caspase inhibitor Z-VAD-FMK supporting activation of the NLRP3-dependent inflammasome. Inoculation of BALB/c mice with ligand-bound microparticles induces a significant increase in circulating levels of IL-1β, TNF-α, and IL-6. Stimulation of BMDC with ligand-bound microparticles increases surface expression of costimulatory and MHC molecules, and enhances migration of BMDC to the draining lymph node. LPS-microparticles stimulate in vivo C57BL/6 BMDC and OT-1 transgenic T cell interactions in the presence of OVA SIINFEKL peptide in lymph nodes, with intact nodes imaged using two-photon microscopy. Formation of in vivo and in vitro immunological synapses between BMDC, loaded with OVA peptide and LPS-microparticles, and OT-1 T cells are presented, as well as elevated intracellular interferon gamma levels in CD8(+) T cells stimulated by BMDC carrying peptide-loaded microparticles. In short, ligand-bound microparticles enhance (1) phagocytosis of microparticles; (2) BMDC inflammasome activation and upregulation of costimulatory and MHC molecules; (3) cellular migration of BMDC to lymphatic tissue; and (4) cellular interactions leading to T cell activation in the presence of antigen.


First demonstration of 3-D lymphatic mapping in breast cancer using freehand SPECT.
Freehand SPECT is a 3-D tomographic imaging modality based on data acquisition with a hand-held detector that is moved freely, in contrast to conventional, fixed gamma camera systems. In this pilot study, the feasibility of freehand SPECT for 3-D lymphatic mapping in breast cancer was evaluated. A total of 85 patients (age: 29-88 years) with an initial diagnosis of invasive breast cancer and no clinical evidence of nodal involvement prospectively underwent sentinel lymph node (SLN) biopsy. Preoperative lymphatic mapping (35-87 MBq (99m)Tc-Nanocoll) included tomographic imaging with a SPECT/CT device (Siemens Symbia T6) serving as reference. Initially, the freehand SPECT approach was assessed in a pilot study consisting of 50 patients. The quality of each freehand SPECT acquisition was assessed and ranked as good, intermediate or poor. In another series comprising a further 35 patients (validation study), a guidance system for the acquisition was implemented based on the results of the pilot study, ensuring acquisitions with good quality. For 3-D tomographic image reconstruction, ad hoc models and iterative reconstruction algorithms were used in all 85 patients. To allow for adequate comparison, SPECT/CT data and freehand SPECT data were registered within the same coordinate system. In the pilot study, freehand SPECT enabled mapping of 24 of 83 SLNs in 20 of 44 patients (3 dropouts, 3 patients without SLN either in SPECT/CT or in freehand SPECT). Using SPECT/CT as reference, the accuracy of freehand SPECT was 77.8% (7/9 nodes) in scans with good quality, while for intermediate and poor quality scans, the accuracy was reduced to 34.3 and 12.8%, respectively. In the validation study, quality feedback improved the results significantly and freehand SPECT enabled the mapping of at least one SLN in 87.5% of the patients (28/32 - 3 dropouts). Compared to the reference method, freehand SPECT showed a sensitivity of 83.3% (35/42 nodes). False-negative findings were related to insufficient scanning time, insufficient coverage of the axillary region, close proximity of the SLN to the injection site and low tracer uptake in the SLNs. In this preliminary study, we could demonstrate that 3-D localization of SLNs is feasible using freehand SPECT technology. Prerequisites for acquisition of a good scan quality, most likely allowing precise SLN mapping, have been defined. This approach has high potential to allow image-guided biopsy and further standardization of SLN dissection, thus bringing 3-D nuclear imaging into the operating room.


Photoreceptor PhyB Involved in Arabidopsis Temperature Perception and Heat-Tolerance Formation.
The influence of temperature on plants is essential. However, our knowledge on the intricate regulation process underlying heat stress (HS) response in plants is limited. Recently, information about thermal sensors in vivo has begun to emerge. In this study, another primary environmental stimulus, light, was verified once again to work with temperature synergistically on plants, through the modulation of numerous biological processes. With the application of transcriptomic analysis, a substantial number of heat-responsive genes were detected involved in both light- and phytohormone-mediated pathways in Arabidopsis. During this process, phytoreceptor phyB acts as a molecular switch to turn on or turn off several other genes HS response, under different light conditions. Furthermore, a morphological study showed the afunction of phyB enhanced plants thermal tolerance, confirming the important role of this phytochrome in temperature perception and response in plants. This study adds data to the picture of light and temperature signaling cross-talk in plants, which is important for the exploration of complicated HS responses or light-mediated mechanisms. Furthermore, based on its influence on Arabidopsis thermal response in both morphological and physiological levels, phyB is a photoreceptor, as revealed before, as well as an essential thermal sensor in plants.


Teenage pregnancy: a psychopathological risk for mothers and babies?
Teen pregnancy remains a public health problem of varying importance in developing and developed countries. There are risks and consequences for teen parents and the child on the medical and socioeconomic level. We conducted a literature search on multiple databases, focusing on the risk and the consequences of teen pregnancy and childbearing. We used different combined keywords as teen pregnancy, teen mother, teenage parents, teenage childbearing, teenage mother depression. Our search included different type of journals to have access on different views (medical, psychological, epidemiologic). The teen mothers are more at risk for postnatal depression, school dropout and bad socioeconomic status. The babies and children are more at risk for prematurity and low birthweight and later for developmental delays and behavior disorders. Pregnancy in adolescence should be supported in an interdisciplinary way (gynecologist, psychologist, child psychiatrist, midwives, pediatrician). We need further studies that allow targeting patients most at risk and personalizing maximum support.


FRNK negatively regulates IL-4-mediated inflammation.
Focal adhesion kinase (FAK)-related nonkinase (PTK2 isoform 6 in humans, hereafter referred to as FRNK) is a cytoskeletal regulatory protein that has recently been shown to dampen lung fibrosis, yet its role in inflammation is unknown. Here, we show for the first time that expression of FRNK negatively regulates IL-4-mediated inflammation in a human model of eosinophil recruitment. Mechanistically, FRNK blocks eosinophil accumulation, firm adhesion and transmigration by preventing transcription and protein expression of VCAM-1 and CCL26. IL-4 activates STAT6 to induce VCAM-1 and CCL26 transcription. We now show that IL-4 also increases GATA6 to induce VCAM-1 expression. FRNK blocks IL-4-induced GATA6 transcription but has little effect on GATA6 protein expression and no effect on STAT6 activation. FRNK can block FAK or Pyk2 signaling and we, thus, downregulated these proteins using siRNA to determine whether signaling from either protein is involved in the regulation of VCAM-1 and CCL26. Knockdown of FAK, Pyk2 or both had no effect on VCAM-1 or CCL26 expression, which suggests that FRNK acts independently of FAK and Pyk2 signaling. Finally, we found that IL-4 induces the late expression of endogenous FRNK. In summary, FRNK represents a novel mechanism to negatively regulate IL-4-mediated inflammation.


Friend support buffers the relationship between maltreatment and nonsuicidal self-injury in adolescence.
Prior studies have mostly focused on the risk factors for nonsuicidal self-injury (NSSI), but only a few studies have emphasized the related protective factors. The present study examined whether maltreatment and behavioral problems were risk factors for NSSI. Moreover, we also sought to understand whether and how friend support provides a buffer against NSSI. A total of 436 adolescents completed self-report surveys that addressed maltreatment, behavioral problems, friend support, and NSSI at three different time points. There were significant positive correlations between maltreatment and NSSI. In the mediation analyses, we found that maltreatment was indirectly associated with NSSI via behavioral problems. Friend support demonstrated a long-term buffering effect on NSSI. Specifically, friend support had a protective effect on NSSI not only under high maltreatment levels, but also under high behavioral problem levels. These findings contribute to the understanding of the influences of both maltreatment, behavioral problems (risk factors), and friend support (protective factors) on NSSI. In the context of intervention and education, it is important to consider the value of friend support when discussing NSSI.


Pregnancy as a window to future health: maternal placental syndromes and short-term cardiovascular outcomes.
Cardiovascular disease is the leading cause of death among women. Identifying risk factors for future cardiovascular disease may lead to earlier lifestyle modifications and disease prevention. Additionally, interpregnancy development of cardiovascular disease can lead to increased perinatal morbidity in subsequent pregnancies. Identification and implementation of interventions in the short term (within 5 years of first pregnancy) may decrease morbidity in subsequent pregnancies. We identified the short-term risk (within 5 years of first pregnancy) of cardiovascular disease among women who experienced a maternal placental syndrome, as well as preterm birth and/or delivered a small-for-gestational-age infant. We conducted a retrospective cohort study using a population-based, clinically enhanced database of women in the state of Florida. Nulliparous women and girls aged 15-49 years experiencing their first delivery during the study time period with no prepregnancy history of diabetes mellitus, hypertension, or heart or renal disease were included in the study. The risk of subsequent cardiovascular disease was compared among women who did and did not experience a placental syndrome during their first pregnancy. Risk was then reassessed among women with placental syndrome and preterm birth or delivering a small-for-gestational-age infant vs those without these adverse pregnancy outcomes. The final study population was 302,686 women and girls. Median follow-up time for each patient was 4.9 years. The unadjusted rate of subsequent cardiovascular disease among women and girls with any placental syndrome (11.8 per 1000 women) was 39% higher than the rate among women and girls without a placental syndrome (8.5 per 1000 women). Even after adjusting for sociodemographic factors, preexisting conditions, and clinical and behavioral conditions associated with the current pregnancy, women and girls with any placental syndrome experienced a 19% increased risk of cardiovascular disease (hazard ratio, 1.19; 95% confidence interval, 1.07-1.32). Women and girls with >1 placental syndrome had the highest cardiovascular disease risk (hazard ratio, 1.43; 95% confidence interval, 1.20-1.70), followed by those with eclampsia/preeclampsia alone (hazard ratio, 1.42; 95% confidence interval, 1.14-1.76). When placental syndrome was combined with preterm birth and/or small for gestational age, the adjusted risk of cardiovascular disease increased 45% (95% confidence interval, 1.24-1.71). Women and girls with placental syndrome who then developed cardiovascular disease experienced a 5-fold increase in health care-related costs during follow-up, compared to those who did not develop cardiovascular disease. Women and girls experiencing placental syndromes and preterm birth or small-for-gestational-age infant are at increased risk of subsequent cardiovascular disease in short-term follow-up. Strategies to identify and improve cardiovascular disease risk in the postpartum period may improve future heart disease outcomes.


Impact of Bone Mineral Density on the Incidence of Age-Related Vertebral Fragility Fracture.
Vertebral fragility fracture (VFF) is a common fracture related to osteoporosis. However, VFF might be asymptomatic and often occurs in patients without osteoporosis. Therefore, we investigated the characteristics of age-related VFF and their correlation with bone mineral density (BMD). Furthermore, we analyzed other factors affecting VFF. Medical records from a single center were retrospectively reviewed for 2,216 patients over 50 years old with vertebral fractures conservatively treated from 2005 to 2016. Patients' age, gender, body mass index (BMI), BMD, fracture level, previous vertebral fractures, and anti-osteoporosis medications were obtained. Patients were divided into fragility/non-fragility groups and age sub-groups. The odds ratio for VFF in relation to BMD was evaluated. We also identified other predictive factors for VFF by age groups. The fragility group had a higher women ratio, older age, lower BMI, lower BMD, and greater incidence of previous vertebral fractures than the non-fragility group. VFFs were seen in 41.18% of normal BMD patients aged 50-59 and 67.82% of those aged 60-69. The proportion of VFFs increased with age in all WHO osteoporosis classifications. Patients with osteopenia and osteoporosis were 1.57 and 2.62 fold more likely to develop VFFs than normal BMD. In the younger group (under 70), age, women, BMD, and previous vertebral fracture were significant factors affecting VFF, and in the older group (70 and over), age, women, and BMD were factors. In the fragility group, anti-osteoporosis medication rates were 25.08% before and 45.96% after fracture. Considerable VFFs occurred in the younger age groups without osteoporosis and age itself was another important predictor of VFF especially in older age groups. The discrepancy between the incidence of VFF and BMD suggests the necessity of supplemental screening factors and anti-osteoporosis treatment guidelines using only BMD should be reconsidered.


[Transurethral holmium laser enucleation of the prostate for the treatment of benign prostatic hyperplasia].
To evaluate the efficacy and safety of transurethral holmium laser enucleation of the prostate (HoLEP) for the treatment of benign prostatic hyperplasia (BPH). A retrospective review was conducted of transurethral (HoLEP) performed on 68 patients, aged 65.7 (50 - 91) with benign prostatic hyperplasia. The efficacy and complications were all assessed. The mean procedure time was 87 mins (45 - 158 mins). The mean specimen weight was 61 g (31 - 128 g). The procedure allows a precise, bloodless field with no need for transfusion. No TUR syndrome and other major complications were encountered during the operation. The mean catheter time and hospital stay were 2.8 d (1 - 4 d) and 3.6 d (2 - 5 d), respectively. Follow-up of 7.6 months (1 - 13 months) revealed that the urination symptoms were markedly improved in all patients, and that the IPSS decreased from 25.7 +/- 6.9 to 7.7 +/- 4.3 (P < 0.01) and the maximum urine flow rate increased from 8.1 +/- 4.2 ml/s to 18.8 +/- 4.6 ml/s (P < 0.01). Postoperative complications occurred in 3 patients. 2 with transient incontinence were recovered within 3 months postoperatively. The other one with mild posterior urethral stricture was treated effectively with urethral sounding. Was associated with high effectiveness, safety, short hospital stay and less complications, HoLEP is a new minimally invasive surgical procedure for BPH.


Aquatic Biofilms-Sink or Source of Microplastics? A Critical Reflection on Current Knowledge.
The scientific understanding regarding sources, occurrence, and effects of microplastics in the aquatic environment has advanced rapidly, leaving some meaningful knowledge gaps virtually untouched. One of them is the interactions of microplastics and biofilms, microbial communities ubiquitous in aquatic ecosystems and fundamental for a range of ecosystem-level processes. It is evident that biofilms can quickly develop on the microplastic surface and consequently change particle properties and, as such, its fate and ecotoxicity. Moreover, microplastics interact with ubiquitous biofilms that are developed on any surfaces in aquatic ecosystems. Although the knowledge about these interactions is at best limited, it is expected that microplastics attach to the water-biofilm interface or penetrate the biofilm matrix. Microplastics can accumulate and ab- or adsorb to those biofilms where they are subjected to transformation processes such as fragmentation. Thus, biofilms may function as a sink. Changes in environmental conditions may, however, stress biofilms initiating their dieback and microplastic release, which could turn biofilms into a source of microplastics. We argue that the accumulation and release dynamics are a largely overlooked but potentially important piece to the puzzle that is a comprehensive understanding of microplastic fate in the environment and thus under the influence of multiple interacting factors. Environ Toxicol Chem 2022;41:838-843. © 2021 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.


The right to genetic ignorance confirmed.
One of the much debated issues around the evolving human genetics is the question of the right to know versus the right not to know. The core question of this theme is whether an individual has the right to know about her own genetic constitution and further, does she also have the right to remain in ignorance. Within liberal traditions it is usually held that people, if they so wish, have the right to all the knowledge available about themselves. This right is based on the value of autonomy or on the right of self-determination, and it is sometimes partly justified as a countermeasure to the authorities' control over people. I do not wish to deny the right to genetic knowledge (about oneself). I think that its existence is self-evident. The argument I want to put forth in this paper is that in liberal societies we should acknowledge people's right to remain in ignorance as well. The only reason for not doing this would be that grave harm to others would follow if people were allowed to make these seemingly self-regarding decisions. Arguments presented against the right to ignorance are two-fold. First there are those arguing against the right to ignorance on the grounds of harm to others, that is, philosophers who do not deny people's right to ignorance in self-related matters but wish to state that genetic ignorance causes harm to others, and this is one of the most commonly accepted reasons for restricting people's freedom. The other line of argument flows from the Kantian view that not even merely self-regarding foolishness (in the eyes of others) should be allowed.


Lignin depletion enhances the digestibility of cellulose in cultured xylem cells.
Plant lignocellulose constitutes an abundant and sustainable source of polysaccharides that can be converted into biofuels. However, the enzymatic digestion of native plant cell walls is inefficient, presenting a considerable barrier to cost-effective biofuel production. In addition to the insolubility of cellulose and hemicellulose, the tight association of lignin with these polysaccharides intensifies the problem of cell wall recalcitrance. To determine the extent to which lignin influences the enzymatic digestion of cellulose, specifically in secondary walls that contain the majority of cellulose and lignin in plants, we used a model system consisting of cultured xylem cells from Zinniaelegans. Rather than using purified cell wall substrates or plant tissue, we have applied this system to study cell wall degradation because it predominantly consists of homogeneous populations of single cells exhibiting large deposits of lignocellulose. We depleted lignin in these cells by treating with an oxidative chemical or by inhibiting lignin biosynthesis, and then examined the resulting cellulose digestibility and accessibility using a fluorescent cellulose-binding probe. Following cellulase digestion, we measured a significant decrease in relative cellulose content in lignin-depleted cells, whereas cells with intact lignin remained essentially unaltered. We also observed a significant increase in probe binding after lignin depletion, indicating that decreased lignin levels improve cellulose accessibility. These results indicate that lignin depletion considerably enhances the digestibility of cellulose in the cell wall by increasing the susceptibility of cellulose to enzymatic attack. Although other wall components are likely to contribute, our quantitative study exploits cultured Zinnia xylem cells to demonstrate the dominant influence of lignin on the enzymatic digestion of the cell wall. This system is simple enough for quantitative image analysis, but realistic enough to capture the natural complexity of lignocellulose in the plant cell wall. Consequently, these cells represent a suitable model for analyzing native lignocellulose degradation.


Continual assembly of desmosomes within stable intercellular contacts of epithelial A-431 cells.
Subclones of human carcinoma-derived A-431 cell line stably producing fusion proteins consisting of the enhanced green fluorescent protein and either human desmoglein 2 (Dsg-GFP) or human plakoglobin (GFP-Pg) were used to examine the behavior of desmosomes in living cells. Immunofluorescence microscopy of the fixed cells showed that both fusion proteins, which were expressed in significantly lower levels relative to their endogenous counterparts, were efficiently recruited into desmosomes. Time-lapse confocal imaging of these cells reveals that such GFP-labeled desmosomes (GFP desmosomes) are stable structures which exhibit various dynamic and motile activities. The most notable are independent lateral mobility and fusion. Furthermore, the continual assembly of new nascent desmosomes is observed within stable contacts located at the middle of the epithelial sheet. A new GFP desmosome appears as a closely apposed group of fine patches which after a few minutes aggregate into a single structure. These three dynamic processes resulted in constant changes of desmosome distribution, numbers, and sizes. In addition, fluorescence recovery after photobleaching experiments showed that fine patches of desmosomal proteins may participate in desmosome maintenance. Such a diverse range of dynamic activities of desmosomes apparently produces flexible but tight cell-cell adhesion required for different morphogenetic events in epithelial structures.


Simultaneous Nanolocal Polymer and In Situ Readout Unit Placement in Mesoporous Separation Layers.
Bioinspired solid-state nanopores and nanochannels have attracted interest in the last two decades, as they are envisioned to advance future sensing, energy conversion, and separation concepts. Although much effort has been made regarding functionalization of these materials, multifunctionality and accurate positioning of functionalities with nanoscale precision still remain challenging. However, this precision is necessary to meet transport performance and complexity of natural pores in living systems, which are often based on nonequilibrium states and compartmentalization. In this work, a nanolocal functionalization and simultaneous localized sensing strategy inside a filtering mesoporous film using precisely placed plasmonic metal nanoparticles inside mesoporous films with pore accessibility control is demonstrated. A single layer of gold nanoparticles is incorporated into mesoporous thin films with precise spatial control along the nanoscale layer thickness. The local surface plasmon resonance is applied to induce a photopolymerization leading to a nanoscopic polymer shell around the particles and thus nanolocal polymer placement inside the mesoporous material. As near-field modes are sensitive to the dielectric properties of their surrounding, the in situ sensing capability is demonstrated using UV-vis spectroscopy. It is demonstrated that the sensing sensitivity only slightly decreases upon functionalization. The presented nanolocal placement of responsive functional polymers into nanopores offers a simultaneous filtering and nanoscopic readout function. Such a nanoscale local control is envisioned to have a strong impact onto the development of new transport and sensor concepts, especially as the system can be developed into higher complexity using different metal nanoparticles and additional design of mesoporous film filtering properties.


In vivo potentiation of 5-fluorouracil cytotoxicity against AKR leukemia by purines, pyrimidines, and their nucleosides and deoxynucleosides.
The effect of various natural pyrimidines and purines and their nucleosides and deoxynucleosides on 5-fluorouracil (FUra) cytotoxicity was examined against the transplantable AKR leukemia in female AKR mice. The spleen colony assay was used for a quantitative evaluation of the antitumor activity of the combination treatments. The base or nucleoside was administered 15 minutes before each mouse received an injection of 0.6 mg FUra. All of the compounds tested, with the exception of adenine, potentiated the cell-killing effect of FUra. On a molar basis (16-30 mumol/mouse), thymine, uracil, thymidine, and uridine enhanced FUra cytotoxicity more than a hundredfold. 2'-Deoxyuridine and the purine nucleosides and deoxynucleosides had similar potentiating activities between tenfold and fortyfold at 30 mumol per mouse. Finally, glucose, also administered 15 minutes before each mouse received an injection of 0.6 mg FUra, enhanced the antitumor activity of the drug by a factor of about five.


Modeling design iteration in product design and development and its solution by a novel artificial bee colony algorithm.
Due to fierce market competition, how to improve product quality and reduce development cost determines the core competitiveness of enterprises. However, design iteration generally causes increases of product cost and delays of development time as well, so how to identify and model couplings among tasks in product design and development has become an important issue for enterprises to settle. In this paper, the shortcomings existing in WTM model are discussed and tearing approach as well as inner iteration method is used to complement the classic WTM model. In addition, the ABC algorithm is also introduced to find out the optimal decoupling schemes. In this paper, firstly, tearing approach and inner iteration method are analyzed for solving coupled sets. Secondly, a hybrid iteration model combining these two technologies is set up. Thirdly, a high-performance swarm intelligence algorithm, artificial bee colony, is adopted to realize problem-solving. Finally, an engineering design of a chemical processing system is given in order to verify its reasonability and effectiveness.


Sjögren's syndrome with multiple cystic lesions and pulmonary arteriovenous fistulae.
A patient presented with Sjögren's syndrome associated with pulmonary multiple cystic lesions and a pulmonary arteriovenous fistulae. A histological examination of the lungs during the autopsy revealed the stenosis of the bronchiole lumens with hyperplasia of goblet cells, proliferation of smooth muscles in the inner wall of the bronchioli and retention of mucus in the airway lumens. These small airway changes were accompanied with chronic inflammatory changes of the airways in Sjögren's syndrome and led to the formation of cystic lesions via a ball-valve mechanism. Arteriovenous fistulae were situated around the cystic lesions. There may have been a correlation between the formation of the fistulae and cysts, but no mechanism was indicated in the histological findings. This report reveals that chronic inflammatory changes of the airways in Sjögren's syndrome are sufficient to cause the formation of cystic lesions.


A potent larvicidal agent against Aedes aegypti mosquito from cardanol.
Cardanol is a constituent of Cashew Nut Shell Liquid that presents larvicidal activity against Aedes aegypti. The isolation of cardanol is somewhat troublesome, however, in this work we describe an efficient and inexpensive method to obtain it as a pure material. The compound was used as starting material to make chemical transformation leading to saturated cardanol, epoxides and, halohydrins. These derivatives were tested for toxicity against Aedes aegypti larvae. The results showed that iodohydrins are very promising compounds for making commercial products to combat the vector mosquito larvae presenting a LC50 of 0.0023 ppm after 72 h of exposure.


Solvatochromic probe behavior within choline chloride-based deep eutectic solvents: effect of temperature and water.
Deep eutectic solvents (DESs) have shown potential as promising environmentally friendly alternatives to conventional solvents. Many common and popular DESs are obtained by simply mixing a salt and a H-bond donor. Properties of such a DES depend on its constituents. Change in temperature and addition of water, a benign cosolvent, can change the physicochemical properties of DESs. The effect of changing temperature and addition of water on solvatochromic probe behavior within three DESs formed from choline chloride combined with 1,2-ethanediol, glycerol, and urea, respectively, in 1:2 mol ratios termed ethaline, glyceline, and reline is presented. Increase in temperature results in reduced H-bond donating acidity of the DESs. Dipolarity/polarizability and H-bond accepting basicity do not change with changing temperature of the DESs. The response of the fluorescence probe pyrene also indicates a decrease in the polarity of the DESs as temperature is increased. Addition of water to DES results in increased dipolarity/polarizability and a decrease in H-bond accepting basicity. Except for pyrene, solvatochromic probes exhibit responses close to those predicted from ideal-additive behavior with slight preferential solvation by DES within the aqueous mixtures. Pyrene response reveals significant preferential solvation by DES and/or the presence of solvent-solvent interactions, especially within aqueous mixtures of ethaline and glyceline, the DESs constituted of H-bond donors with hydroxyl functionalities. FTIR absorbance and Raman spectroscopic measurements of aqueous DES mixtures support the outcomes from solvatochromic probe responses. Aqueous mixtures of ethaline and glyceline possess relatively more interspecies H-bonds as compared to aqueous mixtures of reline, where interstitial accommodation of water within the reline molecular network appears to dominate.


Cerebral salt wasting treated with fludrocortisone in a 17-year-old boy.
Cerebral salt wasting is characterized by inappropriate natriuresis and volume contraction with associated cerebral pathology. It is distinct from the syndrome of inappropriate antidiuretic hormone secretion, which is characterized by inappropriate retention of free water. We report a patient with a porencephalic cyst who developed cerebral salt wasting. His initial treatment was supplementation of water and salt, which did not improve natriuresis or volume contraction. Fludrocortisone administration effectively managed the cerebral salt wasting.


Stress causes alteration in attachment of rat hepatocytes to matrix protein substratum.
The effect of different types of stress on the attachment of rat hepatocytes to various matrix protein substrata, such as collagen IV, fibronectin and laminin, was investigated. Study of the kinetics of attachment of adult hepatocytes subjected to heat-shock at 45 degrees C for 30 min showed significantly lower attachment to collagen IV, fibronectin and laminin substrata when compared to untreated controls. The alteration in attachment was observed after heat-treatment for 10 min and the extent of alteration appeared to increase with duration of the heat-treatment, as well as with increase in temperature. Foetal rat hepatocytes, which appeared to attach much more readily than adult rat hepatocytes to these substrata, particularly to laminin, also showed significantly lower attachment to all three substrata after heat-treatment at 45 degrees C for 30 min. This alteration in attachment appeared to be specific for matrix proteins as there was no significant effect on interaction of cells with non-matrix proteins, such as Con A and asialoglycoproteins. While the attachment of adult hepatocytes appeared to attain near control levels in about 4 h, the foetal cells recovered in about 2 h after heat-shock, indicating that the heat-shock effect is reversible and the recovery is faster in foetal hepatocytes. Other stress-causing agents, such as heavy metals, also caused an alteration in attachment of hepatocytes to these matrix proteins. Attachment of adult and foetal hepatocytes to collagen substratum was reduced by 100-microM concentrations of heavy metals in the order Zn > Cd > La > As > Cu for adult cells and La > Zn > As/Cu > Cd for foetal cells. These heavy metals also caused significant reduction in attachment of adult hepatocytes to fibronectin and laminin, although the extent of inhibition was less than that for collagen substrata. However, these heavy metals did not significantly affect the attachment of foetal hepatocytes to laminin substratum indicating that the effect of heavy metals appeared to vary with the nature of the matrix protein substratum. On heat-shock, incorporation of [3H]leucine into cytoskeletal proteins such as cytokeratins CK8 and CK18 was reduced and significant amounts of two new proteins having an average molecular mass of 80 kDa and 90 kDa were found to be tightly associated with cytoskeletal proteins.


Identifying risk factors for predicting caries in school-aged children using dental health information collected at preschool age.
The study was done to identify toddlers who have an increased risk of developing dental decay at school age. Six variables-Cariostat score, mother's ethnicity, evidence of baby bottle tooth decay, mother;s dental health status, toddler's age at first tooth, and frequency of brushing - showed a significant association with decay status at school age with odds ratios ranging from 1.89 to 2.63. The Cariostat score and the frequency of brushing remained significant in a logistic regression. No interaction terms were significant. The Cariostat caries activity test would be a useful screening tool for identifying toddlers most likely to develop decay or could be used periodically as the deciduous molars erupt and become colonized with oral bacteria. The findings confirm that good oral hygiene practices can have an impact on future dental health, and caregivers should be encouraged to brush young children's teeth regularly.


Development of vertical SU-8 microneedles for transdermal drug delivery by double drawing lithography technology.
Polymer-based microneedles have drawn much attention in transdermal drug delivery resulting from their flexibility and biocompatibility. Traditional fabrication approaches are usually time-consuming and expensive. In this study, we developed a new double drawing lithography technology to make biocompatible SU-8 microneedles for transdermal drug delivery applications. These microneedles are strong enough to stand force from both vertical direction and planar direction during penetration. They can be used to penetrate into the skin easily and deliver drugs to the tissues under it. By controlling the delivery speed lower than 2 μl/min per single microneedle, the delivery rate can be as high as 71%.


Division of Chinese soft-shelled turtle intestine with molecular markers is slightly different from the morphological and histological observation.
The Chinese soft-shelled turtle (Pelodiscus sinensis) is a commercially important species in Asian countries. Knowledge of its nutritional requirements and physiology is essential for determining the appropriate content of the feed for this animal. However, the lack of functional characterization of the intestine of this turtle limits the understanding of its absorption and utilization of nutritional materials. To solve this problem, this work utilized anatomical and histological methods to characterize 9 segments sampled along the anterior-posterior axis of the intestine. Furthermore, 9 genes, which have been well documented in the intestine division of mammals and fish, were employed to functionally characterize the 9 sampled segments. Our results suggest that regions covering from the starting site to S3 (position at 29.9% of the total length from the starting of the intestine) are the equivalent of mammalian dedumonen, and those covering S4 (40.2%) and S5 (65.4%), posterior to S8 (92.7%), are the equivalent of the mammalian ileum and the large intestine, respectively. As to the region spaning S6 (81.3%) and S7 (87.3%), its functional equivalent (small intestine or large intestine) may be variable and depends on the functional genes. This molecular characterization in relation to the division of the intestine of Chinese soft-shelled turtle may contribute to the understanding of the nutritional physiology of the turtle, and promote Chinese soft-shelled turtle production.


Robust half-metallic character and large oxygen magnetism in a perovskite cuprate.
The new perovskite cuprate material Sr8CaRe3Cu4O24, which behaves ferrimagnetically and shows an unusually high Curie temperature (T(C) approximately 440 K), is found from density-functional theory calculation to display several surprising properties after hole doping or chemical substitution: (1) Half metal (HM) is realized by replacing Re with W or Mo while T(C) remains high; (2) hole-doped Sr8CaRe3Cu4O24 is also HM with high T(C). Moreover, we find that the O atoms will carry a large magnetic moment after hole doping, which is in sharp contrast to the generally accepted concept that magnetism in solids requires partially filled shells of d or f electrons in cations. The material Sr8CaRe3Cu4O24 is therefore expected to provide a very useful platform for material design and development.


Ultrafast Growth of Uniform Multi-Layer Graphene Films Directly on Silicon Dioxide Substrates.
To realize the applications of graphene in electronics, a large-scale, high-quality, and uniform graphene film should first be placed on the dielectric substrates. Challenges still remain with respect to the current methods for the synthesis graphene directly on the dielectric substrates via chemical vapor deposition, such as a low growth rate and poor quality. Herein, we present an ultrafast method for direct growth of uniform graphene on a silicon dioxide (SiO2/Si) substrate using methanol as the only carbon source. A 1 × 1 cm2 SiO2/Si substrate square was almost fully covered with graphene within 5 min, resulting in a record growth rate of ~33.6 µm/s. This outcome is attributed to the quick pyrolysis of methanol, with the help of trace copper atoms. The as-grown graphene exhibited a highly uniform thickness, with a sheet resistance of 0.9-1.2 kΩ/sq and a hole mobility of up to 115.4 cm2/V·s in air at room temperature. It would be quite suitable for transparent conductive electrodes in electrophoretic displays and may be interesting for related industrial applications.


Mediators of low-grade chronic inflammation in polycystic ovary syndrome (PCOS).
Chronic low-grade subclinical inflammation has been increasingly recognized as an interposer in the endocrine, metabolic and reproductive disturbances that characterize the polycystic ovary syndrome (PCOS). Abdominal adiposity and obesity are often present in PCOS. Mounting evidence indicates that adipose tissue is involved in innate and adaptive immune responses. Continuous release of inflammatory mediators such as cytokines, acute phase proteins, and adipokines perpetuates the inflammatory condition associated with obesity in women with PCOS, possibly contributing to insulin resistance and other long-term cardiometabolic risk factors. Genetic variants in the genes encoding inflammation-related mediators underlie the development of PCOS and their interaction with environmental factors may contribute to the heterogeneous clinical phenotype of this syndrome. In the future, strategies ameliorating inflammation may prove useful for the management of PCOS and associated conditions.


[Clinical outcome and placenta characteristics of spontaneous twin anemia-polycythemia sequence].
Objective: To investigate the clinical outcome and placental characteristics of spontaneous twin anemia-polycythemia sequence (sTAPS). Methods: Twelve cases with sTAPS delivered in Peking University Third Hospital from May 2013 to August 2016. The data of ultrasound characteristics, gestational age at delivery, and 1 minute Apgar score were analyzed, retrospectively. Placental superficial vascular anastomoses, placental territory discordance and the ratio of umbilical cords insertion distance to the longest placental diameter were also analyzed. Results: (1) Only 1 case of sTAPS was diagnosed prenatally, the others were diagnosed postnatally because the fetal middle cerebral artery(MCA) doppler was not measured regularly. Five cases were complicated with selective intrauterine growth restriction (sIUGR). The median gestational age at delivery was 32.8 weeks (31-37 weeks) . The pregnancies were terminated because 3 cases were sIUGR type Ⅰ, 1 case was sIUGR type Ⅱ, 1 case was sIUGR type Ⅲ, 2 cases were fetal distress, 2 cases were severe pre-eclampsia, 2 cases were premature rupture of membrane, 1 case was fetal hydrops with abnormal doppler waveforms of ductus venouses. (2) When 5 sIUGR cases were excluded, there was no difference between the twins in birth weight [1 797 g (940-2 620 g) , 1 648 g (980-2 500 g) ; P=0.688]. The hemoglobin (Hb) level in all donor was significantly lower than recipient (P=0.000) and the inter-twin Hb difference was 147.6 g/L (84.0-216.0 g/L). While the reticulocyte percentage in donor was significantly higher than recipient (P=0.013) and reticulocyte percentage ratio was 3.60 (1.04-7.50). Five donor newborns had neonatal asphyxia, including 1 severe asphyxia, while no asphyxia happened in the recipient twins. (3) Arterio-arterial (A-A) anastomoses, veno-venous (V-V) anastomoses, arterio-venous (A-V) anastomoses were found in 3, 1 and 11 placentas, respectively. The total number of anastomoses was 2 (1-5) and the total diameter was 1.1 mm (0.4-2.1 mm), including 0 (0-1) A-A anastomoses with 0.2 mm (0.0-0.9 mm) in diameter and 2 (0-5) A-V anastomoses with 0.7 mm (0.0-2.1 mm) in diameter. The placental territory discordance was 0.17 (0.02-0.40) and the ratio of umbilical cords insertion to the longest placental diameter was 0.82 (0.34-0.99). Conclusions: The pathogenesis of sTAPS might result from slow and chronic blood transfusion from donor to recipient through a few minuscule vascular anastomoses in the placenta. In all monochorionic twins, especially sIUGR cases, MCA doppler should be monitored closely in the second and third trimester, in order to diagnose and manage sTAPS in time.


Enhanced suppression of melanoma tumor growth and metastasis by combined therapy with anti-VEGF receptor and anti-TYRP-1/gp75 monoclonal antibodies.
Targeted immunotherapy against tumors or angiogenesis has shown promise as an alternative approach for the treatment of malignant disease. Whether or not combining these two treatment modalities would enhance the antitumor effect was tested in mouse models of malignant melanoma. C57BL/6 mice bearing established subcutaneous B16 tumors were treated with anti-vascular endothelial growth factor receptor (anti-VEGFR) fetal liver kinase-1 (Flk-1) monoclonal antibody (mAb) DC101 and/or anti-TYRP-1/gp75 (tyrosinase-related protein-1) mAb TA99. The growth of subcutaneous B16 tumors was significantly suppressed by the mAb DC101 (63%, p<0.001) and by mAb TA99 (75%, p<0.001) treatment alone. The combined antibody (TA99+DC101) treatment resulted in a significant enhancement (93%, p<0.001) of tumor growth suppression. In a B16 pulmonary metastasis model, combined therapy with mAb DC101 and mAb TA99 resulted in a significant reduction of lung metastases compared to the control (p<0.001) and the single agent treatment groups (p<0.05). A combined modality approach that provides passive immunity to melanoma differentiation antigens as well as inhibiting tumor neovascularization may be valuable for the treatment of malignant melanoma.


A photoswitchable supramolecular complex with release-and-report capabilities.
A self-assembled supramolecular platform has been designed for reversibly controlling the concentration of a compound in solution, via a photochemical reaction. The system utilizes metal-ligand interactions between a Zn-porphyrin dimer and a pyridine-appended dithienylethene (DTE) photoswitch. In addition to reversible compound release, the spectral properties of the release scaffold provide a fluorescence-based reporting function.


Human natural lymphocyte effector cells: definition, analysis of activity, and clinical effectiveness.
Lymphokine-activated killing has enormous potential in the treatment of cancer. Lymphoid effectors have the potential to recognize and lyse a wide array of tumor cells, a phenomenon which has been seen in vitro and to some extent in vivo. However, studies have indicated that complexity exists not only in the nature of the lymphocyte that can be activated ex vivo for therapeutic use, but also in the delivery of such therapy in a clinical setting. This review attempts to deal with both issues. The nature of the cells mediating lymphokine-activated killer activity, their heterogeneous phenotype, their activation requirements, and a hypothetical mechanism of action are discussed. In addition, previous clinical studies are reviewed and key issues are raised that need to be addressed in upcoming clinical trials.


A critical review of cognitive behavioural therapy for hoarding disorder: How can we improve outcomes?
Psychological treatment for hoarding problems has historically been associated with poor outcomes. When treated as a subgroup of obsessive-compulsive disorder, individuals with hoarding beliefs were less likely to respond to treatment than individuals exhibiting other obsessive-compulsive beliefs and behaviours. When treated as its own disorder using cognitive behavioural therapy, individuals report approximately 25% improvement in symptoms on average. However, less than a third of people experience clinically meaningful change. Further, changes in functioning and quality of life are not routinely assessed. In this paper, we review the current conceptualization and treatment of hoarding problems to shed light on how treatment for hoarding disorder may be improved. Utilizing a harm reduction approach before administering treatment may be important to ensure the safety of individuals. Research should test whether treatment outcomes improve by including strategies that enhance a client's interpersonal functioning and ability to regulate emotions (i.e., based on dialectal behaviour therapy and mentalization-based treatments), especially while discarding and organizing belongings. We should also use modern learning theory to improve the delivery of exposure activities.


Nickel-Catalyzed Asymmetric Kumada Cross-Coupling of Symmetric Cyclic Sulfates.
Nickel-catalyzed enantioselective cross-couplings between symmetric cyclic sulfates and aromatic Grignard reagents are described. These reactions are effective with a broad range of substituted cyclic sulfates and deliver products with asymmetric tertiary carbon centers. Mechanistic experiments point to a stereoinvertive SN2-like oxidative addition of a nickel complex to the electrophilic substrate.


High-protein diets augment albuminuria in rats with Heymann nephritis by angiotensin II-dependent and -independent mechanisms.
Urinary albumin excretion (U(alb)V) increases following dietary protein augmentation (DPA) in nephrotic humans and rats. Angiotensin-converting enzyme inhibitors (ACEI) blunt, but do not entirely prevent, increased U(alb)V at doses that reduce blood pressure and entirely block the pressor effect of exogenously administered angiotensin I (Ang-I), suggesting that angiotensin II (Ang-II) might not mediate the effect of DPA on U(alb)V. We determined the effect of losartan (Los), a specific Ang-II receptor antagonist, and compared its effect to that of enalapril (En), an ACEI, on DPA-induced increase in U(alb)V in rats with passive Heymann nephritis (HN). When Los was administered to HN rats for 48 h prior to DPA from 8.5 to 40% casein. U(alb)V increased in an identical fashion in treated and untreated rats, even though Los caused hypotension and prevented the pressor effect of infused Ang-II. Only on day 6 after DPA did U(alb)V decrease. We then measured the effect of duration of pretreatment with Los on Ang-II binding to isolated glomeruli. Maximal inhibition of Ang-II binding required treatment with Los for 6 days. We then pretreated HN rats with either En or Los for 6 days prior to DPA. In contrast to administration of Los for 2 days prior to DPA, pretreatment with either Los or En for 6 days entirely prevented any increase in U(alb)V. We then increased dietary NaCl from 0.2% to 2% (HS) to determine whether En or Los would modulate U(alb)V after DPA when Ang-II activity was suppressed. En reduced the DPA-mediated increase in U(alb)V regardless of dietary NaCl, while Los was effective only in when dietary NaCl was reduced (0.2%), suggesting that under these conditions ACEI reduces U(alb)V by a mechanism that is independent of inhibition of Ang-II and that high protein diets augment U(alb)V by both Ang-II-independent and Ang-II-dependent mechanisms.


Night eating among veterans with obesity.
The obesity rate is higher among veterans than the general population, yet few studies have examined their eating behaviors, and none have examined the presence of night eating and related comorbidities. This study examines night eating syndrome (NES) among veterans seeking weight management treatment, and relationships between NES and weight, insomnia, disordered eating, and psychological variables. The sample consisted of 110 veterans referred to a weight management program at VA Connecticut Healthcare System. More than one out of ten veterans screened positive for NES, and one-third screened positive for insomnia. Most individuals screening positive for NES also screened positive for insomnia. Night eating was associated with higher BMI, and with higher scores on measures of binge eating, emotional overeating, and eating disorder symptomatology. Veterans screening positive for NES were also significantly more likely to screen positive for depression and PTSD. When controlling for insomnia, only the relationships between night eating and binge and emotional eating remained significant. Those screening positive for PTSD were more likely to endorse needing to eat to return to sleep. Findings suggest that both NES and insomnia are common among veterans seeking weight management services, and that NES is a marker for additional disordered eating behavior, specifically binge eating and overeating in response to emotions. Additional studies are needed to further delineate the relationships among NES, insomnia, and psychological variables, as well as to examine whether specifically addressing NES within behavioral weight management interventions can improve weight outcomes and problematic eating behaviors.