Enzymatic barrier protects brain capillaries from leukotriene C4.
Leukotriene C4 (LTC4) increases vascular permeability in systemic, brain tumor, and ischemic brain capillaries, but not in normal brain capillaries. This study examines whether the abundance of gamma-glutamyl transpeptidase (gamma-GTP) in normal brain capillaries might act as an enzymatic barrier to vasoactive leukotrienes in the brain. Blood-brain barrier (BBB) permeability was determined by quantitative autoradiography using 14C-aminoisobutyric acid. Ischemia was produced by occluding the middle cerebral artery. Seventy-two hours after occlusion, gamma-GTP activity in ischemic brain disappeared, and LTC4 (4-micrograms total dose), which was infused into the carotid artery ipsilateral to the occlusion, selectively increased permeability, Ki, approximately twofold within core ischemic tissue and adjacent tissue, compared to vehicle alone in seven brains (15.53 +/- 6.03 vs. 7.29 +/- 3.36, p < 0.05, and 8.76 +/- 4.02 vs. 4.32 +/- 2.65, p < 0.05, respectively). No effect on BBB was seen in nonischemic brain tissue. Twenty-four hours postocclusion, gamma-GTP activity was still present, and LTC4 infusion did not increase permeability within ischemic tissue. However, inhibition of gamma-GTP with acivicin allowed LTC4 to increase permeability even 24 hours after occlusion in ischemic core and adjacent tissue compared to vehicle alone in seven brains (17.21 +/- 16.32 vs. 8.23 +/- 6.58, p < 0.05, and 11.78 +/- 7.96 vs. 4.56 +/- 1.93, p < 0.01, respectively). Acivicin almost completely blocked both the histochemical activity of gamma-GTP in brain capillaries and the metabolism of LTC4 in isolated bovine capillaries. These findings suggest that gamma-GTP may help normal brain capillaries resist the vasoactive effects of LTC4. In contrast, gamma-GTP is lost in injured brain capillaries, which allows LTC4 (in combination with other factors) to increase vascular permeability in ischemic brain and brain tumors.


Nuclear proteins from lactating mammary glands bind to the promoter of a milk protein gene.
The gene for the whey acidic protein (WAP) is expressed specifically in the lactating mammary glands of rodents. We present evidence that nuclear proteins from mammary epithelial cells form a multiple nucleoprotein complex with the WAP gene promoter/upstream region. As monitored by mobility shifts, nuclear proteins from lactating mammary glands and from the mammary cell line MCF-7 form four high affinity complexes with a fragment spanning the region between nucleotides -175 and -88. Nuclear proteins from liver and HeLa cells generate only three high affinity complexes. DNAaseI and ExonucleaseIII protection confirmed the binding of mammary nuclear proteins to specific sequences in the WAP gene upstream region. This is the first report to describe the interaction of nuclear proteins from lactating mammary glands with cognate binding sites in the promoter/upstream region of a milk protein gene. The possibility of the binding sites being candidates for cis-acting regulatory elements governing the regulated expression of the WAP gene is discussed.


The first record of nucleopolyhedrovirus isolated from the satin moth Leucoma salicis L. (Lepidoptera, Lymantriidae) in Turkey.
A nucleopolyhedrovirus was isolated and characterized for the first time from Leucoma salicis L. (Lepidoptera, Lymantriidae) in Turkey. The virus was observed in populations of L. salicis in Gümüşhane. The dimensions of the polyhedrae fell between 2.08 +/- 0.31 (1.51-2.64) microm (N = 50). Virions contain 2 to 15 nucleocapsids per virion as seen in cross-section of polyhedrae. The sizes of the viral particles ranged between 250-290 x 32-40 nm. The virus was determined as a Turkish isolate of Leucoma salicis nucleopolyhedrovirus (LesaNPV-TR).


[Progress in application of three-dimensional imaging technique in complex hepatobiliary surgery].
Hepatobiliary surgery is considered to be technically challenging because of complex intrahepatic and perihilar anatomical structures and variations.Nowadays, three-dimensional imaging technique plays an important role in the time of precise liver surgery.Three-dimensional images depict the spatial location of tumor, and the course, confluence pattern and variation of portal vein, hepatic artery, biliary system and hepatic vein distinctly while showing involved hepatic segments and the relationship with adjacent vessels from omnidirectional view, measuring the length of margin and future remnant liver.With the help of surgical simulation, surgeons can determine the significant vessels preoperatively.The application of three-dimensional imaging technique may improve the resectability and safety of complex hepatobiliary surgery, such as hilar cholangiocarcinoma, centrally located liver tumor, hepatolithiasis and living donor liver transplantation.Meanwhile, three-dimensional visualization facilitates the understanding of two-dimensional images and complicated surgical anatomy for surgeons.


Highly sensitive gold nanoparticle-based colorimetric sensing of mercury(II) through simple ligand exchange reaction in aqueous media.
A strategy for the rational design of a novel colorimetric sensor based on dithioerythritol-modified gold nanoparticles for the selective recognition of Hg2+ in aqueous media is presented. This approach relies on the combination of gold nanoparticles with Hg2+ through sulfur-Hg2+-sulfur interaction. The gold nanoparticles showed high selectivity toward Hg2+ with binding-induced red shift in the absorption spectra, with no response to major interfering cations such as Pb2+, Cd2+, and Cu2+ in the presence of ethylenediamine tetraacetic acid. The system responds to Hg2+ with a detection limit of 100 nM and might open a new avenue for the development of Hg2+ sensing probes.


Pseudohyperkalemia without reported haemolysis in a patient with chronic lymphocytic leukaemia.
Hyperkalemia is a medical condition that requires immediate recognition and treatment to prevent the development of life-threatening arrhythmias. Pseudohyperkalemia is most commonly due to specimen haemolysis and is often recognised by laboratory scientists who subsequently report test results with cautionary warnings. The authors present a case of pseudohyperkalemia in a patient with chronic lymphocytic leukaemia that was the result of white blood cell lysis during phlebotomy. False elevations of potassium from this condition may not be reported with a warning from the laboratory. This places the patient at risk of unnecessary and potentially dangerous treatments. This phenomenon has not been published in the emergency medicine literature to date.


Interstrain differences in the expression and activity of Cyp2a5 in the mouse liver.
Cytochrome P450 2A5 (Cyp2a5), a mouse enzyme orthologous of human CYP2A6, catalyzes a number of toxicologically important reactions, including the metabolism of nicotine, aflatoxin B1, and several other xeno- and endobiotics. Cyp2a5 expression is complex and not yet fully understood. We investigated inter-strain differences in the activity and mRNA expression of hepatic Cyp2a5. Cyp1a1/2 and Cyp2b9/10 activities were evaluated for comparative purposes. Data on the interstrain differences in the expression and activity of Cyp2a5 are important to select a suitable mouse model for studying CYP2A6-mediated metabolism. Activity of Cyp2a5 (coumarin 7-hydroxylase) was highest in DBA-2 and DBA-1, intermediate in B6D2F1 (hybrid) and low in the remaining strains (C57BL/6, C57BL/10, CBA, BALB/cAn, SW). Contrasting with the activity, background levels of Cyp2a4/5 mRNA did not differ between high- and low-activity murine strains. Phenobarbital (PB, 80 mg/kg body weight/day × 3 days, i.p.) increased Cyp2a5, Cyp1a1/2 (ethoxyresorufin-O-deethylase) and Cyp2b9/10 (bezyloxyresorufin-O-debenzylase) activities while only Cyp2a5 was enhanced by pyrazole (PYR, 100 mg/kg body weight/day × 3 days, i.p.). Inductions of Cyp2a5 activity by PYR and PB were accompanied by increases of Cyp2a4/5 mRNA. PYR and PB did not upregulate heme oxygenase-1 (hmox-1) mRNA expression in any strain, a finding that is apparently at odds with the notion that Cyp2a5 and hmox-1 inductions are coordinated events. Since background levels of Cyp2a4/5 gene transcripts of high-activity strains did not differ from those of low-activity mice, distinct constitutive activities did not result from different transcription rates and/or mRNA half-lives. Results therefore suggested that interstrain differences in constitutive activity of Cyp2a5 possibly arise from distinct translation efficiencies, protein half-lives and/or enzyme kinetics toward the substrate. Data from this study indicated that all tested strains are suitable models for studying toxicants that are substrates for human CYP2A6; DBA-2, DBA-1 and the hybrid B62DF1, however, have the advantage of presenting high constitutive activities of Cyp2a5.


[Granulomatosis with polyangiitis - clinical picture and review of current treatment options].
Granulomatosis with polyangiitis (GPA) is a rare disease of unknown aetiology, characterized by necrotizing inflammation of small and medium-sized vessels and formation of granulomas. The disease typically involves the upper and lower respiratory tracts and the kidneys, but it can occur in many other locations, often giving a surprising clinical picture. The majority of patients have autoantibodies against cytoplasm of neutrophils (ANCA), of which a pathogenetic role is postulated. The disease affects mostly middle-aged and elderly people, with a predominance of Caucasians. Before the era of immunosuppressive therapy GPA was associated with high early mortality. Nowadays, we have a treatment that gives remission in the majority of patients. The decision about the method of treatment should be made depending on the clinical form of the disease (local or generalized, refractory). Standard remission induction therapy in the generalized disease is cyclophosphamide in combination with steroids. This therapy, however effective, is associated with a number of side effects. In addition, some patients are resistant to standard therapy, and half of them experience relapses. Therefore, there is need for further research for alternative treatment and maintenance therapy. Currently, hopes are raised by biological agents. Among them, the best studied so far is rituximab, which found a place in the current recommendations of EULAR as an alternative drug for patients with refractory disease. The article discusses the clinical picture of GPA, diagnosis and currently recommended treatment.


Apolipoprotein E (APOE) ϵ4 Allele Is Associated with Increased Symptom Reporting Following Sports Concussion.
Exploring the relationship between genetic factors and outcome following brain injury has received increased attention in recent years. However, few studies have evaluated the influence of genes on specific sequelae of concussion. The purpose of this study was to determine how the ϵ4 allele of the apolipoprotein E (APOE) gene influences symptom expression following sports-related concussion. Participants included 42 collegiate athletes who underwent neuropsychological testing, including completion of the Post-Concussion Symptom Scale (PCSS), within 3 months after sustaining a concussion (73.8% were evaluated within 1 week). Athletes provided buccal samples that were analyzed to determine the make-up of their APOE genotype. Dependent variables included a total symptom score and four symptom clusters derived from the PCSS. Mann-Whitney U tests showed higher scores reported by athletes with the ϵ4 allele compared to those without it on the total symptom score and the physical and cognitive symptom clusters. Furthermore, logistic regression showed that the ϵ4 allele independently predicted those athletes who reported physical and cognitive symptoms following concussion. These findings illustrate that ϵ4+ athletes report greater symptomatology post-concussion than ϵ4- athletes, suggesting that the ϵ4 genotype may confer risk for poorer post-concussion outcome. (JINS, 2016, 22, 89-94).


Self-Reported Concussion Symptomology during Deployment: Differences as a Function of Injury Mechanism and Low-Level Blast Exposure.
Traumatic brain injury (TBI), which can result from either direct impact to the head or blast exposure, has been the leading cause of morbidity and mortality in recent military conflicts. However, little research has compared mTBIs by mechanism of injury. The present research addressed two research questions: (1) Are blast-related mTBIs (mbTBIs) associated with significantly more symptoms than impact-related mTBIs (miTBIs), and (2) are mTBIs associated with more self-reported symptoms among service members with higher (vs. lower) risk of low-level blast (LLB) exposure. We obtained data from 181,423 active duty enlisted United States Marines deployed between 2003 and 2012, who completed the Post-Deployment Health Assessment. We examined the self-reported symptoms of Marines who completed an mTBI screen and could be classified as at high or low risk for LLB exposure, using their military occupation as a proxy (n = 12,013). Symptoms were compared as a function of blast exposure (blast vs. impact), probable mTBI (yes vs. no), occupational risk of LLB (high vs. low), and symptom type (neurological vs. musculoskeletal vs. immunological). Overall, musculoskeletal symptoms were reported more frequently than neurological and immunological symptoms. However, Marines with probable mTBIs (regardless of mechanism of injury) and those with probable mbTBIs specifically reported more neurological symptoms, which rose to the level of musculoskeletal symptom reporting. Among Marines with probable mTBI, those with high risk of LLB exposure also reported significantly more neurological symptoms. Our results indicate that mbTBIs and miTBIs may be fundamentally different, and that LLB may increase susceptibility to injury.


Extending the dosing interval of COVID-19 vaccination leads to higher rates of seroconversion in people living with HIV.
Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an effective way of protecting individuals from severe coronavirus disease 2019 (COVID-19). However, immune responses to vaccination vary considerably. This study dynamically assessed the neutralizing antibody (NAb) responses to the third dose of the inactivated COVID-19 vaccine administered to people living with human immunodeficiency virus (HIV; PLWH) with different inoculation intervals. A total of 171 participants were recruited: 63 PLWH were placed in cohort 1 (with 3-month interval between the second and third doses), while 95 PLWH were placed in cohort 2 (with 5-month interval between the second and third doses); 13 individuals were enrolled as healthy controls (HCs). And risk factors associated with seroconversion failure after vaccination were identified via Cox regression analysis. At 6 months after the third vaccination, PLWH in cohort 2 had higher NAb levels (GMC: 64.59 vs 21.99, P < 0.0001) and seroconversion rate (68.42% vs 19.05%, P < 0.0001). A weaker neutralizing activity against the SARSCoV-2 Delta variant was observed (GMT: 3.38 and 3.63, P < 0.01) relative to the wildtype strain (GMT: 13.68 and 14.83) in both cohorts. None of the participants (including HCs or PLWH) could mount a NAb response against Omicron BA.5.2. In the risk model, independent risk factors for NAb seroconversion failure were the vaccination interval (hazed ration [HR]: 0.316, P < 0.001) and lymphocyte counts (HR: 0.409, P < 0.001). Additionally, PLWH who exhibited NAb seroconversion after vaccination had fewer initial COVID-19 symptoms when infected with Omicron. This study demonstrated that the third vaccination elicited better NAb responses in PLWH, when a longer interval was used between vaccinations. Since post-vaccination seroconversion reduced the number of symptoms induced by Omicron, efforts to protect PLWH with risk factors for NAb seroconversion failure may be needed during future Omicron surges. https://beta.clinicaltrials.gov/study/NCT05075070, identifier NCT05075070.


Haematological values of epileptic patients entering drug trials.
Retrospective comparison of peripheral haematological values in normal volunteers and patients on anti-epileptic drugs over a one year period demonstrated a significant reduction in total white blood cells, neutrophil, eosinophil, lymphocyte and monocyte counts in patients. The red blood cell count, mean cell volume and mean cell haemoglobin were significantly reduced in the patients. These findings need to be taken into account when new anti-epileptic drugs are assessed by adding on to existing therapy.


A proposal for financing postmarketing drug safety studies by augmenting FDA user fees.
I propose to raise funds for postapproval studies of long-term drug safety by augmenting the existing "user-fee" system. Fees would be raised by an amount deemed optimal for revenue collection, and the U.S. Food and Drug Administration (FDA) would direct the incremental funds to a combination of randomized controlled trials, epidemiological studies, and postmarketing surveillance. User-fee augmentation is an achievable, incremental reform that would subsidize information that is now undersupplied in the U.S. health care system; spread the burden of funding postmarketing safety studies among pharmaceutical sponsors; and help restore public, scientific, and professional confidence in the FDA and its user-fee system.


Magnetomicrometry.
We live in an era of wearable sensing, where our movement through the world can be continuously monitored by devices. Yet, we lack a portable sensor that can continuously monitor muscle, tendon, and bone motion, allowing us to monitor performance, deliver targeted rehabilitation, and provide intuitive, reflexive control over prostheses and exoskeletons. Here, we introduce a sensing modality, magnetomicrometry, that uses the relative positions of implanted magnetic beads to enable wireless tracking of tissue length changes. We demonstrate real-time muscle length tracking in an in vivo turkey model via chronically implanted magnetic beads while investigating accuracy, biocompatibility, and long-term implant stability. We anticipate that this tool will lay the groundwork for volitional control over wearable robots via real-time tracking of muscle lengths and speeds. Further, to inform future biomimetic control strategies, magnetomicrometry may also be used in the in vivo tracking of biological tissues to elucidate biomechanical principles of animal and human movement.


Evaluation on the Risk of Water Inrush Due to Roof Bed Separation Based on Improved Set Pair Analysis-Variable Fuzzy Sets.
To study and prevent bed separation water inrush accidents in coal mines, it is necessary to evaluate the risk according to the limited geological data correctly. In this work, based on hydrogeological and mining conditions, we established a risk evaluation model and selected seven important factors, including the aquifer thickness, aquifer water abundance, hydraulic pressure of the aquifer, effective aquifuge thickness, mining failure ratio, mining height of the working face, and advancing distance as evaluation indexes. The intuitionistic fuzzy analytic hierarchy process (IFAHP) and entropy weight method (EWM) were used to analyze the weights of the original data, and the minimum information entropy principle was used to further integrate the abovementioned calculation results. With the weight results, set pair analysis-variable fuzzy set (SPA-VFS) theory was applied to determine the risk grade of each working face, which provided scientific guidance for the safe mining of coal mines. For the working face where water inrush may occur, the risk of bed separation water inrush can be reduced by optimizing the parameters or changing the mining conditions through the model analysis.


Adenine methylation may contribute to endosymbiont selection in a clonal aphid population.
The pea aphid Acyrthosiphon pisum has two modes of reproduction: parthenogenetic during the spring and summer and sexual in autumn. This ability to alternate between reproductive modes and the emergence of clonal populations under favorable conditions make this organism an interesting model for genetic and epigenetic studies. The pea aphid hosts different types of endosymbiotic bacteria within bacteriocytes which help the aphids survive and adapt to new environmental conditions and habitats. The obligate endosymbiont Buchnera aphidicola has a drastically reduced and stable genome, whereas facultative endosymbionts such as Regiella insecticola have large and dynamic genomes due to phages, mobile elements and high levels of genetic recombination. In previous work, selection toward cold adaptation resulted in the appearance of parthenogenetic A. pisum individuals characterized by heavier weights and remarkable green pigmentation. Six adenine-methylated DNA fragments were isolated from genomic DNA (gDNA) extracted from the cold-induced green variant of A. pisum using deoxyadenosine methylase (Dam) by digesting the gDNA with the restriction enzymes DpnI and DpnII, which recognize the methylated and unmethylated GATC sites, respectively. The six resultant fragments did not match any sequence in the A. pisum or Buchnera genomes, implying that they came from facultative endosymbionts. The A1 fragment encoding a putative transposase and the A6 fragment encoding a putative helicase were selected for further comparison between the two A. pisum variants (green and orange) based on Dam analysis followed by PCR amplification. An association between adenine methylation and the two A. pisum variants was demonstrated by higher adenine methylation levels on both genes in the green variant as compared to the orange one. Temperature selection may affect the secondary endosymbiont and the sensitive Dam involved in the survival and adaptation of aphids to cold temperatures. There is a high degree of adenine methylation at the GATC sites of the endosymbiont genes at 8°C, an effect that disappears at 22°C. We suggest that endosymbionts can be modified or selected to increase host fitness under unfavorable climatic conditions, and that the phenotype of the newly adapted aphids can be inherited.


Changes in Whole-Blood microRNA Profiles during the Onset and Treatment Process of Cerebral Infarction: A Human Study.
Circulating miRNA species are promising symptom markers for various diseases, including cardiovascular disease. However, studies regarding their role in the treatment process are limited, especially concerning cerebral infarction. This study aimed to extract miRNA markers to investigate whether they reflect both onset and treatment process of cerebral infarction. A total of 22 patients (P-group) and 22 control subjects (C-group) were examined for their whole-blood miRNA profiles using DNA GeneChip™ miRNA 4.0 Array, with six patients examined after treatment (T-group). A total of 64 miRNAs were found to be differentially expressed between the C- and P-groups. Out of 64 miRNAs, the expression levels of two miRNAs correlated with hypertension. A total of 155 miRNAs were differentially expressed between the P- and T-groups. Five common miRNAs were found among the 64 and 155 miRNAs identified. Importantly, these common miRNAs were inversely regulated in each comparison (e.g., C < P > T), including miR-505-5p, which was previously reported to be upregulated in aortic stenosis patients. Our previous study using rat cerebral infarction models detected the downregulation of an apoptosis repressor, WDR26, which was repressed by one of the five miRNAs. Our results provide novel information regarding the miRNA-based diagnosis of cerebral infarction in humans. In particular, the five common miRNAs could be useful makers for the onset and the treatment process. Trial registration: This study was registered in the UMIN Clinical Trials Registry (UMIN000038321).


Efforts toward the Total Synthesis of Elisabethin A.
We describe our efforts toward the total synthesis of the natural product elisabethin A. The first route was guided by the proposed biosynthesis, assembling the 6,6-ring system before forming the five-membered ring including the quaternary carbon. The second approach includes a high yielding cyclization under Mitsunobu conditions as a key step. It allowed the preparation of an unusual and highly functionalized bicyclic 6,5-spiro compound. Both routes share a common advanced precursor obtained from an "underdeveloped" Claisen rearrangement of an aryl dienyl ether.


Energetic performance of trinitromethyl nitrotriazole (TNMNT) and its energetic salts.
Little is known about trinitromethyl nitrotriazole (TNMNT) since the crystal structure, density, energetic performance, and thermal properties have not been determined. A detailed characterization of TNMNT and its hydrazinium and potassium salts and their potential as solid propellants and oxidizers has been established. TNMNT exhibits a high density (1.96 g cm-3) and positive enthalpy of formation (ΔHf = +84.79 kJ mol-1). TNMNT and its hydrazinium and potassium salts illustrate excellent detonation properties (P = 34.24 to 36.22 GPa, D = 8899 to 9031 ms-1). TNMNT and its hydrazinium salt exhibit outstanding propulsive properties (Isp = 247.28 to 271.19 s), and these are superior to AP (Isp = 156.63 s) and ADN (Isp = 202.14 s). The results suggest opening the door to utilizing TNMNT and its energetic salts in solid rocket propulsion.


Chimeric Singleton Placenta Comprising Placental Mesenchymal Dysplasia and Complete Hydatidiform Mole with Live Birth and Postpartum Diagnosis of Gestational Trophoblastic Neoplasia.
Placental mesenchymal dysplasia (PMD) is a benign lesion that is often misdiagnosed as complete (CHM) or partial hydatidiform mole. PMD usually results in live birth but can be associated with several fetal defects. Herein, we report PMD with CHM in a singleton placenta with live birth. A 34-year-old gravida 2, para 1, living 1 (G2P1L1) woman was referred on suspicion of a molar pregnancy in the first trimester. Maternal serum human chorionic gonadotrophin levels were increased during early pregnancy, with multicystic lesions and placentomegaly observed on ultrasonography. Levels decreased to normal with no fetal structural abnormalities observed. A healthy male infant was delivered at 34 gestational weeks. Placental p57KIP2 immunostaining and short tandem repeat analysis revealed three distinct histologies and genetic features: normal infant and placenta, PMD, and CHM. Gestational trophoblastic neoplasia was diagnosed and up to fourth-line chemotherapy administered. Distinguishing PMD from hydatidiform moles is critical for avoiding unnecessary termination of pregnancy. CHM coexisting with a live fetus rarely occurs. This case is unique in that a healthy male infant was born from a singleton placenta with PMD and CHM.


Electronic and Steric Optimization of Fluorogenic Probes for Biomolecular Imaging.
Fluorogenic probes are invaluable tools for spatiotemporal investigations within live cells. In common fluorogenic probes, the intrinsic fluorescence of a small-molecule fluorophore is masked by esterification until entry into a cell, where endogenous esterases catalyze the hydrolysis of the masking groups, generating fluorescence. The susceptibility of masking groups to spontaneous hydrolysis is a major limitation of these probes. Previous attempts to address this problem have incorporated auto-immolative linkers at the cost of atom economy and synthetic adversity. Here, we report on a linker-free strategy that employs adventitious electronic and steric interactions in easy-to-synthesize probes. We find that X···C═O n→π* interactions and acyl group size are optimized in 2',7'-dichlorofluorescein diisobutyrate. This probe is relatively stable to spontaneous hydrolysis but is a highly reactive substrate for esterases both in vitro and in cellulo, yielding a bright, photostable fluorophore with utility in biomolecular imaging.


Mosquito-Borne Human Viral Diseases: Why Aedes aegypti?
Although numerous viruses are transmitted by mosquitoes, four have caused the most human suffering over the centuries and continuing today. These are the viruses causing yellow fever, dengue, chikungunya, and Zika fevers. Africa is clearly the ancestral home of yellow fever, chikungunya, and Zika viruses and likely the dengue virus. Several species of mosquitoes, primarily in the genus Aedes, have been transmitting these viruses and their direct ancestors among African primates for millennia allowing for coadaptation among viruses, mosquitoes, and primates. One African primate (humans) and one African Aedes mosquito (Aedes aegypti) have escaped Africa and spread around the world. Thus it is not surprising that this native African mosquito is the most efficient vector of these native African viruses to this native African primate. This makes it likely that when the next disease-causing virus comes out of Africa, Ae. aegypti will be the major vector to humans.


Growth Differentiation Factor 15 and Risk of Bleeding Events: The Atherosclerosis Risk in Communities Study.
Background GDF15 (growth differentiation factor 15) is a potent predictor of bleeding in people with cardiovascular disease. However, whether GDF15 is associated with bleeding in individuals without a history of cardiovascular disease is unknown. Methods and Results The study population was from the ARIC (Atherosclerosis Risk in Communities) study. We studied the association of GDF15 with hospitalized bleeding events among 9205 participants (1993-1995) without prior bleeding and cardiovascular disease (mean age 60 years, 57% women, 21% Black). Plasma levels of GDF15 were measured in relative fluorescence units using DNA-based aptamer technology. Bleeding was ascertained using discharge codes. We examined hazard ratios (HRs) of incident bleeding using Cox models and risk prediction with the addition of GDF15 to clinical predictors of bleeding. There were 1328 hospitalizations with bleeding during a median follow-up of 22.5 years. The majority (76.5%) were because of gastrointestinal bleeding. The absolute incidence rate of bleeding per 1000 person-years was 11.64 in the highest quartile of GDF15 versus 5.22 in the lowest quartile. The highest versus lowest quartile of GDF15 demonstrated an adjusted HR of 2.00 (95% CI, 1.69-2.35) for total bleeding. The findings were consistent when we examined bleeding as the primary discharge diagnosis. The addition of GDF15 to clinical predictors of bleeding improved the C-statistic by 0.006 (0.002-0.011) from 0.684 to 0.690, P=0.008. Conclusions Higher levels of GDF15 were associated with bleeding events and improved the risk prediction beyond clinical predictors in individuals without cardiovascular disease.


Biomarkers and Microscopic Colitis: An Unmet Need in Clinical Practice.
One of the most common causes of chronic diarrhea is ascribed to microscopic colitis (MC). MC is classified in subtypes: collagenous colitis (CC) and lymphocytic colitis (LC). Patients with MC report watery, non-bloody diarrhea of chronic course, abdominal pain, weight loss, and fatigue that may impair patient's health-related quality of life. A greater awareness, and concomitantly an increasing number of diagnoses over the last years, has demonstrated that the incidence and prevalence of MC are on the rise. To date, colonoscopy with histological analysis on multiple biopsies collected along the colon represents the unique accepted procedure used to assess the diagnosis of active MC and to evaluate the response to medical therapy. Therefore, the emerging need for less-invasive procedures that are also rapid, convenient, standardized, and reproducible, has encouraged scientists to turn their attention to the identification of inflammatory markers and other molecules in blood or feces and within the colonic tissue that can confirm a MC diagnosis. This review gives an update on the biomarkers that are potentially available for the identification of inflammatory activity, related to CC and LC.


Immunotoxic effects of single and combined pharmaceuticals exposure on a harbor seal (Phoca vitulina) B lymphoma cell line.
The potential risk of pharmaceuticals in the environment to top-predators is still largely unknown. In this study, we assessed the immunotoxic effects of ten pharmaceuticals individually and as mixtures on a harbor seal (Phoca vitulina) B lymphoma cell line. A significant reduction in lymphocyte transformation was observed following an exposure to 12,500μg/L 17α-ethinyl estradiol and 25,000μg/L naproxen. Exposure to 12,500μg/L 17α-ethinyl estradiol decreased the percentage of cell in the G0/G1 phase of the cell cycle while increasing the percentage of cells in the S phase. Carbamazepine exposure increased the amount of cells in the G2/M phase. Binary mixtures showed synergistic effects in lymphocyte transformation, cell cycle and apoptosis assays. Concentrations inducing toxic effects in the cell line were similar to those affecting fish in previous studies. A reduction of functional activities of the immune system may lead to altered host resistance to pathogens in free-ranging pinnipeds.


The Process of Developing a Digital Repository for Online Teaching Using Design-Based Research.
The Purdue Repository for Online Teaching and Learning (PoRTAL) was developed as an Open Educational Resource (OER) for graduate students and faculty in higher education settings to enhance their online teaching skills and strategies. The PoRTAL team used a design-based research approach (DBR; Wang & Hannafin, Educational Technology Research and Development, 53(4), 5-23, 2005). In this study context, we used Van Tiem et al.'s (2012) model to identify problems faced by instructors who struggled with or were new to online teaching from a Human Performance Technology (HPT) standpoint. To address the identified needs, we created resources for online teaching and embedded our research within practical activities to further study our design process. Our efforts resulted in an HPT-OER Model for Designing Digital Repositories. The purpose of this paper is to share the DBR process that we used to develop an OER repository within an HPT model.


Long-term monitoring of atmospheric PCDD/Fs at Mount Lulin during spring season: PCDD/F source apportionment through a simultaneous measurement in Southeast Asia.
A long term assessment of atmospheric polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) at Mt. Lulin, located in center of Taiwan was carried out from 2008 to 2013 (n = 81) assuming Mt. Lulin to be background area. During monitoring processes, PCDD/F samples collected in the field occasionally reached high concentration. To investigate this situation, simultaneous sample collection was carried out in Southeast Asia countries (i.e., Vietnam and Thailand) and Taiwan in 2013. The average concentration of atmospheric PCDD/Fs in biomass-burning source regions, namely Son La and Doi Ang Khang were 19.8 ± 12.1 fg I-TEQ m-3 (n = 19) and 17.8 ± 12.4 fg I-TEQ m-3 (n = 20), respectively. In the downwind area of Mt. Lulin, the average concentration of PCDD/Fs was found to be 4.64 ± 3.77 fg I-TEQ m-3 (n = 18). PCDD/F concentration in the source region was much higher than that in the downwind region. On March 19, 2013, the atmospheric PCDD/F concentrations increased dramatically from 7.71 to 484 fg I-TEQ m-3 at Mt. Lulin, which many times exceeded that of assumed source region in Southeast Asia. Moreover, mainland Southeast Asia and the southeast coast of China was suspected to be the main contributors of atmospheric PCDD/Fs and biomass markers, such as nonsea-salt K+ and NH4+, during the spring. WRF-Chem and Potential Source Contribution Function (PSCF) simulations have confirmed this correlation. It can be concluded that atmospheric PCDD/Fs observed at Mt. Lulin during spring mostly derived from the air mass transport not only from Southeast Asia but also the southeast coast of China.


The rat hepatic corticosteroid-binding globulin receptor: distinction from the asialoglycoprotein receptor.
This investigation was undertaken to ascertain whether rat liver cells contained a receptor for corticosteroid-binding globulin (CBG) that could be differentiated clearly from the asialoglycoprotein receptor. To do this, [125I]CBG, [125I] asialo-CBG, and [125I]asialofetuin were used as probes to differentiate the binding activities of the two receptors. On hepatic membranes, CBG bound to a single set of sites with a Kd of 0.74 microM, asialofetuin bound to a single set of sites with a Kd of 0.018 microM, asialo-CBG bound to two sets of sites with Kd values of 0.004 and 1.4 microM and in the presence of 1 microM asialofetium, asialo-CBG bound to a single set of sites with a Kd of 0.53 microM, not different (P greater than 0.2) from the Kd of CBG. Cross-competition studies using the three 125I-labeled ligands and allowing each to compete with the three radioinert ligands indicated the existence of two separate receptors. Desialylation of hepatic membranes differentially affected the binding of CBG and asialofetuin. Finally, whole cells bound CBG specifically, but internalized it to only a minimal extent (less than 10%). This observation does not support a role for the CBG-receptor system in the entry of steroids into cells.


[Prenatal diagnosis of five cases of monochorionic-diamniotic twins discordant for karyotype analysis].
OBJECTIVE To explore the mechanism and diagnostic method for monochorionic-diamniotic twins discordant for karyotype analysis. METHODS Dual amniocentesis was performed on five pairs of monochorionic-diamniotic twins, which all consisted of a normal twin and one with multiple malformations revealed by ultrasound. Karyotype analysis was performed on amniocytes derived from each of the twins. Zygosity was also determined with DNA extracted from amniocytes with 16 polymorphic microsatellite markers. RESULTS Three cases of 45,X, one case of 47,XX,+9 and one case of 47,XY,+18 were detected among the abnormal twins, while the normal fetuses all had a normal karyotype. DNA analysis suggested that, in all cases, the twins have shared the 16 polymorphic microsatellite markers, which confirmed their monozygosity. CONCLUSION Monochorionic-diamniotic twins may be discordant for karyotyping, for which anaphase lagging, chromosomal non-disjunction and trisomy rescue may be the underlying reasons. As a simple method, dual amniocentesis can be used to obtain amniotic fluid samples for karyotype analysis and determination of zygosity for such twins.


Quality of economic evaluations of ventricular assist devices: A systematic review.
Because of a lack of suitable heart donors, alternatives to transplantation are required. These alternatives can have high costs. The aim of this study was to perform a systematic review of cost-effectiveness studies of ventricular assist devices (VADs) and to assess the level of evidence of relevant studies. The purpose was not to present economic findings. A systematic review was performed using four electronic databases to identify health economic evaluation studies dealing with VADs. The methodological quality and reporting quality of the studies was assessed using three different tools, the Drummond, Cooper, and CHEERS (Consolidated Health Economic Evaluation Reporting Standards) checklists. Of the 1,258 publications identified, thirteen articles were included in this review. Twelve studies were cost-utility analyses and one was a cost-effectiveness analysis. According to the Cooper hierarchy scale, the quality of the data used was heterogeneous. The level of evidence used for clinical effect sizes, safety data, and baseline clinical data was of poor quality. In contrast, cost data were of high quality in most studies. Quality of reporting varied between studies, with an average score of 17.4 (range 15-19) according to the CHEERS checklist. The current study shows that the quality of clinical data used in economic evaluations of VADs is rather poor in general. This is a concern that deserves greater attention in the process of health technology assessment of medical devices.


Bullying Victimization and Life Satisfaction Among Rural Left-Behind Children in China: A Cross-Sectional Study.
Objectives: This study aimed to evaluate the associations between bullying victimization and life satisfaction in primary school children and also investigate the interactive effects of left-behind status and bullying victimization on life satisfaction. Materials and Methods: Bullying victimization was measured using the Chinese version of the revised Olweus Bully/Victim Questionnaire. Life satisfaction was assessed using the Multidimensional Students' Life Satisfaction Scale (MSLSS). Life satisfaction is composed of five domains, namely, family, school, friends, environment, and self-satisfaction. Left-behind status of rural children was defined as one or both their parents migrating to working in cities. The data were analyzed using Mann-Whitney U tests, Chi-square tests, and multivariate linear and logistic regression analyses. Results: A total of 810 primary school children were involved, of which 8.5% reported bullying victimization, and 44.3% were left-behind children (LBC). We found that bullying victimization was negatively associated with all domains of life satisfaction (all p < 0.05). With further left-behind status-stratified analysis, we found that negative association between bullying victimization and friend satisfaction was more profound in the LBC group than in the non-LBC group [b(SE)= -0.133 (0.03) vs. -0.061 (0.026) for LBC and non-LBC, respectively, p < 0.05]. When further interaction analysis was conducted, we identified interaction effects between left-behind status and bullying victimization on friend satisfaction (p interaction = 0.048). Similar interaction effect between bullying victimization and left-behind status on school satisfaction was also found (p interaction = 0.004). Conclusions: Bullying victimization was associated with low life satisfaction (including lower family, friends, school, self, and environment satisfaction). There were significant interactions between left-behind status and bullying victimization on friend satisfaction, as well as school satisfaction. Left-behind status of children may exaggerate the impact of bullying victimization on friends/school satisfaction rating.


Qualitative evaluation of project P.A.T.H.S.: an integration of findings based on program participants.
An integration of the qualitative evaluation findings collected in different cohorts of students who participated in Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programmes) (n = 252 students in 29 focus groups) was carried out. With specific focus on how the informants described the program, results showed that the descriptions were mainly positive in nature, suggesting that the program was well received by the program participants. When the informants were invited to name three metaphors that could stand for the program, positive metaphors were commonly used. Beneficial effects of the program in different psychosocial domains were also voiced by the program participants. The qualitative findings integrated in this paper provide further support for the effectiveness of the Tier 1 Program of Project P.A.T.H.S. in promoting holistic development in Chinese adolescents in Hong Kong.


Megakaryocytic colony-stimulating activity in patients receiving a marrow transplant during hematopoietic reconstitution.
Megakaryocytic colony formation is dependent upon growth-stimulating activities present in human serum or plasma. Factors with diverse biological activities including megakaryocytic colony-stimulating activity (Mk-CSA) are provided by the medium of mitogen stimulated peripheral mononuclear cells or subsets of peripheral T cells. In this communication we describe the stimulatory activity of plasma collected from allogeneic and autologous bone marrow transplant recipients on the growth of megakaryocytic colonies. Mk-CSA was found to increase after transplantation as bone marrow regenerated. The stimulatory activities for CFU-M were greater in plasma from allogeneic bone marrow transplant patients receiving T cell-depleted donor marrow than in patients receiving unmodified donor marrow. Growth-promoting activities derived from mitogen-stimulated lymphocytes of T4 phenotype, a potent source of Mk-CSA, did not increase the frequency of CFU-M when cultured in plasma collected from transplant patients receiving a T cell-depleted donor marrow. However, a further increase in the number of CFU-M was observed when exogenous Mk-CSA was added to the cultures supplemented with plasma from patients receiving unmodified donor marrow. Plasma of patients who received autologous marrow displayed similar Mk-CSA activity when compared with the activity of plasma obtained from transplant recipients receiving an unmodified allogeneic donor marrow. Stimulatory activities supporting multilineage colonies (CFU-GEMM), erythroid bursts (BFU-E), and granulocytic colonies (CFU-C) derived from plasma of the three different transplant groups revealed no statistical difference with respect to the frequency of CFU-GEMM, BFU-E, or CFU-C colonies when compared with pretransplant plasma. The results suggest that MK-CSA may play an important role in the regulation of megakaryopoiesis in vivo. Moreover the data suggest the presence of humoral regulators that appear to be different with respect to the processing of the donor marrow.


Topical nitroglycerin in newborns with ischemic injuries: A systematic review.
Arterial catheterization is frequently performed in neonatal intensive care units with an inherent risk of peripheral ischemic injury, especially in preterm infants. The treatment options following vascular damage involve invasive and non-invasive modalities. The primary objective of this systematic review was to evaluate the evidence of the use of topical nitroglycerine (TNG) either alone or as adjunctive therapy. The secondary aim was to develop an approach to the treatment of catheter induced ischemia in infants based on the available evidence. A comprehensive search was conducted of available databases for relevant articles that involved the treatment of peripheral tissue ischemia in neonates with the use of TNG. Citations were restricted to human subjects. Six hundred and eighty-nine articles were identified, and twenty-seven case reports and case series were compatible with the inclusion and exclusion criteria. Sixty-eight infants out of the 76 published cases (89%) experienced a favorable outcome and 79% (n = 60) demonstrated complete recovery with the topical application of TNG to the ischemic site. The available evidence demonstrates that TNG is effective for the treatment of peripheral ischemia in neonates after standard conservative measures have failed. However, due to the absence of robust evidence for this therapeutic modality, there are no uniform guidelines regarding the frequency, duration, and safety of TNG use. Planning the management of peripheral ischemia in neonates with TNG should be a multidisciplinary decision that includes close surveillance of blood pressure, methemoglobin levels, and follow up cranial ultrasound.


[Myocardial tissue vitality: clinical relevance, pathophysiology and identification].
Heart failure is an increasing clinical problem because of the rising frequency of admissions and the high mortality. Excellent long-term results are obtained with heart transplantation, whereas the long-term prognosis is poor when patients are treated medically. It has recently been demonstrated that, in patients with depressed left ventricular (LV) function, revascularization may be an alternative form of therapy, since improvement of LV function, which is an important prognostic factor, may occur after coronary revascularization. Recovery of LV function after revascularization may occur in patients with dysfunctional but viable myocardium, whereas no recovery can be expected in patients with scar tissue. Improvement of LV function after revascularization can be explained on the basis of the concept of myocardial tissue vitality': chronically ischaemic myocardium temporarily loses the facility to contract, but the contraction is regained after revascularization (once the ischaemia is eliminated). For the selection of patients who may profit by a revascularization procedure, techniques have been developed for the identification of dysfunctional but viable tissue. The myocardial glucose metabolism can be visualized by administration of 18F desoxyglucose (FDG) and imaging by positron emission tomography or 'single photon emission computer tomography'. Vital tissue shows diminished perfusion with intact glucose metabolism (FDG perfusion mismatch); a vital tissue shows diminished perfusion without glucose metabolism (FDG perfusion match). Scintigraphy of the membrane of the myocardial cell can also be investigated using 201Tl scintigraphy. Reserve contractility of the myocardium can be visualized by echocardiography during administration of dobutamine.


Eye movement patterns in REM sleep.
Eye movements in 6 healthy men and women were studied for recurrent patterns during REM sleep. The REM periods of nocturnal polysomnograms, on 2 consecutive nights, were analyzed in each subject. A discrete scale from 1 to 8 was used to record each eye position. The total number of recorded eye positions for the 2 nights of testing varied from 1314 to 3006. The distributions of eye movement were similar for males and females, for both nights of testing for each subject, among individual REM periods, and between subjects. This was in spite of marked differences in the number and length of REM periods, and in the number of eye movements per minute of REM sleep. In 5 of 6 subjects there was a marked tendency for the eyes to move between the 2 opposite lateral positions. Regardless of the eye position, the opposite movement was generally most likely, with an underlying tendency to return to the most opposite of the two lateral positions. In the remaining subject the opposite movement was also favored, but in this subject eye movements were more likely to be vertical rather than horizontal. Our data suggest that eye movements in REM sleep are organized in complex recurring patterns, with marked similarities between subjects. The significance of these patterns and the significance of deviations from these patterns require further study.


Pulsed-field gel electrophoresis (PFGE) analysis of temporally matched Listeria monocytogenes isolates from human clinical cases, foods, ruminant farms, and urban and natural environments reveals source-associated as well as widely distributed PFGE types.
A total of 495 temporally and geographically matched Listeria monocytogenes isolates from human clinical cases, foods, ruminant farms, and urban and natural environments were used to investigate L. monocytogenes pulsed-field gel electrophoresis (PFGE) type diversity. Two-enzyme (AscI and ApaI) PFGE discriminated 310 PFGE types and exhibited higher overall discriminatory power (Simpson's index of discrimination [D] = 0.995) than either EcoRI ribotyping (D = 0.950) or AscI or ApaI single-enzyme PFGE (D = 0.992 for both). Seven PFGE types showed significant associations with specific sources, including one and four PFGE types, respectively, associated with human clinical cases and foods. Spatial analysis of 13 PFGE types occurring >5 times showed that two PFGE types were specific to a single processing facility each, where they appear to have persisted over time. Nine PFGE types were geographically widespread and occurred among isolates from multiple sources. For example, a PFGE type that matched isolates from listeriosis outbreaks in Los Angeles and Switzerland occurred among isolates from farms (n = 7), human clinical cases (n = 4), environmental sources (n = 3), and foods (n = 1). Our data indicate that (i) PFGE is highly discriminatory for the subtyping of L. monocytogenes, (ii) some L. monocytogenes PFGE types are associated with specific sources, and (iii) some L. monocytogenes PFGE types are widely distributed and appear to be stable and pandemic. Large PFGE type databases representing isolates from different sources are thus needed to appropriately interpret subtype data in epidemiological investigations and to identify common as well as source-specific PFGE types.


Fluorescent probes to detect lymphocyte activation.
Fluorescent probes can monitor events in lymphocytes stimulated by mitogens and antigens. Early activation is associated with conformational changes in membrane macromolecules, and has been studied by measurement of fluorescence intensity or polarization of the membrane-localizing probes ANS, NPN, DPH and TMRITC. Subsequent changes in cytoplasmic macromolecules have been detected by altered fluorescence polarization of intracellular fluorescein. Altered metabolic activity in the activated lymphocyte is also revealed by fluorescent probes: the increased red fluorescence of lysosomes seen by AO staining, is attributable to altered lysosome membrane permeability. AO fluorescence has also detected early changes in the nuclear nucleoprotein complex. The later synthesis of new DNA is readily demonstrated by increased staining with the nuclear probes AO, ethidium bromide, propidium iodide, mithramycin and the Hoechst dyes. Adaptation of fluorescent probe analyses to the now rapidly developing flow microfluorimeters is providing rapid and sensitive assays of lymphocyte stimulation. Such methods will permit routine detection of lymphocyte response to particular antigens or mitogens, as well as identification of antigenic substances by their stimulation of known reactive lymphocytes. Last but not least, fluorescent probes are providing new understanding of the cellular events and regulatory mechanisms associated with lymphocyte activation.


[Morphologic and molecular biologic studies of the etiology of equine sarcoid].
From 932 equine skin lesions 421 were diagnosed as sarcoids (about 45%). The most common locations were the ventral body regions, head, neck and sites of thin skin. Most often the fibroblastic type, less frequently the mixed type and most infrequent the verrucous type of sarcoid were diagnosed. Detection of BPV-DNA was performed by polymerase chain reaction (PCR) using an oligonucleotide primer pair located in the E5-open reading frame. DNA of BPV 1 and BPV 2 could be differentiated by digestion with restriction endonucleases. In 97 out of 108 sarcoids BPV-DNA was detected by PCR. Most samples showed a BPV 1 specific pattern in restriction enzyme analysis. Nonradioactive in situ hybridization was carried out on 20 sarcoids. The hybridization signal was associated with the nuclei of fibroblast-like tumor cells, predominantly at the dermo-epidermal junction. In epidermal cells, BPV-DNA could not be detected. This study confirms the opinion that sarcoids are the result of a nonproductive infection in an alien, nonpermissive host with BPV.


Practical use and utility of fluorescence in situ hybridization in the pathological diagnosis of soft tissue and bone tumors.
During routine pathological examination, fluorescence in situ hybridization (FISH) plays a significant role in the genetic analysis of samples. FISH can detect genetic abnormalities such as chromosomal translocations, gene amplifications, and deletions in formalin-fixed, paraffin-embedded (FFPE) specimens. Due to its practical advantages, FISH is already used in many pathology laboratories. It is especially useful for the diagnosis of translocation-related sarcomas (TRSs), which comprise about 25% of soft tissue sarcomas. Because TRSs have specific chimeric genes derived from characteristic chromosomal translocations, their diagnosis would not be possible without FISH. FISH significantly contributes to the genetic confirmation of TRS. Analysis using next-generation sequencing (NGS), the latest powerful method for comprehensive genomic analysis, has recently revealed many kinds of chromosomal translocations in various TRSs. We often use experimental results to create custom probes for FISH and have applied NOCA2 split probes and CIC split, CIC-FOXO4 fusion probes to the pathological diagnosis of soft tissue angiofibroma and CIC-rearranged sarcoma, respectively. Some chimeric fusions detected by NGS induce the expression of related proteins and their detection using immunohistochemistry is beneficial for pathological diagnosis. We previously identified characteristic FOSB expression in pseudomyogenic hemangioendothelioma (PHE) with a specific SERPINE1-FOSB fusion, revealing the usefulness of FOSB immunohistochemistry in the differential diagnosis of PHE and its mimics. Finally, we participated in a central review of a clinical trial of trabectedin monotherapy. We guaranteed an accurate diagnosis by using FISH and genetic confirmation to select appropriate TRS patients and thereby confirm the accuracy of the patient enrollment of the clinical trial. FISH is an essential tool for the pathological diagnosis of soft tissue and bone tumors. It can detect various genetic abnormalities in an "in situ" fashion using FFPE specimens on glass slides during routine examination. It is also an excellent tool for translating the latest experimental findings to practical use in routine pathological diagnosis. Further instrumental improvements in FISH will help it to become the universal method for the genetic analysis of pathological diagnoses.


Human T-lymphotropic virus type 4 and the human immunodeficiency virus in West Africa.
A new human T-lymphotropic virus (HTLV-4) was recently described in healthy people from Senegal. This virus has many properties in common with members of the human T-lymphotropic viruses, particularly the human immunodeficiency virus or HIV, the etiologic agent of acquired immune deficiency syndrome (AIDS), but does not appear to be associated with immunodeficiency-related disorders. In the present study, serum samples were obtained from 4248 individuals from six West African countries, including Senegal, Guinea, Guinea Bissau, Mauritania, Burkina Faso, and Ivory Coast. These samples, collected during 1985-1987, were from people categorized as healthy control, sexually active risk, and disease populations. All samples were analyzed for reactivity to HTLV-4 and HIV by radioimmunoprecipitation-sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting. Evidence for HTLV-4 infection was found in five of the six countries. The seroprevalence varied markedly from country to country. Healthy sexually active individuals in the risk category had the highest levels of HTLV-4 infection compared to individuals in the healthy control category and the disease category, the latter including AIDS patients. The seroprevalence of HIV infection in most of these countries was quite low, although tightly associated with the rare cases of AIDS. The biology of HTLV-4 infection thus differs from that of HIV in Central Africa or the United States and Europe. The presence of these viruses and their different pathogenicities in several countries of West Africa indicate the necessity for serologic assays that will distinguish between them. Further studies of their origin and distribution as well as of their biology will be important in advancing our understanding of AIDS.


Importance of acylcarnitine profile analysis for disorders of lipid metabolism in adolescent patients with recurrent rhabdomyolysis: Report of two cases.
Metabolic myopathies due to disorders of lipid metabolism are a heterogeneous group of diseases. Newborns may present with hypotonia and convulsions, while progressive proximal muscle weakness or recurrent episodes of muscle weakness accompanied by rhabdomyolysis/myoglobinuria may be seen in older ages. There is little knowledge on detection of disorders of lipid metabolism by acylcarnitine profile (ACP) analysis by tandem mass spectrometry outside the neonatal period particularly in cases with recurrent rhabdomyolysis first presenting in adolescence and adulthood. Two adolescent female cases presented with episodes of rhabdomyolysis and muscle weakness. A 13-year-old patient had five episodes of rhabdomyolysis triggered by infections. Tandem mass spectrometry was normal. A 16-year-old female patient was hospitalized eight times due to recurrent rhabdomyolysis. Increased levels of C14:2, C14:1, and C14 were determined in tandem mass spectrometry. Final diagnoses were carnitine palmitoyltransferase II (CPT II) deficiency and very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. Increased serum levels of long-chain acylcarnitine can guide to the diagnosis of lipid metabolism disorders. Serum ACP should be performed before enzyme assay and genetic studies.


Tuning band gap of holoferritin by metal core reconstitution with Cu, Co, and Mn.
Utility of ferritin in molecular electronics, especially in single molecule electronics based devices, has recently been proposed, since the iron core of holoferritin is semiconducting in nature. However, the practical aspects, e.g., how its electronic properties can be varied/tuned, need to be better addressed. In this direction, we have performed direct tunneling experiments using scanning tunneling microscopy (STM) and scanning tunneling spectroscopy (STS) on several metal core reconstituted ferritins, where the reconstitution has been carried out using biocompatible metals like copper, cobalt, and manganese that are found naturally in the human body. We show, for the first time, that, by metal core reconstitution of the ferritin protein, the band gap of the protein can be tuned to different values (here, within the range 1.17-0.00 eV, considering iron-containing holoferritin and apoferritin as well). From the respective current-voltage curves and the well-defined band gaps, clear distinction can be made among the five different ferritins indicating that the metal core has direct contribution in the observed electrical conductivities of ferritins. It is further revealed that the electrical conductivities of the reconstituted ferritins are of the same order as that for the free metal conductivities, meaning that the relative changes in the free metal conductivities are reflected in the contributions of the metals in protein shell-confinement (i.e., the ∼8 nm core of ferritin). This finding could lead to a strategy for fine-tuning ferritin band gap by preselecting a metal on the basis of the free metal conductivity values.


Cerebral monitoring of somatosensory evoked potentials during profoundly hypothermic circulatory arrest.
The factors that influence the functional integrity of the central nervous system during clinical procedures involving profoundly hypothermic circulatory arrest (PHCA) have not been objectively evaluated. Intraoperative monitoring of somatosensory evoked potentials (SEPs) was performed in nine infants undergoing PHCA during repair of congenital cardiac anomalies to investigate the short-term effects of this intervention on neurophysiologic function. Latency prolongation of the primary cortical (N18,P22) and cervical spinal cord (N13) responses, reflecting slowing of neural transmission with hypothermia, occurred as a power function of decreasing systemic temperature (p less than .01). The cortical evoked response disappeared during profound hypothermia (less than 18 degrees C), remaining absent throughout the period of circulatory arrest and for a variable period of time after reperfusion. Regression analysis indicated that the time required for the recovery of the cortical evoked response on reperfusion was a linear function of the time-temperature integral of the arrest period (p less than .001) and the pH at the onset of circulatory arrest (p less than .001). Neurologic complications occurred in three patients and included cortical blindness (n = 2) and a generalized seizure disorder (n = 1). Visual dysfunction was not reflected in the intraoperative SEP recordings, whereas prolonged delay of SEP recovery, indicative of global central nervous system injury, was observed in the patient who experienced seizures after the surgery. This preliminary experience with SEP monitoring during PHCA suggests a role for this modality in determining the short-term effects of this procedure on neurophysiologic function. The recovery characteristics of somatosensory neural transmission appear to be modulated by the duration of, and temperature and pH maintained during, the arrest period.


Estrogen receptor alpha regulates insulin sensitivity through IRS-1 tyrosine phosphorylation in mature 3T3-L1 adipocytes.
There are many clinical and experimental reports demonstrating that estrogens and insulin interact when affecting their target organs. Estrogen receptors consist of two isoforms, estrogen receptors-alpha (ER-alpha) and -beta (ER-beta), but their roles in insulin-induced glucose uptake in mature adipose tissue have yet to be clarified. To evaluate the roles of ER-alpha, expressed predominantly in adipocytes, we have investigated the effects of estradiol (E2), an ER-alpha selective agonist (PPT), and its selective antagonist (MPP) on glucose uptake and insulin action in 3T3-L1 adipocytes. 3T3-L1 adipocytes were exposed to E2 or PPT and/or MPP at different concentrations. The cells were then subjected to 2-deoxy-D-glucose transport assay, western blot analysis, or RT-PCR analysis. Treatment of these cells with E2 or PPT resulted in biphasic effects on glucose transport, that is high (10(-5) M or 3 x 10(-6) M each) and low (10(-8) M) doses produced inhibition and stimulation, respectively. The favorable effect observed at 10(-8) M of E2 was diminished by treatment with MPP. Western bolt analysis revealed that these effects of E2, PPT and MPP paralleled the level of IRS-1 tyrosine phosphorylation. However, IRS-1 serine phosphorylation, suppressor of cytokine signaling (SOCS)-1,-2,-3 and protein tyrosine phosphatase 1B (PTP1B) expression did not change compared to control subjects. Our data clearly show that ER-alpha contributes to insulin stimulated glucose uptake through regulation of the tyrosine phosphorylation of IRS-1 protein.


Impaired cardiac output during exercise in adults operated for ventricular septal defect in childhood: a hitherto unrecognised pathophysiological response.
Recent studies have demonstrated that surgical ventricular septal defect closure in childhood is associated with reduced functional capacity and disruption of the right ventricular force-frequency relationship during exercise. To further describe long-term cardiac function, we performed a non-invasive assessment of cardiac index during exercise in adults having undergone surgery for ventricular septal defect in early childhood. A total of 20 patients (surgical age 2.1±1.4 years, age at examination 22.1±2.2 years) and 20 healthy, matched controls (23.4±2.1 years at examination) underwent continuous supine bicycle ergometry during MRI. Their blood flow was recorded in the ascending aorta and the pulmonary trunk at increasing exercise levels. Cardiac index, retrograde flow, and vessel diameters were determined by blinded, post hoc analyses. The patient group had normal cardiac index at rest (2.9±0.7 L/minute/m2), which was comparable with that of the controls (3.0±0.6 L/minute/m2); however, they had a lower increase in cardiac index during exercise (reaching 7.3±1.3 L/minute/m2 at submaximal exercise) compared with controls (8.2±1.2 L/minute/m2), p<0.05. Patients had a significantly higher ascending aorta retrograde flow than controls at rest and throughout exercise. In the pulmonary artery, the retrograde flow was minimal at rest in both groups, but increased significantly in patients during exercise compared with controls. Young adults with a surgically closed ventricular septal defect have a reduced cardiac index during exercise compared with healthy, young adults. The impaired cardiac index appears to be related to an increasing retrograde flow in the pulmonary artery with progressive exertion.


[Genetic control of formation and reorganization of the chromocenter in drosophila].
The chromocenter integrates the entire Drosophila genome into a unit. The formation and reorganization of chromocenter are genetically determined. Currently, several mutations affecting the structure of chromocenter have been described. In this work, I present evidence on the time of the formation and reorganization of chromocenter in mitotic and meiotic cells of females of the wild type and the ff16 mutant line obtained by selection of mosaic clones produced from mitotic recombination of chromosomes in the dividing embryo cells. In females homozygous for this mutation, the second stage of the formation of chromocenter (joining two groups of nonhomologous chromosomes X-4 and 2-4 into a united ring structure -X-2-3-4-) is disturbed. The differences between the mitotic and meiotic reorganization of chromocenter and the role of chromocenter in the control of chromosome segregation are discussed.


[Diagnosis of Helicobacter pylori infection with urine and stool].
The urine antibody and stool antigen test are newly developed non-invasive tests for Helicobacter pylori (H. pylori) infection. The aim of this study was to assess the diagnostic value of these tests. Urine and stool specimens from 50 consecutive patients who had undergone gastroscopy (28 men, mean age 54 years) were obtained. A kit for antibody against H. pylori (RAPIRUN test) was used for urine specimens and a kit for H. pylori antigen using ELISA (HpSA test) was used for stool specimens. None of patients had ever received any treatment to eradicate H. pylori. The H. pylori status was evaluated based on three different tests (histology, 13C-urea breath test, rapid urease test) and defined as positive when two of three tests were positive. Of 50 patients, 31 patients were diagnosed as H. pylori positive and 15 patients were negative. The RAPIRUN test was positive in 24 of 31 patients (sensitivity 77.4%) and negative in 13 of 15 patients (specificity 86.7%). The HpSA test was positive in 25 of 31 patients (sensitivity 80.1%) and negative in 14 of 15 patients (specificity 93.3%). The accuracies of H. pylori urine antibody and stool antigen test are similar to those of Western studies. These two tests are found to be useful methods for diagnosis of H. pylori infection in Korea.


A Daily Dose of 5 mg Folic Acid for 90 Days Is Associated with Increased Serum Unmetabolized Folic Acid and Reduced Natural Killer Cell Cytotoxicity in Healthy Brazilian Adults.
Background: The effects of high-dose folic acid (FA) supplementation in healthy individuals on blood folate concentrations and immune response are unknown.Objective: The aim of the study was to evaluate the effects of daily consumption of a tablet containing 5 mg FA on serum folate; number and cytotoxicity of natural killer (NK) cells; mRNA expression of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR), interferon γ (IFNG), tumor necrosis factor α (TNFA), and interleukin 8 (IL8) genes; and concentrations of serum inflammatory markers.Methods: This prospective clinical trial was conducted in 30 healthy Brazilian adults (15 women), aged 27.7 y (95% CI: 26.4, 29.1 y), with a body mass index (in kg/m2) of 23.1 (95% CI: 22.0, 24.3). Blood was collected at baseline and after 45 and 90 d of the intervention. Serum folate concentrations were measured by microbiological assay and HPLC-tandem mass spectrometry [folate forms, including unmetabolized folic acid (UMFA)]. We used real-time polymerase chain reaction to assess mononuclear leukocyte mRNA expression and flow cytometry to measure the number and cytotoxicity of NK cells.Results: Serum folate concentrations increased by ∼5-fold after the intervention (P < 0.001), and UMFA concentrations increased by 11.9- and 5.9-fold at 45 and 90 d, respectively, when compared with baseline (P < 0.001). UMFA concentrations increased (>1.12 nmol/L) in 29 (96.6%) participants at day 45 and in 26 (86.7%) participants at day 90. We observed significant reductions in the number (P < 0.001) and cytotoxicity (P = 0.003) of NK cells after 45 and 90 d. Compared with baseline, DHFR mRNA expression was higher at 90 d (P = 0.006) and IL8 and TNFA mRNA expressions were higher at 45 and 90 d (P = 0.001 for both).Conclusion: This noncontrolled intervention showed that healthy adults responded to a high-dose FA supplement with increased UMFA concentrations, changes in cytokine mRNA expression, and reduced number and cytotoxicity of NK cells. This trial was registered at www.ensaiosclinicos.gov.br as RBR-2pr7zp.


[The occurrence and analysis of chosen risk factors of DKA among children with new onset of DMT1].
DKA is still the potentially life-threatening complication of DMT1 especially in children and in newly diagnosed subjects. The aim of the study was the assessment of the DKA frequency and the analysis of chosen risk factors in children with the new onset of DMT1. The group of 186 children with the onset of DM hospitalised in the years 2004-2005 was followed up. Biochemical parameters: pH, glycaemia and HbA1c were analysed. Moreover additional features: clinical symptoms, the duration of symptoms and the numbers of visits preceding right diagnosis were collected. 62 children (33%) presented DKA at the onset of DM. The mean age of these children (8.3+/-4.9 years) was significantly lower than mean age of the whole group (9.6+/-4.9 years, p<0,05). The highest number of DKA episodes was observed in children below 4 years (p<0,001). Apart from the classical symptoms, nocturnal enuresis was the most frequent symptom reported at the onset. The correlations between duration of symptoms and pH as well as delaying of diagnosis and both severity of DKA and age of children have not been observed. The occurrence of DKA was constant in spite of seasonality of DM incidence. At the time of diabetes initial diagnosis DKA episodes have been reported in 1/3 of cases. Among analysed risk factors only the young age has been evidenced as significant in newly diagnosed children.


Microwave coagulation therapy for a liver tumor involving the root of the left hepatic vein of the residual liver after extended right hepatectomy.
A 54-year-old man had received low anterior resection for rectal carcinoma and extended right hepatectomy for a metastatic liver tumor. One year later, imaging studies disclosed a metastatic liver tumor in segment 2 of the liver. The residual left hepatic vein was completely invaded by the tumor from the root of the hepatic vein to the confluence of several branches by intraoperative ultrasonography. To resect partial liver with the involved hepatic vein was deemed impossible. Microwave coagulation therapy was performed on the tumor and the involved hepatic vein, as we had established the safety of microwave irradiation to the main hepatic vein without interference of the hepatic venous flow in an experimental study. The patient remains well 40 months after the surgery without recurrent signs. The hepatic venous flow of the irradiated hepatic vein is maintained well according to serial examination of Doppler ultrasonography.


Localized transmeningeal muscimol prevents neocortical seizures in rats and nonhuman primates: therapeutic implications.
To determine whether muscimol delivered epidurally or into the subarachnoid space can prevent and/or terminate acetylcholine (Ach)-induced focal neocortical seizures at concentrations not affecting behavior and background electroencephalography (EEG) activity. Rats (n = 12) and squirrel monkeys (n = 3) were chronically implanted with an epidural or subarachnoid drug delivery device, respectively, over the right frontal/parietal cortex, with adjacent EEG electrodes. Recordings were performed in behaving rats and chaired monkeys. Via the implants, either a control solution (artificial cerebrospinal fluid, ACSF) or muscimol (0.25-12.5 mm) was delivered locally as a "pretreatment," followed by the similar delivery of a seizure-inducing concentration of Ach. In five additional rats, the quantities of food-pellets consumed during epidural ACSF and muscimol (2.5 mm) exposures were measured. In a last group of four rats, muscimol (0.8-2.5 mm) was delivered epidurally during the ongoing, Ach-induced EEG seizure. In contrast to ACSF pretreatments, epidural muscimol pretreatment in rats completely prevented the seizures at and above 2.5 mm. In the monkeys, subarachnoid muscimol pretreatments at 2.5 mm completely prevented the focal-seizure-inducing effect of Ach, whereas similar deliveries of ACSF did not affect the seizures. Furthermore, 2.5 mm epidural muscimol left the eating behavior of rats intact and caused only slight changes in the EEG power spectra. Finally, muscimol delivery during Ach-induced EEG seizures terminated the seizure activity within 1-3 min. The results of this study suggest that muscimol is a viable candidate for the transmeningeal pharmacotherapy of intractable focal epilepsy.


NMR spectroscopy goes mobile: Using NMR as process analytical technology at the fume hood.
Nuclear magnetic resonance (NMR) is potentially a very powerful process analytical technology (PAT) tool as it gives an atomic resolution picture of the reaction mixture without the need for chromatography. NMR is well suited for interrogating transient intermediates, providing kinetic information via NMR active nuclei, and most importantly provides universally quantitative information for all species in solution. This contrasts with commonly used PAT instruments, such as Raman or Flow-infrared (IR), which requires a separate calibration curve for every component of the reaction mixture. To date, the large footprint of high-field (≥400 MHz) NMR spectrometers and the immobility of superconducting magnets, coupled with strict requirements for the architecture for the room it is to be installed, have been a major obstacle to using this technology right next to fume hoods where chemists perform synthetic work. Here, we describe the use of a small, lightweight 60 MHz Benchtop NMR system (Nanalysis Pro-60) located on a mobile platform, that was used to monitor both small and intermediate scale Grignard formation and coupling reactions. We also show how low field NMR can provide a deceptively simple yes/no answer (for a system that would otherwise require laborious off-line testing) in the enrichment of one component versus another in a kilogram scale distillation. Benchtop NMR was also used to derive molecule specific information from Flow-IR, a technology found in most manufacturing sites, and compare the ease at which the concentrations of the reaction mixtures can be derived by NMR versus IR.


Expression and DNA-binding activity of MYCN/Max and Mnt/Max during induced differentiation of human neuroblastoma cells.
Amplification of MYCN is one of the most important prognostic markers for neuroblastoma and is correlated with rapid tumor progression and poor prognosis. MYCN belongs to the Myc/Max/Mad/Mnt network of proteins that regulate proliferation, apoptosis, and differentiation. It is well established that MYCN is downregulated during induced differentiation of neuroblastoma cells carrying an amplified MYCN gene, but very little is known about other components of the network, i.e., the Max, Mad, and Mnt proteins, during this process. In this study we show that Mad and Mnt expression was only modestly regulated in differentiating SK-N-BE(2) neuroblastoma cells, while MYCN was rapidly downregulated. This downregulation was reflected in a decreased MYCN/Max DNA-binding activity while the Mnt/Max binding did not change during differentiation. In parallel experiments we also analyzed the Myc/Max/Mad expression and DNA binding capacity during induced differentiation in the MYCN single copy neuroblastoma cell line SH-SY5Y. In this cell line only modest changes in expression of the components of the MYCN/Max/Mad/Mnt network was detected, but since the cell line expresses relatively low levels of MYCN and c-Myc, these changes might be of functional significance. Cell cycle analyses of SK-N-BE(2) demonstrated an increase in the G1-phase fraction after RA-treatment. These data show that the decreased MYCN expression and MYCN DNA-binding is correlated with retarded cell cycle progression. Furthermore, when Mad1 or Mnt was overexpressed in SK-N-BE(2) cells they retained the capacity to differentiate, underscoring the notion that MYCN downregulation, and not changes in Mad/Mnt expression, is essential for neuroblastoma cell differentiation.


THE SAFETY AND EFFICACY OF AMIODARONE AND CARVEDILOL COMBINATION IN TREATMENT OF PATIENTS WITH SEVERE CARDIAC RHYTHM DISORDERS.
Different arrhythmias are cause of sudden death in many patients with heart failure. Amiodarone is usually used for prevent this arrhythmias, but it is not drug of choice for treatment the patients with heart failure. We retrospectively analyzed 142 patients with moderate and severe heart failure and history of myocardial infarction. These patients have received amiodarone, carvedilol or combination of these two medications together with standard therapy. In our retrospective analysis, the combination therapy with Amiodarone and Carvedilol had highly significant decrease arrhythmic death compare with carvedilol and amiodarone groups. This therapy is more effective in recovering of sinus rhythm in patients with atrial fibrillation and for control ventricular arrhythmias. The effects of carvedilol on left ventricular remodeling, systolic function and symptomatic status are not affected adversly by concurrent treatment with amiodarone. Carvedilol is an effective additional therapy for the patients with chronic heart failure already receiving Amiodarone. Carvedilol can be added to Amiodarone in patients with severe ventricular rhythm disorders and increased risk of sudden death without expecting of increase adverse events (than either drug alone) or loss of clinical efficacy.


Isolated Focal Infantile Hemangioma of the Alveolar Ridge with Glucose Transporter-1 Reactivity: An Aberrant Presentation.
To give dental practitioners an insight into the unusual presentation of focal infantile hemangioma on the alveolar ridge showing immunoreactivity to glucose transporter-1 (GLT1). We also recommend the importance of using standardized terminologies to describe the type of hemangioma. One of the most commonly seen and misdiagnosed vascular tumors of the skin and soft tissues of the head and neck region in children are infantile hemangiomas. Infantile hemangiomas developing at extracutaneous locations such as the oral cavity are rare, especially without cutaneous involvement. A 9-month-old infant girl presented to the Pediatric Dental Department with a swelling over the maxillary alveolar ridge. The solitary exophytic mass appeared after birth and gradually enlarged in size with episodes of bleeding during feeding. Clinical examination revealed a reddish-pink pedunculated mass that bled profusely on palpation. The lesion was excised by electrocautery and was found to be express glucose transporter-1 confirming the diagnosis of infantile hemangioma. The patient was followed up for 1 year and showed no recurrence. Hemangiomas are usually misinterpreted to be pyogenic granulomas, vascular malformation, reactive granulation tissue, or congenital granular cell tumor. This report highlights the use of glucose transporter-1 when there is suspicion of hemangioma for immunohistochemical distinction from other histologically similar vascular lesions of the oral cavity. Dental surgeons treating vascular lesions of the oral cavity should advocate for surgical management techniques that also produce hemostasis due to the risk of intraoperative bleeding. Natarajan D, Muthukali S, Nachiappan N, et al. Isolated Focal Infantile Hemangioma of the Alveolar Ridge with Glucose Transporter-1 Reactivity: An Aberrant Presentation. Int J Clin Pediatr Dent 2021;14(2):319-322.


Glycoprotein composition along the pistil of Malus x domestica and the modulation of pollen tube growth.
The characteristics of pollen tube growth are not constant, but display distinct patterns of growth within the different tissues of the pistil. In the stigma, the growth rate is slow and autotrophic, whereas in the style, it is rapid and heterotrophic. Very little is known about the interactions between these distinct maternal tissues and the traversing pollen tube and the role of this interaction on the observed metabolism. In this work we characterise pollen tube growth in the apple flower and look for differences in glycoprotein epitope localization between two different maternal tissues, the stigma and the style. While immunocytochemically-detected arabinogalactan proteins were present at high levels in the stigma, they were not detected in the transmitting tissue of the style, where extensins were abundant. Whereas extensins remained at high levels in unpollinated pistils, they were no longer present in the style following pollen tube passage. Similarily, while abundant in unpollinated styles, insoluble polysaccharides such as β-glucans, were depleted in pollinated pistils. The switch from autotropic to heterotrophic pollen tube growth correlates spatially with a change of glycoprotein epitopes between the stigma and the style. The depletion of extensins and polysaccharides following pollen tube passage in the style suggest a possible contribution to the acceleration of heterotrophic pollen tube growth, which would imply an active contribution of female tissues on prezygotic male-female crosstalk.


A methodology for intensive case-finding and monitoring of drug use in Mexican community.
An intensive case-finding model of drug use is presented with respect to its advantages and limitations. Two approaches were used: (a) direct, in which the questions concerning drug use were asked openly by the field-workers, and (b) indirect, where the field-workers obtained information about drug use from general conversation with interviewees. The indirect approach was found to be very useful in contacting new drug users and in assessing the psycho-social context of drug use. This research suggests that the intensive case-finding method is suitable for a community where the majority of drug users form cohesive groups, while it was found to be less effective for the study of isolated cases.


Human keratinocytes contain carbohydrates that are recognized by keratan sulfate-specific monoclonal antibodies.
Monoclonal antibodies that recognize carbohydrate epitopes found in keratan sulfate glycosaminoglycan chains identified both intracytoplasmic and cell-surface carbohydrates of human keratinocytes. These carbohydrates were detected, using indirect immunoperoxidase methods, both in sections of paraffin-embedded tissues and in intact cultured keratinocytes. Of the seven anti-keratan sulfate monoclonal antibodies used in this study, five detected significant amounts of epitopes associated with keratinocytes. This indicates that only certain, specific types of keratan sulfate-like carbohydrates were expressed by these cells. The extent and localization of keratan sulfate-like carbohydrates appeared to be closely related to the differentiation status of cultured keratinocytes. These epitopes were very weakly expressed on surfaces of all monolayer keratinocytes, but flattened, suprabasal cells in high Ca++ cultures strongly expressed keratan sulfate-like carbohydrates on their surfaces. A much larger population of cultured keratinocytes expressed intracellular keratan sulfate-like carbohydrates identified by the same five antibodies that detected surface epitopes. In monolayer cells, keratan sulfate-like carbohydrates were predominantly found in a broad perinuclear zone. In addition, three of the five immunoreactive antibodies detected epitopes that appeared at cell boundaries, specifically at sites of close cell-to-cell contact. Thus, molecules bearing carbohydrates recognized by anti-keratan sulfate antibodies appear at developmentally important stages of keratinocyte differentiation, indicating that these carbohydrates may serve as markers for molecules important in the differentiation of human keratinocytes.


New method for estimation of adult skeletal age at death from the morphology of the auricular surface of the ilium.
A new method for estimating skeletal age at death from the morphology of the auricular surface of the ilium is presented. It uses a multiple regression analysis with dummy variables, and is based on the examination of 700 modern Japanese skeletal remains with age records. The observer using this method needs only to check for the presence or absence of nine (for a male) or seven (for a female) features on the auricular surface and to select the parameter estimates of each feature, calculated by multiple regression analysis with dummy variables. The observer can obtain an estimated age from the sum of parameter estimates. It is shown that a fine granular texture of the auricular surface is typical of younger individuals, whereas a heavily porous texture is characteristic of older individuals, and that both of these features are very useful for estimating age. Our method is shown here to be more accurate than other methods, especially in the older age ranges. Since the auricular surface allows more expedient observations than other parts of the skeleton, this new method can be expected to improve the overall accuracy of estimating skeletal age at death.


Lentiviral vector-mediated IL-9 overexpression stimulates cell proliferation by targeting c-myc and cyclin D1 in colitis-associated cancer.
Colorectal cancer caused by inflammatory bowel disease is referred as colitis-associated cancer (CAC). The mechanism underling CAC is not fully understood. In the present study, the role of interleukin-9 (IL-9) in CAC was examined. The current study included 12 colorectal tissue specimens and matched adjacent tissues from CAC. The expression of IL-9 protein was examined using immunohistochemical staining. The expression of IL-9 in cancer tissues was markedly higher compared with that in adjacent tissues. Furthermore, IL-9 gene overexpression lentiviral vectors were constructed to overexpress IL-9 in RKO and Caco-2 cell lines. The role of IL-9 in cell proliferation was investigated using a Cell Counting Kit-8 assay, and MYC proto-oncogene bHLH transcription factor (c-Myc) and cyclinD1 expression levels were detected by reverse transcription-quantitative polymerase chain reaction. Notably, IL-9 overexpression promoted the proliferation of colonic epithelial cells by upregulating of the expression of c-Myc and cyclinD1. In conclusion, the present results suggested that IL-9 may exhibit an essential role in the pathogenesis of CAC, and IL-9 promotes the proliferation of colonic epithelial RKO and Caco2 cells, partially via the upregulation of c-Myc and cyclinD1 expression.


Investigation of biodegradation potentials of high density polyethylene degrading marine bacteria isolated from the coastal regions of Tamil Nadu, India.
Plastics constitute an important part of our life for many decades. All the wastes produced from human activities finally enters into the aquatic ecosystem. Microbial degradation of plastic is a promising eco-friendly strategy which represents a great opportunity to manage waste plastic materials with minimum adverse impacts. In this present study, totally 248 bacterial isolates were isolated from the plastic waste dumped sites in the coastal region districts of Tamil Nadu, India and screened for HDPE degradation. Based on the results obtained from the weight loss, viability and FT-IR, 10 bacterial isolates were considered to be potent HDPE degraders. The identification of efficient HDPE degrading isolates confirms that most of the bacterial isolates belong to the genus Bacillus spp. and Pseudomonas spp. The present study suggests that the isolated efficient bacterial strains can be used as cost-effective, eco-friendly and safe approach for the elimination of plastic wastes from the environment.


Organ procurement in forensic deaths: French developments.
Organ procurement and transplantation have grown steadily, and the need for organs will only rise in the future. Increasing the number of potential donors is therefore paramount. However, transplant coordination teams face refusals that can be linked to the contexts of the deaths, especially when they involve legal issues. In France, deaths involving legal proceedings are not uncommon (7-10%). In these cases, the prosecutor is immediately contacted, and makes the decision of whether to remove the involved organs. Refusals of this type represent 4% (approximately 30 cases per year) of obstacles to organ removals, and are governed by specific legislation. Thus, the prosecutor must arrange contact with a forensic pathologist and with the organ transplant teams to assemble all of the necessary elements for him to take the decision. To assist prosecutors in their decision making and to ensure them scientific rigour, the French Society of Forensic Medicine sought to develop a national recommendation to harmonise practices; it emerged in early 2013. The guideline makes practical recommendations, including among others: nominating local referents; writing regional protocols between judicial authorities, forensic pathologists and transplant teams; establishing terms for the forensic pathologist's intervention on the donor's body before and after a procurement. This recommendation by the French Society of Forensic Medicine aimed to combine two interests: addressing the shortage of organs, and fulfilling the requisites of a criminal investigation by standardising practices and encouraging communication.


Pleural mesothelioma with cutaneous extension to chest wall scars.
Cutaneous mesothelioma is rare but may occur following local surgical procedures for visceral mesothelioma or as a metastasis. A patient with pleural mesothelioma, who developed papules within chest wall scars, 14 and 15 months after pleural biopsy and thoracentesis, respectively, is reported. Histopathology showed an epithelioid tumor forming tubulopapillary and glandular structures. The diagnosis of mesothelioma was confirmed with immunohistochemistry. Tumor cells stained characteristically for low-molecular-weight cytokeratins 5/6, calretinin, and vimentin and were negative for mucicarmine, carcinoembryonic antigen, thyroid transcription factor 1, prostate-specific antigen, gross cystic disease fluid protein, S-100, factor VIII, and CD31. Histologically, mesothelioma may resemble a primary adnexal neoplasm, metastatic adenocarcinoma, or angiosarcoma. Immunohistochemistry can clarify the diagnosis. Clinicians should be aware of the varied presentations of mesothelioma, as cutaneous presentations are becoming increasingly common.


Eater-oriented knowledge framework for reducing salt and dietary sodium intake (scoping review).
Salt and dietary sodium are ubiquitously present in daily food practices and, at the same time, reducing salt intake presents an important public health issue. Given such an ambivalent position of salt in human diet, we argue that public health guidelines toward dietary sodium reduction require an eater-oriented knowledge framework. In this article we are making the first steps toward a flexible interdisciplinary database which would include nutritional, socio-economic, cultural, material, and socio-psychological determinants of salt consumption for comprehensive public health campaigns. We employ an explorative scoping review of academic articles and reports, limiting our review to the original data on salt or sodium consumption published in English or French between 2000 and 2022. We describe salt consumption as research object, identifying its representation in different research fields, data sources, methodologies, samples, and links with nutritional recommendations. We synthesize existing approaches via four eater-oriented categories: Socio-demographic and cultural descriptors of salt consumers; Knowledge, attitudes, and beliefs on nutritional norms; Salt practices associated with dietary or medical regimes; Salt materialities: interactions and contexts. In each category, we identify the dominant relational features, i.e., what kind of 'eater-salt' relation is being put forward. We thus build an interdisciplinary documentary base of dietary sodium consumption factors. We discuss the results, suggesting that comprehensive nutritional policies for global salt reduction require interdisciplinary eater-oriented data frameworks.


Moderate, Short-Term, Local Hyperglycemia Attenuates Forearm Endothelium-Dependent Vasodilation After Transient Ischemia-Reperfusion in Human Volunteers.
Acute hyperglycemia causes endothelial dysfunction in diabetic patients, abolishes ischemic pre- and postconditioning, and is an independent predictor of adverse outcome after myocardial infarction in nondiabetic patients. Its effects on endothelial-dependent vasodilation are controversial in healthy subjects. The authors studied the effect of moderate short-term local hyperglycemia on forearm endothelium-dependent vasodilation in healthy volunteers. Randomized, crossover, blinded, 2-visit, pilot design. Veterans Affairs Medical Center. Five male and 3 female healthy adult volunteers (23±4 years; height 171±13 cm; weight 66±9 kg; [mean±standard error of the mean]). At each visit, volunteers received an infusion through a brachial artery catheter of either 0.9% saline or dextrose in the experimental, non-dominant arm, to establish mild forearm hyperglycemia. Hemodynamics and forearm blood flow (FBF; plethysmography) were measured at baseline, during brachial artery infusions of acetylcholine in consecutive increments (5, 10, and 15 μg/min), before ischemia (20 min, blood pressure cuff at 200 mmHg), and after 15 minutes of reperfusion. Blood glucose and insulin concentrations were determined from venous samples. The effect of duration of intra-arterial dextrose on FBF was examined. Dextrose increased steady-state blood glucose concentration in the experimental but not the control arm (dominant arm). Dextrose increased FBF compared with saline (4.5±0.5 v 2.6±0.4 mL/min/100 g of tissue, respectively). Acetylcholine caused similar increases in FBF in the absence and presence of dextrose (+239±90% v+203±75%, respectively, during 15 μg/min). The duration of dextrose did not affect this acetylcholine-induced vasodilation. Acetylcholine-stimulated increases in FBF were attenuated in dextrose-treated versus saline after reperfusion (+180±18% v+257±53%, respectively, during 10 μg/min). Interventions in the experimental arm did not affect FBF in the control arm. These results indicated that moderate, short-term, local hyperglycemia induced by intra-arterial administration of dextrose attenuated forearm endothelial-dependent vasodilation after ischemia-reperfusion injury in healthy volunteers.