[Modifications induced on thrombin and plasmin activity by voluntary interruption of pregnancy].
Pregnancy is characterized by plasmatic variations of coagulative factors' concentration and by different haemostatic-fibrinolytic balance. At present it is possible, with EIA methods, to measure fibrinogen (FgDP) and fibrin (FbDP) degradation products with precision and accuracy, as direct indexes of fibrinolysis and the thrombin-antithrombin III complex (TAT) as indirect index of thrombophilia. We have considered the course of those indexes in 61 pregnant women within the tenth week of gestation, before and after voluntary pregnancy interruption (VPI) resulted without complications. The results don't show any peculiar variation of the examined parameters between the pregnant women before VPI and a control group. Comparing the basal data with those obtained three hours after VPI, all indexes are increased, particularly FbDP. After 24 hours the concentration of FgDP, FbDP and TDP decreased in comparison with the three hours control drawing, nevertheless staying higher than the values obtained in the basal drawing. The evolution of FDP and of TAT, in our study, points out that, in the first weeks of pregnancy, the haemostatic-fibrinolytic balance does not differ significantly from the physiological balance. Three hours after VPI fibrinolytic mechanisms prevail as regards the fibrinogenolytic ones. TAT increases after 3 hours and returns to the rules after 24 hours, proposing itself as an indirect index of thrombinic activation and as a direct index of antithrombinic activity.


Preparation and characterization of microporous layers on titanium.
Microporous layers on titanium (Ti) are formed by chemical treatment in highly concentrated alkaline media, and their properties and growth mechanism are examined using electrochemical techniques, in situ resistometry, scanning electron microscopy (SEM), grazing-incident X-ray diffraction (GIXRD), and glow discharge optical emission spectroscopy (GD-OES). Chemical treatment in a 5 M aqueous KOH solution yields results superior to those from the same treatment in a 5 M aqueous NaOH solution, while a 3 M aqueous LiOH solution does not produce porous layers. The cation constituting the solution plays a vital role in the process. An SEM analysis reveals that the KOH solution is the most effective in forming microporosity and that the longer the treatment time, the more porous the near-surface layer. The results of GIXRD analysis show the presence of Na(2)Ti(5)O(11) and K(2)Ti(6)O(13) in the layers formed in the NaOH and KOH solutions, respectively; in the case of the LiOH solution, TiO(2) is formed. Chemical treatment in the NaOH and KOH solutions resembles a general corrosion process with the existence of local cathodic and anodic sites. The reduction reaction produces H(2), some of which becomes absorbed in the near-surface region of Ti, while the oxidation reaction produces the above-mentioned compounds and/or an oxide layer. The presence of hydrogen (H) within the solid is detected using GD-OES. The H-containing near-surface layer partially dissolves, yielding a microporous structure. The development and dissolution of the H-containing near-surface layer of Ti upon chemical treatment in the NaOH and KOH solutions are confirmed by resistometry measurements. They point to the formation of a compact passive layer on Ti upon exposure to the LiOH solution.


Sexual Behaviors in Mexico: The Role of Values and Gender Across Adolescence.
Adolescent sexuality research has expanded to include noncoital behaviors, but there is limited knowledge about individual factors such as cultural values associated with these sexual behaviors outside of industrialized nations. Thus, we examined associations between Latino values (familism, sexual guilt, and importance of female virginity) and three sexual behaviors (making out, oral sex, and vaginal sex), among adolescents ages 12-19 (53% female) in Mexico. Findings indicate that sexual guilt and importance of female virginity were consistently associated with all sexual behaviors. Some associations differed by gender and school level. For instance, sexual guilt was a better predictor of high school girls' oral and vaginal sex. This study expands our understanding of adolescent sexuality in Mexico.


Intracranial pressure after phenoperidine.
The problem of sedating patients requiring prolonged controlled ventilation has recently received considerable attention. Various therapeutic regimes are available and there appears to be a general move away from the use of muscle relaxants towards sedative drugs. Phenoperidine is a popular agent for this purpose. One survey from a district general hospital reported that 66% of their ventilated intensive therapy unit patients received phenoperidine, either alone or as part of a sedation regime. However, enthusiasm for its use must be tempered by recent reports of cardiovascular collapse following its administration. We wish to report a case of intracranial hypertension following the use of phenoperidine in a ventilated patient with a severe head injury.


Recent updates in the indolent lymphomas: Update on marginal zone lymphoma and Waldenström's macroglobulinemia.
Marginal Zone Lymphoma (MZL) and Waldenström's Macroglobulinemia (WM) are indolent lymphomas that both arise from post germinal center lymphocytes. Both can secrete a monoclonal protein but high levels are mostly only seen in WM. The MYD88 L256P somatic mutation that is present in an estimated 95% of patients with WM has helped greatly in differentiating the two lymphomas. Several large clinical studies with new drugs have been performed that have provided new treatment options for both MZL and WM patients. In this short review we will discuss the recent literature published and provide some recommendations.


[Dwarfism, arterial hypertension and hyperkalemic acidosis corrected with thiazides. A case of type II pseudohypoaldosteronism].
Type II pseudohypoaldosteronism is a rare tubulopathy defined by abnormal renal potassium excretion. A 12 1/2 year-old girl, was admitted for dwarfism. Her parents were not consanguineous and her 5 living sibs were normal. At admission, she had moderate hypertension: systolic 130-150 mmHg; diastolic 80-100 mmHg and no pubertal development. pH (arterial): 7.34; bicarbonates: 18-20 mEq/l; chloride: 112-120 mEq/l; potassium: 5.6-7 mEq/l; aldosterone: 200-700 pg/ml (N < 60); plasma renin activity: 0.4 ng/ml/hr (N 2.2 +/- 0.2). The bone maturation was 8 1/2 years. All the other renal function tests were normal. The titratable acidity was 22 mEq/day (N 20-40) and the ammonia excretion 15.2 mEq/l (N 44-61). The fractional excretion of potassium was 6.5% (N 11.8 +/- 1.9). This girl was given polystyrene sulfonate resin followed by hydrochlorothiazide (1 to 3 mg/kg/day). There was a subsequent improvement in all data, a growth spurt and pubertal development. This is the fifth case of type II pseudohypoaldosteronism reported in childhood and the first one with hypertension. The beneficial effect of hydrochlorothiazide is underlined.


Copper-catalyzed propargylic C-H functionalization for allene syntheses.
Allenenitriles bearing different synthetically versatile functional groups have been prepared smoothly from 5-alkynyl fluorosulfonamides in decent yields with an excellent chemo- and regio-selectivity under redox neutral conditions. The resulting allenenitriles can be readily converted to useful functionalized heterocycles. Based on mechanistic study, it is confirmed that this is the first example of radical-based non-activated propargylic C-H functionalization for allene syntheses.


Neratinib is effective in breast tumors bearing both amplification and mutation of ERBB2 (HER2).
Mutations in ERBB2, the gene encoding epidermal growth factor receptor (EGFR) family member HER2, are common in and drive the growth of "HER2-negative" (not ERBB2 amplified) tumors but are rare in "HER2-positive" (ERBB2 amplified) breast cancer. We analyzed DNA-sequencing data from HER2-positive patients and used cell lines and a patient-derived xenograft model to test the consequence of HER2 mutations on the efficacy of anti-HER2 agents such as trastuzumab, lapatinib, and neratinib, an irreversible pan-EGFR inhibitor. HER2 mutations were present in ~7% of HER2-positive tumors, all of which were metastatic but not all were previously treated. Compared to HER2 amplification alone, in both patients and cultured cell lines, the co-occurrence of HER2 mutation and amplification was associated with poor response to trastuzumab and lapatinib, the standard-of-care anti-HER2 agents. In mice, xenografts established from a patient whose HER2-positive tumor acquired a D769Y mutation in HER2 after progression on trastuzumab-based therapy were resistant to trastuzumab or lapatinib but were sensitive to neratinib. Clinical data revealed that six heavily pretreated patients with tumors bearing coincident HER2 amplification and mutation subsequently exhibited a statistically significant response to neratinib monotherapy. Thus, these findings indicate that coincident HER2 mutation reduces the efficacy of therapies commonly used to treat HER2-positive breast cancer, particularly in metastatic and previously HER2 inhibitor-treated patients, as well as potentially in patients scheduled for first-line treatment. Therefore, we propose that clinical studies testing the efficacy of neratinib are warranted selectively in breast cancer patients whose tumors carry both amplification and mutation of ERBB2/HER2.


[Retrospective assessment of childhood trauma: review of the instruments].
Childhood trauma has a crucial and proved role for the development of psychopathology during adulthood. The results of a systematic review on the instruments for the retrospective assessment of childhood trauma are reported in order to compare their reliability, validity, comprehensiveness and use. A literature search on this argument was conducted on Medline electronic archives and by canvassing English-language and other European languages publications. Eligible instruments were restricted to the ones with: available publications, retrospective assessment on adult population, independence from specific diagnostic categories, sufficient data regarding the main features. Of the 19 eligible instruments, the Familial Experiences Interview (FEI) and the Early Trauma Inventory Self Report (ETI-SR) evaluate the highest number of "trauma areas" considered in this review. The reliability and validity data provided by Authors, when available, are reported to be good to excellent. The four most used instruments in the clinical and epidemiological practice appear to be the Parental Bonding Instrument (PBI), the Adult Attachment Interview (AAI), the Childhood Experience of Care and Abuse (CECA.Q) and the Childhood Trauma Questionnaire (CTQ). Our review on the currently available instruments has pointed out some weaknesses that narrow their actual use and evaluation capability. Such issues should be taken in consideration and further discussed especially considering the increasing consent of research on the role of childhood trauma for the development of adult psychopathology.


Cloning and mapping the mouse Crygs gene and non-lens expression of [gamma]S-crystallin.
[gamma]-Crystallins are major structural proteins of the eye lens. While other crystallins have revealed distinct non-lens functions and patterns of expression, [gamma]-crystallins have generally appeared to be the most lens-specific of the crystallins. Here we examine the mouse [gamma]S-crystallin ([gamma]S) gene and its expression. The cDNA and gene for mouse [gamma]S were cloned and sequenced. The Crygs gene was mapped using genetic crosses. Expression patterns in mouse and cow were examined by northern blot, PCR and western blot using a specific peptide antibody. The Crygs gene was sequenced and mapped to mouse chromosome 16, at or near the locus for the genetic cataract Opj. Northern blots of tissues from new born mice, showed lens specific expression of [gamma]S. However, in the mature mouse eye there was, in addition, clear non-lens expression of [gamma]S. In the adult bovine eye RT-PCR shows that [gamma]S is expressed in lens, retina and cornea. A peptide antibody directed against [gamma]S detects bands of the expected size in western blots of mouse lens and in 33 day old mouse retina. These results suggest that [gamma]-crystallins have a non-crystallin role outside the lens, one which may predate the lens in evolutionary terms. Non-lens expression seems to increase with age in young mice, hinting that [gamma]S may have a role similar to that of a stress protein in tissues of the eye, perhaps related to accumulating insults resulting from light exposure.


[Bioremediation of low-level radionuclide contaminated soils and water].
Different anthroponic factors have led up to increasing background concentrations of radionuclides in human ecosystems. As long as these radionuclides enter into soil-water substrates, they can pose hazards to human health through different pathways. Since most conventional chemical or physical procedures are not practical for dealing with low-level radionuclides in the water-soil substrates, new remediation technologies are being developed to tackle the problem. Bioremediation has attracted much attention because of its many advantages such as low cost and less environmental disturbance. The present paper summarizes the sources of radionuclides and introduces the concept of low-level radionuclide bioremediation. The state of the art in the field of bioremediation of low-level radionuclide contaminated water-soil substrates has also been reviewed and summarized in this paper. On the basis of above mentioned discussions the future developing trends were put forward.


Infiltration of Macrophages Correlates with Severity of Allograft Rejection and Outcome in Human Kidney Transplantation.
Despite substantial progress in recent years, graft survival beyond the first year still requires improvement. Since modern immunosuppression addresses mainly T-cell activation and proliferation, we studied macrophage infiltration into the allografts of 103 kidney transplant recipients during acute antibody and T-cell mediated rejection. Macrophage infiltration was correlated with both graft function and graft survival until month 36 after transplantation. Macrophage infiltration was significantly elevated in antibody-mediated and T-cell mediated rejection, but not in kidneys with established IFTA. Treatment of rejection with steroids was less successful in patients with more prominent macrophage infiltration into the allografts. Macrophage infiltration was accompanied by increased cell proliferation as well as antigen presentation. With regard to the compartmental distribution severity of T-cell-mediated rejection was correlated to the amount of CD68+ cells especially in the peritubular and perivascular compartment, whereas biopsies with ABMR showed mainly peritubular CD68 infiltration. Furthermore, severity of macrophage infiltration was a valid predictor of resulting creatinine values two weeks as well as two and three years after renal transplantation as illustrated by multivariate analysis. Additionally performed ROC curve analysis showed that magnitude of macrophage infiltration (below vs. above the median) was a valid predictor for the necessity to restart dialysis. Having additionally stratified biopsies in accordance to the magnitude of macrophage infiltration, differential CD68+ cell infiltration was reflected by striking differences in overall graft survival. The differences in acute allograft rejection have not only been reflected by different magnitudes of macrophage infiltration, but also by compartment-specific infiltration pattern and subsequent impact on resulting allograft function as well as need for dialysis initiation. There is a robust relationship between macrophage infiltration, accompanying antigen-presentation and resulting allograft function.


The role of early visual attention in social development.
Faces convey important information about the social environment, and even very young infants are preferentially attentive to face-like over non-face stimuli. Eye-tracking studies have allowed researchers to examine which features of faces infants find most salient across development, and the present study examined scanning of familiar (i.e., mother) and unfamiliar (i.e., stranger) static faces at 6-, 9-, and 12-months-of-age. Infants showed a preference for scanning their mother's face as compared to a stranger's face, and displayed increased attention to the eye region as compared to the mouth region. Infants also showed patterns of decreased attention to eyes and increased attention to mouths between 6 and 12 months. Associations between visual attention at 6, 9, and 12 months and the Communication and Symbolic Behavior Scales DP (CSBS-DP) at 18 months were also examined, and a significant positive relation between attention to eyes at 6 months and the social subscale of the CSBS-DP at 18 months was found. This effect was driven by infants' attention to their mother's eyes. No relations between face scanning in 9- and 12-month-olds and social outcome at 18 months were found. The potential for using individual differences in early infant face processing to predict later social outcome is discussed.


Miniature neurologgers for flying pigeons: multichannel EEG and action and field potentials in combination with GPS recording.
To study the neurophysiology of large-scale spatial cognition, we analyzed the neuronal activity of navigating homing pigeons. This is not possible using conventional radio-telemetry suitable for short distances only. Therefore we developed a miniaturized data logger ("neurologger") that can be carried by a homing pigeon on its back, in conjunction with a micro-global position system (GPS) logger recording the spatial position of the bird. In its present state, the neurologger permits recording from up to eight single-ended or differential electrodes in a walking or flying pigeon. Inputs from eight independent channels are preamplified, band-pass filtered, and directed to an eight-channel, 10-bit analog-digital converter of the microcontroller storing data on a "Multimedia" or "Secure Digital" card. For electroencephalography (EEG), the logger permits simultaneous recordings of up to eight channels during maximally 47 h, depending on memory, while single unit activity from two channels can be stored over 9 h. The logger permits single unit separation from recorded multiunit signals. The neurologger with GPS represents a better alternative to telemetry that will eventually permit to record neuronal activity during cognitive and innate behavior of many species moving freely in their habitats but will also permit automated high-throughput screening of EEG in the laboratory.


Antimicrobial activity and partial characterization of bacteriocin-like inhibitory substances produced by Lactobacillus spp. isolated from artisanal Mexican cheese.
Lactobacillus spp. from Mexican Cocido cheese were shown to produce bacteriocin-like substances (BLS) active against Staphylococcus aureus,Listeria innocua,Escherichia coli, andSalmonella typhimurium by using the disk diffusion method. Crude extracts of Lactobacillus fermentum showed strong inhibitory activity against Staph. aureus, L. innocua, E. coli, and Salmonella cholerae. Complete inactivation of antimicrobial activity was observed after treatment of crude extracts with proteinase K, pronase, papain, trypsin, and lysozyme, confirming their proteinaceous nature. However, antimicrobial activity was partly lost for some of the crude extracts when treated with α-amylase, indicating that carbohydrate moieties were involved. The antimicrobial activity of the crude extracts was stable at 65°C for 30min over a wide pH range (2-8), and addition of potassium chloride, sodium citrate, ethanol, and butanol did not affect antibacterial activity. However, antimicrobial activity was lost after heating at 121°C for 15min, addition of methanol or Tween 80. Fourteen out of 18 Lactobacillus spp. showed antimicrobial activity against different test microorganisms, and 12 presented bacteriocin-like substances. Generation time and growth rate parameters indicated that the antimicrobial activity of crude extracts from 3 different strains was effective against the 4 indicator microorganisms. One of the crude extracts showed inhibition not only against gram-positive but also against gram-negative bacteria. Bacteriocin-like substances produced by this specific Lactobacillus strain showed potential for application as a food biopreservative.


Shark myelin basic protein: amino acid sequence, secondary structure, and self-association.
Myelin basic protein (MBP) from the Whaler shark (Carcharhinus obscurus) has been purified from acid extracts of a chloroform/methanol pellet from whole brains. The amino acid sequence of the majority of the protein has been determined and compared with the sequences of other MBPs. The shark protein has only 44% homology with the bovine protein, but, in common with other MBPs, it has basic residues distributed throughout the sequence and no extensive segments that are predicted to have an ordered secondary structure in solution. Shark MBP lacks the triproline sequence previously postulated to form a hairpin bend in the molecule. The region containing the putative consensus sequence for encephalitogenicity in the guinea pig contains several substitutions, thus accounting for the lack of activity of the shark protein. Studies of the secondary structure and self-association have shown that shark MBP possesses solution properties similar to those of the bovine protein, despite the extensive differences in primary structure.


Investigation on dynamic calibration for an optical-fiber solids concentration probe in gas-solid two-phase flows.
This paper presents a review and analysis of the research that has been carried out on dynamic calibration for optical-fiber solids concentration probes. An introduction to the optical-fiber solids concentration probe was given. Different calibration methods of optical-fiber solids concentration probes reported in the literature were reviewed. In addition, a reflection-type optical-fiber solids concentration probe was uniquely calibrated at nearly full range of the solids concentration from 0 to packed bed concentration. The effects of particle properties (particle size, sphericity and color) on the calibration results were comprehensively investigated. The results show that the output voltage has a tendency to increase with the decreasing particle size, and the effect of particle color on calibration result is more predominant than that of sphericity.


[Cerebral aspergillosis in an immunocompromised patient with follicular lymphoma].
We present a case of central nervous system aspergillosis in an immunocompromised 69-year-old male with a history of chemotherapeutic treatment for follicular lymphoma. The patient presented with aphasia, apraxia and confusion. An MRI of the central nervous system and Aspergillus antigen in the spinal fluid was suggestive for this invasive fungal infection. Despite treatment with voriconazole the patient succumbed to the infection. A rise in rare, severe infectious complications as presented is expected due to increasing dose-intensity of chemotherapy.


Pulmonary Nodules in Patients With Nonpulmonary Cancer: Not Always Metastases.
The differential diagnosis of pulmonary nodules (PNs) includes metastases, lung cancers, infectious diseases, and scar tissue, among others. Because data regarding whether and when to perform a PN biopsy in patients with cancer are scarce, clinicians tend to assume that PNs are metastatic disease based solely on imaging. The current study evaluated the findings of PN biopsies in a population of patients with cancer and sought to determine the variables that correlated with higher odds of metastatic disease. We conducted a retrospective, single-institution study that included consecutive patients with nonpulmonary solid malignancies who underwent PN biopsy from January 2011 to December 2013. Imaging and clinical variables were analyzed by logistic regression to determine the correlation between such variables and the odds of metastatic disease. Patients with previously known metastatic disease or primary hematologic malignancies were excluded. Two hundred twenty-eight patients were included in the study. Metastatic disease was found in 146 patients (64%), 60 patients (26.3%) were diagnosed with a second primary lung tumor, and 22 patients (9.6%) had no cancer on biopsy. On multivariate analysis, the presence of multiple PNs (> 5 mm) and cavitation/necrosis were the only variables associated with higher odds (P < .05) of metastatic disease. We registered six (2.6%) procedure complications demanding active interventions, and no procedure-related death occurred. Multiple PNs (> 5 mm) and cavitation were the two characteristics associated with the highest chances of metastatic disease. Our findings demonstrate that PNs should not be assumed to be metastases without performing a biopsy. This assumption may lead to high rates of misdiagnosis. Tissue sampling is fundamental for accurately diagnosing patients with cancer.


Prevalence of gestational diabetes mellitus: variations related to screening strategy used.
To determine the prevalence of gestational diabetes mellitus in a large general obstetric population and its variations depending on the presence of risk factors, and to evaluate how the gestational diabetes screening strategies applied might modify the observed prevalence in the population. A retrospective cohort study. The study population was a total of 2574 pregnant women. Information about risk factors, screening and diagnosis of gestational diabetes was obtained. Frequency of risk factors under the American College of Obstetrics and Gynecologists (ACOG) and the American Diabetes Association (ADA) criteria, and observed and expected prevalence of gestational diabetes mellitus were calculated and compared for statistical significance. Age > or = 30 years, family history of diabetes, obesity and previous fetal macrosomia were the most frequent risk factors. Under ACOG recommendations, 45% of our general obstetric population would have been exempt from gestational diabetes mellitus screening, as compared with only 15.5% under ADA guidelines. Sixty-five patients were diagnosed as having gestational diabetes mellitus, giving an overall prevalence of 2.5% (confidence interval 2.0-3.2). Among the low-risk women, prevalence values were 0.6% and 0.5% respectively under ACOG and ADA criteria, whereas for those presenting one or more risk factors rates were 4% and 2.9% respectively. In our general obstetric population, gestational diabetes mellitus prevalence was found to be approximately six times lower among low-risk gravidae than among the high-risk subjects, suggesting that selective screening might be beneficial. Nevertheless, selective gestational diabetes mellitus screening under ADA criteria seems to entail the same disadvantages as the selective screening strategies without any apparent benefits.


TDAG8 activation attenuates cerebral ischaemia-reperfusion injury via Akt signalling in rats.
T-cell death-associated gene 8 (TDAG8), a member of the proton-sensitive G-protein-coupled receptor (GPCR) class with an immune-specific expression profile, was recently shown to be expressed in the rat brain; however, its role in ischaemic stroke remains unknown. We initially confirmed the time-dependent expression of TDAG8 in rat brain tissue after ischaemic stroke and reperfusion. Further evaluations were performed to increase TDAG8 expression 6h prior to middle cerebral artery occlusion (MCAO) by injecting a specific agonist, BTB09089, into the lateral ventricle to increase TDAG8 expression. Twenty-four hours before MCAO, a specific small interfering RNA (siRNA) was introduced. The infarction volume, neurological deficit score and cleaved caspase-3 and Bcl-2 expression were used to assess the effects of TDAG8 on ischaemic stroke. Finally, the effects of TDAG8 on the development of primary cortical neurons exposed to oxygen-glucose deprivation (OGD) were investigated. TDAG8 expression increased both in vivo and in vitro. Pretreatment with BTB09089 up-regulated TDAG8 and Bcl-2 expression and down-regulated cleaved caspase-3 expression, while the infarction volume was reduced, and neurological deficits were ameliorated 24 and 72h after MCAO. However, the protective effects of TDAG8 were reversed when its level was reduced in TDAG8-deficient rats. More importantly, these findings are consistent with data from neurons subjected to OGD. TDAG8 plays an important neuroprotective role through inhibition of neuronal apoptosis and alleviation of neurological deficits by activating the Akt signalling pathway in rats.


Mass spectrometric studies of the variety of beta-amyloid proteoforms in Alzheimer's disease.
This review covers the results of the application of mass spectrometric (MS) techniques to study the diversity of beta-amyloid (Aβ) peptides in human samples. Since Aβ is an important hallmark of Alzheimer's disease (AD), which is a socially significant neurodegenerative disorder of the elderly worldwide, analysis of its endogenous variations is of particular importance for elucidating the pathogenesis of AD, predicting increased risks of the disease onset, and developing effective therapy. MS approaches have no alternative for the study of complex samples, including a wide variety of Aβ proteoforms, differing in length and modifications. Approaches based on matrix-assisted laser desorption/ionization time-of-flight and liquid chromatography with electrospray ionization tandem MS are most common in Aβ studies. However, Aβ forms with isomerized and/or racemized Asp and Ser residues require the use of special methods for separation and extra sensitive and selective methods for detection. Overall, this review summarizes current knowledge of Aβ species found in human brain, cerebrospinal fluid, and blood plasma; focuses on application of different MS approaches for Aβ studies; and considers the potential of MS techniques for further studies of Aβ-peptides.


Update on the status of infrarenal AAA devices.
There are a variety of endografts currently available for endovascular repair of abdominal aortic aneurysms. Aneurysms of increasing anatomic complexity are being repaired with devices that are either newly approved or redesigned relative to the initial published experience with infrarenal endovascular aortic aneurysm repair (EVAR). This article describes the contemporary devices approved for infrarenal EVAR in the United States and includes an up-to-date compilation of the data addressing outcomes specific to each device.


Thrombocytopenia associated with pregnancy in a patient with type IIB von Willebrand's disease.
Thrombocytopenia may accompany variant (type IIB) von Willebrand's disease (vWD) and is thought to result from binding of the abnormal von Willebrand factor (vWF) to the patient's platelets with subsequent platelet aggregate formation and clearance. We have studied a patient with type IIB vWD who became thrombocytopenic during two pregnancies. During the third trimester of pregnancy, her platelet counts dropped to 20,000 to 30,000/microL, and an increase in the intermediate-sized vWF multimers was seen on agarose gel electrophoresis. During this time her platelet-rich plasma showed spontaneous platelet aggregation, and her plasma caused spontaneous aggregation of normal washed platelets. Antibody to platelet glycoprotein Ib completely blocked the spontaneous platelet aggregation, while antibody to platelet glycoprotein IIb/IIIa did not block the response at the concentrations used. Inhibitors of platelet function that elevate platelet cyclic AMP also blocked the response, but aspirin had no effect on the spontaneous platelet aggregation. The patient illustrates that the platelet counts in one individual can vary greatly in type IIB vWD and that the thrombocytopenia that occurs can appear under physiologic conditions that stimulate the endogenous production of the patient's abnormal vWF. The mechanisms leading to spontaneous platelet aggregation and thrombocytopenia appear to be similar to those described for other patients with type IIB vWD.


MiR-323a-3p acts as a tumor suppressor by suppressing FMR1 and predicts better esophageal squamous cell carcinoma outcome.
Esophageal squamous cell carcinoma (ESCC) has unfavorable outcomes with the highest incidence seen in China. Accordingly, exploring effective molecular biomarkers is of great value. MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression and modulate numerous biological processes in tumors. Our study aimed to identify prognostic miRNAs and investigate their role in ESCC. Prognosis-related plasma miRNAs were detected by miRNA microarray and qRT-PCR. Functional assays and molecular mechanism studies were used to investigate the role of miRNA in ESCC. Over-expression of miR-323a-3p was associated with a favorable prognosis. MiR-323a-3p negatively regulated proliferation, migration, and invasion. Through biological predictions, the fragile X mental retardation 1 (FMR1) was found to be a potential target of miR-323a-3p. Further investigation revealed that miR-323a-3p directly targeted and suppressed FMR1. MiR-323a-3p and FMR1 mRNA, as well as miR-323a-3p and the FMR1-encoded protein FMRP, showed negative correlations. Luciferase activity of FMR1-3'-UTR, but not mutant counterparts, was decreased by mimic compared with that of the control. The compromised cell proliferation, migration, and invasion induced by transfection with miR-323a-3p mimic were rescued by transfection with a FMR1 expression plasmid. Tumors induced by miR-323a-3p overexpressed ESCC cells grew significantly slower in vivo and resulted in smaller tumor masses. Metastatic lung colonization was also inhibited by miR-323a-3p overexpression. MiR-323a-3p was significantly associated with survival and acted as a tumor suppressor by inhibiting proliferation, migration, and invasion via the regulation of FMR1. MiR-323a-3p is a promising biomarker and may be a potential therapeutic target.


[Relation between membrane potential changes and DNA, RNA and protein synthesis in regenerating liver cells after partial hepatectomy].
Variations in the membrane potential and in DNA, RNA and protein synthesis were studied in experiments on rats at varying times after hepatectomy. Hyperpolarization of the hepatocyte plasmatic membrane was shown to develop during liver regeneration along with activation of DNA, RNA and protein synthesis. Actinomycin D prevented the development of hyperpolarization and activation of RNA and protein synthesis. Administration of liver filtrates from hepatectomized rats to intact recipients induced hyperpolarization of liver cells. Activation of protein biosynthesis following hepatectomy resulted in hyperpolarization of the cell membrane, this action being mediated via formation of a specific membrane-active factor.


Macleayins A From Macleaya Promotes Cell Apoptosis Through Wnt/β-Catenin Signaling Pathway and Inhibits Proliferation, Migration, and Invasion in Cervical Cancer HeLa Cells.
Macleayins A (MA), a novel compound, was isolated from Macleaya cordata (Willd.) R. Br. and Macleaya microcarpa (Maxim.) Fedde. The plant species are the member of Papaveraceae family and have been used traditionally for diverse therapeutic purposes. According to the reported studies, the chemical constituents, as well as crude extracts of these plants, could attenuate the proliferation of several cancer cell lines, such as HL-60, A549, HepG2, and MCF-7. The current study aimed to investigate the anticervical cancer activity of MA and its related molecular mechanism. Isolation of MA was carried out using various column chromatographic methods, and its structure was elucidated with 1H NMR. The cytotoxicity of MA was determined against HeLa cell lines via CCK-8 assay. The cell proliferation, apoptosis, cell cycle, migration, and invasion were measured by EdU labeling, Annexin-V APC/7-AAD double staining, PI staining, and transwell assay, respectively. The protein expression levels of c-Myc, β-catenin, cyclin D1, and MMP-7 in the cells were evaluated by western blotting. The Wnt/β-catenin signaling cascade activation was verified using the Dual-Glo® Luciferase assay. We found that MA inhibited the growth of HeLa cells at 72 h (IC50 = 26.88 µM) via inducing apoptotic process, reduced the proliferation rate by 29.89%, and decreased the cells migration and invasion as compared to the untreated group. It arrested the cell cycle at the G1 phase and its treatment inhibited the expression of related proteins c-Myc, β-catenin, cyclin D1, and MMP-7 in the Wnt/β-catenin signaling cascade. Further, the Wnt/β-catenin signaling cascade activation in MA-treated HeLa cells was attenuated in a dose-dependent manner. These findings demonstrate the anticancer effects of MA on a mechanistic level, thus providing a basis for MA to become a potential candidate drug for resistance of cervical carcinoma.


The ultrastructural relationships between Sertoli cells and spermatogenic cells in the rat.
The cell-to-cell junctions between Sertoli cells and between Sertoli cells and spermatogenic cells have been described and illustrated in the rat seminiferous tubule. The most important junction is a zonula (or macula) adherens which exists between Sertoli cells on the one hand and spermatogonia on the other. No such junctions are observable between Sertoli cells and late spermatids in the Golgi, acrosomal or cap phases. Mitochondria in these spermatids are the 'energized' type and are lined up close to the inner aspect of the cell membrane; whereas in all other spermatogenic cells they are 'non-energized' and randomly orientated. Almost all the ultrastructural characteristics of steroid hormone-secreting cells have been observed in Sertoli cells. The functional significance of these findings is discussed.


Clinical outcomes of hypogastric artery occlusion for endovascular aortic aneurysm repair.
To determine the midterm outcomes of internal iliac artery (IIA) coverage by a stent-graft in endovascular aortic aneurysm repair (EVAR) under specific anatomic and technical circumstances. From January 2003 until January 2014, 57 patients with aortoiliac aneurysms, including 20 with 24 IIA aneurysms (IIAAs), underwent EVAR with IIA coverage. IIAA diameter change or IIA thrombosis, buttock claudication, type II endoleak, and secondary interventions related to the IIA were studied. Twenty-five of the 37 patients without IIAA were embolized prior to stent-graft placement, all unilateral, and in 12, the IAA orifice was only overstented. Buttock claudication occurred in only nine (20%) of the embolization patients (9/49 IIA's) (p = .14), while one IIA-related type II endoleak, occurred in the nonembolization group (p = .16). In patients with IIAA(s), the aneurysm diameter decreased in 16 cases (67%). Buttock claudication occurred in 75% of bilateral, and in 14.6% of unilateral embolizations (p = .046). Carefully selected patients with aortoiliac aneurysm without IIAA may safely undergo hypogastric artery overstenting without preemptive embolization during EVAR. IIA embolization is associated with buttock claudication and should be avoided if possible. Otherwise, at least one IIA should be preserved.


Molecular rotors as simple models to study amide NH-aromatic interactions and their role in the folding of peptide-like structures.
The conformational behavior of designed macrocyclic naphthalenophanes (1a,b and 2a,b) derived from amino acids (Phe and Val) has been used for studying NH...pi interactions. The cycles having 16- and 17-membered rings showed a dynamic process within the NMR time scale, produced by the flipping of the aromatic naphthalene moiety with respect to the macrocyclic main plane. We used the temperature dependence of 1H NMR to obtain activation parameters of the energetic barrier for the process (variable temperature NMR and line shape analysis). The rate of the movement clearly depends on the macrocyclic ring size and, more interestingly, on the nature of the peptidomimetic side chain, the energetic barrier being higher for the compounds bearing aromatic side chains. A largely negative entropic contribution to the free energy of activation was observed, with clear differences due to the side chain nature. Molecular modeling studies suggest that the aromatic rings interact with intramolecularly H-bonded amide NH groups, protecting them from solvation and thus leading to a larger unfavorable activation entropy. This NH...pi interaction has been exploited for the preparation of new systems (1c and meso-1b) with designed conformational preferences, in which aromatic rings tend to fold over amide NH groups. Thus, these minimalistic molecular rotors have served us as simple model systems for the study of NH...pi interactions and their implication in the folding of peptide-like molecules.


Heat shock proteins hsp90 and hsp70 protect neuronal cells from thermal stress but not from programmed cell death.
Prior exposure to a mild thermal stress can protect neuronal cells from a subsequent more severe stress including high temperature, ischemia, glutamate toxicity, or stimuli inducing apoptosis. Although the protective effect of thermal stress correlates with the elevated expression of the heat shock proteins (hsps), the protective effect of individual hsps has never been directly demonstrated in neuronal cells. Here we show that the constitutive overexpression of either of the major hsps, hsp90 or hsp70, can protect neuronal cells from thermal stress but not from stimuli that induce apoptosis. The possible mechanisms by which thermal stress can protect neuronal cells from apoptosis are discussed.


Immunomodulation: the future cure for allergic diseases.
Allergies are the result of aberrant immune reactivity against common innocuous environmental proteins (allergens). A pivotal component of allergic pathogenesis is the generation of allergen-specific Th cells with an effector phenotype. These Th cells activate a complex immune cascade that triggers the release of potent mediators and enhances the mobilization of several inflammatory cells types, which in turn elicit the acute allergic reactions and promote the development of chronic inflammation. The current therapies for allergic diseases focus primarily on pharmacological control of symptoms and suppression of inflammation. This approach is beneficial, but not curative, since the underlying immune pathology is not inhibited. In an attempt to develop more effective therapeutic strategies, the scientific interest has been directed toward methods down-modulating the immune mechanisms that initiate and maintain the allergic cascade. Today, the only widely used disease-modifying form of allergy treatment is the specific immunotherapy with allergen extracts. More recently the use of anti-IgE has been approved for patients with allergic asthma. Other immunomodulatory methods being currently explored are the administration of microbial adjuvants that inhibit Th2 reactivity and the design of molecules that interrupt the activity of key allergic cytokines, chemokines, or other Th2 effector mediators.


Superatomic Two-Dimensional Semiconductor.
Structural complexity is of fundamental interest in materials science because it often results in unique physical properties and functions. Founded on this idea, the field of solid state chemistry has a long history and continues to be highly active, with new compounds discovered daily. By contrast, the area of two-dimensional (2D) materials is young, but its expansion, although rapid, is limited by a severe lack of structural diversity and complexity. Here, we report a novel 2D semiconductor with a hierarchical structure composed of covalently linked Re6Se8 clusters. The material, a 2D structural analogue of the Chevrel phase, is prepared via mechanical exfoliation of the van der Waals solid Re6Se8Cl2. Using scanning tunneling spectroscopy, photoluminescence and ultraviolet photoelectron spectroscopy, and first-principles calculations, we determine the electronic bandgap (1.58 eV), optical bandgap (indirect, 1.48 eV), and exciton binding energy (100 meV) of the material. The latter is consistent with the partially 2D nature of the exciton. Re6Se8Cl2 is the first member of a new family of 2D semiconductors whose structure is built from superatomic building blocks instead of simply atoms; such structures will expand the conceptual design space for 2D materials research.


Discriminant analysis to predict graduation--nongraduation in a master's degree program in nursing.
Discriminant analysis was used to predict graduation and two categories of nongraduation from readily available admissions data at the University of Kansas nursing master's degree program. The traditional admissions indices, baccalaureate grade point average (GPA) and Graduate Record Examination (GRE)-verbal and -quantitative scores, were used as predictors. Criterion categories were composed of 102 graduates, 103 individuals who dropped out of the program, and 65 individuals who were not accepted. The first discriminant function was, chi 2 (6) = 87.567, p less than .0001, and extracted 98% of the variance of the discriminant space. Follow-up procedures using one-way ANOVA's and Scheffé multiple comparisons indicated that the baccalaureate GPA and GRE-verbal and -quantitative scores independently differentiated the graduate and dropout groups from the not-accepted group at a statistically significant level (p less than .05). Practical significance of the independent contribution of these variables to group differentiation, as measured by omega 2 was 22% for the baccalaureate GPA, 13% for the GRE-verbal scores, and 10% for the GRE-quantitative scores. Implications for future research are discussed.


Gene regulation by temperature-sensitive p53 mutants: identification of p53 response genes.
The ability of the p53 protein to act as a sequence-specific transcriptional activator suggests that genes induced by p53 may encode critical mediators of p53 tumor suppression. Using a tetracycline-regulated p53 expression system and cDNA library subtraction procedure, we identified several p53-induced gene transcripts in human Saos-2 osteosarcoma cells that are novel on the basis of their size, regulation, and low abundance. Wild-type p53-dependent induction of these transcripts was observed in cells that are growth arrested by p53, as well as in cells that undergo apoptosis upon expression of an inducible wild-type p53 transgene. These results show that p53 activates the expression of numerous response genes and suggest that multiple effectors may play a role in mediating cellular functions of p53.


A 3D-investigation shows that angiogenesis in primate cerebral cortex mainly occurs at capillary level.
This paper describes the use of a new 3D high-resolution imaging technique dedicated to functional vessels for a systematic quantitative study of angiogenesis in the primate cortex. We present a new method which permits, using synchrotron X-ray micro-tomography imaging, the identification of micro-vascular components as well as their automatic numerical digitalization and extraction from very large 3D image analysis and post-treatments. This method is used to analyze various levels of micro-vascular organization and their postnatal modifications. Comparing newborn- and adult marmosets, we found an increase in vascular volume (270%), exchange surface (260%) and vessel length (290%) associated to a decrease in distances between vessel and tissue (32%). The increase in relative vascular volumes between the two ages, examined through the whole cortical depth, has been found to be mainly sustained by events occurring at the capillary level, and only marginally at the perforating vessel level. This work shows that the postnatal cortical maturation classically described in terms of synaptogenesis, gliogenesis and connectivity plasticity is accompanied by an intensive remodeling of micro-vascular patterns.


CT volumetry for gastric adenocarcinoma: association with lymphovascular invasion and T-stages.
To determine whether gross tumor volume of resectable gastric adenocarcinoma on multidetector computed tomography could predict presence of lymphovascular invasion and T-stages. Gross tumor volume increased with the lymphovascular invasion (r = 0.426, P < 0.0001) and T stage (r = 0.656, P < 0.0001). Univariate analysis showed gross tumor volume could predict lymphovascular invasion (P < 0.0001). Multivariate analyses indicated gross tumor volume as an independent risk factor of lymphovascular invasion (P = 0.026, odds ratio = 2.284). The Mann-Whitney U test showed gross tumor volume could distinguish T2 from T3, T1 from T2-T4a, T1-T2 from T3-T4a and T1-T3 from T4a (P = 0.000). In the development cohort, gross tumor volume could predict lymphovascular invasion (cutoff, 15.92 cm3; AUC, 0.760), and distinguish T2 from T3 (cutoff, 10.09 cm3; AUC, 0.828), T1 from T2-T4a (cutoff, 8.20 cm3; AUC, 0.860), T1-T2 from T3-T4a (cutoff, 15.88 cm3; AUC, 0.883), and T1-T3 from T4a (cutoff, 21.53 cm3; AUC, 0.834). In validation cohort, gross tumor volume could predict presence of lymphovascular invasion (AUC, 0.742), and distinguish T2 from T3 (AUC, 0.861), T1 from T2-T4a (AUC, 0.859), T1-T2 from T3-T4a (AUC, 0.875), and T1-T3 from T4a (AUC, 0.773). 360 consecutive patients with gastric adenocarcinoma were retrospectively identified. Gross tumor volume was evaluated on multidetector computed tomography images. Statistical analysis was performed to determine whether gross tumor volume could predict presence of lymphovascular invasion and T-stages. Cutoffs of gross tumor volume were first investigated in 212 patients and then validated in an independent 148 patients using area under the receiver operating characteristic curve (AUC) for predicting lymphovascular invasion and T-stages. Gross tumor volume of resectable gastric adenocarcinoma at multidetector computed tomography demonstrated capability in predicting lymphovascular invasion and distinguishing T-stages.


Marking Drosophila suzukii (Diptera: Drosophilidae) With Rubidium or 15N.
Drosophila suzukii Matsumura (Diptera: Drosophilidae) has caused significant economic damage to berry and stone fruit production regions. Markers that are systemic in plants and easily transferred to target organisms are needed to track D. suzukii exploitation of host resources and trophic interactions. High and low concentrations of the trace element, rubidium (Rb), and the stable isotope, 15N, were tested to mark D. suzukii larvae feeding on fruits of enriched strawberry plants grown in containers under greenhouse conditions. Fly marker content and proportion of flies marked 1, 7, and 14 d after emergence from enriched fruits and fly dry mass were analyzed. Nearly 100% of the flies analyzed 14 d after emerging from 15N-enriched plants were marked, whereas only 30-75% and 0-3% were marked 14 d after emerging from high and low Rb concentration plants, respectively. Rapid Rb decay, strong 15N persistence, and the economics of using these markers in the field to elucidate D. suzukii pest ecology are discussed.


A systematic review of datasets that can help elucidate relationships among gene expression, race, and immunohistochemistry-defined subtypes in breast cancer.
Scholarly requirements have led to a massive increase of transcriptomic data in the public domain, with millions of samples available for secondary research. We identified gene-expression datasets representing 10,214 breast-cancer patients in public databases. We focused on datasets that included patient metadata on race and/or immunohistochemistry (IHC) profiling of the ER, PR, and HER-2 proteins. This review provides a summary of these datasets and describes findings from 32 research articles associated with the datasets. These studies have helped to elucidate relationships between IHC, race, and/or treatment options, as well as relationships between IHC status and the breast-cancer intrinsic subtypes. We have also identified broad themes across the analysis methodologies used in these studies, including breast cancer subtyping, deriving predictive biomarkers, identifying differentially expressed genes, and optimizing data processing. Finally, we discuss limitations of prior work and recommend future directions for reusing these datasets in secondary analyses.


Plasticity of motor cortex excitability induced by rehabilitation therapy for writing.
The mechanisms of rehabilitation-induced plasticity in the motor system after stroke are not defined. The authors studied seven patients with residual poststroke agraphia, aphasia, and right hemiparesis. After a 40-minute rehabilitation therapy that promoted use of the paretic hand for writing, the authors observed a task-specific increase in recruitment of ipsilateral corticospinal pathways. Rehabilitation aimed to increase the use of the paretic hand may induce recruitment of previously silent ipsilateral corticospinal pathways even in poorly recovered poststroke patients.


Characterization of the 5' untranslated region of alpha and beta isoforms of the human thromboxane A2 receptor (TP). Differential promoter utilization by the TP isoforms.
In humans, thromboxane (TX) A2 signals through two TXA2 receptor (TP) isoforms, TPalpha and TPbeta, that diverge within their carboxyl terminal cytoplasmic (C) tail regions and arise by differential splicing. The human TP gene contains three exons E1-E3; while E1 exclusively encodes 5' untranslated region (UTR) sequence, E2 and E3 represent the main coding exons. An additional noncoding exon, E1b was identified within intron 1. Additionally, the TP gene contains two promoters P1 and P2 located 5' of E1 and E1b, respectively. Herein, we investigated the molecular basis of the differential expression of the TP isoforms by characterizing the 5' UTR of the TP transcripts. While E1 and E1b were found associated with TP transcript(s), their expression was mutually exclusive. 5' rapid amplification of cDNA ends (5' RACE) established that the major transcription initiation (TI) sites were clustered between -115 and -92 within E1 and at -99 within E1b. While E1 and E1b sequences were identified on TPalpha transcript(s), neither existed on TPbeta transcript(s). More specifically, TPalpha and TPbeta transcripts diverged within E2 and the major TI sites for TPbeta transcripts mapped to -12/-15 therein. Through genetic reporter assays, a previously unrecognized promoter, termed P3, was identified on the TP gene located immediately 5' of -12. The proximity of P3 to the TI site of TPbeta suggests a role for P3 in the control of TPbeta expression and implies that TPalpha and TPbeta, in addition to being products of differential splicing, are under the transcriptional control of distinct promoters.


Immunogenicity and safety of measles vaccine in ill African children.
A concurrent prospective study was conducted in Rwanda to compare the immunogenicity and safety of live, attenuated measles vaccine in ill and well children. Five hundred and eighteen children aged 8 to 19 months were selected from children attending the acute care and immunization services of two clinics. Two hundred and sixty-seven ill children and 251 well children were enrolled and examined. Serological tests were performed on blood samples obtained before and 40 days after measles immunization. Among the 208 ill children and 215 well children who were seronegative at baseline and had unequivocal follow-up serological results, seroconversion rates were 81% and 80%, respectively. Side effects were modest and were equally frequent in the two study groups (15.4% among ill children versus 15.1% among well children). These results support a change in measles immunization policy in developing countries with respect to immunization of children with acute illnesses. Such a change would make a great contribution to decreasing the enormous burden of measles in the developing world through increased immunization coverage.


Elevated temperatures translate into reduced dispersal abilities in a natural population of an aquatic insect.
Rising global temperatures force many species to shift their distribution ranges. However, whether or not (and how fast) such range shifts occur depends on species' dispersal capacities. In most ecological studies, dispersal-related traits (such as the wing size or wing loading in insects) are treated as fixed, species-specific characteristics, ignoring the important role of phenotypic plasticity during insect development. We tested the hypothesis that dispersal-related traits themselves vary in dependence of ambient environmental conditions (temperature regimes, discharge patterns and biotic interactions during individual development). We collected data over 8 years from a natural population of the crane fly Tipula maxima in central Germany. Using linear mixed-effect models, we analysed how phenotypic traits, phenological characteristics and population densities are affected by environmental conditions during the preceding 3, 6 and 12 months. We found a moderate (5.6%) increase in wing length per 1°C increase in mean annual temperatures during the previous year. At the same time, body weight increased by as much as 17.8% in females and 26.9% in males per 1°C, likely driven by increased habitat productivity, which resulted in a 16.4% (female) and 19.3% (male) increased wing loading. We further found a shorter, more synchronized emergence period (i.e. a narrower time frame for dispersal) with increasing temperatures. Altogether, our results suggest that dispersal abilities of T. maxima were negatively affected by elevated temperatures, and we discuss how similar patterns might affect the persistence of populations of other aquatic insects, especially stenoecious taxa with narrow distribution ranges. Our study calls for integration of information on temperature-induced phenotypic plasticity of dispersal-related traits into models forecasting range shifts in the face of climate change. Furthermore, the patterns reported here are likely to affect metapopulation dynamics of aquatic insects under climate change conditions and may contribute to the ongoing decline of insect biomass and diversity.


Pharmacologic interventions in nuclear radiology: indications, imaging protocols, and clinical results.
Nuclear radiology is valuable in assessing pathophysiology of a variety of organ systems. Pharmacologic interventions are often employed in radionuclide imaging to monitor the physiologic changes, which in turn facilitate the diagnosis. Metoclopramide, erythromycin, and cisapride have been used for gastric emptying studies. To overcome false-negative results, cimetidine, pentagastrin, and glucagon have been used in imaging of Meckel diverticula. Pharmacologic intervention with either cholecystokinin-8 or morphine is used primarily for the assessment of diseases of the gallbladder, common bile duct, and sphincter of Oddi. Pharmacologic interventions performed during renography include diuretic administration, angiotensin-converting enzyme inhibition, and aspirin renography. Recombinant thyrotropin can be used in patients with previously treated thyroid carcinoma who require lifelong follow-up for recurrent disease. Cardiac pharmacologic stress agents fall into two categories: coronary vasodilating agents, such as dipyridamole and adenosine, and cardiac positive inotropic agents, such as dobutamine and arbutamine. Measurement of hemodynamic responses to pharmacologic flow augmentation with carbon dioxide or acetazolamide is valuable in cerebrovascular perfusion studies.


Impact of acquired del(17p) in multiple myeloma.
The high-risk abnormality del(17p) can be detected by fluorescence in situ hybridization on malignant plasma cells (PCs) and has an adverse prognostic impact in patients with multiple myeloma (MM). Patients with del(17p) have reduced overall survival (OS). Patients who acquire del(17p) later during the disease course are not well described. The disease characteristics at diagnosis predicting for acquired del(17p) and its overall impact on patient survival is not known. We compared 76 patients with MM who were negative for del(17p) at diagnosis and acquired it later with 152 control MM patients who did not acquire del(17p) at a comparable time point. Patients acquired del(17p) at a median of 35.6 months (range, 4.6-116.1 months) from diagnosis of MM after a median of 2 lines of therapy (range, 1-10 lines of therapy). When compared with controls, patients with acquired del(17p) had shorter median progression-free survival (PFS) (30.1 vs 23.0 months; P = .032) and OS (106.1 vs 68.2 months; P < .001) from diagnosis. After the detection of del(17p), the median PFS was 5.4 months and the median OS was 18.1 months. High lactate dehydrogenase level (odds ratio [OR], 3.69; 95% confidence interval [CI], 1.11-12.24) and presence of t(4;14) (OR, 2.66; 95% CI, 1.09-6.48) or any high-risk translocation (OR, 2.23; 95% CI, 1.00-4.95) at diagnosis predicted acquisition of del(17p). High PC proliferative rate predicted shorter OS from detection of del(17p) (hazard ratio, 2.28; 95% CI, 1.31-3.96; P = .004). Our study shows that acquisition of del(17p) is an important molecular event associated with reduction in OS in MM. Certain baseline factors may predict acquisition of del(17p). This needs validation in prospective data sets.


Large-cell transformation of chronic lymphocytic leukemia and follicular lymphoma during or soon after treatment with fludarabine-rituximab-containing regimens: natural history- or therapy-related complication?
Novel therapeutic regimens containing purine analogs and monoclonal antibodies have led to significant improvement in the course of indolent lymphoproliferative diseases (LPD). Complete clinical and even molecular remissions have been achieved in an increasing proportion of patients. In parallel to their tumor cytotoxic effect, these agents are inevitably associated with prolonged immunosuppression inherent to their mechanism of antilymphocytic activity. Until now, attention has been paid mainly to opportunistic infection occurring as a result of the above drug-induced immunosuppression and less to other possible complications, such as malignancy or tumor progression in the immunocompromised host. Here we briefly report nine patients with previously treated indolent LPD in whom the onset of large-cell transformation occurred during or shortly after the initiation of regimens containing these agents before transformation occurred. One patient had received rituximab alone, three fludarabine-containing regimens and five received sequential regimens containing both agents. This


Receptor for the Advanced Glycation End Products (RAGE) Pathway in Adipose Tissue Metabolism.
Advanced glycation end products (AGEs) are mediators in the process of cellular dysfunction in response to hyperglycemia. Numerous data indicate that the accumulation of AGEs in the extracellular matrix plays a key role in the development of obesity-related adipose tissue dysfunction. Through binding of their membrane receptor (RAGE), AGEs affect numerous intracellular pathways and impair adipocyte differentiation, metabolism, and secretory activity. Therefore, inhibiting the production and accumulation of AGEs, as well as interfering with the metabolic pathways they activate, may be a promising therapeutic strategy for restoring normal adipose tissue function and, thus, combating obesity-related comorbidities. This narrative review summarizes data on the involvement of the RAGE pathway in adipose tissue dysfunction in obesity and the development of its metabolic complications. The paper begins with a brief review of AGE synthesis and the RAGE signaling pathway. The effect of the RAGE pathway on adipose tissue development and activity is then presented. Next, data from animal and human studies on the involvement of the RAGE pathway in obesity, diabetes, and cardiovascular diseases are summarized. Finally, therapeutic perspectives based on interference with the RAGE pathway are discussed.


Personality risk factors associated with trajectories of tobacco use.
The purpose of this longitudinal, prospective study was to evaluate trajectories of smoking in a cohort of African-American and Puerto Rican young adults and describe personality and behavioral factors associated with specific smoking trajectory group membership. Participants consisted of African-American and Puerto Rican male and female young adults (N = 451, mean age 26) from an inner-city community. Data were collected at four time points over a period of 13 years using structured interviews. Interviews took place within the schools and the participants' homes. Scales with adequate psychometric properties were adapted from previously validated measures. Variables that were examined for this study came from the domains of internalizing behaviors, externalizing behaviors, drug use, and demographic information. Data were analyzed using latent growth mixture modeling to explore discrete smoking trajectories. Logistic regression analyses were then used to examine the risk factors associated with the various smoking trajectory groups. Four trajectory groups were determined to best fit the data: nonsmokers, maturing-out smokers, late-starting smokers, and early-starting continuous smokers. Subjects who were unconventional, experienced intrapersonal distress, and used alcohol and illegal drugs were more likely to belong to one of the smoking trajectory groups than to the nonsmoking group. The early-starting continuous group scored highest on these personal risk attributes. The long-term impact of unconventional behavior, intrapersonal distress, and drug use on developmental trajectories of smoking support the importance of early intervention and prevention.


[Dorsal and lumbar paraspinal electromyographic study. Multi-MUP analysis and drawing up normal values in a reference population].
The aim of this study was to contribute to draw up reference values relating to electromyographic (EMG) parameters in dorsal and lumbar paraspinal muscles. 75 healthy subjects without back pain underwent electromyography of multifidus bundles, which are innervated uni-segmentally by the dorsal ram of the spinal nerve. T8, L3, L4, L5 and S1 myotomes were systematically explored. Output variables were spontaneous denervation activity and quantitative EMG data obtained by multi-MUP (Motor Unit action Potential) analysis. No abnormal insertional or spontaneous activity (such as fibrillation, positive sharp waves or fasciculation) was recorded at rest. Neither sex nor age influenced motor unit action potential features in our series. Reference values were drawn up for T8 and L5 segmental levels using the mean values of 20 motor unit potentials in each patient studied, the reference interval being defined by the lower and the upper outlier limits on individual values. This study offers reference data to electromyographers to help better identifying possible myogenic or neurogenic pathological changes, especially in lumbosacral radiculopathies.


Evidence for in vivo internalization of human leukocyte elastase by alveolar macrophages.
Cell lysates from cultured human alveolar macrophages contain detectable amounts of an elastinolytic enzyme. Although particulate elastin was solubilized only after prolonged incubations, lysates readily hydrolyzed T-OC-alanyl-p-nitrophenol-ester. Hydrolysis of the latter substrate was inhibited by the leukocyte elastase site-specific inhibitor, N-ac-(ala)4-chloromethyl ketone. In addition, radioimmunoelectrophoresis of concentrated alveolar macrophage lysates, previously incubated with 3H diisopropyl-phosphofluoridate (DFP), revealed the presence of DFP binding material that comigrated with inactivated human leukocyte elastase. Human leukocyte elastase can cause lung lesions resembling pulmonary emphysema in experimental animals; therefore, the clearance of this enzyme by alveolar macrophages may represent a significant route for the removal of this potentially pathogenic enzyme from the lung.


Montelukast and Coronavirus Disease 2019: A Scoping Review.
Coronavirus disease 2019 (COVID-19) is an emerging worldwide issue, that has affected a large number of people around the world. So far, many studies have aimed to develop a therapeutic approach against COVID-19. Montelukast (MK) is a safe asthma controller drug, which is considered as a potential antiviral drug for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This review has a systematic approach to investigate the reports on the use of MK as a part of treatment or a prophylactic agent in COVID-19. The search was conducted in PubMed, Web of Science, and Scopus databases and yielded 35 studies containing the influence of MK on SARS-CoV-2. Ultimately, MK appears to be worth being used as an adjuvant therapeutic and prophylactic drug against SARS-CoV-2. Nevertheless, more clinical trials are required to accurately investigate its effectiveness.


Comparative Proteomic Analysis of Rat Bronchoalveolar Lavage Fluid after Exposure to Zinc Oxide Nanoparticles.
Zinc oxide nanoparticles (ZnO NPs) are one of the most widely used nanomaterials in consumer products and industrial applications. As a result of all these uses, this has raised concerns regarding their potential toxicity. We previously found that candidate markers of idiopathic pulmonary fibrosis and lung cancer were significantly up-regulated in rat bronchoalveolar lavage fluid (BALF) following exposure to ZnO NPs by using a liquid chromatography (LC)-based proteomic approach. To achieve comprehensive protein identification analysis, we conducted the two-dimensional gel electrophosis (2-DE)-based proteomic workflow to analyze the differences in BALF proteins from rats that had been exposed to a high dose of 35 nm ZnO NPs. A total of 31 differentially expressed protein spots were excised from the gels and analyzed by nanoLC-tandem mass spectrometry (MS/MS). Gene ontology (GO) annotation of these proteins showed that most of the differentially expressed proteins were involved in response to stimulus and inflammatory response processes. Moreover, pulmonary surfactant-associated protein D and gelsolin, biomarkers of idiopathic pulmonary fibrosis, were significantly up-regulated in rat BALF after ZnO NPs exposure (2.42- and 2.84-fold, respectively). The results obtained from this present study could provide a complementary consequence with our previous study and contribute to a better understanding of the molecular mechanisms involved in ZnO NP-induced lung disorders.


Construction of Specific Primers for Rapid Detection of South African Exportable Vegetable Macergens.
Macergens are bacteria causing great damages to the parenchymatous tissues of vegetable both on the field and in transit. To effectively and rapidly investigate the diversity and distribution of these macergens, four specific primers were designed by retrieving 16S rDNA sequences of pectolytic bacteria from GenBank through the National Center for Biotechnology Information (NCBI). These were aligned using ClusterW via BioEdit and primers were designed using Primer3Plus platform. The size and primer location of each species and PCR product size were accurately defined. For specificity enhancement, DNA template of known macergens (Pectobacterium chrysanthermi) and fresh healthy vegetable were used. These primers yielded expected size of approximately 1100 bp product only when tested with known macergens and no amplicon with fresh healthy vegetable was detected. Rapid detection of macergens in rotten vegetable samples was then carried out using these primers. Nucleotide sequences of macergens identified were deposited into the GenBank and were assigned accession numbers. Hence, with these specific primers, macergens can be identified with minimal quantities of the vegetable tissues using molecular techniques, for future use of the quarantine section of the Agricultural Department of the country for quick and rapid detection of macergens before exportation.


[The French Red Cross: a network of care centers dedicated to HIV-AIDS].
The commitment of the French Red Cross Society to the fight against HIV/AIDS in Africa and Asia is based on day care centers (DCC) set up and operated within public hospitals. These outpatient facilities offer global care including clinical and biologic follow-up for patients undergoing anti-retroviral treatment. In most countries these DCC have become reference centers providing support for national decentralization policies. To reinforce the impact of their activities, centers offer regular educational programs and provide extensive training for medical personnel.


[The chemoprevention of oral carcinoma with vitamin A and/or N-acetylcysteine].
EUROSCAN (EUROpean Study on Chemoprevention with vitamin A and N-acetylcysteine) is a study which has the aim to demonstrate the efficacy of vitamin A and N-acetylcysteine in the prevention of second primary tumours in patients treated for lung, larynx and oral cancer. In this study are involved more than 50 medical centres in all Europe, co-ordinated by European Organization for research and Treatment of Cancer (EORTC). In December 1993 almost 2300 patients have been randomized; at the present day, in our department, we follow 29 patients curatively treated for oral cancer (pTNM: pT1N0M0, pT2N0M0, pT2N1M0) and, for this reason, at high risk to develop local recurrences or second primary tumours. These patients are allocated to four different arms according to the drugs they take: vitamin A as retinol palmitate (300,000 UI a day for the first year and 150,000 UI for the second year), N-acetylcysteine (600 mg a day for two years), both these drugs, no drugs (control group). During follow-up all the patients have clinical examinations and blood tests (in patients taking vitamin A) every 3-6 months. The randomization is expected to stop around September 1994, when, probably, the number of 2600 patients will be reached. The first analysis allowing a conclusion on chemopreventive efficacy of retinol and N-acetylcysteine will be performed not before September 1996 with a median follow-up time of more than 3 years.(ABSTRACT TRUNCATED AT 250 WORDS)


Achieving triple treatment goals in multi-ethnic Asian patients with type 2 diabetes mellitus in primary care.
Achieving optimal glycated hemoglobin (HbA1c), blood pressure (BP), and LDL-Cholesterol (LDL-C) in patients mitigates macro- and micro-vascular complications, which is the key treatment goal in managing type 2 diabetes mellitus (T2DM). This study aimed to determine the proportion of patients in an urban community with T2DM and the above modifiable conditions attaining triple vascular treatment goals based on current practice guidelines. A questionnaire was distributed to adult Asian patients with dyslipidemia at two primary care clinics (polyclinics) in northeastern Singapore. The demographic and clinical data for this sub-population with both T2DM and dyslipidemia were collated with laboratory and treatment information retrieved from their electronic health records. The combined data was then analyzed to determine the proportion of patients who attained triple treatment goals, and logistic regression analysis was used to identify factors associated with this outcome. 665 eligible patients [60.5% female, 30.5% Chinese, 35% Malays, and 34.4% Indians] with a mean age of 60.6 years were recruited. Of these patients, 71% achieved LDL-C ≤2.6 mmol/L, 70.4% had BP <l40/90 mmHg, and 40.9% attained HbAlc ≤7%. Overall, 22% achieved the triple treatment goals for glycemia, BP, and LDL-C control. The major determinants were the number of diabetic medications and intensity of statin therapy. Eight in ten patients with T2DM failed to achieve concurrent glycemic, BP, and LDL-C treatment goals, subjecting them to risks of vascular complications. Primary healthcare professionals can mitigate these risks by optimizing therapeutic treatment to maximize glycemia, dyslipidemia, and BP control.


Intraocular pressure with rebound tonometry and effects of topical intraocular pressure reducing medications in guinea pigs.
To investigate the intraocular pressure (IOP) of adult guinea pig eyes with rebound tonometry (RBT), and assess the effects of four distinctive topical IOP reducing medications including Carteolol, Brimonidine, Brinzolamide and Latanoprost. The IOPs of twenty-four 12-week-old guinea pigs (48 eyes) were measured every two hours in one day with RBT as baselines. All the animals were then divided into four groups (Carteolol, Brimonidine, Brinzolamide and Latanaprost groups, n=6). The IOPs were measured and compared to the baseline 1, 2, 3, 5, 7, 9, 15 and 24h after treatment. The mean baseline IOP of 24 guinea pigs (48 eyes) was 10.3±0.36 mm Hg (6-13 mm Hg) and no binocular significant differences of IOPs were observed (t=1.76, P>0.05). No significant difference of IOP in Carteolol group at each time point was observed before and after treatment (t=1.48, P>0.05). In Brimonidine group, IOP was 2.2±1.9 mm Hg lower than the baseline after one hour (t=3.856, P=0.003) and lasted for one hour. In Brinzolamide group, IOP was 1.4±1.1 mm Hg lower than the baseline after one hour (t=4.53, P=0.001) and lasted for 7h and the IOP declined most at 3h. In Latanaprost group, IOP was 2.1±1.3 mm Hg lower than the baseline after one hour (t=6.11, P=0.001) and lasted for one hour. The IOP of guinea pig eyes is relatively stable compared to human eyes. In four reducing IOP medications, no significant effect of Carteolol is observed. Brinzolamide has the longest duration, while the Brimonidine has the shortest duration and the maximum level of treatment.


Inhibiting effect of p-Coumaric acid on U87MG human glioblastoma cell growth.
p-Coumaric acid (pCA) is a hydroxycinnamic acid derivative commonly found in many natural products that has been extensively studied for its anticancer activity in multiple cell lines. In this report we investigated the effects of this phytochemical as adjuvant therapy to treat glioblastoma, an infaust brain tumour characterized by the acquired or innate resistance to the conventional chemotherapy temozolomide (TMZ). U87Mg glioblastoma cell growth and viability was assessed by growth rate curves and MTT assay incubating cells with 0.5 and 1 mM pCA for 24 h, 48 h and 72 h. Cell cycle analysis, performed by flow cytometry, showed that pCA led the accumulation of GBM cells in G2/M phase. Western blot analysis shows that pCA induced CDK4 cyclin-dependent kinase reduction and p53 increase, followed by induction of the CDK inhibitor p21. Furthermore, pCA treatment mediated the activation of apoptosis and the inhibition of migration of U87Mg cells. Finally, the treatment of glioblastoma cells in vitro with pCA concomitantly with the TMZ revealed a synergistic effect between the natural substance and the chemotherapy. In conclusion, our results demonstrated that pCA acts influencing the cell viability and cell cycle of U87Mg cells by promoting cell cycle arrest in G2/M phase and apoptosis.


[The Metaverse: A New Frontier for Healthcare].
We discuss leveraging a cutting-edge technology known as the Metaverse to tackle healthcare challenges, with a particular focus on enhancing patient satisfaction and improving working conditions for medical professionals. We plan to achieve this by improving real-digital collaboration and utilizing the advantages of the Metaverse, such as novel communication and experiences and increased work efficiency and quality. This article showcases several concrete examples of Metaverse services in the medical field, as demonstrated by the "Medical Metaverse Joint Research Course" established through a collaboration between IBM and Juntendo University, and also highlights possible future prospects.


[Loosely bound proteins and membrane ultrastructure of erythrocyte ghosts].
The loosely bound erythrocyte ghost proteins, extracted by distilled water, 5 mM EDTA, tris-HCI buffer at pH 8.5, veronal-acetate buffer at pH 8.5 and by a 1.5% solution of acetic acid, were studied electrophoretically using a polyacrilamid gel with 0.1% sodium docecyl sulphate. 20% proteins with m.v.12 000-120 000 polypeptid chains were released from ghosts transferred from phosphate buffer to distilled water. 5 mM EDTA extracts, in addition, a m. w. 215000 protein. The increase of the negative change brought about the extraction of proteins of the molecular weight equal to 12 000-250 000. After extraction of 12% or more loosely bound proteins the reduction of membrane-attached materials was seen with the electron microscope. Shifts of pH from 6.3 to 7.4 and the treatment with 5mM EDTA resulted in reduction of the premembrane material, ghosts sticking together after the latter procedure.


Effects of stress and corticosterone on activity and plasticity in the amygdala.
The basolateral amygdala (BLA) has been repeatedly shown to mediate the effects of stress on memory-related processes. However, the way in which stress influences BLA itself has not been fully explored. We studied the effects of stress and corticosterone (CORT) on activity and plasticity in the BLA in the rat, using the electrophysiological procedure of long-term potentiation (LTP) induction in vivo. Rats were exposed to an acute elevated-platform stress or administered vehicle or 5 mg/kg, 10 mg/kg, or 25 mg/kg of CORT systemically, after which they were anesthetized and prepared for field potential recording in the BLA, in response to stimulation of the entorhinal cortex. The elevated platform stress enhanced baseline responses in BLA and plasma CORT but inhibited amygdalar LTP. Systemic injections of CORT enhanced baseline responses in BLA in a dose-dependent manner but did not influence amygdalar LTP. Posttetanic potentiation (PTP) was similarly reduced in CORT- and vehicle-injected groups, possibly because of an additional stress from the injection, thus implying that PTP and LTP in the amygdala differentially react to stress. These results suggest that the increase in amygdalar baseline activity following the exposure to stress may be mediated by the concomitant increase in plasma CORT. However, the suppression of amygdalar LTP is not a result of elevated levels of CORT, suggesting that activity and plasticity in the amygdala might be mediated by different mechanisms.


PAM-2 Cl, HI-6, and HGG-12 in soman and tabun poisoning.
Acute sc toxicity of soman increased in the order, mice----rats----guinea pigs----dogs, being 12.6 times more toxic to dogs (LD50 = 0.05 mumol/kg) than to mice. It was 2.8 times more toxic than tabun to mice and 35 times more toxic to dogs. HI-6 was the least toxic and had similar toxicity values to the four animal species studied and HGG-12 the most toxic of the three oximes used. HGG-12 has shown the greatest interspecies variation (rats:dogs = 1:19.5). HI-6, HGG-12, and PAM-2 Cl (in conjunction with atropine and diazepam) revealed the best protective effect in soman-poisoned dogs, with the respective protective indices of 9, 6.3, and 3.5, followed by guinea pigs. In tabun poisoning the best, but relatively low, protective effect was found only in guinea pigs. The introduction of diazepam increased the protective effects of atropine-oxime combination in soman and tabun poisoning by 10 to 80%. We suggest that the high toxicity of soman and low toxicity of HI-6 may be anticipated in man. The inefficiency of HI-6, HGG-12, and PAM-2 Cl in tabun poisoning points either to the search of new compounds or to the use of the mixture of the oximes found to be effective against the known chemical warfare nerve agents.


Inexpensive approach for production of high-surface-area silica nanoparticles from rice hulls biomass.
In this study, we prepared amorphous and crystalline silica nanoparticles from rice hulls biomass using pyrolysis technique at different processing temperatures such as 923, 973, 1023, 1073, 1123 and 1173 K. X-ray fluorescence studies show that the purity of all the synthesised silica nanoparticles is in the range of 98-99.7%. X-ray diffraction studies reveal that amorphous silica nanoparticles are formed at 923-1023 K, whereas crystalline particles at 1073-1173 K. Morphology and microstructure of silica nanoparticles are studied by scanning electron and transmission electron microscopes. Silica nanoparticles obtained at different processing temperatures yield particle size in the range of 6-100 nm. Chemical composition and surface functionalities of the particles are examined by energy-dispersive X-ray diffraction and Fourier transform infrared spectroscopic studies. The developed method effectively uses rice hulls biomass as a green natural source in the synthesis of amorphous and crystalline silica nanoparticles with high-specific surface area. The optimised processing temperature (1023 K) enables amorphous silica nanoparticles to have high-specific surface area of 538 m(2)g(-1).


No immediate analgesic effect of diadynamic current in patients with nonspecific low back pain in comparison to TENS.
Chronic nonspecific low back pain (CNSLBP) has major socioeconomic as well as personal impact in many industrialized and developing countries. Physiotherapy is a common intervention for this group of patients and using anti-pain physical modalities is a common part of the physical therapy. In a randomized controlled trial we investigated the immediate effect of the Diadynamic current in comparison to TENS on reducing the pain in patients suffering from non specific chronic low back pain. Thirty patients were randomized into the Diadynamic current and TENS groups. Electrical stimulation was applied for 10 min in the Diadynamic group and for 15 min in the TENS group for one session. Pain, on a 100 mm Visual Analog Scale, and Pressure Pain Threshold (PPT), using an Algometer, was measured before the treatment, after the current application, 20 min later and after 48 h. Pain was decreased significantly after 20 min following the current application only in the TENS group, with no improvement at all measurement points in the group receiving Diadynamic current. PPT was increased immediately after current application in both groups but did not last until later measurements. Diadynamic current had no positive effect on prompt relief of pain in patients suffering from recurrent CNSLBP.


Key Signaling Pathways in Psoriasis: Recent Insights from Antipsoriatic Therapeutics.
Psoriasis is a common chronic inflammatory skin disease associated with several comorbidities and reduced quality of life. In the past decades, highly effective targeted therapies have led to breakthroughs in the management of psoriasis, providing important insights into the pathogenesis. This article reviews the current concepts of the pathophysiological pathways and the recent progress in antipsoriatic therapeutics, highlighting key targets, signaling pathways and clinical effects in psoriasis.


Real World Pharmacological First Treatment Patterns of Patients With Parkinson Disease and Disease Duration: A Large-Scale Cohort Study Using an Health Maintenance Organization Database.
Real-world data were used to describe first antiparkinsonian drug (FAPD) prescription patterns among Parkinson disease (PD) patients and to evaluate disease duration until levodopa (l-DOPA) treatment and until death, as related to FAPD, by age group. The community-based cohort (2000-2012) included 6243 patients, members of an Israeli Health Maintenance Organizations. Time from FAPD purchase to 2 end points (l-DOPA purchase and death) was calculated. Cox regressions were used to estimate adjusted heart rate (HR) to either end point as related to FAPD type, by age group. During a mean follow-up of 4.8 ± 3.2 years, one third of the cohort died. The percent of l-DOPA use as a start drug increased with age, whereas the percent of dopamine agonists (DAs) and monoamine oxidase inhibitor B inhibitor (MAO-BI) decreased with age. Younger women were treated more often with DA as a start drug compared with younger men. In ages of younger than 50 years, time to l-DOPA start in the initial DA-group was 4 times longer than in the initial MAO-BI group (HR, 0.23; 95% confidence interval, 0.08-0.43; 1/0.23, 4.35). All age groups exhibited a similar survival time trend associated with initial drug type. An age-pooled HR with initial l-DOPA-group as a reference group yielded that survival time was 2.4 times longer for the initial DA group (HR, 0.41; 95% confidence interval, 0.31-0.55; 1/0.41, 2.44), 1.9 times and 1.4 times for initial MAO-BI or amantadine, respectively. First antiparkinsonian drug choice might be associated with time until l-DOPA initiation but may represent disease severity at the time of prescription, thus also affecting survival time as well. Real-world data illustrated that this choice is also age and sex dependent.


Current trends and future perspectives of dental pulp capping materials: A systematic review.
To systematically review the literature to analyze the current trends and future perspectives of dental pulp capping materials through an analysis of scientific and technological data. This study is reported in accordance with the PRISMA Statement. Nine databases were screened: PubMed (MedLine), Lilacs, IBECS, BBO, Web of Science, Scopus, SciELO, Google Scholar, and The Cochrane Library. Additionally, the following patent applications were searched online in Questel Orbit (Paris, France), USPTO, EPO, JPO, INPI, and Patentscope databases. A total of 716 papers and 83 patents were included. Calcium hydroxide was the main type of material studied, especially for direct pulp capping, followed by MTA. Patents related to adhesives or resins increased from 1998 e 2008, while in the last years, a major increase was observed in bioactive materials (containing bioactive proteins), materials derived from MTA (calcium silicate, calcium phosphate and calcium aluminate-based cements) and MTA. It was possible to obtain a scientific and technological overview of pulp capping materials. MTA has shown favorable results in vital pulp therapy that seem to surpass the disadvantages of calcium hydroxide. Recent advances in bioactive materials and those derived from MTA have shown promising results that could improve biomaterials used in vital pulp treatments. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1358-1368, 2018.


A conservative management of iatrogenically damaged distal root of the mandibular second molar.
Trauma to the adjacent hard and soft tissue is the most common iatrogenic injury during extraction of the mandibular third molar. As every functional component of the dental arch is of prime importance in contemporary dental practice, the major concern must be in conserving the tooth and its structure as much as possible. The present case discusses the application of this conservative approach for management of iatrogenically damaged distal root of the mandibular second molar during extraction of impacted third molar, in which excessive guttering of alveolar bone and fractured apical third of distal root of 37 was observed radiographically. A conservative and noninvasive approach was successfully achieved to restore the damaged root by the bioactive material. Sealing of the remaining root with mineral trioxide aggregate allowed regeneration of soft and hard tissue around it.


[Evaluation on applicationof virtual reality technology in dental implant process training].
Objective: To explore the application effect and evaluation of virtual reality technology in oral implant therapy training. Methods: In November 2018, one adult patient (female, 36 years old) with missing right mandibular first molar was treated in the Department of Implantology, School and Hospital of Stomatology, Fujian Medical University. The three-dimensional virtual models of mandible and implant surgery tools were established, and the virtual reality software (Unity 3D 5.5.1) was imported. Combined with the virtual reality head mounted display, a virtual reality training system simulating the dental implant treatment process was independently developed. Ten refresher doctors and 20 graduate students in Department of Implantology, School and Hospital of Stomatology, Fujian Medical University from September 2018 to December 2019 were recruited as the experimental objects (no clinical experience was found). According to the level and seniority of doctors, they were randomly divided into virtual training group and conventional training control group, which made the two groups comparable, with 15 in each group. Subjective scores (including anatomical structure, surgical field of vision, cavity preparation, implant placement and process mastery) were given after the corresponding training in the two groups, and the virtual reality training system was used to test. The mesial and distal direction, buccolingual direction, depth and angle deviation of implants before and after the training were analyzed, and the differences between the two groups were compared. Results: The subjective scores of five dimensions in the virtual training group were significantly higher than those in the conventional training control group (P<0.05). In the virtual training group, the mesial and distal, buccolingual, depth and angle deviation of implants were (0.73±0.33), (0.78±0.41), (0.61±0.32) mm and 6.66°±3.87°. All of them were significantly lower than those in the control group [(0.85±0.32), (1.12±0.38), (0.89±0.24) mm and 9.68°±3.74°] (P<0.05). Conclusions: The self-developed virtual reality system of oral implant has good application effect, good operability and predictability. It can be effectively carried out in implant education and training, and it can strengthen skills of doctors, and is conducive to the practical operation.


[Use of mobile applications by interns at Ibn-Rochd University Hospital in Casablanca, Morocco].
Introduction: Mobile applications are now increasingly used by trainee and practising physicians due to the wide range of applications available in the field of healthcare and their ease of use. The objective of this study was to estimate the frequency and describe the use of these applications by interns at Ibn-Rochd University Hospital in Casablanca. Methods: A cross-sectional survey was conducted in December 2014 on a sample of Ibn-Rochd interns. Participants from multiple disciplines and medical specialties completed an anonymous self-administered questionnaire. Results: One hundred and thirteen interns participated in the study with a 94.2% response rate: 95% of these interns had a smartphone and 85.2% had at least one healthcare mobile applications with an average of 3.57 applications per interns (SD = 3.14). Interns used these applications at least once a day and the most frequently downloaded applications were those devoted to diagnosis and patient care (61%). No statistically significant correlation was observed between the number of applications and the intern's specialty, the type of operating system used or the intern's gender. Conclusion: The use of healthcare mobile applications and the support they provide to Ibn-Rochd interns allowed an assessment of the importance of these new tools in medical training and practice. However, supervision and support by seniors are essential in view of the risks involved.


Production of brain-derived neurotrophic factor in Escherichia coli by coexpression of Dsb proteins.
When brain-derived neurotrophic factor (BDNF) is produced in the Escherichia coli periplasm, insoluble BDNF proteins with low biological activity and having mismatched disulfide linkages are formed. The coexpression of cysteine oxidoreductases (DsbA and DsbC) and membrane-bound enzymes (DsbB and DsbD), which play an important role in the formation of disulfide bonds in the periplasm, was investigated to improve the production of soluble and biologically active BDNF. The expression levels of Dsb proteins changed when the growth medium and the Dsb expression plasmids were changed, and the production rate of soluble BDNF was almost proportional to the expression level of DsbC protein with disulfide isomerase activity in the case of a low expression level of BDNF. The rate of soluble BDNF production with coexpression of DsbABCD was as high as 35%. These results show that coexpression of BDNF and Dsb proteins can effectively increase the production of soluble and biologically active BDNF.


[Evaluation of current imaging in restaging rectal cancer after neoadjuvant therapy].
The combination of preoperative chemoradi-otherapy and surgery has become the standard treatment for locally advanced rectal cancer. Up to 30% of patients received pathologic complete response(pCR) after neoadjuvant therapy, for whom low rates of local recurrence and improved outcome after surgery were achieved. Given that, some authors have recommended local resection for clinical extensive response or non operative "wait and see" policy for clinical complete response(cCR) respectively, in which radical surgery-associated complication and dysfunction can be avoided. Current imaging can provide excellent accuracy in primary staging of rectal cancer, however, when used for restaging, the ability is less satisfactory, especially for pCR prediction, as a result of modification on tumor and surrounding tissue induced by neoadjuvant therapy. The question on how to identify patients with pCR before surgery has received more attention recently. On the basis of pathological findings after surgery, in this article, we review the reliability and predictive ability of current imaging for restaging and pCR after preoperative chemoradiotherapy in rectal cancer.


Localized Heat Urticaria from 95-GHz Millimeter Waves.
Local heat urticaria is a physical urticaria caused by the environmental stimulus of heat. Typically, the resultant lesion, a wheal, is pruritic (itches) and is sometimes accompanied by a burning sensation. It is a self-limited phenomenon that resolves after 1.5-2 h. The prevalence of local heat urticaria in the general population has been estimated as 1 in 200,000 persons. The subject, a 39-yr-old active duty man, participated in a test of a 95-GHz energy beam designed to heat the skin. He had delayed presentation of raised, erythematous, nonpruritic, nonpainful areas at five of the exposure sites where the skin temperature exceeded 54°C. All wheals resolved within 2 h of the exposures.Gibbons JA. Localized heat urticaria from 95-GHz millimeter waves. Aerosp Med Hum Perform. 2017; 88(6):586-588.