Relation between dopaminergic control of pituitary lactotroph function and deceleration of age-related changes in serum prolactin of diet-restricted rats.
Pituitary lactotroph function has been examined in diet-restricted (6 hr/day) male and female rats and compared with that in animals fed ad lib. After 12 months the age-related increase in serum prolactin concentration was significantly attenuated in diet-restricted female rats. Similar effects were not observed in male rats. Isolated superfused anterior pituitary glands removed from rats on both feeding regimens at 12 or 18 months and challenged with dopamine in vitro (5 microM) did not show differential prolactin secretion. No significant differences were observed in serum prolactin secretion in vivo after administration of bromocriptine (3 mg/kg body weight, sc) or haloperidol (1.75 mg/kg body weight, ip). These results do not support an altered dopamine receptor function in the anterior pituitary lactotrophs. In contrast, central dopamine receptor function in rats 12 months of age was altered by dietary restriction, since the frequency of cataleptic responses to haloperidol injection (2 mg/kg body weight, ip) was significantly depressed in the test animals.


[Proposal for a diagnostic approach to long COVID].
The objective of this communication is to provide a proposal for a diagnostic approach to persistent COVID based on the various current etiopathogenic theories and to serve as a guide on how to start the diagnostic process in a patient affected by this syndrome according to the prevailing symptomatology and the basic studies and of extension that can be requested and even assisted by commercial kits that would help a better diagnosis.


Association between intrauterine device type and risk of perforation and device expulsion: results from the Association of Perforation and Expulsion of Intrauterine Device study.
Intrauterine devices, including levonorgestrel-releasing and copper devices, are highly effective long-acting reversible contraceptives. The potential risks associated with intrauterine devices are low and include uterine perforation and device expulsion. This study aimed to evaluate the risk of perforation and expulsion associated with levonorgestrel-releasing devices vs copper devices in clinical practice in the United States. The Association of Perforation and Expulsion of Intrauterine Device study was a retrospective cohort study of women aged ≤50 years with an intrauterine device insertion during 2001 to 2018 and information on intrauterine device type and patient and medical characteristics. Of note, 4 research sites with access to electronic health records contributed data for the study: 3 Kaiser Permanente-integrated healthcare systems (Northern California, Southern California, and Washington) and 1 healthcare system using data from a healthcare information exchange in Indiana (Regenstrief Institute). Perforation was classified as any extension of the device into or through the myometrium. Expulsion was classified as complete (not visible in the uterus or abdomen or patient reported) or partial (any portion in the cervix or malpositioned). We estimated the crude incidence rates and crude cumulative incidence by intrauterine device type. The risks of perforation and expulsion associated with levonorgestrel-releasing intrauterine devices vs copper intrauterine devices were estimated using Cox proportional-hazards regression with propensity score overlap weighting to adjust for confounders. Among 322,898 women included in this analysis, the incidence rates of perforation per 1000 person-years were 1.64 (95% confidence interval, 1.53-1.76) for levonorgestrel-releasing intrauterine devices and 1.27 (95% confidence interval, 1.08-1.48) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 0.22% (95% confidence interval, 0.20-0.24) and 0.63% (95% confidence interval, 0.57-0.68) for levonorgestrel-releasing intrauterine devices and 0.16% (95% confidence interval, 0.13-0.20) and 0.55% (95% confidence interval, 0.44-0.68) for copper intrauterine devices, respectively. The incidence rates of expulsion per 1000 person-years were 13.95 (95% confidence interval, 13.63-14.28) for levonorgestrel-releasing intrauterine devices and 14.08 (95% confidence interval, 13.44-14.75) for copper intrauterine devices; 1-year and 5-year crude cumulative incidence was 2.30% (95% confidence interval, 2.24-2.36) and 4.52% (95% confidence interval, 4.40-4.65) for levonorgestrel-releasing intrauterine devices and 2.30% (95% confidence interval, 2.18-2.44) and 4.82 (95% confidence interval, 4.56-5.10) for copper intrauterine devices, respectively. Comparing levonorgestrel-releasing intrauterine devices with copper intrauterine devices, the adjusted hazard ratios were 1.49 (95% confidence intervals, 1.25-1.78) for perforation and 0.69 (95% confidence intervals, 0.65-0.73) for expulsion. After adjusting for potential confounders, levonorgestrel-releasing intrauterine devices were associated with an increased risk of uterine perforation and a decreased risk of expulsion relative to copper intrauterine devices. Given that the absolute numbers of these events are low in both groups, these differences may not be clinically meaningful.


A multicomponent method for Fusarium toxins in cereal based food and feed samples using HPLC-MS/MS.
A reliable, sensitive and selective multicomponent method has been developed to determine 12 differentFusarium mycotoxins (trichothecenes type A and B, zearalenone) simultaneously in cereal and grain samples using liquid chromatography tandem mass spectrometry (LC-ESI-MS/MS). The sample preparation based on a standard extraction step followed by two different kinds of solid phase clean-up (multifunctional MycoSep(®) material) for trichothecenes, and an immuno-affinity purification which combined antibodies for aflatoxins, ochratoxin A and zearalenone (AOZ-IAC). For quantification of zearalenone (ZON) an internal standard (zearalanone, ZAN) was used, whereas for trichothecenes a recovery standard (verrucarol, VOL) was applied. The average recoveries for the trichothecenes ranged from 65% for nivalenol (NIV) up to 96% for deoxynivalenol (DON) and 89% for zearalenone. The limit of quantification is different for each of the individual trichothecenes and in the range of 1 ppb to 10 ppb.


Denaturation map of the ribosomal DNA of Lytechinus variegatus sperm.
Electron microscopy of the partially heat denatured ribosomal DNA (rDNA) from sea urchin (Lytechinus variegatus) sperm has demonstrated that it consists of repeating units of 3.6 +/- 0.2 micron, corresponding to a mol.wt of 7.2 +/- 0.4 x 10(6). Based on differential denaturability, each repeat unit is divided into 2 regions. The larger region of 2.47 +/- 0.11 micron (mol.wt 4.9 +/- 0.22 x 10(6)) corresponds in length to the ribosomal precursor RNA of sea urchins and the smaller, GC-rich, subunit of 1.16 +/- 0.09 micrometer (mol.wt 2.3 +/- 0.18 x 10(6)) is presumed to contain non-transcribed spacer sequences.


Clinical assessment of an enzyme immunoassay (EMIT) for measurement of serum salicylate.
Salicylic acid concentrations in serum were compared using a homogenous enzyme immunoassay (EMIT) and an automated colorimetric analysis (ACA) technique. Analysis of samples showed similar within-day and day-to-day coefficients of variation (CV): 1.3% and 4.6% by EMIT and 1.0% and 2.6% by ACA, respectively. Quantification of serum containing added salicylate and serum from patients receiving salicylate therapy showed a slight positive bias towards the ACA method over the range of 0-600 mg/l. No significant difference in reliability was found between the two methods. The EMIT assay showed no interference from other antiflammatory drugs being taken by patients who were not taking salicylates. If decisions to alter salicylate dosage are made with due regard to the drug's saturation kinetics, measurements using either EMIT or ACA should allow the clinician to titrate patients' serum concentrations accurately within the narrow therapeutic range.


HIV-2 viral protein X (Vpx) ubiquitination is dispensable for ubiquitin ligase interaction and effects on macrophage infection.
HIV-2 Vpx, a virus-associated accessory protein, is critical for infection of non-dividing myeloid cells. To understand the function of Vpx ubiquitination, interaction with an E3 ubiquitin ligase complex, and ability to overcome an inhibition of reverse transcription, we analyzed Vpx lysine mutants for their function and replication capability in macrophages. Both Wt Vpx and Vpx TA (lysine-less Vpx) localized to the cytoplasm and nucleus in HeLa cells. All HIV-2 Vpx lysine mutants were functional in virion packaging. However, ubiquitination was absent with Vpx TA and Vpx K84A mutants, indicating a lack of ubiquitin on positions K68 and K77. Mutants Vpx K68A and K77A were unable to infect macrophages due to impaired reverse transcription from loss of interaction with the ubiquitin substrate receptor, DCAF1. Even though Vpx K84A lacked ubiquitination, it bound DCAF1, and infected macrophages comparable to Wt Vpx.


Mothers' union histories and the mental and physical health of adolescents born to unmarried mothers.
As nonmarital childbearing becomes a dominant pathway to family formation, understanding its long-term consequences for children's well-being is increasingly important. Analysis of linked mother-child data from the 1979 National Longitudinal Survey of Youth indicates a negative association of having been born to a never-married mother with adolescent self-assessed health but not with depressive symptoms. We also consider the role of mothers' subsequent union histories in shaping the adolescent health outcomes of youth born to unmarried mothers. With two exceptions, unmarried mothers' subsequent unions appear to have little consequence for the health of their offspring during adolescence. Adolescents whose mothers subsequently married and remained with their biological fathers reported better health, yet adolescents whose mothers continuously cohabited with their biological fathers without subsequent marriage reported worse adolescent mental health compared with adolescents whose mothers remained continually unpartnered.


Spinal anesthesia for elective lumbar spine surgery.
To evaluate a large series of elective lumbar spine surgical procedures by a single surgeon whose patients were all offered spinal anesthesia. Retrospective chart review. Tertiary-care teaching hospital. The records of all elective lumbar spine procedures between 1984 and 1995 performed by one surgeon (GRB) were obtained, and 803 were identified. Of those 803 patients, 611 accepted spinal anesthesia. Data collected included patient demographics, details of the spinal and general anesthesia, perioperative complications, and impact of the spinal anesthetic options on the outcome of spinal anesthesia. General and spinal anesthesia patients were comparable for age, gender, height, and ASA physical status. Patients who received spinal anesthesia were significantly heavier than the general anesthesia patients. Among perioperative complications, nausea and deep venous thrombosis occurred significantly more often in the general than spinal anesthesia patients. Mild hypotension and decreased heart rate (HR) were the most common hemodynamic changes with spinal anesthesia, whereas hypertension and increased HR were the result of general anesthesia. Among spinal anesthetic drugs, plain bupivacaine was associated with the lowest incidence of supplemental local anesthetic use intraoperatively compared to hyperbaric bupivacaine or hyperbaric tetracaine. Spinal anesthesia is an effective alternative to general anesthesia for lumbar spine surgery and has a reduced rate of minor complications.


A feasibility study of telemedicine for paediatric sickle cell patients living in a rural medically underserved area.
Sickle cell disease (SCD) is the most common inherited haematological disease, with potentially devastating complications. Improvements in therapies have increased the life span of patients with SCD, but this is contingent on receiving timely evidence-based medical care, including regular evaluations with haematologists, disease-specific education and psychosocial care. Our objective was to evaluate the feasibility of utilizing telemedicine for the provision of subspecialty paediatric SCD care in a rural medically underserved area. This was a cross-sectional, observational, feasibility study. All patients 0-21 years old with SCD seen at Riley Hospital for Children Comprehensive Pediatric Sickle Cell Clinic who lived within 30 miles of the spoke telemedicine facility were eligible for recruitment. The Telehealth Satisfaction Scale (TeSS) was adapted for the SCD population and administered at each visit. Ten SCD patients, ranging in age from 10 months to 18 years old, initiated telemedicine visits during this timeframe. Some 60% were lost to follow-up or did not attend >50% of scheduled visits prior to beginning telemedicine visits. Following initiation of telemedicine, all Hb SS patients were started and/or maintained on hydroxyurea. Nine out of 10 patients who participated during this timeframe had a 100% follow-up rate. All who participated rated the comfort and ease of using the telehealth system as good or excellent and would do a telemedicine visit again. This study provides critical information to determine the feasibility and acceptability of a telemedicine intervention to aid in SCD care. To our knowledge, this is the first study to examine the effectiveness of telemedicine to deliver comprehensive paediatric SCD care. Future research with a larger sample size is needed to confirm findings of our study, including expansion of telemedicine sites to include more urban areas.


Commercial Harvesting Has Driven the Evolution of Camouflage in an Alpine Plant.
Color in nature mediates numerous among and within species interactions,1 and anthropogenic impacts have long had major influences on the color evolution of wild animals.2 An under-explored area is commercial harvesting, which in animals can exert a strong selection pressure on various traits, sometimes greater even than natural selection or other human activities.3,4 Natural populations of plants that are used by humans have likely also suffered strong pressure from harvesting, yet the potential for evolutionary change induced by humans has received surprisingly little attention.5 Here, we show that the leaf coloration of a herb used in traditional Chinese medicine (Fritillaria delavayi) varies among populations, with leaves matching their local backgrounds most closely. The degree of background matching correlates with estimates of harvest pressure, with plants being more cryptic in heavily collected populations. In a human search experiment, the time it took participants to find plants was greatly influenced by target concealment. These results point to humans as driving the evolution of camouflage in populations of this species through commercial harvesting, changing the phenotype of wild plants in an unexpected and dramatic way.


Effect of intraluminal oxygen on endotoxin absorption in experimental occlusion of the superior mesenteric artery.
Absorption of bacterial endotoxin has been shown to occur after release of the occluded superior mesenteric artery in the rat. A significant reduction in endotoxin absorption was observed as a result of the infusion of gaseous oxygen into the bowel lumen during the period of ischaemia (P less than 0-001). The methods of endotoxin identification and assay are described, and the possible reasons for this effect of intraluminal oxygen are discussed.


Effects of remote ischemic conditioning on conditioned pain modulation and cardiac autonomic modulation in women with knee osteoarthritis: placebo-controlled randomized clinical trial protocol.
It is estimated that over 240 million people worldwide have osteoarthritis, which is a major contributor to chronic pain and central changes in pain processing, including endogenous pain modulation. The autonomic nervous system plays a crucial role in the pain regulatory process. One of the main mechanisms of remote ischemic conditioning is neuronal signaling from the preconditioned extremity to the heart. This study aims to analyze the acute effect of remote ischemic conditioning on local pain, conditioned pain modulation, and cardiac autonomic control in women with knee osteoarthritis and to see if there is a correlation between them. Women more than 50 years with knee osteoarthritis diagnosed according to the American College of Rheumatology criteria in the postmenopausal period will be considered eligible. The study will have blind randomization, be placebo-controlled, and be balanced in a 1:1 ratio. The total of 44 participants will be divided into two groups (22 participants per group): (i) remote ischemic conditioning and (ii) placebo remote ischemic conditioning. Protocol consisting of four cycles of total ischemia, followed immediately by four cycles of 5 min of vascular reperfusion, totaling 40 min. The primary outcomes in the protocol are conditioned pain modulation, which has the pressure pain threshold (kgf/cm2) as its primary outcome measure, and cardiac autonomic modulation, which has the indices found in heart rate variability as its primary outcome measure. Comparisons will be performed using generalized linear mixed models fitted to the data. For correlation, the Pearson or Spearman test will be used depending on the normality of the data. All analyses will assume a significance level of p < 0.05. It is believed that the results of this study will present a new perspective on the interaction between the pain processing system and the cardiovascular system; they will provide the professional and the patient with a greater guarantee of cardiovascular safety in the use of the intervention; it will provide knowledge about acute responses and this will allow future chronic intervention strategies that aim to be used in the clinical environment, inserted in the multimodal approach, for the treatment of osteoarthritis of the knee. ClinicalTrials.gov NCT05059652. Registered on 30 August 2021. Last update on 28 March 2023.


[The role of magnetic resonant tomography in the diagnosis of primary and metastatic brain tumors].
1035 patients of suspected brain formations have been examined in a low-field magnetic resonance tomography (MPT) study. Various patterns of brain tumors were identified in 772 cases and diagnosis was verified by other procedures. Among the most frequent were neuro-epithelial tumors (157), meningiomas (161) and metastatic lesions (136). The MRT technique condition suggest histological pattern. Although less expensive and easier to service, low-field MRT's yield as much information for brain tumor diagnosis as medium- and high-field tomographs do.


Oral administration of an HSP90 inhibitor, 17-DMAG, intervenes tumor-cell infiltration into multiple organs and improves survival period for ATL model mice.
In the peripheral blood leukocytes (PBLs) from the carriers of the human T-lymphotropic virus type-1 (HTLV-1) or the patients with adult T-cell leukemia (ATL), nuclear factor kappaB (NF-κB)-mediated antiapoptotic signals are constitutively activated primarily by the HTLV-1-encoded oncoprotein Tax. Tax interacts with the I κB kinase regulatory subunit NEMO (NF-κB essential modulator) to activate NF-κB, and this interaction is maintained in part by a molecular chaperone, heat-shock protein 90 (HSP90), and its co-chaperone cell division cycle 37 (CDC37). The antibiotic geldanamycin (GA) inhibits HSP90's ATP binding for its proper interaction with client proteins. Administration of a novel water-soluble and less toxic GA derivative, 17-dimethylaminoethylamino-17-demethoxygeldanamycin hydrochloride (17-DMAG), to Tax-expressing ATL-transformed cell lines, C8166 and MT4, induced significant degradation of Tax. 17-DMAG also facilitated growth arrest and cellular apoptosis to C8166 and MT4 and other ATL cell lines, although this treatment has no apparent effects on normal PBLs. 17-DMAG also downregulated Tax-mediated intracellular signals including the activation of NF-κB, activator protein 1 or HTLV-1 long terminal repeat in Tax-transfected HEK293 cells. Oral administration of 17-DMAG to ATL model mice xenografted with lymphomatous transgenic Lck-Tax (Lck proximal promoter-driven Tax transgene) cells or HTLV-1-producing tumor cells dramatically attenuated aggressive infiltration into multiple organs, inhibited de novo viral production and improved survival period. These observations identified 17-DMAG as a promising candidate for the prevention of ATL progression.


Occupational asthma caused by a prepolymer but not the monomer of toluene diisocyanate (TDI).
Isocyanates are the most common cause of occupational asthma. Isocyanate monomers and prepolymers are widely used in the manufacture of polyurethane compounds. However, prepolymers are generating increasing interest because of their lower volatility. No distinction has yet been made between asthmatic reactions caused by the monomers and the prepolymers of isocyanates, and asthmatic reactions caused by one type of isocyanate but not the other type have not been reported. We describe two wood-roof maintenance workers who developed asthma after being exposed to a varnish containing a prepolymer of toluene diisocyanate (TDI) with only small amounts of the monomer. Specific inhalation-challenge tests with the TDI monomer did not elicit significant airway obstruction, whereas exposure to the varnish and to the purified TDI prepolymer induced late asthmatic reactions. Specific antibodies against TDI monomer human serum albumin and TDI prepolymer human serum albumin conjugates could not be demonstrated. These observations demonstrate that isocyanate prepolymers can cause occupational asthma and that asthmatic reactions caused by isocyanate prepolymers, but not to the corresponding monomer, can occur in some exposed workers.


Selectivity for large nonmanipulable objects in scene-selective visual cortex does not require visual experience.
The principles that determine the organization of object representations in ventral temporal cortex (VTC) remain elusive. Here, we focus on the parahippocampal place area (PPA), a region in medial VTC that has been shown to respond selectively to pictures of scenes. Recent studies further observed that this region also shows a preference for large nonmanipulable objects relative to other objects, which might reflect the suitability of large objects for navigation. The mechanisms underlying this selectivity remain poorly understood. We examined the extent to which PPA selectivity requires visual experience. Fourteen congenitally blind and matched sighted participants were tested on an auditory size judgment experiment involving large nonmanipulable objects, small objects (tools), and animals. Sighted participants additionally participated in a picture-viewing experiment. Replicating previous work, we found that the PPA responded selectively to large nonmanipulable objects, relative to tools and animals, in the sighted group viewing pictures. Importantly, this selectivity was also observed in the auditory experiment in both sighted and congenitally blind groups. In both groups, selectivity for large nonmanipulable objects was additionally observed in the retrosplenial complex (RSC) and the transverse occipital sulcus (TOS), regions previously implicated in scene perception and navigation. Finally, in both groups the PPA showed resting-state functional connectivity with TOS and RSC. These results provide new evidence that large object selectivity in PPA, and the intrinsic connectivity between PPA and other navigation-relevant regions, do not require visual experience. More generally, they show that the organization of object representations in VTC can develop, at least partly, without visual experience.


Immunogold localisation of microcystins in cryosectioned cells of Microcystis.
Insights into the origins, function(s), and fates of cyanobacterial toxins may be obtained by an understanding of their location within cyanobacterial cells. Here, we have localised microcystins in laboratory cultures of Microcystis PCC 7806 and PCC 7820 by immunogold labelling. Cryosectioning was used for immunoelectron microscopy since microcystins were extracted during the ethanol-based dehydration steps routinely used for sample preparation. Microcystins were specifically localised in the nucleoplasm and were associated with all major inclusions of the microcystin-producing strains Microcystis PCC 7806 (MC(+)) and Microcystis PCC 7820, and labelling was preferentially associated with the thylakoids and around polyphosphate bodies. A mutant strain of Microcystis PCC 7806 (MC(-)) which does not produce microcystins was used as a control. Distribution of total gold label within each cell region or associated with inclusions indicated that most of the cells' microcystin pool was associated with the thylakoids (69%, PCC 7806 (MC(+)); 78%, PCC 7820), followed by the nucleoplasmic region (19%, PCC 7806 (MC(+)); 12%, PCC 7820). Cryosectioning is a useful technique since it reduces the extraction of microcystins during sample preparation for electron microscopy.


Differential expression of coagulation pathway-related proteins in diabetic urine exosomes.
Coagulation function monitoring is important for the occurrence and development of diabetes. A total of 16 related proteins are involved in coagulation, but how these proteins change in diabetic urine exosomes is unclear. To explore the expression changes of coagulation-related proteins in urine exosomes and their possible roles in the pathogenesis of diabetes, we performed proteomic analysis and finally applied them to the noninvasive monitoring of diabetes. Subject urine samples were collected. LC-MS/MS was used to collect the information on coagulation-related proteins in urine exosomes. ELISA, mass spectrometry and western blotting were used to further verify the differential protein expression in urine exosomes. Correlations with clinical indicators were explored, and receiver operating characteristic (ROC) curves were drawn to evaluate the value of differential proteins in diabetes monitoring. Analyzing urine exosome proteomics data, eight coagulation-related proteins were found in this study. Among them, F2 was elevated in urine exosomes of diabetic patients compared with healthy controls. The results of ELISA, mass spectrometry and western blotting further verified the changes in F2. Correlation analysis showed that the expression of urine exosome F2 was correlated with clinical lipid metabolism indexes, and the concentration of F2 was strongly positively correlated with blood TG levels (P < 0.05). ROC curve analysis showed that F2 protein in urine exosomes had a good monitoring value for diabetes. Coagulation-related proteins were expressed in urine exosomes. Among them, F2 was increased in diabetic urine exosomes and may be a potential biomarker for monitoring diabetic changes.


Artificial intelligence in digital pathology of cutaneous lymphomas: A review of the current state and future perspectives.
Primary cutaneous lymphomas (CLs) represent a heterogeneous group of T-cell lymphomas and B-cell lymphomas that present in the skin without evidence of extracutaneous involvement at time of diagnosis. CLs are largely distinct from their systemic counterparts in clinical presentation, histopathology, and biological behavior and, therefore, require different therapeutic management. Additional diagnostic burden is added by the fact that several benign inflammatory dermatoses mimic CL subtypes, requiring clinicopathological correlation for definitive diagnosis. Due to the heterogeneity and rarity of CL, adjunct diagnostic tools are welcomed, especially by pathologists without expertise in this field or with limited access to a centralized specialist panel. The transition into digital pathology workflows enables artificial intelligence (AI)-based analysis of patients' whole-slide pathology images (WSIs). AI can be used to automate manual processes in histopathology but, more importantly, can be applied to complex diagnostic tasks, especially suitable for rare disease like CL. To date, AI-based applications for CL have been minimally explored in literature. However, in other skin cancers and systemic lymphomas, disciplines that are recognized here as the building blocks for CLs, several studies demonstrated promising results using AI for disease diagnosis and subclassification, cancer detection, specimen triaging, and outcome prediction. Additionally, AI allows discovery of novel biomarkers or may help to quantify established biomarkers. This review summarizes and blends applications of AI in pathology of skin cancer and lymphoma and proposes how these findings can be applied to diagnostics of CL.


Ossifying granulomatous periostitis in the course of erythema nodosum.
The author records a case of ossifying periostitis of the tibia apparently due to erythema nodosum. This does not appear to have been recorded previously. The histology, aetiology and differential diagnosis are discussed. The mechanism is probably one of direct spread from skin to periosteum.


Flexible feeding in anaerobic digestion - Impact on process stability, performance and microbial community structures.
Biogas has the potential to contribute to some of the most urgent issues of the energy transition, including mobility, energy storage, and grid stability. Flexibilization has been discussed as a means to improve the economics of biogas production, ideally restricting the production of electricity to times of strong need. Here the possibility of demand-driven, flexible biogas production is investigated, which saves substrates and storage capacity, while still enabling control over the production of electricity. Effects of different flexible feeding regimes were tested in a continuously operated 200 L reactor. After a period of 300 days under steady conditions (6.4 kg feed m-3d-1), varying flexible feeding patterns were applied over the next 700 days. Biogas production, volatile organic acid concentrations, and microbial dynamics were documented. Reduction of feeding resulted in reducing the gas production by up to 80% within a day. By increasing the feed, gas production could rapidly be reinitiated at similar levels as before even after fasting periods of up to 22 days. CH4-contents of the produced biogas were nearly constant over the investigation period. As a response to the flexible feeding, a reorganization of the microbial community was observed, which came to an end after 800 days and then was no longer affected by further changes in the feeding patterns or the substrate composition. Dominating archaea were of the order Methanosarcinales. During the experiment, representatives from the class Methanosaetaceae replaced representatives from the class Methanosarcinaceae.


Effects of myocardial hypertrophy on neural reflexes controlling cardiovascular function.
There are clinical and experimental evidences that the cardiopulmonary reflex function is impaired in chronic hypertension, but it could be due to myocardial hypertrophy rather than to hypertension itself. To test this hypothesis we evaluated the Bezold-Jarisch reflex in experimental conditions of myocardial hypertrophy and arterial normotension. Adult male Wistar rats were subjected to myocardial hypertrophy (MHR) treating them with the beta-adrenoceptor agonist isoproterenol (0.3 mg/kg/day, s.c.) for 15 days and compared with vehicle injected control rats (CR). No significant changes in body weight (283+/-14 vs. 299+/-9 g), resting mean arterial pressure (104+/-4 vs. 110+3 mm Hg) or heart rate (330+/-11 vs. 358+/-18 bpm) were observed in MHR compared to CR. As expected, MHR showed left and right ventricular and left atrial hypertrophy when compared to CR. The bradycardia and hypotension that characterizes the Bezold-Jarisch reflex, induced by the 5-HT3, agonist phenyldiguanide (1.5-24.0 microg/kg, i.v.), were significantly decreased in MHR compared to CR. Cardiac muscarinic responsiveness, which was assessed by electrical stimulation of the efferent vagus in anesthetized animals or by stimulation of muscarinic receptors in isolated hearts, was unchanged or increased, respectively, in MHR compared to CR. Additional studies showed that the baroreflex and chemoreflex were also attenuated in MHR compared to CR. These data indicate that cardiac hypertrophy impairs the Bezold-Jarisch reflex probably due to changes at central integrative areas of the reflex.


Role of Cardiac MRI in the Assessment of Cardiomyopathy.
Combining the diagnostic utilities of cardiac structures, myocardial perfusion, and various tissue characterizing pulse sequence methods in matching scan planes within a single imaging session, cardiac magnetic resonance imaging (CMR) provides a novel interrogation of myocardial physiology and abnormal anatomy from various forms of cardiomyopathy. Establishment of technical imaging standards and clinical adaptation in the past years has helped recognize the distinguishing features of different cardiomyopathies, with CMR currently assuming a pivotal role in the diagnosis of cases of new-onset cardiomyopathy in experienced centers. Quantitative measurements such as ventricular volumes, myocardial iron content, and extent of late gadolinium enhancement can effectively monitor disease status, guide medical therapy, and impact patient outcomes in specific clinical settings. This chapter will aim to summarize these current CMR applications with case examples.


Interaction between Laser Light and Osteoblasts: Photobiomodulation as a Trend in the Management of Socket Bone Preservation-A Review.
Bone defects are the main reason for aesthetic and functional disability, which negatively affect patient's quality of life. Particularly, after tooth extraction, the bone of the alveolar process resorbs, limiting the optimal prosthetic implant placement. One of the major pathophysiological events in slowly- or non-healing tissues is a blood supply deficiency, followed by a significant decrease in cellular energy amount. The literature shows that photons at the red and infrared wavelengths can interact with specific photoacceptors located within the cell. Through this mechanism, photobiomodulation (PBM) can modify cellular metabolism, by increasing mitochondrial ATP production. Here, we present a review of the literature on the effect of PBM on bone healing, for the management of socket preservation. A search strategy was developed in line with the PRISMA statement. The PubMed and Scholar electronic databases were consulted to search for in vivo studies, with restrictions on the year (<50 years-old), language (English), bone socket preservation, and PBM. Following the search strategy, we identified 269 records, which became 14, after duplicates were removed and titles, abstract and inclusion-, exclusion-criteria were screened. Additional articles identified were 3. Therefore, 17 articles were included in the synthesis. We highlight the osteoblast-light interaction, and the in vivo therapeutic tool of PBM is discussed.


Characterization and signature pattern analysis of Korean clade HIV-1 using nef gene sequences.
Phylogenetic studies of the HIV-1 gene sequences isolated from Korean patients have suggested that most of Korean isolates belong to the subtype B strain. This study aims to characterize the Korean clade by molecular phylogenetic analysis using all of the Korean nef gene sequences registered in the NCBI GenBank (N=422), in addition to 41 reference strains and 94 foreign isolates. Through phylogenetic analyses, we verified that most of the Korean isolates belonged to the subtype B, where 78.8% are clustered exclusively of foreign isolates. This cluster has been named the Korean clade subtype B (KCB) in order to distinguish it from other subtype B clusters. Genetic distance analysis suggested that the KCB cluster was more homogeneous and clearly distinctive from the non-Korean clade subtype B (NKCB). Comparison of consensus amino acid sequences from KCB and NKCB revealed that characteristic KCB signature amino acid patterns composed of 11 amino acid residues, whose frequencies in the KCB were significantly higher than in the NKCB. The KCB signature amino acid residues were critical in identifying KCB from NKCB, since substitution of the NKCB sequences with KCB signature amino acids relocated them to the Koran clade, and vice versa.


Neonatal screening for sickle cell disorders in Ouagadougou, Burkina Faso: a pilot study.
To determine the incidence of sickle cell disorders (SCDs) and the feasibility of a neonatal screening programme in Ouagadougou. During 2000, 2003 and 2004, 2341 cord blood samples obtained in five maternity hospitals in Ouagadougou were screened for SCDs using an isoelectric focusing technique. The feasibility of a neonatal screening programme was evaluated. The incidence of SCD was 1:57; 14 neonates were homozygous for haemoglobin (Hb)S and 27 were compound heterozygotes for HbSC. Thirty-two neonates were homozygous for HbC. The incidence of the HbC trait was 1:6; incidence of the HbS trait was 1:14. A centralized laboratory for neonatal screening of SCDs was established. SCDs should be considered a major public health problem in Ouagadougou. A neonatal screening programme should be implemented, but to be effective it requires strategies adapted to the local situation.


Crown Ether-Derived Chiral BINOL: Enantioselective Michael Addition of Alkenyl Boronic Acids to α,β-Unsaturated Ketones.
A new class of aza-crown ether-derived chiral BINOL catalysts were designed, synthesized, and applied in the asymmetric Michael addition of alkenylboronic acids to α,β-unsaturated ketones. It was found that introducing aza-crown ethers to the BINOL catalyst could achieve apparently higher enantioselectivity than a similar BINOL catalyst without aza-crown ethers did, although the host-guest complexation of alkali ions by the aza-crown ethers could not further improve the catalysis effectiveness. Under mediation of the aza-crown ether-derived chiral BINOL and in the presence of a magnesium salt, an array of chiral γ,δ-unsaturated ketones were furnished in good enantioselectivities (81-95% ees).


Partial trisomy of distal 8q derived from mother with mosaic 8q23.3----24.13 deletion, and relatively mild expression of trichorhinophalangeal syndrome I.
A 17-month-old girl with a partial trisomy of distal 8q derived from her mother, who has a mosaic 8q23.3----q24.13 deletion, was studied. Both showed a relatively mild phenotype of trichorhinophalangeal syndrome I. The karyotype of the proposita was designated as: 46,XX,-8,+der(8),inv ins(8;8)(p23.1;q24.13q23.3)mat. Her phenotype was considered similar to that of her mother despite the trisomies of distal 8q. She seems to be the first example of a partial trisomy of distal 8q derived from a parent with an interstitial deletion of a distal 8q segment and trichorhinophalangeal syndrome I.


Evolution of the epidermoid formation and its role in the development of the middle ear and tympanic membrane during the first trimester.
In a study of 20 ears from embryos and early fetuses, 16 contained structures recognizable as precursors of the epidermoid formation (EF). The earliest were small, but later they took the form of a long epithelial bud which emanated from the tip of the tubotympanic recess or Eustachian tube. At a later stage still the EF protruded into the lumen of the Eustachian tube. The early formation of the tympanic membrane, the middle ear cavity and the osseous tympanic ring all take place in the vicinity of the EF precursor. It is possible that the EF precursor may act as an organizer, playing a prominent part in the migration of the first pharyngeal pouch towards the first branchial groove and the development of the middle ear and tympanic membrane.


DEG9, a serine protease, modulates cytokinin and light signaling by regulating the level of ARABIDOPSIS RESPONSE REGULATOR 4.
Cytokinin is an essential phytohormone that controls various biological processes in plants. A number of response regulators are known to be important for cytokinin signal transduction. ARABIDOPSIS RESPONSE REGULATOR 4 (ARR4) mediates the cross-talk between light and cytokinin signaling through modulation of the activity of phytochrome B. However, the mechanism that regulates the activity and stability of ARR4 is unknown. Here we identify an ATP-independent serine protease, degradation of periplasmic proteins 9 (DEG9), which localizes to the nucleus and regulates the stability of ARR4. Biochemical evidence shows that DEG9 interacts with ARR4, thereby targeting ARR4 for degradation, which suggests that DEG9 regulates the stability of ARR4. Moreover, genetic evidence shows that DEG9 acts upstream of ARR4 and regulates the activity of ARR4 in cytokinin and light-signaling pathways. This study thus identifies a role for a ubiquitin-independent selective protein proteolysis in the regulation of the stability of plant signaling components.


Does obesity confer an increased risk and/or more severe course of post-ERCP pancreatitis?: a retrospective, multicenter study.
Pancreatitis is the most common major complication of endoscopic retrograde cholangiopancreatography (ERCP). Recent studies have suggested that obesity may serve as a prognostic indicator of poor outcome in non-ERCP-induced acute pancreatitis. However, to our knowledge, no one has ever investigated the potential association of obesity and ERCP-induced pancreatitis. Thus, the purpose of our study was to determine whether obesity conferred an increased risk and/or more severe course of post-ERCP pancreatitis. A 160 variable database was prospectively collected by a defined protocol on patients undergoing diagnostic or therapeutic ERCP at 15 centers in the Midwest Pancreaticobiliary Group and participating in a randomized controlled study, evaluating whether prophylactic corticosteroids reduces the incidence of post-ERCP pancreatitis. Body mass indices (BMIs) were available on 964 of the 1115 patients from the original study. A BMI > or = 30 kg/m2 was defined as obese (World Health Organization) and used as a cutoff point in this study. BMIs were analyzed in a retrospective fashion to determine whether obesity confers an increased risk and/or more severe course of post-ERCP pancreatitis. Data were collected before the ERCP, at the time of procedure, and 24 to 72 hours after discharge. Standardized criteria were used to diagnose and grade the severity of postprocedure pancreatitis. Nine hundred sixty four patients were enrolled in the study. Pancreatitis occurred in 149 patients (15.5%) and was graded as mild in 101 (67.8%), moderate in 42 (28.2%), and severe in 6 (4.0%). The patients were categorized by BMI (kg/m2) using the following breakdowns: BMI < 20, 20 to < 25, 25 to < 30, and > or = 30, as well as BMI < 30 or > or = 30. The groups were similar with respect to the patient and procedure risk factors for post-ERCP pancreatitis except the group with BMI > or = 30 had a higher frequency of females, were younger, had less frequent chronic pancreatitis, a lower number of pancreatic duct injections, and fewer patients received more than 2 pancreatic duct injections. Of the patients with a BMI < 30, 119 (16.4%) developed post-ERCP pancreatitis compared with 30 (12.5%) of those with a BMI > or = 30 (P=0.14). There was no association between the presence of obesity and the severity of pancreatitis (P=0.74). Patients with a BMI < 20, 20 to < 25, 25 to < 30, and > or = 30 had a similar incidence of post-ERCP pancreatitis. Obesity did not seem to confer an increased risk for ERCP-induced pancreatitis. A statistically significant association between obesity and the severity of ERCP-induced pancreatitis was not apparent.


Gas-phase fragmentation of oligoproline peptide ions lacking easily mobilizable protons.
The fragmentation of peptides containing quaternary ammonium group, but lacking easily mobilizable protons, was examined with the aid of deuterium-labeled analogs and quantum-chemical modeling. The fragmentation of oligoproline containing quaternary ammonium group involves the mobilization of hydrogens localized at α- and γ- or δ-carbon atoms in the pyrrolidine ring of proline. The study of the dissociation pattern highlights the unusual proline residue behavior during MS/MS experiments of peptides.


Integration of canonical and noncanonical Wnt signaling pathways patterns the neuroectoderm along the anterior-posterior axis of sea urchin embryos.
Patterning the neuroectoderm along the anterior-posterior (AP) axis is a critical event in the early development of deuterostome embryos. However, the mechanisms that regulate the specification and patterning of the neuroectoderm are incompletely understood. Remarkably, the anterior neuroectoderm (ANE) of the deuterostome sea urchin embryo expresses many of the same transcription factors and secreted modulators of Wnt signaling, as does the early vertebrate ANE (forebrain/eye field). Moreover, as is the case in vertebrate embryos, confining the ANE to the anterior end of the embryo requires a Wnt/β-catenin-dependent signaling mechanism. Here we use morpholino- or dominant negative-mediated interference to demonstrate that the early sea urchin embryo integrates information not only from Wnt/β-catenin but also from Wnt/Fzl5/8-JNK and Fzl1/2/7-PKC pathways to provide precise spatiotemporal control of neuroectoderm patterning along its AP axis. Together, through the Wnt1 and Wnt8 ligands, they orchestrate a progressive posterior-to-anterior wave of re-specification that restricts the initial, ubiquitous, maternally specified, ANE regulatory state to the most anterior blastomeres. There, the Wnt receptor antagonist, Dkk1, protects this state through a negative feedback mechanism. Because these different Wnt pathways converge on the same cell fate specification process, our data suggest they may function as integrated components of an interactive Wnt signaling network. Our findings provide strong support for the idea that the sea urchin ANE regulatory state and the mechanisms that position and define its borders represent an ancient regulatory patterning system that was present in the common echinoderm/vertebrate ancestor.


The effects of ACTH on adrenal steroidogenesis and blood corticosteroid levels in the echidna (Tachyglossus aculeatus).
1. The effects of short-term (S.T., 30 min) and long-term (L.T., 4 days) administration of ACTH on peripheral blood corticosteroid levels and on in vitro steroidogenesis were investigated. 2. Control levels of cortisol, corticosterone and aldosterone were 58 +/- 12, 130 +/- 26 and 10 +/- 6 (SEM) ng/100 ml respectively. 3. Corticosterone was 70% higher after S.T. and 150% higher after L.T., when cortisol was 800% higher. 4. Adrenal homogenates from control echidnas converted [14C]progesterone predominantly to 11-deoxycorticosterone (45%) and 11-deoxycortisol (12%). 5. After L.T. the principal product was corticosterone (25%), but S.T. had no effect. 6. In control echidnas the Km and V for 11 beta-hydroxylation of 11-deoxycorticosterone were 20 microM and 2.8 rho mol/min/mg respectively. After L.T. V increased to 10 rho mol/min/mg.


ERK inhibitor ASN007 effectively overcomes acquired resistance to EGFR inhibitor in non-small cell lung cancer.
The emergence of acquired resistance limits the long-term efficacy of EGFR tyrosine kinase inhibitors (EGFR TKIs). Thus, development of effective strategies to overcome resistance to EGFR TKI is urgently needed. Multiple mechanisms to reactivate ERK signaling have been successfully demonstrated in acquired resistance models. We found that in EGFR mutant non-small cell lung cancer (NSCLC) patients, acquired resistance to EGFR TKIs was accompanied by increased activation of ERK. Increased ERK activation was also found in in vitro models of acquired EGFR TKI resistance. ASN007 is a potent selective ERK1/2 inhibitor with promising antitumor activity in cancers with BRAF and RAS mutations. ASN007 treatment impeded tumor cell growth and the cell cycle in EGFR TKI-resistant cells. In addition, combination treatment with ASN007 and EGFR TKIs significantly decreased the survival of resistant cells, enhanced induction of apoptosis, and effectively inhibited the growth of erlotinib-resistant xenografts, providing the preclinical rationale for testing combinations of ASN007 and EGFR TKIs in EGFR-mutated NSCLC patients. This study emphasizes the importance of targeting ERK signaling in maintaining the long-term benefits of EGFR TKIs by overcoming acquired resistance.


Development and validation of spectrophotometric methods for estimation of antimigraine drug eletriptan hydrobromide in pure form and pharmaceutical formulations.
The present study aims to develop and validate four simple, sensitive, reproducible, and low-cost spectrophotometric methods for the determination of antimigraine drug (eletriptan hydrobromide) in pure form and pharmaceutical formulations. The methods are based on the formation of yellow colored ion-pair complex between eletriptan hydrobromide and four acid dyes, namely, bromocresol purple (BCP), bromocresol green (BCG), bromophenol blue (BPB), and bromothymol blue (BTB) with absorption maxima at 410, 420, 414 and 416nm, respectively. Several parameters such as pH, buffer type and volume, reagent volume, sequence of addition and effect of extracting solvent were optimized. Under the optimum experimental conditions, beer's law is obeyed over the concentration ranges of 1.0-20 and 1.0-16μgmL-1 for (BCP or BCG) and (BPB or BTB), respectively with good correlation coefficients (0.9995-0.9999). The apparent molar absorptivity and Sandell's sensitivity values are reported for all methods. The limit of detection (LOD) and the limit of quantification (LOQ) values are found to be 0.27, 0.28, 0.25, and 0.30μgmL-1 and 0.90, 0.93, 0.83, and 1.0μgmL-1 for BCP, BCG, BPB and BTB, respectively. The stoichiometric ratio of the formed ion-pair complexes was found to be 1:1 (drug: reagent) for all methods. The developed methods were successfully applied for the determination of eletriptan hydrobromide in pharmaceutical formulations with good accuracy and precision. Statistical comparison of the results was performed using Student's t-test and variance ratio F-test at the 95% confidence level and there was no significant difference between the reported and proposed methods regarding accuracy and precision. Further, the validity of the proposed methods was confirmed by recovery studies via standard addition method.


Inositol-requiring enzyme 1 (IRE1) plays for AvrRpt2-triggered immunity and RIN4 cleavage in Arabidopsis under endoplasmic reticulum (ER) stress.
Many stresses induce the accumulation of unfolded and misfolded proteins in the endoplasmic reticulum, a phenomenon known as ER stress. In response to ER stress, cells initiate a protective response, known as unfolded protein response (UPR), to maintain cellular homeostasis. The UPR sensor, inositol-requiring enzyme 1 (IRE1), catalyzes the cytoplasmic splicing of bZIP transcription factor-encoding mRNAs to activate the UPR signaling pathway. Recently, we reported that pretreatment of Arabidopsis thaliana plants with tunicamycin, an ER stress inducer, increased their susceptibility to bacterial pathogens; on the other hand, IRE1 deficient mutants were susceptible to Pseudomonas syringae pv. maculicola (Psm) and failed to induce salicylic acid (SA)-mediated systemic acquired resistance. However, the functional relationship of IRE1 with the pathogen and TM treatment remains unknown. In the present study, we showed that bacterial pathogen-associated molecular patterns (PAMPs) induced IRE1 expression; however, PAMP-triggered immunity (PTI) response such as callose deposition, PR1 protein accumulation, or Pst DC3000 hrcC growth was not altered in ire1 mutants. We observed that IRE1 enhanced plant immunity against the bacterial pathogen P. syringae pv. tomato DC3000 (Pst DC3000) under ER stress. Moreover, TM-pretreated ire1 mutants were more susceptible to the avirulent strain Pst DC3000 (AvrRpt2) and showed greater cell death than wild-type plants during effector-triggered immunity (ETI). Additionally, Pst DC3000 (AvrRpt2)-mediated RIN4 degradation was reduced in ire1 mutants under TM-induced ER stress. Collectively, our results reveal that IRE1 plays a pivotal role in the immune signaling pathway to activate plant immunity against virulent and avirulent bacterial strains under ER stress.


Endoscopic Spine Surgery of the Cervicothoracic Spine: A Review of Current Applications.
Endoscopic spine surgery in the cervicothoracic spine is generating continued interest in a rapidly evolving field. The authors present 4 techniques for fully endoscopic cervical spine surgery: (1) posterior cervical unilateral laminectomy and bilateral decompression, (2) posterior cervical foraminotomy, (3) anterior cervical discectomy, and (4) anterior transcorporal discectomy. Two techniques for fully endoscopic thoracic spine surgery are also presented: (1) posterior thoracic unilateral laminectomy and bilateral decompression and (2) transforaminal thoracic endoscopic discectomy and foraminotomy. We describe 6 different surgical approaches and review the relevant literature about each technique. The clinical application of endoscopic spine surgery techniques has evolved over the past 40 years. Recent data suggest comparable outcomes to other procedures and perhaps fewer complications and quicker recovery when these techniques are used in the cervical and thoracic spine. Significant variability exists in these approaches depending on the goal of canal decompression, root decompression, and the site of the pathology. Each endoscopic approach in the cervicothoracic spine has its technical nuances, outcomes, advantages, and disadvantages, making fully endoscopic cervicothoracic spine surgery an exciting and growing field.


Efficient internal pallidal stimulation in Gilles de la Tourette syndrome: a case report.
The usefulness of deep brain stimulation (DBS) of thalamic nuclei in Gilles de la Tourette syndrome (GTS) has recently been advocated. We report on a 14-month follow-up study of a patient with intractable GTS in whom bilateral DBS of the internal globus pallidus was carried out. Tic frequency per minute decreased by 73% in the postoperative phase and in particular the vocal tics became less intense. Pronation/ supination bradykinesia of the left extremities was a well-tolerated, permanent side effect. Pallidal DBS could become a valuable rescue therapy for otherwise intractable GTS.


Role of the 5-lipooxygenase pathway in obstructive nephropathy.
Leukotrienes are products of the 5-lipooxygenase pathway of arachidonic acid metabolism that possess potent inflammatory properties. We examined the potential role of this pathway in the decrease in glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) observed in rats after unilateral release of bilateral ureteral obstruction (BUO) of 24 hours duration. Isolated glomeruli from rats with BUO produced significantly greater amounts of leukotriene B4 (LTB4) than glomeruli from sham-operated rats (SOR; P less than 0.0001). Glomeruli from rats with BUO given MK886, an inhibitor of the 5-lipooxygenase enzyme, or from rats with BUO subjected to both total body irradiation to prevent the leukocyte infiltration of the kidney and also given MK886 prior to obstruction, produced amounts of LTB4 not significantly different from those in glomeruli of SOR. Glomeruli from rats with BUO that had only total body irradiation prior to obstruction produced significantly less LTB4 than glomeruli from untreated BUO rats, but LTB4 production was still significantly greater than in glomeruli from SOR. There were no significant differences in GFR among SOR, SOR given MK886, and SOR subjected to total body irradiation. However, SOR given MK886 had significantly higher ERPF and lower renal vascular resistance (RVR) than SOR not pretreated with the lipooxygenase inhibitor. Rats with BUO given MK886, or subjected to total body irradiation, or both, prior to obstruction had significantly greater GFR and ERPF values and lower RVR than untreated BUO rats. Glomeruli from rats with BUO which were not pretreated had three times the leukocytes of glomeruli from SOR. This leukocyte infiltrate was composed of macrophages (about 55%) and neutrophils (about 45%).(ABSTRACT TRUNCATED AT 250 WORDS)


Conservative treatment of endometriosis externa: the effects of danazol therapy.
This report presents the clinical responses of 39 women who underwent danazol treatment for conservative therapy of proven endometriosis. The patients were treated with 800 mg of danazol daily for a mean duration of 7.3 months and were clinically reevaluated at 16.9 months (mean) following the end of treatment. Complete subjective pain relief was noted in 38 patients (97%) within 6 weeks of the onset of danazol therapy. One patient noted only partial amelioration of pain. Recurrence of pain was noted in 38% of all patients at a mean of 6.9 months following therapy. More advanced disease was associated with an increased likelihood and rapidity of recurrence. Twenty-nine of the women were infertile. After treatment, nine conceived (33%). However, when patients with infertility potentially due to other causes also present were excluded, the corrected pregnancy rate was 56%. The side effects of danazol therapy were minimal and cleared rapidly following termination of the drug. These results compare favorably with other study populations where recurrence of disease and corrected pregnancy rates were specifically considered.


Presence of protein at the termini of intracellular adenovirus type 5 DNA.
Adenovirus type 5 contains linear double-stranded DNA with protein covalently attached to the ends of the molecules. The presence of protein at the termini of intracellular viral DNA in adenovirus type 5-infected cells was investigated at different stages during the replication process. The intracellular viral DNA was isolated from the nuclei by lysis in 4 M guanidine hydrochloride. Electrophoresis on agarose gels of HsuI restriction enzyme fragments and sucrose gradient centrifugation were used to detect protein on intracellular viral DNA. After uncoating parental DNA still contains protein attached to the termini of the viral genome. Replicating and mature progeny viral DNA can also be isolated in the form of DNA-protein complexes. These complexes exhibit the same properties as the DNA-protein complex isolated from purified virions. These results suggest that the protein at the termini of intracellular viral DNA is identical to the protein attached to the 5'-ends of the DNA extracted from virions and that it is possibly involved in the replication of viral DNA.


"Spontaneous" seizing in open-field tests by mongolian gerbils fed magnesium at different rates.
Accounts of so-called "spontaneous" seizures by individual Mongolian gerbils during open-field tests resemble descriptions of magnesium tetany. A possible association between relative magnesium deficiency and tendency toward "spontaneous" seizures was explored through feeding groups of gerbils different rates of magnesium and subjecting the groups to open-field tests at intervals. Hypomagnesemia was related in degree of severity to length of survival, onset of seizing, and frequency of seizures.


Sensorimotor recovery from cortical injury is accompanied by changes on norepinephrine and serotonin levels in the dentate gyrus and pons.
Monoamines such as norepinephrine (NE) and serotonin (5-HT) have shown to play an important role in motor recovery after brain injury. The effects elicited by these neurotransmitters have been reported as distal from the area directly affected. Remote changes may take place over minutes to weeks and play an important role in post-stroke recovery. However, the mechanisms involved in spontaneous recovery have not been thoroughly delineated. Therefore, we determined the NE and 5-HT content, in the pons and hippocampal dentate gyrus (DG) as well as motor deficit and spontaneous activity in rats after 3, 10 and 20 days cortical iron injection. Three days post-lesion the pontine NE content diminished, this effect was accompanied by deficient spontaneous activity and impaired sensorimotor evaluation. Ten and twenty days after lesion the NE levels were similar to those of control group, and animals also showed behavioral recovery. Monoamines content on DG 3 days post-lesion showed no differences as compared to controls. Interestingly, ten and twenty days after cortical injury, animals showed increased NE and 5-HT. These results suggest that behavioral recovery after brain damage involve changes on monoamines levels on DG, an important structure to plastic processes. In addition, the results herein support evidence to propose these neurotransmitters as key molecules to functional recovery in the central nervous system.


MEK inhibition affects STAT3 signaling and invasion in human melanoma cell lines.
Elevated activity of the mitogen-activated protein kinase (MAPK) signaling cascade is found in the majority of human melanomas and is known to regulate proliferation, survival and invasion. Current targeted therapies focus on decreasing the activity of this pathway; however, we do not fully understand how these therapies impact tumor biology, especially given that melanoma is a heterogeneous disease. Using a three-dimensional (3D), collagen-embedded spheroid melanoma model, we observed that MEK and BRAF inhibitors can increase the invasive potential of ∼20% of human melanoma cell lines. The invasive cell lines displayed increased receptor tyrosine kinase (RTK) activity and activation of the Src/FAK/signal transducers and activators of transcription-3 (STAT3) signaling axis, also associated with increased cell-to-cell adhesion and cadherin engagement following MEK inhibition. Targeting various RTKs, Src, FAK and STAT3 with small molecule inhibitors in combination with a MEK inhibitor prevented the invasive phenotype, but only STAT3 inhibition caused cell death in the 3D context. We further show that STAT3 signaling is induced in BRAF-inhibitor-resistant cells. Our findings suggest that MEK and BRAF inhibitors can induce STAT3 signaling, causing potential adverse effects such as increased invasion. We also provide the rationale for the combined targeting of the MAPK pathway along with inhibitors of RTKs, SRC or STAT3 to counteract STAT3-mediated resistance phenotypes.


Induction of apoptosis by Paljin-Hangahmdan on human leukemia cells.
Paljin-Hangahmdan is an Oriental herbal formulation under intensive investigation for its ability to modulate growth and survival in cancer cells. This research was performed to study the anticancer effects of Paljin-Hangahmdan water extract (PHWE) in human promyelocytic leukemia (HL-60) cells. After HL-60 cells were routinely cultured, tetrazolium-based colorimetric assay was performed for cytotoxicity test. Cytotoxicity of PHWE (200-800 microg/ml) in HL-60 cells was increased in a dose- and time-dependent manner. However, PHWE (200-800 microg/ml) had less cytotoxicity in peripheral blood mononuclear cells isolated from a healthy subject. To explore the mechanism of cytotoxicity, we used several measures of apoptosis to determine whether these processes were involved in PHWE-induced leukemic cell death. Our results showed PHWE induced the cell shrinkage, cell membrane blebbing, apoptotic body, and DNA fragmentation. In addition, the flow cytometric analysis revealed PHWE (200-800 microg/ml) dose-dependently increased apoptotic cells with hypodiploid DNA contents. These results indicate that PHWE can control leukemic HL-60 cells through apoptosis and may have a possibility of potential anticancer activities.


TP53 polymorphism may contribute to genetic susceptibility to develop Hashimoto's thyroiditis.
p53, which is encoded by the tumor suppressor gene TP53, plays a crucial role in the regulation of mechanisms of cell cycle arrest and apoptosis. Some SNPs of TP53, involving a different apoptotic ability of p53, have been associated with increased susceptibility to develop autoimmune diseases as well as cancer. We investigated the genotypic distribution of TP53 exon 4 SNPs in a cohort of Caucasian patients affected by Hashimoto's thyroiditis (HT). Peripheral blood for DNA extraction was collected from 109 Caucasian unrelated subjects, 79 HT patients and 30 healthy controls. SNPs analysis was carried out by amplification and sequencing of exon 4 TP53. For the Pro72Arg (rs 1042522) SNP we found these rates in HT patients: 11.4% wild-type C/C (Pro72Pro), 24.0% heterozygous G/C (Pro72Arg), 64.6% homozygous G/G (Arg72Arg). The corresponding rates in healthy controls were 10, 46.7 and 43.3%, respectively. Thus, significantly different were G/C heterozygosity (24.0 vs 46.7 %, p = 0.039) and G/G homozygosity (64.6 vs 43.3%, p = 0.042). These differences were also confirmed when comparing our study population to published Caucasian control groups. The other described SNPs (Pro34Pro rs 11575998, Pro36Pro rs1800370, Pro47Ser rs1800371, and Arg110Leu rs 11540654) were absent or very rare in our study population. Our preliminary data, the first on a Caucasian population, indicate an increased prevalence of the homozygous genotype Arg/Arg and a decreased prevalence of heterozygous genotype Arg/Pro of rs 1042522 in HT patients compared to controls, suggesting that such SNP may contribute to confer susceptibility to HT.


The trinomial health, safety and happiness promote rural tourism.
Health and safety protocols have become a requirement to promote rural tourism (PRT). From this perspective, this paper empirically analyses how the health and safety dimensions influence the happiness of hotel managers and rural tourists in the post-Covid 19 era. A theory-based structural equation model will be carried out of activation of norms, that measure variables: sanitary, socioeconomic, and safety. Precisely, we will measure how those three attributes affect the managers-guests' health in rural areas and their search for happiness at the rural destination. Based on the above, a field of study has been 215 rural tourist accommodations in the Extremadura region (Spain) and a sample population of 443 guests. Data were organised through the SEM-PLS path modelling. The results achieved statistically show the need to undertake a new model of healthier and safer tourism consumption that values the tourist resources of rural areas, especially nearby and sustainable destinations, based on the guiding principles of safety, health, and happiness. The first conclusion is that promoting tourist destinations under safe and healthy conditions has become a priority objective in the tourism industry. The second conclusion that follows from the first is that the variables safety and health and the pursuit of happiness are essential factors in promoting tourist destinations for rural hotel managers and rural tourists. The third conclusion related to the first two is that the opportunity that this study provides to develop strategies of an innovative, sustainable, and creative nature based on the relationships of the new trinomial of health, safety and happiness, from the perspective of happiness management.


A long-term clinical follow-up study after arthroscopic intra-articular Bankart repair using absorbable tacks.
The aim of the study was to perform an independent long-term evaluation after arthroscopic Bankart repair using absorbable tacks. We hypothesise that arthroscopic Bankart repair using absorbable tacks will result in stable shoulders. Eighty-one consecutive patients (84 shoulders) with symptomatic, recurrent, anterior, post-traumatic shoulder instability were included in the study. All the patients had a Bankart lesion. The age of the patients was 28 (15-62) years. The number of dislocations prior to surgery was five (sublux-50). The operation was performed 28 (3-360) months after the index injury by one of three surgeons with a special interest in shoulder surgery using an intra-articular arthroscopic Bankart procedure involving absorbable Suretac fixators. Seventy-six/84 (90%) of the shoulders (50 male, 23 female patients) were re-examined by two independent observers, after a follow-up period of 98 (46-129) months. In the long-term, the failure rate in terms of stability was 8/76 (11%) dislocations and a further 6/76 (8%) had experienced or had clinical signs of subluxation. The Rowe score was 91 (38-98) points at follow-up and the Constant score was 90 (56-100) points. The Constant score for the contralateral shoulder was 93 (69-100) points (P < 0.001). In the long-term, the arthroscopic Bankart procedure using Suretac fixators resulted in stable, well-functioning shoulders in the majority of patients. Eighteen per cent of the patients had experienced signs of instability during the follow-up period in terms of dislocations or subluxations.


DNA ploidy of primary hepatocellular carcinoma and pulmonary metastases.
To better comprehend the differences in deoxyribonucleic acid (DNA) content between a primary hepatocellular carcinoma (HCC) and pulmonary metastatic nodules, tissue specimens taken at autopsy of 25 patients who had not received any drugs to treat the malignancy were examined using microspectrophotometry. The DNA distribution patterns were classified into Types I-III, and low (Types I and II) or high (Type III) ploidies, according to DNA distribution. Changes in the DNA content from high to low ploidies, namely DNA ploidy reduction from the primary lesion to pulmonary metastatic lesions, was evident in 9 of the 25 patients (36%), and changes from low to high were noted in 2 of the 25 patients (8%). The remaining 14 (56%) showed no evidence of changes in the DNA ploidy pattern. Reduction of DNA ploidy seen in HCC and its metastatic lesions in the lung may be one of the aspects of clonal evolution or selection mechanisms during the progression of tumor growth and metastasis.


Visual evoked responses to pattern-reversal stimulation in patients with amblyopia and/or defective binocular functions.
The visual evoked responses to monocular and binocular pattern-reversal stimulation were recorded in ten normal subjects and in ten cases with amblyopia and/or defective binocular functions. Seven of the ten patients showed a considerable amplitude asymmetry to monocular stimulation or lack of normal increase of amplitude to binocular stimulation. Two patients displayed prolonged latency on stimulation of the amblyopic eye.


Normal variations in personality are associated with coital orgasmic infrequency in heterosexual women: a population-based study.
As many as 20-30% of women report an inability to orgasm during sexual intercourse. Some female sexual problems have been reported to cluster with psychological and social problems. Underlying personality type may play a role in the development or maintenance of such problems. The aim of this study was to investigate whether certain domains of personality are associated with female coital orgasmic infrequency. To our knowledge this is the first such study in a large unselected population. A total of 2632 women (mean age 51) from the TwinsUK registry completed questionnaires relating to personality and sexual behavior. Personality domains were assessed using the validated Ten-Item Personality Index (TIPI). Coital orgasmic frequency was measured using a seven-point Likert scale. Using logistic regression, we investigated whether variations in five domains of personality are associated with female coital orgasmic infrequency. Discordant twin analysis was used to verify findings. Introversion (odds ratio [OR] 2.5, 95% confidence interval [CI] 1.7-3.7), emotional instability (OR 2.0, 95% CI 1.3-3.1), and not being open to new experience (OR 2.4, 95% CI 1.6-3.6) were significantly associated with orgasmic infrequency, whereas indices of agreeableness and conscientiousness were not significantly associated with orgasm frequency. Specific personality subtypes appear to be significant risk factors for orgasmic infrequency. Consideration of these behavioral risk factors may need to be incorporated into research into female orgasmic disorder, and possible approaches to its treatment.


Testicular cancer risk according to county of birth and county of diagnosis in Norway, 1958-2007.
The etiology of testicular germ cell cancer (TGCC) is still poorly understood, but biological and epidemiological evidence suggest that TGCC originates early in life. The aim of the present study was to analyze heterogeneity in TGCC risk within Norway, comparing county of birth to county of diagnosis, in order to assess the relative contribution of risk factors acting early and later in life. A further aim was to present the Norwegian TGCC incidence rates (1958-2007). All TGCC cases (n = 7130) reported to the Cancer Registry of Norway, 1958-2007, were analyzed by county of diagnosis in 10-year intervals. The relative risk of TGCC based on county of birth, was estimated by Poisson regression analysis of all new TGCC cases (n = 1943), based on the mother's county of residence at the time of the son's birth, 1967-2007, obtained by linkage between the Cancer Registry and the Medical Birth Registry of Norway. Between the first (1958-67) and last (1998-2007) 10-year period, the average incidence rate more than tripled from 3.3 to 10.5 per 100 000 person-years (world adjusted), respectively. The average incidence rate during 1968-2007 was highest in the county of Rogaland (8.6) and lowest in Hedmark (5.3), the ratio between them being 1.6. The relative risk of TGCC based on county of birth (1967-2007) varied between 1.43 (Møre og Romsdal) and 0.95 (Buskerud), giving a ratio of 1.5. The ratio between the relative risk in the highest and lowest county was basically similar when comparing counties of birth with counties of diagnosis. Thus, our data do not shed light on the relative contribution of risk factors acting early versus later in life. The incidence rate of TGCC in Norway is among the highest in the world, and the increase in incidence rate does not seem to level off.


Single-cell lipidomics enabled by dual-polarity ionization and ion mobility-mass spectrometry imaging.
Single-cell (SC) analysis provides unique insight into individual cell dynamics and cell-to-cell heterogeneity. Here, we utilize trapped ion mobility separation coupled with dual-polarity ionization mass spectrometry imaging (MSI) to enable high-throughput in situ profiling of the SC lipidome. Multimodal SC imaging, in which dual-polarity-mode MSI is used to perform serial data acquisition runs on individual cells, significantly enhanced SC lipidome coverage. High-spatial resolution SC-MSI identifies both inter- and intracellular lipid heterogeneity; this heterogeneity is further explicated by Uniform Manifold Approximation and Projection and machine learning-driven classifications. We characterize SC lipidome alteration in response to stearoyl-CoA desaturase 1 inhibition and, additionally, identify cell-layer specific lipid distribution patterns in mouse cerebellar cortex. This integrated multimodal SC-MSI technology enables high-resolution spatial mapping of intercellular and cell-to-cell lipidome heterogeneity, SC lipidome remodeling induced by pharmacological intervention, and region-specific lipid diversity within tissue.


Quality assurance of monoclonal antibody pharmaceuticals based on their charge variants using microchip isoelectric focusing method.
Monoclonal antibody (mAb) pharmaceuticals are much more complex than small-molecule drugs. Such complex characteristics raise challenging questions for regulatory evaluation. Although heterogeneity in mAbs based on their charge variants has been mainly evaluated using gel-based isoelectric focusing (IEF) method, recent development in capillary electrophoresis and microchip electrophoresis has made it possible to assure their heterogeneities in more easy and rapid manner. In the present paper, we customized the imaged microchip isoelectric focusing (mIEF) for the analysis of mAbs, and compared the customized version with the conventional capillary isoelectric focusing (cIEF) method, and found that mIEF has much higher performance in operations, and its resolving powers are comparable with those obtained by cIEF.


A two-step mitochondrial import pathway couples the disulfide relay with matrix complex I biogenesis.
Mitochondria critically rely on protein import and its tight regulation. Here, we found that the complex I assembly factor NDUFAF8 follows a two-step import pathway linking IMS and matrix import systems. A weak targeting sequence drives TIM23-dependent NDUFAF8 matrix import, and en route, allows exposure to the IMS disulfide relay, which oxidizes NDUFAF8. Import is closely surveyed by proteases: YME1L prevents accumulation of excess NDUFAF8 in the IMS, while CLPP degrades reduced NDUFAF8 in the matrix. Therefore, NDUFAF8 can only fulfil its function in complex I biogenesis if both oxidation in the IMS and subsequent matrix import work efficiently. We propose that the two-step import pathway for NDUFAF8 allows integration of the activity of matrix complex I biogenesis pathways with the activity of the mitochondrial disulfide relay system in the IMS. Such coordination might not be limited to NDUFAF8 as we identified further proteins that can follow such a two-step import pathway.


Association of 71 cardiovascular disease-related plasma proteins with pulmonary function in the community.
It has been speculated that shared mechanisms underlie respiratory and cardiovascular diseases (CVD) including systemic inflammation or mutual risk factors. In this context, we sought to examine the associations of CVD-related plasma proteins with lung function as measured by spirometry in a large community-based cohort of adults. The study included 5777 Framingham Heart Study participants who had spirometry and measurement of 71 CVD-related plasma proteins. The association of plasma proteins with lung function was assessed cross-sectionally and longitudinally using models accounting for familial correlations. Linear mixed models were used for the following measurements: FEV1%predicted, FVC%predicted, and FEV1/FVC ratio with secondary analyses examining obstructive and restrictive physiology at baseline and their new onset during follow up. Among the 71 CVD-related plasma proteins, 13 proteins were associated in cross-sectional analyses with FEV1%predicted, 17 proteins were associated with FVC%predicted, and 1 protein was associated with FEV1/FVC. The proteins with the greatest inverse relations to FEV1%predicted and FVC%predicted included leptin, adrenomedullin, and plasminogen activator inhibitor-1; in contrast there were three proteins with positive relations to FEV1%predicted and FVC%predicted including insulin growth factor binding protein 2, tetranectin, and soluble receptor for advanced glycation end products. In longitudinal analyses, three proteins were associated with longitudinal change in FEV1 (ΔFEV1) and four with ΔFVC; no proteins were associated with ΔFEV1/FVC. Our findings highlight CVD-related plasma proteins that are associated with lung function including markers of inflammation, adiposity, and fibrosis, representing proteins that may contribute both to respiratory and CVD risk.


SF3B14 is involved in the centrosome regulation through splicing of TUBGCP6 pre-mRNA.
Splicing precursor messenger RNA (pre-mRNA) is a critical step to produce physiologically functional protein. Splicing failure not only gives rise to dysfunctional proteins but also generates abnormal protein function, which causes several diseases. Several pre-mRNA splicing factors are reported to regulate mitosis directly at mitotic structures and/or indirectly through controlling the pre-mRNA splicing for mitotic proteins. In this study, we described the mitotic functions of SF3B14, a component of the spliceosomal U2 small nuclear ribonucleoprotein (snRNP), which we identified as a candidate involved in mitosis based on the large-scale RNA interference (RNAi) screen of the nucleolar proteome database. We observed that SF3B14 depletion caused prolonged mitosis and several mitotic defects, such as monopolar spindle and chromosome misalignment during metaphase. Although SF3B14 was found in the nucleolar proteome database, our immunofluorescent stainings demonstrated that SF3B14 was predominantly localized in the nucleoplasm and excluded from the nucleolus during interphase. In addition, SF3B14 did not colocalize with specific mitotic structures during mitosis, which is not in line with its direct mitotic function. Notably, we found that the SF3B14 depletion reduced protein levels of TUBGCP6, required for centrosome regulation, and increased the unspliced/spliced ratio of its mRNA. Taken together, we propose that the pre-mRNA of TUBGCP6 is one of the targets for SF3B14 splicing through which SF3B14 controls mitotic chromosome behavior.


A sodium-ion sulfide solid electrolyte with unprecedented conductivity at room temperature.
Solid electrolytes are key materials to enable solid-state rechargeable batteries, a promising technology that could address the safety and energy density issues. Here, we report a sulfide sodium-ion conductor, Na2.88Sb0.88W0.12S4, with conductivity superior to that of the benchmark electrolyte, Li10GeP2S12. Partial substitution of antimony in Na3SbS4 with tungsten introduces sodium vacancies and tetragonal to cubic phase transition, giving rise to the highest room-temperature conductivity of 32 mS cm-1 for a sintered body, Na2.88Sb0.88W0.12S4. Moreover, this sulfide possesses additional advantages including stability against humid atmosphere and densification at much lower sintering temperatures than those (>1000 °C) of typical oxide sodium-ion conductors. The discovery of the fast sodium-ion conductors boosts the ongoing research for solid-state rechargeable battery technology with high safety, cost-effectiveness, large energy and power densities.


Evaluation of the anticonvulsant and biochemical activity of CGS 8216 and CGS 9896 in animal models.
CGS 8216, a benzodiazepine-receptor ligand with inverse agonistic properties, and CGS 9896, which possesses partial agonistic or mixed agonist-antagonist properties were compared in a number of epilepsy models. The effect of CGS 9896 on the decrease in GABA levels induced by isoniazid was also investigated. CGS 9896 inhibited the kindling process in rats in that it delayed the development of overt seizures and the increase in the duration of afterdischarges. In a genetic rat model characterized by absence-like EEG patterns, CGS 9896 dose-dependently suppressed these spontaneously occurring discharges, while CGS 8216 had no effect. However, CGS 8216 antagonized the anticonvulsant action of CGS 9896. CGS 9896 protected mice against seizures induced by beta-vinyllactic acid, whereas CGS 8216 shortened the latency period before convulsions occurred. CGS 9896 retarded the onset of convulsive fits caused by isoniazid without preventing the decrease in GABA levels produced by that drug. These results confirm the anticonvulsant activity of CGS 9896 and demonstrate the inverse agonistic activity of CGS 8216. The profile of CGS 9896 in the above tests suggests that it might be an effective anticonvulsant, primarily in absence-type seizures.


Ethical issues in end-of-life geriatric care: the approach of three monotheistic religions-Judaism, Catholicism, and Islam.
Ethical dilemmas pervade modern geriatric medicine. What is considered right or wrong will differ depending on, among other things, the patient's religion. The three Abrahamic monotheistic religions, Judaism, Christianity (its Catholic variant), and Islam all have carefully considered positions on medical ethics. Although much is held in common, there are significant differences. The authors present three clinical cases, each of which presents ethical dilemmas typical of geriatric care, especially at the end of life. On the basis of these scenarios, the normative ethical position of each religion is compared and contrasted. It is hoped that this approach will offer the geriatrician a useful approach to treating patients in an increasingly multicultural society.


Decreased Interferon γ Production in CD3+ and CD3- CD56+ Lymphocyte Subsets in Metastatic Regional Lymph Nodes of Melanoma Patients.
As lymphogenic dissemination is very common in melanoma, regional lymph nodes (LN)s represent first immunological barriers to tumor invasion and play a complex role in antitumor immune defense. In this sense, their most prominent role is the presentation of tumor-derived antigens to naïve T cells and generation of cell-mediated adaptive immune response. Since tumor micro-environment affects immune cell function in this study we have evaluated the ability of T cells and NK cells in metastatic (involved) and non-metastatic regional LNs to produce interferon γ (IFNγ), a pleiotropic cytokine that regulates adaptive antitumor immune response. Our results show reduced IFNγ production in both T and NK lymphocyte subsets and decreased prevalence of T cells in metastatic regional LNs of melanoma patients. The decrease of IFNγ production in T cells was more pronounced with increased number of involved regional LNs indicating tumor-induced functional impairment of both T and NK cell lymphocyte subsets in involved regional LNs. Therefore, shown low IFNγ production in metastatic LNs may represent an obstacle in adaptive cell-mediated antitumor immune response and hence may enable tumor progression.


Effect of weight loss after bariatric surgery on left ventricular mass and ventricular repolarization in normotensive morbidly obese patients.
To assess the effect of weight loss on ventricular repolarization in morbidly obese patients, 39 normotensive subjects whose baseline body mass indexes were ≥40 kg/m(2) before weight loss from bariatric surgery were studied. All patients were free of underlying organic heart disease, heart failure, and conditions that might affect ventricular repolarization. Twelve-lead electrocardiography and transthoracic echocardiography were performed just before surgery and at the nadir of postoperative weight loss. The corrected QT interval (QTc) was derived using Bazett's formula. QTc dispersion was calculated by subtracting the minimum from the maximum QTc on the 12-lead electrocardiogram. Echocardiographic left ventricular (LV) mass was indexed to height(2.7). The mean body mass index decreased from 42.8 ± 2.1 to 31.9 ± 2.2 kg/m(2) (p <0.0005). For the entire group, weight loss was associated with significant reductions in mean QTc (from 428.7 ± 18.5 to 410.5 ± 11.9 ms, p <0.0001) and mean QTc dispersion (from 44.1 ± 11.2 to 33.2 ± 3.3 ms, p <0.0005). Mean QTc and QTc dispersion decreased significantly with weight loss in patients with LV hypertrophy but not in subjects without LV hypertrophy. Multivariate analysis identified pre-weight loss LV mass/height(2.7) as the most important predictor of pre-weight loss QTc and QTc dispersion and also identified weight loss-induced change in LV mass/height(2.7) as the most important predictor of weight loss-induced changes in QTc and QTc dispersion. In conclusion, LV hypertrophy is a key determinant of QTc and QTc dispersion in normotensive morbidly obese patients. Regression of LV hypertrophy associated with weight loss decreases QTc and QTc dispersion.


The critical closing pressure of the cerebral circulation.
The critical closing pressure (CrCP) of the cerebral circulation indicates the value of arterial blood pressure (ABP) at which cerebral blood flow (CBF) approaches zero. Measurements in animals and in humans, have shown that the CrCP is significantly greater than zero. A simple mathematical model, incorporating the effects of arterial elasticity and active wall tension, shows that CrCP can be influenced by several structural and physiological parameters, notably intracranial pressure (ICP) and active wall tension. Due to the non-linear shape of the complete ABP-CBF curve, most methods proposed for estimation of CrCP can only represent the linear range of the pressure-flow (or velocity) relationship. As a consequence, only estimates of apparent CrCP can be obtained, and these tend to be significantly higher than the true CrCP. Estimates of apparent CrCP have been shown to be influenced by arterial PCO2, ICP, cerebral autoregulation, intra-thoracic pressure, and mean ABP. There is a lack of investigation, under well-controlled conditions, to assess whether CrCP is altered in disease states. Studies of the cerebral circulation need to take CrCP into account, to obtain more accurate estimates of cerebrovascular resistance changes, and to reflect the correct dynamic relationship between instantaneous ABP and CBF.


REM latency: development in the first year of life.
The development of REM latency in the first year of life was investigated in two groups of 10 infants each. While 10 infants were normal, the other 10 underwent continuous feeding for various gastrointestinal diseases. Each infant was continuously recorded polygraphically for 24 h. While younger infants (less than or equal to 3 months) manifested predominantly shorter REM latencies (less than or equal to 8 min), older infants (4-13 months) produced a mixed distribution of short and long REM latencies. The total distribution of the REM latencies appears to be bimodal with latencies either shorter than 8 min or longer than 16 min. It is only in the group of older infants that the temporal distribution of REM latencies constitutes a diurnal rhythm, with the longest latencies in the interval between 12:00 and 16:00 and the shortest between 4:00 and 8:00. In the group of older infants, REM latency also depends on the duration of prior wakefulness. Long REM latencies are significantly more often preceded by long episodes of wakefulness than are short REM latencies. The different feeding conditions had only a minor effect on REM latency.


Acute effects of methylenedioxymethamphetamine (MDMA) on several complex brain functions in monkeys.
The effects of MDMA were assessed in rhesus macaques using behavior in an operant test battery (OTB) consisting of five food-reinforced tasks designed to model aspects of time estimation, short-term memory, and attention, motivation, learning, and color and position discrimination. Testing occurred 30 min after intramuscular, injections of MDMA (0.0, 0.1, 0.3, and 1.0 mg/kg). The behavioral endpoints monitored included percent task completed, response rate or latency, and response accuracy. Percent task completed was significantly decreased in the time estimation, learning, and motivation tasks at 1.0 mg/kg as compared to saline controls. Response accuracies in the time estimation and learning tasks were also decreased at 1.0 mg/kg. Response rate was decreased at 1.0 mg/kg in the motivation task but was not significantly affected in any other tasks. No behavioral endpoints were significantly affected in the short-term memory and attention and color and position discrimination tasks at any dose tested. Results indicate that time estimation, motivation, and learning are more sensitive to the acute effects of MDMA than are short-term memory and attention and color and position discrimination.


Spread of COVID-19 and policy responses in Vietnam: An overview.
Despite the proximity and high travel flows with China, Vietnam has been able to contain the spread of coronavirus disease 2019 (COVID-19). This study describes the characteristics of COVID-19 infections in Vietnam and policy responses to identify potential factors contributing to the relative success of Vietnam in containing this pandemic. Narrative analyses were applied to describe the pandemic and policy responses. Descriptive statistics, generalized linear regression, and a susceptible-infected-recovered model were used to explore the effectiveness of Vietnamese policy responses to COVD-19. To date, Vietnam is one of the few countries that have successfully control the spread of COVID-19. As of 26 October 2020, Vietnam has had 1169 cases of COVID-19, of which 1061 people recovered and 35 people died from the disease. COVID-19 infected patients in Vietnam were relatively younger than those in other countries with an average age of 36. Most of the infected cases were from international travels. Policy responses in Vietnam were implemented early and strictly. Despite the proximity to China, where COVID-19 emerged, Vietnam has experienced a small number of COVID-19 infections and fatalities compared with other countries. Most infected patients were relatively young, and exposure was attributed to international travel. Early policy interventions were the main factors that contributed to the success of Vietnam to date.


Pelviureteric junction obstruction. The value of a post-micturition view in 99mTc DTPA diuretic renography.
Eighty-one 99mTc DTPA renograms were performed in 31 children who had previously undergone pyeloplasty for pelviureteric junction obstruction (PUJ). A post-micturition image following a diuretic stimulus excluded obstruction in 50% of the patients in whom the frusemide T75 was abnormally prolonged beyond 10 min. Evaluating the 99mTc DTPA renogram and the response to a diuretic without both changing the patient's position and ensuring an empty bladder may lead to incorrect diagnosis of PUJ obstruction.


Regeneration of the neurogliovascular unit visualized in vivo by transcranial live-cell imaging.
Functional imaging in behaving animals is essential to explore brain functions. Real-time optical imaging of brain functions is limited by light scattering, skull distortion, timing resolution and subcellular precision that altogether, make challenging the rapid acquisition of uncorrupted functional data of cells integrated de novo in the neurogliovascular unit. We report multimodal transcranial in vivo optical imaging for the fast and direct visualization of microcirculation in the perfusion domain where new cells incorporated in the neurogliovascular unit during the progression of a seizure disorder and its treatment. Using this methodology, we explored the performance improvement of cells integrated de novo in the neurogliovascular unit. We report fast transcranial imaging of blood microcirculation at sites of pericyte turnover in the epileptic brain and after treatment with a trophic factor that revealed key features of the regenerating neurogliovascular unit.


[Genital location of a clear-cell hidradenoma].
Clear cell hidradenoma of the penile prepuce progressing to malignancy transformation is rare and arises from the adnexal glands of the skin. It may present in nodular or ulcerated forms, which make it almost impossible to distinguish from spinocellular carcinoma. Treatment is by wide surgical excision. Local recurrence and distant metastasis rare.


Regio- and Stereoselective Synthesis of Enol Carboxylate, Phosphate, and Sulfonate Esters via Iodo(III)functionalization of Alkynes.
β-Iodo(III)enol carboxylates, phosphates, and tosylates can be efficiently synthesized through regio- and stereoselective iodo(III)functionalization of alkynes. The combination of chlorobenziodoxole and silver salt has proven to generate a versatile cationic iodine(III) electrophile to activate alkynes and engage various carboxylic acids, triethyl phosphate, and p-toluenesulfonic acid as nucleophiles. The β-iodo(III)enol esters serve as starting materials for the synthesis of multisubstituted alkenes through sequential cross-coupling of the C-I(III) and C-O bonds.


Quantification of tumor vascularity with contrast-enhanced ultrasound for early response of transcatheter arterial chemoembolization for hepatocellular carcinoma: a report of three cases.
Many contrast-enhanced ultrasound (CE-US) studies have been conducted by qualitative analysis of blood flow, such as classification of enhancement pattern. We evaluated early response of transcatheter arterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) by quantitative analysis of intratumoral vascularity with CE-US in three patients. Three patients (one man, two women) with HCCs were treated in July 2009. CE-US with perfluorocarbon microbubbles (Sonazoid) and CT were performed serially before and 5 days after TACE. Post-processing enhancement intensity on US was analyzed to determine mean transit time (s), time to peak (s), enhancement peak intensity (dB), and "A" (scaling factor) by ultrasound quantification software after the data were fitted to a gamma variate curve. Mean transit time was prolonged by TACE in all three patients. Mean transit time rates on CE-US were 64.3, 33.8, and 65.6%, respectively, whereas the avascular rates on CT were 59.07, 31.71, and 62.25%, respectively. Mean transit time rates on CE-US approximated avascular rates on CT. Mean transit time rate may quantitatively indicate the early response of HCC to TACE.


Cerebral hemodynamic change and metabolic alteration in severe hemorrhagic shock.
Understanding the biological mechanism and identifying biomarkers of hemorrhagic shock is important for diagnosis and treatment. We aim to use optical imaging to study how the cerebral blood circulation and metabolism change during the progression of severe hemorrhagic shock, especially the decompensatory stage. We used a multi-parameter (blood pressure (BP), cerebral blood flow (CBF), functional vascular density (FVD), blood oxygenation and mitochondrial NADH signal) cerebral cortex optical imaging system to observe brain hemodynamic change and metabolic alteration of rats in vivo for 4 h. Cerebral circulation and mitochondrial metabolism could be well preserved in the compensatory stage but impaired during the decompensatory stage. The changes of brain hemodynamics and metabolism may provide sensitive indicators for various shock stages including the transition from compensatory stage to decompensatory stage. Our novel imaging observations of hemodynamic and metabolic signals in vivo indicated that the rat brains under hemorrhagic shock suffered irreversible damage which could not be compensated by the autoregulation mechanism, probably due to injured mitochondria.