Temperature-controlled radiofrequency tonsil ablation for the treatment of halitosis.
The objective of the study was to evaluate the efficacy and safety of temperature-controlled radiofrequency (RF) tonsil ablation in the treatment of halitosis caused by chronic tonsillitis with caseum. The study method was retrospective. The medical records of 58 patients undergoing temperature-controlled RF tonsil ablation due to chronic tonsillitis with caseum between November 1, 2005 and November 30, 2008 were reviewed. Forty-nine (84.4%) of 58 patients reported complete disappearance of bad breath after the first treatment; five patients (8.6%) reported as having insufficient improvement and four (6.9%) patients had no change. Two patients from "insufficient group" and all four patients from "no change" group agreed to a repeat treatment. After the second session, four (6.9%) patients reported complete disappearance of halitosis with the disappearance of caseum formation. But two patients still suffered from halitosis. One of these patients underwent tonsillectomy, other patient is under our follow-up. Overall, complete elimination of halitosis was accomplished with one session in 49 (84.4%) patients, two sessions in four (6.9%) patients, making a total of 53 (91.3%) patients. Postoperative morbidities included one transient mild bleeding, one secondary bleeding and one mild edema. Temperature-controlled RF tonsil ablation is an effective method for treating halitosis which derived from chronic tonsillitis with caseum. This well-tolerated technique avoids the post-procedure morbidities and discomfort of more invasive surgical modalities currently used.


Development of a PCR system for the characterisation of Salmonella flagellin genes.
Analysis of flagellin genes was carried out on strains of Salmonella Typhimurium, Salmonella Hadar, Salmonella Abortusequi, Salmonella Enteritidis and Salmonella Gallinarum serovars, using a PCR system designed in this study. The purpose of these studies was to explore the flagellin genes of biphasic and monophasic Salmonellae for future targeted genetic interventions. The PCR primers were designed for two different structural genes of flagellin (fliC, fljB), for the repressor of fliC (fljA), for the operator region of fliC, and for the invertase system responsible for phase variation in Salmonella (hin, hixL, hixR). PCR analysis revealed that all of the examined genes (fliC, fliC-operator, fljB, fljA, hin, hixL, hixR) were present in all S. Typhimurium (n = 10) and S. Hadar (n = 10) strains tested. The results obtained on S. Typhimurium and S. Hadar strains confirmed their biphasic character at DNA level. However, the S. Enteritidis (n = 46) and S. Gallinarum (n = 5) strains lacked the invertase system (hin, hixL, hixR) as well as the fljA and fljB genes, while fliC and its operator were detectable. Consequently, the S. Enteritidis strains could only express fliC gene resulting in phase H1 flagellin. The examined S. Gallinarum strains were also demonstrated to have a cryptic flagellin gene (fliC). On the other hand, PCR results on S. Abortusequi (n = 2) indicated that both flagellin genes (fliC, fljB) and the whole phase variation system were present in both strains tested but only the H2 phase gene (fljB) was expressed. The phenotype of these strains could be clarified by motility test and/or by classical flagellar serology. The findings are also substantiated by the results of serovar-specific PCR for S. Typhimurium and S. Enteritidis. In conclusion, the PCR system developed in this study proved to be suitable for characterisation of Salmonella flagellin genes and confirmed serological results regarding all S. Typhimurium, S. Hadar and S. Enteritidis strains. This system could also identify cryptic flagellar genes of S. Abortusequi and S. Gallinarum.


[The situation in the German forensic commitment-Results of a survey by the DGPPN].
In German forensic psychiatry detention under Sections 63 and 64 of the German Penal Code have been repeatedly reformed over the past years; however, despite the most recent amendments to the law on detention, clinics and state authorities warn of insufficient capacities and worrying conditions. Media reports paint a defiant picture. At the same time, there is a lack of valid data that would allow an objective description of the situation in forensic psychiatry. Against this background the management of institutions in Germany has been surveyed. The survey was conducted as an online survey and sent to all 78 forensic hospitals in Germany. The survey covered topics such as structural data of the facilities, the occupancy and staffing situation, incidents, support from supervisory authorities and funding agencies, and patient characteristics. The results are presented descriptively. Of the 78 facilities contacted, 45 (approximately 60%) participated at least partially in the survey. Many of the clinics (68.5%) complained of significant overcrowding. A clear lack of staff and rooms was reported, at the same time it was stated that patients do not receive adequate treatment. Approximately 1 in 5 patients have a length of stay for more than 10 years and one third of the clinics reported an increasing number of physical assaults by patients. This overview shows that the forensic psychiatric hospitals are in very different but generally strained situations. A significant number of clinics are under great pressure. Financial, structural, spatial and personnel resources were described as insufficient to properly and professionally fulfill the legal mandate. The treatment standards presented by the DGPPN in 2017 are not met in many clinics.


Experimental Salmonella enterica serovar Pullorum infection in two commercial varieties of laying hens.
An experiment was carried out to investigate the biology of Salmonella Pullorum in two varieties of laying hens, from 5 days of age up to 9 months. One variety was resistant to systemic salmonellosis (light layers producing white eggs) and the other was considered susceptible (brown layers producing brown eggs). The brown birds were more affected by the infection, showing signs of clinical disease in the first month of life. Later, these signs disappeared, but postmortem examination revealed persistent gross pathological changes in the liver, spleen, heart and ovary. The rapid agglutination test detected reactors throughout the experiment, with the strongest agglutination from 1 to 7 months post-infection. S . Pullorum was isolated from some of the organs and the eggs laid throughout the experiment. The relationship between white birds and S . Pullorum was less intense, and there were no noticeable signs of disease. There were few gross pathological changes, and the bacteria were isolated infrequently and only for a brief period after infection, although contaminated eggs were laid by these birds. The strongest serological response in the white chickens occurred between the second and the fifth month post-infection.


Cysteine-rich intestinal protein 2 (CRIP2) acts as a repressor of NF-kappaB-mediated proangiogenic cytokine transcription to suppress tumorigenesis and angiogenesis.
Chromosome 14 was transferred into tumorigenic nasopharyngeal carcinoma and esophageal carcinoma cell lines by a microcell-mediated chromosome transfer approach. Functional complementation of defects present in the cancer cells suppressed tumor formation. A candidate tumor-suppressor gene, cysteine-rich intestinal protein 2 (CRIP2), located in the hot spot for chromosomal loss at 14q32.3, was identified as an important candidate gene capable of functionally suppressing tumor formation. Previous studies have shown that CRIP2 is associated with development. To date, no report has provided functional evidence supporting a role for CRIP2 in tumor development. The present study provides unequivocal evidence that CRIP2 can functionally suppress tumorigenesis. CRIP2 is significantly down-regulated in nasopharyngeal carcinoma cell lines and tumors. CRIP2 reexpression functionally suppresses in vivo tumorigenesis and angiogenesis; these effects are induced by its transcription-repressor capability. It interacts with the NF-κB/p65 to inhibit its DNA-binding ability to the promoter regions of the major proangiogenesis cytokines critical for tumor progression, including IL6, IL8, and VEGF. In conclusion, we provide compelling evidence that CRIP2 acts as a transcription repressor of the NF-κB-mediated proangiogenic cytokine expression and thus functionally inhibits tumor formation and angiogenesis.


The Influence of Hemorrhagic Shock on the Disposition and Effects of Intravenous Anesthetics: A Narrative Review.
The need to reduce the dose of intravenous anesthetic in the setting of hemorrhagic shock is a well-established clinical dogma. Considered collectively,; the body of information concerning the behavior of intravenous anesthetics during hemorrhagic shock, drawn from animal and human data, confirms that clinical dogma and informs the rational selection and administration of intravenous anesthetics in the setting of hemorrhagic shock. The physiologic changes during hemorrhagic shock can alter pharmacokinetics and pharmacodynamics of intravenous anesthetics. Decreased size of the central compartment and central clearance caused by shock physiology lead to an altered dose-concentration relationship. For most agents and adjuncts, shock leads to substantially higher concentrations and increased effect. The notable exception is etomidate, which has relatively unchanged pharmacokinetics during shock. Increased concentrations lead to increased primary effect as well as increased side effects, notably cardiovascular effects. Pharmacokinetic changes are essentially reversed for all agents by fluid resuscitation. Propofol is unique among agents in that, in addition to the pharmacokinetic changes, it exhibits increased potency during shock. The pharmacodynamic changes of propofol persist despite fluid resuscitation. The persistence of these pharmacodynamic changes during shock is unlikely to be due to increased endogenous opiates, but is most likely due to increased fraction of unbound propofol. The stage of shock also appears to influence the pharmacologic changes. The changes are more rapid and pronounced as shock physiology progresses to the uncompensated stage. Although scant, human data corroborate the findings of animal studies. Both the animal and human data inform the rational selection and administration of intravenous anesthetics in the setting of hemorrhagic shock. The well-entrenched clinical dogma that etomidate is a preferred induction agent in patients experiencing hemorrhagic shock is firmly supported by the evidence. Propofol is a poor choice for induction or maintenance of anesthesia in severely bleeding patients, even with resuscitation; this can include emergent trauma cases or scheduled cases that routinely have mild or moderate blood loss.


Asymptotically optimal blind estimation of multichannel images.
Optimal estimation of a two-dimensional (2-D) multichannel signal ideally decorrelates the data in both channel and space and weights the resulting coefficients according to their SNR. Many scenarios exist where the required second-order signal and noise statistics are not known in which the decorrelation is difficult or expensive to calculate. An asymptotically optimal estimation scheme proposed here uses a 2-D discrete wavelet transform to approximately decorrelate the signal in space and the discrete Fourier transform to decorrelate between channels. The coefficient weighting is replaced with a wavelet-domain thresholding operation to result in an efficient estimation scheme for both stationary and nonstationary signals. In contrast to optimal estimation, this new scheme does not require second-order signal statistics, making it well suited to many applications. In addition to providing vastly improved visual quality, the new estimator typically yields signal-to-noise ratio gains 12 dB or higher for hyperspectral imagery and functional magnetic resonance images.


[Anesthesia in magnetic resonance tomography].
Sixty patients were anesthesized for MRI. Intravenous and/or intramuscular anesthesia with ketamine, diazepam, pipolphen (promethazine) was supplemented by aminazine (chlorpromazine) or tisercin for adult patients. Spontaneous respiration was maintained, which helped avoid problems with endotracheal intubation and assisted ventilation. The method is safe, economic, and its side effects are negligible. Main features of MRI and specific anesthesiological problems associated with this method are discussed.


The Progression of Cavitation in Earlywood Vessels of Fraxinus mandshurica var japonica during Freezing and Thawing.
For an examination of the progression of cavitation in large-diameter earlywood vessels of a deciduous ring-porous tree, potted saplings of Fraxinus mandshurica var japonica Maxim. were frozen and then thawed. The changes in the amount and distribution of water in the lumina of the current year's earlywood vessels during the course of the freezing and thawing were visualized by cryo-scanning electron microscopy. When samples were frozen, most of the current year's earlywood vessels were filled with water. After the subsequent thawing, the percentage of cavitated current-year earlywood vessels gradually increased with time. All of the current year's earlywood vessels were cavitated within 24 h, and only limited amounts of water remained in the lumina of earlywood vessels. Similar cavitation of earlywood vessels was observed after thawing of frozen, excised stem pieces. In contrast, many vessels of the current year's latewood retained water in the lumina during freezing and thawing. These observations indicate that the cavitation of the current year's earlywood vessels is not produced during freezing but progresses during rewarming after freezing in F. mandshurica var japonica.


Functional dissociations between four basic arithmetic operations in the human posterior parietal cortex: a cytoarchitectonic mapping study.
Although lesion studies over the past several decades have focused on functional dissociations in posterior parietal cortex (PPC) during arithmetic, no consistent view has emerged of its differential involvement in addition, subtraction, multiplication, and division. To circumvent problems with poor anatomical localization, we examined functional overlap and dissociations in cytoarchitectonically defined subdivisions of the intraparietal sulcus (IPS), superior parietal lobule (SPL) and angular gyrus (AG), across these four operations. Compared to a number identification control task, all operations except addition, showed a consistent profile of left posterior IPS activation and deactivation in the right posterior AG. Multiplication and subtraction differed significantly in right, but not left, IPS and AG activity, challenging the view that the left AG differentially subserves retrieval during multiplication. Although addition and multiplication both rely on retrieval, multiplication evoked significantly greater activation in right posterior IPS, as well as the prefrontal cortex, lingual and fusiform gyri, demonstrating that addition and multiplication engage different brain processes. Comparison of PPC responses to the two pairs of inverse operations: division versus multiplication and subtraction versus addition revealed greater activation of left lateral SPL during division, suggesting that processing inverse relations is operation specific. Our findings demonstrate that individual IPS, SPL and AG subdivisions are differentially modulated by the four arithmetic operations and they point to significant functional heterogeneity and individual differences in activation and deactivation within the PPC. Critically, these effects are related to retrieval, calculation and inversion, the three key cognitive processes that are differentially engaged by arithmetic operations. Our findings point to distribute representation of these processes in the human PPC and also help explain why lesion and previous imaging studies have yielded inconsistent findings.


A Structural Comparison of Ordered and Non-Ordered Ion Doped Silicate Bioactive Glasses.
One of the key benefits of sol-gel-derived glasses is the presence of a mesoporous structure and the resulting increase in surface area. This enhancement in textural properties has a significant effect on the physicochemical properties of the materials. In this context the aim of this study was to investigate how sol-gel synthesis parameters can influence the textural and structural properties of mesoporous silicate glasses. We report the synthesis and characterization of metal ion doped sol-gel derived glasses with different dopants in the presence or absence of a surfactant (Pluronic P123) used as structure-directing templating agent. Characterization was done by several methods. Using a structure directing agent led to larger surface areas and highly ordered mesoporous structures. The chemical structure of the non-ordered glasses was modified to a larger extent than the one of the ordered glasses due to increased incorporation of dopant ions into the glass network. The results will help to further understand how the properties of sol-gel glasses can be controlled by incorporation of metal dopants, in conjunction with control over the textural properties, and will be important to optimize the properties of sol-gel glasses for specific applications, e.g., drug delivery, bone regeneration, wound healing, and antibacterial materials.


A systematic review and meta-analysis of the treatments of varicose veins.
Several treatment options exist for varicose veins. In this review we summarize the available evidence derived from comparative studies about the relative safety and efficacy of these treatments. We searched MEDLINE, Embase, Current Contents, Cochrane Central Register of Controlled Trials (CENTRAL) expert files, and the reference section of included articles. Eligible studies compared two or more of the available treatments (surgery, liquid or foam sclerotherapy, laser, radiofrequency ablations, or conservative therapy with compression stockings). Two independent reviewers determined study eligibility and extracted descriptive, methodologic, and outcome data. We used random-effects meta-analysis to pool relative risks (RR) and 95% confidence intervals (CI) across studies. We found 39 eligible studies (30 were randomized trials) enrolling 8285 participants. Surgery was associated with a nonsignificant reduction in the risk of varicose vein recurrence compared with liquid sclerotherapy (RR, 0.56; 95% CI, 0.29-1.06) and all endoluminal interventions (RR, 0.63; 95% CI, 0.37-1.07). Studies of laser and radiofrequency ablation and foam sclerotherapy demonstrated short-term effectiveness and safety. The quality of evidence presented in this review was limited by imprecision (small number of events), short-term follow-up, and indirectness (use of surrogate outcomes). Low-quality evidence supports long-term safety and efficacy of surgery for the treatment of varicose veins. Short-term studies support the efficacy of less invasive treatments, which are associated with less periprocedural disability and pain.


Trypsin-induced increase in cyclic AMP concentration in rat thymocytes. An effect independent of calcium and calmodulin.
Trypsin produces a dose-related increase in cellular cyclic AMP concentration in rat thymocytes [Shneyour, Patt & Trainin (1976) J. Immunol. 117, 2143-2149; Segal & Ingbar (1983) Clin. Res. 31, 277A]. In the present study, I examined whether this effect of trypsin requires Ca2+ and whether it is modified by calmodulin. In fresh thymocytes suspended in standard medium (containing 1 mM-Ca2+), trypsin produced a concentration-dependent increase in cytoplasmic free Ca2+ concentration, which was evident at a concentration of 50 micrograms of trypsin/ml and reached maximal values at about 1 mg/ml. This effect of trypsin was very prompt in onset, almost immediate, and reached maximal values within 2-3 min. But in cells suspended in essentially Ca2+-free medium (6 nM free Ca2+), trypsin had no effect on cytoplasmic free Ca2+ concentration, which indicates that trypsin acted by increasing Ca2+ uptake rather than Ca2+ release from an intracellular pool. However, the increase in thymocyte cyclic AMP concentration produced by trypsin was independent of extracellular Ca2+ and was not influenced by calmodulin, because it was the same in the presence or absence of Ca2+ and was not changed by the calmodulin inhibitor trifluoperazine. I therefore suggest that in rat thymocytes the trypsin-induced increase in cyclic AMP concentration does not require Ca2+ and is not influenced by calmodulin.


Biological markers of alcohol intake among 4796 subjects injured in accidents.
An epidemiological survey was carried out in France in 1982-3 to study the proportions of occasional and chronic drinkers among people injured in accidents of all kinds. The characteristics of 4796 victims recruited in the emergency units of 21 hospitals were recorded. Systematic blood sampling was performed to determine the blood alcohol concentration and two markers of chronic alcohol consumption--gamma-glutamyltransferase activity and mean corpuscular volume. Alcohol was present in the blood of 35% of the injured people, with concentrations exceeding 17.4 mmol/l (0.8 g/l) in one man out of four and in one woman out of 10. gamma-Glutamyltransferase values and mean corpuscular volume were also much higher than in a reference population of healthy subjects, indicating that most of the intoxicated subjects were probably chronic drinkers. This was confirmed by a discriminant analysis which showed an overall proportion of 30% of chronic drinkers among casualties. In France, therefore, the policy for preventing accidents should focus on chronic as much as on occasional drinking.


EGP-314 is expressed differentially in three brain zones at an early time in an experimentally induced ischemia rat model.
Gene expression in frontal, occipital, and hippocampal regions of rat brains at 15 min of ischemic injury was studied in a rat model by producing focal cerebral ischemia through middle cerebral artery (MCA) occlusion without reperfusion. Catalase, epithelial glycoprotein (EGP-314), cytochrome C oxidase-subunit 1, ribosomal L31 protein, and ceruloplasmin were found to be differentially expressed. Specific primers were designed to study this newly reported brain EGP-314, a cellular adhesion molecule involved in cell-cell and cell-extracellular matrix interactions and related with cytoskeletal organization, differentiation, and proliferation. In the frontal and occipital lobes, EGP-314 expression was low in control and ischemic conditions and increased in sham injured conditions, whereas in the hippocampal region its expression was induced only by ischemia. In situ hybridization and immunohistochemistry revealed that EGP-314 mRNA and the protein were present in the ischemic hippocampus pyramidal neurons. DNA fragmentation was demonstrated by TUNEL and LM-PCR analysis in hippocampus region. TUNEL positive pyramidal neurons were observed at 15 min of ischemia. DNA ladder was found at 12 and 15 min of ischemia.


1981N1: A Neptune Arc?
An object in the vicinity of Neptune detected in 1981 by simultaneous stellar occultation measurements at observatories near Tucson, Arizona, was interpreted as a new Neptune satellite. A reinterpretation suggests that it may have instead been a Neptune arc similar to one observed in 1984. The 1981 object, however, did not occult the star during simultaneous observations at Flagstaff, Arizona. This result constrains possible arc geometries.


Influence of genotyping error in linkage mapping for complex traits--an analytic study.
Despite the current trend towards large epidemiological studies of unrelated individuals, linkage studies in families are still thoroughly being utilized as tools for disease gene mapping. The use of the single-nucleotide-polymorphisms (SNP) array technology in genotyping of family data has the potential to provide more informative linkage data. Nevertheless, SNP array data are not immune to genotyping error which, as has been suggested in the past, could dramatically affect the evidence for linkage especially in selective designs such as affected sib pair (ASP) designs. The influence of genotyping error on selective designs for continuous traits has not been assessed yet. We use the identity-by-descent (IBD) regression-based paradigm for linkage testing to analytically quantify the effect of simple genotyping error models under specific selection schemes for sibling pairs. We show, for example, that in extremely concordant (EC) designs, genotyping error leads to decreased power whereas it leads to increased type I error in extremely discordant (ED) designs. Perhaps surprisingly, the effect of genotyping error on inference is most severe in designs where selection is least extreme. We suggest a genomic control for genotyping errors via a simple modification of the intercept in the regression for linkage. This study extends earlier findings: genotyping error can substantially affect type I error and power in selective designs for continuous traits. Designs involving both EC and ED sib pairs are fairly immune to genotyping error. When those designs are not feasible the simple genomic control strategy that we suggest offers the potential to deliver more robust inference, especially if genotyping is carried out by SNP array technology.


Comparative epidemiological study of non-melanoma skin cancer between Spanish and north and central European residents on the Costa del Sol.
Non-melanoma skin cancer (NMSC) is the most common tumour in white people. The progressive increase of these malignancies in such populations as those found in Europe represents an important public health concern which it is presumed will have a great impact on healthcare costs. However, the lack of comparable epidemiological information between countries hinders the development of a common health policy. The aim of this study was to describe the epidemiological, clinical and therapeutic aspects of NMSC in the public health area of the western part of the Costa del Sol, in southern Spain, and study the differences between the Spanish (S) population and that originally between the north and centre of Europe (N). We undertook a retrospective analysis of all patients with histologically confirmed tumours in both populations during the period 1 January 2006 to 30 June 2009. In comparison with the Spanish, the patients from the north and centre of Europe were more likely to have phototype I/II (S: 56.9%; N: 85.8%), recreational photoexposure (S: 48.4%; N: 83.8%), multiple carcinomas (S: 16.8%; N: 28.2%) and more carcinomas per patient (S: 1.7 ± 1.3; N: 2.3 ± 2.3). The tumours were more often located on the trunk and limbs (S: 28.3%; N: 50.2%) with a predominance of the less aggressive histological types (S: 34.7%; N: 42.6%) and non-invasive treatments in patients from the north and centre of Europe (S: 25.6%; N: 35.3%) when compared with the Spanish population. Persons from the north and centre of Europe living on the Costa del Sol present a different pattern of NMSC to the local Spanish population and usually require a less invasive therapeutic approach. These findings highlight the need to define prevention and treatment policies for NMSC according to the characteristics of each particular population. This would help reduce not only the frequency but also the associated morbimortality of this disease, particularly in high-risk populations.


Immediate endovascular repair for descending thoracic aortic transection secondary to blunt trauma.
To report the immediate endovascular treatment of a thoracic aortic tear secondary to blunt trauma. A 39-year-old man was injured in a motor vehicle collision. In addition to significant trauma to the head, chest, and abdomen, there were signs of a deceleration injury to the thoracic aorta. After urgent celiotomy to repair a lacerated spleen, the thoracic aortic transection was treated intraluminally using an endograft made of Gianturco Z-stents covered with polytetrafluoroethylene. The patient recovered from his injuries, and the thoracic endograft shows no evidence of endoleak 7 months after treatment. Endoluminal techniques can be used successfully in the immediate repair of thoracic aortic injuries.


Mental Fatigue and Spatial References Impair Soccer Players' Physical and Tactical Performances.
This study examined the effects of mental fatigue and additional corridor and pitch sector lines on players' physical and tactical performances during soccer small-sided games. Twelve youth players performed four Gk+6vs6+Gk small-sided games. Prior to the game, one team performed a motor coordination task to induce mental fatigue, while the other one performed a control task. A repeated measures design allowed to compare players' performances across four conditions: (a) with mental fatigue against opponents without mental fatigue in a normal pitch (MEN), (b) with mental fatigue on a pitch with additional reference lines (#MEN); (c) without mental fatigue against mentally fatigued opponents on a normal pitch (CTR); and (d) without mental fatigue on a pitch with reference lines (#CTR). Player's physical performance was assessed by the distance covered per minute and the number of accelerations and decelerations (0.5-3.0 m/s2; > -3.0 m/s2). Positional data was used to determine individual (spatial exploration index, time synchronized in longitudinal and lateral directions) and team-related variables (length, width, speed of dispersion and contraction). Unclear effects were found for the physical activity measures in most of the conditions. There was a small decrease in time spent laterally synchronized and a moderate decrease in the contraction speed when MEN compared to the CTR. Also, there was a small decrease in the time spent longitudinally synchronized during the #MEN condition compared to MEN. The results showed that mental fatigue affects the ability to use environmental information and players' positioning, while the additional reference lines may have enhanced the use of less relevant information to guide their actions during the #MEN condition. Overall, coaches could manipulate the mental fatigue and reference lines to induce variability and adaptation in young soccer players' behavior.


[Notes on the laboratory diagnosis of dengue virus].
Some aspects of interests connected with the virological, serological and molecular diagnosis of dengue and its most severe form, dengue hemorrhagic fever, which has turned into the most important arthropod-borne viral disease, are updated.


Specific inhibition of mitochondrial fatty acid oxidation by 2-bromopalmitate and its coenzyme A and carnitine esters.
1. The CoA and carnitine esters of 2-bromopalmitate are extremely powerful and specific inhibitors of mitochondrial fatty acid oxidation. 2. 2-Bromopalmitoyl-CoA, added as such or formed from 2-bromopalmitate, inhibits the carnitine-dependent oxidation of palmitate or palmitoyl-CoA, but not the oxidation of palmitoylcarnitine, by intact liver mitochondria. 3. 2-Bromopalmitoylcarnitine inhibits the oxidation of palmitoylcarnitine as well as that of palmitate or palmitoyl-CoA. It has no effect on succinate oxidation, but inhibits that of pyruvate, 2-oxoglutarate or hexanoate; however, the oxidation of these substrates (but not of palmitate, palmitoyl-CoA or palmitoyl-carnitine) is restored by carnitine. 4. In damaged mitochondria, added 2-bromopalmitoyl-CoA does inhibit palmitoylcarnitine oxidation; pyruvate oxidation is unaffected by the inhibitor alone, but is impaired if palmitoylcarnitine is subsequently added. 5. The findings have been interpreted as follows. 2-Bromopalmitoyl-CoA inactivates (in a carnitine-dependent manner) a pool of carnitine palmitoyltransferase which is accessible to external acyl-CoA. This results in inhibition of palmitate or palmitoyl-CoA oxidation. A second pool of carnitine palmitoyltransferase, inaccessible to added acyl-CoA in intact mitochondria, can generate bromopalmitoyl-CoA within the matrix from external 2-bromopalmitoylcarnitine; this reaction is reversible. Such internal 2-bromopalmitoyl-CoA inactivates long-chain beta-oxidation (as does added 2-bromopalmitoyl-CoA if the mitochondria are damaged) and its formation also sequesters intramitochondrial CoA. Since this CoA is shared by pyruvate and 2-oxoglutarate dehydrogenases, the oxidation of their substrates is depressed by 2-bromopalmitoylcarnitine, unless free carnitine is available to act as a ;sink' for long-chain acyl groups. 6. These effects are compared with those reported for other inhibitors of fatty acid oxidation.


Should we reconsider the apoptosis as a strategic player in tissue regeneration?
Apoptosis plays a central role in organs development and homeostasis. Impaired regulation of this process is often associated with the onset of several human diseases, such as developmental disorders and cancer. The last scientific investigations have discovered interesting connections between apoptosis, stem cells, tissue regeneration and cancer. The role of "programmed cell death" in stem cells and tissue engineering is extremely promising; in fact, it holds great potential for regenerative purposes. However, several questions still remain unsolved: do we really know all the main molecular actors able to switch ON/OFF the apoptosis? Is it possible to modulate these players, to obtain a predictable regeneration of tissues and organs? But primarily: should we reconsider the apoptosis as a strategic player in tissue regeneration? In this topical review, we have carefully examined the most recent discoveries about the role of apoptosis in stem cells and, specifically, in mesenchymal stem cells. The pivotal molecules involved in the activation and inhibition of the apoptotic pathways will be carefully described, with the aim to shed an overall light on the complex scenario of stem cell life and death, and on a novel strategy for tissue regeneration.


StemBell therapy stabilizes atherosclerotic plaques after myocardial infarction.
After a myocardial infarction (MI) atherosclerosis is accelerated leading to destabilization of the atherosclerotic plaque. mesenchymal stromal cells are a promising therapeutic option for atherosclerosis. Previously, we demonstrated a novel stem cell delivery technique, with adipose stem cells coupled to microbubbles (i.e., StemBells) as therapy after MI. In this study, we aim to investigate the effect of StemBell therapy on atherosclerotic plaques in an atherosclerotic mouse model after MI. MI was induced in atherosclerotic Apolipoprotein E-deficient mice that were fed a high-fat Western diet. Six days post-MI, the mice received either 5 × 105/100 µL StemBells or vehicle intravenously. The effects of StemBell treatment on the size and stability of aortic root atherosclerotic plaques and the infarcted heart were determined 28 days post-MI via (immuno)histological analyses. Moreover, monocyte subtypes and lipids in the blood were studied. StemBell treatment resulted in significantly increased cap thickness, decreased intra-plaque macrophage density and increased percentage of intra-plaque anti-inflammatory macrophages and chemokines, without affecting plaque size and serum cholesterol/triglycerides. Furthermore, StemBell treatment significantly increased the percentage of anti-inflammatory macrophages within the infarcted myocardium but did not affect cardiac function nor infarct size. Finally, also the average percentage of anti-inflammatory monocytes in the circulation was increased after StemBell therapy. StemBell therapy increased cap thickness and decreased intra-plaque inflammation after MI, indicative of stabilized atherosclerotic plaque. It also induced a shift of circulating monocytes and intra-plaque and intra-cardiac macrophages towards anti-inflammatory phenotypes. Hence, StemBell therapy may be a therapeutic option to prevent atherosclerosis acceleration after MI.


A point mutation (D79N) of the alpha2A adrenergic receptor abolishes the antiepileptogenic action of endogenous norepinephrine.
Norepinephrine serves as a neurotransmitter for a population of neurons the cell bodies of which reside in a brainstem nucleus and the axons of which project widely to discrete subsets of forebrain neurons. Norepinephrine powerfully inhibits epileptogenesis in the kindling model. Pharmacological methods have demonstrated that the antiepileptogenic actions of norepinephrine are exerted via alpha2 adrenergic receptors residing on targets of noradrenergic neurons. The existence of three alpha2 adrenergic receptor subtypes together with the lack of subtype-specific ligands has precluded understanding the role of individual alpha2 adrenergic receptor subtypes in the antiepileptogenic actions of norepinephrine. Gene targeting was used to introduce a point mutation into the alpha2A adrenergic subtype in the mouse genome. The mutation produced a marked enhancement of epileptogenesis and abolished the proepileptogenic actions of the alpha2 adrenergic receptor antagonist idazoxan. These studies reveal the crucial contribution of the alpha2A receptor subtype in suppression of epileptogenesis. Development of agents that promote selective activation of the alpha2A receptor subtype may provide novel therapeutic strategies for the prophylaxis of epilepsy.


When to be born? Prolonged pregnancy or incubation enhances locomotor performance in neonatal lizards (Scincidae).
The degree of offspring development at hatching (or birth) varies among species within most major vertebrate lineages; altricial vs. precocial birds offer the clearest example of a trade-off between early hatching and the degree of locomotor development of the hatchling. No such diversity has been reported for reptiles, but we suggest that natural selection may fine-tune the time of hatching (in oviparous species) or birth (in viviparous species) to optimize offspring phenotypes and hence, maximize fitness. This hypothesis predicts enhanced neonatal performance after more prolonged incubation or gestation, within as well as among populations. Both published and original data on Australian scincid lizards support this prediction. In a field study, viviparous alpine skinks (Niveoscincus microlepidotus) that gave birth later in the season had faster-running offspring, that had a higher probability of surviving through the first year of life. The enhanced performance and survival were not secondary results of larger offspring size. After controlling for effects of mean incubation temperature, prolonged development also correlated with enhanced locomotor performance in hatchlings from eggs of an oviparous skink (Bassiana duperreyi) incubated at warm temperatures (> 20 degrees C) but not at cooler temperatures (< 20 degrees C). We suggest that embryonic reptiles control their date of hatching or birth and thus, their stage of development at this critical life-history transition.


Virus entry as a target for anti-HIV intervention.
The replicative cycle of the human immunodeficiency virus (HIV) can be interrupted at several stages. Until recently only the viral reverse transcriptase and protease were the only enzymes targeted by antiretroviral agents. However, the first HIV entry inhibitor (T-20, Enfuvirtide, Fuseon) to be used in humans has been approved by the Food and Drug Administration (FDA). The HIV entry process is considered as an attractive target for chemotherapeutic intervention, as blocking HIV entry into its target cell leads to suppression of viral infectivity, replication and the cytotoxicity induced by virus-cell contacts. HIV-1 entry into target cells is a multistep process: virus attachment is initiated by the binding of trimeric envelope glycoprotein gp120 complexes on the virions to glycosylated T-cell surface receptor (CD4) and HIV GPCR coreceptors (CCR5 or CXCR4) leading to envelope glycoprotein gp41-dependent fusion-pore formation and membrane fusion. A number of compounds are being developed to specifically target each of these steps leading to virus entry and some compounds have reached early clinical development. Conversely, agents such as the CCR5 antagonist Tak-779 and the CXCR4 antagonist AMD3100 are not longer being thought as relevant anti-HIV agents but have given way to new analogues with improved properties. This review summarizes the current state of HIV entry inhibitors, their mechanisms of action and their therapeutic value against HIV infection and AIDS.


Acute epiglottitis presenting as the sensation of a foreign body in the throat.
A 49-year-old man presented with dysphagia and the sensation of a foreign body in the throat, after he had swallowed chicken meat that contained bones during the previous evening. There were no respiratory symptoms. A plain lateral soft-tissue X-ray of the neck and oesophagogastroduodenoscopy showed a grossly swollen epiglottis. His condition improved rapidly with intravenous antibiotic therapy. As acute epiglottitis may be a sudden life-threatening condition, a high index of suspicion should be maintained for patients who present with an obstructive sensation in the throat.


Kocher-Debré-Semelaigne syndrome with rhabdomyolysis and increased creatinine.
Association of Kocher-Debré-Semelaigne syndrome-a myopathy of hypothyroidism in childhood characterized by muscular hypertrophy, with rhabdomyolysis is very rare. We present a case of Kocher-Debré-Semelaigne syndrome with rhabdomyolysis secondary to Hashimoto's thyroiditis. He had muscular symptoms simulating poly/dermatomyositis, massively elevated creatine kinase (CK) levels and high creatinine levels. All of the findings reversed on treatment of hypothyroidism. The response to the therapy strongly suggested that Kocher-Debré-Semelaigne (KDS) syndrome was the underlying etiology. Serum thyroid- stimulating hormone levels should be routinely determined in all patients with muscular symptoms and/or elevation of CK and creatinine, keeping KDS syndrome in mind.


Need for open data on COVID-19 vaccine uptake among pregnant people in the Caribbean: a call to action.
Pregnant people with coronavirus disease 2019 (COVID-19) have a higher risk of adverse maternal and fetal outcomes compared with pregnant people without COVID-19. In 2021, large increases in maternal mortality were reported in Jamaica, almost half of which were attributable to COVID-19. COVID-19 vaccination has been shown to reduce these risks, but low- and middle-income countries lack free, publicly available data, known as open data, on COVID-19 vaccine uptake for their pregnant populations. The objectives of this paper were to: review how high-income countries use open data to detect trends in COVID-19 vaccine uptake among pregnant people and develop vaccination distribution strategies; outline barriers to making open data available for maternal COVID-19 vaccination in the Caribbean; and propose a multipronged strategy that would increase the availability of open data on maternal COVID-19 vaccination in the Caribbean. A multipronged strategy to fill the data void would involve: (i) utilizing existing Caribbean maternal immunization data collection entities; (ii) adapting digital software tools to establish maternal electronic immunization registries; and (iii) collaborating with local partners skilled in data analytics. Making open data available for COVID-19 vaccine uptake among pregnant people in the Caribbean could offer substantial benefits, including the development of measurable maternal COVID-19 vaccination goals and the facilitation of vaccine decision-making discussions between providers and pregnant people.


[Evaluation of systematic orientation for speech rehabilitation on laryngectomized patients].
None of the surgeries performed today produces greater physiological and psychological changes than laryngectomy. After surgery, patients find themselves to be unable to speak, breathing through tracheotomy, with decreased smell and taste and most of the times suspecting they have cancer. The purpose of this work is to lest the method learning of esophageal speech intended to assist in rehabilitating laryngectomized patients. We have concluded that the method used to develop esophageal speech had satisfactory results; that the nurse has the skill required to guide this learning and to help laryngectomized patients with communication difficulties along with many others inherent to this condition.


Genetically modified chondrocytes expressing TGF-β1: a revolutionary treatment for articular cartilage damage?
Currently, joint arthroplasty remains the only definitive management of osteoarthritis, while other treatment modalities only provide temporary and symptomatic relief. The use of genetically engineered chondrocytes is currently undergoing clinical trials. Specifically, it has been designed to induce cartilage growth and differentiation in patients with degenerative arthritis, with the aim to play a curative role in the disease process. This treatment involves the incorporation of TGF-β1, which has been determined to play an influential role in chondrogenesis and extracellular matrix synthesis. Using genetic manipulation and viral transduction, TGF-β1 is incorporated into human chondrocytes and administered in a minimally invasive fashion directly to the affected joint. Following a database literature search, we evaluated the current evidence on this product and its outcomes. Furthermore, we also briefly reviewed other treatments developed for chondrogenesis and cartilage regeneration for comparison. This treatment method has sustained positive effects on functional outcomes and cartilage growth in initial trials. It allows administration in a minimally invasive manner that does not require extended recovery time. Although several treatment modalities are currently under investigation and appear promising, we hope that these effects can be sustained in further studies. Ultimately, we anticipate that the results may be reproducible in many clinical settings and allow us to effectively treat cartilage damage in patients with degenerative arthritis.


Factor analysis and evaluation of each item of the tinnitus handicap inventory.
This study aims to examine the availability of subscales in the Tinnitus Handicap Inventory (THI) originally proposed by Newman and the possibility of other useful subscales. We also examine whether each item of the THI could be used to better understand the status of patients with tinnitus. This study included 1332 patients who answered the THI on their first visit. Confirmatory factor analysis was conducted to the 25 items of the THI to confirm the usefulness of the emotional, functional, and catastrophic subscales. Exploratory factor analysis was performed to discover the availability of other suitable subscales in addition to the proposed subscales. The proportion of patients who chose "yes" in each item of the THI was also examined to understand the status of patients with tinnitus. In the confirmatory factor analysis, the emotional, functional, and catastrophic subscales did not fit the model. In the exploratory factor analysis, data were extremely biased to one factor. Examination of each item of the THI showed the tendency of worsening of comorbid symptoms when tinnitus handicap became worse. As a result of the factor analysis, only the total score, not any subscale, would be clinically useful in the THI. Examination of each item of the THI was helpful to understand the status of patients with tinnitus and comorbid symptoms of tinnitus. It is necessary to consider treatment by taking these comorbid symptoms into account.


Insecticide control of vector-borne diseases: when is insecticide resistance a problem?
Many of the most dangerous human diseases are transmitted by insect vectors. After decades of repeated insecticide use, all of these vector species have demonstrated the capacity to evolve resistance to insecticides. Insecticide resistance is generally considered to undermine control of vector-transmitted diseases because it increases the number of vectors that survive the insecticide treatment. Disease control failure, however, need not follow from vector control failure. Here, we review evidence that insecticide resistance may have an impact on the quality of vectors and, specifically, on three key determinants of parasite transmission: vector longevity, competence, and behaviour. We argue that, in some instances, insecticide resistance is likely to result in a decrease in vector longevity, a decrease in infectiousness, or in a change in behaviour, all of which will reduce the vectorial capacity of the insect. If this effect is sufficiently large, the impact of insecticide resistance on disease management may not be as detrimental as previously thought. In other instances, however, insecticide resistance may have the opposite effect, increasing the insect's vectorial capacity, which may lead to a dramatic increase in the transmission of the disease and even to a higher prevalence than in the absence of insecticides. Either way-and there may be no simple generality-the consequence of the evolution of insecticide resistance for disease ecology deserves additional attention.


Insights into the molecular mechanism of amyloid filament formation: Segmental folding of α-synuclein on lipid membranes.
Recent advances in the structural biology of disease-relevant α-synuclein fibrils have revealed a variety of structures, yet little is known about the process of fibril aggregate formation. Characterization of intermediate species that form during aggregation is crucial; however, this has proven very challenging because of their transient nature, heterogeneity, and low population. Here, we investigate the aggregation of α-synuclein bound to negatively charged phospholipid small unilamellar vesicles. Through a combination of kinetic and structural studies, we identify key time points in the aggregation process that enable targeted isolation of prefibrillar and early fibrillar intermediates. By using solid-state nuclear magnetic resonance, we show the gradual buildup of structural features in an α-synuclein fibril filament, revealing a segmental folding process. We identify distinct membrane-binding domains in α-synuclein aggregates, and the combined data are used to present a comprehensive mechanism of the folding of α-synuclein on lipid membranes.


Imaging Features and Pathological Correlation in Mixed Microcystic and Angiomatous Meningioma: A Case Report.
Meningiomas are the most common intracranial tumors. However, microcystic and angiomatous meningiomas are very rare subtypes that present unusual imaging findings. Hence, radiological diagnosis of these tumors can be challenging. We herein describe a case of mixed angiomatous and microcystic meningioma in an 81-year-old male. MRI revealed an extra-axial mass with high T2 signal intensity, measuring 1.5 cm in diameter, with multiple tiny intralesional cysts and entrapped peritumoral cyst formation. After tumor resection, a histopathological diagnosis of mixed angiomatous and microcystic meningioma was made.


Structure and magnetism of the first strictly dinuclear compound containing paramagnetic 3d and 5f metal ions. Major influence of the Cu(II) ion coordination on the exchange Cu(II)-U(IV) interaction.
The dinuclear compound [CuL2(py)U(acac)2] has been synthesized by treating [Cu(H2L2)] with U(acac)4 (L2 = N,N'-bis(3-hydroxysalicylidene)-2-methyl-1,2-propanediamine) and shows the antiferromagnetic Cu-U interaction; the distinct magnetic behaviour of the trinuclear complexes [(CuL2)2U] (antiferromagnetic) and [[CuL1(py)]U[CuL1]] (ferromagnetic) revealed the major influence of the Cu(II) ion coordination on the exchange interaction (L1 = N,N'-bis(3-hydroxysalicylidene)-2,2-dimethyl-1,3-propanediamine).


Boytchev procedure for the treatment of anterior shoulder instability.
Most of the operative techniques described for the treatment of recurrent anterior dislocations or subluxations of the shoulder have two distinct disadvantages: the need to immobilize the arm for several weeks and loss of external rotation. These disadvantages provided an incentive for conducting a clinical evaluation of an operation originally described by Boytchev and modified by the author. In this procedure, the conjoined tendons of the coracobrachialis and the short head of the biceps with the detached tip of the coracoid process are rerouted posterior to the subscapularis muscle and reattached to the coracoid process, providing a dynamic muscular sling immediately anteroinferior to the glenohumeral joint, especially when the arm is in a vulnerable position of abduction and external rotation. A total of 26 repairs with a minimal follow-up period of two years were reviewed. There were 22 men and four women with an average age of 22 years. The results were satisfactory in all patients. Loss of external rotation of less than 15 degrees was noted in eight patients. There were no redislocations. This procedure provides immediate stability to the shoulder allowing range of motion exercises to begin from the first postoperative day.


Failure to immunize the elderly: a systems problem or a statement of personal values?
Despite the proven efficacy of the influenza vaccine in reducing the risk for pneumonia, hospitalization, and death and the potential savings in costs, most elderly persons do not receive annual immunizations. The study tested the influence of health care delivery system characteristics and individual personal values on the influenza immunization status. The study involved a secondary data analysis based on the results of a mailed survey of 3,362 seniors 65 years of age and older enrolled in HealthPartners, a mixed-model health maintenance organization in Minnesota. The three care delivery systems in which respondents were enrolled varied in the intensity and consistency with which they addressed immunization. The immunization rate for this population (77.1%) was higher than the state rate (64%). After controlling for many variables historically known to influence the likelihood of immunization, both care delivery system characteristics and personal values remained significantly associated with immunization status. Elderly individuals getting care in delivery systems with well-developed immunization programs were more likely to be immunized. Those who avoided going to the physician and who practiced risky behaviors such as smoking were less likely to be immunized, regardless of the care delivery system they were enrolled in. Managed care can provide a number of system improvements to assist in meeting national health care objectives such as influenza immunization for the elderly. It has reduced some common barriers to immunization, such as cost and access. Yet to achieve the full benefits of a successful influenza immunization program, the role of individual values, as well as implementing systems solutions, needs to be addressed.


The Human Vaccines Project: Towards a comprehensive understanding of the human immune response to immunization.
Although the success of vaccination to date has been unprecedented, our inadequate understanding of the details of the human immune response to immunization has resulted in several recent vaccine failures and significant delays in the development of high-need vaccines for global infectious diseases and cancer. Because of the need to better understand the immense complexity of the human immune system, the Human Vaccines Project was launched in 2015 with the mission to decode the human immune response to accelerate development of vaccines and immunotherapies for major diseases. The Project currently has three programs: 1) The Human Immunome Program, with the goal of deciphering the complete repertoire of B and T cell receptors across the human population, termed the Human Immunome, 2) The Rules of Immunogenicity Program, with the goal of understanding the key principles of how a vaccine elicits a protective and durable response using a system immunology approach, and 3) The Universal Influenza Vaccine Initiative (UIVI), with the goal of conducting experimental clinical trials to understand the influence of influenza pre-exposures on subsequent influenza immunization and the mechanisms of protection. Given the dramatic advances in computational and systems biology, genomics, immune monitoring, bioinformatics and machine learning, there is now an unprecedented opportunity to unravel the intricacies of the human immune response to immunization, ushering in a new era in vaccine development.


Effectiveness analysis of resistance and tolerance to infection.
Tolerance and resistance provide animals with two distinct strategies to fight infectious pathogens and may exhibit different evolutionary dynamics. However, few studies have investigated these mechanisms in the case of animal diseases under commercial constraints. The paper proposes a method to simultaneously describe (1) the dynamics of transmission of a contagious pathogen between animals, (2) the growth and death of the pathogen within infected hosts and (3) the effects on their performances. The effectiveness of increasing individual levels of tolerance and resistance is evaluated by the number of infected animals and the performance at the population level. The model is applied to a particular set of parameters and different combinations of values. Given these imputed values, it is shown that higher levels of individual tolerance should be more effective than increased levels of resistance in commercial populations. As a practical example, a method is proposed to measure levels of animal tolerance to bovine mastitis. The model provides a general framework and some tools to maximize health and performances of a population under infection. Limits and assumptions of the model are clearly identified so it can be improved for different epidemiological settings.


Intra-tumoral molecular heterogeneity in benign and malignant pheochromocytomas and extra-adrenal sympathetic paragangliomas.
Pheochromocytomas (PCCs) and extra-adrenal sympathetic paragangliomas (sPGLs) are catecholamine-producing tumors occurring in the context of hereditary tumor syndromes, with known germline mutations, and as sporadic tumors. The pathogenesis of sporadic PCC and sPGL is poorly understood, and little is known about intra-tumoral heterogeneity with respect to molecular aberrations. Since knowledge on intra-tumoral heterogeneity is important for understanding the pathogenesis of these tumors, we investigated 12 benign and 8 malignant PCCs and sPGLs for loss of heterozygosity (LOH) on DNA extracted from different regions of each tumor and from metastases. LOH markers were selected on chromosomal regions frequently deleted in PCC, including 1p, 3q, 3p, and 11p. Benign tumors were found to have less intra-tumoral heterogeneity (overall 8%) than malignant tumors (overall 23%), with the highest frequencies for chromosome 1p36 in the benign tumors (17%) and 1p13 and 3q24 in malignant tumors (both 38%). In addition, differences in LOH patterns were detected between paired primary malignant tumors, and their metastases and different LOH patterns were observed in bilateral PCC of a multiple endocrine neoplasia type 2 patient. We demonstrate that malignant PCC and sPGL have more intra-tumoral molecular heterogeneity than benign tumors, which suggests that benign and malignant PCC and sPGL have a different pathogenesis.


Role of leucocytes in free radical production during myocardial revascularisation.
To evaluate the role of leucocytes in free radical production in patients with depressed or normal ejection fraction undergoing coronary bypass. Two randomised control trials. Tertiary care centre. In the first study, 22 patients with ejection fractions of < or = 40% received blood cardioplegic reperfusion with (n = 11) or without (n = 11) leucocyte depletion. In the second study, 22 patients with ejection fractions > or = 45% received either leucocyte depleted (n = 11) or blood cardioplegia (n = 11). Glutathione, hypoxanthine, and lipid peroxidation products were measured in coronary sinus blood and plasma before aortic cross clamping and at 0, 15, and 30 minutes after unclamping. Haemodynamic variables and creatine kinase MB isoenzymes were monitored on the first postoperative day. Comparison between treatments was performed on difference (delta) between measurements at time 0 and at baseline, and on slopes obtained by fitting measurements after unclamping with a linear regression model. At unclamping no difference in delta for plasma glutathione redox ratio (oxidised/total glutathione, %) was observed between treated and control groups with low ejection fraction (delta = 16 (SD 8.39) and 24 (7.0) redox ratio %, respectively). Baseline value recovery rate (redox ratio %/min) was significantly faster in treated v control patients (slope -0.912 (0.380) v -0.158 (0.200), P < 0.005, respectively). Cardiac index showed a trend to greater improvement in the treated group (slope 0.04 (0.03) v 0.003 (0.002) 1/min/m2/h, P < 0.02, treated v controls, respectively). In patients with normal ejection fraction, leucocyte depletion did not result in significant improvement v controls. Leucocyte depletion seems to provide benefit only in patients with left ventricular dysfunction.


Surface properties of the euglenoid flagellum.
New structural details of the Euglena flagellum have led to a modified interpretation of the arrangement of the mastigoneme sheath and its internal attachment. A paraaxial ribbon is described which is located between the flagellar membrane and the axonemal microtubules. This fine ribbon apparently binds mastigoneme units and in turn is bonded to three peripheral microtubule doublets in a position approximately opposite that of the paraflagellar rod. The latter structure seems to anchor one half of the flagellar sheath while the paraaxial ribbon anchors the other one half of the flagellar sheath. Immunological labelling of Euglena mastigonemes has demonstrated that mastigonemes are present in the reservoir as well as on the flagellar surface if monovalent Fab' is used on deflagellated cells. Pulse labelling with anti-mastigoneme Fab' in regenerating cells showed the initial reservoir label was lost and indicated that the labelled mastigonemes were transferred to the flagellum. The reservoir is thus demonstrated to contain a surface pool for flagellar mastigonemes. Flagellar regeneration is partially inhibited irreversibly by the glycoprotein synthesis inhibitor tunicamycin. Experiments with cycloheximide and tunicamycin suggest each antibiotic affects different moieties and that some glycoprotein(s) is limiting to flagellar growth in Euglena. It is postulated that mastigonemes are possible candidates for that rate-limiting component.


Benign cellular changes in Pap smears. Causes and significance.
We reviewed consecutive cases classified as benign cellular changes (BCC) over a four-month period. Cases classified as BCC were retrieved from the cytology files. A search was carried out to identify the previous Pap smears and concomitant cervical biopsies. One thousand one hundred three cases (23% of our gynecologic smears) were classified as BCC. Ninety-two patients (8.3%) underwent concurrent cervical biopsies. Specific infections accounted for 8% of BCC cases; reactive changes accounted for 92%. Of the biopsy specimens, 8.3% had no significant pathologic change. The most common biopsy diagnoses were cervicitis (31.5%), immature squamous metaplasia (16.3%) and reserve cell hyperplasia (10.8%). Miscellaneous benign diagnoses accounted for 21.7%. Cervical intraepithelial neoplasia (CIN) 1/human papillomavirus (HPV) was present in 14% of cases. All patients with biopsy diagnoses of CIN 1 had at least two previous abnormal Pap smears. Previous biopsy reports were available for review in 127 (12%) of the 1,103 patients. Of these 127 cases, 53.5% had a previous diagnosis of CIN/HPV; 9.4% had invasive carcinoma. A benign diagnosis was reported in 36.5%. The majority of BCC cases are due to reactive and inflammatory processes. In patients with a previous history of CIN, BCC may be of some significance. In patients with no significant prior cervical abnormalities, a Pap smear classified as BCC represents a reactive process.


The DNA binding protein Rfg1 is a repressor of filamentation in Candida albicans.
We have identified a repressor of hyphal growth in the pathogenic yeast Candida albicans. The gene was originally cloned in an attempt to characterize the homologue of the Saccharomyces cerevisiae Rox1, a repressor of hypoxic genes. Rox1 is an HMG-domain, DNA binding protein with a repression domain that recruits the Tup1/Ssn6 general repression complex to achieve repression. The C. albicans clone also encoded an HMG protein that was capable of repression of a hypoxic gene in a S. cerevisiae rox1 deletion strain. Gel retardation experiments using the purified HMG domain of this protein demonstrated that it was capable of binding specifically to a S. cerevisiae hypoxic operator DNA sequence. These data seemed to indicate that this gene encoded a hypoxic repressor. However, surprisingly, when a homozygous deletion was generated in C. albicans, the cells became constitutive for hyphal growth. This phenotype was rescued by the reintroduction of the wild-type gene on a plasmid, proving that the hyphal growth phenotype was due to the deletion and not a secondary mutation. Furthermore, oxygen repression of the hypoxic HEM13 gene was not affected by the deletion nor was this putative ROX1 gene regulated positively by oxygen as is the case for the S. cerevisiae gene. All these data indicate that this gene, now designated RFG1 for Repressor of Filamentous Growth, is a repressor of genes required for hyphal growth and not a hypoxic repressor.


Glomerular accumulation of monocytes and macrophages in experimental glomerulonephritis associated with Trypanosoma rhodesiense infection.
Experimental infection in rabbits with a human isolate of Trypanosoma rhodesiense led to the formation of circulating immune complexes and glomerulonephritis. Granular deposits of C3 and lesser amounts of IgM and IgG were seen deposited in the glomeruli in a primarily mesangial pattern. The glomeruli became hypercellular beginning on day 7. This was associated with diffuse swelling and vacuolation of endothelial cells with focal loss of fenestrae, as well as vacuolation of mesangial cells processes protruding into the capillary lumina. The hypercellularity became maximal on day 21 and was accompanied by proteinuria and increased tubular hyaline droplets. The hypercellularity was in large part due to the accumulation of monocytes as demonstrated by nonspecific cytoplasmic esterase stains. Counts of the number of monocytic cellular profiles per glomerulus showed that maximal numbers were reached on the 21st day of the infection. Ultrastructural examination confirmed the presence of monocytes within capillary lumina and macrophages within mesangial regions. Electron-dense deposits were rarely seen by transmission electron microscopy, and the heavy granular deposits of IgM and C3 observed by immunofluorescence were attributed to ingested proteins within macrophages. This study implies an active role for monocytes and macrophages in immune complex-mediated glomerulonephritis.


The comparison of mean crowding between two groups.
The infrapopulation size, or crowding, is an important measure in parasitology because of its impact on many facets of parasite biology. However, crowding values are difficult to handle statistically because of dependencies. Therefore, a bootstrap procedure was proposed in order to compare crowding between 2 groups or samples of hosts. Here, we propose Lepage's location-scale test based on intensities as an alternative to test whether there is a difference in mean crowding. Simulation results indicate that Lepage's test is superior to the bootstrap, even when sample sizes are large as needed for the bootstrap procedure. Lepage's test, however, can also be applied with moderate or small sample sizes.


Variation between Point-of-care and Laboratory HbA1c testing in Clinical Practice.
The aim of this study was to identify potential disparities between point-of-care testing (POCT) and laboratory hemoglobin A1c (HbA1c) reporting at a Federally Qualified Health Center (FQHC). The electronic medical record was reviewed to identify POCT HbA1c done at a FQHC and centralized laboratory venous HbA1c performed on the same day. Manual data extraction was used to identify potential variables that could account for disparities between POCT and laboratory testing. A total of 42 samples in 40 patients were identified. The median HbA1c difference was 1.5 mmol/mol (0.15%) and ranged from -26 to 52 mmol/mol (-2.4 to 4.8%). Of the patients in the study, two had underlying comorbidities that could affect the POCT HbA1c. Point-of-care HbA1c testing should not be used in solidarity to diagnosis pre-diabetes and diabetes. When using HbA1c results to guide therapy, self-monitoring of blood glucose and symptoms of both hypo- and hyperglycemia should be correlated to help determine appropriate therapy.


Prospective study on the clinical relevance of 18F-DOPA positron emission tomography/computed tomography in patients with medullary thyroid carcinoma.
18F-DOPA Positron Emission Tomography/Computed Tomography (18F-DOPA PET/CT) is a sensitive functional imaging method (65-75%) for detecting disease localization in medullary thyroid cancer (MTC). We aimed: (i) to assess the clinical usefulness of 18F-DOPA PET/CT in patients with MTC and elevated calcitonin (Ctn) and CEA levels and, (ii) to evaluate changes in disease management secondary to the findings encountered with this methodology. Thirty-six patients with MTC and Ctn levels ≥150 pg/ml were prospectively included. Neck ultrasound, chest contrast-enhanced CT, liver magnetic resonance imaging/abdominal three-phase contrast-enhanced CT and bone scintigraphy were carried out up to 6 months before the 18F DOPA PET/CT. Seventy eight percent of patients were female and 27% had hereditary MTC. Median Ctn level was 1450 pg/ml [150-56620], median CEA level 413 ng/ml [2.9-7436]. Median Ctn DT was 37.5 months [5.7-240]; median CEA DT was 31.8 [4.9-180]. 18F-DOPA PET/CT was positive in 33 patients (91.6%); in 18 (56%) uptake was observed in lymph nodes in the neck or mediastinum, in seven cases (22%) distant metastases were diagnosed, and in eight additional patients (24%) both locoregional and distant sites of disease were found. Ctn and CEA levels were higher in patients with ≥3 foci of distant metastases. In 14 patients (38.8%), findings on 18F-DOPA PET/CT led to changes in management; surgery for locoregional lymph nodes was the most frequent procedure in 8 patients (22%). 18F-DOPA PET/CT was useful for the detection of recurrent disease in MTC, providing incremental value over conventional imaging procedures that led to modification in treatment strategies in nearly 40% of patients.


McLeod phenotype without the McLeod syndrome.
McLeod neuroacanthocytosis syndrome is a late-onset X-linked multisystem disorder affecting the peripheral and central nervous systems, red blood cells (RBCs), and internal organs. A variety of mutations have been found in the responsible gene (XK) including single nonsense and missense mutations, nucleotide mutations at or near the splice junctions of introns of XK, and different deletion mutations. To date no clear phenotype-genotype correlation is apparent. The clinical details of one case of McLeod phenotype without apparent neuromuscular abnormalities have been reported. Here the clinical details of two additional cases are presented, of which the genetic details have previously been published. Two asymptomatic or minimally symptomatic cases at ages expected to manifest the McLeod syndrome (MLS) were evaluated. The first case had been authenticated as a genuine McLeod both by serology and by genotyping (R222G missense mutation) and the second case had a mutation in XK (IVS2+5G>A) and by serology exhibited very weak Kx antigen and no detectable Kell antigens, except extremely low k antigen by adsorption-elution technique. The patients were examined for hematologic, neurologic, and other clinical abnormalities. Despite documented McLeod phenotype on RBCs, and identified mutations of XK, neurologic and other clinical findings were minimal at ages expected to manifest MLS. The different XK mutations may have different effects upon the XK gene product and thus may account for the variable phenotype.


Atherosclerosis imaging using 3D black blood TSE SPACE vs 2D TSE.
To compare 3D Black Blood turbo spin echo (TSE) sampling perfection with application-optimized contrast using different flip angle evolution (SPACE) vs 2D TSE in evaluating atherosclerotic plaques in multiple vascular territories. The carotid, aortic, and femoral arterial walls of 16 patients at risk for cardiovascular or atherosclerotic disease were studied using both 3D black blood magnetic resonance imaging SPACE and conventional 2D multi-contrast TSE sequences using a consolidated imaging approach in the same imaging session. Qualitative and quantitative analyses were performed on the images. Agreement of morphometric measurements between the two imaging sequences was assessed using a two-sample t-test, calculation of the intra-class correlation coefficient and by the method of linear regression and Bland-Altman analyses. No statistically significant qualitative differences were found between the 3D SPACE and 2D TSE techniques for images of the carotids and aorta. For images of the femoral arteries, however, there were statistically significant differences in all four qualitative scores between the two techniques. Using the current approach, 3D SPACE is suboptimal for femoral imaging. However, this may be due to coils not being optimized for femoral imaging. Quantitatively, in our study, higher mean total vessel area measurements for the 3D SPACE technique across all three vascular beds were observed. No significant differences in lumen area for both the right and left carotids were observed between the two techniques. Overall, a significant-correlation existed between measures obtained between the two approaches. Qualitative and quantitative measurements between 3D SPACE and 2D TSE techniques are comparable. 3D-SPACE may be a feasible approach in the evaluation of cardiovascular patients.


A global land cover training dataset from 1984 to 2020.
State-of-the-art cloud computing platforms such as Google Earth Engine (GEE) enable regional-to-global land cover and land cover change mapping with machine learning algorithms. However, collection of high-quality training data, which is necessary for accurate land cover mapping, remains costly and labor-intensive. To address this need, we created a global database of nearly 2 million training units spanning the period from 1984 to 2020 for seven primary and nine secondary land cover classes. Our training data collection approach leveraged GEE and machine learning algorithms to ensure data quality and biogeographic representation. We sampled the spectral-temporal feature space from Landsat imagery to efficiently allocate training data across global ecoregions and incorporated publicly available and collaborator-provided datasets to our database. To reflect the underlying regional class distribution and post-disturbance landscapes, we strategically augmented the database. We used a machine learning-based cross-validation procedure to remove potentially mis-labeled training units. Our training database is relevant for a wide array of studies such as land cover change, agriculture, forestry, hydrology, urban development, among many others.


Youth's Family and Non-Family Roles as Predictors of Subjective Adulthood in Three Low-Income Agricultural Settings.
Subjective adulthood, or feeling like an adult, captures identity development relative to the local context that shapes life course processes. Most research on this topic is conducted in wealthy developed countries. Instead, we draw on household-based survey data from the Family Migration and Early Life Outcomes project (FAMELO) to estimate ordinal logistic regression models predicting how often adolescents aged 11-17 in Jalisco, Mexico (n = 1,567); Gaza Province, Mozambique (n = 1,368); and the Chitwan Valley, Nepal (n = 1,898), identify as adults. The relationships between adult roles, family capital, youth characteristics, and youth's adult identities vary substantially across the sites. The findings highlight how the transition to adulthood reflects the cultural and structural conditions of adult identities.


Overlap between neurodegenerative disorders.
Neurodegenerative disorders are characterized by the formation of distinct pathological changes in the brain, including extracellular protein deposits, cellular inclusions, and changes in cell morphology. Since the earliest published descriptions of these disorders, diagnosis has been based on clinicopathological features, namely, the coexistence of a specific clinical profile together with the presence or absence of particular types of lesion. In addition, the molecular profile of lesions has become an increasingly important feature both in the diagnosis of existing disorders and in the description of new disease entities. Recent studies, however, have reported considerable overlap between the clinicopathological features of many disorders leading to difficulties in the diagnosis of individual cases and to calls for a new classification of neurodegenerative disease. This article discusses: (i) the nature and degree of the overlap between different neurodegenerative disorders and includes a discussion of Alzheimer's disease, dementia with Lewy bodies, the fronto-temporal dementias, and prion disease; (ii) the factors that contribute to disease overlap, including historical factors, the presence of disease heterogeneity, age-related changes, the problem of apolipoprotein genotype, and the co-occurrence of common diseases; and (iii) whether the current nosological status of disorders should be reconsidered.


Human CD34+ hematopoietic stem cells capable of multilineage engrafting NOD/SCID mice express flt3: distinct flt3 and c-kit expression and response patterns on mouse and candidate human hematopoietic stem cells.
The cytokine tyrosine kinase receptors c-kit and flt3 are expressed and function in early mouse and human hematopoiesis. Through its ability to promote ex vivo expansion and oncoretroviral transduction of primitive human hematopoietic progenitors, the flt3 ligand (FL) has emerged as a key stimulator of candidate human hematopoietic stem cells (HSCs). However, recent studies in the mouse suggest that though it is present on short-term repopulating cells, flt3 is not expressed on bone marrow long-term reconstituting HSCs, the ultimate target for the development of cell replacement and gene therapy. Herein we demonstrate that though only a fraction of human adult bone marrow and cord blood CD34+long-term culture-initiating cells (LTC-ICs) express flt3, most cord blood lymphomyeloid HSCs capable of in vivo reconstituting nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice are flt3+. The striking difference in flt3 and c-kit expression on mouse and candidate human HSCs translated into a corresponding difference in flt3 and c-kit function because FL was more efficient than SCF at supporting the survival of candidate human HSCs. In contrast, SCF is far superior to FL as a viability factor for mouse HSCs. Thus, the present data provide compelling evidence for a contrasting expression and response pattern of flt3 and c-kit on mouse and human HSCs.


Anti-thyrotrophin receptor antibodies in Graves' disease as demonstrated directly by immunoprecipitation assay.
An immunoprecipitation assay was developed to determine the presence of antibodies against human TSH receptors. With this assay we were able to demonstrate that in comparison with sera from normal controls. 24 out of 30 (80%) sera from patients with untreated Graves' disease could immunoprecipitate more [125I]TSH-TSH receptor complexes. In 9 assays, an average of 14.1 +/- 3.7% (SD) of the [125I]TSH-TSH receptor complexes was immunoprecipitated by the 30 Graves' sera vs 9.8 +/- 3.0% by the normal pool serum (n = 23) (P less than 0.001) and 7.7 +/- 2.8% by the 22 normal sera (P less than 0.001). One serum of the 24 positive Graves' sera was studied in detail. The results suggest that this serum contained an anti-TSH receptor auto-antibody directed towards a different determinant on the TSH receptor than the TSH binding site.


[Circulating immune complexes in the diagnosis of Mycoplasma pneumoniae infection].
The possibility of detecting M. pneumoniae antigen and antibodies to it, incorporated into immune complexes, in the sera of patients with acute pneumonia by means of erythrocyte diagnosticums was studied, and the immunological characterization of these complexes was made. In patients with mycoplasmal pneumonia M. pneumoniae antigen and specific antibodies, both free and incorporated into immune complexes, were found to circulate in the blood. In children, antigenemia was detected twice as frequently as in adults. Dissociated M. pneumoniae antigens had different molecular weight, their location on the gel chromatogram of the serum being in fractions 7S and 19S. The dissociation of immune complexes permits the detection of M. pneumoniae antigen and antibodies to it in a bound state by means of the passive hemagglutination test, thus increasing the frequency of positive results in the diagnosis of M. pneumoniae infection.


Observation of hysteresis effects in POLICRYPS holographic gratings.
We report on the observation of hysteresis effects that take place in the electro-optical response of a polymer-liquid-crystal-polymer slice grating named POLICRYPS. Investigation of transmittance as a function of an applied external voltage reveals an hysteresis area that is strongly correlated to the delay between consecutive applications of square wave voltages of different amplitude. A suitable software has been implemented to control this delay: when it is long, results show a large hysteresis area, which can be reduced by diminishing the delay. In addition, correlation between this area and the frequency of the applied voltage is analyzed, taking into account that the effect of impurity ions migration is not negligible in the case of low frequencies.


The Aachen Falls Prevention Scale: Multi-Study Evaluation and Comparison.
Fall risk assessment is a time-consuming and resource-intensive activity. Patient-driven self-assessment as a preventive measure might be a solution to reduce the number of patients undergoing a full clinical fall risk assessment. The aim of this study was (1) to analyze test accuracy of the Aachen Falls Prevention Scale (AFPS) and (2) to compare these results with established fall risk assessment measures identified by a review of systematic reviews. Sensitivity, specificity, and receiver operating curves (ROC) of the AFPS were calculated based on data retrieved from 2 independent studies using the AFPS. Comparison with established fall risk assessment measures was made by conducting a review of systematic reviews and corresponding meta-analysis. Electronic databases PubMed, Web of Science, and EMBASE were searched for systematic reviews and meta-analyses that reviewed fall risk assessment measures between the years 2000 and 2018. The review of systematic reviews was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. The Revised Assessment of Multiple SysTemAtic Reviews (R-AMSTAR) was used to assess the methodological quality of reviews. Sensitivity, specificity, and ROC were extracted from each review and compared with the calculated values of the AFPS. Sensitivity, specificity, and ROC of the AFPS were evaluated based on 2 studies including a total of 259 older adults. Regarding the primary outcome of the AFPS subjective risk of falling, pooled sensitivity is 57.0% (95% CI 0.467-0.669) and specificity is 76.7% (95% CI 0.694-0.831). If 1 out of the 3 subscales of the AFPS is used to predict a fall risk, pooled sensitivity could be increased up to 90.0% (95% CI 0.824-0.951), whereas mean specificity thereby decreases to 50.0% (95% CI 0.42-0.58). A systematic review for fall risk assessment measures produced 1478 articles during the study period, with 771 coming from PubMed, 530 from Web of Science, and 177 from EMBASE. After eliminating doublets and assessing full text, 8 reviews met the inclusion criteria. All were of sufficient methodological quality (R-AMSTAR score ≥22). A total number of 9 functional or multifactorial fall risk assessment measures were extracted from identified reviews, including Timed Up and Go test, Berg Balance Scale, Performance-Oriented Mobility Assessment, St Thomas's Risk Assessment Tool in Falling Elderly, and Hendrich II Fall Risk Model. Comparison of these measures with pooled sensitivity and specificity of the AFPS revealed a sufficient quality of the AFPS in terms of a patient-driven self-assessment tool. It could be shown that the AFPS reaches a test accuracy comparable with that of the established methods in this initial investigation. However, it offers the advantage that the users can perform the self-assessment independently at home without involving trained health care professionals.


A 21st century roadmap for human health risk assessment.
The Health and Environmental Sciences Institute (HESI)-coordinated Risk Assessment in the 21st Century (RISK21) project was initiated to develop a scientific, transparent, and efficient approach to the evolving world of human health risk assessment, and involved over 120 participants from 12 countries, 15 government institutions, 20 universities, 2 non-governmental organizations, and 12 corporations. This paper provides a brief overview of the tiered RISK21 framework called the roadmap and risk visualization matrix, and articulates the core principles derived by RISK21 participants that guided its development. Subsequent papers describe the roadmap and matrix in greater detail. RISK21 principles include focusing on problem formulation, utilizing existing information, starting with exposure assessment (rather than toxicity), and using a tiered process for data development. Bringing estimates of exposure and toxicity together on a two-dimensional matrix provides a clear rendition of human safety and risk. The value of the roadmap is its capacity to chronicle the stepwise acquisition of scientific information and display it in a clear and concise fashion. Furthermore, the tiered approach and transparent display of information will contribute to greater efficiencies by calling for data only as needed (enough precision to make a decision), thus conserving animals and other resources.


Sparking interest in public health amongst future doctors to tackle our NHS sustainability crisis.
This article was migrated. The article was marked as recommended. The new NHS 'Long Term Plan' has a particular focus on the public health issues of disease prevention and reducing health inequalities. However, medical students often perceive public health as abstract and irrelevant to clinical practice. We believe students need to be encouraged to appreciate wider public health issues and ultimately be able to apply clinical and public health tools to achieve change for patients and populations. Our aim is for all medical graduates to be able to apply public health and evidence-based principles to their chosen specialties. In the undergraduate curriculum, we hope to extend problem-, case-, and simulation-based learning into public health education, emphasise the context around statistics and epidemiology teaching, and make the teaching more relevant, tangible and enjoyable. Intercalated BSc students will gain an interdisciplinary perspective by joining Master of Public Health (MPH) students to learn about the prevention and control of disease and the promotion of health and wellbeing. They will also have opportunities to join the new Health Intelligence Team (H.I.T.), on a voluntary reserve list to support Public Health Wales in the event of real investigations. We will evaluate these strategies, and we hope that medical educators worldwide will share their experience of innovative approaches to public health and evidence-based medicine teaching in response to this article, so that public health teaching may be improved.


Phospholipase C inhibitor, U73122, releases intracellular Ca2+, potentiates Ins(1,4,5)P3-mediated Ca2+ release and directly activates ion channels in mouse pancreatic acinar cells.
It is recognized in many cellular systems that the receptor/G-protein activation of phospholipase C and Ins(1,4,5)P3 production is the transduction pathway regulating the release of Ca2+ from internal stores. Ca2+ signals can now be monitored at the level of single cells but the biochemical detection of Ins(1,4,5)P3 cannot match this resolution. It is often difficult or impossible to directly attribute responses evoked in single cells by putative phospholipase C-coupled agonists to changes in Ins(1,4,5)P3 levels. U73122 is an aminosteroid that is reported to act as a specific inhibitor of phospholipase C and it has become an important tool in establishing the link between phospholipase C activation and cellular Ca2+ signalling. In the present study we use both patch-clamp electrophysiology and the imaging of fluorescent Ca2+ indicators to investigate the effect of U73122 in mouse pancreatic acinar cells. The study reveals that U73122 has effects other than the inhibition of phospholipase C. U73122 can directly activate ion channels. It can itself promote the release of Ca2+ from intracellular stores in permeabilized cells and in intact cells it triggers a release of Ca2+ that is initiated specifically at the secretory pole of these morphologically and functionally polarized cells. We also present evidence that U73122 can potentiate the response to Ins(1,4,5)P3; this is seen both in permeabilized cells and in patch-clamp protocols in which cells are internally dialysed with submaximal concentrations of Ins(1,4,5)P3. The effects of U73122 are therefore multiple and not specific for the inhibition of phospholipase C. Importantly, all the effects described influence Ca2+ signalling yet in many experimental protocols some of these effects can go unnoticed and might in error be attributed simply to the inhibition of Ins(1,4,5)P3 production.


Refining the latent structure of neuropsychological performance in schizophrenia.
Elucidating the cognitive architecture of schizophrenia promises to advance understanding of the clinical and biological substrates of the illness. Traditional cross-sectional neuropsychological approaches differentiate impaired from normal cognitive abilities but are limited in their ability to determine latent substructure. The current study examined the latent architecture of abnormal cognition in schizophrenia via a systematic approach. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were carried out on a large neuropsychological dataset including the Brief Assessment of Cognition in Schizophrenia, Continuous Performance Test, Wisconsin Card Sorting Test, Benton Judgment of Line Orientation Test, and Wechsler Abbreviated Scale of Intelligence matrix reasoning derived from 1012 English-speaking ethnic Chinese healthy controls and 707 schizophrenia cases recruited from in- and out-patient clinics. An initial six-factor model fit cognitive data in healthy and schizophrenia subjects. Further modeling, which accounted for methodological variance between tests, resulted in a three-factor model of executive functioning, vigilance/speed of processing and memory that appeared to best discriminate schizophrenia cases from controls. Factor analytic-derived g estimands and conventionally calculated g showed similar case-control discrimination. However, agreement analysis suggested systematic differences between both g indices. Factor structures derived in the current study were broadly similar to those reported previously. However, factor structures between schizophrenia subjects and healthy controls were different. Roles of factor analytic-derived g estimands and conventional composite score g were further discussed. Cognitive structures underlying cognitive deficits in schizophrenia may prove useful for interrogating biological substrates and enriching effect sizes for subsequent work.


[Diagnostic significance of detecting respiratory virus antigens in cerebrospinal fluid and brain cells].
Cerebrospinal fluid (CSF) from 202 patients (114 children and 88 adults) was studied by immunofluorescent techniques. Antigens of respiratory viruses in the CSF were most frequently encountered (22%) in patients with the involvement of the central nervous system (usually meningoencephalitis) in the presence of acute respiratory disease. In lethal outcomes in the same group viral antigens in brain cells were also identified. Clinical and morphological findings suggest that these lesions are infectious-allergic in nature. In rare cases (4%) viral antigens in the CSF and brain cells may also be found in patients with acute respiratory diseases without central nervous system involvement which happens when patients' blood-brain barrier is especially permeable.


[Origin of newborn screening programs and their beginnings in Spain].
The first newborn screening programs to detect congenital errors of the metabolism and other endocrinal diseases started in the late 1950s and, one decade later, were introduced in Spain. Since then they have evolved considerably, but in a very heteroge-neous way, at both the international level and the regional level. The continuous scientific and technological advances, basically since the year 2000, have accentuated these inequalities, making this question into an inexhaustible subject of review, debate and argument up until the present. This review aims to gather, in summarized fashion, the origins of the newborn screening programs and their beginnings in Spain as a first step in analyzing their development, evolution and current situation. This year updating is expected to take place in all the Spanish autonomous regions following publication in November 2014 of a state order that regulates and attempts to homogenize these programs.


A cortical mechanism linking saliency detection and motor reactivity in rhesus monkeys.
Sudden and surprising sensory events trigger neural processes that swiftly adjust behavior. To study the phylogenesis and the mechanism of this phenomenon, we trained two male rhesus monkeys to keep a cursor inside a visual target by exerting force on an isometric joystick. We examined the effect of surprising auditory stimuli on exerted force, scalp electroencephalographic (EEG) activity, and local field potentials (LFP) recorded from the dorso-lateral prefrontal cortex. Auditory stimuli elicited (1) a biphasic modulation of isometric force: a transient decrease followed by a corrective tonic increase, and (2) EEG and LFP deflections dominated by two large negative-positive waves (N70 and P130). The EEG potential was maximal at the scalp vertex, highly reminiscent of the human 'vertex potential'. Electrocortical potentials and force were tightly coupled: the P130 amplitude predicted the magnitude of the corrective force increase, particularly in the LFPs recorded from deep rather than superficial cortical layers. These results disclose a phylogenetically-preserved cortico-motor mechanism supporting adaptive behavior in response to salient sensory events.Significance Statement Survival in the natural world depends on an animal's capacity to adapt ongoing behavior to unexpected events. To study the neural mechanisms underlying this capacity, we trained monkeys to apply constant force on a joystick while we recorded their brain activity from the scalp and, invasively, from the prefrontal cortex contralateral to the hand holding the joystick. Unexpected auditory stimuli elicited a biphasic force modulation: a transient reduction followed by a corrective adjustment. The same stimuli also elicited EEG and LFP responses, dominated by a biphasic wave that predicted the magnitude of the behavioral adjustment. These results disclose a phylogenetically-preserved cortico-motor mechanism supporting adaptive behavior in response to unexpected events.


Group V secretory phospholipase A2 reveals its role in house dust mite-induced allergic pulmonary inflammation by regulation of dendritic cell function.
We have previously shown that group V secretory phospholipase A(2) (sPLA(2)) regulates phagocytosis of zymosan and Candida albicans by a mechanism that depends on fusion of phagosomes with late endosomes in macrophages. In this study, we report that group V sPLA(2) (Pla2g5)-null mice exposed to an extract of house dust mite Dermatophagoides farinae had markedly reduced pulmonary inflammation and goblet cell metaplasia compared with wild-type (WT) mice. Pla2g5-null mice had also impaired Th2-type adaptive immune responses to D. farinae compared with WT mice. Pla2g5-null bone marrow-derived dendritic cells (BMDCs) activated by D. farinae had delayed intracellular processing of allergen and impaired allergen-dependent maturation, a pattern recapitulated by the native lung DCs of D. farinae-challenged mice. Adoptively transferred D. farinae-loaded Pla2g5-null BMDCs were less able than D. farinae-loaded WT BMDCs to induce pulmonary inflammation and Th2 polarization in WT mice. However, Pla2g5-null recipients transferred with WT or Pla2g5-null D. farinae-loaded BMDCs exhibited significantly reduced local inflammatory responses to D. farinae, even though the transfer of WT BMDCs still induced an intact Th2 cytokine response in regional lymph nodes. Thus, the expression of group V sPLA(2) in APCs regulates Ag processing and maturation of DCs and contributes to pulmonary inflammation and immune response against D. farinae. Furthermore, an additional yet to be identified resident cell type is essential for the development of pulmonary inflammation, likely a cell in which group V sPLA(2) is upregulated by D. farinae, and whose function is also regulated by group V sPLA(2).