Fluvoxamine: A Review of Its Mechanism of Action and Its Role in COVID-19.
Fluvoxamine is a well-tolerated, widely available, inexpensive selective serotonin reuptake inhibitor that has been shown in a small, double-blind, placebo-controlled, randomized study to prevent clinical deterioration of patients with mild coronavirus disease 2019 (COVID-19). Fluvoxamine is also an agonist for the sigma-1 receptor, through which it controls inflammation. We review here a body of literature that shows important mechanisms of action of fluvoxamine and other SSRIs that could play a role in COVID-19 treatment. These effects include: reduction in platelet aggregation, decreased mast cell degranulation, interference with endolysosomal viral trafficking, regulation of inositol-requiring enzyme 1α-driven inflammation and increased melatonin levels, which collectively have a direct antiviral effect, regulate coagulopathy or mitigate cytokine storm, which are known hallmarks of severe COVID-19.


Fragmentation of inhaled 238PuO2 particles in lung.
Beagle dogs were exposed by inhalation to monodisperse aerosols of 238PuO2. Autoradiographs of lung sections were studied for nine dogs sacrificed from 4 to 730 days after exposure. Fragmentation of particles in lung was observed autoradiographically. A simple mathematical model fitted to the fragmentation and lung retention data for dogs suggests that lung clearance from intact particles (65%) and particle fragments (32%) were important to the removal of 238PuO2 deposited in the lung by inhalation. The increased surface area resulting from fragmentation should increase dissolution and risk to other organs from irradiation by translocated plutonium.


Long-acting antibiotic formulations in the treatment of calf pneumonia: a comparative study of tilmicosin and oxytetracycline.
The treatment of an outbreak of acute pneumonia in 50 four- to eight-month-old Friesian and Friesian cross calves is described. At the first visit (day 0) 16 calves received 20 mg/kg bodyweight of oxytetracycline dihydrate intramuscularly and 15 received 10 mg/kg of the macrolide tilmicosin subcutaneously. The remaining 19 in-contact animals were not considered ill enough to be included in the trial and received 20 mg/kg of oxytetracycline dihydrate. The rectal temperature, demeanour, respiratory rate and respiratory effort of each calf was assessed on days 1, 2, 3, 9, 14, 21 and 28, and calves which had not responded were given repeat injections of the same antibiotic. All the calves recovered from the outbreak and of the 19 calves treated strategically, three required a second injection. Among the calves with clinical pneumonia, fewer treatments (P less than 0.01) were required by those treated with tilmicosin. The rectal temperatures of both groups decreased (P less than 0.05) after the first injection, but on day 3 the decrease was greater (P less than 0.05) in the group treated with tilmicosin. Respiratory rates varied widely but respiratory effort was less (P less than 0.05) on day 2 in the calves treated with tilmicosin. When long-acting antibiotic injections are used to treat enzootic pneumonia it is suggested that a second visit should be made on day 3 to assess the animals' response to treatment.


LAMP-based molecular sexing in a gonochoric marine bivalve (Macoma balthica rubra) with divergent sex-specific mitochondrial genomes.
Taking advantage of the unique system of doubly uniparental inheritance (DUI) of mitochondria, we developed a reliable molecular method to sex individuals of the marine bivalve Macoma balthica rubra. In species with DUI (~100 known bivalves), both sexes transmit their mitochondria: males bear both a male- and female-type mitogenome, while females bear only the female type. Male and female mitotypes are sufficiently divergent to reliably PCR-amplify them specifically. Loop-mediated isothermal amplification (LAMP) is a precise, economical and portable alternative to PCR for molecular sexing and we demonstrate its application in this context. We used 154 individuals sampled along the Atlantic coast of France and sexed microscopically by gonad examination to test for the congruence among gamete type, PCR sexing and LAMP sexing. We show an exact match among the sexing results from these three methods using the male and female mt-cox1 genes. DUI can be disrupted in inter-specific hybrids, causing unexpected distribution of mitogenomes, such as homoplasmic males or heteroplasmic females. To our knowledge, DUI disruption at the intra-specific scale has never been tested. We applied our sexing protocol to control for unexpected heteroplasmy caused by hybridization between divergent genetic lineages and found no evidence of disruption in the mode of mitochondrial inheritance in M. balthica rubra. We propose LAMP as a useful tool to accelerate eco-evolutionary studies of DUI. It offers the opportunity to investigate the potential role of, previously unaccounted-for, sex-specific patterns such as sexual selection or sex-specific dispersal bias in the evolution of free-spawning benthic species.


Ablation of the Galnt3 gene leads to low-circulating intact fibroblast growth factor 23 (Fgf23) concentrations and hyperphosphatemia despite increased Fgf23 expression.
Familial tumoral calcinosis is characterized by ectopic calcifications and hyperphosphatemia. The disease is caused by inactivating mutations in fibroblast growth factor 23 (FGF23), Klotho (KL), and uridine diphosphate-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 (GALNT3). In vitro studies indicate that GALNT3 O-glycosylates a phosphaturic hormone, FGF23, and prevents its proteolytic processing, thereby allowing secretion of intact FGF23. In this study we generated mice lacking the Galnt3 gene, which developed hyperphosphatemia without apparent calcifications. In response to hyperphosphatemia, Galnt3-deficient mice had markedly increased Fgf23 expression in bone. However, compared with wild-type and heterozygous littermates, homozygous mice had only about half of circulating intact Fgf23 levels and higher levels of C-terminal Fgf23 fragments in bone. Galnt3-deficient mice also exhibited an inappropriately normal 1,25-dihydroxyvitamin D level and decreased alkaline phosphatase activity. Furthermore, renal expression of sodium-phosphate cotransporters and Kl were elevated in Galnt3-deficient mice. Interestingly, there were sex-specific phenotypes; only Galnt3-deficient males showed growth retardation, infertility, and significantly increased bone mineral density. In summary, ablation of Galnt3 impaired secretion of intact Fgf23, leading to decreased circulating Fgf23 and hyperphosphatemia, despite increased Fgf23 expression. Our findings indicate that Galnt3-deficient mice have a biochemical phenotype of tumoral calcinosis and provide in vivo evidence that Galnt3 plays an essential role in proper secretion of Fgf23 in mice.


Weight Estimation of Mediterranean Food Images using Random Forest Regression Algorithm.
The daily nutrition management is one of the most important issues that concern individuals in the modern lifestyle. Over the years, the development of dietary assessment systems and applications based on food images has assisted experts to manage people's nutritional facts and eating habits. In these systems, the food volume estimation is the most important task for calculating food quantity and nutritional information. In this study, we present a novel methodology for food weight estimation based on a food image, using the Random Forest regression algorithm. The weight estimation model was trained on a unique dataset of 5,177 annotated Mediterranean food images, consisting of 50 different foods with a reference card placed next to the plate. Then, we created a data frame of 6,425 records from the annotated food images with features such as: food area, reference object area, food id, food category and food weight. Finally, using the Random Forest regression algorithm and applying nested cross validation and hyperparameters tuning, we trained the weight estimation model. The proposed model achieves 22.6 grams average difference between predicted and real weight values for each food item record in the data frame and 15.1% mean absolute percentage error for each food item, opening new perspectives in food image-based volume and nutrition estimation models and systems.Clinical Relevance- The proposed methodology is suitable for healthcare systems and applications that monitor an individual's malnutrition, offering the ability to estimate the energy and nutrients consumed using an image of the meal.


Laparoscopic transabdominal anterior bilateral adrenalectomy (La-TABA): an alternative approach for severe Cushing's syndrome.
Severe uncontrolled Cushing's syndrome (CS) is an acute life-threatening condition. As it is often not responsive to medical therapy, emergency bilateral adrenalectomy (BA) may present the only therapeutic option. Moreover, multiple bone fractures, representing one of the clinical consequences of hypercortisolism, may not permit both prone and lateral patient's positioning during surgery, thus making minimally invasive approaches nonfeasible. We report our preliminary experience with an alternative approach in this selected patients' category. Among 613 patients who underwent endoscopic adrenalectomy at our centre (34-5.6% BA) between January 1997 and October 2021, 3 patients were scheduled for laparoscopic transabdominal anterior bilateral adrenalectomy (La-TABA). Surgery was performed with patient in supine position, with fastened arms and legs to allow Trendelenburg and anti-Trendelenburg movements and lateral rotations. The procedure consisted in a synchronous bilateral adrenalectomy. A modern multi-articulated operative table provided rotations on the right and left side to perform left and right adrenalectomy, respectively. One male and two female patients with a mean age of 34 ± 3.1 years underwent La-TABA. Mean operative time was 200 ± 138.3 min. No perioperative complications were registered. Mean postoperative hospital stay was 8 ± 4.4 days. In very severe ACTH-dependent CS, BA should be performed as soon as possible. La-TABA may represent the most appropriate therapeutic option, as this patients' category is not able to tolerate prone and lateral positioning required during the conventional surgery. Despite the higher technical complexity of the procedure compared with the other endoscopic approaches to adrenalectomy, it retains the benefits of minimally invasive surgery in terms of postoperative complications and recovery.


Evaluation of relationship between retinal nerve fiber layer thickness progression and visual field progression in patients with glaucoma.
To evaluate the capability of optical coherence tomography (OCT), retinal nerve fiber layer (RNFL) thickness, and visual field (VF) measurements in glaucoma progression detection. The study examined 62 eyes of 37 glaucoma patients observed over a 3-year period. All eyes underwent at least four serial RNFL measurements performed by Cirrus OCT, with the first and last measurements separated by at least 3 years. VF testing was performed by using the Swedish interactive threshold algorithm (SITA) Standard 30-2 program of the Humphrey field analyzer (HFA) on the same day as the RNFL imaging. Both serial RNFL thicknesses and VF progression were assessed by the guided progression analysis (GPA) software program. RNFL thickness progression was evaluated by event analysis. Total deviation (TD) in the superior or inferior hemifield was also examined. A total of 295 OCT scans and 295 VFs were analyzed. Five eyes exhibited progression by OCT only and 8 eyes exhibited progression by VF GPA only. When the analysis was based on the combined measurement findings, progression was noted in 6 eyes. The average of the progressive hemifield TD at baseline for combined RNFL and VF progression was -3.21±1.38 dB, while it was -2.17±1.14 dB for RNFL progression and -9.12±3.75 dB for VF progression. The average of the progressive hemifield TD indicated a significant advancement of VF progression as compared to RNFL progression (P=0.002). When a mild VF defect is present, OCT RNFL thickness measurements are important in helping discern glaucoma progression.


[MR-guided biopsies with high-resolution ultrafast T2-weighted turbo spin-echo sequence LoLo: initial clinical experience].
The feasibility of the "LoLo"-technique for MR guidance of biopsy procedures was tested. MR-guided biopsies were performed on 10 patients employing a 1.5 T system. The "LoLo"-technique used is a single shot turbo spin echo technique. Only a small field of view is covered in order to yield images with a resolution of 1 mm2 in 600 ms. The orthogonal orientation of the slice selective radio frequency pulses to each other prevents foldover artifacts. No complications occurred. All biopsy procedures yielded sufficient material to diagnose the underlying disease. The "LoLo"-technique enabled good depiction of the needle tip in all cases. T2-weighted contrast typical for turbo spin echo images was observed. No foldover artifacts were detectable. MR-guided biopsies are possible with the "LoLo"technique. Compared to gradient echo sequences T2-weighting and smaller susceptibility artifacts proved to be advantageous.


Novel Therapies in Takayasu Arteritis.
Takayasu Arteritis (TAK) is a large-vessel vasculitis that preferentially involves the aorta and its primary branches. Cardiac involvement is frequent in TAK and is a major determinant of the patient's outcome. Glucocorticoids (GC) are the mainstay of therapy for TAK, with high doses of GC effective to induce remission. However, relapses are common and lead to repeated and prolonged GC treatments with high risk of related adverse events. Potential GC toxicity is a major concern, especially because patients with TAK are young and need to be treated for several years, often for the whole life. Conventional immunosuppressive drugs are used in patients with severe manifestations but present some limitations. New therapeutic approaches are needed for patients with refractory disease or contraindications to conventional therapies. Fortunately, major progress has been made in understanding TAK pathogenesis, leading to the development of targeted biotherapies. In particular, IL-6 and TNF-α pathways seems to be the most promising therapeutic targets, with emerging data on Tocilizumab and TNF inhibitors. On the other hand, new insights on JAK-Inhibitors, Rituximab, Ustekinumab and Abatacept have been explored in recent studies. This review summarizes the emerging therapies used in TAK, focusing on the most recent studies on biologics and analyzing their efficacy and safety.


The Impact of Severe Maternal Morbidity on Very Preterm Infant Outcomes.
To estimate the prevalence of severe maternal morbidity among very preterm births and determine its association with very preterm infant mortality and morbidity. This study used New York City Vital Statistics birth and death records linked with maternal and newborn discharge abstract data for live births between 2010 and 2014. We included 6901 infants without congenital anomalies born between 240/7 and 326/7 weeks of gestation. Severe maternal morbidity was identified as life-threatening conditions or life-saving procedures. Outcomes were first-year infant mortality, severe neonatal morbidity (bronchopulmonary dysplasia, severe necrotizing enterocolitis, stage 3-5 retinopathy of prematurity, and intraventricular hemorrhage grades 3-4), and a combined outcome of death or morbidity. Twelve percent of very preterm live-born infants had a mother with severe maternal morbidity. Maternal and pregnancy characteristics associated with occurrence of severe maternal morbidity were multiparity, being non-Hispanic black, and preexisting health conditions, but gestational age and the percentage small for gestational age did not differ. Infants whose mothers experienced severe maternal morbidity had higher first-year mortality, 11.2% vs 7.7% without severe maternal morbidity, yielding a relative risk of 1.39 (95% CI: 1.14-1.70) after adjustment for maternal characteristics, preexisting comorbidities, pregnancy complications, and hospital factors. Severe neonatal morbidity was not associated with severe maternal morbidity. Severe maternal morbidity is an independent risk factor for mortality in the first year of life among very preterm infants after consideration of other maternal and pregnancy risk factors.


[Preliminary data on "fibrillary centers" of the nucleolus of various cells of the ovarian follicle of a lizard Lacerta muralis Laur].
The nucleolus of the thecal cells and little cells of the granulosa contains generally a single "fibrillar center" surrounded by the dense fibrous material of the nucleolus. The "fibrillar centers" are in contact with nucleolar associated heterochromatin. Cytochemical results show that "fibrillar centers" are chiefly composed of proteins which are revealed as ribonucleoproteins with the EDTA method, but the amount of RNA associated with these proteins seems to be small. It is possible that the fibrillar center also contains a little DNA.


Egr-1 regulates expression of the glial scar component phosphacan in astrocytes after experimental stroke.
Ischemic brain injury causes tissue damage and neuronal death. The deficits can often be permanent because adult neurons fail to regenerate. One barrier to neuronal regeneration is the formation of the glial scar, a repair mechanism that is otherwise necessary to seal off necrotic areas. The process of gliosis has been well described, but the mechanisms regulating the robust production of scar components after injury remain poorly understood. Here we show that the early growth response 1 transcriptional factor (Egr-1, also called Krox24, Zif268, and NGFI-A) is expressed in astrocytes in the ventricular wall, corpus callosum, and striatum of normal mouse brain. After experimental stroke caused by permanent occlusion of the middle cerebral artery, Egr-1 was expressed long term in reactive astrocytes that accumulate around the injury site. Gain- and loss-of-function studies in primary astrocytes indicated that Egr-1 regulates the transcription of chondroitin sulfate proteoglycans genes, the main extracellular matrix proteins of the glial scar. Egr-1 bound to a site within the phosphacan promoter and transactivated its expression. Egr-1-deficient mice accumulated lower levels of phosphacan RNA and protein than wild-type mice after stroke, but there were no measurable differences in neurite outgrowth toward the infarct area between the two groups. Our findings suggest that Egr-1 is an important component of the transcriptional network regulating genes involved in gliosis after ischemic injury.


The incidence of alcohol abuse and coagulopathy in penetrating abdominal trauma.
Preexisting coagulopathy or hepatic dysfunction is a potential problem in the alcoholic with penetrating abdominal trauma. This study reviews 36 patients with penetrating abdominal trauma to determine evidence of acute and/or chronic alcohol abuse, evidence of hepatic dysfunction, preexisting coagulopathy, pattern of blood use, and severity of injury. Sixty-four per cent of patients had detectable blood alcohol concentrations (BAC) on admission and 50% were legally intoxicated. Alcohol consumption histories were available for 24 patients, and 15 (63%) were chronic alcohol abusers. There was little evidence of hepatic dysfunction and minimal coagulopathy. There was a significant difference in the number of chronic alcohol abusers who received blood and in the amount used by any individual. There is nothing in this study to suggest this increased blood use would be lessened by including fresh frozen plasma, Vitamin K, or platelet packs in the initial resuscitation of the alcoholic patient with penetrating abdominal trauma.


EDTP/MTMR14: A novel target for improved survivorship to prolonged anoxia and cellular protein aggregates.
Drosophila egg-derived tyrosine phosphatase (EDTP), a lipid phosphatase that removes 3-position phosphate at the inositol ring, has dual functions in oogenesis and muscle performance in adults. A mammalian homologous gene MTMR14, which encodes the myotubularin-related protein 14, negatively regulates autophagy. Mutation of EDTP/MTMR14, however, causes at least three deleterious consequences: (1) the lethality in early embryogenesis in Drosophila; (2) a "jumpy" phenotype with apparently impaired motor functions; and (3) an association with a rare genetic disorder called centronuclear myopathy. The potential benefit of EDTP/MTMR14 downregulation is likely masked by the lethality or severe muscle defects due to ubiquitous loss of this gene. Here we show that flies carrying a heterozygous EDTP mutation had increased survivorship to prolonged anoxia; tissue-specific downregulation of EDTP in non-muscle tissues, particularly motoneurons, extended lifespan and improved survivorship to beta-amyloid peptides (Aβ42) and polyglutamine protein aggregates. These data highlight the significance of selective downregulation of EDTP in non-muscles for beneficial consequences. MTMR14 expression was evident in the hippocampus and cortex in C57BL/6 J and APP/PS1 mice. Compared with C57BL/6 J mice, APP/PS1 mice had reduced MTMR14 in the cortex. Hippocampal expression of MTMR14 was increased and plateaued at 9-17 months compared with 2-6 months in C57BL/6 J mice. Additionally, MTMR14 was inducible by Aβ42 in the rat primarily hippocampal neurons and mouse Neuro2a neuroblasts. We demonstrate a novel approach of tissue-specific downregulation of the disease-associated gene EDTP/MTMR14 for extended lifespan and improved survivorship to cellular protein aggregates. This approach could be extended from insects to mammals.


Anabolic steroids.
Anabolic steroids are synthetic derivatives of testosterone modified to enhance the anabolic rather than the androgenic actions of the hormone. The anabolic effects are considered to be those promoting protein synthesis, muscle growth and crythopoiesis. There are numerous side-effects to anabolic steroids, including hypertension and atherosclerosis, blood clotting, jaundice, hepatic carcinoma, tendon damage, psychiatric and behavioural effects and, in males, reduced fertility and gynaccomastia. Anabolic steroids were added to the International Olympic Committee's list of banned substances in 1975. The majority of 'evidence' concerning the efficacy of anabolic steroids as performance enhancing agents is anecdotal. In the main, experimental investigations have been poorly designed scientifically, clinically and statistically. The percentage of positive test results from IOC accredited laboratories has remained consistently low. However, athletes take their steroids during training and out-of-competition testing is not conducted in all countries, although international co-operation is now under consideration. Despite the lack of conclusive evidence, steroids users will continue to hold the view that their effects are efficacious and they are therefore unlikely to be persuaded to curtail their use.


Cx36 expression in the AII-mediated rod pathway is activity dependent in the developing rabbit retina.
Gap junctions are composed of connexin 36 (Cx36) and play a critical role in the rod photoreceptor signaling pathways of the vertebrate retina. Despite the fact that their connection and modulation in various rod pathways have been extensively studied in adult animals, little is known about the contribution and regulation of gap junctions to the development of the AII amacrine cell (AC)-mediated rod pathway. Using immunohistochemistry and microinjection, this study demonstrates a steady increase in relative Cx36 protein expression in both plexiform layers of the rabbit retina at around the time of eye opening. However, immediately after eye opening, most Cx36 immunoreactive AII ACs show no gap junction coupling pattern to neighboring cells and it is not until the third postnatal week that AII cells begin to exhibit an adult-like tracer-coupling pattern. Moreover, studies using dark-rearing and AMPA receptor blockade during postnatal development both revealed that relative levels of Cx36 immunoreactivity in AII ACs were increased when neural activity was inhibited. Our findings suggest that Cx36 expression in the AII-mediated rod pathway is activity dependent in the developing rabbit retina.


The effect of seed mass and gap size on seed fate of tropical rain forest tree species in guyana.
For eleven tree species, differing in seed mass, germination success (emergence success for two small-seeded species) and the causes of failure to germinate were studied in the forest understorey and in logging gaps in the tropical rain forests of Guyana. In the forest understorey, germination success increased with seed mass. However, as gap size increased the difference between smaller and larger seeded species diminished because germination success of smaller-seeded species increased slightly, while that of larger-seeded species decreased dramatically. The negative effect of gap size on germination success of larger-seeded species was caused by an increased risk of desiccation with gap size, which was a far more important seed mortality agent for larger than for smaller-seeded species. Generally, seeds of smaller-seeded species suffered more from insect predation and were removed at higher rates than larger-seeded species. On the other hand, larger-seeded species were eaten more by mammals than smaller-seeded species. It is concluded that logging can result in shifts in the species composition in the tropical rain forests of Guyana which are dominated by species with large seeds, since germination success of larger-seeded species is dramatically reduced in large logging gaps.


Validation of the Measurement of Need Frustration.
Until recently, need frustration was considered to be the absence of need satisfaction, rather than a separate dimension. Whilst the absence of need satisfaction can hamper growth, experiencing need frustration can lead to malfunctioning and subsequent psychopathology. Therefore, examining these constructs separately is vital, as they produce different outcomes, with the consequences of need frustration potentially more severe. This study sought to examine predictors of need frustration using undergraduate students and individuals from the wider community (N = 510, females N = 404, M age = 24.15). Participants completed the new need satisfaction frustration scale and measures of anxiety, stress, depression, and negative and positive affect. Support for the position that need frustration is separate to Need Satisfaction and is related to psychological health problems (i.e., ill-being) was found. However, autonomy frustration was not found to be a significant predictor of ill-being. Extending previous research, this study found relationships of stress and somatic anxiety with need frustration. Further, a relationship between need frustration with anxiety and depression occurred, when these symptom dimensions were examined separately, through distinct questionnaires. Support for the construct of need frustration highlights the necessity of examining need frustration in addition to need satisfaction within future studies. Interventions specific to reducing need frustration, specifically competence and relatedness frustration within both the educational and workplace setting are outlined.


Irreversible inhibition of putrescine-stimulated S-adenosyl-L-methionine decarboxylase by berenil and pentamidine.
The putrescine-stimulated S-adenosyl-L-methionine decarboxylases from rat liver and yeast were strongly inhibited by Berenil and to a lesser extent by Pentamidine. Ten times greater drug concentrations were needed to achieve a similar level of inhibition of a Mg2+-stimulated bacterial enzyme. The inhibition was irreversible in that extensive dialyses or precipitation with (NH4)2SO4 did not restore enzyme activity. Putrescine did not protect the enzyme against Berenil, but adenosylmethionine either alone or with putrescine partially protected the irreversible action of Berenil. The compound 4,4'-diamidinodiphenylamine, which differs from Berenil only in lacking the azo group between benzene rings, was a weaker inhibitor than Berenil, and its inhibition was reversible. Berenil also inhibited the activity of adenosylmethionine decarboxylase in vivo, by depressing the activity of the enzyme in normal rat liver, for at least 24 h after a single injection (50 mg/kg body wt.) of the drug.


Assessment of COVID-19 progression on day 5 from symptoms onset.
A major limitation of current predictive prognostic models in patients with COVID-19 is the heterogeneity of population in terms of disease stage and duration. This study aims at identifying a panel of clinical and laboratory parameters that at day-5 of symptoms onset could predict disease progression in hospitalized patients with COVID-19. Prospective cohort study on hospitalized adult patients with COVID-19. Patient-level epidemiological, clinical, and laboratory data were collected at fixed time-points: day 5, 10, and 15 from symptoms onset. COVID-19 progression was defined as in-hospital death and/or transfer to ICU and/or respiratory failure (PaO2/FiO2 ratio < 200) within day-11 of symptoms onset. Multivariate regression was performed to identify predictors of COVID-19 progression. A model assessed at day-5 of symptoms onset including male sex, age > 65 years, dyspnoea, cardiovascular disease, and at least three abnormal laboratory parameters among CRP (> 80 U/L), ALT (> 40 U/L), NLR (> 4.5), LDH (> 250 U/L), and CK (> 80 U/L) was proposed. Discrimination power was assessed by computing area under the receiver operating characteristic (AUC) values. A total of 235 patients with COVID-19 were prospectively included in a 3-month period. The majority of patients were male (148, 63%) and the mean age was 71 (SD 15.9). One hundred and ninety patients (81%) suffered from at least one underlying illness, most frequently cardiovascular disease (47%), neurological/psychiatric disorders (35%), and diabetes (21%). Among them 88 (37%) experienced COVID-19 progression. The proposed model showed an AUC of 0.73 (95% CI 0.66-0.81) for predicting disease progression by day-11. An easy-to-use panel of laboratory/clinical parameters computed at day-5 of symptoms onset predicts, with fair discrimination ability, COVID-19 progression. Assessment of these features at day-5 of symptoms onset could facilitate clinicians' decision making. The model can also play a role as a tool to increase homogeneity of population in clinical trials on COVID-19 treatment in hospitalized patients.


[Surveillance of Haemophilus influenzae serotypes and antimicrobial resistance in Colombia, 1994-2002].
Invasive disease caused by Haemophilus influenzae serotype b results in high rates of morbidity and mortality among children. In 1994, the Microbiology Group at the Instituto Nacional de Salud (Colombia) initiated a program to detect antimicrobial resistance in H. influenzae. Invasive isolates were collected by hospitals and public health laboratories as part of surveillance programs for acute respiratory infections and acute bacterial meningitis. To determine the evolution of serotypes and antimicrobial resistance patterns, invasive H. influenzae isolates collected from 1994 to 2002 were compared, and the impact of Hib conjugated vaccine in Colombia was reassessed. The analysis included 683 isolates, 379 (55.5%) were recovered from male patients, 370 (54.2%) from children under one year, 227 (33.2%) from children aged 1 to 5, 19 (2.8%) from children aged 6 to 14, and 38 (5.6%) from children over 14 years; 29 (4.2%) with no age data. Clinical classification recorded 493 (72.2%) of the samples were from patients with meningitis, 181 (26.5%) with pneumonia, and 9 (0.9%) with other diseases. Eighty five percent of isolates corresponded to H. influenzae serotype b, 12.9% were non capsular, and 2.0% corresponded to other serotypes (10 a, 1 d, 1 e and 2 f). Of the total number of isolates, 12.0% produced beta lactamase, 13.9% were resistant to ampicillin, 12.7% to trimethoprim sulfamethoxazole (SXT), 5.4% to chloramphenicol, 1% to cefuroxime. All isolates were susceptible to ceftriaxone. During the 10-year period, resistance to SXT increased from 5% to 13%. A significant decrease in meningitis cases was detected among children under one-year old and in the 1 to 5 age group. Before introducing the vaccine, an annual average of 43 and 23 isolates for each of these groups were received. During 2002, 10 and 6 isolates, respectively, were received for each group. Surveillance of invasive H. influenzae isolates has allowed the evaluation of Hib vaccine impact, as well as the detection of an increase of non-capsular isolates, and changes in resistance patterns.


Chronic pancreatitis and pancreatic carcinoma.
The differential diagnosis between pancreatic cancer and chronic pancreatitis is very important as the management and prognosis of these two diseases is different. In most patients with pancreatic disease, the diagnosis can be established but there is a subgroup of patients in whom it is difficult to differentiate between these conditions because the clinical presentation is often similar and currently available diagnostic tests may be unable to distinguish between an inflammatory or neoplastic pancreatic mass. This paper reviews the aetiology, pathology and clinical features of these diseases and discusses the limitations of conventional diagnostic methods and how newer techniques may be of value in the differential diagnosis.


[Pancreatic cancer. Evidence based management guidelines of the Hungarian Pancreatic Study Group].
Pancreatic cancer is a disease with a poor prognosis usually diagnosed at a late stage. Therefore, screening, diagnosis, treatment and palliation of pancreatic cancer patients require up-to-date and evidence based management guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available scientific evidence and international guidelines. The preparatory and consultation board appointed by the Hungarian Pancreatic Study Group translated and complemented/modified the recent international guidelines. 37 clinical statements in 10 major topics were defined (Risk factors and genetics, Screening, Diagnosis, Staging, Surgical care, Pathology, Systemic treatment, Radiation therapy, Palliation and supportive care, Follow-up and recurrence). Evidence was graded according to the National Comprehensive Cancer Network (NCCN) grading system. The draft of the guideline was presented and discussed at the consensus meeting in September 12, 2014. Statements were accepted with either total (more than 95% of votes, n = 15) or strong agreement (more than 70% of votes, n = 22). The present guideline is the first evidence-based pancreatic cancer guideline in Hungary that provides a solid ground for teaching purposes, offers quick reference for daily patient care and guides financing options. The authors strongly believe that these guidelines will become a standard reference for pancreatic cancer treatment in Hungary.


Optimal matching with minimal deviation from fine balance in a study of obesity and surgical outcomes.
In multivariate matching, fine balance constrains the marginal distributions of a nominal variable in treated and matched control groups to be identical without constraining who is matched to whom. In this way, a fine balance constraint can balance a nominal variable with many levels while focusing efforts on other more important variables when pairing individuals to minimize the total covariate distance within pairs. Fine balance is not always possible; that is, it is a constraint on an optimization problem, but the constraint is not always feasible. We propose a new algorithm that returns a minimum distance finely balanced match when one is feasible, and otherwise minimizes the total distance among all matched samples that minimize the deviation from fine balance. Perhaps we can come very close to fine balance when fine balance is not attainable; moreover, in any event, because our algorithm is guaranteed to come as close as possible to fine balance, the investigator may perform one match, and on that basis judge whether the best attainable balance is adequate or not. We also show how to incorporate an additional constraint. The algorithm is implemented in two similar ways, first as an optimal assignment problem with an augmented distance matrix, second as a minimum cost flow problem in a network. The case of knee surgery in the Obesity and Surgical Outcomes Study motivated the development of this algorithm and is used as an illustration. In that example, 2 of 47 hospitals had too few nonobese patients to permit fine balance for the nominal variable with 47 levels representing the hospital, but our new algorithm came very close to fine balance. Moreover, in that example, there was a shortage of nonobese diabetic patients, and incorporation of an additional constraint forced the match to include all of these nonobese diabetic patients, thereby coming as close as possible to balance for this important but recalcitrant covariate.


Semantic description of aerial images using stochastic labeling.
This paper discusses the application of stochastic labeling to a general symbolic image description problem. A method used to compute initial likelihoods and compatibilities is described. It was derived from an earlier symbolic matching procedure, but was modified to provide the data needed for application of the labeling method. This labeling procedure differs from simpler ones, in that it minimizes a global criterion at each iteration. This technique is compared to other matching methods, and results on two scenes are presented.


Intercellular communication in Helicobacter pylori: luxS is essential for the production of an extracellular signaling molecule.
Individual bacteria of numerous species can communicate and coordinate their actions via the production, release, and detection of extracellular signaling molecules. In this study, we used the Vibrio harveyi luminescence bioassay to determine whether Helicobacter pylori produces such a factor. Cell-free conditioned media from H. pylori strains 60190 and 26695 each induced >100-fold-greater luminescence in V. harveyi than did sterile culture medium. The H. pylori signaling molecule had a molecular mass of <10 kDa, and its activity was unaffected by heating to 80 degrees C for 5 min or protease treatment. The genome sequence of H. pylori 26695 does not contain any gene predicted to encode an acyl homoserine lactone synthase but does contain an orthologue of luxS, which is required for production of autoinducer-2 (AI-2) in V. harveyi. To evaluate the role of luxS in H. pylori, we constructed luxS null mutants derived from H. pylori 60190 and 26695. Conditioned media from the wild-type H. pylori strains induced >100-fold-greater luminescence in the V. harveyi bioassay than did conditioned medium from either mutant strain. Production of the signaling molecule was restored in an H. pylori luxS null mutant strain by complementation with a single intact copy of luxS placed in a heterologous site on the chromosome. In addition, Escherichia coli DH5alpha produced autoinducer activity following the introduction of an intact copy of luxS from H. pylori. Production of the signaling molecule by H. pylori was growth phase dependent, with maximal production occurring in the mid-exponential phase of growth. Transcription of H. pylori vacA also was growth phase dependent, but this phenomenon was not dependent on luxS activity. These data indicate that H. pylori produces an extracellular signaling molecule related to AI-2 from V. harveyi. We speculate that this signaling molecule may play a role in regulating H. pylori gene expression.


Black sexuality, social construction, and research targeting 'The Down Low' ('The DL').
The purpose of this commentary is to explain how social constructions of black sexuality are relevant to research targeting black sexual behavior and the ostensibly new and race-specific phenomenon known as "the Down Low" (the DL). The term "the DL" is widely used to refer to black men publicly presenting as heterosexual while secretly having sex with other men and presumably spreading human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) to unsuspecting women. We briefly review lay and public health literature from 1998 to 2004 about the DL, describe existing social constructions of black sexuality, discuss two implications for epidemiologic research, and offer recommendations to guide future research. The lifestyle referenced by the term the DL is neither new nor limited to blacks, and sufficient data linking it to HIV/AIDS disparities currently are lacking. Common perceptions about the DL reflect social constructions of black sexuality as generally excessive, deviant, diseased, and predatory. Research targeting black sexual behavior that ignores these constructions may unwittingly reinforce them. Unaddressed social constructions of black sexuality have implications for epidemiologic research targeting black sexual behavior. Explicit examination of these concerns is necessary to eliminate fundamental causes of health disparities.


Pragmatic Expansion of a Neonatal Antibiotic Stewardship Program in a Community Health Care System.
Previously published neonatal antibiotic stewardship efforts have been primarily implemented in single centers. Piedmont Athens Regional began work to decrease antibiotic use in the NICU with spread to the newborn nursery (NBN) and, subsequently, 13 other NICUs and NBNs throughout a health care system over a 4-year period. This quality improvement initiative was conducted in the context of a multicenter learning collaborative from 2016 to 2019. The primary aim was a 10% reduction in antibiotic days per 1000 patient days (antibiotic utilization rate [AUR]) among newborns in the NICU and NBN at each hospital by December 2018. Change ideas were implemented by using plan-do-study-act cycles. The primary outcome measure was AUR with a balancing measure of antibiotic restarts. Piedmont Athens Regional decreased the NICU AUR by 46% and NBN AUR by 83%. Piedmont Healthcare decreased the NICU AUR by 40% and NBN AUR by 74%. Seven of 8 NICUs and 5 of 7 NBNs achieved a >10% reduction in AUR and 8 of 8 intervention hospitals showed a sustained drop in AUR in the NBN, NICU, or both during the 1.5-year postobservation period. Decreases in antibiotic initiation resulted in 335 fewer antibiotic courses in the NICU and 189 fewer infants started on antibiotics in the NBN in 2020 versus 2017. This initiative achieved reductions in AUR across multiple hospitals in the network. The system-wide approach facilitated information technology (IT) and electronic health record modifications. Common drivers of NICU improvement were involvement for at least 2 years, multidisciplinary teams, and the highest baseline AUR. The common driver of nursery improvement was the implementation of a neonatal sepsis risk calculator.


Impaired thymic negative selection causes autoimmune graft-versus-host disease.
Animal models with impaired thymic negative selection do not always cause autoimmune diseases despite the development of an autoreactive T-cell repertoire. We investigated the requirements for the development of systemic autoimmune disease by using bone marrow chimeras that lacked expression of major histocompatibility complex (MHC) class II on thymic antigen-presenting cells (APCs), leading to impaired negative selection. We found that impaired negative selection mediated by absence of MHC class II, but not MHC class I, permitted the development of systemic autoimmune disease that is indistinguishable from acute graft-versus-host disease (GVHD). Thymectomy prevented disease, confirming the causal association of the thymus with its development. Adoptive transfer of CD4+ T cells caused GVHD in secondary hosts only when they were irradiated, and cotransfer of peripheral CD4+ and CD8+ T cells from naive mice prevented the disease. These results demonstrate that impaired thymic negative selection can cause lethal autoimmune disease indistinguishable from acute GVHD in the context of a proinflammatory milieu when peripheral regulatory mechanisms are absent.


A modular strategy for engineering orthogonal chimeric RNA transcription regulators.
Antisense RNA transcription attenuators are a key component of the synthetic biology toolbox, with their ability to serve as building blocks for both signal integration logic circuits and transcriptional cascades. However, a central challenge to building more sophisticated RNA genetic circuitry is creating larger families of orthogonal attenuators that function independently of each other. Here, we overcome this challenge by developing a modular strategy to create chimeric fusions between the engineered transcriptional attenuator from plasmid pT181 and natural antisense RNA translational regulators. Using in vivo gene expression assays in Escherichia coli, we demonstrate our ability to create chimeric attenuators by fusing sequences from five different translational regulators. Mutagenesis of these functional attenuators allowed us to create a total of 11 new chimeric attenutaors. A comprehensive orthogonality test of these culminated in a 7 × 7 matrix of mutually orthogonal regulators. A comparison between all chimeras tested led to design principles that will facilitate further engineering of orthogonal RNA transcription regulators, and may help elucidate general principles of non-coding RNA regulation. We anticipate that our strategy will accelerate the development of even larger families of orthogonal RNA transcription regulators, and thus create breakthroughs in our ability to construct increasingly sophisticated RNA genetic circuitry.


Cutaneous manifestations in patients suspected of chikungunya disease.
An epidemic of chikungunya disease occurred in India during late 2005 through 2006 affecting nearly 1,400,000 people. To study the cutaneous manifestations in suspected cases of chikungunya disease. Patients who attended our outpatient departments from January 2006 to September 2006 were prospectively included if they had symptoms of chikungunya disease according to the 'case definition' of the National Institute of Communicable Diseases, Directorate General of Health Services, Government of India. The criteria were an acute illness characterized by the sudden onset of fever and several symptoms such as joint pain, headache, backache, photophobia, and eruption during an epidemic of chikungunya fever in the absence of confirmatory serological tests. A total of 115 patients (65 men and 50 women) who satisfied the above criteria were enrolled for the study. An erythematous maculopapular rash subsiding without any sequelae in 3-4 days was the most common cutaneous finding in our patients. Genital ulcers distributed predominantly over the scrotum and base of the penile shaft in men and labia majora in women were the second most common manifestation. Other manifestations included tenderness/edema of hands and feet, grouped hyperpigmented macules over the nose and cheeks, fixed drug eruptions, erythema nodosum, erythema multiformae, generalized urticarial eruptions, and flare up of pre-existing psoriasis and lichen planus. To conclude, a plethora of cutaneous manifestations were noted in suspected cases of chikungunya disease. Genital ulcers, to the best of our knowledge, have not been reported during the earlier epidemics but have been reported by others during the present one.


Tumor vascular status controls oxygen delivery facilitated by infused polymerized hemoglobins with varying oxygen affinity.
Oxygen (O2) delivery facilitated by hemoglobin (Hb)-based O2 carriers (HBOCs) is a promising strategy to increase the effectiveness of chemotherapeutics for treatment of solid tumors. However, the heterogeneous vascular structures present within tumors complicates evaluating the oxygenation potential of HBOCs within the tumor microenvironment. To account for spatial variations in the vasculature and tumor tissue that occur during tumor growth, we used a computational model to develop artificial tumor constructs. With these simulated tumors, we performed a polymerized human hemoglobin (hHb) (PolyhHb) enhanced oxygenation simulation accounting for differences in the physiologic characteristics of human and mouse blood. The results from this model were used to determine the potential effectiveness of different treatment options including a top load (low volume) and exchange (large volume) infusion of a tense quaternary state (T-State) PolyhHb, relaxed quaternary state (R-State) PolyhHb, and a non O2 carrying control. Principal component analysis (PCA) revealed correlations between the different regimes of effectiveness within the different simulated dosage options. In general, we found that infusion of T-State PolyhHb is more likely to decrease tissue hypoxia and modulate the metabolic rate of O2 consumption. Though the developed models are not a definitive descriptor of O2 carrier interaction in tumor capillary networks, we accounted for factors such as non-uniform vascular density and permeability that limit the applicability of O2 carriers during infusion. Finally, we have used these validated computational models to establish potential benchmarks to guide tumor treatment during translation of PolyhHb mediated therapies into clinical applications.


Measuring azimuthal and radial modes of photons.
With the emergence of the field of quantum communications, the appropriate choice of photonic degrees of freedom used for encoding information is of paramount importance. Highly precise techniques for measuring the polarisation, frequency, and arrival time of a photon have been developed. However, the transverse spatial degree of freedom still lacks a measurement scheme that allows the reconstruction of its full transverse structure with a simple implementation and a high level of accuracy. Here we show a method to measure the azimuthal and radial modes of Laguerre-Gaussian beams with a greater than 99 % accuracy, using a single phase screen. We compare our technique with previous commonly used methods and demonstrate the significant improvements it presents for quantum key distribution and state tomography of high-dimensional quantum states of light. Moreover, our technique can be readily extended to any arbitrary family of spatial modes, such as mutually unbiased bases, Hermite-Gauss, and Ince-Gauss. Our scheme will significantly enhance existing quantum and classical communication protocols that use the spatial structure of light, as well as enable fundamental experiments on spatial-mode entanglement to reach their full potential.


Surface plasmon spectroscopy of gold-poly-N-isopropylacrylamide core-shell particles.
Highly uniform, core-shell microgels consisting of single gold nanoparticle cores and cross-linked poly-N-isopropylacrylamide (PNIPAM) shells were prepared by a novel, versatile protocol. The synthetic pathway allows control over the polymer shell thickness and its swelling behavior. The core-shell structure was investigated by electron microscopy and atomic force microscopy, whereas the swelling behavior of the shell was studied by means of dynamic light scattering and UV-vis spectroscopy. Furthermore, the latter method was used to investigate the optical properties of the hybrid particles. By modeling the scattering contribution from the PNIPAM shells, the absorption spectra of the gold nanoparticle cores could be recovered. This allows the particle concentration to be determined, and this in turn permits the calculation of the molar mass of the hybrid particles as well as the refractive index of the shells.


Shape- and nitric oxide flux-dependent bactericidal activity of nitric oxide-releasing silica nanorods.
Silica nanorods (SNRs) are synthesized and then functionalized with aminoalkoxysilanes to prepare a new class of nitric oxide (NO)-releasing materials. The aspect ratio and size of the SNRs are tuned by varying the temperature, pH, and silane concentration used during the surfactant-templated synthesis. N-Diazeniumdiolate nitric oxide (NO) donors are formed on the secondary amine-functionalized SNRs by reaction with NO gas under basic conditions. Particle surface modifications are employed to manipulate the NO release kinetics. The diverse morphology (i.e., aspect ratio ∼1-8), NO-release kinetics (2000-14,000 ppb NO/mg particle) and similar sizes (i.e., particle volume ∼0.02 μm³) of the resulting NO-releasing SNRs facilitates further studies of how particle shape and NO flux impacts bactericidal activity against Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Pseudomonas aeruginosa (P. aeruginosa) bacteria. The bactericidal efficacies of these materials improves with increasing particle aspect ratio and initial NO flux. Both chemical (i.e., NO-release kinetics) and physical (i.e., morphology) properties greatly influenced the bactericidal activity of these materials.


Anthropometric indices of failure to thrive.
To compare five anthropometric methods of classifying failure to thrive in order to ascertain their relative merits in predicting developmental, dietary, and eating problems. The five anthropometric methods were compared in 83 children with failure to thrive. The methods were inconsistent in classification of severity, and no one method was superior in predicting problems. Weight alone, being the simplest, is still the most reasonable marker for failure to thrive and associated problems.


Promoting professional identity, motivation, and persistence: Benefits of an informal mentoring program for female undergraduate students.
Women are underrepresented in a number of science, technology, engineering, and mathematics (STEM) disciplines. Limited diversity in the development of the STEM workforce has negative implications for scientific innovation, creativity, and social relevance. The current study reports the first-year results of the PROmoting Geoscience Research, Education, and SuccesS (PROGRESS) program, a novel theory-driven informal mentoring program aimed at supporting first- and second-year female STEM majors. Using a prospective, longitudinal, multi-site (i.e., 7 universities in Colorado/Wyoming Front Range & Carolinas), propensity score matched design, we compare mentoring and persistence outcomes for women in and out of PROGRESS (N = 116). Women in PROGRESS attended an off-site weekend workshop and gained access to a network of volunteer female scientific mentors from on- and off-campus (i.e., university faculty, graduate students, and outside scientific professionals). The results indicate that women in PROGRESS had larger networks of developmental mentoring relationships and were more likely to be mentored by faculty members and peers than matched controls. Mentoring support from a faculty member benefited early-undergraduate women by strengthening their scientific identity and their interest in earth and environmental science career pathways. Further, support from a faculty mentor had a positive indirect impact on women's scientific persistence intentions, through strengthened scientific identity development. These results imply that first- and second- year undergraduate women's mentoring support networks can be enhanced through provision of protégé training and access to more senior women in the sciences willing to provide mentoring support.


Enhancement of Dye-Sensitized Solar Cells Efficiency Using Mixed-Phase TiO2 Nanoparticles as Photoanode.
Dye-sensitized solar cell (DSSC) is a potential candidate to replace conventional silicon-based solar cells because of high efficiency, cheap cost, and lower energy consumption in comparison with silicon chip manufacture. In this report, mixed-phase (anatase and rutile nanoparticles) TiO2 photoanode was synthesized to investigate material characteristics, carriers transport, and photovoltaic performance for future DSSC application. Field-emission scanning electron microscope (SEM), X-ray diffraction (XRD), photoluminescence (PL), and UV-visible spectroscopy were used to characterize mixed TiO2 particles. Subsequently, various mixed-phase TiO2 anodes in DSSC devices were measured by electrical impedance spectra (EIS) and energy efficiency conversion. The overall energy conversion efficiency of DSSC chip was improved as a result of the increase of rutile phase of TiO2 (14%) in anatase matrix. Synergistic effects including TiO2 crystallization, reduction of defect density level in energy band, longer lifetime of photoexcited electrons, and lower resistance of electron pathway all contributed to high efficiency of light energy conversion.


Expression of recombinant alpha Ains-crystallin and not alpha A-crystallin inhibits bacterial growth.
alpha A-Crystallin and alpha Ains-crystallin are derived from the alpha A-crystallin gene via alternative splicing. They are identical except for the presence of a polypeptide, 23 amino acids long, encoded by the 'insert' exon. Evolutionary logic would suggest that the insertion of a 23 amino acid peptide in the middle of alpha A-crystallin, a protein evolving more slowly than either histone H1, cytochrome c or hemoglobin, would lead to appreciable structural and functional changes. However, based on physico-chemical studies, it is presently believed that alpha A-crystallin and alpha Ains-crystallin are functionally equivalent and that the presence of the 'insert' peptide in alpha Ains-crystallin is inconsequential. We report here that the independent expression of recombinant alpha Ains-crystallin, and not alpha A-crystallin, inhibits growth of the bacterial host. These observations were confirmed in coexpression experiments, wherein both the proteins were expressed in the same cell. Interestingly, growth inhibition is reversible. Importantly, the data demonstrate that it is catalytic amounts and not the gross accumulation of alpha Ains-crystallin which causes growth inhibition. Given the prior knowledge that alpha A-crystallin and alpha Ains-crystallin differ by a peptide of 23 amino acids, these data suggest that the "insert peptide' in alpha Ains-crystallin imparts properties on this protein that are different from alpha A-crystallin.


Red wine consumption does not affect oxidizability of low-density lipoproteins in volunteers.
Phenolic compounds in red wine may protect low-density lipoproteins (LDL) against oxidative modification, thereby reducing the risk of cardiovascular morbidity. However, in vivo data are scarce. We gave 13 healthy volunteers 550 mL red wine and another 11 volunteers white wine for 4 wk in a randomized double-blind trial. Interference by alcoholic components of wine was eliminated by reducing the alcohol content to 3.5% Red wine did not affect the susceptibility of LDL to Cu2+ -mediated oxidative modification [lag time before and after red wine drinking (chi +/- SD) 61.8 +/- 7.7 and 62.7 +/- 11.8 min, respectively; lag time before and after white wine drinking: 64.5 +/- 10.4 and 63.3 +/- 10.8 min, respectively]. Concentrations of the antioxidants urate, vitamin C, and glutathione in plasma and of vitamin E and ubiquinol-10 in LDL were also unchanged after either red or white wine consumption. The results of this study do not show a beneficial effect of red wine consumption on LDL oxidation.


Oral mobility reflects rate of progression in advanced Friedreich's ataxia.
Our objective was to identify a sensitive marker of disease progression in Friedreich's ataxia. We prospectively evaluated speech, voice, and oromotor function in 40 patients at two timepoints. The mean disease duration was 20.8 ± 9.8 years and mean SARA score 23.7 ± 8.6 at baseline. Oral motor mobility, assessed by a combination of movements of the face, eyes, cheeks, lips, and tongue, decreased significantly after 1 year (P < 0.0001). The standardized response mean over 12 months was considered as large for oral mobility (1.26) but small for SARA (0.12). Oral mobility could therefore be a sensitive marker in therapeutic trials.


Two-dimensional 1H NMR studies of histidine-containing protein from Escherichia coli. 3. Secondary and tertiary structure as determined by NMR.
Sequence-specific resonance assignments of the 1H NMR spectrum of the 85-residue histidine-containing phosphocarrier protein (HPr) are complete [Klevit, R. E., Drobny, G. P., & Waygood, E. B. (1986) Biochemistry (first paper of three in this issue)]. Additional side-chain assignments have been made with long-range coherence transfer experiments [Klevit, R. E., & Drobny, G. P. (1986) Biochemistry (second paper of three in this issue)]. In this paper, the NMR assignments were used to determine the secondary structure and the tertiary folding of HPr in solution. The secondary structural elements of the protein were determined by visual inspection of the pattern of nearest-neighbor nuclear Overhauser effects (NOEs) and the presence of persistent amide resonances. Escherichia coli HPr consists of four beta-strands, three alpha-helices, four reverse turns, and several regions of extended backbone structure. Long-range NOEs, especially among side-chain protons, were used to determine the tertiary structure of the protein by use of the secondary structural components. The four beta-strands form a single antiparallel beta-pleated sheet. The hydrophobic faces of the alpha-helices interact to form a hydrophobic core and sit above the hydrophobic face of the beta-sheet, forming an open-face beta-sheet sandwich structure. The active site histidine, His-15, is on a short kinked segment of backbone that is accessible to the solvent. The positively charged phosphorylation site (His-15 and Arg-17) interacts with the negatively charged carboxyl terminus of the protein (Glu-85).(ABSTRACT TRUNCATED AT 250 WORDS)


Classification of somatosensory-evoked potentials recorded from patients with severe head injuries.
The problem of sensory evoked potential (EP) assessment in the critical care setting to isolate damage in specific neuronal pathways, as manifested by certain abnormalities in the response waveform is being addressed using neural networks. An existing visually based grading scheme (GGS, for Greenberg grading system) for somatosensory EPs collected from patients with severe head injuries is being automated. The collection of data used in this research, which consist of somatosensory-evoked potential (SEP) waveforms collected from patients with head injuries is described. The way the system (called Pathfinder) works is described, and results obtained with it are presented.


Development of a novel set of microsatellite markers for Lippia alba (Verbenaceae).
Microsatellite primers were developed and optimized for Lippia alba to characterize the L. alba germplasm bank of Universidade de São Paulo. A genomic library enabled the design of 9 microsatellite primers. Six of the 9 primers yielded polymorphic products, which defined 2 groups in the bank. The data provide support to characterize germplasm banks, genetic breeding programs for L. alba, and other genetic diversity studies and classifications of species in the genus Lippia.


Incident Dialysis Access in Patients With End-Stage Kidney Disease: What Needs to Be Improved.
The initiation of dialysis is a challenging time of transition for patients, families, and their supporters. Patients with exposure to a comprehensive chronic kidney disease clinic may have had education and subsequent decision making regarding dialysis modality and access; however, many patients with or without prior education will require an urgent start to dialysis, requiring quick decisions regarding dialysis modality and access. In many countries, hemodialysis (HD) using a central venous catheter (CVC) is the most common initial renal replacement modality and dialysis access. Multiple factors, both remedial and nonremedial, contribute to this including late referral, rapid decrease in kidney function, delay in delivery or acceptance of education, and decision making and other system delays. Recent use of urgent peritoneal dialysis as the initial dialysis modality has resulted in decreased exposure to CVCs and in-center HD. This article addresses the current state of incident dialysis access, recent trends toward urgent peritoneal dialysis start, and opportunities to avoid the use of CVCs for HD when appropriate, with a focus on considering dialysis access as a critical component of the end-stage kidney disease life-plan, which requires consideration of future modalities and access when making the choice of the initial dialysis access.


Recursive information granulation: aggregation and interpretation issues.
This paper contributes to the conceptual and algorithmic framework of information granulation. We revisit the role of information granules that are relevant to several main classes of technical pursuits involving temporal and spatial granulation. A detailed algorithm of information granulation, regarded as an optimization problem reconciling two conflicting design criteria, namely, a specificity of information granules and their experimental relevance (coverage of numeric data), is provided in the paper. The resulting information granules are formalized in the language of set theory (interval analysis). The uniform treatment of data points and data intervals (sets) allows for a recursive application of the algorithm. We assess the quality of information granules through application of the fuzzy c-means (FCM) clustering algorithm. Numerical studies deal with two-dimensional (2D) synthetic data and experimental traffic data.


Elevated mechanical loading when young provides lifelong benefits to cortical bone properties in female rats independent of a surgically induced menopause.
Exercise that mechanically loads the skeleton is advocated when young to enhance lifelong bone health. Whether the skeletal benefits of elevated loading when young persist into adulthood and after menopause are important questions. This study investigated the influence of a surgically induced menopause in female Sprague-Dawley rats on the lifelong maintenance of the cortical bone benefits of skeletal loading when young. Animals had their right forearm extrinsically loaded 3 d/wk between 4 and 10 weeks of age using the forearm axial compression loading model. Left forearms were internal controls and not loaded. Animals were subsequently detrained (restricted to cage activities) for 94 weeks (until age 2 years), with ovariectomy (OVX) or sham-OVX surgery being performed at 24 weeks of age. Loading enhanced midshaft ulna cortical bone mass, structure, and estimated strength. These benefits persisted lifelong and contributed to loaded ulnas having greater strength after detraining. Loading also had effects on cortical bone quality. The benefits of loading when young were not influenced by a surgically induced menopause because there were no interactions between loading and surgery. However, OVX had independent effects on cortical bone mass, structure, and estimated strength at early postsurgery time points (up to age 58 weeks) and bone quality measures. These data indicate skeletal loading when young had lifelong benefits on cortical bone properties that persisted independent of a surgically induced menopause. This suggests that skeletal loading associated with exercise when young may provide lifelong antifracture benefits by priming the skeleton to offset the cortical bone changes associated with aging and menopause.


Coexistence of Cardiovascular Risk Factors and Blood Renalase Concentration.
Cardiovascular diseases (CVDs) are one of the biggest health challenges facing health systems around the world. There are certain risk factors (CVRFs) that contribute to CVD. Risk factors associated with lifestyle such as tobacco consumption are particularly essential. Renalase is a recently discovered flavoprotein that may be involved in the progression of cardiometabolic diseases. The aim of the study was to investigate the relation between CVRFs and blood renalase concentration (BRC). The study group consisted of 96 people (51% women) who were hospitalized in the internal medicine department. CVRFs were measured using the AHA Life 7 scale. The E3109Hu ELISA kit was used to assess BRC. We found higher BRC in groups with a lower number of CVRFs (p < 0.05). We found a negative correlation between BRC and the number of CVRFs (r = -0.41). With the regression analysis, obesity, smoking, and a lack of physical activity (LoPE) were independently associated with lower blood renalase concentration. ROC analysis indicated the highest accuracy of BRC < 38.98 ng/mL in patients with ≥5 CVRFs. In conclusion, patients with a higher number of CVRFs had lower BRCs. The CVRFs particularly associated with a lower BRC were obesity, smoking, and LoPE.


The neuropsychology of infants' pro-social preferences.
The current study is the first to investigate neural correlates of infants' detection of pro- and antisocial agents. Differences in ERP component P400 over posterior temporal areas were found during 6-month-olds' observation of helping and hindering agents (Experiment 1), but not during observation of identically moving agents that did not help or hinder (Experiment 2). The results demonstrate that the P400 component indexes activation of infants' memories of previously perceived interactions between social agents. This leads to suggest that similar processes might be involved in infants' processing of pro- and antisocial agents and other social perception processes (encoding gaze direction, goal directed grasping and pointing).


Abnormal FSH hypersecretion as an endocrinological manifestation of POEMS syndrome.
Two patients with POEMS syndrome had high basal levels of FSH in the absence of primary hypogonadism. They were fertile eugonadal men with normal serum testosterone and estradiol levels. Provocation with LH-releasing hormone revealed blunted response of FSH secretion, but normal response of LH secretion in both patients, and one had pituitary microadenoma on brain MRI. This report adds primary FSH hypersecretion in the absence of primary testicular failure to the list of endocrinopathy of POEMS syndrome.


The relationship between attention networks and individual differences in visual mental imagery vividness - An EEG study.
Previous research has established a strong link between attention and visual mental imagery, but it's remained uncertain whether attention networks influence individual differences in the vividness of visual mental imagery. In our study, we examined 140 participants, assessing the vividness of imagery using the Vividness of Visual Imagery Questionnaire in both eyes-open and eyes-closed conditions. We employed the Attention Network Test, coupled with EEG recording, to characterize three attention sub-networks: alerting, orienting, and executive control. To pinpoint the specific attentional networks associated with the vividness of visual mental imagery, we utilized latent profile analysis to categorize participants into distinct subgroups. Additionally, we constructed a regression mixture model to explore how attention networks predict different latent categories of visual imagery vividness. Our findings revealed that the efficiency of the alerting network, as indicated by the N1 component, demonstrated a positive correlation with the vividness of visual imagery. This electrophysiological evidence underscores the role of the alerting network in shaping individual differences in the vividness of visual mental imagery.


Modulation by copper of the products of nitrite respiration in Pseudomonas perfectomarinus.
A synthetic growth medium was purified with the chelator 1,5-diphenylthiocarbazone to study the effects of copper on partial reactions and product formation of nitrite respiration in Pseudomonas perfectomarinus. This organism grew anaerobically in a copper-deficient medium with nitrate or nitrite as the terminal electron acceptor. Copper-deficient cells had high activity for reduction of nitrate, nitrite, and nitric oxide, but little activity for nitrous oxide reduction. High rates of nitrous oxide reduction were observed only in cells grown on a copper-sufficient (1 micro M) medium. Copper-deficient cells converted nitrate or nitrite initially to nitrous oxide instead of dinitrogen, the normal end product of nitrite respiration in this organism. In agreement with this was the finding that anaerobic growth of P. perfectomarinus with nitrous oxide as the terminal electron acceptor required copper. This requirement was not satisfied by substitution of molybdenum, zinc, nickel, cobalt, or manganese for copper. Reconstitution of nitrous oxide reduction in copper-deficient cells was rapid on addition of a small amount of copper, even though protein synthesis was inhibited. The results indicate an involvement of copper protein(s) in the last step of nitrite respiration in P. perfectomarinus. In addition we found that nitric oxide, a presumed intermediate of nitrite respiration, inhibited nitrous oxide reduction.


Paeoniflorin ameliorates antipsychotic-induced hyperprolactinemia in rats by attenuating impairment of the dopamine D2 receptor and TGF-β1 signaling pathways in the hypothalamus and pituitary.
Paeoniflorin, a prominent component in some Chinese formulas for hyperprolactinemia-associated disorders, has been found to inhibit prolactin secretion in prolactinoma cells. To examine the efficacy of paeoniflorin on hyperprolactinemia and the underlying mechanisms of action. Hyperprolactinemia in female rats was generated by administration of olanzapine (5 mg/kg, by a gavage method, once daily, × 13 weeks). The rats were co-treated with paeoniflorin (10 and 50 mg/kg). Prolactin and TGF-β1 concentrations were detected by ELISA. Protein expression was determined by Western blot. The effect in MMQ cells was also examined. Paeoniflorin inhibited olanzapine-induced increases in plasma prolactin concentration and prolactin protein overexpression in the pituitary and hypothalamus of rats. Further, paeoniflorin restored olanzapine-induced downregulation of pituitary and hypothalamic dopamine D2 receptor (D2R) protein expression. More importantly, paeoniflorin attenuated olanzapine-suppressed protein expression of transforming growth factor (TGF)-β1 and its downstream genes, type II TGF-β receptor, type I TGF-β receptor and phosphorylated SMAD3 in the tissues. However, paeoniflorin did not affect plasma TGF-β1 concentration and hepatic TGF-β1 protein expression. In accord, olanzapine-induced increase in prolactin concentration, upregulation of prolactin protein expression, and downregulation of protein expression of the D2R and TGF-β1 signals in MMQ cells were attenuated. This study demonstrates that paeoniflorin ameliorates olanzapine-induced hyperprolactinemia in rats by attenuating impairment of the D2R and TGF-β1 signaling pathways in the hypothalamus and pituitary. Our findings may provide evidence to support the use of paeoniflorin-contained Chinese herbs and formulas for hyperprolactinemia and its associated disorders.


Mutation-selection balance under genomic imprinting at an autosomal locus.
I model the effect of genomic imprinting on the equilibrium allele frequencies at an autosomal diallelic locus subject to viability selection and mutation. The population size is assumed to be very large; male and female mutation rates may be unequal. Different models examine cases of the inactivation of one gene (with both complete and partial penetrance) and of differential expression of genes according to the parent of origin. In the simplest cases the frequency of the deleterious allele is approximately twice that of a dominant nonimprinting mutant, but considerably less than that of a recessive nonimprinting mutant. Under imprinting, selection and unequal mutation rates interact: other things being equal, male-biased mutation leads to lower mutant frequencies under maternal imprinting and higher frequencies under paternal imprinting. I also model cases where just one allele is imprintable (and the other not). These models allow us to predict the frequency of a failure to imprint in a normally imprinting system, as well as the frequency of imprinting at a standard nonimprinting locus.


A comparison of the post-marketing safety of four selective serotonin re-uptake inhibitors including the investigation of symptoms occurring on withdrawal.
1. We have addressed the question of whether there is a 'serotonin withdrawal syndrome' by analysis of spontaneous reports of suspected adverse drug reactions (ADRs) associated with four SSRIs. A comparison of the post-marketing safety profiles of the four SSRIs has also been made. 2. The UK database of ADRs was examined for reactions associated with fluoxetine, fluvoxamine, paroxetine and sertraline. The safety profiles of the four SSRIs were similar. However, withdrawal reactions with paroxetine constitute a greater proportion of reports (5.1%) than with the other SSRIs (0.06-0.9%). They have been reported more often with paroxetine (0.3 reports per thousand prescriptions) than with sertraline and fluvoxamine (0.03), and least often with fluoxetine (0.002). 3. Descriptions of withdrawal reactions received and further details of 217 reports of withdrawal reaction with paroxetine obtained by mailing a questionnaire to the reporting doctor were examined. Withdrawal symptoms were diverse but most commonly comprised dizziness, paraesthesia, tremor, anxiety, nausea and palpitation. They usually occurred after 2 days and lasted for an average of 10 days. There was no evidence of a physical drug dependency syndrome. 4. Symptoms different from the previous depressive illness occur after discontinuing an SSRI, and are reported most often with paroxetine. Paroxetine is the most pharmacologically specific of the SSRIs, but it is not clear whether the reactions constitute a 'serotonin withdrawal syndrome'.


High SARS-CoV-2 seroprevalence but no severe course of COVID-19 disease among people on opioid agonist treatment in Zurich: a cross-sectional study.
Among people on opioid agonist treatment (OAT), social-environmental and behavioural risk factors may promote the spread of SARS-CoV-2, and somatic comorbidities are highly prevalent. Thus, this population is considered at elevated risk for being infected as well as for developing a more severe course of COVID-19 disease. The aim was to assess the SARS-CoV-2 seroprevalence among people in ongoing OAT, to explore whether the antibody positive group differed from the antibody negative group, and to compare the SARS-CoV-2 seroprevalence among OAT patients with the prevalence in the regional general population. The nationwide Corona Immunitas study assessed the participants' Sars-CoV-2 antibody status, social characteristics and behavioural data after the first wave of the corona pandemic in Switzerland, between the end of June and beginning of September 2020. We analysed the subsample of OAT patients (n = 122) and the subsample from the general population of the canton of Zurich (n = 472). SARS-CoV-2 seroprevalence in the general population (mean age ± standard deviation 44.7 ± 11.7 years; 50.9% female) was 3.5% (95% confidence interval [CI] 2.2-4.8%) vs 9.8% (5.1-17.2%) in the OAT population age 44.3 ± 9.4 years; 30.3% female), corresponding to a prevalence ratio of 2.9 (95% CI 1.37-5.94; p = 0.004). OAT patients had a significantly worse health status than the general population. In the OAT group, we found no significant difference between seropositive and seronegative individuals regarding socioeconomic status, risk behaviour, COVID-19-related symptoms or comorbidity. None of the OAT patients who tested positive had a severe course of COVID-19. The 3-fold higher seroprevalence suggests a higher than average viral exposure in the OAT group. Nevertheless, no severe COVID-19 course occurred, although the number of study participants was relatively small. One possible reason for this could be possible cross-immunity to SARS-CoV-2 due to frequent viral contacts in OAT patients.


An investigation of uterine nitric oxide production in mares susceptible and resistant to persistent breeding-induced endometritis and the effects of immunomodulation.
The first objective of this study was to evaluate intrauterine nitric oxide (NO) and endometrial inducible NO synthase (iNOS) in mares susceptible or resistant to persistent breeding-induced endometritis (PBIE) within 24 h after breeding. Mares susceptible (n = 6) or resistant (n = 6) to PBIE were inseminated over five cycles, and uterine secretions and endometrial biopsies were collected before and 2, 6, 12 and 24 h after insemination. Uterine secretions were analysed for NO and biopsies were analyzed for iNOS expression. A second experiment evaluated the effect of treatment with dexamethasone or mycobacterial cell wall extract (MCWE) on uterine NO production and endometrial iNOS mRNA expression. Six susceptible mares were inseminated over three cycles with (i) killed spermatozoa without treatment (control), (ii) killed spermatozoa with 50 mg of dexamethasone IV or (iii) MCWE IV 24 h prior to insemination with killed spermatozoa. Six resistant mares were inseminated with killed spermatozoa as a control. Six hours after breeding, uterine biopsies and secretions were collected and evaluated for NO and iNOS mRNA. In Experiment 1, resistant mares had an increase in iNOS mRNA expression 2 h post-breeding compared to baseline (p = 0.045), 12 h (p = 0.014) and 24 h (p = 0.001). Susceptible mares had higher expression 2 h compared to 6 h (p = 0.046). No differences were observed in mRNA or protein expression of iNOS between resistant and susceptible mares. Resistant mares had a relatively steady amount of total intrauterine NO over 24 h, while susceptible mares had an increase over time, with a significantly higher increase in total NO than resistant mares at 6 (p = 0.04) and 12 h (p = 0.032). In Experiment 2, no differences were observed for iNOS mRNA expression. Susceptible mares had increased NO when compared to resistant mares (p = 0.008) and MCWE decreased NO (p = 0.047).


Modeling water transport properties in carbon nanotubes: Interplay between force-field flexibility and geometrical parameters.
Modeling water and other liquids in computational simulations requires a large set of parameters. Many works have been devoted to finding new, improved water models, with almost all of them designed for bulk systems. Here, we use carbon nanotubes as a play model to investigate the effects of introducing flexibility in water force fields during molecular dynamics simulations of nanoconfined water. We explore six different models to show that viscosity, diffusion, and dipole orientation are vastly influenced by the flexibility and the family of force fields used. Particularly, we found the level of confinement (decreasing the nanotube's diameter) to increase discrepancies in the description of the dipole alignment. In smaller (10,10) nanotubes, the flexible version of the transferable intermolecular potential with three points (TIP3P/Fs) features a high directionality, while its rigid counterpart shows a more distributed dipole orientation. Both viscosity and diffusion are also extremely dependent on the force-field family, with the flexible version of the simple point charge (SPC/Fw) featuring the lower confidence interval.


Biochemical properties and primary structure of elastase inhibitor AFUEI from Aspergillus fumigatus.
An elastase inhibitor from Aspergillus fumigatus (AFUEI) was isolated, and its biochemical properties and primary structure examined. The inhibitor was purified by column chromatography using DE52 cellulose and Sephadex G-75, and was found to be homogeneous as indicated by a single band following discontinuous PAGE and SDS-PAGE. A molecular mass of 7525.1 Da was observed by matrix-assisted desorption/ionization time-of-flight mass spectroscopy. The elastolytic activity of elastases from A. fumigatus, Aspergillus flavus and human leukocytes was inhibited by AFUEI. However, the elastolytic activity of porcine pancreas elastase, Pseudomonas aeruginosa elastase and elastase from snake venom was not affected by AFUEI. No inhibitory effect of DTT or 2-mercaptoethanol on the elastase inhibitory activity of AFUEI was observed. The amino acid sequence of AFUEI peptides derived from digests utilizing clostripain was determined by Edman sequencing. AFUEI was composed of 68 aa and had a calculated molecular mass of 7526.2 Da. The search for amino acid homology with other proteins demonstrated that aa 1-68 of AFUEI are 100 % identical to aa 20-87 of the hypothetical protein AFUA 3G14940 of A. fumigatus.


An epigrammatic status of the 'azole'-based antimalarial drugs.
The development of multidrug resistance in the malarial parasite has sabotaged majority of the eradication efforts by restraining the inhibition profile of first line as well as second line antimalarial drugs, thus necessitating the development of novel pharmaceutics constructed on appropriate scaffolds with superior potency against the drug-resistant and drug-susceptible Plasmodium parasite. Over the past decades, the infectious malarial parasite has developed resistance against most of the contemporary therapeutics, thus necessitating the rational development of novel approaches principally focused on MDR malaria. This review presents an epigrammatic collation of the epidemiology and the contemporary antimalarial therapeutics based on the 'azole' motif.


Kinetic solvent isotope effects on the deacylation of specific acyl-papains. Proton inventory studies on the papain-catalysed hydrolyses of specific ester substrates: analysis of possible transition state structures.
1. The hydrolyses of the p-nitrophenyl esters of N-benzyloxycarbonylglycine, alpha-N-benzyloxycarbonyl-L-lysine and N-methoxycarbonyl-L-phenylalanylglycine catalysed by papain (EC 184.108.40.206) have been studied in solvents having a variable composition of 2H2O and H2O. 2. kcat., which represents deacylation in the papain-catalysed hydrolysis of reactive esters, is some 2.3-fold less in 2H2O compared with H2O. The magnitude of kcat. has been determined as a function of the 2H atom fraction of the solvent. 3. Both linear and non-linear methods of least-square regression analysis have been applied to the data in order to obtain best-fit parameter values for several three-parameter models which express kcat. in terms of the 2H atom fraction of the solvent. These models represent some possible modes of restructuring of the active site protonic configuration consequent upon transition state formation. 4. The results of curve fitting reveal an essentially linear dependence of kcat. upon the 2H atom fraction, and it may therefore be concluded that the isotope effect originates from a single proton which is in the process of transfer in the transition state. 5. It is postulated on the basis of this and other evidence that the mobile proton is transferred from an attacking water molecule to the imidazole side chain of His-159 during tetrahedral intermediate formation. This has the effect of stabilizing the transition state and promoting catalysis. The role of His-159 in deacylation is therefore to provide general base catalysis. 6. Models that involve two or more protons, such as a two-proton relay system analogous to that proposed for the serine proteinases, or a multiproton 'medium' effect, are considered unlikely on the basis of the data reported in this paper. 7. A more detailed examination of possible transition state structures reveals that the only structure compatible with available experimental data and consistent with certain theoretical predictions is one in which the proton translocated in concern with reorganization of the heavy atom framework. In addition, the transition state vibrations of the mobile proton are strongly coupled to those of the heavy atoms. These properties of the transition state are also manifest in the transition state for the deacylation of serine proteinases.


Quantum-confined Stark effect measurements in Ge/SiGe quantum-well structures.
We investigate the room-temperature quantum-confined Stark effect in Ge/SiGe multiple quantum wells (MQWs) grown by low-energy plasma-enhanced chemical vapor deposition. The active region is embedded in a p-i-n diode, and absorption spectra at different reverse bias voltages are obtained from optical transmission, photocurrent, and differential transmission measurements. The measurements provide accurate values of the fraction of light absorbed per well of the Ge/SiGe MQWs. Both Stark shift and reduction of exciton absorption peak are observed. Differential transmission indicates that there is no thermal contribution to these effects.


Conversion of the Nikon C1 confocal laser-scanning head for multiphoton excitation on an upright microscope.
Most commercial laser-scanning imaging systems used for confocal fluorescence microscopy can be readily adapted for use with two-photon fluorescence excitation. We report here on the details of the conversion of the Nikon C1 (product released November 2001) with two channels of nondescanned detection of two-photon-excited fluorescence. One of the goals of the design was to utilize off-the-shelf components as much as possible to minimize the use of custom machining and electronics assembly. We also give some initial characterization of the imaging properties of the system.


ST-elevation acute coronary syndromes in the Platelet Inhibition and Patient Outcomes (PLATO) trial: insights from the ECG substudy.
Ticagrelor, when compared with clopidogrel, reduced the 12-month risk of vascular death/myocardial infarction and stroke in patients with ST-elevation acute coronary syndromes intended to undergo primary percutaneous coronary intervention in the PLATelet inhibition and patient Outcomes (PLATO) trial. This prespecified ECG substudy explored whether ticagrelor's association with vascular death and myocardial infarction within 1 year would be amplified by (1) the extent of baseline ST shift and (2) subsequently associated with fewer residual ST changes at hospital discharge. ECGs were evaluated centrally in a core laboratory in 3122 ticagrelor- and 3084 clopidogrel-assigned patients having at least 1 mm ST-elevation in 2 contiguous leads as identified by site investigators on the qualifying ECG. Patients with greater ST-segment shift at baseline had higher rates of vascular death/myocardial infarction within 1 year. Among those who also had an ECG at hospital discharge (n=4798), patients with ≥50% ΣST-deviation (ΣST-dev) resolution had higher event-free survival than those with incomplete resolution (6.4% versus 8.8%, adjusted hazard ratio 0.69 (0.54-0.88), P=0.003). The extent of ΣST-dev resolution was similar irrespective of treatment assignment. The benefit of ticagrelor versus clopidogrel on clinical events was consistent irrespective of the extent of baseline ΣST-dev (P(interaction)=0.728). When stratified according to conventional times from symptom onset, ie, ≤3 hours, 3 to 6 hours, >6 hours, the extent of baseline ΣST-dev declined progressively over time. As time from symptom onset increased beyond 3 hours, the benefit of ticagrelor appeared to be more pronounced; however, the interaction between time and treatment was not significant (P=0.175). Ticagrelor did not modify ΣST-dev resolution at discharge nor was its benefit affected by the extent of baseline ΣST-dev. These hypothesis-generating observations suggest that the main effects of ticagrelor may not relate to the rapidity or the completeness of acute reperfusion, but rather the prevention of recurrent vascular events by more powerful platelet inhibition or other mechanisms. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00391872.


[Diagnosis and therapy of erosive intervertebral osteochondrosis].
Pathogenically the erosive intervertebral osteochondrosis is the destructive form of the intervertebral osteochondrosis. This paper aims to define this acute variant by means of diagnostic criteria. In differential diagnosis a spondylodiscitis, an ankylosing spondylitis, a destructive spondylo-arthropathy and a morbus Scheuermann must be considered. Fifteen patients with erosive osteochondrosis were treated at the Department of Orthopaedic Surgery of the University of Mainz between 1990 and 1994. The diagnosis on admission into hospital was incorrect in all cases. Plain X-rays showed a decrease in height in the affected intervertebral room and bony erosions of the adjacent vertebral endplates. Distinction to spondylodiscitis was possible in MRT. In contrast to erosive osteochondrosis in spondylodiscitis edema cannot only be seen in the adjoining vertebrae but also in the affected disc. In later paravertebral inflammatory abscess often can be found. After conservative treatment four patients were free of complaints. 11 patients were operated on due to neurologic symptoms or increasing kyphosis of the lumbar spine. At average follow-up of 16 months intervertebral fusion was found in all operated patients. Lack of publicity and severance to spondylodiscitis seem to be major problems in diagnosing erosive osteochondrosis.


Trueness of Fit of Biphasic Transversely Isotropic Parameters Model in the Porcine Temporomandibular Joint Disc and Mandibular Condylar Cartilage and Regional Dependence.
Temporomandibular joint (TMJ) disorders (TMDs) are not well understood and the mechanical differences between the regions of the mandibular condylar cartilage (MCC) and the TMJ disc have not been thoroughly compared. As of now, there are no commercially available regenerative therapies for the TMJ. Elucidating the mechanical properties of these two structures of the articulating joint will help future efforts in developing tissue engineering treatments of the TMJ. In this study, we evaluate the compressive properties of the porcine disc and mandibular condylar cartilage by performing unconfined compression at 10% strain with 4.5%/min strain rate. Punches (4 mm biopsy) from both tissues were taken from five different regions of both the MCC and TMJ: anterior, posterior, lateral, medial, and central. Previously, theoretical models of compression in the porcine tissue did not fit the whole ramp-relaxation behavior. Thus, the data stress-relaxation was fitted to the biphasic transversely isotropic model, for both the TMJ disc and cartilage. From the results found in the disc, it was found that the posterior region had the highest values in multiple viscoelastic parameters when compared to the other regions. The mandibular condylar cartilage was only found to be significantly different in the transverse modulus between the posterior and lateral regions. Both the TMJ disc and MCC had similar magnitudes of values (for the modulus and other corresponding compressive properties) and behavior under this testing modality.


Diagnosis and treatment of infections due to Mycobacterium avium complex.
MYCOBACTERIUM AVIUM complex (MAC) consists of nontuberculous mycobacteria that cause disease in immunocompromised and immunocompetent hosts. The organisms are ubiquitous in the environment, and acquisition occurs through ingestion or inhalation of aerosols from soil, water, or biofilms. Disease may manifest as disseminated infection, soft tissue infection, chronic pneumonia, or hypersensitivity pneumonitis. Nontuberculous mycobacteria are increasingly associated with pulmonary disease, with MAC being the most common nontuberculous mycobacteria to cause pulmonary disease in the United States. Pulmonary symptoms, nodular or cavitary opacities on a chest radiograph or high-resolution computed tomographic scan with multifocal bronchiectasis and multiple small nodules, plus positive culture results from two sputum specimens or one bronchoscopic specimen are consistent with MAC pulmonary disease. Treatment consists of a macrolide, rifamycin, and ethambutol given three times weekly for noncavitary disease and daily with or without an aminoglycoside for cavitary disease.


Impact of CD40 ligand, B cells, and mast cells in peanut-induced anaphylactic responses.
The effector immune mechanisms underlying peanut-induced anaphylaxis remain to be fully elucidated. We investigated the relative contribution of Igs, mast cells (MCs), and FcepsilonRI in the elicitation of anaphylaxis in a murine model. Assessment of peanut hypersensitivity reactions was performed clinically and biologically. Our data show that wild-type (WT; C57BL/6 strain) mice consistently developed severe anaphylaxis (median clinical score: 3.5/5), an approximately 8 degrees C drop in core body temperature, and significantly increased plasma levels of histamine and leukotrienes. CD40 ligand- and B cell-deficient mice presented evidence of allergic sensitization as demonstrated by production of Th2-associated cytokines by splenocytes and a late-phase inflammatory response that were both indistinguishable to those detected in WT mice. However, CD40 ligand- and B cell-deficient mice did not exhibit any evidence of anaphylaxis. Our data also show that MC-deficient (Kit(W)/Kit(W-v)) mice did not suffer, unlike their littermate controls, anaphylactic reactions despite the fact that serum levels of peanut-specific Igs were similarly elevated. Finally, FcepsilonRI-deficient mice experienced anaphylactic responses although to a significantly lesser degree than those observed in WT mice. Thus, these data demonstrate that the presence of peanut-specific Abs along with functional MCs comprise a necessary and sufficient condition for the elicitation of peanut-induced anaphylaxis. That the absence of FcepsilonRI prevented the development of anaphylaxis only partially insinuates the contribution of an IgE-independent pathway, and suggests that strategies to impair MC degranulation may be necessary to improve the efficacy of anti-IgE therapy.