Localization of growth hormone-releasing hormone in the human hypothalamus and pituitary stalk.
The localization of the recently identified GH-releasing hormone (GHRH) in the human hypothalamus and pituitary stalk was determined by microdissection techniques and a specific RIA for GHRH. The highest concentrations of GHRH immunoreactivity (IR-GHRH) in the hypothalamus were found in the area of the infundibular nucleus (83 +/- 4 ng/mg protein; average +/- range). Lower quantities were found in other hypothalamic regions. Very high concentrations of IR-GHRH were present in the upper portion of the pituitary stalk (1454 +/- 48 ng/mg protein), and they decreased gradually toward the distal end of the stalk (21 +/- 3 ng/mg). This concentration gradient suggests that the peptide reaches the anterior pituitary mainly by way of the long portal vessels. Somatostatin, the second neuropeptide involved in the regulation of GH secretion from the anterior pituitary, had a pattern of distribution along the pituitary stalk very similar to that of IR-GHRH.


The Hedgehog target Gli1 is not required for bleomycin-induced lung fibrosis.
Sonic Hedgehog (SHH) signaling, a developmental pathway promoting lung mesenchymal expansion and differentiation during embryogenesis, has been increasingly recognized as a profibrotic factor in mature lung, where it might contribute to the pathogenesis of lung fibrosis. Pathway inhibition at the level of the downstream Gli transcription factors Gli1 and Gli2 (by GANT61) ameliorates lung fibrosis in the bleomycin model, whereas inhibition proximally at the level of HH ligand (by anti Hh antibody 5E1) or Smo (by GDC-0449) of the canonical pathway does not, implicating Gli1 and/or Gli2 as a key target. The fact that both the Gli1-labelled cell lineage and Gli1 expressing cells expand during fibrosis formation and contribute significantly to the pool of myofibroblasts in the fibrosis scars suggests a fibrogenic role for Gli1. Therefore to further dissect the roles of Gli1 and Gli2 in lung fibrosis we evaluated Gli1 KO and control mice in the bleomycin model. Monitoring of Gli1+/+ (n = 12), Gli1lZ/+ (n = 37) and Gli1lZ/lZ (n = 18) mice did not reveal differences in weight loss or survival. Lung evaluation at the 21-day endpoint did not show differences in lung fibrosis formation (as judged by morphology and trichrome staining), Ashcroft score, lung collagen content, lung weight, BAL protein content or BAL cell differential count. Our data suggest that Gli1 is not required for bleomycin-induced lung fibrosis.


Understanding the relation between expectancies and drinking among DUI offenders using expectancy categories.
In the context of several recent studies that have found negative expectancies to predict drinking-related variables, the present study was designed to examine the relationships among positive expectancies, negative expectancies and drinking, in a sample of DUI offenders. Participants (N = 96; 75% male) recruited from a 3-day residential alcohol education program completed a demographic data sheet, the Negative Alcohol Expectancy Questionnaire (NAEQ), the Alcohol Expectancy Questionnaire (AEQ) and the Customary Drinking Record upon admission to treatment. At a 3-month follow-up assessment, these measures were re-administered to 49% of the sample. Hierarchical multiple regression revealed that both positive and negative expectancies were related to number of drinks in the previous 30 days. Stepwise multiple regression revealed that baseline drinking and negative expectancies were both related to number of drinking days at the 3-month follow-up assessment. To assess the interplay of positive and negative expectancies as they relate to drinking, participants were categorized as "low" or "high" on both the AEQ and the NAEQ. The low positive/low negative group drank more than the low positive/high negative group. There was no statistically significant difference in drinking between the high positive/low negative and the high positive/high negative group. This study provides additional evidence that negative alcohol expectancies are related to drinking. These findings suggest that the proposed restraining influence of negative expectancies on drinking may be reduced when a drinker has concurrent positive expectancies which are high.


Differential transport and integration into the nuclear lamina for lamins A, B, and C.
Lamins A, B, and C are the major proteins of the mammalian nuclear lamina and have been well studied in BHK-21 cells. Using in vivo labelling, cell fractionation, and immunoprecipitation, we have found that lamins have different patterns of nuclear transport and solubility. Newly synthesized lamin A is translocated to the nucleus faster than lamin C or B. It is the most tightly bound lamin and cannot be extracted from the lamina by nonionic detergent or high-salt buffers. Lamins B and C migrate more slowly to the nucleus. Partitioning between cytoskeleton and detergent-soluble fractions shows that integration of lamins B and C is not completed before a 1-h chase. For lamin C this process is dependent upon protein synthesis and can be inhibited with cycloheximide. Even though lamins A and C are almost identical, lamin C is never firmly bound to the lamina and can be partially solubilized upon high-salt treatment.


The Potential Use of Isothermal Amplification Assays for In-Field Diagnostics of Plant Pathogens.
Rapid, sensitive, and timely diagnostics are essential for protecting plants from pathogens. Commonly, PCR techniques are used in laboratories for highly sensitive detection of DNA/RNA from viral, viroid, bacterial, and fungal pathogens of plants. However, using PCR-based methods for in-field diagnostics is a challenge and sometimes nearly impossible. With the advent of isothermal amplification methods, which provide amplification of nucleic acids at a certain temperature and do not require thermocyclic equipment, going beyond the laboratory has become a reality for molecular diagnostics. The amplification stage ceases to be limited by time and instruments. Challenges to solve involve finding suitable approaches for rapid and user-friendly plant preparation and detection of amplicons after amplification. Here, we summarize approaches for in-field diagnostics of phytopathogens based on different types of isothermal amplification and discuss their advantages and disadvantages. In this review, we consider a combination of isothermal amplification methods with extraction and detection methods compatible with in-field phytodiagnostics. Molecular diagnostics in out-of-lab conditions are of particular importance for protecting against viral, bacterial, and fungal phytopathogens in order to quickly prevent and control the spread of disease. We believe that the development of rapid, sensitive, and equipment-free nucleic acid detection methods is the future of phytodiagnostics, and its benefits are already visible.


Integrating Dually Encapsulated Si Architecture and Dense Structural Engineering for Ultrahigh Volumetric and Areal Capacity of Lithium Storage.
High-theoretical-capacity silicon anodes hold promise in lithium-ion batteries (LIBs). Nevertheless, their huge volume expansion (∼300%) and poor conductivity show the need for the simultaneous introduction of low-density conductive carbon and nanosized Si to conquer the above issues, yet they result in low volumetric performance. Herein, we develop an integration strategy of a dually encapsulated Si structure and dense structural engineering to fabricate a three-dimensional (3D) highly dense Ti3C2Tx MXene and graphene dual-encapsulated Si monolith architecture (HD-Si@Ti3C2Tx@G). Because of its high density (1.6 g cm-3), high conductivity (151 S m-1), and 3D dense dual-encapsulated Si architecture, the resultant HD-Si@Ti3C2Tx@G monolith anode displays an ultrahigh volumetric capacity of 5206 mAh cm-3 (gravimetric capacity: 2892 mAh g-1) at 0.1 A g-1 and a superior long lifespan of 800 cycles at 1.0 A g-1. Notably, the thick and dense monolithic anode presents a large areal capacity of 17.9 mAh cm-2. In-situ TEM and ex-situ SEM techniques, and systematic kinetics and structural stability analysis during cycling demonstrate that such superior volumetric and areal performances stem from its dual-encapsulated Si architecture by the 3D conductive and elastic networks of MXene and graphene, which can provide fast electron and ion transfer, effective volume buffer, and good electrolyte permeability even with a thick electrode, whereas the dense structure results in a large volumetric performance. This work offers a simple and feasible strategy to greatly improve the volumetric and areal capacity of alloy-based anodes for large-scale applications via integrating a dual-encapsulated strategy and dense-structure engineering.


[International Test Commission Guidelines for test translation and adaptation: second edition].
Adapting tests across cultures is a common practice that has increased in all evaluation areas in recent years. We live in an increasingly multicultural and multilingual world in which the tests are used to support decision-making in the educational, clinical, organizational and other areas, so the adaptation of tests becomes a necessity. The main goal of this paper is to present the second edition of the guidelines of the International Test Commission (ITC) for adapting tests across cultures. A task force of six international experts reviewed the original guidelines proposed by the International Test Commission, taking into account the advances and developments of the field. As a result of the revision this new edition consists of twenty guidelines grouped into six sections: Precondition, test development, confirmation, administration, score scales and interpretation, and document. The different sections are reviewed, and the possible sources of error influencing the tests translation and adaptation analyzed. Twenty guidelines are proposed for translating and adapting tests across cultures. Finally we discuss the future perspectives of the guidelines in relation to the new developments in the field of psychological and educational assessment.


Effects of PM Exposure on the Methylation of Clock Genes in a Population of Subjects with Overweight or Obesity.
The expression of clock genes, regulating the synchronization of metabolic and behavioral processes with environmental light/dark cycles, is regulated by methylation and might be influenced by short-term exposure to airborne particulate matter (PM), especially in individuals that are hypersensitive to proinflammatory cues. The present study aimed to evaluate the effects of PM2.5 and PM10 on the methylation profile of the clock genes ARNTL, CLOCK, CRY1, CRY2, PER1, PER2, and PER3 in a population of 200 women with obesity. A significant association between PM10 exposure and the methylation of clock genes was found, namely, this was negative for PER2 gene and positive for the CLOCK, CRY1, CRY2, and PER3 genes. PM2.5 was negatively associated with methylation of PER2 gene and positively with methylation of CRY2 gene. Evidence was observed for effect modification from body mass index (BMI) regarding the PER1 gene: as PM2.5/10 increases, DNA methylation increases significantly for relatively low BMI values (BMI = 25), while it decreases in participants with severe obesity (BMI = 51). PM may therefore alter the epigenetic regulation of clock genes, possibly affecting circadian rhythms. Future studies are needed to clarify how alterations in clock gene methylation are predictive of disease development and how obesity can modulate the adverse health effects of PM.


[Molecular mechanisms involved in kidney ischemia-reperfusion].
Acute renal failure (ARF) is still associated with high mortality. It is the consequence of a set of phenomena leading to a low glomerular filtration rate resulting, at least partly, from a misregulation of renal blood flow resulting itself from injuries at the epithelial and endothelial level. The outer medulla seems to be the region of the kidney the most affected by ischemia. Investigation at the histological level reveals a partial destruction of the renal epithelium generated by necrosis and/or apoptosis, loss of cell polarity, cell desquamation into the lumen and endothelial cell swelling. The recent advances in the comprehension of this pathology underline the major role of inflammation, which is probably responsible for the worsening and the persistence of ARF. Studies at the molecular level have pinpointed the implication of many signalling pathways such as apoptosis, G-protein signalling, various receptor and kinase activation. The characterisation of the molecular events involved in ARF should help in our approaches to prevent and treat ARF. The understanding of the adaptation mechanisms to ischemic stress (conditioning) is probably one of the most promising research area of this field in terms of medical applications.


Effects of anti-B7 monoclonal antibodies on humoral immune responses.
The costimulatory interaction between CD28 on T cells and B7-related molecules on antigen presenting cells plays an important role in a broad range of functions of the immune system, including protective immunity, tolerance induction, allograft rejection, and the development of autoimmune diseases. Monoclonal antibodies to B7-1 and B7-2 have been used in vivo to examine the mechanisms underlying these processes and to evaluate costimulation antagonism as an approach to treatment of chronic autoimmune diseases. To determine whether anti-B7 mAb might elicit, or inhibit, a host immune response that could influence the effects of these antibodies in vivo, we assessed the immune response to rat anti-B7-1 and anti-B7-2 mAb in healthy (BALB/c) mice and in lupus-prone NZB/NZW F1(B/W) mice. In BALB/c mice, low doses (1-10 microg) of mAb to B7-1 and mAb to B7-2 elicited brisk immune responses that occurred earlier and were significantly greater than the immune response to an isotype-matched control rat mAb to ovalbumin. In contrast, at higher doses (100-500 microg), both anti-B7 mAb, but not the control mAb, blocked the mouse anti-rat response. No such blockade occurred in B/W mice, who generated a significant mouse anti-rat response even at very high doses of anti-B7 mAb (1,000-4,000 microg). Blockade of the immune response to the anti-B7 mAb in BALB/c mice apparently did not reflect generalized immune suppression, because high doses of these mAb had little, if any effect on the humoral immune response to another antigen. These findings indicate that: (1) mAb to B7-1 and B7-2 can elicit either a potent immune response or no immune response at all depending upon the dose administered; (2) blockade of the immune response to anti-B7 mAb may be more difficult in the setting of autoimmunity; and (3) neither anti-B7-1 nor anti-B7-2 causes generalized suppression of humoral immunity.


Effect of GnRH and its antagonist (Antarelix) on LH release from cultured bovine anterior pituitary cells.
In the following investigations, the LH secretion of cells from pituitaries in heifers on days 16-18 of their oestrous cycle (n = 14) was analysed. Cells were dissociated with trypsin and collagenase and maintained in a static culture system. For the estimation of LH release, the cells were incubated with various concentrations of mammalian GnRH (Lutrelef) for 6 h. To determine the action of Antarelix (GnRH antagonist), the cells were preincubated for 1 h with concentrations of 10(-5) or 10(-4) M Antarelix followed by 10(-6) M GnRH coincubation for a further 6 h. At the end of each incubation, the medium was collected for LH analysis. Parallel, intracellular LH was qualitatively detected by immunocytochemistry. Changes in the intensity of LH staining within the cells in dependence of different GnRH concentrations were not observed, but a significant increase LH secretion in pituitary cells was measured at 10(-6) M GnRH. Antarelix had no effect on basal LH secretion at concentrations of 10(-4) and 10(-5) M. After coincubation of pituitary cells with Antarelix and GnRH, Antarelix blocked the GnRH-stimulated LH secretion with a maximal effect of 10(-4) M, but the staining of immunoreactive intracellular LH was detected at approximately the same level compared to the pituitary cells treated with exogenous GnRH alone. These data demonstrate that Antarelix is effective in influencing the GnRH-stimulated LH secretion of pituitary cells in vitro. After administration of Antarelix in vivo, the GnRH-stimulated LH secretion of cultured pituitary cells was not inhibited.


Antibacterial activity of aqueous and methanol extracts of selected species used in livestock health management.
Salvadora persica L. (Salvadoraceae), Colophospermum mopane (J.Kirk ex Benth.) J. Léonard (Leguminosae) and Dichrostachys cinerea (L.) Wight & Arn. (Leguminosae) crude extracts are used by local farmers against many livestock infections with little or no side effects usually associated with synthetic antimicrobials. However, their efficacy has rarely been tested. These plants were tested for potential antibacterial activity against clinical isolates of Staphylococcus aureus ATCC33862 and Escherichia coli ATCC25922. Minimal inhibitory concentrations (MIC) of the crude plant extracts were determined. Aqueous and methanol extraction of 100 g each of the bark of C. mopane, roots of D. cinerea and leaves of S. persica was done by placing the samples in 250 mL of either water or methanol. Nutrient broth was used as growth medium for the bacteria, and McFarland standard for bacterial standardization. 2,3,5-Triphenyltetrazoliumchloride (TTC) was the indicator salt. Each of the aqueous and methanol extracts (100 μL) was tested. Gentamycin and ampicillin were the controls. MIC of aqueous extracts ranged from 1.03-14.6 mg/mL against S. aureus, and from 12.1-34.3 mg/mL against E. coli. Methanol extracts ranged between 5.31 and 9.64 mg/mL against S. aureus, and between 7.86 and 13.6 mg/mL against E. coli. Aqueous and methanol extracts of S. persica were significantly higher (p < 0.05) than C. mopane and D. cinerea. Colophospermum mopane, S. persica and D. cinerea exhibited antibacterial activity, with methanol extracts performing better than aqueous extracts, justifying use as ethnoveterinary medicine. Further study to isolate the active components should be pursued.


[Are mental disorders the cause of reflex sympathetic dystrophy: a review].
Predisposition to reflex sympathetic dystrophy (RSD) is defined as personal susceptibility to produce and maintain an excessive reaction in response to nociceptive stimulation. There is suggested that certain psychological traits predispose one to develop RSD, however, some authors claim that emotional and behavioural disturbances are the result rather than the cause of this painful condition. The review of the literature concerning the relations between psychological factors and RSD is presented in the paper. The review revealed no valid evidence to support the opinion that there is particular psychological or personality pattern predisposing one to develop RSD. Nevertheless, the internal susceptibility to RSD has not been completely precluded. On the other hand, there is enough evidence in the literature to substantiate the view that psychological and emotional disturbances are secondary to persistent disease. These changes, however, are not characteristics for RSD but occur also in other patients suffering from severe pain of other origin. There is emphasized in the paper that psychological support has significantly positive effect in the treatment of RSD.


Transformed diffuse large B-cell lymphoma from marginal zone lymphoma in the anterior mediastinum: A case report and review of the literature.
Marginal zone lymphoma (MZL) arising from the anterior mediastinum is rare. In the majority of reported cases, the tumor was incidentally discovered, reflecting its indolent clinical features. We present a 38-year-old woman who had no medical history, and presented with a bulky anterior mediastinal tumor complicated by life-threatening compression of the vasculature and bronchi. Biopsy specimens of the neoplasm suggested transformed diffuse large B-cell lymphoma (DLBCL) from MZL. To our best knowledge, this is the first case report of anterior mediastinum MZL associated with an aggressive clinical course and life-threatening complications likely due to transformation to DLBCL.


[Technique of Linac radiosurgery for cerebral arteriovenous malformations].
Description of the irradiation technique used by our group since 1986 for radiosurgery of cerebral arteriovenous malformations using Xrays minibeams from a linear accelerator. Method. The technique was elaborated by O. Betti in the early 80. He used several coronal arcs to irradiate the center of the target with X rays circular minibeams. Their diameter (6 to 20 mm) is chosen according to the size of the nidus. The patient is seated in a specially built armchair. His head is immobilized with the Talairach frame afixed in the calvarium by 4 special screws: they allow to remove the frame after stereotactic angiography and/or CTscan and to replace it to perform the stereotactic irradiation. The frame and the head rotate around an horizontal axis passing by the linac isocenter ie the center of the target volume. The combination of both movements: rotation of the Linac and rotation of the stereotactic frame covers a spherical sector representing the surface of portals of entry of the minibeams. The frame can slide on a plate allowing access to the entire brain. Results. The special seat and the frame are movable on curved rails allowing to avoid or reduce irradiation of the body of the patient. We have been using this system of irradiation in the seated position since 1986 to treat more than 900 patients.


Development of allergic contact dermatitis requires activation of both tumor necrosis factor-receptors.
We investigated the role of the TNF receptors, type I (p55TNFR) and type II (p75TNFR), in a mouse model of contact hypersensitivity, i.e., a model of a delayed type hypersensitivity (DTH) allergic reaction. Mice deficient for p55TNFR or p75TNFR were used to investigate the functions of these receptors in development of the DTH reaction. We show that both TNF receptors have a strong influence on the overall outcome of the DTH reaction, with the two TNF receptors exerting distinct functions. Dendritic cells of mice lacking p55TNFR had a defect in allergen uptake but showed normal migration into regional lymph nodes. In contrast, dendritic cells of p75TNFR-deficient mice showed diminished migration into regional lymph nodes after allergen contact, whereas the allergen uptake was independent of the p75TNFR. Thus, both TNF receptors are required for the development of a complete DTH reaction.


Inflammation and obstructive sleep apnea syndrome pathogenesis: a working hypothesis.
Obstructive sleep apnea syndrome (OSAS) afflicts about 5% of adults in Western countries and is thought to play an important role in the pathogenesis of cardiovascular disorders and diabetes mellitus. Although the etiology of OSAS is uncertain, intense local and systemic inflammation are present in these patients. In the upper airway, this process may promote oropharyngeal inspiratory muscle dysfunction and amplify upper airway narrowing and collapsibility thereby worsening the frequency and duration of apneas during sleep. The presence of systemic inflammation, characterized by elevated levels of certain potent pro-inflammatory mediators, such as C-reactive protein, leptin, TNF-alpha, IL-1beta, IL-6, reactive oxygen species and adhesion molecules, may predispose to the development of cardiovascular complications observed in patients with OSAS. Treatment with nasal CPAP abrogates, in part, local and systemic inflammation in these patients. Whether therapeutic interventions aimed at abating inflammation could be a useful adjunct in the treatment of OSAS merits further investigation.


Can we prevent fractures?
The primary aim of any intervention in osteoporosis is the prevention of fractures in individuals who have not yet fractured or the prevention of the progression of the disease in individuals with fragility fractures. There is currently insufficient evidence to recommend either a population-based prevention strategy or a strategy based on general screening with treatment of those individuals identified at high risk. Identification of subjects with strong clinical risk factors for osteoporotic fractures with subsequent measurement or not of bone mineral density as well as those with fragility fractures constitute at present the most rational approach to fracture prevention. Current measures to prevent osteoporotic fractures aim mainly at influencing bone mass and bone turnover and reducing the risk and impact of falls. Interventions that can reduce effectively the frequency of osteoporotic fractures in subjects at risk are available and new or alternative interventions are being developed. Issues related to the impact of these interventions on public health and health economics need to be addressed and methods to calculate the clinical outcomes in a way allowing comparison with outcomes of interventions in other common diseases should be developed.


The effect of Ca+ free medium on the two different tricarboxylate cycles in the rat brain cortex slices.
The authors studied the effect of calcium-free saline-glucose medium on labelled amino acid and [14C]CO2 synthesis from U-[14C]-glucose and 1-[14C]-acetate in rat brain cortex slices. Respiration was stimulated parallel with increased synthesis of labelled amino acids and of [14C]CO2 from glucose to [to 150 % and 170 % respectively]. Specific glutamate, aspartate and neutral amino acid activity rose, GABA and glutamine were unaffected. Amino acid synthesis from 1-[14C]-acetate was inhibited [58%], while [14C]CO2 release was unchanged. This indicates that oxygen consumption via the tricarboxylase cycle associated with the small glutamate pool [and probably localized in the glia cells] did not alter in calcium-free medium, although conversion to amino acids was impaired.


Determining counselling communication strategies associated with successful quits in the National Health Service community pharmacy Stop Smoking programme in East London: a focused ethnography using recorded consultations.
To determine communication strategies associated with smoking cessation in the National Health Service community pharmacy Stop Smoking programme. 11 community pharmacies in three inner east London boroughs. 9 stop smoking advisers and 16 pairs of smokers who either quit or did not quit at 4 weeks, matched on gender, ethnicity, age and smoking intensity. 1-3 audio-recorded consultations between an adviser and each pair member over 5-6 weeks were analysed using a mixed-method approach. First a content analysis was based on deductive coding drawn from a theme-oriented discourse analysis approach and the Roter Interaction Analysis System. Core themes were identified through this quantification to explore in detail the qualitative differences and similarities between quitters and non-quitters. Quantitative analysis revealed advisers used a core set of counselling strategies that privileged the 'voice of medicine' and often omitted explicit motivational interviewing. Smokers tended to quit when these core strategies were augmented by supportive talk, clear permission for smokers to seek additional support from the adviser between consultations, encouragement for smokers to use willpower. The thematic analysis highlighted the choices made by advisers as to which strategies to adopt and the impacts on smokers. The first theme 'Negotiating the smoker-adviser relationship' referred to adviser judgements about the likelihood the smoker would quit. The second theme, 'Roles of the adviser and smoker in the quit attempt', focused on advisers' counselling strategies, while the third theme, 'Smoker and adviser misalignment on reasons for smoking, relapsing and quitting', concerned inconsistencies in the implementation of National Centre for Smoking Cessation and Training recommendations. Advisers in community pharmacies should use the advantages of their familiarity with smokers to ensure appropriate delivery of patient-centred counselling strategies and reflect on the impact on their counselling of early judgements of smoker success.


Pseudo-hypoaldosteronism secondary to infantile urinary tract infections: role of ultrasound.
The biochemical hallmarks of transient pseudo-hypoaldosteronism associated with a pyelonephritis include hyponatremia, hyperkalemia, and acidosis. We tested if the kidney-urinary tract ultrasound helps in predicting the diagnosis of overt pseudo-hypoaldosteronism in infants with a pyelonephritis. Between 2013 and 2020, we managed 71 previously healthy infants 4 weeks to 24 months of age with a pyelonephritis (42 males and 29 females) and made the biochemical diagnosis of pseudo-hypoaldosteronism in 17 (24%). Infants with and without pseudo-hypoaldosteronism did not significantly differ with respect to the prevalence of kidney-urinary tract ultrasound abnormalities, graded by means of the UTD classification system of urinary tract abnormalities. Kidney-urinary tract ultrasound is almost routinely obtained in children with a febrile urinary tract infection. Our experience does not support the hypothesis that ultrasound might be relevant for the diagnosis of overt transient pseudo-hypoaldosteronism in babies affected by a urinary tract infection. Our data confirm the assumption that negative studies may be important for advancing clinical practice.


Thickness of fibrous capsule after implantation of hydroxyapatite in subcutaneous tissue in rats.
The present study evaluates in rats the histomorphometrical thickness of fibrous capsules that surround hydroxyapatite (HA) disks after implantation. HA disks were implanted into the subcutaneous tissue of 79 rats for 1 day to 20 months. Decalcified histological sections stained with hematoxylin and eosin were examined. Fibrous capsule thickness (FCT) was measured using an objective micrometer. On the fourteenth day, primary fibrous capsules formed around implants. From that time point FCT increased with time of implantation. Within a given sample, FCT differed from one portion of the fibrous capsule to another, depending on which site faced the disks. FCT was thickest at the upper and lower portions of the disks, thinner at the lateral portions, and thinnest at the upper and lower ring-shaped portions. Two possible explanations for the above findings are discussed in this paper: (1) The area of contact between disk and tissue differs. (2) Chemical stimulation of implanted material caused by demineralization and remineralization may result from the varying thicknesses of fibrous capsules. FCT from upper and lower portions of HA disks increased by over 200% in the first 10 months and steadily increased about 20% over the next 10 months. Many studies have concluded that HA is useful for reconstructive surgery, so the long-term effects of FCT need further study.


A Highly Sensitive and Flexible Metal-Organic Framework Polymer-Based H2S Gas Sensor.
We report the fabrication of a novel metal-organic framework (MOF)-polymer mixed-matrix flexible membrane for the detection of hydrogen sulfide (H2S) gas at room temperature. This high-performance gas sensor is based on MOF-5 microparticles embedded on a conductivity-controlled chitosan (CS) organic membrane. The conductivity of the organic membrane is controlled by blending it with a glycerol ionic liquid (IL) at different concentrations. The sensor showed a remarkable detection sensitivity for H2S gas at a concentrations level as low as 1 ppm at room temperature. The MOF-5/CS/IL gas sensor demonstrates a highly desirable detection selectivity, fast response time (<8 s), recovery time of less than 30 s, and outstanding sensing stability averaging at 97% detection with 50 ppm of H2S gas. This composite having high sensitivity, low-power consumption, and flexibility holds great promise for addressing current challenges pertinent to environmental sustainability.


Inositol and gradient phytase supplementation in broiler diets during a 6-week production period: 1. effects on growth performance and meat yield.
An experiment was conducted to evaluate effects of inositol and gradient phytase supplementation on growth performance and meat yield of broilers from 1 to 41 d of age. A total of 1,920 Yield Plus × Ross 708 male chicks were placed in 64 floor pens (30 birds per pen). Each pen received one of the 8 dietary treatments (8 replicate pens) from 1 to 15, 16 to 29, and 30 to 40 d of age. Treatment 1 was formulated to contain 0.165 and 0.150% lower calcium and phosphorus, respectively, than treatment 7 (positive control). Phytase was added to treatment 1 at concentration of 500, 1,500, 4,500, 13,500, and 40,500 phytase units (FTU)/kg to establish treatments 2 to 6, respectively. Treatment 8 was formulated by adding inositol to treatment 7 based on the expected inositol liberation in treatment 6. Feed and birds were weighed at 1, 15, 29, and 40 d of age to determine BW gain, feed intake, and feed conversion. Twelve birds per pen were processed at 41 d of age to determine carcass characteristics. From 1 to 40 d of age, log-quadratic effects of phytase (treatments 1-6) were observed for BW gain (P = 0.002) and feed conversion in broilers (P = 0.018), whereas feed intake increased log-linearly (P = 0.045). The addition of 40,500 FTU/kg of phytase increased cumulative BW gain (P = 0.001) and decreased cumulative feed conversion (P = 0.005) by 4.7 and 2.6%, respectively, compared with birds subjected to treatment 8. Log-quadratic effects of phytase additions were observed for carcass (P < 0.001) and breast meat weights (P = 0.004). Growth performance and carcass characteristics of broilers subjected to treatment 7 were similar (P > 0.05) to those of birds subjected to treatment 8. These data demonstrate that the extraphosphoric effects of phytase may be associated with increased feed intake of broilers. Inositol supplementation did not provide additional benefits to broilers in this study.


Clinical Features of COVID-19 Patients in Xiaogan City.
On February 6, 2020, Xiaogan City became the second most seriously affected city with coronavirus disease 2019 (COVID-19), outside Wuhan district, Hubei Province, China. The objectives are to study the clinical features of COVID-19 patients and assess the relationship between the severity of COVID-19, age, and C-reactive protein (CRP) levels. The retrospective data of 134 COVID-19 patients hospitalized in 3 hospitals of Xiaogan City, between February 1 and March 1, 2020, was collected. This study documented COVID-19 patients. Clinical data in terms of body temperature, history of travel, and direct contact with COVID-19 patients, and incubation period was collected. Out of the 134 patients, only 5 required intensive care. Moreover, 2 patients succumbed during this period. The median age of patients was 45 (33-56) years. The most common symptoms at the onset of disease were fever (66.4%), cough (33, 6%), and sore throat (14.7%). Amongst the medicines used, antiviral agents (92.3%) followed by the traditional Chinese medicine (89.5%) were most commonly used. In both the crude and adjusted (I to III) models, odds ratio and its 95% confidence interval for both age and CRP levels were > 1. Moreover, the smooth curve fitting graph reflected that the severity of COVID-19 was positively correlated with both age and CRP levels (all P value < 0.05). The signs and symptoms of COVID-19 patients were fairly moderate. The health care professionals treating the COVID-19 patients should be aware of the increased likelihood of progression to severe COVID-19 in elderly patients and those with high CRP levels.


Diagnostic investigations. Part 1. Lumbar puncture.
This article, the first in a three-part series on clinical investigations, discusses the technique and uses of lumbar puncture. This diagnostic procedure involves making a puncture into the subarachnoid space of the spinal cord, to remove an excess of fluid; to obtain fluid for examination and analysis, or to inject medication. The article includes an explanation of the relevant anatomy and the composition and role of cerebrospinal fluid, a detailed description of the procedure and the interpretation of results.


Abdominal visceral adipose tissue volume is associated with increased risk of erosive esophagitis in men and women.
Data on the association between erosive esophagitis and obesity are inconsistent because of variations in study populations and methods used to determine obesity. Participants in a prospective health-screening cohort underwent esophagogastroduodenoscopy and computed tomography. The association between erosive esophagitis and obesity (measured by body mass index [BMI], waist circumference, and abdominal visceral adipose tissue volume) was estimated with odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for confounding factors. We also analyzed the association between obesity and erosive esophagitis by sex. The prevalence of erosive esophagitis was 9.3% (495/5329). The OR for erosive esophagitis correlated with obesity measured by BMI, waist circumference, and abdominal visceral adipose tissue volume (P < .001 for each factor). The multivariate OR for erosive esophagitis was 1.97 (95% CI: 1.34-2.90) for a visceral adipose tissue volume of 500-999 cm(3), 2.27 (95% CI: 1.51-3.39) for 1000-1499 cm(3), and 2.94 (95% CI: 1.87-4.62) for ≥1500 cm(3), compared with participants who had visceral adipose tissue volumes less than 500 cm(3). When measures of obesity were analyzed simultaneously, abdominal visceral adipose tissue volume, but not BMI or waist circumference, was associated with erosive esophagitis. The 3 measures of obesity were significantly associated with erosive esophagitis in males, but only visceral adipose tissue volume was associated with erosive esophagitis in females (P = .002). In contrast to BMI or waist circumference, abdominal visceral adipose tissue volume is associated with an increased risk of erosive esophagitis in males and females.


Monocephalus diprosopus, a rare form of conjoined twins, and associated congenital anomalies.
Craniofacial duplication (diprosopus) is a rare form of conjoined twins. A case of monocephalus diprosopus with anencephaly, cervicothoracolumbar rachischisis, and duplication of the respiratory tract and upper gastrointestinal tract is reported. The cardiovascular system remained single but the heart showed transposition of the great vessels. We present this case due to its rarity, and compare our pathologic findings with those already reported.


Structure of silica in matt water-based lacquer.
A model for the structure of silica matting agent in water-based lacquers is presented. It is assumed that, during film formation, the air that lies between the silica particles in the dry powder is replaced by polymer. At a critical concentration this leads to a silica structure similar to that of the dry powder. We assume the bulk volume occupied by the dry silica powder (silica and air) equals the dried lacquer film (polymer, silica, and residual air). Since the silica structure in the dry powder percolates, the silica in the dried lacquer is tested for percolation. Experimentally, a percolation threshold is found close to the critical concentration predicted by the model. Two further silica structures are also seen under different conditions. At low silica concentrations, the silica particles are suspended in the lacquer matrix and isolated. Above the percolation threshold, where the bulk volume of the dry silica exceeds that of the film, the silica structure can undergo collapse. This is caused by volume reduction in the lacquer as water evaporates. The lacquer is imaged with confocal laser scanning microscopy, to produce three-dimensional images of the bulk of the 50-microm film. Resolution is enhanced with image reconstruction via deconvolution. Computational image analysis is then used to investigate the structure quantitatively.


Characterization of a culturable alphaproteobacterial symbiont common to many marine sponges and evidence for vertical transmission via sponge larvae.
A closely related group of alphaproteobacteria were found to be present in seven genera of marine sponges from several locations and were shown to be transferred between sponge generations through the larvae in one of these sponges. Isolates of the alphaproteobacterium were cultured from the sponges Axinella corrugata, Mycale laxissima, Monanchora unguifera, and Niphates digitalis from Key Largo, Florida; Didiscus oxeata and Monanchora unguifera from Discovery Bay, Jamaica; an Acanthostronglyophora sp. from Manado, Indonesia; and Microciona prolifera from the Cheasapeake Bay in Maryland. Isolates were very similar to each other on the basis of 16S rRNA gene sequence (>99% identity) and are closely related to Pseudovibrio denitrificans. The bacterium was never isolated from surrounding water samples and was cultured from larvae of M. laxissima, indicating that it is a vertically transmitted symbiont in this sponge. Denaturing gradient gel electrophoresis, 16S rRNA gene clone library analysis, and fluorescent in situ hybridization with probes specific to the alphaproteobacterium confirmed the presence of this bacterium in the M. laxissima larvae. The alphaproteobacterium was densely associated with the larvae rather than being evenly distributed throughout the mesohyl. This is the first report of the successful culture of a bacterial symbiont of a sponge that is transferred through the gametes.


The Role of Major Histocompatibility Complex in Organ Transplantation- Donor Specific Anti-Major Histocompatibility Complex Antibodies Analysis Goes to the Next Stage.
Organ transplantation has progressed with the comprehension of the major histocompatibility complex (MHC). It is true that the outcome of organ transplantation largely relies on how well rejection is managed. It is no exaggeration to say that to be well acquainted with MHC is a shortcut to control rejection. In human beings, MHC is generally recognized as human leukocyte antigens (HLA). Under the current circumstances, the number of alleles is still increasing, but the function is not completely understood. Their roles in organ transplantation are of vital importance, because mismatches of HLA alleles possibly evoke both cellular and antibody-mediated rejection. Even though the control of cellular rejection has improved by recent advances of immunosuppressants, there is no doubt that antibody-mediated rejection (AMR), which is strongly correlated with donor-specific anti-HLA antibodies (DSA), brings a poor outcome. Thus, to diagnose and treat AMR correctly is a clear proposition. In this review, we would like to focus on the detection of intra-graft DSA as a recent trend. Overall, here we will review the current knowledge regarding MHC, especially with intra-graft DSA, and future perspectives: HLA epitope matching; eplet risk stratification; predicted indirectly recognizable HLA epitopes etc. in the context of organ transplantation.


Green-to-red photoconvertible mEosFP-aided live imaging in plants.
Numerous subcellular-targeted probes have been created using a monomeric green-to-red photoconvertible Eos fluorescent protein for understanding the growth and development of plants. These probes can be used to create color-based differentiation between similar cells, differentially label organelle subpopulations, and track subcellular structures and their interactions. Both green and red fluorescent forms of mEosFP are stable and compatible with single colored FPs. Differential highlighting using mEosFP probes greatly increases spatiotemporal precision during live imaging.


Is phantom tooth pain a deafferentation (neuropathic) syndrome? Part II: Psychosocial considerations.
The symptoms of phantom tooth pain are often considered to be of psychological origin by those unfamiliar with its clinical characteristics. Part of the problem is that phantom tooth pain is often confused with atypical facial pain. Extensive literature exists for the latter that suggests a psychological cause. Many studies of atypical facial pain, however, suffer from one or more of four methodologic problems. In the present study, 115 phantom tooth pain cases are compared with a contrast group of 151 facial pain cases and 137 nonpain controls on a variety of personality characteristics. Only one trait personality factor, locus of control, statistically differentiates the three groups. The chief psychological difference of the phantom tooth pain sample compared with the control and contrast groups was higher scores on a measure of demoralization. Demoralization can be interpreted as a consequence as well as an antecedent of the chronic pain state. Evidence for each opinion is presented. Suggestions for obtaining informed consent of prospective endodontic patients are suggested. This study has not demonstrated that phantom tooth pain cases are characterized by a specific premorbid personality.


The Human Genome Project and gene therapy: a genetic counselor's perspective.
The Human Genome Project (HGP) and clinical trials of gene therapy create an expanded role for genetic counselors, nurses, and other health care practitioners. Translating fundamental advances in genetics into a benefit of clinical practice can be challenging. In addition to patients, the public and other professionals, including judges and lawyers, need to be educated about genetics and genetic testing and the potential for genetic intervention. The article provides an overview of the HGP, explains the concept of gene transfer, provides examples of clinical trials for specific diseases, and addresses practical issues related to the role of the coordinator in clinical trials of gene transfer.


Immunocytochemical features of the vestibular nuclei in the monkey and cat.
Immunocytochemical studies of the vestibular nuclei (VN) were done in the squirrel monkey and cat using polyclonal antisera. Brain stem sections were processed using the Avidin-Biotin peroxidase complex with diaminobenzidine as the chromagen. Choline acetyltransferase immunoreactivity (ChAT-IR) was most prevalent in the caudal medial (MVN), inferior (IVN) and peripheral superior (SVN) VN. Nearly all cells of groups x and z were ChAT-positive. None of the giant cells of the lateral vestibular nucleus (LVN) was ChAT-IR. Glutamate immunoreactivity (GLU-IR) was abundant in all VN and in cells of the vestibular ganglion (VG). Gamma-aminobutyric acid immunoreactivity (GABA-IR), was found in cells of rostral MVN, cell group y and in granules about giant cells in dorsal LVN. Substance P immunoreactive (SP-IR) was present in a small cells in MVN, IVN and the VG and in granules surrounding all large cells in LVN in both monkey and cat; SP-IR granules were most intense in ventral LVN in the monkey. Some cells in the dorsal parts of the fastigial nucleus (FN) were outlined by SP-IR granules in both species. Leucine-enkephalin immunoreactivity (ENK-IR) was identified only in granules surrounding cells of group x in the monkey. GLU was the only immunoreactive substance found in the giant cells of LVN. The disposition of ChAT-IR in the VN suggested participation in commissural systems, as well as projections to spinal cord and/or cerebellum. Small GABA-IR neurons in MVN probably represented both commissural and projection neurons; GABA-IR granules about cells in dorsal LVN and some cells in MVN and SVN appeared to represent Purkinje cell (PC) terminals. SP-IR granules surrounding cells in ventral LVN appeared to represent terminals of small SP-positive VG cells. The source of SP-IR granules around cells in dorsal LVN and some cells in FN and SVN remains unknown, but these fibers may originate from portions of the reticular formation known to contain large numbers of SP-positive neurons.


Common genetic variants of the FADS1 FADS2 gene cluster and their reconstructed haplotypes are associated with the fatty acid composition in phospholipids.
Fatty acid composition in membranes plays an important role in cellular processes and has shown to be associated with the aetiology of several complex diseases in humans. We report strong associations between variants in the human delta-5 and delta-6 desaturase genes FADS1 FADS2 and fatty acid composition in serum phospholipids. Eighteen polymorphisms located in this gene cluster were genotyped in 727 adults from Erfurt, a German centre of the European Community Respiratory Health Survey. The cluster is located at chromosome 11q12-11q13.1, a region repeatedly found to be linked with atopy and other complex diseases. Polymorphisms and statistically reconstructed haplotypes of FADS1 and the upstream region of FADS2 showed strongest associations with the level of the direct precursor of inflammatory eicosanoids, the n-6 fatty acid arachidonic acid (C20:4n-6), also strong associations with levels of the n-6 fatty acids C18:2n-6, C18:3n-6, C20:2n-6, C20:3n-6, C22:4n-6 and of the n-3 fatty acids C18:3n-3, C20:5n-3 and C22:5n-3 (P-values < 1.0 x 10(-13)). Carriers of the rare alleles of several SNPs and their respective haplotypes had a lower prevalence of allergic rhinitis and atopic eczema. No association was found for total and specific IgE levels.


An intractable hematoma after cranioplasty cured by scalp cryohemostasis treatment.
We report an intractable post cranioplasty hematoma which required multiple operations. The titanium cranioplasty was for a cranial defect from surgery for an intracranial hemorrhage. Despite removal of the cranioplasty the haematoma repeatedly recurred. So we applied the cryohemostasis by the ice packs 4 times a day for 30 minutes. With this simple cooling method haemostasis was achieved.


Copper-catalyzed synthesis of benzoxazoles via a regioselective C-H functionalization/C-O bond formation under an air atmosphere.
An efficient method for the synthesis of functionalized benzoxazoles is described that involves a copper(II)-catalyzed regioselective C-H functionalization/C-O bond formation protocol. The use of dichlorobenzene as a solvent at 160 degrees C allows the use of air as the terminal oxidant in the catalytic synthesis of benzoxazoles in a process that has high functional group tolerance. The presence of a directing group at the meta position markedly improves the reaction efficacy and a variety of 7-substituted benzoxazoles are selectively produced under mild reaction conditions. The mechanism of the reaction is also discussed in this report.


Mechanisms of bradykinin-induced catecholamine release in pithed spontaneously hypertensive rats.
Kinins have the potential to modulate the sympathetic system. However, the kinin receptor subtypes and secondary mediators involved in vivo are not fully characterized. Earlier studies failed to show complete inhibition by B1- or B2-antagonists of bradykinin-induced catecholamine release, and were impeded by direct stimulatory actions of those substances. Such effects may arise from the involvement of histamine, the release of which is known to be stimulated by bradykinin and kinin-receptor antagonists. The present study was designed to evaluate the significance of B2-receptors and histamine in the bradykinin-induced enhancement of plasma catecholamines in pithed spontaneously hypertensive rats. The effects of bradykinin, the B2-receptor antagonist HOE 140, histamine and the H1-receptor antagonist mepyramine were tested. Administration of histamine dose-dependently increased catecholamine release whereby a marked preference for adrenaline over noradrenaline was seen. The H1-receptor antagonist mepyramine (0.3 mg/kg) prevented this effect. Bradykinin (7.2 microg/kg) enhanced plasma adrenaline and noradrenaline. In doses > or = 10 microg/kg, HOE 140 completely suppressed the bradykinin-induced increase in plasma noradrenaline, while a slight stimulation of adrenaline that even persisted after a high dose of HOE 140 (100 microg/kg), was only abolished by additional administration of mepyramine (0.3 mg/kg). The H1-receptor antagonist at this dose did not influence the effectivity of bradykinin. It is concluded that the bradykinin-induced enhancement of catecholamine release during electrical stimulation is completely (noradrenaline) or predominantly (adrenaline) mediated by B2-receptors. A minor stimulating effect of bradykinin on plasma adrenaline is provoked independently of B2-receptors via histamine acting on H1-receptors.


Screening for texturing Leuconostoc and genomics behind polysaccharide production.
Synthesis of polysaccharides by Leuconostoc can result in improved texture of fermented products. A total of 249 Leuconostoc strains were screened for homo-polysaccharide production and for texturing capabilities in milk. A total of six Ln. mesenteroides strains with superior texturing properties had the genetic blueprint for both homo- (HoPS) and hetero-polysaccharide (HePS) synthesis. Only one strain produced texture in milk without added sucrose, suggesting HePS synthesis via the Wzy dependent pathway. In milk acidification experiments with added sucrose, all six strains depleted the sucrose and released fructose. Thus, they can be used for both texture and possibly also for sweetness enhancement.


Transient proteolysis reduction of Nicotiana benthamiana-produced CAP256 broadly neutralizing antibodies using CRISPR/Cas9.
The hypersensitive response is elicited by Agrobacterium infiltration of Nicotiana benthamiana, including the induction and accumulation of pathogenesis-related proteins, such as proteases. This includes the induction of the expression of several cysteine proteases from the C1 (papain-like cysteine protease) and C13 (legumain-like cysteine protease) families. This study demonstrates the role of cysteine proteases: NbVPE-1a, NbVPE-1b, and NbCysP6 in the proteolytic degradation of Nicotiana benthamiana (glycosylation mutant ΔXTFT)-produced anti-human immunodeficiency virus broadly neutralizing antibody, CAP256-VRC26.25. Three putative cysteine protease cleavage sites were identified in the fragment crystallizable region. We further demonstrate the transient coexpression of CAP256-VRC26.25 with CRISPR/Cas9-mediated genome editing vectors targeting the NbVPE-1a, NbVPE-1b, and NbCysP6 genes which resulted in a decrease in CAP256-VRC26.25 degradation. No differences in structural features were observed between the human embryonic kidney 293 (HEK293)-produced and ΔXTFT broadly neutralizing antibodies produced with and without the coexpression of genome-editing vectors. Furthermore, despite the presence of proteolytically degraded fragments of plant-produced CAP256-VRC26.25 without the coexpression of genome editing vectors, no influence on the in vitro functional activity was detected. Collectively, we demonstrate an innovative in planta strategy for improving the quality of the CAP256 antibodies through the transient expression of the CRISPR/Cas9 vectors.


Sexual function in females with severe cervical spinal cord injuries: a controlled study with the Female Sexual Function Index.
The objective of this study was to identify the sexual adjustment of females with severe cervical spinal cord injuries (SCI) using the Female Sexual Function Index (FSFI). The 19-item questionnaire of the FSFI concerns sexual function and satisfaction in sex life. This study, conducted by the Orthopaedic and Psychiatry Departments of Patras University, used a sample of a series of 39 consecutive female patients with severe traumatic SCI. We compared these female patients with an age-economic-educational level- and marital status-matched control group of the general population. Sexual activity was lower among females with SCI, but the desire, the emotional quality of sex life and overall sexual satisfaction did not differ from the controls. These results demonstrate that sexual life in females with SCI remains almost unaffected.


Insulin-like growth factor (IGF) system in the oocyte and somatic cells of bovine preantral follicles.
Many studies have highlighted the role of the insulin-like growth factor (IGF) system in the control of antral follicular growth. However, much less is known about the involvement of the IGF system in the regulation of preantral follicular development. In an attempt to address this lack of knowledge, the present study describes the spatial and temporal patterns of expression of mRNA encoding components of the IGF system in bovine follicles during preantral stages of development. mRNA was detected by in situ hybridization using frozen sections (14 microm) of bovine ovarian tissue. Serial sections were probed with 35S-labelled bovine riboprobes. Type 1 IGF receptor mRNA was detected in granulosa cells and in the oocyte of preantral follicles; however, in this study, as in previous studies, it was not possible to detect mRNA encoding either IGF-I or -II. IGF binding protein (IGFBP)-2 mRNA was present in granulosa cells and oocytes of preantral follicles, and immunoreactive IGFBP-2 was detected around granulosa cells during this early stage of development. Occasionally, preantral follicles were identified in which there was no expression of IGFBP-2 in granulosa cells or the oocyte. IGFBP-3 mRNA was detected in the oocyte of preantral follicles and in the surrounding stromal tissue. mRNAs encoding IGFBP-2 and -3, and type 1 IGF receptor were first detected in type 2 follicles. In conclusion, although the IGF ligands are not expressed in preantral follicles, mRNAs encoding the type 1 IGF receptor, and IGFBP-2 and -3 were present and showed unique spatial patterns of expression within preantral follicles.


Life history and ecology of the elusive European short-snouted seahorse Hippocampus hippocampus.
To improve the understanding of the life history and ecology of one of Europe's most elusive fishes, the short-snouted seahorse Hippocampus hippocampus, data from wild populations in a shallow coastal lagoon in southern Portugal were analysed. The data were collected from 17 tagged seahorses on a focal-study grid as well as from >350 seahorses encountered during underwater visual surveys and a fishery-independent study using beach seines. These populations of settled juveniles and adults had a mean population density of 0·009 m-2 . During the study period (2000-2004), reproduction peaked in July and August. Juveniles recruited to the lagoon at c. 66 mm standard length (LS ) and 0·5 years of age and established small home ranges (0·8 to 18·2 m2 ). First reproduction was estimated at 100 mm and 1 year of age. Based on a fitted von Bertalanffy model, H. hippocampus grew quickly (growth coefficient K = 0·93) to a maximum theoretical size L∞ = 150 mm and have a maximum lifespan of c. 3·2 years. Courtship behaviours were consistent with the maintenance of pair bonds and males brooded multiple batches of young per year. Estimated annual reproductive output averaged 871 young (±632). Together these analyses provide the first life-history parameters for this species and indicate that H. hippocampus bears characteristics of opportunist and intermediate strategists. Such populations are predicted to exhibit large fluctuations in abundance, making them vulnerable to extended periods of poor recruitment.


"Isla Calma", a Novel Virtual Reality Environment for Pain and Anxiety Distraction: Report on Usability, Acceptability, and Subjective Experience.
This report presents a new virtual reality-based tool named "Isla Calma" (IC), which is based on distracting procedures that facilitate competency among different stimuli and loads the individual's limited attention capabilities. An incidental sample composed of 35 users (42.9 percent female) from northern Spain, with a mean age of 28.21 years (SD=5.67), was recruited to test IC. Tests were held in a room with two deck chairs and one complete set of IC equipment for each of them. A questionnaire with issues about usability, acceptability, game immersion, and subjective experience was administered. Participants did not experience any difficulty in "moving" throughout the island. The map was considered useful by most of the users, and so were the narrator's instructions and voice. Previous experience with technology or with the controller did not affect the usability rates. In terms of acceptability, 92.3 percent of the users reported the wish to use IC again if they had the chance, and 73.6 percent would recommend its use in different medical procedures. In terms of immersion, the difference between actual and perceived time using IC was statistically significant (z=-4,141, P<0.001), with the generalized perception of having used less time than what it was actually required. Preliminary results in dental clinical settings are also presented. IC was seen as a highly relaxing and pain distracting tool with potential clinical applications in different settings. It is expected that future research on IC will provide results on its applicability in different clinical settings.


Cushing syndrome in pregnancy.
The occurrence of pregnancy in the face of untreated Cushing syndrome is rare because of the high incidence of ovulatory disturbances experienced by patients with the disorder. A total of 58 patients with 65 pregnancies has been reported in the literature to date. Although pituitary-dependent adrenal hyperplasia is the most common etiology of Cushing syndrome in the general population, adrenal adenoma is more common in the pregnant population. Significant maternal morbidity is attributable to hypertension, congestive heart failure, and poor tissue healing. Prematurity and intrauterine growth retardation account for most of the perinatal morbidity; perinatal mortality is substantial. Treatment directed at relieving hypercortisolism has been instituted during pregnancy: Pituitary or adrenal surgery, chemotherapy, and pituitary irradiation have all been reported, with variable results. Information is lacking on any alteration of maternal morbidity after treatment. The impact of therapy on perinatal outcome appears limited to a reduction in the prematurity rate, but overall numbers are small and such a conclusion should be viewed with caution. No significant maternal or perinatal complications secondary to treatment itself were reported.


[Old and new antibiotics for therapy of multidrug resistant bacteria].
The lack of new antibiotics for multidrug-resistant bacteria is a matter of concern in microorganisms such as Pseudomonas aeruginosa, ESBL- and carbapenemase-producing Enterobacteriaceae, Acinetobacter baumannii, methicillin-resistant Staphylococcous aureus and vancomycin-resistant Enterococcus faecium. This situation has conditioned the reuse of "old" antibiotics (colistin, fosfomycin), the use of more recent antibiotics with new indications or dosage regimens (tigecycline, meropenem) and the introduction of "new" antibiotics (β-lactams, lipoglycopeptides, oxazolidinones) that are the subject of this review.


Efficacy of Bimatoprost Plus Timolol Fixed Combination in Open Angle Glaucoma Patients Previously Treated with Dorzolamide Plus Timolol Fixed Combination.
To evaluate the efficacy and safety of bimatoprost plus timolol fixed combination (BTFC) in patients with primary open angle glaucoma (POAG) previously treated with dorzolamide plus timolol fixed combination (DTFC). Retrospective, medical records review study. Medical records of patients with POAG previously treated with DTFC and then switched to BTFC for poor intraocular pressure (IOP) control or ocular discomfort were included in the analysis. One baseline IOP diurnal curve, and one diurnal curve under each treatment were required to be eligible for this study. The primary outcome was to compare the mean diurnal IOP between DTFC and BTFC. Secondary outcomes were to compare the IOP diurnal fluctuation, and the percentage of patients achieving a target IOP <14, <16, and <18 mmHg between the two treatments. Medical records of 96 patients were analyzed (mean age 65.8 years ± 7.2, range 39-89 years). The mean diurnal IOP was 23.7 ± 3.8 mmHg at baseline, 16.9 ± 3.4 mmHg with DTFC and 15.1 ± 2.9 mmHg after therapy was switched to BTFC (p < 0.0001 each treatment vs baseline; p < 0.0001 DTFC vs BTFC). The proportion of patients achieving a mean diurnal IOP <18, <16, and <14 mmHg was 76%, 35.4%, and 12.5% with DTFC and 81.2%, 68.8%, and 37.5% with BTFC (p = 0.20, p < 0.01, and p < 0.0001 between the two treatments, respectively). IOP fluctuation did not differ significantly between the treatments. BTFC can provide additional lowering in the mean diurnal IOP in patients previously treated with DTFC with no significant differences in the safety and tolerability profile.


Airway management in a Helicopter Emergency Medical Service (HEMS): a retrospective observational study of 365 out-of-hospital intubations.
Airway management is a key skill in any helicopter emergency medical service (HEMS). Intubation is successful less often than in the hospital, and alternative forms of airway management are more often needed. Retrospective observational cohort study in an anaesthesiologist-staffed HEMS in Switzerland. Patient charts were analysed for all calls to the scene (n = 9,035) taking place between June 2016 and May 2017 (12 months). The primary outcome parameter was intubation success rate. Secondary parameters included the number of alternative techniques that eventually secured the airway, and comparison of patients with and without difficulties in airway management. A total of 365 patients receiving invasive ventilatory support were identified. Difficulties in airway management occurred in 26 patients (7.1%). Severe traumatic brain injury was the most common indication for out-of-hospital Intubation (n = 130, 36%). Airway management was performed by 129 different Rega physicians and 47 different Rega paramedics. Paramedics were involved in out-of-hospital airway manoeuvres significantly more often than physicians: median 7 (IQR 4 to 9) versus 2 (IQR 1 to 4), p < 0.001. Despite high overall success rates for endotracheal intubation in the physician-staffed service, individual physicians get only limited real-life experience with advanced airway management in the field. This highlights the importance of solid basic competence in a discipline such as anaesthesiology.


CCR8-targeted specific depletion of clonally expanded Treg cells in tumor tissues evokes potent tumor immunity with long-lasting memory.
Foxp3-expressing CD25+CD4+ regulatory T cells (Tregs) are abundant in tumor tissues. Here, hypothesizing that tumor Tregs would clonally expand after they are activated by tumor-associated antigens to suppress antitumor immune responses, we performed single-cell analysis on tumor Tregs to characterize them by T cell receptor clonotype and gene-expression profiles. We found that multiclonal Tregs present in tumor tissues predominantly expressed the chemokine receptor CCR8. In mice and humans, CCR8+ Tregs constituted 30 to 80% of tumor Tregs in various cancers and less than 10% of Tregs in other tissues, whereas most tumor-infiltrating conventional T cells (Tconvs) were CCR8- CCR8+ tumor Tregs were highly differentiated and functionally stable. Administration of cell-depleting anti-CCR8 monoclonal antibodies (mAbs) indeed selectively eliminated multiclonal tumor Tregs, leading to cure of established tumors in mice. The treatment resulted in the expansion of CD8+ effector Tconvs, including tumor antigen-specific ones, that were more activated and less exhausted than those induced by PD-1 immune checkpoint blockade. Anti-CCR8 mAb treatment also evoked strong secondary immune responses against the same tumor cell line inoculated several months after tumor eradication, indicating that elimination of tumor-reactive multiclonal Tregs was sufficient to induce memory-type tumor-specific effector Tconvs. Despite induction of such potent tumor immunity, anti-CCR8 mAb treatment elicited minimal autoimmunity in mice, contrasting with systemic Treg depletion, which eradicated tumors but induced severe autoimmune disease. Thus, specific removal of clonally expanding Tregs in tumor tissues for a limited period by cell-depleting anti-CCR8 mAb treatment can generate potent tumor immunity with long-lasting memory and without deleterious autoimmunity.


Retrorectal tumors.
Primary neoplasms of the retrorectal (presacral) space are very rare. These lesions may be congenital or acquired, benign or malignant. They often arise with subtle clinical symptoms, or they may be found incidentally during evaluation for other conditions. Preoperative imaging can provide useful information for operative planning; however, it does not eliminate the need for surgery. Approaches for resection include posterior only and combined abdominoperineal, depending on the characteristics of the lesion. Successful treatment of these enigmatic lesions requires extensive knowledge of pelvic anatomy and expertise in pelvic surgery.


Tumorigenicity of MCF-7 human breast cancer cells lacking the p38α mitogen-activated protein kinase.
We have generated cell lines with significantly reduced expression of the p38 mitogen-activated protein kinase (p38 MAPK), Min-p38 MAPK cells, and used these cells to investigate p38 MAPK's role in tumorigenesis of breast cancer cells. MCF-7 cells were stably transfected with a plasmid producing small interfering RNA that inhibited the expression of p38 MAPK. Control cells were stably transfected with the same plasmid producing non-interfering RNA. The reduction in the p38 MAPK activity caused a significant increase in the expressions of estrogen receptor-α (ERα) and the progesterone receptor, but eliminated the expression of ERβ. Min-p38 MAPK cells showed an enhanced overall growth response to 17β-estradiol (E₂), whereas GH plus epidermal growth factor were largely ineffective growth stimulators in these cells compared to controls. Although the long-term net growth rate of the Min-p38 MAPK cells was increased in response to E₂, their proliferation rate was lower compared to controls in short-term cultures. However, the Min-p38 MAPK cells did show a significant decreased rate of apoptosis after E₂ treatment and a reduction in the basal phosphorylation of p53 tumor suppressor protein compared to controls. When the Min-p38 MAPK cells were xenografted into E₂-treated athymic nude mice, their tumorigenicity was enhanced compared to control cells. Increased tumorigenicity of Min-p38 MAPK cells was caused mainly by a decrease in the apoptosis rate indicating that the lack of the p38 MAPK caused an imbalance to increase the ERα:ERβ ratio and a reduction in the activity of the p53 tumor suppressor protein.


Total hip replacement in the middle-aged patient. Contemporary cementing for fixation of the femoral component.
Important advances have been made in the preparation and use of cement and the design of femoral components. Additionally, we have a greater understanding of the biologic basis of osteolysis, previously considered a manifestation of 'cement disease.' The results now emerging as an outcome of modern cementing techniques and component designs represent a major step forward and raise serious doubts about the justification for cementless fixation of the femoral component, given the present state of the art.


Iterative surgical resections in non-small cell lung cancer.
We reviewed our surgical preferences and the prognosis for recurrent and second primary tumors in patients who underwent surgical treatment for non-small cell lung carcinoma (NSCLC). We report our experience with patients undergoing iterative pulmonary resection for lung cancer. Among patients who underwent anatomical resection for primary NSCLC, those who underwent a second surgical resection between 2010 and 2020 due to recurrent or second primary tumor were included in the study. Operative mortality, survival, and prognostic factors were investigated. In total, 77 cases were included: 31 (40.3%) underwent the second resection for the recurrent disease and 46 (59.7%) underwent the second resection for the second primary tumor. Postoperative mortality occurred in 8 (10.4%) patients. All patients with postoperative mortality were in the group that underwent thoracotomy in both surgical procedures. The 5-year survival rate was 46.5%. The 5-year survival of those operated on for recurrent or second primary tumor was 32.8% and 51.1%, respectively (p = 0.81). The 5-year survival rate was 68.8% in patients under the age of 60 years, while it was 27.5% in patients aged 60 years and above (p = 0.004). The 5-year survival was 21.8% in patients with an interval of 36 months or less between two operations and 72.2% in those with a longer interval (p = 0.028). Our study shows that survival results similar to or better than primary NSCLC surgery can be obtained with lower mortality if more limited resections are performed via video-assisted thoracic surgery, especially in young patients. In addition, the prognosis is better in patients with an interval of more than 36 months between two operations.


Stress and activity of molybdenum-containing complex (molybdenum cofactor) in winter wheat seeds.
Molybdenum, applied in vivo, restored the damage from low temperature with winter wheat (Triticum aestivum, var "Sadovo 1") grown on acid soil and, in addition, sharply increased productivity (G Salcheva, D Georgieva, 1982; G Salcheva et al., 1977, 1979). Two fractions with molybdenum-cofactor activity in seeds were detected. One of them has a molecular weight of about 230 kilodaltons corresponding to xanthine oxidase activity and leaf nitrate reductase activity. The other has a molecular weight of about 60 kilodaltons. The ratio between the molybdenum-cofactor activity of these fractions was different in ;mother' seeds used in the experiment, in seeds obtained from the damaged plants, and in seeds obtained from the damaged plants restored by in vivo molybdenum addition. Every one of these fractions consisted of several components in which molybdenum-cofactor activity and stability in vitro was different. We suggest that plants store molybdenum as molybdenum carriers in these low molecular weight fractions.


Comparison of multiplanar reformatted CT lung tumor measurements to axial tumor measurement alone: impact on maximal tumor dimension and T stage.
The purpose of this study was to compare measurements of lung tumor size between axial and multiplanar reformatted CT images, as well as to establish whether the difference between these measurements leads to a change in T stage. Patients with lung tumors who underwent chest CT up to 31 days before lung resection between December 2010 and March 2012 were included. Axial, sagittal, and coronal CT images were evaluated by two independent readers (1 and 2) who were blinded to clinical data. In 89 patients, lung tumors categorized as T1a (54%), T1b (19%), T2a (24%), or T2b (3%) were analyzed. The longest tumor diameter using multiplanar reformatted CT was compared and correlated with axial CT alone and pathologic T stage. Statistical analysis included a Wilcoxon rank sum test to evaluate differences between measurements, intraclass correlation coefficient (ICC), and kappa statistic to assess agreement. Prediction of T stage using axial CT alone compared with multiplanar reformatted CT agreed in 82% of patients for reader 1 (κ = 0.660 [95% CI, 0.531-0.789]) and 80% of patients for reader 2 (κ = 0.695 [95% CI, 0.572-0.818]). Prediction of T stage using multiplanar reformatted CT resulted in upstaging in 18% and 20% of patients (for readers 1 and 2, respectively). Interobserver agreement (ICC [95% CI]) was 0.900 (0.803-0.954) for axial, 0.874 (0.772-0.946) for sagittal, and 0.754 (0.556-0.921) for coronal planes. Radiologic measurement of lung tumor T stage was higher using multiplanar reformatted CT as compared with axial CT alone. When available, multiplanar reformatted CT should be used to measure tumor dimension and thus assign an accurate lung cancer T stage.


Synergistic pathogenicity in sequential coinfection with fowl adenovirus type 4 and avian orthoreovirus.
Hydropericardium hepatitis syndrome (HHS) is a fatal disease caused by fowl adenovirus serotype 4 (FAdV-4). Avian viral arthritis is an infectious disease characterized by movement disorders caused by avian orthoreovirus (ARV). In the early 2019, our epidemiologic survey on poultry diseases in eight commercial broiler farms in China showed that FAdV-4 and ARV have a high coinfection rate, accounting for 63 % of all ARV-positive samples. We designed chicken embryo and animal models to investigate the synergistic pathogenicity of FAdV-4 and ARV. Weakness and inappetence were observed in all specific-pathogen-free (SPF) chickens of the experimental group. FAdV-4 and ARV coinfection caused severe embryonic body and hepatic hemorrhage in SPF chicken embryos. Compared with the singular ARV-infected group, joint swelling was more severe in all coinfected groups. Compared with single virus infection, the coinfection of the two viruses increased the mortality of SPF chicken embryos and chickens. FAdV-4 and ARV coinfection resulted in significantly severe macroscopic and microscopic lesions of the liver, spleen, and kidney of SPF chickens. The detection results of viral load in allantoic fluid, liver, and cloacal swabs indicated that ARV enhanced FAdV-4 replication in SPF chicken embryos and chickens. Cytokine detection showed a significant change in interleukin-1 (IL-1), IL-6, and interferon-α (IFN-α) levels in coinfected groups compared with those in the single-infected groups. Additionally, FAdV-4 and ARV coinfection caused severe damage to the SPF chicken's immune system. In summary, these findings provide insights into the pathology, prevention, and treatment of FAdV-4 and ARV coinfection.


LABORATORY ANIMALS: Congress OKs Plan for Retired Chimps.
On 6 December, the Senate put the final stamp of approval on the Chimpanzee Health Improvement, Maintenance, and Protection Act. It authorizes the Department of Health and Human Services to spend $30 million to set up and administer a system of retirement sanctuaries for chimpanzees no longer needed for research. But the National Institutes of Health's opposition to such a network casts doubt on where the money will come from.


[Organ-salvaging surgeries for highly differentiated thyroid cancer in children].
Retrospective analysis of results of organpreserving operations for the thyroid gland cancer (TGC) in 55 children and juveniles for 1981-1997 yrs period was done. The informativity of preoperative cytological (96.4%) and intraoperative express--histological (95.6%) investigations was determined. In cases of the cytological and express--histological diagnosis complexities the possibility of organpreserving intervention of hemithyroidectomy with the isthmus extirpation was noted. Primary thyroidectomy is operation of choice in the established diagnosis of TGC.


Peer-Generated Health Information: The Role of Online Communities in Patient and Caregiver Health Decisions.
Individuals increasingly access peer-generated health information (PGHI) through social media, especially online health communities (OHCs). Previous research has documented PGHI topics, credibility assessment strategies, and PGHI's connection with well-being. However, there is limited evidence on where, when, and why individuals seek PGHI and how they use PGHI in health decisions. We conducted in-person and online focus groups with verified OHC members (N = 89)-representing 50 different medical conditions and 77 OHCs-to explore these topics. Two researchers independently coded transcripts with NVivo 9.2 and thematically analyzed responses. Most individuals accidentally discovered PGHI during Web searches rather than intentionally seeking it. Individuals valued PGHI primarily as an alternative information source about treatment options, self-care activities, and health care provider questions rather than a source of emotional support, and they acknowledged PGHI's limitation as anecdotal evidence. Individuals used PGHI as a springboard for additional research and patient-provider discussions, ultimately making treatment decisions alongside providers. These findings suggest that individuals use PGHI in much the same way they use traditional online health information and that PGHI facilitates, rather than obstructs, shared decision making with health care providers.


Atypically localized glomus tumor causing anterior interosseous nerve syndrome: A case report.
This article presents a 48-year-old male patient who presented with pain in the left forearm and weakness and clumsiness in the left hand of 6 months' duration. Flexor motor strength loss of the thumb and the index finger was present and neurophysiologic tests showed findings compatible with axonal injury in the anterior interosseous nerve (AIN) innervated muscles. Magnetic resonance imaging revealed a space-occupying lesion in the proximal forearm resembling a glomus tumor. Excision of the mass and release of the AIN were performed. Histopathology confirmed a glomus tumor, and the patient remains asymptomatic at 1 year postoperatively. We stress the importance of imaging studies in patients when a suspected secondary nature of nerve entrapment is present.


Pay-for-performance remuneration for pharmacist prescribers' management of hypertension: A substudy of the RxACTION trial.
To be sustainable, pharmacists providing direct patient care must receive appropriate payment for these services. This prespecified substudy of the RxACTION trial (a randomized trial of pharmacist prescribing vs usual care in patients with above-target blood pressure [BP]) aimed to determine if BP reduction achieved differed between patients whose pharmacist was paid by pay-for-performance (P4P) vs fee-for-service (FFS). Within RxACTION, patients with elevated BP assigned to the pharmacist prescribing group were further randomized to P4P or FFS payment for the pharmacist. In FFS, pharmacists received $150 for the initial visit and $75 for follow-up visits. P4P included FFS payments plus incentives of $125 and $250 for each patient who reached 50% and 100% of the BP target, respectively. The primary outcome was difference in change in systolic BP between P4P and FFS groups. A total of 89 patients were randomized to P4P and 92 to the FFS group. Patients' average (SD) age was 63.0 (13.2) years, 49% were male and 76% were on antihypertensive drug therapy at baseline, taking a median of 2 (interquartile range = 1) medications. Mean systolic BP reductions in the P4P and FFS groups were 19.7 (SD = 18.4) vs 17.0 (SD = 16.4) mmHg, respectively (p = 0.47 for the comparison of deltas and p = 0.29 after multivariate adjustment). This trial of pharmacist prescribing found substantial reductions in systolic BP among poorly controlled hypertensive individuals but with no appreciable difference when pharmacists were paid by P4P vs FFS.


Analysis and Refinement of Host-Guest Interactions in Metal-Organic Frameworks.
ConspectusMetal-organic frameworks (MOFs) are a class of hybrid porous materials characterized by their periodic assembly using metal ions and organic ligands through coordination bonds. Their high crystallinity, extensive surface area, and adjustable pore sizes make them promising candidates for a wide array of applications. These include gas adsorption and separation, substrate binding, and catalysis, of relevance to tackling pressing global issues such as climate change, energy challenges, and pollution. In comparison to traditional porous materials such as zeolites and activated carbons, the design flexibility of organic ligands in MOFs, coupled with their orderly arrangement with associated metal centers, allows for the precise engineering of uniform pore environments. This unique feature enables a rich variety of interactions between the MOF host and adsorbed gas molecules, which are fundamental to understanding the observed uptake capacity and selectivity for target gas molecules and thus the overall performance of the material.In this Account, a data set for three-dimensional MOFs has been constructed based upon the structural analysis of host-guest interactions using the largest experimental database, the Cambridge Structural Database (CSD). A full screening was performed on structures with guest molecules of H2, C2H2, CO2, and SO2, and the relationship between the primary binding site, the isosteric heats of adsorption (Qst), and the adsorption uptake was extracted and established. We review the methodologies to refine host-guest interactions based primarily on our studies on the host-guest chemistry of MOFs. The methods include ligand functionalization, variation of metal centers, formation of defects, addition of single atom sites, and control of pore size and structure. In situ structural and dynamic investigations using diffraction and spectroscopic techniques are powerful tools to visualize the details of host-guest interactions upon the above modifications, affording key insights into functional performance at a molecular level. Finally, we give an outlook of future research priorities in the study of host-guest chemistry in MOF materials. We hope this Account will encourage the rational development and improvement of future MOF-based sorbents for applications in challenging gas adsorption, separations, and catalysis.


Ethylene, a regulator of young fruit abscission.
In an earlier study we reported that detached cotton flowers produced sufficient ethylene before the period of natural abscission to suggest that ethylene might be a natural regulator of young fruit abscission. The present report explores this probability further. Intact cotton (Gossypium hirsutum L.) fruits produced ethylene at rates as high as 36 mul ethylene/kg fresh wt.hr during the 2 days before they abscised. Direct measurements of ethylene in gas samples withdrawn from fruits indicated that production of 1 mul ethylene/kg fresh wt.hr is equivalent to an internal concentration of approximately 0.1 mul/l. Fumigation of fruiting cotton plants with only 0.5 mul/l caused 100% abscission of young fruits and floral buds within 2 days. This correlated with the estimated endogenous levels of ethylene. Reduced pressure, which reduced the internal levels of ethylene, delayed abscission of young fruits and leaves, a result which supports our conclusion from this study- that ethylene is one of the regulators of young fruit abscission in cotton.


Safety and efficacy of jaktinib in the treatment of Janus kinase inhibitor-naïve patients with myelofibrosis: Results of a phase II trial.
Myelofibrosis (MF) is associated with several constitutional symptoms. Currently, there are few therapeutic options for MF. Jaktinib, a novel, small-molecule inhibitor of JAK, is currently being studied for its potential to treat MF. This phase 2 trial investigated efficacy and safety of jaktinib in the treatment of MF patients. The primary end point was the proportion of patients with ≥35% reduction in spleen volume (SVR35, proportion of patients with ≥35% reduction in spleen volume) at week 24. The secondary end points included improvement of anemia, rates of symptom response, and safety profile. Between January 8, 2019 and August 29, 2020, 118 patients were recruited and treated with either jaktinib 100 mg BID or 200 mg QD. At week 24, 54.8% (34/62) of patients in the 100 mg BID group and 31.3% (15/48) in the 200 mg QD group achieved SVR35 (p = .0199). Jaktinib treatment increased hemoglobin level to ≥20 g/L in 35.6% (21/59) of patients with hemoglobin ≤100 g/L at baseline. The proportion of patients who achieved a ≥50% improvement in total symptom score at week 24 was 69.6% (39/56) in the BID group and 57.5% (23/40) in the QD group. The most common ≥ grade 3 hematological treatment-emergent adverse events (TEAEs; ≥ 10%) were anemia (100 mg BID: 24.2%, 200 mg QD: 28.8%), thrombocytopenia (16.7%, 11.5%), and neutropenia (3.0%, 11.5%). All non-hematological TEAEs were mild. These results indicate that jaktinib can shrink the spleen, improve anemia, and other clinical symptoms with good tolerability.


Bedaquiline Targets the ε Subunit of Mycobacterial F-ATP Synthase.
The tuberculosis drug bedaquiline inhibits mycobacterial F-ATP synthase by binding to its c subunit. Using the purified ε subunit of the synthase and spectroscopy, we previously demonstrated that the drug interacts with this protein near its unique tryptophan residue. Here, we show that replacement of ε's tryptophan with alanine resulted in bedaquiline hypersusceptibility of the bacteria. Overexpression of the wild-type ε subunit caused resistance. These results suggest that the drug also targets the ε subunit.


beta2-Adrenergic receptor downregulation and performance decrements during high-intensity resistance exercise overtraining.
Previous research on overtraining due to excessive use of maximal resistance exercise loads [100% 1 repetition maximum (1 RM)] indicates that peripheral muscle maladaptation contributes to overtraining-induced performance decrements. This study examined the cellular and molecular responses of skeletal muscle to performance decrements due to high-relative-intensity (%1 RM) resistance exercise overtraining. Weight-trained men were divided into overtrained (OT, n = 8) and control (Con, n = 8) groups. The OT group performed 10 x 1 at 100% 1 RM daily for 2 wk, whereas the Con group performed normal training 2 days/wk. Muscle biopsies from the vastus lateralis muscle, voluntary static and dynamic muscle performances, and nocturnal urinary epinephrine were assessed before (pre) and after (post) overtraining. Overtraining occurred as indicated by a decrease in 1-RM strength for the OT group (mean +/- SE; OT pre = 159.3 +/- 10.1 kg, OT post = 151.4 +/- 9.9 kg, Con pre = 146.0 +/- 12.9 kg, Con post = 144.9 +/- 13.3 kg), as well as a 36.3% decrease in mean power at 100% 1-RM loads. Normal training could be resumed only after 2-8 wk of training cessation. Muscle beta(2)-adrenergic receptor (beta(2)-AR; fmol/mg protein) density significantly decreased by 37.0% for the OT group and was unchanged for the Con group (-1.8%). Nocturnal urinary epinephrine for the OT group increased by 49%, although this was not significant (effect size = 0.42). The ratio of nocturnal urinary epinephrine to beta(2)-AR density suggested a decreased beta(2)-AR sensitivity for the OT group (2.4-fold increase). Overtraining occurred based on decreased muscular force and power. Desensitization of the beta(2)-AR system suggests that this may be an important contributor to performance decrements due to excessive use of maximal resistance exercise loads.


A Look Into the Power of fNIRS Signals by Using the Welch Power Spectral Estimate for Deception Detection.
Neuroimaging technologies have improved our understanding of deception and also exhibit their potential in revealing the origins of its neural mechanism. In this study, a quantitative power analysis method that uses the Welch power spectrum estimation of functional near-infrared spectroscopy (fNIRS) signals was proposed to examine the brain activation difference between the spontaneous deceptive behavior and controlled behavior. The power value produced by the model was applied to quantify the activity energy of brain regions, which can serve as a neuromarker for deception detection. Interestingly, the power analysis results generated from the Welch spectrum estimation method demonstrated that the spontaneous deceptive behavior elicited significantly higher power than that from the controlled behavior in the prefrontal cortex. Meanwhile, the power findings also showed significant difference between the spontaneous deceptive behavior and controlled behavior, indicating that the reward system was only involved in the deception. The proposed power analysis method for processing fNIRS data provides us an additional insight to understand the cognitive mechanism of deception.


Surfactant convertase action is not essential for surfactant film formation.
A serine-active enzyme, "surfactant convertase", is required for the conversion of surfactant from the tubular myelin (TM) form to the small vesicular (SV) form. This transformation involves at least two steps, the conversion of TM to a surface-active film at the air-fluid interface and the reorientation of the film into the surface-inactive SV form; we asked if convertase was required for the first of these steps. Rat and mouse TMs were pretreated with diisopropyl fluorophosphate (DFP) to inactivate endogenous convertase activity or with vehicle and then were analyzed for their ability to lower surface tension in vitro as an index of the conversion of TM to a surface film. DFP pretreatment did not alter the ability of TM preparations to lower surface tension, as assessed by pulsating bubble, and it did not affect the behavior of TM in a surface balance. In an experiment designed to test the ability of TM to feed a surface film to exhaustion, TMs that had been pretreated with DFP or vehicle performed similarly. These experiments show that convertase activity is not required for the conversion of TM to a monolayer and suggest, instead, that convertase acts at a post surface film stage.


Treatment response to bortezomib in multiple myeloma correlates with plasma hepatocyte growth factor concentration and bone marrow thrombospondin concentration.
Multiple myeloma (MM) is associated with increased rate of bone marrow angiogenesis. Increased concentration of hepatocyte growth factor (HGF) is associated with poor prognosis in patients treated with conventional chemotherapy or thalidomide. We have shown previously that decreased level of thrombospondin, an angiogenesis inhibitor, correlates with poor response to high-dose chemotherapy. The aim of our current study was to evaluate association between therapeutic response to bortezomib and thrombospondin and HGF levels. Peripheral blood plasma concentration of HGF and bone marrow plasma concentration of thrombospondin were measured in patients with MM prior to the initiation of bortezomib therapy. Overall, 58 patients were enrolled, 44/58 (76%) of them with relapsed disease. Treatment outcomes were analyzed for possible associations with pretreatment HGF and thrombospondin levels. Patients who achieved complete response had significantly higher pretreatment HGF levels and lower pretreatment thrombospondin levels than others. More than 70% of patients with low pretreatment HGF and high pretreatment thrombospondin concentrations achieved very good partial response or complete response, in contrast to only 20% of patients with high HGF and low thrombospondin levels. High pretreatment thrombospondin and low pretreatment HGF concentrations are associated with therapeutic response to bortezomib in patients with MM.


Base excess and lactate as prognostic indicators for patients admitted to intensive care.
To examine whether values of arterial base excess or lactate taken on admission to a general intensive care unit indicate prognosis, and whether this can be used as a screening tool for future intensive care admissions. Observational study. University teaching hospital general adult intensive care unit. 148 consecutive patients admitted to the intensive care unit. Arterial blood samples were obtained on admission to the intensive care unit and 24 h following admission. Arterial base excess and lactate concentrations were measured from the blood samples. Both base excess and arterial lactate samples on admission have good prognostic abilities (area under the curve on receiver operator characteristic analysis of 0.73, 0.78, respectively). The value of base excess on admission with the best predictive ability was a base excess more negative than -4 mmol/l, and the corresponding value for lactate was greater than 1.5 mmol/l. The combination of these two markers on admission to the intensive care unit led to a sensitivity of 80.3 % and a specificity of 58.7 % for mortality. The achievement of this combination was associated with an increased mortality (50.6 % vs. 15 %, p < 0.0001), older age (70 vs. 61.5 years, p < 0.05), a greater requirement for inotropic support (30.9 % vs. 4.5%, p < 0.0001) and higher organ failure scores both on admission and for the subsequent 24 h. Both base excess and lactate, or the combination of the two, can be used to predict outcome in patients admitted to the intensive care unit. These variables could be utilized to identify patients who have a high risk for mortality and thus who should be admitted to the intensive care unit.


A review of Khoi-San and Cape Dutch medical ethnobotany.
ETHNOPHARMACOLOGICAL CONTEXT: Cape herbal medicine as a distinct and unique healing system is conceptualized for the first time, together with a first compilation of the authentic materia medica of the system. The early literature on Khoikhoi (Hottentot), San (Bushman) and Cape Dutch medicinal plants and medical practices is reviewed, with a focus on the Cape Floristic Region (from Namaqualand to the Eastern Cape). To avoid recent additions and modern cultural influences in the results, the date of publication of the last volume of Marloth's Flora of South Africa (1932) was chosen as a cut-off date. The recorded Cape materia medica (up to 1932) is briefly summarized, giving the scientific names, vernacular names (in Afrikaans or Khoi-San/Nama) and main uses. It comprises about 170 items and includes mainly indigenous and endemic plant species, some exotic (garden) plants, and a few other items (fungi, seaweeds, lichens, hyraceum and natural potassium nitrate). Most of the plants (and hyraceum) are still widely used today, especially in rural areas. The combination of unique cultural practices and a diverse, highly endemic flora has led to the development of a distinct herbal healing system, here called Cape herbal medicine, but hitherto rather vaguely and inaccurately referred to as Khoi-San medicine, Cape Dutch medicine or boererate (farm remedies). The data allows for a more informed consideration of indigenous knowledge and intellectual property rights associated with particular plants (e.g. Hoodia and Pelargonium). It also offers opportunities for linking modern ethnobotanical field studies with historical data.