Improved diagnosis of central venous catheter-related bloodstream infections using the HB&L UROQUATTRO™ system.
The diagnosis of catheter-related bloodstream infections (CRBSIs) in febrile patients with indwelling central venous catheters (CVCs) needs improvement. To diagnose CRBSIs more efficiently, we have developed a novel culture approach using the catheter tips removed from febrile patients. CVCs and blood cultures from 1,070 patients with only CVC-related infections were obtained over a period of 3 years (January 2009 to December 2011). The CVCs were evaluated by a semi-quantitative catheter culture method according to Maki's method and by our novel method, which is based on the use of the HB&L UROQUATTRO™ system (Alifax, Padova, Italy). Using our new method, 571 (571/1,070) of the infections were confirmed as CRBSIs. The remaining 487 patients had infections that were associated with hematologic malignancies, neutropenia, prior exposure to antibiotics, and a decreased CVC removal rate. Twelve samples were identified as false-positives. The percentage of patients with CRBSIs confirmed using the HB&L UROQUATTRO™ system was 53.36 % versus 34.95 % (p-value 0.004) using Maki's method (374/1,070 CVC Maki-positive samples). Our results indicate that our new culture method allows for an improved CRBSI diagnosis rate. A significant number of tip cultures (18.41 %) tested positive for CRBSIs using our system but were negative when tested using Maki's method. Moreover, the use of the HB&L UROQUATTRO™ system allowed us to significantly reduce diagnosis time; a negative CRBSI diagnosis could be made within 6 h and a positive diagnosis could be made within 22-28 h.


Proton Beam Therapy for Thymic Carcinoma with Pericardial Involvement.
Thymic malignancies are the most common anterior mediastinal tumors. Advanced thymic carcinoma treatment relies on chemotherapy and definitive radiation therapy when possible. However, pericardial involvement is problematic for radiation therapy treatment planning owing to significant cardiac radiation exposure. We report the first case of definitive proton beam therapy (PBT) for an advanced thymic carcinoma with pericardial invasion. We report the case of a 69-year-old patient treated with definitive radiation therapy for a stage IVB thymic carcinoma with pericardial invasion. Mean doses delivered to critical organs at risk were compared between deep inspiration breath-hold (DIBH) volumetric modulated arc therapy (VMAT) and DIBH-PBT. When compared to DIBH-VMAT, DIBH-PBT reduced the mean doses delivered to the heart by 3.72 Gy (19.0% dose reduction), to the right lung by 5.9 Gy (41.7% dose reduction), to the left lung by 3.63 Gy (19.0% dose reduction), and to the esophagus by 3.57 Gy (21.3% dose reduction). Despite an early mediastinal relapse after 3.0 months, our patient is still alive after a 14-month follow-up, without any radiation-induced cardiac adverse events and is undergoing pembrolizumab-based immunotherapy. Proton beam therapy is an option for definitive irradiation of thymic malignancies invading the pericardium; in this situation, PBT reduces doses to the heart and may help to reduce cardiotoxicity when compared with photon techniques.


Enhanced Supercontinuum Generation through Dispersion-Management.
We show in theory and simulation that the supercontinuum generation from an initial continuous wave field in a highly nonlinear fiber operating near the zero-dispersion point can be significantly enhanced with the aid of dispersion management. We characterize the spectral broaden-ing as a process initiated by modulational instability, but driven by the zero-dispersion dynamics of an N-soliton interacting with the asymmetric phase profile generated by the Raman effect, self-steepening effect, and/or higher-order dispersion. Higher N-soliton values lead to shorter pulses and a broader spectrum. This insight allows us to use dispersion management in conjunction with modulational instability to effectively increase the N value and greatly enhance the supercontiuum generation process.


[Effectiveness of revaccinating hamadryas baboons with NISS live dried plague vaccine and fraction I of the plague microbe].
The effectiveness of some vaccine preparations for the revaccination of hamadryas baboons after their primary immunization with live plague vaccine " NIIS " administered in the form of aerosol was studied. The study was carried out under the conditions of the aerosol challenge of the animals with Y. pestis. The subcutaneous injection of plague vaccine " NIIS " was found to have advantages over its aerosol administration. Revaccination with Y. pestis fraction I, absorbed, was found to be 8 times more effective than the administration of plague vaccine " NIIS " by inhalation and not inferior to the subcutaneous injection of this vaccine. Y. pestis lipopolysaccharide, when injected simultaneously with fraction I, produced an immunosuppressive effect. The development of chemical plague vaccine on the basis of fraction I, intended for revaccination, was shown to have good prospects.


Low empathy-like behaviour in male mice associates with impaired sociability, emotional memory, physiological stress reactivity and variations in neurobiological regulations.
Deficits in empathy have been proposed to constitute a hallmark of several psychiatric disturbances like conduct disorder, antisocial and narcissistic personality disorders. Limited sensitivity to punishment, shallow or deficient affect and reduced physiological reactivity to environmental stressors have been often reported to co-occur with limited empathy and contribute to the onset of antisocial phenotypes. Empathy in its simplest form (i.e. emotional contagion) is addressed in preclinical models through the evaluation of the social transmission of emotional states: mice exposed to a painful stimulus display a higher response if in the presence of a familiar individual experiencing a higher degree of discomfort, than in isolation. In the present study, we investigated whether a reduction of emotional contagion can be considered a predictor of reduced sociality, sensitivity to punishment and physiological stress reactivity. To this aim, we first evaluated emotional contagion in a group of Balb/cJ mice and then discretised their values in four quartiles. The upper (i.e. Emotional Contagion Prone, ECP) and the lower (i.e. Emotional Contagion Resistant, ECR) quartiles constituted the experimental groups. Our results indicate that mice in the lower quartile are characterized by reduced sociability, impaired memory of negative events and dampened hypothalamic-pituitary-adrenocortical reactivity to external stressors. Furthermore, in the absence of changes in oxytocin receptor density, we show that these mice exhibit elevated concentrations of oxytocin and vasopressin and reduced density of BDNF receptors in behaviourally-relevant brain areas. Thus, not only do present results translate to the preclinical investigation of psychiatric disturbances, but also they can contribute to the study of emotional contagion in terms of its adaptive significance.


Meiotic maturation of mouse oocytes in vitro: protein synthesis in nucleate and anucleate oocyte fragments.
Nucleate and anucleate fragments of mouse oocytes have been isolated following treatment of fully grown oocytes with cytochalasin B. The nucleate oocyte fragments resume meiosis in vitro, progressing from dictyate of the first meiotic prophase to metaphase II ('meiotic maturation'), and exhibit all of the changes in protein synthesis normally associated with meiotic maturation of mouse oocytes. The anucleate oocyte fragments also undergo certain of the changes in protein synthesis associated with meiotic maturation, despite the absence of nuclear progression. These results suggest that the acquisition of meiotic competence (i.e. the ability to undergo meiotic maturation) during growth of the mammalian oocyte is due to changes in the quality, rather than the quantity, of cytoplasm and that the reprogramming of protein synthesis during meiotic maturation is directed by RNA templates already present in the cytoplasm. The behaviour of anucleate oocyte fragments is discussed in terms of the proposed role for nucleoplasm in the initiation of changes in protein synthesis during meiotic maturation of mouse oocytes.


Cross-diffusion-induced convective patterns in microemulsion systems.
Cross-diffusion phenomena are experimentally shown to be able to induce convective fingering around an initially stable stratification of two microemulsions with different compositions. Upon diffusion of a salt that entrains water and AOT micelles by cross-diffusion, the miscible interface deforms into fingers following the build-up of a non-monotonic density profile in the gravitational field. A diffusion model incorporating cross-diffusion effects provides an explanation for the mechanism of the buoyancy-driven hydrodynamic instability and for the properties of the convective fingers.


A Descriptive Account of the Nature and Extent of Transgender Homicide in America, 2010 to 2021.
There is a growing acknowledgment of transgender homicide as a serious social and public health issue; indeed, the American Medical Association has even referred to violence against transgender people as an "epidemic." Addressing this issue, however, requires understanding the patterns associated with this violence. Yet, reliable data for doing so does not currently exist, especially in recent years. As such, the prevalence of these incidents and their key features are not easily understood. The current study addresses this issue using a comprehensive nationwide database on 305 instances of homicide directed against transgender people between 2010 and 2021, collected through extensive open-source data collection methods. The descriptive analyses of these incidents demonstrate pronounced increases in homicide victimization over time, and clear geographic clustering by state, such that roughly one in four incidents occurred in just three states: Texas, Florida, and California. After accounting for the estimated size of the transgender population, Louisiana, Mississippi, and Missouri emerge as the most dangerous states with the highest risk of homicide victimization. The results also clearly demonstrate the intersectional nature of transgender homicide, in finding that most homicide victims are young Black or Hispanic transgender women. We conclude by emphasizing the need for multipronged policy responses to this issue that recognize the uniquely dangerous intersection of social problems that contribute to the vulnerable social position of many transgender people, including their vulnerability to homicide victimization.


First Report of Colletotrichum fioriniae Causing Postharvest Decay on 'Nittany' Apple Fruit in the United States.
Bitter rot of apple is caused by Colletotrichum acutatum and C. gleosporioides and is an economically important disease in the mid-Atlantic and southern regions of the United States (1). However, other Colletotrichum spp. have been found to infect apple and pear fruit in Croatia that include C. fioriniae and C. clavatum (3). The disease is favorable under wet, humid conditions and can occur in the field or during storage causing postharvest decay (2). In February 2013, 'Nittany' apples with round, brown, dry, firm lesions having acervuli in concentric rings were observed at a commercial cold storage facility in Pennsylvania. Samples were placed on a paper tray in an 80-count apple box and immediately transported to the lab. Fruit were rinsed with sterile water, and lesions were sprayed with 70% ethanol until runoff. The skin was aseptically removed with a scalpel, and tissue under the lesion was placed onto potato dextrose agar (PDA) petri dishes. Dishes were incubated at 25°C with constant light, and a single-spore isolate was propagated on PDA. Permanent cultures were maintained as PDA slants stored at 4°C in darkness. The isolate was identified as a Colletotrichum sp. based on culture morphology, having light gray mycelium with a pinkish reverse and abundant pin-shaped melanized acervuli oozing pink conidia on PDA. Conidia were fusiform, pointed at one or both ends, one-celled, thin-walled, aseptate, hyaline, and averaged 10.5 μm (7.5 to 20 μm) long and 5.1 μm (5 to 10 μm) wide (n = 50). Genomic DNA was extracted from mycelia and amplified using conventional PCR and gene specific primers for 313 bp of the Histone 3 gene and with ITS4/5 primers for the internal transcribed spacer (ITS) rDNA region. MegaBLAST analysis of both gene sequences showed that our isolate was identical to other Colletotrichum fioriniae sequences in GenBank and was 100% identical to culture-collection C. fioriniae isolate CBS:128517, thus confirming the morphological identification. To prove pathogenicity, Koch's postulates were conducted using organic 'Gala' apple fruit that were washed with soap and water, sprayed with 70% ethanol, and wiped dry. The fruit were wounded with a sterile nail to a 3-mm depth, inoculated with 50 μl of a conidial suspension (1 × 104 conidia/ml), and stored at 25°C in 80-count boxes on paper trays for 14 days. Lesion diameter was measured from 10 replicate fruit with a digital micrometer and averaged 31.2 mm (±2.5 mm) over two experiments (n = 20). Water-only controls were symptomless. Artificially inoculated 'Gala' apples had identical external and internal symptoms (v-shaped decay pattern when the fruit were cut in half) to those observed on 'Nittany' apples that were originally obtained from cold storage. Bitter rot caused by C. fioriniae may become an emerging problem for the pome fruit growing industry in the near future, and may require investigation of new disease management practices to control this fungus. This is the first report of postharvest decay caused by C. fioriniae on apple fruit from cold storage in the United States. References: (1) H. W. Anderson. Diseases of Fruit Crops. McGraw-Hill, New York, 1956. (2) A. R. Biggs et al. Plant Dis. 85:657, 2001. (3) D. Ivic et al. J. Phytopathol. 161:284, 2013.


Cannabidiol as Self-Assembly Inducer for Anticancer Drug-Based Nanoparticles.
Cannabidiol (CBD) is a biologically active compound present in the plants of the Cannabis family, used as anticonvulsant, anti-inflammatory, anti-anxiety, and more recently, anticancer drug. In this work, its use as a new self-assembly inducer in the formation of nanoparticles is validated. The target conjugates are characterized by the presence of different anticancer drugs (namely N-desacetyl thiocolchicine, podophyllotoxin, and paclitaxel) connected to CBD through a linker able to improve drug release. These nanoparticles are formed via solvent displacement method, resulting in monodisperse and stable structures having hydrodynamic diameters ranging from 160 to 400 nm. Their biological activity is evaluated on three human tumor cell lines (MSTO-211H, HT-29, and HepG2), obtaining GI50 values in the low micromolar range. Further biological assays were carried out on MSTO-211H cells for the most effective NP 8B, confirming the involvement of paclitaxel in cytotoxicity and cell death mechanism.


Comparison of valproate concentrations in human plasma, CSF and brain tissue after administration of different formulations of valproate or valpromide.
The concentration of valproate was measured in plasma, CSF and brain tissue of patients who underwent resective surgical treatment because of severe temporal lobe epilepsy after pretreatment with either a sustained release formulation of valproate (Depakine Chrono; 5 patients), the conventional formulation of valproate (Depakine; 6 patients) or valpromide (Depamide; 2 patients). With a mean serum value for all 13 patients of 32.3 micrograms/g valproate, the mean brain/serum ratio was 15.1% (SD 6.1%). The valproate concentration of the hippocampus was significantly higher than that of the amygdala and patients who had the sustained release formulation had significantly higher valproate concentration in the CSF and in the hippocampal formation than those patients who had the conventional valproate. Since a few patients had tumors, whereas others had varying degrees of gliosis, it cannot be ruled out that these differences are the result of different histopathological conditions with related differences in blood-brain barrier functions.


Prolonged weight-shift and altered spinal coordination during sit-to-stand in practitioners of the Alexander Technique.
The Alexander Technique (AT) is used to improve postural and movement coordination and has been reported to be clinically beneficial, however its effect on movement coordination is not well-characterized. In this study we examined the sit-to-stand (STS) movement by comparing coordination (phasing, weight-shift and spinal movement) between AT teachers (n=15) and matched control subjects (n=14). We found AT teachers had a longer weight-shift (p<0.001) and shorter momentum transfer phase (p=0.01), than control subjects. AT teachers also increased vertical foot force monotonically, rather than unweighting the feet prior to seat-off, suggesting they generate less forward momentum with hip flexors. The prolonged weight-shift of AT teachers occurred over a greater range of trunk inclination, such that their weight shifted continuously onto the feet while bringing the body mass forward. Finally, AT teachers had greatly reduced spinal bending during STS (cervical, p<0.001; thoracic, p<0.001; lumbar, p<0.05). We hypothesize that the low hip joint stiffness and adaptive axial postural tone previously reported in AT teachers underlies this novel "continuous" STS strategy by facilitating eccentric contractions during weight-shift.


Anterior visual system imaging to investigate energy failure in multiple sclerosis.
Mitochondrial failure and hypoxia are key contributors to multiple sclerosis pathophysiology. Importantly, improving mitochondrial function holds promise as a new therapeutic strategy in multiple sclerosis. Currently, studying mitochondrial changes in multiple sclerosis is hampered by a paucity of non-invasive techniques to investigate mitochondrial function of the CNS in vivo. It is against this backdrop that the anterior visual system provides new avenues for monitoring of mitochondrial changes. The retina and optic nerve are among the metabolically most active structures in the human body and are almost always affected to some degree in multiple sclerosis. Here, we provide an update on emerging technologies that have the potential to indirectly monitor changes of metabolism and mitochondrial function. We report on the promising work with optical coherence tomography, showing structural changes in outer retinal mitochondrial signal bands, and with optical coherence angiography, quantifying retinal perfusion at the microcapillary level. We show that adaptive optics scanning laser ophthalmoscopy can visualize live perfusion through microcapillaries and structural changes at the level of single photoreceptors and neurons. Advantages and limitations of these techniques are summarized with regard to future research into the pathology of the disease and as trial outcome measures.


[Chromosomal polymorphism in 2 synanthropous populations of the gray rat (Rattus norwegicus Berk.)].
Chromosome sets of 155 Norway rats from Ufa and 86 from Sverdlovsk are studied. The polymorphism for 3rd and 12th chromosomes is observed in both populations. Frequencies of different morphological forms of the 3rd chromosome are practically the same for Ufa and Sverdlovsk (over 90% of animals are homozygous for the telocentric, about 4-6% are heterozygous, homozygous for the subtelocentric rats are absent). The frequency of the telocentric form of the 12th chromosome in the Sverdlovsk population is significantly higher than in the Ufa one: there are 94,8% homozygous for the subtelocentric rats in Ufa, while in Sverdlovsk 83,7; 5,2 and 15,1% of the animals respectively are heterozygous; no homozygous for the telocentric rats were discovered in Ufa, and in Sverdlovsk they comprised 1,2%. The average size of litter of heterozygous for 3rd or 12th autosome females is by 30% lower than that of homozygous for the telocentric chromosome 3 and the subtelocentric chromosome 12 females. It may be suggested that the telocentric form of the 3rd chromosome supplants its subtelocentric form in populations investigated.


Advanced Age Does Not Impact Outcomes After 1-level or 2-level Lateral Lumbar Interbody Fusion.
This was a retrospective comparative study. The objective of this study was to assess the effect of increased age on perioperative and postoperative complication rates, reoperation rates, and patient-reported pain and disability scores after lateral lumbar interbody fusion (LLIF). LLIF was developed to minimize soft tissue trauma and reduce the risk of vascular injury; however, there is little evidence regarding the effect of advanced age on outcomes of LLIF. Patients who underwent LLIF from 2009 to 2019 at one institution with a minimum 6-month follow-up were retrospectively reviewed. Patients less than 18 years old with musculoskeletal tumor or trauma were excluded. The primary outcome was the preoperative to postoperative change in the Numeric Pain Rating Scale (NPRS) for back pain. Operative time, estimated blood loss, length of stay, perioperative and 90-day complications, unplanned readmissions, reoperations, and change in Oswestry Disability Index were also evaluated. Relationships with age were assessed both with age as a continuous variable and segmenting by age below 70 versus 70+. In total, 279 patients were included. The median age was 65±13 years and 159 (57%) were female. Age was not related to improvements in back NPRS and Oswestry Disability Index. Operative time, estimated blood loss, length of stay, perioperative and 90-day complications, unplanned readmissions, reoperations, and radiographic fusion rate also were not related to age. After multivariable risk adjustment, increasing age was associated with greater improvements in back NPRS. The decrease in back NPRS was 0.68 (95% confidence interval: 0.14, 1.22; P=0.014) points greater for every 10-year increase in age. Age was not associated with rates of complication, readmission, or reoperation. LLIF is a safe and effective procedure in the elderly population. Advanced age is associated with larger improvements in preoperative back pain. Surgeons should consider the benefits of LLIF and other minimally invasive techniques when evaluating elderly candidates for lumbar fusion. Level III.


67Gallium scans in Löfgren's syndrome.
Comparison of 67Gallium scans of head and neck showed no significant difference in intensity of uptake between patients with Löfgren's syndrome and sarcoidosis patients with similar chest x rays having other modes of onset. Uptake was the same in the 12 white and 18 black patients studied. Thus, the increased bronchoaveolar lavage lymphocytosis which has been shown to be a feature of Löfgren's syndrome is not paralleled by gallium uptake. Gallium scores had no predictive value regarding outcome showing no significant difference between 13 patients who recovered within a year and 15 patients who developed chronic disease. The outcome was more favorable in white patients and in those whose onset was with Löfgren's syndrome.


c-Met autocrine activation induces development of malignant melanoma and acquisition of the metastatic phenotype.
The molecular and genetic events that contribute to the genesis and progression of cutaneous malignant melanoma, a complex and aggressive disease with a high propensity for metastasis, are poorly understood due in large part to the dearth of relevant experimental animal models. Here we used transgenic mice ectopically expressing hepatocyte growth factor/scatter factor (HGF/SF) to show that the Met signaling pathway is an important in vivo regulator of melanocyte function, whose subversion induces malignant melanoma. Tumorigenesis occurred in stages, beginning with the abnormal accumulation of melanocytes in the epidermis and dermis and culminating in the development of metastatic melanoma. Oncogenesis in this model was driven by creation of HGF/SF-Met autocrine loops through forced expression of the transgenic ligand and apparent selection of melanocytes overexpressing endogenous receptor, rather than paracrine stimulation or mutational activation of c-met. Preference for liver as a metastatic target correlated with high HGF/SF-Met autocrine activity, consistent with the notion that such activity may influence colonization. Although basic fibroblast growth factor and its receptor were both weakly expressed in the majority of melanomas examined, high levels were found only in those rare neoplasms with low or undetectable HGF/SF and Met expression, suggesting that these two tyrosine kinase receptor autocrine loops serve a critical overlapping function in melanocytic tumorigenesis. Our data support a causal role for HGF/SF-Met signaling in the development of melanoma and acquisition of the metastatic phenotype. Moreover, this transgenic mouse should serve as a highly useful model, facilitating our understanding of mechanisms by which human melanoma progresses to malignancy and expediting the development of efficacious therapeutic modalities designed to constrain metastasis.


Disability among Women and Men Who Married in Childhood: Evidence from Cross-Sectional Nationally Representative Surveys Undertaken in 37 Low- and Middle-Income Countries.
Child marriage, which the UN's Sustainable Development Goal seeks to eliminate by 2030, represents a violation of the human rights of children. These concerns are driven by the negative impact of child marriage on the health of children married in childhood and their children. Little is known about the association between child marriage and disability. We sought to estimate the strength of association between disability and child marriage among women and men in middle- and low-income countries (LMICs). Secondary analysis was undertaken of nationally representative samples involving 423,164 women in 37 LMICs and 95,411 men in 28 LMICs. Results were aggregated by random effects meta-analysis and mixed effects multilevel multivariate modelling. The prevalence of disability was significantly greater among women and men who were married in childhood, especially among those married under the age of 16. The strength of these associations varied by age group and age at first marriage. Further research is required to understand the causal pathways responsible for the increased likelihood of disability among women and men married in childhood. National initiatives to eliminate child marriage may need to consider making reasonable accommodations to policies to ensure these are equally effective for women and men with disabilities.


Cervical Cutaneous Emphysema after Laser Microsurgery for Treatment of Laryngeal Cancer: Case Report.
Laser laryngectomy is a minimally invasive surgical technique that offers advantages such as precise and limited resections, magnification of the surgical field by microscopy, and improved patient outcomes. However, it is not without risks, and intraoperative complications have been reported, including cervical-cutaneous emphysema. This case report presents a rare complication of cervical-cutaneous emphysema after laser laryngectomy occurring in a 57-year-old patient with glottic carcinoma. The patient underwent laser cordectomy, and after an uneventful procedure, the patient experienced an intense coughing episode followed by swelling and progressive emphysema. The patient was kept under surveillance in the intensive care unit and received ampicillin sulbactam, protective orotracheal intubation, and voice rest. The patient had a good clinical evolution, and the emphysema resolved within 8-10 days. This case highlights the importance of prompt recognition and management of complications that can arise from laser laryngectomy. Although this technique offers several advantages, it is not risk-free, and intraoperative complications can occur. As such, careful consideration and patient selection are important to minimize the risks and achieve successful outcomes.


Nitric oxide. To block or enhance its production during sepsis?
Although it has been suggested that over-production of nitric oxide (NO) is responsible for death during endotoxic shock or sepsis, recent studies indicate that NO inhibition under such conditions is detrimental. The reason for these seemingly controversial findings may be because most studies were not standardized, ie, they were conducted at different stages of sepsis. To determine whether differential alterations in endothelium-derived NO occur at different stages of sepsis. DESIGN, INTERVENTION, AND MAIN OUTCOME MEASURES: Rats were subjected to sepsis by cecal ligation and puncture (CLP) or sham operation, followed by injection of 3 mL/100 g of body weight saline solution. At 2, 3.5, 10, or 20 hours after CLP, the thoracic aorta was isolated and responses to an endothelium-dependent vasodilator, acetylcholine (via NO), and an endothelium-independent vasodilator, nitroglycerine (directly providing NO) were determined. Endothelium-dependent relaxation increased at 2 hours (ie, very early after the onset of sepsis), returned to sham levels at 3.5 hours, but decreased at 10 and 20 hours after CLP (ie, later stage of hyperdynamic sepsis and hypodynamic sepsis, respectively). Moreover, the acetylcholine concentration, required to produce half-maximum relaxation, decreased at 2 hours but increased at 20 hours after CLP. No significant difference in nitroglycerine-induced relaxation was seen, however, in the tested groups. The increased vascular relaxation at 2 hours after CLP was not due to the upregulation of prostacyclin since cyclooxygenase inhibition did not reverse this phenomenon. This study points out the complexity of the alterations in NO production with the progression of sepsis. The triphasic response of endothelium-derived NO should be taken into account when attempting to manipulate NO levels during sepsis.


Two pediatric cases of variant neurogenic stress cardiomyopathy after intracranial hemorrhage.
Takotsubo cardiomyopathy, also known as stress-induced cardiomyopathy, is an acquired form of left ventricular systolic dysfunction seen in the setting of physiologic stress and the absence of coronary artery disease. It is thought to be caused by excessive sympathetic stimulation. It is well described in the adult literature associated with subarachnoid hemorrhage where it is known as neurogenic stress cardiomyopathy (NSC), but few such pediatric cases have been reported. We describe our experience with 2 children (13- and 10-year-old girls) who presented with spontaneous intracranial hemorrhage followed by pulmonary edema and shock. Echocardiography revealed similar patterns of left ventricular wall motion abnormalities consistent with NSC, inverted Takotsubo variant. One child progressed to death, whereas the other made a remarkable recovery, including significant improvement in cardiac function over the course of 1 week. We argue that at least 1 of these cases represents true stress-induced cardiomyopathy. This report will alert pediatricians to this transient cardiomyopathy that is likely underdiagnosed in pediatric intensive care. We also highlight the challenges of managing both shock and elevated intracranial pressure in the setting of NSC.


Risk factors for mortality after hip fracture surgery in Japan using the National Database of Health Insurance Claims and Specific Health Checkups of Japan.
We investigated the risk factors for mortality of hip fracture in the elderly using the National Database of Health Insurance Claims in Japan, and survival was significantly related to sex, age, fracture type, surgical procedure, delayed operative date, comorbidities, blood transfusions, and pulmonary embolism. Hip fracture is the most common fracture in the elderly and is known to have a high mortality rate. In Japan, to the best of our knowledge, no studies have reported on mortality risk factors for hip fracture using nationwide registry databases. This study aimed to determine the number of occurrences of hip fracture and factors that increase mortality using the National Database of Health Insurance Claims and Specific Health Checkups of Japan. This study included extracted data from patients who were hospitalized and underwent surgical treatment for hip fracture between 2013 and 2021, using a nationwide health insurance claims database in Japan. Patient characteristics, such as sex, age, fracture type, surgical procedure, delayed operative date, comorbidities, blood transfusions, and pulmonary embolism, were tabulated to obtain 1-year and in-hospital mortality rates. Both 1-year and in-patient survival were significantly lower in men, older patients, patients who underwent surgery after 3 days of admission, and patients with trochanteric and subtrochanteric fractures, internal fixation, more preoperative comorbidities, blood transfusions, and pulmonary embolism. Survival was significantly related to sex, age, fracture type, surgical procedure, delayed operative date, comorbidities, blood transfusions, and pulmonary embolism. As the number of male patients with hip fracture will increase with the aging of society, medical staff must provide sufficient information before surgery to avoid postoperative mortality.


A neurobehavioral account for individual differences in resilience to chronic military stress.
Military training is a chronic stressful period that often induces stress-related psychopathology. Stress vulnerability and resilience depend on personality trait anxiety, attentional threat bias and prefrontal-limbic dysfunction. However, how these neurobehavioral elements interact with regard to the development of symptoms following stress remains unclear. Fifty-five healthy combat soldiers undergoing intensive military training completed functional magnetic resonance imaging (fMRI) testing while performing the dot-probe task (DPT) composed of angry (threat) and neutral faces. Participants were then stratified according to their bias tendency to avoidance (n = 25) or vigilance (n = 30) groups, categorized as high or low trait anxiety and assessed for post-stress symptom severity. Avoidance compared to vigilance tendency was associated with fewer post-trauma symptoms and increased hippocampal response to threat among high anxious but not low anxious individuals. Importantly, mediation analysis revealed that only among high anxious individuals did hippocampal activity lead to lower levels of symptoms through avoidance bias tendency. However, in the whole group, avoidance bias was modulated by the interplay between the hippocampus and the dorsal anterior cingulate cortex (dACC). Our results provide a neurobehavioral model to explain the resilience to post-trauma symptoms following chronic exposure. The model points to the importance of considering threat bias tendency in addition to personality traits when investigating the brain response and symptoms of trauma. Such a multi-parametric approach that accounts for individual behavioral sensitivities may also improve brain-driven treatments of anxiety, possibly by targeting the interplay between the hippocampus and the dACC.


Postsynaptic modulation of synaptic efficacy at mixed synapses on the Mauthner cell.
Extracellular application of dopamine in the synaptic bed of the lateral dendrite of the goldfish Mauthner (M-) cell enhances both the electrical and chemical components of the mixed excitatory postsynaptic potential (EPSP) evoked by ipsilateral eighth nerve stimulation (Pereda et. al., 1992). We describe here results of experiments designed to determine the locus of action of dopamine and the underlying cellular mechanisms. This amine acts independently on the two modes of transmission, since (1) the percentage increases in the two were not correlated, (2) the time courses of their modifications were independent, and (3) the observed increases in synaptic responses cannot be attributed to a generalized effect on M-cell input conductance, which was increased by dopamine, a change that would rather be expected to shunt the synaptic potentials. Also, dopamine does not produce presynaptic spike broadening and does not modify paired-pulse facilitation, two indications that it acts postsynaptically. The alterations in the mixed EPSP are presumably due to activation of a postsynaptic cAMP-dependent phosphorylation pathway. Specifically, they did not occur if the cAMP-dependent protein kinase inhibitor PKI5-24 was injected intradendritically prior to dopamine application, and they could, on the other hand, be mimicked by injections of the catalytic subunit of the cAMP-dependent protein kinase, PKACAT. In contrast, neither manipulation altered the M-cell input conductance directly or affected the dopamine-induced increase in conductance, suggesting this effect of dopamine is cAMP independent.(ABSTRACT TRUNCATED AT 250 WORDS)


Binding of retinoids to beta-lactoglobulin isolated by bioselective adsorption.
Binding of the retinoids, all-trans-retinol, all-trans-retinal, all-trans-retinyl acetate, and all-trans-retinoic acid, to beta-lactoglobulin (LG) (96% purity) that had been prepared by bioselective adsorption on N-retinyl-Celite was determined from changes in the fluorescence quenching (332 nm) of the protein tryptophanyl residues. High affinity binding of all of these compounds occurred at pH 7.0, and the apparent dissociation constant ranged from 1.7 to 3.6 x 10(-8) M. Furthermore, a stoichiometry of 1.0 mol.mol-1 of protein was obtained for each case, indicating that all of the sites in the protein preparation were available. When beta-LG in whey protein isolate (57.4% beta-LG) was studied, a stoichiometry of 0.65 to 0.82 mol.mol-1 of protein was obtained, indicating that a large number of the sites already had bound lipid or that the protein had been denatured. As the pH was lowered toward 5.15, the affinity decreased about fourfold, but the stoichiometry of binding was unchanged. Far UV circular dichroism spectra indicated that the secondary structure of the protein was not significantly affected by ligand binding; however, the near UV spectra were changed, indicating that the flexibility of tryptophanyl residues decreased. The latter effect is consistent with the change in fluorescence quenching and suggests that a tryptophan is in the binding site.


The Effects of a Walking Intervention on Gait Parameters in Older Adults Residing in Long-Term Care: A Randomized Controlled Trial.
We examined the effects of a walking intervention in older adults residing in long-term care (LTC) homes on gait velocity (primary outcome), and stride length, cadence and heel-to-heel base of support (secondary outcomes) compared to those in an interpersonal interaction control group and a care-as-usual control group at 16-weeks post-intervention. These previously unpublished gait data were collected as part of a larger prospective, randomized, three group study. One hundred and sixty-eight participants residing in 12 LTC homes were randomized into: a) a walking group (n=57) - 1:1 supervised, individualized, progressive, 30 minutes, five times a week walking program for 16 weeks; b) an interpersonal interaction group (n=55) - stationary 1:1 conversation time with research personnel; and, c) a care-as-usual control group (n=56). Gait was assessed at baseline and 16-weeks post-intervention using the GAITRite® computerized system. One-way Analysis of Covariance (ANCOVA), controlling for age, sex, cognitive status and baseline gait parameter (velocity, stride length, cadence, heel-to-heel base of support) was used to examine differences among groups for velocity, stride length, cadence, and heel-to-heel base of support at 16-weeks post-intervention. Ninety-one participants with available data were included in this analysis: walking group (n=31/57, mean age=82.77±6.75 years); interpersonal interaction group (n=31/55, mean age=82.74±9.27 years); care-as-usual control group (n=29/56, mean age=85.40±8.78 years). ANCOVA showed a significant difference in the mean gait velocity at 16-weeks post-intervention [F(2, 84) =6.99, p=0.0006); η2 (95%CI)=0.16 (0.02, 0.27)]. Post hoc comparisons using Sidak test showed that the estimated marginal mean (EMM) for velocity for the walking group [EMM (SE), 0.51m/s (0.03)] was significantly higher compared to the interpersonal interaction group [EMM (SE), 0.38m/s (0.03); t(83)=3.15, p=0.007] and the care-as-usual control group [EMM (SE), 0.38m/s (0.03)]; t(83)=3.32, p=0.004]. No significant difference was observed between groups for stride length, cadence or heel-to-heel base of support. LTC residents with limited physical functioning showed significant improvement in gait velocity but not in stride length, cadence or heel-to-heel base of support after a 16-week walking intervention.


Assessment of carprofen and buprenorphine on recovery of mice after surgical removal of the mammary fat pad.
The purpose of this study was to determine the level of pain elicited by mammary fat pad removal surgery and the effects of postoperative analgesics on recovery. Female FVB mice were anesthetized, and mammary fat pad removal was performed. After surgery, mice received carprofen, buprenorphine, a combination of carprofen and buprenorphine, or saline treatment. Additional mice received anesthesia but no surgery or treatment. Food and water intake, body weight, wheel running activity, and a visual assessment score were recorded daily for 4 d after surgery and compared with presurgical findings. Corticosterone metabolites in fecal samples were analyzed at 12 and 24 h postsurgically and compared with baseline values. All surgical groups had significantly decreased food intake at 24 h, with a return to baseline by 48 h. The combination treatment resulted in a significantly decreased water intake and body weight at 24 h. All surgical groups had significantly decreased wheel running activity at 24 h only. The visual assessment scores indicated mild pain for all surgical groups, with the buprenorphine treated mice showing the highest pain index scores, as compared with nonsurgical controls. Fecal corticosterone metabolite levels did not differ significantly between any of the groups or across time. The parameters used in this study did not indicate that administration of these analgesic regimens improved recovery as compared with that of saline-treated mice. Care should be taken when using visual assessment scores to evaluate pain in mice, given that analgesics may have side effects that inadvertently elevate the score.


Augmentation of fear extinction by infusion of glycine transporter blockers into the amygdala.
It is known that fear extinction is blocked by the N-methyl D-aspartate (NMDA) receptor antagonist. In this study, we investigate whether extinction could be facilitated by the enhancement of NMDA response, achieved by the blocking of glycine transporters. In amygdala slices, NMDA at a concentration that normally does not have a long-term effect was found to reduce the cellular levels of postsynaptic density protein 95 and synapse-associated protein 97, in addition to the surface expression of GluR1/2, in the presence of a glycine transporter blocker, N[3-(4-fluorophenil)-3-(4'-phenilphenoxy)] propylsarcosine (NFPS). In in vivo experiments, extinction training applied 24 h after conditioning reduced startle potentiation without influencing the conditioning-induced increase in the surface expression of GluR1/2. However, NFPS augmented extinction and reversed the conditioning-induced increase in GluR1/2 when infused bilaterally into the amygdala before extinction training. The effects of NFPS were therefore blocked by the NMDA antagonist. In parallel, NFPS treatment in conjunction with extinction reversed the conditioning-induced alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/NMDA ratio. In behavioral tests, Tat-GluR2(3Y), a synthetic peptide that has been shown to block AMPA receptor endocytosis, inhibited only the additional reduction caused by NFPS treatment, rather than returning the fear potentiation levels to those of fear-conditioned animals that did not undergo extinction. These results suggest that NFPS in combination with extinction training reverses GluR1/2 surface expression and thus augments the extinction of conditioned fear.


The crystal structure of human cytosolic serine hydroxymethyltransferase: a target for cancer chemotherapy.
Serine hydroxymethyltransferase (SHMT) is a ubiquitous enzyme found in all prokaryotes and eukaryotes. As an enzyme of the thymidylate synthase metabolic cycle, SHMT catalyses the retro-aldol cleavage of serine to glycine, with the resulting hydroxymethyl group being transferred to tetrahydrofolate to form 5, 10-methylene-tetrahydrofolate. The latter is the major source of one-carbon units in metabolism. Elevated SHMT activity has been shown to be coupled to the increased demand for DNA synthesis in rapidly proliferating cells, particularly tumour cells. Consequently, the central role of SHMT in nucleotide biosynthesis makes it an attractive target for cancer chemotherapy. We have solved the crystal structure of human cytosolic SHMT by multiple isomorphous replacement to 2.65 A resolution. The monomer has a fold typical for alpha class pyridoxal 5'-phosphate (PLP) dependent enzymes. The tetramer association is best described as a 'dimer of dimers' where residues from both subunits of one 'tight' dimer contribute to the active site. The crystal structure shows the evolutionary relationship between SHMT and other alpha class PLP-dependent enzymes, as the fold is highly conserved. Many of the results of site-directed mutagenesis studies can easily be rationalised or re-interpreted in light of the structure presented here. For example, His 151 is not the catalytic base, contrary to the findings of others. A mechanism for the cleavage of serine to glycine and formaldehyde is proposed.


Cellulose microfibril orientation in Oocystis solitaria: proof that microtubules control the alignment of the terminal complexes.
In the green alga Oocystis solitaria microtubules control the regular deposition of cellulose microfibrils. Although it has frequently been suggested that the influence of the cortical microtubules is mediated through the alignment of structures in the plasma membrane, e.g. the cellulose-synthesizing enzymes, experimental proof is lacking. In Oocystis the putative cellulose-synthesizing units, the so-called terminal complexes, can be visualized following freeze-fracture. With respect to the synthesis of a given layer of microfibrils two distinct situations are observable: terminal complex doublets occur before the start of cellulose formation, but are subsequently separated into single terminal complexes by pressure exerted by the crystallizing microfibrils. In order to investigate the effect of anti-microtubular substances on the orientation of the terminal complexes, the state of cellulose deposition at the time of drug application was marked by short (15-30 min) treatment with Congo Red, which causes a morphological change in the terminal complexes. The characteristic alignment of the terminal complexes, both doublets and fragmented single ones, is severely disturbed in cells treated with the herbicide amiprophosmethyl, which is known to interfere with the action of microtubules. The results provide strong evidence that microtubules control the alignment of the putative cellulose-forming units in Oocystis. The observed pattern of interference indicates that the microtubules most probably achieve their control by imposing fluidity channels on the membrane and not via direct links with the terminal complexes.


A pervasive scientific overview on mangiferin in the prevention and treatment of various diseases with preclinical and clinical updates.
Natural products are increasing used in preventing and treating various diseases. Mangiferin belongs to the xanthone family, and has potential antiangiogenic, anticancer, immunomodulatory and anti-inflammatory activity along with the antioxidant activity. It is also used in the treatment of cardiac problem, diabetes and neurodegenerative disease. Finding of various researchers proves that mangiferin has a broad spectrum therapeutic application. Motive of this review is to describe the various studies performed on mangiferin for its different pharmacological activities. It also discusses various challenges associated with mangiferin such as stability and bioavailability. Strategies and approaches to improve bioavailability of mangiferin have also been discussed. Both research and review articles were used to write the manuscript. They were collected from various search engines like Pub Med, Science Direct and Google Scholar, using keywords like mangiferin, polyphenol, bioavailability enhancement, solubility enhancement, and antioxidant. Mangiferin being a potent antioxidant is effective in the treatment of various diseases. With novel drug delivery approaches we can overcome poor solubility and bioavailability problem which eventually can result to better utilisation of mangiferin in treating a variety of diseases and make mangiferin a revolutionary drug.


Fiber Force: A Fiber Diet Intervention in an Advanced Course-Based Undergraduate Research Experience (CURE) Course.
Course-based undergraduate research experiences (CUREs) are an effective way to introduce students to contemporary scientific research. Research experiences have been shown to promote critical thinking, improve understanding and proper use of the scientific method, and help students learn practical skills including writing and oral communication. We aimed to improve scientific training by engaging students enrolled in an upper division elective course in a human microbiome CURE. The "Fiber Force" course is aimed at studying the effect of a wholesome high-fiber diet (40 to 50 g/day for two weeks) on the students' gut microbiomes. Enrolled students participated in a noninvasive diet intervention, designed health surveys, tested hypotheses on the effect of a diet intervention on the gut microbiome, and analyzed their own samples (as anonymized aggregates). The course involved learning laboratory techniques (e.g., DNA extraction, PCR, and 16S sequencing) and the incorporation of computational techniques to analyze microbiome data with QIIME2 and within the R software environment. In addition, the learning objectives focused on effective student performance in writing, data analysis, and oral communication. Enrolled students showed high performance grades on writing, data analysis and oral communication assignments. Pre- and post-course surveys indicate that the students found the experience favorable, increased their interest in science, and heightened awareness of their diet habits. Fiber Force constitutes a validated case of a research experience on microbiology with the capacity to improve research training and promote healthy dietary habits.


Requirement of perioperative stress doses of corticosteroids: a systematic review of the literature.
To determine the requirement for perioperative supplemental (stress) doses of corticosteroids in patients receiving long-term corticosteroid therapy and undergoing a surgical procedure. Corticosteroids are among the most commonly prescribed medications and will predictably result in suppression of the hypothalamic-pituitary-adrenal axis with long-term use. Patients receiving therapeutic dosages of corticosteroids frequently require surgery; these patients are almost universally treated with stress doses of corticosteroids during the perioperative period. MEDLINE, EMBASE, Cochrane Register of Controlled Trials, and citation review of relevant primary and review articles. Randomized controlled trials (RCTs) comparing stress doses of corticosteroids with placebo and cohort studies that followed up patients after surgery in which perioperative stress doses of corticosteroids were not administered. Data were abstracted on the study design, study size, study setting, patient population, dosage and duration of previous corticosteroid therapy, adrenal function testing results, surgical intervention, corticosteroid dosing regimen, intraoperative and postoperative hemodynamic profile, and incidence of adrenal crisis. Nine studies met our inclusion criteria, including 2 RCTs and 7 cohort studies. These studies enrolled a total of 315 patients who underwent 389 surgical procedures. In the 2 RCTs, there was no difference in the hemodynamic profile between patients receiving stress doses of corticosteroids compared with patients receiving only their usual daily dose of corticosteroid. In the 5 cohort studies in which patients continued to receive their usual daily dose of corticosteroid without the addition of stress doses, no patient developed unexplained hypotension or adrenal crisis. One patient in each of the 2 cohort studies (5% and 1% of the cohort) in which the usual daily dose of corticosteroid was stopped 48 and 36 hours before surgery developed unexplained hypotension; both of these patients responded to hydrocortisone and fluid administration. Patients receiving therapeutic doses of corticosteroids who undergo a surgical procedure do not routinely require stress doses of corticosteroids so long as they continue to receive their usual daily dose of corticosteroid. Adrenal function testing is not required in these patients because the test is overly sensitive and does not predict which patient will develop an adrenal crisis. Patients receiving physiologic replacement doses of corticosteroids owing to primary disease of the hypothalamic-pituitary-adrenal axis, however, require supplemental doses of corticosteroids in the perioperative period.


Portable plasma medical device for infection treatment.
The purpose of this study was to determine the effects of plasma treatment on bacteria in liquid phases. We predict that the plasma gas can penetrate the liquid culture media and plasma treatment will efficiently kill the bacteria at unique time and distance parameters. It is also hypothesized that less stringent plasma treatment will negatively affect the growth rate of some species of bacteria and possibly their pathogenicity. The bacteria were exposed to hot and cold plasma at various time lengths and distance parameters. Our results indicated that 2 minutes of hot plasma treatment with the plasma torch 5 cm away from the liquid culture is effective in killing/sterilizing cultures of S. aureus, S. pyogenes, Salmonella spp, N. meningitidis, and E. coli. Five minutes of cold plasma with the probe immersed 1-2 cm inside the liquid culture were needed to kill the bacteria. The portable nonthermal plasma system can be used for infection treatment and wound healing applications affected by the microbes studied in this research.


Live imaging of intra- and extracellular pH in plants using pHusion, a novel genetically encoded biosensor.
Changes in pH are now widely accepted as a signalling mechanism in cells. In plants, proton pumps in the plasma membrane and tonoplast play a key role in regulation of intracellular pH homeostasis and maintenance of transmembrane proton gradients. Proton transport in response to external stimuli can be expected to be finely regulated spatially and temporally. With the ambition to follow such changes live, a new genetically encoded sensor, pHusion, has been developed. pHusion is especially designed for apoplastic pH measurements. It was constitutively expressed in Arabidopsis and targeted for expression in either the cytosol or the apoplast including intracellular compartments. pHusion consists of the tandem concatenation of enhanced green fluorescent protein (EGFP) and monomeric red fluorescent protein (mRFP1), and works as a ratiometric pH sensor. Live microscopy at high spatial and temporal resolution is highly dependent on appropriate immobilization of the specimen for microscopy. Medical adhesive often used in such experiments destroys cell viability in roots. Here a novel system for immobilizing Arabidopsis seedling roots for perfusion experiments is presented which does not impair cell viability. With appropriate immobilization, it was possible to follow changes of the apoplastic and cytosolic pH in mesophyll and root tissue. Rapid pH homeostasis upon external pH changes was reflected by negligible cytosolic pH fluctuations, while the apoplastic pH changed drastically. The great potential for analysing pH regulation in a whole-tissue, physiological context is demonstrated by the immediate alkalinization of the subepidermal apoplast upon external indole-3-acetic acid administration. This change is highly significant in the elongation zone compared with the root hair zone and control roots.


Efficacy of recombinant human erythropoietin in the treatment of refractory anemias without excess of blasts in myelodysplastic syndromes.
To determine the efficacy of recombinant human erythropoietin at pharmacological doses in myelodysplastic syndromes (MDS) without excess of blasts, 20 patients with refractory anemias (RA) or refractory anemias with ring sideroblasts (RARS) were treated in an open study with escalating doses from 40 U/kg to 300 U/kg three times a week subcutaneously during a period of 3 months. Maintenance therapy at the lowest effective dose was continued in responders. A dose response of CFU-E and BFU-E to Epo was analysed at the entry. Bone marrow examination with an in vitro study of hematopoietic progenitors was performed before and after the first three months. Seven of 20 patients responded: a total recovery was observed in 3 patients; one became transfusion independent and a reduction of 50% of the transfusion requirement was achieved in 3 others. 3 patients are still receiving treatment for 2, 3 and 4 years. No significant correlation was found between the in vitro and clinical response. A non parametric analysis of responders and non responders emphasised the importance of a long delay between the diagnosis and the treatment, (p = 0.024) and an endogenous Epo level less than 100 mU/ml (p = 0.025) in order to predict the efficacy of rhEpo. This study offers evidence that patients with refractory anemias without excess of blasts in the bone marrow respond to rhEpo at pharmacological doses. Larger studies are required in order to define the patients who may respond and to elucidate the mechanism of the positive effect of rhEpo.


Comparative proteomic analysis of brains of naturally aging mice.
We used comparative proteomic techniques to identify aging-related brain proteins in normal mice from neonate to old age. By 2-dimensional electrophoresis (2-DE), matrix assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) and peptide mass fingerprint (PMF) analysis, 39 proteins were identified, among which 6 stayed unchanged since 3 months, 6 increased and 27 decreased in various manners during aging. They are mainly involved in processes usually with destructive changes during aging, such as metabolism, transport, signaling, stress response and apoptosis. The 27 proteins' decrease may be responsible for brain aging. In particular, decrease of proteasome alpha subunits 3/6, ubiquitin carboxyl-terminal esterase L3, valosin-containing protein and calreticulin may be responsible for the declination of protein quality control; glutamate dehydrogenase 1, isocitrate dehydrogenase 1 and ubiquinol cytochrome c reductase core protein 2 for the shortage of energy and reducing agent; ubiquitin-conjugating enzyme E2N and heterogeneous nuclear ribonucleoprotein A2/B1 for the increase of DNA damage and transcription detuning; calbindin 1 and amphiphysin for the disturbance of synaptic transport and ion signals. The six proteins' increase may be involved in anti-aging processes. In particular, transketolase, mitochondrial creatine kinase 1 and ribosomal protein L37 may help to enhance energy metabolism; triosephosphate isomerase 1 may help to resist oxidative stress. Moreover, most of these proteins were found for the first time to be involved in the natural senescence of brain, which would provide new clues about the mechanism of brain aging.


Self reported involvement in emergency medicine among GPs in Norway.
To examine general practitioners' (GPs') perception of their role in emergency medicine and participation in emergency services including ambulance call outs, and the characteristics of the GPs and casualty clinics associated with the GPs' involvement in emergency medicine. Cross-sectional online survey. General practice. General practitioners in Norway (n = 1002). Proportion of GPs perceiving that they have a large role in emergency medicine, regularly being on call, and the proportion of ambulance callouts with GP participation. Forty six percent of the GPs indicated that they play a large role in emergency medicine, 63 percent of the GPs were regularly on call, and 28 percent responded that they usually took part in ambulance call outs. Multivariable logistic regression analyses indicated that these outcomes were strongly associated with participation in multidisciplinary training. Furthermore, the main outcomes were associated with traits commonly seen at smaller casualty clinics such as those with an absence of nursing personnel and extra physicians, and based on the distance to the hospital. Our findings suggest that GPs play an important role in emergency medicine. Multidisciplinary team training may be important for their continued involvement in prehospital emergencies. Key Points Health authorities and other stakeholders have raised concerns about general practitioner's (GPs) participation in emergency medicine, but few have studied opinions and perceptions among the GPs themselves. • Norwegian GPs report playing a large role in emergency medicine, regularly being on call, and taking part in selected ambulance call outs. • A higher proportion of GPs who took part in team training perceived themselves as playing a large role in emergency medicine, regularly being on call, and taking part in ambulance call outs. • These outcomes were also associated with attributes commonly seen at smaller casualty clinics.


Porous SnO2/C Nanofiber Anodes and LiFePO4/C Nanofiber Cathodes with a Wrinkle Structure for Stretchable Lithium Polymer Batteries with High Electrochemical Performance.
Stretchable lithium batteries have attracted considerable attention as components in future electronic devices, such as wearable devices, sensors, and body-attachment healthcare devices. However, several challenges still exist in the bid to obtain excellent electrochemical properties for stretchable batteries. Here, a unique stretchable lithium full-cell battery is designed using 1D nanofiber active materials, stretchable gel polymer electrolyte, and wrinkle structure electrodes. A SnO2/C nanofiber anode and a LiFePO4/C nanofiber cathode introduce meso- and micropores for lithium-ion diffusion and electrolyte penetration. The stretchable full-cell consists of an elastic poly(dimethylsiloxane) (PDMS) wrapping film, SnO2/C and LiFePO4/C nanofiber electrodes with a wrinkle structure fixed on the PDMS wrapping film by an adhesive polymer, and a gel polymer electrolyte. The specific capacity of the stretchable full-battery is maintained at 128.3 mAh g-1 (capacity retention of 92%) even after a 30% strain, as compared with 136.8 mAh g-1 before strain. The energy densities are 458.8 Wh kg-1 in the released state and 423.4 Wh kg-1 in the stretched state (based on the electrode), respectively. The high capacity and stability in the stretched state demonstrate the potential of the stretchable battery to overcome its limitations.


Population assessment and habitat associations of the Visayan Hornbill (Penelopides panini) in Northwest Panay, Philippines.
Seven out of ten hornbill species in the Philippines are threatened with extinction. Among these is the endangered Visayan Hornbill (Penelopides panini), found on the islands of Panay and Negros. Threatened by habitat loss and hunting, its population size is thought to have declined from 1800 individuals 20 years ago to less than 1000. However, a recent study on Negros estimated 3564 individuals across three core forest blocks. This study aims to quantify the Visayan Hornbill population size in and around the Northwest Panay Peninsula Natural Park (NWPPNP) on Panay, the largest contiguous low-elevation forest landscape remaining across its range, and its broad habitat associations across a gradient of environmental degradation. Hornbills were surveyed using 10-min distance sampling point counts (n = 367) along transects (average length 1.1 km). Environmental variables were recorded along transects, while habitat was classified into primary forest, secondary forest, plantation, or open habitat. Distance software was used to estimate population densities stratified by habitat, with the overall population estimate taken as a mean of habitat density estimates weighted by habitat area. Using generalized linear mixed models, hornbill occurrence was modelled using combinations of nine environmental variables as main and two-way fixed effects. Surveys covered 204.4 km2 of the 374.8 km2 Northwest Panay Peninsula. Hornbills were not recorded in plantations or open habitats. Hornbill density was significantly higher in primary forest (17.8 individuals/km2 ± 26.9% CV) than in secondary forest (3.7 individuals/km2 ± 33.2% CV; z = 15.212, P < 0.001). The overall population estimate for the NWPPNP and environs is 2109 individuals, and 2673 individuals for the entire Northwest Panay Peninsula. Hornbill presence was best explained by a model including distance from the Park boundary alongside five interaction effects and transect as a random effect. Distance, and the interaction between distance and medium-sized trees were significant predictors of hornbill presence. Our study evidences the habitat preference of the Visayan Hornbill, highlights the importance of the NWPPNP for the species' conservation, and provides strong evidence for re-assessing the global population size. The online version contains supplementary material available at 10.1186/s40657-021-00303-3.


Cannabidiol inhibits multiple cardiac ion channels and shortens ventricular action potential duration in vitro.
Cannabidiol (CBD) is a non-psychoactive component of Cannabis which has recently received regulatory consideration for the treatment of intractable forms of epilepsy such as the Dravet and the Lennox-Gastaut syndromes. The mechanisms of the antiepileptic effects of CBD are unclear, but several pre-clinical studies suggest the involvement of ion channels. Therefore, we have evaluated the effects of CBD on seven major cardiac currents shaping the human ventricular action potential and on Purkinje fibers isolated from rabbit hearts to assess the in vitro cardiac safety profile of CBD. We found that CBD inhibits with comparable micromolar potencies the peak and late components of the NaV1.5 sodium current, the CaV1.2 mediated L-type calcium current, as well as all the repolarizing potassium currents examined except Kir2.1. The most sensitive channels were KV7.1 and the least sensitive were KV11.1 (hERG), which underly the slow (IKs) and rapid (IKr) components, respectively, of the cardiac delayed-rectifier current. In the Purkinje fibers, CBD decreased the action potential (AP) duration more potently at half-maximal than at near complete repolarization, and slightly decreased the AP amplitude and its maximal upstroke velocity. CBD had no significant effects on the membrane resting potential except at the highest concentration tested under fast pacing rate. These data show that CBD impacts cardiac electrophysiology and suggest that caution should be exercised when prescribing CBD to carriers of cardiac channelopathies or in conjunction with other drugs known to affect heart rhythm or contractility.


Recognition of a hidden mineral deposit by an artificial intelligence program.
A computer program that uses artificial intelligence techniques has successfully identified the location of a porphyry molybdenum deposit. Given geological maps of readily available predrilling exploration data for Mount Tolman in Washington State and using rules obtained from a porphyry molybdenum exploration specialist, the program (called PROSPECTOR) identified the location of previously unknown ore-grade mineralization. This appears to be the first reported determination of the location of mineralization by such a computer-based approach.


Nursing Shift Handoff Process: Using an Electronic Health Record Tool to Improve Quality.
Nursing shift handoffs can be frustrating for nursing staff when information received about a patient is inaccurate or inadequate. The safety of the patient may be compromised, and missed opportunities for care interventions may occur. The electronic health record (EHR) provides healthcare professionals with useful information that can highlight the most important items the nurse needs to prioritize patient care. A unit leadership team at a large academic hospital developed a peer-to-peer training plan to provide evidence-based nursing education using the nursing handoff feature in the EHR.


[Spin label study of the surface of lipid bilayers].
The surface of liposomes and natural membranes has been studied by the method of "spin label--spin probe". Various nitroxyl radicals have been attached to membranes either dueto covalent binding with NH2-groups of phosphatidylethanolamine or due to hydrophobic interactions. Addition of paramagnetics of different charge signs (potassium ferricyanide and dibenzenechromium iodide) to spin labeled membranes results in a decrease of the EPR line intensity without marked broadening. Since the paramagnetic is attached to the membrane surface near the label it broadens the label's EPR spectrum so that it can not be observed. In this case one can observe only the spectrum of labels which have no paramagnetics in the vicinity, the nitroxyl part of radicals being inaccessible to direct paramagnetic impacts. The constants of binding of paramagnetics to the membrane surface have been determined from these experiments. All results (including the assymetry of label rotation) can be explained most simply by assuming that the polar lipid groups are oriented parallel to the membranes surface.


Associations of medically documented psychiatric diagnoses and risky health behaviors in highly active antiretroviral therapy-experienced perinatally HIV-infected youth.
The Longitudinal Epidemiologic Study to Gain Insight into HIV/AIDS in Children and Youth (LEGACY) study is a prospective, multisite, longitudinal cohort of U.S. HIV-infected youth. This analysis was limited to perinatally HIV-infected youth (n=197), 13 years and older, with selected variables completely abstracted from HIV diagnosis through 2006. We evaluated relationships between ever having one or more nonsubstance related medically documented psychiatric diagnoses and three risky health behaviors (substance abuse, preadult sexual activity, and treatment adherence problems) recorded between 2001 and 2006. Logistic regression was used for all binary outcomes and participant age was included as a covariate when possible. All 197 participants included in the analysis were prescribed antiretroviral therapy during the study period; 110 (56%) were female, 100 (51%) were black non-Hispanic, and 86 (44%) were Hispanic; mean age at the last visit was 16.8 years, ranging from 13 to 24 years. One hundred forty-six (74%) participants had a history of at least one risky health behavior. There were 108 (55%) participants with at least one medically documented psychiatric diagnosis, 17 (9%) with at least one record of substance abuse, 12 (6%) with documented preadult sexual activity, and 142 (72%) participants with reported adherence problems. In the final model, a history of at least one psychiatric diagnosis was associated with having at least one of the three risky behaviors (odds ratio [OR]=2.33, p=0.015). There is a need for a continued close partnership between HIV specialty care providers and mental health services treating perinatally HIV-infected youth with an added focus on improving treatment adherence.


Neurofibromatosis, acute myelomonocytic leukemia, and disseminated tuberculosis: an adult case report.
Leukemia associated with neurofibromatosis has been reported to be predominantly nonlymphocytic and limited to childhood; it is rare in adulthood. An adult case is reported; the patient had nonfamilial peripheral neurofibromatosis (NF) (von Recklinghausen's disease), contracted acute myelomonocytic leukemia and disseminated tuberculosis (TB). After a four-month periods of anti-TB medication that disease was much improved, but the leukemic picture was still progressing. Chemotherapy was not given. This case further illustrated an association between acute nonlymphocytic leukemia (ANLL) and neurofibromatosis type 1 (NF-1) in adulthood. An attempt was made also to explain the relationship between disseminated tuberculosis and, in this instance, hematological abnormalities.


Hepatitis C virus infection and hospital-related outcomes: a systematic review protocol.
People living with hepatitis C virus (HCV) infection are disproportionately over-represented in the healthcare system due to various individual and contextual circumstances, including comorbidities and socioeconomic marginalisation. With growing trends in morbidity and mortality related to HCV infection, HCV is becoming a significant health and financial burden on the healthcare system, particularly in acute hospital settings. It is noteworthy that with the advent of direct-acting antiviral therapy the increasing number of patients who are cured of HCV could potentially result in different patterns of hospital-related outcomes over time. We will conduct a systematic review of published literature to retrieve quantitative research articles pertaining to hospital outcomes among patients living with HCV. Primary outcomes include hospitalisation rates, length of stay, leaving against medical advice, readmission and in-hospital mortality. In total, five databases will be searched (MEDLINE, EMBASE, CINAHL, PsycINFO and Web of Science). Titles, abstracts and full texts will be independently reviewed by two investigators in three separate stages. The methodological quality of included quantitative research studies will be assessed using a validated tool. Data from included articles will be extracted using a standardised form and synthesised in a narrative account. Results of this systematic review could provide a better understanding on how to optimise health systems and services to improve patient outcomes and care. The results of this study may provide future research with a foundation to guide decision-making and for designing and implementing systems-level interventions to improve treatment and care delivery for people living with HCV. Ethical approval for this study was received by the University of British Columbia/Providence Health Care Research Ethics Board. Findings from this study will be disseminated through peer-reviewed publications, presentations, reports and community forums PROSPERO REGISTRATION NUMBER: CRD42017081082; Pre-results.


Elements of the art of practice in mental health.
This qualitative study explored elements of artful practice of therapists practicing in mental health treatment settings. In-depth interviews were conducted with three occupational therapists practicing in mental health who were considered exemplars of artful practice. Themes pertaining to their perspectives and approaches to practice were synthesized from interview data. The prevailing themes--therapeutic work as a vehicle for healing, collaborative guidance, and the Zen of therapy--are seen as elements forged by the therapist's compassion and unique personal style into a dynamic therapist-client interplay that creates a space for growth and healing to occur. Results affirmed the view of the art of practice in mental health as an intricate interplay of personal traits, interpersonal skills, and skilled use of meaningful activities within the context of a client's environment. The art of practice is a fluid, experiential process that takes place on a developmental continuum. The therapist's inner awareness of the subtlety of a multilayered healing process is an important basis of artful practice. One's practice art can be informed by knowledge of specific elements that contribute to artful practice and can be developed through education, self-reflection, personal growth, and the maturation process.


Mandibular first premolar with four canals.
A case of endodontic treatment of a mandibular first premolar exhibiting a total of four distinct root canals and four apical foramina is described. This occurrence in mandibular first premolar has rarely been reported in the endodontic literature. Endodontic treatment that considers the anatomic variation of root canal morphology is important to ensure a favorable healing outcome, and its identification could be enhanced by careful examination using a dental operating microscope. Obturation of root canals using a warm vertical compaction technique with a highly-radiopaque root canal sealer, such as AH Plus, after careful ultrasonic activated irrigation with ethylenediaminetetraacetic acid might allow the flow of sealer into the narrowed but unprepared part of the canal. This offers valuable adjuncts for the successful negotiation of calcified main canals, thereby facilitating optimum chemo-mechanical debridement of the root canal system.


Enhanced anti-PD-1 therapy in hepatocellular carcinoma by tumor vascular disruption and normalization dependent on combretastatin A4 nanoparticles and DC101.
Anti-programmed cell death protein 1 (PD-1) therapy has shown promising efficacy in hepatocellular carcinoma (HCC), but its response rates in advanced HCC are lower than 20%. A critical reason for this is the imbalance between CD8+ T cells and tumor burden. Here, a novel concept of vascular disruption and normalization dependent on a polymeric vascular disrupting agent (VDA) poly (L-glutamic acid)-graft-methoxy poly (ethylene glycol)/combretastatin A4 (CA4-NPs) + a vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) inhibitor DC101 is applied to improve anti-PD-1 therapy, wherein CA4-NPs reduce tumor burden and DC101 simultaneously increases the number of intratumoral CD8+ T cells, successfully regulating the abovementioned imbalance in an H22 tumor model. Methods: Blood vessel density, tumor cell proliferation, and necrosis were evaluated to reveal the effects on reducing tumor burden by CA4-NP treatment. Pericyte coverage of blood vessels, tumor blood vessel perfusion, tumor hypoxia, and intratumoral immune cells were examined to verify their role in vascular normalization and immune cell homing of DC101. Furthermore, the effects of CA4-NPs + DC101 on reducing tumor burden and increasing the number of immune cells were studied. Finally, tumor suppression, intratumoral CD8+ T cell activation, and the synergistic effects of anti-PD-1 combined with CA4-NPs + DC101 were verified. Results: The tumor inhibition rate of anti-PD-1 antibody combined with CA4-NPs + DC101 reached 86.4%, which was significantly higher than that of anti-PD-1 (16.8%) alone. Importantly, the Q value reflecting the synergy between CA4-NPs + DC101 and anti-PD-1 was 1.24, demonstrating a strong synergistic effect. Furthermore, CA4-NPs + DC101 improved anti-PD-1 therapy by increasing the number of intratumoral CD8+ T cells (anti-PD-1, 0.31% vs triple drug combination, 1.18%). Conclusion: These results reveal a novel approach to enhance anti-PD-1 therapy with VDAs + VEGF/VEGFR2 inhibitors in HCC.


The thyroid in ulverative colitis and Crohn's disease. II. Thyroid enlargement and hyperthyroidism in ulcerative colitis.
The frequency of thyroid disease has been surveyed in 300 patients with ulcerative colitis (UC) and 600 controls. The controls were drawn from visitors to the general medical wards of the Radcliffe Infirmary and were matched for age and sex with the UC patients. Two observers independently assessed all these subjects for thyroid enlargement of the simple goitre type. Although there were minor variations between the results obtained by the two observers, they found simple goitre in 8.7-6.3 percent among the UC patients compared with 4.3-3.3% percent among the controls; a difference which is significant. A history of thyrotoxicosis was obtained in 3.7 percent of the UC patients compared with 0.8 percent of the controls (p greater than 0.01). In more than half of the UC patients with a history of hyperthyroidism, the hyperthyroidism occurred years before the onset of the colitis. It is therefore highly unlikely that hyperthyroidism is a complication of the colitismpossible reasons for the association of the two diseases are discussed but it is concluded that no satisfactory explanation exists at present.


Mild maternal hyperglycemia in INSC93S transgenic pigs causes impaired glucose tolerance and metabolic alterations in neonatal offspring.
Alongside the obesity epidemic, the prevalence of maternal diabetes is rising worldwide, and adverse effects on fetal development and metabolic disturbances in the offspring's later life have been described. To clarify whether metabolic programming effects are due to mild maternal hyperglycemia without confounding obesity, we investigated wild-type offspring of INSC93S transgenic pigs, which are a novel genetically modified large-animal model expressing mutant insulin (INS) C93S in pancreatic β-cells. This mutation results in impaired glucose tolerance, mild fasting hyperglycemia and insulin resistance during late pregnancy. Compared with offspring from wild-type sows, piglets from hyperglycemic mothers showed impaired glucose tolerance and insulin resistance (homeostatic model assessment of insulin resistance: +3-fold in males; +4.4-fold in females) prior to colostrum uptake. Targeted metabolomics in the fasting and insulin-stimulated state revealed distinct alterations in the plasma metabolic profile of piglets from hyperglycemic mothers. They showed increased levels of acylcarnitines, gluconeogenic precursors such as alanine, phospholipids (in particular lyso-phosphatidylcholines) and α-aminoadipic acid, a potential biomarker for type 2 diabetes. These observations indicate that mild gestational hyperglycemia can cause impaired glucose tolerance, insulin resistance and associated metabolic alterations in neonatal offspring of a large-animal model born at a developmental maturation status comparable to human babies.


The Association With Physical Fitness and Academic Performance at America's Military Medical School.
Undergraduate and graduate medical education both have been reported to have high rates of depression, anxiety, and burnout as a result of the rigors of their educational curricula. Wellness, including physical fitness, is important to the profession because it may help mitigate these increased rates of depression and anxiety. While several studies examine physical fitness and academic performance in primary and secondary education, few studies have examined the association between fitness and performance in health professions education. Given the demands of medical school, this investigation aimed to investigate the possibility of an association between physical fitness and body mass index (BMI) with academic performance. Another goal was to examine the change in physical fitness and BMI throughout medical school. Standardized measures of physical fitness were examined in 192 Army students from the Uniformed Services University of Health Sciences over 4 years from the classes of 2017-2019. Measurements include (1) body composition (BMI); (2) muscular endurance (timed push-ups); (3) aerobic endurance (timed run), and (4) total fitness defined as total points from sit-ups, run, and push-ups (everything but BMI). Pearson correlation analysis was conducted between physical fitness and academic performance measures such as United States Medical Licensing Examination (USMLE) Step 1, USMLE Step 2 Clinical Knowledge (CK), and average core clerkship National Board of Medical Examiners (NBME) exam scores. A repeated measures analysis of variance was conducted to examine the differences of students' fitness total points and BMI over 4 fitness measurements spanning approximately 1.7 years. There were weak positive correlations, 0.20 and 0.22, between USMLE Step 2 CK exam scores and push-up points and total fitness points, respectively. There also were weak positive correlations, 0.21 and 0.24, between core clerkship average NBME exam scores and push-up points and total fitness points, respectively. No statistically significant change of individual students' fitness total point change was observed (F(2.52, 334.93 = 1.37, P = 0.26)). There was also no individual BMI change (F(2.36, 274.21 = 2.78, P = .06)) over the first four assessment measurements (about 1.7 years lapse). However, the class means over the four measurements showed a decrease of fitness total points and an increase of BMI. Our investigation suggests that there may be correlations between physical fitness and clinical exam performance such as USMLE Step 2 CK and average core clerkship NBME exams. Although there is no statistically significant change in individual fitness total points or BMI, the study suggests that physical fitness and BMI may decline during medical school. This may be as a result of increasing academic demands while balancing clinical duties from clerkship rotations.


The DSM-III personality disorders. Perspectives from psychology.
Although psychiatry and psychology have shared an interest in the classification of personality throughout the history of both professions, the efforts of each have largely been independent, with little collaboration or communication. We attempt to bridge this gap by describing a number of research programs in psychology that have implications for the psychiatric diagnosis of personality disorders. We discuss in particular the prototypal model of categorization, the use of behavioral indicators, the identification of prototypic acts, the aggregation of behavior across time and situations, the dimensional model of classification, and the interpersonal circumplex.


The role of allopurinol and deferoxamine in preventing pressure ulcers in pigs.
Ischemia and reperfusion may be important in the pathogenesis of pressure ulcers. On the basis of this hypothesis, the effects of intermittent pressure and the anti-free radical agents allopurinol and deferoxamine were studied in a pig model in which a pressure of 150 mmHg was applied intermittently to the scapulae. Cutaneous blood flow, transcutaneous oxygen tension, skin and muscle damage, and muscle levels of adenosine triphosphate were quantified. A control group of pigs (n = 6) was untreated, the allopurinol group (n = 6) received oral allopurinol beginning 2 days before the experiment, and the deferoxamine group (n = 6) received an intramuscular injection of deferoxamine 2 hours before the experiment. Pressure (150 mmHg) was applied to the scapulae for 210 minutes, and it was relieved for 30 minutes. This 4-hour cycle was repeated continuously for 48 hours, and it resulted in pressure injuries in all animals. Allopurinol and deferoxamine improved cutaneous blood flow and tissue oxygenation, but only deferoxamine could significantly reduce cutaneous and skeletal muscle necrosis (p < 0.001). This study suggests a future role for anti-free radical agents in the reduction of pressure-induced injury.


Compound A, a plant origin ligand of glucocorticoid receptors, increases regulatory T cells and M2 macrophages to attenuate experimental autoimmune neuritis with reduced side effects.
Experimental autoimmune neuritis (EAN) is a helper T cell-mediated autoimmune demyelinating inflammatory disease of the peripheral nervous system and serves as the animal model for human inflammatory demyelinating polyneuropathies. Compound A, a plant-derived phenyl aziridine precursor, was reported to activate glucocorticoid receptors to exert transrepression but not transactivation properties. In this study, we investigated the effects of Compound A in EAN rats. Compound A greatly suppressed paraparesis in EAN, even when administrated after the appearance of the first neurological signs. Accumulation of macrophages and lymphocytes, demyelination, and mRNA levels of inflammatory molecules in sciatic nerves of EAN were greatly attenuated by Compound A. In addition, Compound A inhibited progression of neuropathic pain and repressed microglia but not astrocyte activation and IL-1beta and TNF-alpha up-regulation in EAN spinal cords. In EAN sciatic nerves, Compound A treatment increased numbers of anti-inflammatory M2 macrophages. Furthermore, Compound A induced the switch of macrophages from inflammatory M1 type to anti-inflammatory M2 type in vitro. In lymph nodes of EAN rats, Compound A depressed Th1 and Th17 cytokines, but increased Th2 cytokine and Foxp3 expression. An increase of Foxp3(+)/CD4(+) regulatory T cells was seen in peripheral blood of EAN rats following Compound A treatment. In addition, Compound A did not cause a hyperglycemia effect in EAN rats as compared with the immunosuppressive steroid prednisolone. Therefore, our data demonstrated that Compound A could effectively suppress EAN with reduced side effects by attenuating inflammation, suggesting that Compound A could be a potent candidate for treatment of autoimmune neuropathies.


Estimation of rabbit myocardial metabolic rate for glucose using fluorodeoxyglucose.
The isolated arterially perfused rabbit interventricular septum was used to determine the feasibility of using the glucose analogue 18F-2-deoxy-2-fluoro-d-glucose (DG) with a tracer kinetic model to estimate the rate of exogenous glucose utilization. FDG was delivered to the septum by constant infusion, and tissue 18F radioactivity was measured as a function of time by external coincidence counting. The following four conditions were studied: flow rates of 0.5, 1.0, and 1.5 ml/min with a heart rate of 72 beats/min and flow at 1.5 ml/min with 96 beats/min. The rate constants for FDG forward and reverse transport between the vascular and extravascular compartments (k*1, k*2, respectively), phosphorylation of FDG (k*3), and dephosphorylation of FDG-6-phosphate (FDG-6-P) (k*4) were determined from the tissue curves using a tracer kinetic model. The lumped constant (LC) of the deoxyglucose model calculated using Fick-derived myocardial metabolic rates of glucose (MMRGlc), was 0.60 +/- 0.10 and was stable over the range of conditions studied. Average k*'s and LC were used to calculate MMRGlc's employing the model and were not significantly (P greater than 0.05) different from those determined by the Fick method. Tissue analyses using high-pressure liquid chromatography documented that tissue 18F radioactivity wa due to FDG and FDG-6-P, and their relative fractions agreed well with the values predicted from the tracer kinetic model. Only FDG was detected in the effluent. These studies also indicate the presence of a myocardial enzyme that can hydrolyze FDG-6-P to FDG. Thus our results support the use of the FDG method with positron-computed tomography for the in vivo determination of the myocardial rate of exogenous glucose utilization.


[Paths of corticosteroid biosynthesis in the adrenal glands of rhesus monkeys].
In experiments in vitro corticosteroid formation from radioactive cholesterol in tha adrenal glands of monkeys (Macaca rhesus) was studied. A conclusion was drawn that pregnenolone and its hydroxy-derivatives were of the leading significance in the cortizol and corticosterone synthesis in the adrenal glands of monkeys. Progesteron was produced in insignificant amounts and was almost unutilized for steroidogenesis. The formation of 17.21-dioxypregnenolone was revealed; its role in the capacity of cortizol precursor was proved; 17-oryprogesteron was found to be of no great significance in cortizol synthesis; 21-oxypregnenolone, but not progesteron proved to serve as the principal intermediate product in corticosterone formation.


Expression of progesterone receptor related to the polymorphism in the PGR gene in the rabbit reproductive tract.
The association of the 2464G > A SNP found in the promoter region of the rabbit progesterone receptor gene with progesterone receptor (PR) expression was evaluated by Western blot analysis. This SNP was associated with 2 lines divergently selected for uterine capacity, the high line selected to increase uterine capacity and the low line selected to decrease uterine capacity. Two progesterone isoforms were obtained using a commercial monoclonal antibody: the PR-B isoform described previously in rabbits, and the PR-A isoform, not described previously in rabbits. The GG genotype, the genotype more frequent in the high line, showed less PR-B and PR-A expression than the AA genotype in the oviduct (GG/AA(PR-B) = 0.81 and GG/AA(PR-A) = 0.73) and uterus (around 0.70 in both isoforms). The GA genotype showed similar PR-A expression in both tissues and also similar PR-B expression in the oviduct to the GG genotype. Conversely, the GG genotype showed less PR-B expression than the GA genotype in the uterus (GG/GA(PR-B) = 0.79). Similar expression of both PR isoforms was found in the uterus at d 2 and 3 of gestation; meanwhile, an increase of both isoforms was observed in the oviduct. Similar PR-A expression was observed in the ampulla and isthmus; meanwhile, the PR-B expression in the isthmus was double that in the ampulla.


Chromosome displacement and spindle tubule polymerization. 2. Effect of alterations of extracellular calcium on displacement parameters.
Human lymphocytes were grown for either the entire culture period of 72 h or the final 6 h of culture, in media with different concentrations of calcium. Cultures were harvested without colchicine or hypotonic treatment and 'displaced' chromosomes were analysed. Long or short term exposure to various concentrations of calcium gave similar results. The frequency of cells showing displacement and the median number of displaced chromosomes per cell were highly correlated with calcium concentration (r = 1). Only the smaller chromosomes, 13-22, showed a significant correlation for displacement rate and calcium concentration. Individual chromosomes showed a consistent response to calcium which appeared to be specific for each chromosome. Chromosome 17 was the most sensitive to calcium, but chromosomes 16, 19 and most C-group chromosomes showed no response. The acrocentric chromosomes 13, 14, 15, 21 and 22 all showed a modest but similar response. An hypothesis is advanced that these responses may be controlled by specific amounts of microtubular associated proteins and/or calmodulin in the spindle tubules attached to the different chromosomes.


Maturation of the Intestinal Epithelial Barrier in Neonatal Rats Coincides with Decreased FcRn Expression, Replacement of Vacuolated Enterocytes and Changed Blimp-1 Expression.
The intestinal barrier is immature in newborn mammals allowing for transfer of bioactive macromolecules, e.g. protecting antibodies, from mother's milk to the blood circulation and in neonatal rodents lasts until weaning. This passage involves the neonatal-Fc-receptor (FcRn) binding IgG in the proximal and highly endocytic vacuolated enterocytes in the distal immature small intestine (SI). Recent studies have suggested an involvement of the transcription factor B-lymphocyte-induced maturation-protein-1 (Blimp-1) in the regulation of SI maturation in mice. Hence, the objective of the present study was to monitor the development of the intestinal barrier function, in relation to Blimp-1 expression during both natural and precociously induced intestinal maturation in rats. During the suckling period IgG plasma levels increased, while after gut closure it temporarily decreased. This corresponded to a high expression of FcRn in the proximal SI epithelium and the presence of vacuolated enterocytes in the distal SI. The immature foetal-type epithelium was replaced after weaning or induced precocious maturation, by an adult-type epithelium with FcRnneg cells in the proximal and by non-vacuolated enterocytes in the distal SI. In parallel to this epithelial shift, Blimp-1 expression decreased in the distal SI. The switch from foetal- to adult-type epithelium, with decreased proximal expression of FcRn and distal replacement of vacuolated enterocytes, was concurrent in the two SI regions and could be used for monitoring SI maturation in the rat. The changes in expression of Blimp-1 in the distal SI epithelium followed the maturation pattern.


Application of molecular genetics in public health: improved follow-up in a neonatal hemoglobinopathy screening program.
Newborn screening for the hemoglobinopathies has been shown to reduce morbidity and mortality, particularly for sickle cell anemia, by facilitating initiation of penicillin prophylaxis by 4 months of age. The purpose of the current investigation was to determine whether molecular genetic follow-up testing could be introduced into a neonatal hemoglobinopathy screening program and, if successfully introduced, whether it would reduce time to diagnostic confirmation. Between July 1, 1991, and October 7, 1992, 518 original dried blood specimens were referred from the Texas Department of Health Neonatal Hemoglobinopathy Screening Program for molecular genetic follow-up testing. Allele-specific cleavage (ASC) after amplification with matched and mismatched polymerase chain reaction primers was compared to allele-specific oligonucleotide (ASO) hybridization. By November 2, 1992, molecular genetic analyses were definitive in 506, and agreement was observed between ASC and ASO hybridization in all specimens analyzed. Approximately 13% of those initially screened FS were considered probable S/beta-thal by DNA and RNA testing. Rapid molecular genetic analysis contributed to a substantial reduction of the mean age at confirmation by approximately 50%, to about 2 months of age. ASC is a reliable method for molecular genetic analysis of dried blood specimens, providing methodology which can be readily automated. An automated method is demonstrated that is based on microtiter plate technology and will significantly reduce labor intensity and costs, while increasing sample throughput. Even with current manual testing methods, DNA and RNA analysis of initial newborn screening specimens will reduce the age at confirmation well under 4 months, the age cut-off for effective initiation of penicillin prophylaxis.