Weight Management in Older Adults.
As the number of older adults increases rapidly, the national epidemic of obesity is also affecting our aging population. This is particularly concerning given the numerous health risks and increased costs associated with this condition. Weight management is extremely important for older adults given the risks associated with abdominal adiposity, which is a typical fat redistribution during aging, and the prevalence of comorbid conditions in this age group. However, approaches to weight loss must be considered critically given the dangers of sarcopenia (a condition that occurs when muscle mass and quality are lost), the increased risk of hip fracture with weight loss, and the association between reduced mortality and increased BMI in older adults. This overview highlights the challenges and implications of measuring adiposity in older adults and the dangers and benefits of weight loss in this population and provides an overview of the new Medicare Obesity Benefit. In addition, we provide a summary of outcomes from successful weight loss interventions for older adults and discuss implications for advancing clinical practice.


Suberin fatty acids isolated from outer birch bark improve moisture barrier properties of cellulose ether films intended for tablet coatings.
We showed that the addition of suberin fatty acids (SFAs) even at small concentrations significantly improves the water vapor barrier properties of hydroxypropyl methylcellulose (HPMC) films. SFAs were isolated from the outer birch bark using extractive hydrolysis. The effects of SFAs on the film formation of aqueous HPMC were investigated with free films plasticized with polyethylene glycol (PEG 400). Special attention was paid on the physical solid-state, moisture barrier and mechanical stress-strain properties of films intended for tablet film coatings. Topography and surface morphology, glass transition temperature (Tg), tensile strength, Young's modulus, and water vapor permeation (WVP) of films were studied. The addition of SFAs lowered the Tg of films suggesting partial enhancement in film plasticization. The WVP of films decreased with increasing SFAs concentration up to 15% (calculated as a % w/w from a polymer weight). The WVP value for a non-suberized reference film and suberized film plasticized with PEG 400 was 2.13×10(-6) and 0.69[×10(-6) g/(mm(2)×h)×mm/Pa], respectively. The addition of SFAs impaired the mechanical stress-strain properties of HPMC films by reducing the deformation capacity of film. In conclusion, the film properties and performance of aqueous HPMC can be modified by including SFAs in the films.


Low concentrated phosphorus sorption in aqueous medium on aragonite synthesized by carbonation of seashells: Optimization, kinetics, and mechanism study.
Phosphorus (P) concentration beyond threshold limit can trigger eutrophication in stagnant water bodies nevertheless it is an indispensable macronutrient for aquatic life. Even in low P concentration (≤1 mg L-1), P can be detrimental for ecosystem's health, but this aspect has not been thoroughly investigated. The elimination of low P content is rather expensive or complex. Therefore, a unique and sustainable approach has been proposed in which valorized bivalve seashells can be used for the removal of low P content. Initially, acicular shaped aragonite particles (~21 μm) with an aspect ratio of around 21 have been synthesized through the wet carbonation process and used to treat aqueous solutions containing P in low concentration (P ≤ 1 mg L-1). Response surface methodology based Box-Behnken design has been employed for optimization study which revealed that with aragonite dosage (140 mg), equilibrium pH (~10.15), and temperature (45 °C), a phosphorus removal efficiency of ~97% can be obtained in 10 h. The kinetics and isotherm studies have also been carried out (within the range P ≤ 1 mg L-1) to investigate a probable removal mechanism. Also, aragonite demonstrates higher selectivity (>70%) towards phosphate with coexisting anions such as nitrate, chloride, sulfate, and carbonate. Through experimental data, elemental mapping, and molecular dynamic simulation, it has been observed that the removal mechanism involved a combination of electrostatic adsorption of Ca2+ ions on aragonite surface and chemical interaction between the calcium and phosphate ions. The present work demonstrates a sustainable and propitious potential of seashell derived aragonite for the removal of low P content in aqueous solution along with its unconventional mechanistic approach.


Two-Dimensional SiO2/VO2 Photonic Crystals with Statically Visible and Dynamically Infrared Modulated for Smart Window Deployment.
Two-dimensional (2D) photonic structures, widely used for generating photonic band gaps (PBG) in a variety of materials, are for the first time integrated with the temperature-dependent phase change of vanadium dioxide (VO2). VO2 possesses thermochromic properties, whose potential remains unrealized due to an undesirable yellow-brown color. Here, a SiO2/VO2 core/shell 2D photonic crystal is demonstrated to exhibit static visible light tunability and dynamic near-infrared (NIR) modulation. Three-dimensional (3D) finite difference time domain (FDTD) simulations predict that the transmittance can be tuned across the visible spectrum, while maintaining good solar regulation efficiency (ΔTsol = 11.0%) and high solar transmittance (Tlum = 49.6%). Experiments show that the color changes of VO2 films are accompanied by NIR modulation. This work presents a novel way to manipulate VO2 photonic structures to modulate light transmission as a function of wavelength at different temperatures.


Lethal acute aortic dissection complicated with ischemic bowels in the third trimester of pregnancy: A case report.
Aortic dissection is a rare but lethal disease. We demonstrate a rare case of acute complicated Stanford type A aortic dissection in the third trimester. A 41-year-old primiparous patient with chronic hypertension was brought to our emergency department at 34 weeks of gestation. She presented with acute tearing chest pain radiating to her back. Computed tomography revealed a Stanford type A aortic dissection. Primary cesarean section followed by open cardiovascular surgery was performed. However, ischemic bowels and bowel perforation occurred on the 9th and 11th postoperative days, respectively, and the patient died of septic shock on the 12th postoperative day. Aortic dissection must be taken into consideration for pregnant women with chronic hypertension who present with acute tearing chest pain and pulseless unilateral extremities. Bowel ischemia may occur in patients with complicated Stanford type A aortic dissection.


Cytogenetic changes in plant cells as influenced by mycotoxins.
The effect of mycotoxins DON, DAS and F-2 on actively dividing cells of cereals and field bean was studied. In general, mycotoxins resulted in a decrease of mitotic activity. However, the F-2 treatment increased the mitotic index in rye. DON appeared a strong inhibitor of cell divisions in wheat and field bean. DAS retarded divisions at the stage of methaphase and changes spiralization and colourabi1ity of metaphase chromosomes. The cytological picture of the DAS-treated cells indicates that this compound disturbs the functioning of the karyokinetic spindle leading to the formation of cells of multiplied number of chromosomes.


Focused ultrasound thalamotomy for tremor treatment impacts the cerebello-thalamo-cortical network.
High-intensity Magnetic Resonance-guided Focused Ultrasound (MRgFUS) is a recent, non-invasive line of treatment for medication-resistant tremor. We used MRgFUS to produce small lesions in the thalamic ventral intermediate nucleus (VIM), an important node in the cerebello-thalamo-cortical tremor network, in 13 patients with tremor-dominant Parkinson's disease or essential tremor. Significant tremor alleviation in the target hand ensued (t(12) = 7.21, p < 0.001, two-tailed), which was strongly associated with the functional reorganization of the brain's hand region with the cerebellum (r = 0.91, p < 0.001, one-tailed). This reorganization potentially reflected a process of normalization, as there was a trend of increase in similarity between the hand cerebellar connectivity of the patients and that of a matched, healthy control group (n = 48) after treatment. Control regions in the ventral attention, dorsal attention, default, and frontoparietal networks, in comparison, exhibited no association with tremor alleviation and no normalization. More broadly, changes in functional connectivity were observed in regions belonging to the motor, limbic, visual, and dorsal attention networks, largely overlapping with regions connected to the lesion targets. Our results indicate that MRgFUS is a highly efficient treatment for tremor, and that lesioning the VIM may result in the reorganization of the cerebello-thalamo-cortical tremor network.


Correction to: Task context load induces reactive cognitive control: An fMRI study on cortical and brain stem activity.
The article Task context load induces reactive cognitive control.


An efficient and biodegradable alginate-gelatin hydrogel beads as bait against Aedes aegypti and Aedes albopictus.
The effective control of Aedes mosquitoes using traditional control agents is increasingly challenging due to the presence of insecticide resistance in many populations of key mosquito vectors. An alternative strategy to insecticides is the use of toxic sugar baits, however it is limited due to short-term efficacy. Alginate-Gelatin hydrogel beads (AGHBs) may be an effective alternative by providing longer periods of mosquito attraction and control, especially of key vectors of dengue viruses such as Aedes aegypti and Aedes albopictus. Sodium alginate (ALG) and gelatin (GLN) are natural polymers, which can be a potential candidate to develop the AGHBs baits due to their biodegradability and environmental safety. Here we provide an assessment of the preparation of AGHBs optimized by varying the concentrations of ALG, GLN, and its cross-linking time (TIME). Fourier transform infrared spectroscopy (FTIR) analysis results in the determination of liquid bait loaded in the AGHBs. The evaluation of AGHBs' effectiveness as the potential baiting tool based on the mortality rate of mosquitoes after the bait consumption. The 100 % percent mortality of Aedes mosquitoes was obtained within 72 h of bait consumption. The field evaluation also justifies the applicability of AGHBs for outdoor applications. We conclude that the AGHBs are applicable as a baiting tool in carrying liquid bait in achieving mosquito mortality.


Applying molecular docking to pesticides.
Pesticide creation is related to the development of sustainable agricultural and ecological safety, and molecular docking technology can effectively help in pesticide innovation. This paper introduces the basic theory behind molecular docking, pesticide databases, and docking software. It also summarizes the application of molecular docking in the pesticide field, including the virtual screening of lead compounds, detection of pesticides and their metabolites in the environment, reverse screening of pesticide targets, and the study of resistance mechanisms. Finally, problems with the use of molecular docking technology in pesticide creation are discussed, and prospects for the future use of molecular docking technology in new pesticide development are discussed. © 2023 Society of Chemical Industry.


Immunoglobulin D lambda multiple myeloma and amyloidosis with predominant soft tissue involvement.
Multiple myeloma (MM) is associated with amyloidosis in approximately 15% of the patients. The most frequent presenting signs of such an association are nephrotic syndrome, cardiomyopathy and peripheral neuropathy. Amyloid arthropathy is not a frequent feature. We report a patient with immunoglobulin D (IgD) lambda type MM with presenting symptoms related to mucocutaneous amyloidosis and also amyloid arthropathy. He had no clinical and laboratory involvement due to nephrotic syndrome or cardiomyopathy. IgD myeloma is a rare form of MM and therefore much of the information about the disease is derived from case reports describing patients with associated symptoms. Our case also shows an unusual organ distribution of amyloid.


Effect of Bacillus subtilis and Oregano Oil on Performance, Gut Microbiome, and Intestinal Morphology in Pullets.
This study aimed to examine the effect of probiotics containing Bacillus subtilis and oregano essential oil on the growth performance, intestinal morphology, and cecal microbial composition in pullets aged 0-18 weeks. A total of 324 day-old Hy-Line Brown chicks were randomly assigned to three treatment groups, with six replicates per group and 18 birds per pen. The experimental treatments consisted of the following: a control group receiving a basal diet (Con), a group receiving a basal diet supplemented with 1 g/kg (3 × 108 cfu/kg) of Bacillus subtilis (BS), and a group receiving a basal diet supplemented with 0.3 g/kg of oregano essential oil (ORO). The groups supplemented with BS and ORO demonstrated significantly higher villus height/crypt depth ratios than the Con group. Microbial richness was significantly higher in groups supplemented with BS (p = 0.0317) and ORO (p = 0.00794) than in the Con group. These findings revealed a distinct separation between gut microbial communities of the Con group and those supplemented with ORO, based on unweighted and weighted UniFrac indices. Therefore, supplementation with Bacillus subtilis and oregano oil improved the composition of the microbiota, suggesting their positive effects on the gut health of pullets.


Characterization of a TM-4 type tropomyosin that is essential for myofibrillogenesis and contractile activity in embryonic hearts of the Mexican axolotl.
A striated muscle isoform of a Tropomyosin (TM-4) gene was characterized and found to be necessary for contractile function in embryonic heart. The full-length clone of this isoform was isolated from the Mexican axolotl (Ambystoma mexicanum) and named Axolotl Tropomyosin Cardiac-3 (ATmC-3). The gene encoded a cardiac-specific tropomyosin protein with 284 amino acid residues that demonstrated high homology to the Xenopus cardiac TM-4 type tropomyosin. Northern blot analysis indicates a transcript of approximately 1.25 kb in size. RT-PCR and in situ hybridization demonstrated that this isoform is predominantly in cardiac tissue. Our laboratory uses an animal model that carries a cardiac lethal mutation (gene c), this mutation results in a greatly diminished level of tropomyosin protein in the ventricle. Transfection of ATmC-3 DNA into mutant hearts increased tropomyosin levels and promoted myofibrillogenesis. ATmC-3 expression was blocked in normal hearts by transfection of exon-specific anti-sense oligonucleotide (AS-ODN). RT-PCR confirmed lower transcript expression of ATmC-3 and in vitro analysis confirmed the specificity of the ATmC-3 exon 2 anti-sense oligonucleotide. These AS-ODN treated hearts also had a disruption of myofibril organization and disruption of synchronous contractions. These results demonstrated that a striated muscle isoform of the TM-4 gene was expressed embryonically and was necessary for normal structure and function of the ventricle.


Hips in cerebral palsy: A clinico-radiological evaluation of hip subluxation in cerebral palsy.
The study was done on children with cerebral palsy in the ages of 2-18 years, with focus on hip subluxation. The objectives of the study were to look at the distribution of different types of CP in the target population; the prevalence of hip subluxation and its association with types and severity of CP. This is a cross sectional descriptive observational study, done on a hospital out-patient setting. Children with cerebral palsy of ages 2-18 years were recruited and clinically evaluated. Radiological evaluation of the pelvis was done for all subjects. Primary outcome measure was presence of hip subluxation described as Migration Percentage >30% in one or both hips. Prevalence of subluxation and its association with various subtypes of CP were assessed. 203 subjects with cerebral palsy underwent the study. Spastic type of presentation constituted the majority (82.8%). Quadriplegic distribution (53.2%) and functional level of GMFCS 5 (39.4%) were most prevalent. Hip subluxation was noted in 105 of the 203 children with CP (51.7%). 3 patients had complete dislocation of the hip (1.4%). There was an increased prevalence of hip subluxation noted with increasing GMFCS E&R score as well as increasing topographical distribution, which were both statistically significant on univariate analysis (p < 0.005). On multivariate analysis, it was found that neither topographical distribution nor GMFCS E&R score were independent risk factors. Hip subluxation is a significant, debilitating and common treatable complication in children with CP. Subjects with widespread topographical distribution and poor functional ambulatory status are at an increased risk of developing hip subluxation. There also exists a correlation between GMFCS scores and topographical classification and hence, neither are risk factors independent of each other. This study is a first of its kind in the Indian scenario and it hopes to be a step in the direction towards risk stratification, early diagnosis and prompt specific treatment of hip complications in children with cerebral palsy.


The pliable obstetrical vacuum cup: application and opinions in The Netherlands.
A questionnaire was sent to all hospital obstetric units in The Netherlands to obtain information about the use of soft cups for vacuum extraction. Over 90% of the 156 units responded. Vacuum extraction was used twice as often as forceps for instrumental vaginal delivery. In 12 units the flexible cup was applied in the majority of vacuum extractions and without specific restrictions. In 47 units a minority of vacuum extractions was performed with a flexible cup: its use was generally restricted to anticipated easy low outlet extractions. It is concluded that in The Netherlands the flexible cup is an accepted instrument used in about 13% of vacuum extraction deliveries.


Analysis of cardiac myosin binding protein-C phosphorylation in human heart muscle.
A unique feature of MyBP-C in cardiac muscle is that it has multiple phosphorylation sites. MyBP-C phosphorylation, predominantly by PKA, plays an essential role in modulating contractility as part of the cellular response to β-adrenergic stimulation. In vitro studies indicate MyBP-C can be phosphorylated at Serine 273, 282, 302 and 307 (mouse sequence) but little is known about the level of MyBP-C phosphorylation or the sites phosphorylated in heart muscle. Since current methodologies are limited in specificity and are not quantitative we have investigated the use of phosphate affinity SDS-PAGE together with a total anti MyBP-C antibody and a range of phosphorylation site-specific antibodies for the main sites (Ser-273, -282 and -302). With these newly developed methods we have been able to make a detailed quantitative analysis of MyBP-C phosphorylation in heart tissue in situ. We have found that MyBP-C is highly phosphorylated in non-failing human (donor) heart or mouse heart; tris and tetra-phosphorylated species predominate and less than 10% of MyBP-C is unphosphorylated (0, 9.3 ± 1%: 1P, 13.4 ± 2.7%: 2P, 10.5 ± 3.3%: 3P, 28.7 ± 3.7%: 4P, 36.4 ± 2.7%, n=21). Total phosphorylation was 2.7 ± 0.07 mol Pi/mol MyBP-C. In contrast in failing heart and in myectomy samples from HCM patients the majority of MyBP-C was unphosphorylated. Total phosphorylation levels were 23% of normal in failing heart myofibrils (0, 60.1 ± 2.8%: 1P, 27.8 ± 2.8%: 2P, 4.8 ± 2.0%: 3P, 3.7 ± 1.2%: 4P, 2.8 ± 1.3%, n=19) and 39% of normal in myectomy samples. The site-specific antibodies showed a distinctive distribution pattern of phosphorylation sites in the multiple phosphorylation level species. We found that phosphorylated Ser-273, Ser-282 and Ser-302 were all present in the 4P band of MyBP-C but none of them were significant in the 1P band, indicating that there must be at least one other site of MyBP-C phosphorylation in human heart. The pattern of phosphorylation at the three sites was not random, but indicated positive and negative interactions between the three sites. Phosphorylation at Ser-282 was not proportional to the number of sites available. The 2P band contained 302 but not 273; the 3P band contained 273 but not 302.


Systemic Therapy Improvements Will Render Locoregional Treatments Obsolete for Patients with Cancer with Liver Metastases.
Hepatic metastases are a major cause of morbidity and mortality for patients with cancer. Apart from curative resection, which offers patients the potential for long-term survival, an array of locoregional therapies, with limited evidence of improving survival, are used to treat them. The authors use examples from the realm of gastrointestinal cancer, largely focusing on the experience of patients with neuroendocrine cancer, hepatobiliary cancer, and colorectal cancer, to suggest that current systemic therapies offer, at minimum, similar survival outcomes for patients compared with these locoregional approaches.


Comparing resistome profiles from anthropogenically impacted and non-impacted areas of two South Shetland Islands - Maritime Antarctica.
Whalers Bay, in Deception Island, has one of the most anthropogenically impacted areas in Maritime Antarctica. However, considering the volcanic nature (high concentrations of heavy metals) of Deception Island's soils, this putative anthropogenic impact should be carefully investigated. In this context, the objective of this study was to compare resistome profiles of impacted and non-impacted areas in Deception Island (Whalers Bay, Crater Lake, and Fumarole Bay) and Livingston Island (Hannah Point) in order to investigate the microbiome tolerance/resistance mechanisms selected as a function of environmental drivers. Metagenomics was used to search for genes conferring resistance/tolerance to antibiotics, biocides, and heavy metals. Whalers Bay has a greater diversity of antibiotic, biocide, and heavy metal resistance classes found in its microbiomes. However, Hannah Point, at Livingston Island, has a greater abundance of antibiotic and biocide resistance/tolerance genes. The microbiome of Deception Island's non-impacted areas (Crater Lake and Fumarole Bay) showed resistance/tolerance genes almost entirely to heavy metals. Pb was found in higher concentrations in Whalers Bay soil in comparison to the other areas, indicating human contamination. The non-metric multidimensional scaling (NMDS) analysis revealed that Pb concentrations influenced resistome profiles in Whalers Bay soil. Despite the effect of Pb on the microbial communities of Whalers Bay, most heavy metal concentrations did not have a significant impact on resistome genes, suggesting that the volcanic soil heavy metal concentration of Deception Island has little biological influence.


Genetics of chromosome 15q13-q14 in schizophrenia.
Positive genetic linkage to the 15q13-q14 region has been found in 11 studies, and several association reports support this locus as a candidate region for schizophrenia. The locus is unusual in that it was first linked to an endophenotype found in schizophrenia, the P50 deficit, and subsequently to schizophrenia. There is also biological data showing that a candidate gene in the region, the alpha7 nicotinic receptor CHRNA7, plays a seminal role in the linked endophenotype, and is decreased in expression in the patient population. The 15q13-q14 region is complicated by a partial duplication of the CHRNA7 gene that includes exons 5-10 and considerable sequence downstream. Evidence from multiple studies supports a broad region of genetic linkage around the marker D15S1360.


[Hidden allergens in processed food. The consumer perspective].
Despite improved allergen-labeling and careful avoidance strategies, hidden allergens in food are a substantial risk for unintended reactions in food allergy sufferers. Unpublished data from a survey of the German Allergy and Asthma Association (Deutscher Allergie- und Asthmabund, DAAB) show that 85% of 738 questioned food allergic patients have experienced at least one allergic reaction from each prepacked products as well as food sold loose. Almost half of the participants said to have not received information of a food allergen as an ingredient or possible trace on the label. Different possibilities are discussed under which food allergens can be hidden in processed products, like incomprehensible labeling, labeling gaps, unexpected occurrence of allergens as well as cross contaminations or allergens in loose products. To each of the seven highlighted sources of hidden allergens in food, practical examples are given as well as proposals for the improvement of the situation from consumer view. The aim is to indicate possibilities and measures for politics and industry by which allergic consumers and their social circle are able to make an informed choice concerning the safe consumption of a certain product and to protect themselves from unintentional reactions.


Structural dynamics in an electron-transfer complex.
The dynamic behaviour of the complex of horse cytochrome c with cytochrome c peroxidase, an electron-transfer complex, was studied in solution by a hydrogen exchange labelling method together with two-dimensional NMR analysis. Although cytochrome c hydrogens in the expected binding region exhibit slowed exchange, the measured slowing factors are very small, indicating that hydrogen-exchange occurs with little hindrance from within the binding interface. The complex in solution must therefore be highly mobile rather than rigidly defined, as implied by the crystalline complex. This result is in conflict with the concept that biological electron transfer occurs by way of predetermined covalent pathways.


Baicalin attenuates focal cerebral ischemic reperfusion injury by inhibition of protease-activated receptor-1 and apoptosis.
To investigate the neuro-protective effects of baicalin in Wistar rats with focal cerebral ischemic reperfusion injury. Ninety adult male Wistar rats weighing 320-350 g were randomly divided into the following groups (n=5): (a) sham control group; (b) vehicle group, subjected to middle cerebral artery occlusion and received vehicle intraperitoneally; (c-e) baicalin groups, which were subjected to the middle cerebral artery occlusion and treated with baicalin 25, 50 and 100 mg/kg, respectively. The neurological scores were determined at postoperative 1, 3 and 7 d after the treatment. The expression of protease-activated receptor-1 (PAR-1), PAR-1 mRNA and Caspase-3 were determined using Western blot, reverse transcription polymerase chain reaction (RTPCR) analysis and immunohistochemistry, respectively. Significant decrease was noted in the neurological score in the baicalin group compared with that of the vehicle group (P<0.01). Additionally, down-regulation of PAR-1 mRNA, PAR-1 and Caspase-3 was observed in the baicalin groups compared with those obtained from the vehicle group (P<0.01). Compared with the low-dose baicalin group (25 mg/kg), remarkable decrease was noted in neurological score, and the expression of PAR-1 mRNA, PAR-1 as well as Caspase-3 in the high-dose group (P<0.05). Baicalin showed neuro-protective effects in focal cerebral ischemic reperfusion injury through inhibiting the expression of PAR-1 and apoptosis.


Effect of nitric oxide on mucin production in experimental otitis media.
The purpose of this study was to determine the role of nitric oxide (NO) in the pathogenesis of mucoid otitis media (OM) in lipopolysaccharide (LPS)-induced OM. OM was induced in chinchillas by injecting S-nitroso-N-acetylpenicillamine (SNAP), LPS, and LPS + SNAP into the superior bullae. Auditory brainstem response thresholds were measured every 24 hours. Samples of middle ear fluid were collected and analyzed for mucin by the periodic acid-Schiff method. At the end of each experiment, temporal bones were harvested for histopathologic study. Mucin concentration was greatest in the LPS + the SNAP group and least in the SNAP-alone group. Auditory brainstem response threshold was highest in the LPS group and lowest in the SNAP group, although not significantly. Histopathology showed the greatest mucosal thickening and inflammation in the LPS + SNAP group. The addition of NO in LPS-induced OM increased the mucin concentration in middle ear fluid and increased mucosal thickness and inflammation in middle ear mucosa. In the OM disease process, NO may contribute to the pathogenesis of mucoid OM.


The case for the green banana: Using fruit to improve tenaculum placement simulation.
The purpose of this study was to identify a fruit that would resemble the 'feel' of a uterine cervix when compared to plastic pelvic models. A group of experienced clinicians tested six different fruits and evaluated their suitability as a cervical simulation for tenaculum placement. An unripe (green) banana was rated the highest in seven out of eight characteristics and was the only fruit to achieve a consensus for overall simulation above 70%. A green banana is an affordable and accessible option to simulate a cervix for procedures requiring tenaculum placement on a cervix.


Molecular characterization of hasA from an operon required for hyaluronic acid synthesis in group A streptococci.
The mechanism by which group A streptococci produce the antiphagocytic hyaluronate (hyaluronic acid) capsule is incompletely understood. Enzymes known to be essential for synthesis of this polysaccharide include the membrane-associated hyaluronate synthase as well as those required for production of the substrate sugars UDP-N-acetylglucosamine and UDP-glucuronic acid. In this study, a Tn916 insertion that inactivates hyaluronate synthetic activity was localized to a gene designated hasA in the hyaluronic acid synthesis operon. This gene has recently been preliminarily identified as the group A streptococcal hyaluronate synthase. The DNA sequence and transcription start site of hasA were determined, and the predicted HasA protein was shown to have characteristics of a membrane protein. Amino acid sequence homology suggests that HasA is related to a family of proteins involved in polysaccharide production and cell differentiation. Finally, in addition to the loss of hyaluronate synthase activity, the hasA::Tn916 insertion was demonstrated to correlate with a loss of UDP-glucuronic acid dehydrogenase activity. These results suggest that the genes required for hyaluronate synthase activity and production of the UDP-glucuronic acid substrate are transcribed as a unit in group A streptococci.


The neuroprotective actions of corticotropin releasing hormone.
Corticotropin-releasing hormone (CRH) modulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis, and has a key role in mediating neuroendocrine effects that occur in response to stressful stimuli. Disruption of the CRH system however has been shown to be closely associated with the progression of Alzheimer's disease (AD), and these observations prompted an investigation into the potential neuroprotective effects of the hormone. In addition to its regulatory affects on the molecular processes that underlie AD i.e., amyloid precursor protein (APP) processing and potentially tau phosphorylation, evidence is provided that the neuroprotective effects of CRH are mediated by a number of diverse mechanisms. These stem from activation of its high affinity receptor, the CRH type 1 receptor, and involve the induction of protective intracellular pathways including PKA-CREB that eventually lead to expression of neurotrophic factors. Conversely, inhibition of harmful events, such as caspase activation during apoptosis may also occur. Taken together, an impressive amount of evidence has accumulated recently, highlighting this new and potentially important function of CRH.


Venodilator action of an organotransition-metal nitrosyl complex.
Nitrovasodilators, such as nitroglycerin, cause endothelium-independent dilatation of arterial and capacitance vessels via the release of nitric oxide (NO). This study examined the venodilator effect of CpCr(NO)(2)Cl (organotransition-metal nitrosyl complex) relative to that of nitroglycerin in conscious, unrestrained rats. Organotransition-metal nitrosyl complexes have releasable NO directly attached to metal centres. The dose-response effects of CpCr(NO)(2)Cl and nitroglycerin on the mean arterial pressure and the mean circulatory filling pressure (index of the body venous tone) were obtained in rats continuously infused with either normal saline or noradrenaline. The results show that both CpCr(NO)(2)Cl and nitroglycerin reduced the mean arterial pressure in rats with normal or elevated vasomotor tone. However, maximum depressor response of CpCr(NO)(2)Cl was greater than that of nitroglycerin. In vehicle-treated rats, both compounds increased the mean circulatory filling pressure. In rats with elevated vasomotor tone through the infusion of noradrenaline, both agents reduced the mean circulatory filling pressure. These results show that CpCr(NO)(2)Cl is an efficacious depressor and venodilator agent.


Hepatic cryotherapy for liver tumors. Development and clinical evaluation of a high-efficiency insulated multineedle probe system for open and laparoscopic use.
A high-efficiency hepatic cryosurgical unit has been developed and evaluated. It is capable of simultaneously driving three implantable insulated cryoneedle probes. The system has been used to treat 18 patients with secondary and 4 patients with primary liver cancer: open (n = 12), total laparoscopic (n = 6), laparoscopic assisted (n = 4). In three patient laparoscopic cryotherapy was repeated inside 6 months. Intraoperative bleeding was encountered in three patients undergoing high-volume hepatic freezing but the bleeding was easily controlled. A fall in the core body temperature was encountered in 10 out of 22 patients and averaged 0.4 degree C. There was one postoperative death from liver failure in an 80-year-old patient in whom a large hepatoma was frozen. The most consistent postoperative biochemical change was hyperbilirubinaemia (n = 3). A right-sided pleural effusion developed in two patients after freezing of lesions on the superior surface of the right lobe. A survival benefit was encountered in three patients, one with central cholangiocarcinoma and the other two with large solitary secondary deposits (melanoma, colon cancer). Seven patients with multiple metastases and two patients with large hepatomas developed recurrence at the frozen site or elsewhere in the liver inside 12 months of follow-up and no clinical benefit could be demonstrated by cryotherapy in this group. In nine patients, the follow-up has been too short (< 18 months) to permit any conclusion on outcome. The current limitations of hepatic cryotherapy are largely due to incomplete tumor destruction.(ABSTRACT TRUNCATED AT 250 WORDS)


Progestin effects on growth in the human breast cancer cell line T-47D--possible therapeutic implications.
In order to determine growth effects of the progestin R5020, (promegestone), we have utilized the progesterone-receptor rich human breast cancer cell line T-47D, growing the cells in the absence of the pH indicator phenol red, which has recently been found to be estrogenic. In contrast to reports on cells grown in the presence of phenol red, we find that promegestone alone, at physiological progestin concentration, significantly stimulates growth. Estradiol alone, at physiological concentration, stimulates growth much more. Promegestone in combination with estradiol is antiestrogenic for growth; that is, it significantly decreases the growth stimulatory effect of estradiol. These results raise the possibility that estrogen receptor and progesterone receptor-rich breast cancer patients might benefit more from a combination of anti-progestin and anti-estrogen therapy than from anti-estrogens alone.


Atherosclerotic splenic artery aneurysm in a decompensated cirrhotic patient.
Splenic artery aneurysm is a rare condition with potential lethal complications. If associated with severe diseases, the diagnosis and management may be challenging. Usually, ultrasound examination is the first step in the diagnosis, and the specific ultrasound features suggest the diagnosis. When combined with contrast-enhanced ultrasound examination, the accuracy of ultrasound increases and can therefore rule out some severe complications. We present the case of a patient hospitalized with decompensated cirrhosis in whom the ultrasound examination revealed the presence of a high-risk splenic artery aneurysm. However, the treatment decisions were profoundly influenced by the liver disease complications.


A Peptide Pair Coordinates Regular Ovule Initiation Patterns with Seed Number and Fruit Size.
Ovule development in Arabidopsis thaliana involves pattern formation, which ensures that ovules are regularly arranged in the pistils to reduce competition for nutrients and space. Mechanisms underlying pattern formation in plants, such as phyllotaxis, flower morphogenesis, or lateral root initiation, have been extensively studied, and genes controlling the initiation of ovules have been identified. However, the fundamental patterning mechanism that determines the spacing of ovule anlagen within the placenta remained unexplored. Using natural variation analysis combined with quantitative trait locus analysis, we found that the spacing of ovules in the developing gynoecium and fruits is controlled by two secreted peptides, EPFL2 and EPFL9 (also known as Stomagen), and their receptors from the ERECTA (ER) family that act from the carpel wall and the placental tissue. We found that a signaling pathway controlled by EPFL9 acting from the carpel wall through the LRR-receptor kinases ER, ERL1, and ERL2 promotes fruit growth. Regular spacing of ovules depends on EPFL2 expression in the carpel wall and in the inter-ovule spaces, where it acts through ERL1 and ERL2. Loss of EPFL2 signaling results in shorter gynoecia and fruits and irregular spacing of ovules or even ovule twinning. We propose that the EPFL2 signaling module evolved to control the initiation and regular, equidistant spacing of ovule primordia, which may serve to minimize competition between seeds or facilitate equal resource allocation. Together, EPFL2 and EPFL9 help to coordinate ovule patterning and thereby seed number with gynoecium and fruit growth through a set of shared receptors.


Sustained efficacy of the novel topical repellent TT-4302 against mosquitoes and ticks.
Mosquitoes and ticks are blood-feeding pests of humans and animals that can vector many important aetiological agents of disease. Previous research demonstrated that TT-4302 (Guardian(®) Wilderness) containing 5% geraniol applied to human subjects gave 5-6 h of repellency against mosquitoes (depending on species) and was repellent to ticks in vitro. This study was conducted to obtain an independent third-party evaluation of TT-4302 against Stegomyia aegypti (= Aedes aegypti) (Diptera: Culicidae) mosquitoes and to test the efficacy of the product in the field against ticks. TT-4302 provided an average of 6.5 h of repellency of ≥ 95% [Weibull mean protection time: 7.4 h, 95% confidence interval (CI) 5.8-11.3 h] for St. aegypti, whereas a 15% DEET formulation provided 4.7 h of repellency (Weibull mean protection time: 5.2 h, 95% CI 3.7-6.9 h). In tick field trials, the efficacy of TT-4302 did not differ significantly from that of a 25% DEET formulation against Amblyomma americanum (Ixodida: Ixodidae). TT-4302 was 81.3% repellent at 2.5 h after application, whereas DEET was 77.2% repellent at the same time-point. Results at 3.5 h after application were 71.4% for TT-4302 and 72.9% for DEET.


Inspiratory muscular activation during threshold therapy in elderly healthy and patients with COPD.
Inspiratory muscles training in COPD is controversial not only in relation to the load level required to produce muscular conditioning effects but also in relation to the group of patients benefiting from the training. Consequently, inspiratory muscular response assessment during Threshold therapy may help optimizing training strategy. The objective of this study was to evaluate the participation of the diaphragm and the sternocleidomastoid (SMM) muscle to overcome with a 30% Threshold load using surface electromyography (sEMG) and to analyze the correlation between SMM activation, maximum strength level of inspiratory muscles (MIP) and obstruction degree in COPD patients (FEV1). We studied seven healthy elderly subjects, mean age of 68+/-4 years and seven COPD patients, FEV1 45+/-17% of the predicted value, with mean age 66+/-8 years. sEMG analysis of SMM muscles and diaphragm were obtained through RMS (root-mean-square) during three stages: pre-loading, loading and post-loading. In the COPD group, the RMS of the SMM increased 28% during load (p<0.05) while the RMS of the diaphragm remained constant. In the elderly there was a trend of a 11% increase in diaphragm activity and of 7% in SMM activity but, without reaching significance levels. SMM activity demonstrated good correlation with the obstruction level (r=-0.537). To overcome the load required by Threshold therapy, COPD patients demonstrated an increase of accessory muscles activity, represented by SMM. For the same relative load this increase seems to be proportional to the degree of pulmonary obstruction.


Aneurysms of the portal venous system. Gray-scale and color Doppler ultrasonographic findings with CT and MRI correlation.
Two cases of incidentally detected aneurysms involving the portal venous system are described with emphasis on gray-scale and color Doppler ultrasonographic (US) findings. Appearing on US as anechoic masses showing direct luminal continuity with the right portal vein and superior mesenteric vein, the lesions displayed spectral findings characteristic of portal venous system on color Doppler US. Dynamic helical computed tomography (CT) demonstrated simultaneous enhancement with the portal system, while the aneurysms were hypointense owing to flow void on T1-weighted spin-echo magnetic resonance (MR) images.


Management of trigeminal autonomic cephalgias and hemicrania continua.
The trigeminal autonomic cephalgias (TACs) are a group of primary headache disorders characterised by unilateral trigeminal distribution pain that occurs in association with ipsilateral cranial autonomic features. This group of headache disorders includes cluster headache, paroxysmal hemicrania and short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT syndrome). Although hemicrania continua has previously been classified amongst the TACs, its nosological status remains unclear. Despite their similarities, these disorders differ in their clinical manifestations and response to therapy, thus underpinning the importance of recognising them. We have outlined the clinical manifestations, differential diagnoses, diagnostic workup and the treatment options for each of these syndromes.


Quantitative Analysis of Retinal Structure Using Spectral-Domain Optical Coherence Tomography in RPGR-Associated Retinopathy.
To quantify retinal structure and progression using spectral-domain optical coherence tomography (SDOCT) in patients with retinitis pigmentosa (RP) associated with retinitis pigmentosa GTPase regulator gene (RPGR) mutations. Retrospective observational case series. Setting: Moorfields Eye Hospital, London, United Kingdom. Both eyes of 32 patients. SDOCT follow-up period of >1 year (3.1 ± 1.4 years). Ellipsoid zone (EZ) width (EZW) and outer nuclear layer (ONL) and inner retinal layer (IRL) thickness measurements. Progression rates, interocular symmetry, and association with age and genotype were investigated. Significant differences were observed between baseline and final measurements of EZW and ONL thickness, but not for IRL thickness. Baseline and final EZWs were 2438 ± 1646 μm and 1901 ± 1423 μm for right eyes (P < .0001); 2420 ± 1758 μm and 1922 ± 1482 μm for left eyes (P < .0001). EZW constriction rates were 176.6 ± 130.1 μm/year and 173.1 ± 146.8 μm/year for right and left eyes. ONL thinning rates were 2.58 ± 2.85 μm/year and 2.52 ± 3.54 μm/year for right and left eyes. Interocular differences in EZW and ONL progression were not significant (P = .8609 and P = .6735, respectively). Strong correlations were found between EZW constriction rates of right and left eyes (rs = 0.627, P = .0002) and between EZW constriction and baseline EZW (rs = 0.714, P < .0001). There was moderate negative correlation between EZW constriction and age (rs = -0.532, P < .0001). Correlation between ONL thinning and age was not significant, as were differences between EZW and ONL progression rates with respect to genotype. This study provides SDOCT progression rates for RPGR-associated RP. There is overall interocular symmetry with implications for future treatment trials where 1 eye could serve as a control.


Variation in readmission rates by emergency departments and emergency department providers caring for patients after discharge.
The role of the emergency department (ED) provider and ED facility in readmissions of recently discharged patients who visit the ED has not been studied. To determine the variation in readmission rates by ED facility and ED providers caring for patients after discharge. Retrospective cohort study using multilevel, multivariable models of 100% Texas Medicare claims data from the years 2007 to 2011. Texas acute-care hospitals and ED facilities. Medicare beneficiaries who visited an ED within 30 days of discharge from a hospital. None. Readmission after an ED visit within 30 days of discharge from an initial hospitalization defined as a hospitalization starting the day of or the day following the ED visit. The mean readmission rate following an ED visit was 52.67%. In 2-level models, 14.2% of ED providers readmitted significantly more patients (mean readmission rate of 67.2%) than the mean; 14.7% of ED providers readmitted significantly fewer patients (mean readmission rate of 36.8%) than the mean. After accounting for the ED facility in 3-level models, the variance for the ED providers decreased 65% from 0.2532 to 0.0893. The risk of readmission varies by ED provider caring for patients after discharge. A large part of this variation is explained by the ED facility in which the ED providers practice. Thus, ED provider practices patterns and ED facility systems of care may be a target for interventions to reduce readmissions.


A model to facilitate transformative learning in nursing education.
Transformative learning is a learner-centered process of learning. Learners are actively engaged through critical reflection and discourse to question assumptions and expectations. The purpose of this article is to describe a model to facilitate transformative learning in nursing education. A qualitative, exploratory, descriptive and contextual design for theory generation was selected in this study to describe a model to facilitate transformative learning in nursing education. Concept analysis of transformative learning was done in the first stage of the main study using Walker and Avant's eight step approach to clarify the conceptual identification and meaning. The results of concept analysis guided data collection in the second stage. Eleven individual agenda semi-structured interviews were conducted with nurse educators to explore and describe their perceptions regarding how transformative learning can be facilitated in nursing education. Matrix building approach was used to analyse the collected data. The third stage constituted the conceptualisation of findings from the second stage using relevant literature within the elements of practice theory. The fourth stage focused on the description and evaluation of a model to facilitate transformative learning in nursing education. Four themes and nine sub-themes emerged and were conceptualised within the six elements of practice theory namely the context, agent, recipient, dynamic, process and procedure and outcome. The relation statements provided the basis for model description. Reliable method was used to describe and evaluate the model. The refinement of the model by experts in model development and qualitative research was made.


Kinetic study of free fatty acid esterification reaction catalyzed by recoverable and reusable hydrochloric acid.
The catalytic performance and recoverability of several homogeneous acid catalysts (hydrochloric, sulfuric, and nitric acids) for the esterification of enzyme-hydrolyzed free fatty acid (FFA) and methanol were studied. Although all tested catalysts drove the reaction to a high yield, hydrochloric acid was the only catalyst that could be considerably recovered and reused. The kinetics of the esterification reaction catalyzed by hydrochloric acid was investigated under varying catalyst loading (0.1-1M), reaction temperature (303-343K), and methanol/FFA molar ratio (1:1-20:1). In addition, a pseudo-homogeneous kinetic model incorporating the above factors was developed. A good agreement (r(2)=0.98) between the experimental and calculated data was obtained, thus proving the reliability of the model. Furthermore, the reusability of hydrochloric acid in FFA esterification can be predicted by the developed model. The recoverable hydrochloric acid achieved high yields of FFA esterification within five times of reuse.


"Opening up a well of emotions": A qualitative study of men's emotional experiences in the transition to fatherhood.
To explore the emotional changes and reactions men experience in their transition to fatherhood. This study used a qualitative design. Data were collected through in-depth interviews with 13 Norwegian fathers. Through thematic analysis, three main themes were developed: (1) from self-focus to family perspective; (2) emotional vulnerability; and (3) from insecurity to self-assurance. The themes describe fathers' emotional process during the child's first year of life, ranging from positive feelings like affection and mastery, to challenging feelings like exclusion, jealousy and exhaustion. Many fathers describe taboos and shame over their own emotional reactions, although these can be considered a natural part of the postnatal period.


Opening up a tailored tutor qualification program for medical students to other healthcare students - a mixed-method study.
Peer-led tutorials are widely used in medical education to promote practical skills acquisition and support faculty staff. Typically, student tutors are custom trained for this specific task. We investigated whether opening up an existing medical tutor qualification program to other degree programs is successful in terms of acceptance among students, acquisition of tutor-specific and interprofessional competencies, and which factors contribute to success or failure. We developed a two-day tutor qualification program and conducted it annually from 2016 to 2020 with medical and other healthcare students. At the end of each course, we administered a written survey in which the participants rated the following items: their attitudes towards interprofessional learning (using the UWE-IP-D Interprofessional Learning Scale), the interprofessional learning setting, the teaching approach, and their competency acquisition (each on a five-point Likert scale; 1 = strongly agree, 5 = strongly disagree). Furthermore, we assessed participants' qualitative feedback in free-text fields and performed inductive content analyses. The study participation rate was high (response rate 97%; medical students: n = 75; healthcare students: n = 22). Participants stated high levels of competency acquisition (total M = 1.59, individual items' M's ranging from 1.20 to 2.05) and even higher satisfaction with the teaching approach (total M = 1.28, individual items' M's ranging from 1.43 to 1.05). Overall satisfaction with the training was M = 1.22; SD = 0.58. No significant differences in ratings were found between the student groups. The qualitative results showed that students appreciated the interprofessional setting and experienced it as enriching. The most positive feedback was found in didactics/teaching methods on role-plays and group work; most suggestions for improvement were found in the area of structure and organisation on breaks and time management. Opening up an existing medical tutor qualification program to other student groups can be seen as fruitful to teach not only tutor-related aspects but also interprofessional competencies. The results demonstrate the importance of detailed planning that considers group composition and contextual conditions and provides interactive teaching methods to promote interprofessional experiences. This study offers important information about prerequisites and methodological implementation that could be important for the interprofessional redesign of existing training programs.


Hyperactive behaviour of growth differentiation factor- 15 (GDF-15) in conjunction with iron trafficking transporters and suppression of Nrf-2 gene in diabetes and metabolic syndrome.
Multiple parallel factors are frequently interrogated with various toxic radicals which are abundantly generated in the liver, heart, and pancreas in stress conditions. They are actively involved in the development of diabetes and metabolic aberrations. However, whether over-activation of GDF-15mRNA and influxes of iron-by-iron trafficking genes are directly suppressing the Nrf-2 gene in patients with diabetes and metabolic aberrations in context with undiagnosed individuals with diabetes and metabolic aberrations? Therefore, we have investigated inter and intra- related Zip8/14 mRNA, GDF-15mRNA, and Nrf-2 mRNA expressions in diabetes and metabolic syndrome as it is expected to be up to 134 million by 2045 in India. We recruited 120 subjects from the Department of Medicine, Endocrinology and Metabolic Clinic, All India Institute of Medical Sciences, New Delhi, India. Various investigations related to anthropometry, nutritional, hematological, biochemical, cytokine, and oxidative stress were measured in diabetes, metabolic syndrome, diabetes with metabolic aberration, and healthy controls. Relative expression of GDF-15, ZIP8, ZIP14, Nrf-2, and housekeeping genes was done in all subjects. Stress-responsive cytokines are highly expressed in patients with metabolic aberration with respect to body weight, IR, waist circumference, and fat mass. IL-1β, TNF-α, and IL-6 levels were significantly higher in metabolic syndrome, whereas Adiponectin levels were profoundly lower side. MDA levels were significantly raised in diabetes with metabolic syndrome while SOD activities were lowered (p = 0.001). GDF-15 mRNA expression was 1.79-fold upregulated in group III as compared with Group I while 2-threefold down-regulation of Nrf-2 expression was observed in diabetes with metabolic aberration groups. Zip 8 mRNA expressions were downregulated (p = 0.014), and Zip 14 mRNA expressions were upregulated (p = 0.06) in diabetes and metabolic aberrations. The association of GDF-15 and Nrf-2 mRNA expression was found contradictory and highly interlinked with ROS. Zip 8/14mRNA expressions were also dysregulated in diabetes and metabolic-associated complications.


Corrigendum: Identification of novel therapeutic candidates against SARS-CoV-2 infections: An application of RNA sequencing toward mRNA based nanotherapeutics.
[This corrects the article DOI: 10.3389/fmicb.2022.901848.].


Sapling growth and survivorship as affected by light and flooding in a river floodplain forest of southeast Texas.
We investigated the effects of light and flooding on growth and survivorship of saplings in a river floodplain forest of southeast Texas. Growth responses to light were consistent with the expectation that shade-intolerant species grow faster than shade-tolerant species in high light, and vice versa. Mortality risk was not associated with shade tolerance level unless high mortality risks associated with a period of high flooding were removed. These results support the hypothesis that shade-tolerant species in floodplains may be limited by flooding as previous studies suggested. Also, compared to their performance at a nearby mesic site, common species showed little intraspecific difference in shade tolerance, especially for shade-intolerant species. Finally, the positive correlation between low-light growth and survivorship suggests that carbon allocation to continued growth may be favored as a sapling strategy in floodplains.


Mechanism of Siglec-8-induced human eosinophil apoptosis: role of caspases and mitochondrial injury.
Sialic acid binding immunoglobulin like lectin (Siglec)-8 crosslinking with specific antibodies causes human eosinophil apoptosis. Mechanisms by which Siglec-8 crosslinking induces apoptosis are not known. Peripheral blood eosinophils were examined for caspase, mitochondria and reactive oxygen species (ROS) involvement after incubating the cells with anti-Siglec-8 crosslinking Abs or control Abs, in the presence or absence of selective inhibitors. Siglec-8 crosslinking induced rapid cleavage of caspase-3, caspase-8, and caspase-9 in eosinophils. Selective caspase-8 and/or caspase-9 inhibitors inhibited this apoptosis. Siglec-8 crosslinking on eosinophils increased dissipation of mitochondrial membrane potential upstream of caspase activation. Rotenone and antimycin, inhibitors of mitochondrial respiratory chain components, completely inhibited apoptosis. Additional experiments with an inhibitor of ROS, diphenyleneiodonium, demonstrated that ROS was also essential for Siglec-8-mediated apoptosis and preceded Siglec-8-mediated mitochondrial dissipation. These experiments show that Siglec-8-induced apoptosis occurs through the sequential production of ROS, followed by induction of mitochondrial injury and caspase cleavage.


Humanized Mice for the Study of Dengue Disease Pathogenesis: Biological Assays.
Dengue is one of the most prevalent infectious diseases around the world, present in all continents and mainly affecting developing countries. With few tools to fight and study this disease, it is imperative to have reliable animal models that not only recapitulate human disease but also contain human components to understand the pathogenic mechanism and immune responses, allowing the development of new treatments and vaccines against dengue. Humanized mice are a significant advance in the development of in vivo models to understanding the relation of the human immune system and target organs such as the liver during the infection by dengue virus, allowing basic and preclinical research. In this chapter, we describe the use of humanized NSG mice (huNSG) for the study of dengue disease. The first model describes reconstitution of the human immune system by transplanting human CD34+ stem cells in newborn or adult NSG mice. The second model combines the reconstitution with CD34+ stem cells with the transplant of human primary hepatocytes. This dual reconstituted animal will have two of the major players involved in the development of dengue infection. However, there are still more biological components missing in this model for dengue, but researchers continue working to improve the huNSG model to reconstitute other human components.


A novel strategy of gene screen based on multi-omics in Streptomyces roseosporus.
Daptomycin is a new lipopeptide antibiotic for treatment of severe infection caused by multi-drug-resistant bacteria, but its production cost remains high currently. Thus, it is very important to improve the fermentation ability of the daptomycin producer Streptomyces roseosporus. Here, we found that the deletion of proteasome in S. roseosporus would result in the loss of ability to produce daptomycin. Therefore, transcriptome and 4D label-free proteome analyses of the proteasome mutant (Δprc) and wild type were carried out, showing 457 differential genes. Further, five genes were screened by integrated crotonylation omics analysis. Among them, two genes (orf04750/orf05959) could significantly promote the daptomycin synthesis by overexpression, and the fermentation yield in shake flask increased by 54% and 76.7%, respectively. By enhancing the crotonylation modification via lysine site mutation (K-Q), the daptomycin production in shake flask was finally increased by 98.8% and 206.3%, respectively. This result proved that the crotonylation modification of appropriate proteins could effectively modulate daptomycin biosynthesis. In summary, we established a novel strategy of gene screen for antibiotic biosynthesis process, which is more convenient than the previous screening method based on pathway-specific regulators. KEY POINTS: • Δprc strain has lost the ability of daptomycin production • Five genes were screened by multi-omics analysis • Two genes (orf04750/orf05959) could promote the daptomycin synthesis by overexpression.


The virtual classroom and Ebola preparedness.
A hospital in Sierra Leone has collaborated in the development of computer-based training for Ebola management. Clare Sansom reports.


Verification of in-treatment tumor position using kilovoltage cone-beam computed tomography: a preliminary study.
Three-dimensional tumor position during rotational dose delivery was evaluated by acquiring in-treatment kilovoltage (kV) cone-beam CT (CBCT) to ensure treatment quality. The CBCT projection data of a phantom were acquired during rotational megavoltage (MV) dose delivery up to 6 Gy to evaluate image quality under MV beam irradiation. A lung tumor patient was treated with a total dose of 48 Gy in four fractions, each fraction including seven coplanar and noncoplanar beams, as well as a full-angle rotational beam. Tumor registration was performed between a planning CT image and a CBCT image immediately after patient setup. The patient couch was adjusted according to the registration results, and then the registration was repeated three times: immediately before treatment, during treatment, and immediately after treatment. The phantom image quality of the kV CBCT was not visually degraded up to the rotational MV dose of 6 Gy. Tumor position during rotational dose delivery was verified for the first time using kV CBCT.


Whole-transcriptome profiles of Chrysanthemum seticuspe improve genome annotation and shed new light on mRNA-miRNA-lncRNA networks in ray florets and disc florets.
Chrysanthemum seticuspe has emerged as a model plant species of cultivated chrysanthemums, especially for studies involving diploid and self-compatible pure lines (Gojo-0). Its genome was sequenced and assembled into chromosomes. However, the genome annotation of C. seticuspe still needs to be improved to elucidate the complex regulatory networks in this species. In addition to the 74,259 mRNAs annotated in the C. seticuspe genome, we identified 18,265 novel mRNAs, 51,425 novel lncRNAs, 501 novel miRNAs and 22,065 novel siRNAs. Two C-class genes and YABBY family genes were highly expressed in disc florets, while B-class genes were highly expressed in ray florets. A WGCNA was performed to identify the hub lncRNAs and mRNAs in ray floret- and disc floret-specific modules, and CDM19, BBX22, HTH, HSP70 and several lncRNAs were identified. ceRNA and lncNAT networks related to flower development were also constructed, and we found a latent functional lncNAT-mRNA combination, LXLOC_026470 and MIF2. The annotations of mRNAs, lncRNAs and small RNAs in the C. seticuspe genome have been improved. The expression profiles of flower development-related genes, ceRNA networks and lncNAT networks were identified, laying a foundation for elucidating the regulatory mechanisms underlying disc floret and ray floret formation.


Potential application of synchronous fluorescence spectroscopy to determine benzo[a]pyrene in soil extracts.
Benzo[a]pyrene (BaP) is a significant environmental pollutant and rapid, accurate methods to quantify this compound in soil for both research and environmental investigation purposes are required. In this work, solvent extracts from five contrasting soils spiked with four different polycyclic aromatic hydrocarbons (PAHs) were rapidly analysed by using a synchronous fluorescence spectroscopy (SFS) method. The SFS method was validated using HPLC with ultraviolet detection. A good correlation for the quantification of BaP in soil extracts by the two methods was observed. The detection limit of the SFS method was 1.6 x 10(-9) g/ml in CTAB micellar medium (7.8 mmol/l). The work demonstrates that SFS has potential as a sensitive, accurate, rapid, simple and economic methodology and an efficient alternative to HPLC for fast confirmation and quantification of BaP in complex soil extracts.


Stimulation of D1- or D2-receptors in drug-naive rats with different degrees of unilateral nigro-striatal dopamine lesions.
We had previously found that in animals with moderate nigro-striatal dopamine (DA) lesions (i.e. 45-65% residual neostriatal DA) the mixed D1/D2-agonist apomorphine induced ipsiversive rather than the usual contraversive turning found after more radical DA lesions. Since this result promised to provide a behavioral animal model for pre-clinical Parkinson's disease, we hoped to delineate the responsible receptor by challenging with selective D1- and D2-agonists. Thus, in the present study, the behavioral effects of the D1-agonist SKF38393 (5.0 mg/kg) and the D2-agonist LY171555 (0.5 mg/kg) were tested in drug-naive rats with unilateral 6-hydroxydopamine lesions of the nigro-striatal DA system. This analysis was performed dependent on the degree of the lesion, classified post-mortem with respect to the level of residual DA in the neostriatum: < 20%, 20-45%, 45-65%, and > 65% (as percentage of the intact hemisphere). The measures of turning, thigmotactic scanning and locomotion did not yield differences between animals treated with the D1-agonist and vehicle-treated rats. For example, animals with severe lesions (residual DA < 20%) showed ipsiversive asymmetries in turning and scanning, which were similar after vehicle or the D1-agonist, both with respect to degree and time-course. However, the analysis of grooming behavior, which was performed in a subset of animals with moderate lesions yielded differences between vehicle and the D1-agonist, since the duration of grooming was increased after SKF38393. In contrast to the D1-agonist, behavioral effects after the D2-agonist LY17155 were evident in all behavioral measures. The general response to this agonist could be characterized by a rapid decrease of behavioral activity including turning, scanning, locomotion and grooming. Although we failed to find significant behavioral asymmetries with either agonist, a micro-analysis showed evidence for selective effects after the D2-agonist, since a contraversive asymmetry in turning (and scanning) became apparent between 45 and 60 min after injection in animals with severe lesions (residual DA of about 10% or less), and since there was a weak ipsiversive turning asymmetry in animals with residual DA levels of 45-65%. Such asymmetries were not observed after vehicle or the D1-agonist. The possible physiological mechanisms of these effects, i.e. DA receptor mechanisms and DA availability, are discussed in the context of results from previous experiments using lesioned or intact animals.


Photoperiodic regulation of vasopressin receptor binding in female Syrian hamsters.
During long "summer-like" photoperiods, female Syrian hamsters display a regular 4-day estrous cycle. However, during short "winter-like" photoperiods (<12.5 h of light/day) hamsters become anestrus. Short photoperiod exposure eliminates reproductive behavior but social behaviors such as aggression and scent marking continue to be displayed. In long photoperiods, the types and intensity of social behaviors change as a function of the estrous cycle. For example, aggression and scent marking tend to occur at higher levels on diestrus 1 and diestrus 2 than on proestrus or estrus. Aggression and scent marking may be regulated, at least in part, by changes in the density of arginine vasopressin-V(1a) receptors (V(1a)R). In Experiment 1, it was hypothesized that the density of V(1a)R would change across the estrous cycle in several subcortical regions implicated in the regulation of aggression and scent marking. In Experiment 2, it was hypothesized that exposure to short photoperiod would alter the density of V(1a)R in several regions involved in the regulation of social behavior. Interestingly, there were no dramatic changes in V(1a)R binding across the estrous cycle within any of the neuroanatomical areas measured. However, in hamsters housed in short photoperiod, there were lower levels of V(1a)R binding within the medial preoptic nucleus (MPN), medial preoptic area (MPO), lateral hypothalamus (LH), central nucleus of the amygdala (Ce) and bed nucleus of the stria terminalis (BST) than in hamsters housed in long photoperiod. These data suggest that photoperiodic mechanisms can alter the density of V(1a)R in subset of V(1a) binding sites thought to be involved in the regulation of social behaviors in female hamsters.


Infraorbital Hyaluronic Acid Filler: Common Aesthetic Side Effects With Treatment and Prevention Options.
Infraorbital hollows can give a fatigued or aged appearance, which can be treated by volumizing the segmented transition from the tear trough to the cheek with hyaluronic acid filler. Due to thin skin and the complex anatomy of the infraorbital area, both short- and long-term side effects (SEs) from this treatment are very common. While some patients are clear surgical candidates vs filler candidates, in real-world practice, many, if not most, patients are on a continuum where either procedure is appropriate, and the treatment decision is individualized based on each person's risk vs benefit profile. Common aesthetic SEs from hyaluronic acid filler treatment in the infraorbital area will be reviewed, including their etiology, prevention, detection, and treatment. The author's experience from injecting the infraorbital areas of more than 800 patients in private clinical practice and observations from both short- and long-term follow-ups over 8 years is leveraged to provide detailed guidance. Recommendations on injection techniques, patient selection, and patient education are presented along with algorithms for the prevention and management of bruising, short- and long-term swelling, bumps, and blue discoloration (which is usually secondary to swelling from the filler rather than just the filler alone placed or migrating too superficially). For nearly all patients, complete dissolution of filler with hyaluronidase is not required to address the issue, and the guidelines provided here will assist clinicians in the management of SEs to increase patient satisfaction with their treatment and aesthetic outcome.


Severe cerebral abscess associated with pulmonary arteriovenous fistula: case report and literature review.
A rare case of cerebral abscess concurrent with pulmonary arteriovenous fistula (PAVF), hyperhemoglobinemia, and hypoxemia was reported. A 37-year-old man was admitted with a headache, nausea, vomiting, fever, and numbness of the left cheek and upper limb for 10 days. Cerebral magnetic resonance imaging (MRI) shows the lesion in his right frontal lobe. Blood gas analysis indicated lower blood oxygen saturation level, and blood routine test showed hemoglobin elevation. Craniotomy for the lesion and decompressive craniotomy were performed. Brain abscess was confirmed by pathology examination. The chest computed tomography angiography (CTA) revealed a pulmonary arteriovenous fistula (PAVF) in his right lower lung. After 1 month, embolization of PAVF was performed. Anoxic symptom improved after surgery. Cranioplasty was performed after 7 months. The author reported a rare case of cerebral abscess associated with pulmonary arteriovenous fistula. Brain abscess, hyperhemoglobinemia, and hypoxemia might be secondary to PAVF. Treatment of patients includes not only craniotomy for abscess removal but also embolization of PAVF which can prevent recurrence of brain abscess.


Positive feedback loops between fibroblasts and the mechanical environment contribute to dermal fibrosis.
Dermal fibrosis is characterized by excessive deposition of extracellular matrix in the dermis and affects millions of people worldwide and causes limited movement, disfigurement and psychological distress in patients. Fibroblast dysfunction of plays a central role in the pathogenesis of dermal fibrosis and is controlled by distinct factors. Recent studies support the hypothesis that fibroblasts can drive matrix deposition and stiffening, which in turn can exacerbate the functional dysregulation of fibroblasts. Ultimately, through a positive feedback loop, uncontrolled pathological fibrosis develops. This review aims to summarize the phenomenon and mechanism of the positive feedback loop in dermal fibrosis, and discuss potential therapeutic targets to help further elucidate the pathogenesis of dermal fibrosis and develop therapeutic strategies. In this review, fibroblast-derived compositional and structural changes in the ECM that lead to altered mechanical properties are briefly discussed. We focus on the mechanisms by which mechanical cues participate in dermal fibrosis progression. The mechanosensors discussed in the review include integrins, DDRs, proteoglycans, and mechanosensitive ion channels. The FAK, ERK, Akt, and Rho pathways, as well as transcription factors, including MRTF and YAP/TAZ, are also discussed. In addition, we describe stiffness-induced biological changes in the ECM on fibroblasts that contribute to the formation of a positive feedback loop. Finally, we discuss therapeutic strategies to treat the vicious cycle and present important suggestions for researchers conducting in-depth research.


Vaginal progesterone for contraception.
Silastic vaginal rings impregnated with progesterone (P) or progesterone and estradiol (E) were used in nine women for thirty 21-day cycles to study the effect on ovarian function. The average daily rates of release of P and E from the rings were 2.2 mg/day and 220 microgram/day, respectively. In anovulatory treatment cycles the mean plasma level of P was 0.9 ng/ml. E levels fluctuated in the range seen in normally cycling women due to endogenous E production. In a menopausal woman the E levels increased to 50 to 100 pg/ml during treatment and FSH levels declined. Ovulation occurred in 18 (60%) of the treated cycles, and resulted in one pregnancy. Although the results rule out the use of these rings for contraceptive purposes, they indicate that at higher dosages the Silastic vaginal ring offers a mode of administration of natural steroids to be used in hormonal contraception.


Pumping iron: a potential target for novel therapeutics against schistosomes.
Parasites, as with the vast majority of organisms, are dependent on iron. Pathogens must compete directly with the host for this essential trace metal, which is sequestered within host proteins and inorganic chelates. Not surprisingly, pathogenic prokaryotes and eukaryotic parasites have diverse adaptations to exploit host iron resources. How pathogenic bacteria scavenge host iron is well characterized and is reasonably well known for a few parasitic protozoa, but is poorly understood for metazoan parasites. Strategies of iron acquisition by schistosomes are examined here, with emphasis on possible mechanisms of iron absorption from host serum iron transporters or from digested haem. Elucidation of these metabolic mechanisms could lead to the development of new interventions for the control of schistosomiasis and other helminth diseases.


In situ and real-time monitoring of mechanochemical milling reactions using synchrotron X-ray diffraction.
We describe the only currently available protocol for in situ, real-time monitoring of mechanochemical reactions and intermediates by X-ray powder diffraction. Although mechanochemical reactions (inducing transformations by mechanical forces such as grinding and milling) are normally performed in commercially available milling assemblies, such equipment does not permit direct reaction monitoring. We now describe the design and in-house modification of milling equipment that allows the reaction jars of the operating mill to be placed in the path of a high-energy (∼90 keV) synchrotron X-ray beam while the reaction is taking place. Resulting data are analyzed using conventional software, such as TOPAS. Reaction intermediates and products are identified using the Cambridge Structural Database or Inorganic Crystal Structure Database. Reactions are analyzed by fitting the time-resolved diffractograms using structureless Pawley refinement for crystalline phases that are not fully structurally characterized (such as porous frameworks with disordered guests), or the Rietveld method for solids with fully determined crystal structures (metal oxides, coordination polymers).


phoH-carrying virus communities responded to multiple factors and their correlation network with prokaryotes in sediments along Bohai Sea, Yellow Sea, and East China Sea in China.
Viruses carrying phoH genes are an important functional group that may boost phosphate metabolism of their prokaryote hosts and affect phosphorus cycle in the ocean. However, at present, very little is known about the phoH-carrying viruses' community structure and diversity in marine sediments, as well as their correlation network with prokaryotes and environment. Here, via a large spatial scale investigation along the Bohai Sea, Yellow Sea, and East China Sea, for the first time, diverse unknown benthic phoH-carrying viruses were uncovered, which were mainly affiliated to three clusters. Interestingly, these viruses presented a very distinct community structure compared to those in seawaters. Correlation network analysis implied that these viruses might mainly infect the prokaryotes of Gamm-/Delta-proteobacteria, Thaumarchaeota, and Cyanobacteria in sediments. Distinct virus-prokaryote correlation network modules were shown in different sea areas. These modules' highly nested feature implied their coevolution with prokaryotes during long-term arms race. Their distribution in sediments was influenced by multiple factors including geographic separation and the key environmental variables of total organic carbon and total phosphorus, and responded to terrestrial inputs and coastal aquaculture activities. The results of this study provide novel insights into the benthic virus communities potentially participating in phosphorus cycling in the ocean.


Validation of a Prediction Score for Drug-Resistant Microorganisms in Community-acquired Pneumonia.
Rationale: Recommended initial empiric antimicrobial treatment covers the most common bacterial pathogens; however, community-acquired pneumonia (CAP) may be caused by microorganisms not targeted by this treatment. Developed in 2015, the PES (Pseudomonas aeruginosa, extended-spectrum β-lactamase-producing Enterobacteriaceae, and methicillin-resistant Staphylococcus aureus) score was developed in 2015 to predict the microbiological etiology of CAP caused by PES microorganisms.Objective: To validate the usefulness of the PES score for predicting PES microorganisms in two cohorts of patients with CAP from Valencia and Mataró.Methods: We analyzed two prospective observational cohorts of patients with CAP from Valencia and Mataró. Patients in the Mataró cohort were all admitted to an intensive care unit (ICU).Results: Of the 1,024 patients in the Valencia cohort, 505 (51%) had a microbiological etiology and 31 (6%) had a PES microorganism isolated. The area under the receiver operating characteristic curve was 0.81 (95% confidence interval [95% CI], 0.74-0.88). For a PES score ≥5, sensitivity, specificity, the negative and positive predictive values as well as the negative and positive likelihood ratios were 72%, 74%, 98%, 14%, 0.38, and 2.75, respectively. Of the 299 patients in the Mataró cohort, 213 (71%) had a microbiological etiology and 11 (5%) had a PES microorganism isolated. The area under the receiver operating characteristic curve was 0.73 (95% CI 0.61-0.86). For a PES score ≥ 5, sensitivity, specificity, the negative and positive predictive values, and the negative and positive likelihood ratios were 36%, 83%, 96%, 11%, 0.77, and 2.09, respectively. The best cutoff for patients admitted to the ICU was 4 points, which improved sensitivity to 86%. The hypothetical application of the PES score showed high rates of overtreatment in both cohorts (26% and 35%, respectively) and similar rates of undertreatment.Conclusions: The PES score showed good accuracy in predicting the risk for microorganisms that required different empirical therapy; however, its use as a single strategy for detecting noncore pathogens could lead to high rates of overtreatment. Given its high negative predictive value, the PES score may be used as a first step of a wider strategy that includes subsequent advanced diagnostic tests.


Elongation of fetal chick long bone in vitro is formed by a mitogenic activity preparation from porcine bone.
Elongation of fetal chick long bone rudiments is formed by a mitogenic activity from porcine bone in vitro. Fractions of mitogenic activity from a heat- and acid-treated extract and from sequential chromatography on hydroxyapatite and from gel-filtration in 4 M guanidine-HCl increase diaphyseal elongation of metatarsals. The bone elongation-forming activity is associated with the mitogenic activity estimated by the incorporation of [3H]-methyl thymidine into the DNA of cells from embryonic chick periosteum. Histological examination of the mitogen-treated embryonic chick long bone shows that the partially purified fractions with a preferential effect on osteogenic cells increase diaphyseal elongation via cartilage cell proliferation.


Disseminated intravascular coagulation following air embolism during orthotropic liver transplantation: is this just a coincidence?
During orthotopic liver transplantation, venous air embolism may occur due to iatrogenic injury of the inferior vena cava. However, venous air embolism followed by coagulopathy is a rare event. In this case report, we discuss a possible connection between venous air embolism and disseminated intravascular coagulation. A 37-year-old male patient with chronic hepatitis B- and C-induced liver cirrhosis was admitted for orthotopic liver transplantation. During the dissection phase of the surgery, arterial blood pressure, heart rate, saturation and end-tidal carbon dioxide levels suddenly decreased, indicating the occurrence of venous air embolism. After stabilizing the patient's condition, various coagulation issues started developing. Venous air embolism-induced coagulopathy was handled by administering transfusions of various blood products. However, the patient's condition continued to deteriorate leading to a complete asystole. This is a rare case of venous air embolism-induced disseminated intravascular coagulation. The real connection remains unclear as disseminated intravascular coagulation for end-stage liver disease patients can be induced by various causes during different stages of liver transplantation. Certainly, both venous air embolism and coagulopathy were significant and led to an unfavorable outcome. Further studies are needed to better understand the possible mechanisms and correlation between these two life-threatening complications.


Reactivation and aging of phosphorylated brain acetylcholinesterase from fish and rodents.
Species-related differences in sensitivity to acute intoxication by anticholinesterase compounds have been attributed, in large part, to differences in the kinetics of inhibition of acetylcholinesterase (AChE) in vitro. Since inhibition of AchE is also influenced by the stability of the phosphorylated enzyme complex, it was of interest to compare the rates at which the inhibited enzyme from different species subsequently either reactivates or ages. Brain AChE from rats, mice, fathead minnows, or rainbow trout was preincubated with an IC90 concentration of either paraoxon or malaoxon. The first-order rate constants for both the reactivation and aging of paraoxon-inhibited AChE from rats and mice were significantly greater than those observed for either species of fish. Following malaoxon inhibition, however, rodent AChE reactivated more rapidly but aged more slowly than did the enzyme from minnows. Therefore, the data suggest that compared to rodents, intermittent or continuous exposure of fish to sublethal concentrations of anticholinesterase compounds is more likely to result in a cumulative toxicity owing to the relative irreversibility of AChE inhibition.


[Reaction time and Békésy audiometry (author's transl)].
Electrophysiological work has elaborated that subjects having positive recruitment exhibit shorter response latencies than non-recruiting subjects do. Correspondingly we have investigated in this paper, if subjectively measured reaction times also decrease in case of recruiting subjects. Our measurements have shown that the averaged reaction time (at 4 kHz) of recruiting subjects is significantly (p = 0.05) shorter than the value of a non-recruiting group. Because of the interindividual scattering of the results, however, measuring of reaction time ist not suitable to distinguish subjects with loudness recruitment from those having no recruitment. Comparison of reaction time and Békésy audiogram as recruitment test shows Békésy tracing to be more reliable. Finally the number of oscillations (N) per octave in Békésy tracing is discussed as a function of oscillation width (W). A general mathematical representation of this correlation is given by N = a.Wb. Constants a and b, depending on attenuation rate (2.5 dB/s) and frequency change rate (1 oct./min), are evaluated by statistical and graphical methods (a = 36.08, b = -0.71).


Alcohol tolerance in a cholinergic nerve terminal: relation to the membrane expansion-fluidization theory of ethanol action.
Phrenic nerve terminals from rats subjected to long-term ethanol treatment were more resistant to ethanol (in vitro) than terminals from sucrose-fed rats, as measured by the effect of ethanol on the frequency of miniature end plate potentials. Long-term ethanol exposure may thus induce the synthesis of more rigid membrane lipids, reducing membrane "fluidizability". This may provide a neurocellular basis for ethanol tolerance and cross-tolerance with anesthetics and barbiturates.


Bismuth-213 radioimmunotherapy with C595 anti-MUC1 monoclonal antibody in an ovarian cancer ascites model.
Control of ovarian cancer (OC) ascites remains a major objective in post-surgical treatment. The aim of this study was to investigate the effect of targeted alpha therapy (TAT) for the control of ascites in an OC ascites mouse model; the biodistribution of (213)Bi-C595 and its long term toxicity. The expression of tumor-associated antigen mucin-1 (MUC-1) in OVCAR3 ascites cells in mice and OC cancer tissues in patients was detected by indirect immmunostaining. The monoclonal antibody (MAb) C595 was labeled with (213)Bi using the chelator cDTPA to form the alpha-immunoconjugate (AIC). Mice were injected with different concentrations of AIC by i.p administration. Changes in tumor progression were assessed by measurement of the circumference of the abdomen. MUC-1 is strongly expressed in 73% of OC tissues. At 9 days post-cell inoculation in mice, a single injection of 355 MBq/kg of (213)Bi-C595 can prolong survival by 25 days. A high tumor: blood ratio (5.8) was found in biodistribution study. The maximum tolerance dose (MTD) was more than 1180 MBq/kg up to 21 weeks. C595 is a specific targeting vector for ovarian cancer cells, which show a high percentage of expression of MUC1. (213)Bi-C595 can effectively target and kill ovarian cancer cells in vitro and in vivo. (213)Bi-C595 is the recommended alpha conjugate for a Phase I clinical trial for ovarian cancer.


Effect of moisture on H(2)S adsorption by copper impregnated activated carbon.
The aim of this study is to investigate the effect of moisture on adsorption efficiency of hydrogen sulfide (H(2)S) by impregnated activated carbon (IAC). Copper(II) nitrate was used as an impregnant. Two humidification conditions of IAC, pre-moistened and gas stream containing moisture, were studied. The experimental results revealed that the copper species onto the IAC was suggested to be Cu(OH)(2) that deposited on activated carbon during the impregnation process. The adsorption mechanism of H(2)S by copper impregnated IAC was proposed, involving physic-sorption and chemical reactions. Moreover, the H(2)S breakthrough capacity decreased with increasing the relative humidity of gas stream. The causes were attributed to three points as follow: the competition adsorption occurred between moisture and H(2)S; the copper(II) species reduced to copper(I) species leading to IAC deactivation; and the rate of chemical reaction restrained by moisture.


Cytotoxic lymphocytes generated in vivo with acute measles virus infection.
We studied the generation of cytotoxic lymphocytes in adults during an outbreak of acute measles virus infection. Nine patients were studied determining in particular whether virus-specific cytotoxic T lymphocytes could be directly detected in peripheral blood during this acute infection. The cytotoxicity of PBL was assayed against measles virus-infected and uninfected phytohemagglutinin-induced blast cells of matched and mismatched HLA, A, B, and C types, in a standard 4-h 51Cr release assay. There was greater cytotoxicity against measles virus-infected than uninfected target cells in at least one sample from every patient. In 4 patients this preferential lysis of virus infected cells was greater (a difference of more than 10% virus-specific lysis) against HLA-matched than mismatched targets. This preference for HLA A and B matched infected target cells was also clearly seen when the effector PBL were depleted of FC receptor bearing cells. The other 5 subjects exhibited no evidence of preferential lysis of HLA-matched measles virus-infected cells. All 9 patients limited the spread of measles virus infection and recovered equally from the acute infection. These studies provide some evidence to suggest that MHC-restricted virus-specific CTL are detectable in human peripheral blood during acute measles virus infection, albeit only with low frequency, but are not necessarily associated with recovery from disease.


The transport of dimer-X to the subarachnoid cisterns and convexity of the brain in normal people: case reports.
Computerized axial tomographic scans were performed on 7 patients, 3, 8 and 20 hours after lumbar myelography with Dimer-X. This contrast agent was seen in the subarachnoid cisterns 3 and 8 hours after injection, and 24 hours after injection it had completely disappeared.


Atopy in people aged 40 years and over: Relation to airflow limitation.
Previous studies have reached conflicting conclusions about the role of atopy as a risk factor for COPD. In part, this is attributable to variation in the definitions of airflow limitation and the treatment of people with asthma. To establish whether there is any independent association between atopy and post-bronchodilator airflow limitation in the general population aged 40 years and over. A cross-sectional survey was conducted in a general population sample of 2415 people aged 40 years and over in Australia. A history of ever being diagnosed with asthma was elicited by questionnaire. Atopy was defined as any skin prick test weal to common aeroallergens ≥4 mm. Airflow limitation was defined as post-bronchodilator spirometric (FEV1 /FVC) ratio <lower limit of normal. Analyses were adjusted for potential confounding due to age, sex, smoking, race and socio-economic status. The prevalence of atopy, ever diagnosed asthma and post-bronchodilator airflow obstruction was 44.8%, 19.3% and 7.5%, respectively. In the population as a whole, atopy was associated with lower FEV₁ (adjusted difference -0.068L, 95% confidence interval (CI) -0.104 to -0.032), FVC (adj. difference -0.043L, 95% CI -0.086 to -0.0009) and post-bronchodilator FEV₁/FVC ratio (adj. difference -0.011, 95% CI -0.017 to -0.0055). The effect of atopy on lung function was no longer apparent when participants who reported ever diagnosed asthma were excluded (FEV₁ -0.011L, [95% CI -0.05 to 0.028L], FVC -0.012L [95% CI -0.060 to 0.036] and FEV₁/FVC ratio -0.0012 [95% CI -0.0072 to 0.0047L]). The apparent association between atopy and post-bronchodilator airflow limitation in the general population appears to be explained by the association between atopy and having ever diagnosed asthma and the effect of asthma on lung function.


Direct assay for testosterone in saliva: relationship with a direct serum free testosterone assay.
A direct non-extraction radioimmunoassay for salivary testosterone is described using a modified commercial kit procedure that is in use for total serum testosterone (T). Serum free testosterone was also measured by direct radioimmunoassay. A significant correlation (r = 0.83, p less than 0.01, n = 194) was obtained between salivary and serum free testosterone in matched serum and saliva samples over a wide range of concentrations. Within- and between-batch precision for the salivary testosterone method was 11% and 18%, respectively at a concentration of 170 pmol/l. Recovery of added T was 89% +/- 15% (mean +/- 2 SD) dilution of high samples showed parallelism. Salivary testosterone measured by direct radioimmunoassay offers a simple cheaper alternative to serum free testosterone measurement with the additional advantages of a stress-free non-invasive sampling procedure.


Evaluation of the Efficacy and Safety of a Compound of Micronized Flavonoids in Combination With Vitamin C and Extracts of Centella asiatica, Vaccinium myrtillus, and Vitis vinifera for the Reduction of Hemorrhoidal Symptoms in Patients With Grade II and III Hemorrhoidal Disease: A Retrospective Real-Life Study.
Background and Aim: Several evidences have shown how, in hemorrhoidal disease, phlebotonic flavonoid agents such as quercetin reduce capillary permeability by increasing vascular walls resistance, how rutin and vitamin C have antioxidant properties, and that Centella asiatica has reparative properties towards the connective tissue. A retrospective study was designed in order to evaluate the efficacy and safety of a compound consisting of micronized flavonoids in combination with vitamin C and extracts of C. asiatica, Vaccinium myrtillus, and Vitis vinifera for grade II and III hemorrhoidal disease. Patients and Methods: Data of 49 patients, over 18, who were following a free diet regimen, not on therapy with other anti-hemorrhoid agents, treated with a compound consisting of 450 mg of micronized diosmin, 300 mg of C. asiatica, 270 mg of micronized hesperidin, 200 mg of V. vinifera, 160 mg of vitamin C, 160 mg of V. myrtillus, 140 mg of micronized quercetin, and 130 mg of micronized rutin (1 sachet or 2 tablets a day) for 7 days were collected. Hemorrhoid grade according to Goligher's scale together with anorectal symptoms (edema, prolapse, itching, thrombosis, burning, pain, tenesmus, and bleeding) both before treatment (T0) and after 7 days of therapy (T7) were collected. Primary outcomes were the reduction of at least one degree of hemorrhoids according to Goligher's scale assessed by proctological examination and compound safety. The secondary outcome was the reduction of anorectal symptoms assessed by questionnaires administered to patients. Results: Forty-four patients (89.8%) presented a reduction in hemorrhoidal grade of at least one grade (p < 0.001). No adverse events with the use of the compound were noted. A significant reduction was observed in all anorectal symptoms evaluated (p < 0.05). No predictors of response to the compound were identified among the clinical and demographic variables collected. Conclusion: The compound analyzed was effective and safe for patients with grade II and III hemorrhoidal disease according to Goligher's scale.


Design and synthesis of SH3 domain binding ligands: modifications of the consensus sequence XPpXP.
Spirolactam-based Pro-Pro mimetics incorporated in the consensus sequence XPpXP, lead to effective nonpeptide ligands of SH3 domains.


[Primary pancreatic tuberculosis in an immunocompetent patient: first case report in Spain].
Primary pancreatic tuberculosis (PPTB) is an extremely rare entity defined by an isolated pancreatic lesion with microbiological confirmation, in the absence of previously identified tuberculosis (TB) and involvement of any other organ. We report the case of a 47-year-old man referred for abdominal pain and weight loss, in whom several imaging techniques revealed a solid mass in the head of the pancreas. CT-guided fine-needle aspiration cytology was consistent with necrotic granuloma. Intradermic tuberculin reaction was positive, but acid fast bacilli staining was negative in repeat cytology. No additional evidence of TB was found after exhaustive diagnostic work-up. Exploratory laparotomy was proposed for a definitive diagnosis, but cultures grew Mycobacterium tuberculosis at 50 days. The pancreatic lesion disappeared after 4 months of antitubercular therapy. This is the first case report of PPTB in an immunocompetent person in Spain. A high index of suspicion and accurate samples for microbiology are mandatory to avoid unnecessary surgical procedures.


Detailed study of the distribution of activation inside the magnet coils of a compact PET cyclotron.
We determined the distribution of activation products inside the magnet coils of a medical cyclotron that has been operational for fifteen years. Besides FLUKA, we based our approach on new software tools (RAW and ActiWiz) developed for high-energy accelerators at CERN. A combined analysis of measurements on the coils with Monte-Carlo simulations resulted in a detailed three-dimensional radiological characterisation of the coils. Our results provide the required information for the radiation protection expert to identify the appropriate waste elimination scheme.