Multicenter Population Pharmacokinetics and Exposure-Efficacy Analysis of Pirfenidone in Patients with Idiopathic Pulmonary Fibrosis.
Pirfenidone is an antifibrotic agent that has been proven to slow down the progression of idiopathic pulmonary fibrosis (IPF). This study aimed to characterize the population pharmacokinetics (PK) and exposure-efficacy analysis of pirfenidone in patients with IPF. Data from 10 hospitals with 106 patients were used to develop a population PK model. The annual decline in forced vital capacity (FVC) over 52 weeks was integrated with pirfenidone plasma concentration to characterize the exposure-efficacy relationship. A linear one-compartment model with first-order absorption and elimination processes and lag time best described the pirfenidone PK. The population estimates of clearance and central volume of distribution at steady-state were 13.37 L/h and 53.62 L, respectively. Bodyweight and food were statistically correlated with PK variability but had no significant influence on pirfenidone exposure. Annual decline in FVC with pirfenidone plasma concentration was described by a maximum drug effect (Emax) model. The typical EC50 was 1.73 mg/L (1.18-2.31 mg/L) and the corresponding EC80 was 2.18 mg/L (1.49-2.87 mg/L). Simulations showed that two dosing regimens of 500 and 600 mg three times daily were predicted to generate 80% of the Emax. In patients with IPF, covariates such as bodyweight and food might not be sufficient for dose adjustment, and a low dose of 1500 mg/day could also provide 80% of the Emax, as the standard dose (1800 mg/day).


Identifying Posterior Fossa Abnormality in Pediatric Aerodigestive Patients, a Case Series.
Multidisciplinary clinics like Aerodigestive programs focus on issues associated with airway, pulmonary, and gastrointestinal issues. Rarely, significant neurological issues like posterior fossa abnormality are identified as the primary etiology. We describe 3 such patients and compare their clinical presentation to the other patients seen in Aerodigestive clinic. A retrospective chart review was conducted to review the 3 posterior fossa patients and the remainder of children that were referred to the Aerodigestive Clinic at Children's Hospital Los Angeles from June 2016 to August 2018. Clinical characteristics including triple endoscopies and sleep studies were recorded. Of the 110 patients included for review, 3 patients (3%) had an underlying posterior fossa abnormality; all of whom had symptoms of sleep disordered breathing along with dysphagia compared with 30% incidence of this symptom profile in the remaining Aerodigestive population. Presence of sleep disordered breathing and dysphagia, with underlying vomiting history, warrants considering evaluation for posterior fossa abnormalities in addition to traditional workup for aerodigestive disorders. Due to the rarity of this presentation and small sample size, future studies with multicenter collaboration may help better describe identifiers to delineate this population with similar aerodigestive symptoms and clarify diagnostic algorithms.


Postpartum onset of panic disorder: a coincidental event?
This study investigated whether the onset of panic for the first time during the postpartum period represented a coincidental occurrence. Sixty-four childbearing women diagnosed with panic disorder who had been treated at the Yale Anxiety Research Clinic were interviewed. Postpartum panic was defined as the first panic occurring within 12 weeks of the woman's first childbirth. Seven women (10.9%) met criteria for postpartum onset, which is significantly greater than the expected age-corrected percentage of 0.92%, Z = 2.29, p < .02. The onset of panic in the first postpartum period is not a coincidental event.


Association between denture use and food form in older adults requiring long-term care: A multicenter cross-sectional study.
This study aimed to determine whether denture use contributes to maintaining and improving food forms in long-term care facility (LTCFs) residents. In 888 residents of 37 LTCFs in Japan, the following were investigated: nutritional intake status, food forms, age, sex, Barthel index (BI), clinical dementia rating (CDR), number of teeth present, number of occlusal supports, swallowing function, and use of dentures. Among all residents, those who were well-nourished and had ≤9 occlusal supports were analyzed. Based on standardized criteria, the food forms consumed by the subjects were divided into two groups: dysphagia and normal diet, which were further classified into four levels. Analysis was performed using a generalized estimation equation with the four levels of food forms as dependent variables and age, sex, BI, CDR, presence of dysphagia, number of teeth present, and use of dentures as independent variables. The final analysis included 622 (70.0%) residents. Of these, 380 (61.1%) used dentures. The analyses revealed that food form was significantly associated with age (adjusted odds ratio [OR], 0.98), BI (OR, 1.04), number of teeth present (OR, 1.03), presence of dysphagia (OR, 0.44), and use of dentures (OR, 2.82). Denture use was associated with food forms among Japanese LTCF residents. This indicates that the use of dentures is related to the maintenance of food forms, even in the elderly who participate in few activities of daily living, have reduced cognitive function, and require long-term care.


The development of monitoring techniques in mobile coronary care.
Mobile coronary care was first introduced by Pantridge and Geddes at the Royal Victoria Hospital in 1966. Traditional emergency equipment i.e. defibrillation and monitors were unsuitable for application in this environment. In the succeeding years the defibrillator was made highly portable, and significantly reduced in size. Specialized monitoring apparatus was also developed to provide display and recording facilities to meet the special needs of the mobile coronary care unit. However, current display systems utilize the cathode ray oscilloscope, which does not lend itself to miniaturization, is fragile, and cannot be placed at close proximity to the patient. A flat screen electroluminescent matrix of 256 X 128 dots has been developed as a physiological data display. The panel achieves a line density of approximately 83 per inch and with a time compressed memory and interpolated drive technique provides an acceptable display.


The role of ExbD in periplasmic pH homeostasis in Helicobacter pylori.
Helicobacter pylori, a neutralophile, colonizes the acidic environment of the human stomach by employing acid acclimation mechanisms that regulate periplasmic and cytoplasmic pH. The regulation of urease activity is central to acid acclimation. Inactive urease apoenzyme, UreA/B, requires nickel for activation. Accessory proteins UreE, F, G, and H are required for nickel insertion into apoenzyme. The ExbB/ExbD/TonB complex transfers energy from the inner to outer membrane, providing the driving force for nickel uptake. Therefore, the aim of this study was to determine the contribution of ExbD to pH homeostasis. A nonpolar exbD knockout was constructed and survival, growth, urease activity, and membrane potential were determined in comparison with wildtype. Survival of the ΔexbD strain was significantly reduced at pH 3.0. Urease activity as a function of pH and UreI activation was similar to the wildtype strain, showing normal function of the proton-gated urea channel, UreI. The increase in total urease activity over time in acid seen in the wildtype strain was abolished in the ΔexbD strain, but recovered in the presence of supraphysiologic nickel concentrations, demonstrating that the effect of the ΔexbD mutant is due to loss of a necessary constant supply of nickel. In acid, ΔexbD also decreased its ability to maintain membrane potential and periplasmic buffering in the presence of urea. ExbD is essential for maintenance of periplasmic buffering and membrane potential by transferring energy required for nickel uptake, making it a potential nonantibiotic target for H. pylori eradication.


Ectopic expression of the HAM59 gene causes homeotic transformations of reproductive organs in sunflower (Helianthus annuus L.).
The function of the HAM59 MADS-box gene in sunflower (Helianthus annuus L.) was studied to clarify homeotic C activity in the Asteraceae plant family. For the first time, transgenic sunflower plants with a modified pattern of HAM59 expression were obtained. It was shown that the HAM59 MADS-box transcription factor did mediate C activity in sunflower. In particular, it participated in termination of the floral meristem, repression of the cadastral function of A-activity, and together with other C-type sunflower protein HAM45-in the specification of the identity of stamens and pistils.


Neotabrizicola shimadae gen. nov., sp. nov., an aerobic anoxygenic phototrophic bacterium harbouring photosynthetic genes in the family Rhodobacteraceae, isolated from a terrestrial hot spring.
A bacteriochlorophyll-containing bacterium, designated as strain N10T, was isolated from a terrestrial hot spring in Nagano Prefecture, Japan. Gram-stain-negative, oxidase- and catalase-positive and ovoid to rod-shaped cells showed the features of aerobic anoxygenic phototrophic bacteria, i.e., strain N10T synthesised bacteriochlorophylls under aerobic conditions and could not grow anaerobically even under illumination. Genome analysis found genes for bacteriochlorophyll and carotenoid biosynthesis, light-harvesting complexes and type-2 photosynthetic reaction centre in the chromosome. Phylogenetic analyses based on the 16S rRNA gene sequence and 92 core proteins revealed that strain N10T was located in a distinct lineage near the type species of the genera Tabrizicola and Xinfangfangia and some species in the genus Rhodobacter (e.g., Rhodobacter blasticus). Strain N10T shared < 97.1% 16S rRNA gene sequence identity with those species in the family Rhodobacteraceae. The digital DNA-DNA hybridisation, average nucleotide identity and average amino acid identity values with the relatives, Tabrizicola aquatica RCRI19T (an aerobic anoxygenic phototrophic bacterium), Xinfangfangia soli ZQBWT and R. blasticus ATCC 33485T were 19.9-20.7%, 78.2-79.1% and 69.1-70.1%, respectively. Based on the phenotypic features, major fatty acid and polar lipid compositions, genome sequence and phylogenetic position, a novel genus and species are proposed for strain N10T, to be named Neotabrizicola shimadae (= JCM 34381T = DSM 112087T). Strain N10T which is phylogenetically located among aerobic anoxygenic phototrophic bacteria (Tabrizicola), bacteriochlorophyll-deficient bacteria (Xinfangfangia) and anaerobic anoxygenic phototrophic bacteria (Rhodobacter) has great potential to promote studies on the evolution of photosynthesis in Rhodobacteraceae.


Post-market quality assessment of 22 ciprofloxacin brands by HPLC available in Bangladesh market.
Antibiotic resistance has been recognized as a public health threat in recent years, and mortality due to resistance is increasing alarmingly every year. Antibiotic resistance, among many factors, may arise due to the consumption of substandard antibiotic brands that provide subnormal levels of the drug in the blood. Post-market evaluation can provide important information in assessing pharmaceutical products in terms of quality, purity, and therapeutic aspects. Ciprofloxacin, a broad-spectrum antibiotic, has been used against a wide range of infectious diseases in Bangladesh. The present study aimed to determine the quality attributes of twenty-two commonly prescribed brands of ciprofloxacin 500 mg tablet collected from Dhaka city and the rural regions of Jessore. RP-HPLC coupled with UV-visible spectrophotometry was used to determine the potency of ciprofloxacin in tablets, and the zone of inhibition was determined using Kirby-Bauer's disc diffusion method to assess the antimicrobial efficacy against different strains of microorganisms. We found that 95.45% of brands (21 out of 22 brands) of ciprofloxacin tablets met United States Pharmacopoeia (USP) and British Pharmacopoeia (BP) specified potency, whereas one brand failed. From dissolution studies, we observed that 68.2% of brands (15 out of 22 brands) followed USP/NF dissolution test specifications, whereas 31.8% (7 out of 22 brands) failed to release 80% of the labeled amount of drug within 30 min. Drug release kinetics data showed that most brands followed the Weibull drug release kinetic model. Fit factor analysis exhibited that 8 brands out of 22 (36.4%) failed to comply similar dissolution profiles with the reference product. Minimum inhibitory concentrations, assessed against five bacterial strains, further showed good antimicrobial sensitivity by all brands.


Evaluation of saliva pools method for detection of congenital human cytomegalovirus infection.
Human cytomegalovirus (HCMV) is the most frequent cause of congenital infection, leading to long-term sequelae especially sensorineural hearing loss (SNHL). Since 5-15 % of the asymptomatic newborns will develop late sequelae, the implementation of a universal screening would allow the identification of infected children and early intervention. The aim of this study was to validate the use of saliva pools of 10 and 20 samples for the detection of HCMV congenital infection. Four spiking samples (negative saliva matrix added with known concentration of AD169 strain culture supernatant) and a set of 12 saliva samples, collected from newborns with confirmed congenital infection in their first three weeks of life, were tested individually and after dilution in 10 and 20 pools by an "in-house" RT-PCR. Both pool methodologies, 10-pool and 20-pool samples, had 100 % sensitivity and specificity when compared with individual samples. This methodology could allow a cost reduction close to 85 % and 89 %, respectively for the 10-pool and 20-pool approach, when compared with testing each sample individually. This significant reduction may open the possibility to perform the newborn screening for HCMV in a large-scale.


Analysis of zebrafish development using explant culture assays.
Two fundamental questions of developmental biology are when cells become committed to a certain lineage and what cell interactions are involved in establishing this commitment. These questions can be answered using explant or transplant assays. We have developed explant assays to study zebrafish development. These assays involve isolating by microdissection small regions of the embryo at specific times during development, and determining their fate after culture in isolation (lineage commitment assays) or after exposure to a putative inducing tissue (induction assays). In our laboratory, we have used these assays to address questions of neural development, including those of commitment to anterior and posterior neural lineages, and the signals involved in making these decisions. This chapter contains detailed guidelines for designing explant assays. These include suggestions for the isolation and successful culture of explants, and descriptions of the methods used to assay the final fate of explants after culture. Step-by-step protocols are given for the isolation of specific explants that can be used in specification and induction assays. The application of this technique is illustrated with descriptions of experiments. Explant assays will continue to generate key information concerning the establishment of lineage commitment of many embryonic tissues and will provide extremely valuable for analysis of new genes identified molecularly and in mutant screens.


Manganese-Catalyzed N-Formylation of Amines by Methanol Liberating H2 : A Catalytic and Mechanistic Study.
The first example of a base metal (manganese) catalyzed acceptorless dehydrogenative coupling of methanol and amines to form formamides is reported herein. The novel pincer complex (iPr-PNH P)Mn(H)(CO)2 catalyzes the reaction under mild conditions in the absence of any additives, bases, or hydrogen acceptors. Mechanistic insight based on the observation of an intermediate and DFT calculations is also provided.


Perspectives on educating pharmacy students about the science of safety.
To identify opinions about pharmacy graduates' science of safety (SoS) educational needs. Semi-structured interviews were performed with 25 educators and researchers at US pharmacy colleges and schools and 5 individuals from associations engaged in drug safety-related issues. Themes that emerged from the 30 interviews with key informants included: pharmacists should meet minimum SoS requirements; medication safety education is inconsistent; and barriers exist to improving SoS curricula. Student deficiencies noted included the lack of: student acceptance of a "culture of safety": ability to effectively communicate verbally about medication safety; knowledge of the drug development process; and quality improvement skills. Key informants did not agree on how to address these gaps. While educators, researchers, and other leaders in drug safety-related issues thought that US colleges and schools of pharmacy covered portions of SoS well, there were perceived deficiencies. Minimum standards should be set to assist with curricular adoption of SoS.


Sex-based differences in early and late uveal melanoma-related mortality.
It is debated if there are sex-based differences in survival for patients with uveal melanoma. Previous observations of higher mortality for men in studies with <10-year follow-up have not been replicated in studies with longer follow-up. It is therefore hypothesized that women have a worse survival in later periods. All patients diagnosed with primary uveal melanoma in Sweden between 1980 and 2017 were included (n = 2032). Survival differences between men and women in early (<10 years from diagnosis) and late (≥10 years) periods were analyzed. At baseline, there were no significant differences in mean patient age, tumor thickness, diameter, ciliary body involvement, primary treatment modality, or in American Joint Committee on Cancer (AJCC) T-category between men and women. In total, 764 patients (425 women and 339 men) survived and were followed ≥10 years. In this group, men were significantly younger, but there were no differences in baseline tumor thickness, diameter, ciliary body involvement, primary treatment, or AJCC T-category. In competing risk analysis, women had higher incidence of uveal melanoma-related mortality in the late period (p = 0.036). In univariate Cox regression, male (HR 1.2, p = 0.049) and female sex (HR 1.8, p = 0.034) were significant predictors of uveal melanoma-related mortality in the early and late periods, respectively. Women with uveal melanoma have better survival in the first decade after diagnosis. Thereafter, female survivors are significantly older than men and have a higher incidence of uveal melanoma-related mortality.


Orthodontic and Surgical Considerations for Treating Impacted Teeth.
Impacted teeth occur in a significant number of patients. Their management requires coordinated efforts of orthodontists and oral and maxillofacial surgeons. Specifically, optimal results require a prompt orthodontic diagnosis and treatment plan with execution of either closed or open exposure of impacted teeth by the oral and maxillofacial surgeon. Failure to consider orthodontic mechanics and proper surgical technique can lead to suboptimal results. Thus, orthodontist/oral and maxillofacial surgeon communication is essential for success and patient education and shared decision-making is mandatory before initiating treatment.


Handling and performance characteristics of a new small caliber radiopaque embolic microsphere.
The in vitro and in vivo handling and performance characteristics of a small caliber radiopaque embolic microsphere, 40-90 μm DC Bead LUMI™ (LUMI40-90), were studied. Microsphere drug loading and elution and effects on size, suspension, and microcatheter delivery were evaluated using established in vitro methodologies. In vivo evaluations of vascular penetration (rabbit renal artery embolization), long-term biocompatibility and X-ray imaging properties, pharmacokinetics and local tissue effects of both doxorubicin (Dox) and irinotecan (Iri) loaded microspheres (swine hepatic artery embolization) were conducted. Compared to 70-150 μm DC Bead LUMI (LUMI70-150), LUMI40-90 averaged 70 μm versus 100 μm, which was unchanged upon drug loading. Handling, suspension, and microsphere delivery studies were successfully performed. Dox loading was faster (20 min) and Iri equivalent (<10 min) while drug elution rates were similar. Contrast suspension times were longer with no delivery complications. Vascular penetration was statistically greater (rabbit) with no unexpected adverse safety findings (swine). Microspheres ± drug were visible under X-ray imaging (CT) at 90 days. Peak plasma drug levels and area under the curve were greater for LUMI40-90 compared to LUMI70-150 but comparable to 70-150 μm DC BeadM1™ (DC70-150). Local tissue effects showed extensive hepatic necrosis for Dox, whereas Iri displayed lower toxicity with more pronounced lobar fibrosis. LUMI40-90 remains suspended for longer and have greater vessel penetration compared to the other DC Bead LUMI sizes and are similarly highly biocompatible with long-term visibility under X-ray imaging. Drug loading is equivalent or faster with pharmacokinetics similar to DC70-150 for both Dox and Iri.


Organochlorine compounds in ice melt water from Italian Alpine rivers.
Organochlorine chemicals (OCs) (dichlorodiphenyltrichloroethanes, hexachlorocyclohexanes, and hexachlorobenzene) were measured in ice melt water from five glaciers in the Italian Alps. Even though the data collected may not be sufficient for a precise description of persistent organic pollutant release patterns from glacier melting, they have, however, highlighted the potential for surface water contamination. Concentrations were of the same order of magnitude in all glacial streams, indicating comparable contamination levels in different glaciers of the alpine region. OC levels in nonglacial springs sampled in the same areas are usually lower. Even if differences during the melting season (from spring to autumn) have been identified, a regular seasonal pattern in OC concentrations was not observed. Risk for the aquatic environment is excluded through direct water exposure, but it is likely to occur through biomagnification and secondary poisoning exposure.


Anuran olfactory bulb organization: embryology, neurochemistry and hodology.
In Xenopus laevis, we analyzed the origin of the projection neurons and interneurons in the developing olfactory bulbs by studying the expression patterns of the genes x-Eomes, x-Lhx5, x-Dll3 and x-Pax6. Olfactory bulb interneurons were characterized by using four conserved molecular markers for distinct subpopulations: gamma-aminobutyric acid, calretinin, calbindin, and tyrosine hydroxylase. Immunohistochemistry was combined with tract-tracing experiments to demonstrate the projection neurons and the interneurons of the olfactory bulbs simultaneously. Taken together, the results showed: (1) the pallial nature of the olfactory bulb and its projection neurons in Xenopus, like in mammals with comparable central projection areas, (2) the subpallial origin of the interneurons that, most likely, follow migratory pathways comparable to those described for mammals, (3) the different interneuron types possess neurochemical characteristics similar to mammals. Therefore, the present results show that the origin, chemoarchitecture and central connections of the olfactory bulbs are highly conserved in evolution.


Monolithic column in gas chromatography.
Monolithic columns invented in chromatographic praxis almost 40 years ago gained nowadays a lot of popularity in separations by liquid chromatographic technique. At the same time, application of monolithic columns in gas chromatography is less common and only a single review published by Svec et al. covers this field of research. Since that time a lot of new findings on application and properties of monolithic columns in gas chromatography have been published in the literature deserving consideration and discussion. This review considers preparation of monolithic columns for GC, an impact of preparation conditions on column performance, optimization of separation conditions for GC analysis on monolithic columns and other important aspects of preparation and usage of monolithic capillary columns in GC. A final part of the review discusses the modern trends and possible applications in the future of capillary monolithic columns in GC.


[The effect of some non-narcotic analgetics on respiration (author's transl)].
Report on a Hungarian analgetic "Probon" belonging in its effects to the minor analgetics. It does not show any depressing action on the respiratory centre and has a bronchodilatory effect. It does not cause sideeffects nor dependence and does not lose in efficacy even in long lasting application and in old people.


Assessing the Risk of Hemorrhagic Complication following Transjugular Liver Biopsy in Bone Marrow Transplantation Recipients.
To determine if recipients of bone marrow transplants (BMTs) are at increased risk of hemorrhagic complications following transjugular liver biopsy (TJLB). TJLBs in BMT and non-BMT patients between January 2007 and July 2014 were reviewed. Patient demographic and pre- and postprocedural laboratory data were reviewed. Mean platelet count and International Normalized Ratio were 174,300 × 10(3)/µL ± 107.3 (standard deviation) and 1.2 ± 0.4, respectively, for BMT recipients, compared with 88,100 × 10(3)/µL ± 70.9 and 1.2 ± 0.5, respectively, for non-BMT. Patients in whom hemoglobin level decreased by > 1 g/dL and/or required transfusion within 15 days of TJLB were reviewed to determine the presence of a biopsy-related hemorrhagic complication. A total of 1,600 TJLBs in 1,120 patients were analyzed. Of these, 183 TJLBs in 159 BMT recipients and 1,417 TJLBs in 961 patients non-BMT patients were performed. Thirteen TJLBs were complicated by hemorrhage: five in BMT (2.9%) and eight in the non-BMT cohorts (0.6%; P < .01). Preprocedural platelet counts were within normal range (57-268 × 10(3)/µL) in all but one patient (8 × 10(3)/µL). BMT recipients had an odds ratio of 4.9 (95% confidence interval, 1.25-17.3) for post-TJLB bleeding/hemorrhage compared with those without BMTs (P < .01). TJLB continues to be a safe procedure in the vast majority of patients. However, hemorrhagic complications occurred at a rate of 2.9% in BMT recipients, compared with 0.6% in patients without BMTs, and therefore caution should be exercised when performing TJLB in this group.


Is it time to stop living in a HeartMate II world?
Despite improving outcomes with modern pump technology, left ventricular assist device (LVAD) utilization for patients with end-stage heart failure (HF) has declined significantly in the preceding half-decade. Here, we examine this trend, noting an inherent contradiction in the declining utilization of an improving therapeutic option. We propose a series of provocative questions as a "call to action" for the field of advanced HF to consider both scientifically and clinically, focusing on our evaluation parameters for LVAD candidacy, our approach to dichotomous LVAD vs transplant decisions, and our current management paradigms. We conclude that modernization in these areas to match the advantages of modern pump technology is required to best serve patients with advanced HF.


The Final Rule for 2022: What's New and How Changes in the Medicare Physician Fee Schedule and Quality Payment Program Affect Dermatologists.
The Centers for Medicare & Medicaid Services (CMS) 2022 final rule, which went into effect on January 1, 2022, contains updates affecting the practice of dermatology. This article reviews many of the changes to the Medicare Physician Fee Schedule (PFS) and Quality Payment Program (QPP) and their impact on clinical practice.


[Cesarean-section narcosis using Tricuran (Gallamine as a long-lasting muscle relaxans before delivery of the infant].
The use of long term non-depolarizing muscle relaxants facilitates the carrying out of anaesthesia at caesarean section. We compared the Apgar-score of two groups of 20 newborns after caesarean section, whose mothers got only succinylcholine or succinylcholine and gallamine before delivery by a hexobarbiturate - nitrous oxide - oxygen anaesthesia. The Apgar-score was practically identical in both groups. 70% of infants of the succinylcholine group and 75% of infants of the gallamine group showed an Apgar-score between 7 and 10 after 1 minute. A later decrease was noticed in no case. The use of gallamine is without danger for the newborn.


Low-Intensity Training and the C5a Complement Antagonist NOX-D21 Rescue the mdx Phenotype through Modulation of Inflammation.
Inflammatory events occurring in dystrophic muscles contribute to the progression of Duchenne muscular dystrophy (DMD). Low-intensity training (LIT) attenuates the phenotype of mdx mice, an animal model for DMD. Therefore, we postulated that LIT could have anti-inflammatory properties. We assessed levels of inflammatory cytokines and infiltrated immune cells in gastrocnemius muscle of mdx mice after LIT. We detected high levels of complement component C5a, chemokine ligand (CCL) 2, CD68+ monocytes/macrophages, and proinflammatory M1 macrophages in muscles of mdx mice. LIT decreased CCL2 levels, increased CD68+ cell numbers, and shifted the macrophage population to the regenerative M2 type. We investigated whether inhibition of C5a or CCL2 with L-aptamers could mimic the effects of LIT. Although no effect of CCL2 inhibition was detected, treatment with the C5a inhibitor, NOX-D21, rescued the phenotype of nonexercised mdx mice, but not of exercised ones. In both cases, the level of CD68+ cells increased and macrophage populations leaned toward the inflammatory M1 type. In muscles of nonexercised treated mice, the level of IL-1 receptor antagonist increased, damage decreased, and fibers were switched toward the glycolytic fast type; in muscles of exercised mice, fibers were switched to the oxidative slow type. These results reveal the effects of LIT on the inflammatory status of mdx mice and suggest that NOX-D21 could be an anti-inflammatory drug for DMD.


[The employment of pharmacodynamic tests in the radiological examination of the digestive tract (author's transl)].
The indications, contraindications and usefulness of pharmacodynamic tests in current radiological diagnosis of diseases of the digestive tract are reviewed and iscussed. Various examples are presented.


Prognostic factors in lung cancer in a defined geographical area over two decades with a special emphasis on gender.
Many studies over recent decades report an increasing incidence of lung cancer in female patients. Female gender is often reported as a good prognostic factor. The aim of the present study was to investigate prognostic factors with a special emphasis on gender. During 1989-2008, 1497 patients in eastern Scania, a part of southern Sweden with 202,000 inhabitants, were referred to one Central Hospital and prospectively registered. All patients were grouped into four 5-year periods and were analysed for occurrence of lung cancer, patient performance status, types and stages of lung cancer and the relation to gender. The incidence of lung cancer more than doubled in women. The proportion of adenocarcinomas increased in females and in males to 57% (P=0.028) and 42% (P=0.001), respectively, while the frequency of small cell lung carcinomas (SCLCs) decreased in both genders to approximately 14%. Females had significantly more frequent stage 1 (16.6%) and higher surgery rate (23.1%) than males (12% and 18.2%, respectively). Females showed a higher 5-year survival rate than males (20.1% and 11.5%, respectively; P<0.001). Patients with non-small cell lung carcinoma (NSCLC) had a higher 5-year survival rate than those with SCLC (16.5% and 7.5%, respectively; P<0.01); however, there was no significant survival difference in females between NSCLC and SCLC. Female patients exhibited longer survival than males for both NSCLC and SCLC, and this was not explained by a higher frequency of stage 1 or surgery in NSCLC.


Tracing the pathways by which flood duration impacts soil bacteria through soil properties and water-extractable dissolved organic matter: A soil column experiment.
Soil microbial communities control biogeochemical processes, nutrient cycling, and organic carbon storage and release in wetlands, which are influenced by flooding. To predict soil nutrient function in wetland ecosystems, understanding the effect of flooding on soil biogeochemical cycling and energy flux, including soil properties, dissolved organic matter (DOM), and microbial communities is essential. This study investigated how different flood durations (1, 3, 8, 16, and 30 d) affect the interactions between physicochemical properties and bacterial communities in a river wetland. The DOM composition was measured using ultraviolet/visible spectrophotometry coupled with fluorescence spectroscopy, and the bacterial communities were identified using 16S rRNA sequencing. Simpson's diversity index varied from 0.92 to 0.94, indicating high bacterial diversity throughout the treatments; the highest and lowest bacterial diversities were found at 1 and 8 flooding days, respectively. The abundance of Desulturomonadales, Clostridiales, Bacteroidales, and Gaiellales was positively correlated with pH, electrical conductivity, water-extractable dissolved organic carbon (WEOC), and water-extractable total dissolved nitrogen (TDN) but negatively correlated with dissolved oxygen (DO) and soil organic matter (SOM), suggesting complex interactions among these factors in response to flooding. Structural equation model revealed that flooding directly increased TDN but indirectly increased WEOC through increasing soil pH; and directly decreased DO and SOM, leading to decreases in total protein-like fraction. Three significant pathways were identified, showing the impacts of flooding on bacterial diversity: (1) flood duration decreased DO, resulting in decreased bacterial diversity; (2) flood duration decreased SOM, leading to increased bacterial diversity; and (3) flood duration decreased DO and SOM, leading to increased bacterial diversity via decreased total protein-like fraction. This study indicated that prolonged flooding has both positive and negative impacts on bacterial diversity, depending on environmental factors. It highlights the importance of flooding in shaping soil bacterial communities, with implications for nutrient cycling and carbon storage in wetlands.


Evolution of China's water issues as framed in Chinese mainstream newspaper.
There is an urgent need globally to trigger fundamental societal changes in water management away from existing unsustainable paradigms. This paper attempts to understand the evolution of newspaper coverage of water issues in China by analyzing water-related articles in a major national newspaper, the People's Daily, over the period 1946-2012 using a content analysis approach. The major findings include the following: (1) water issues were in relatively prominent positions in the newspaper; (2) the reporting of water issues in China experienced three stages: 1946 to the middle of 1980s-flood and drought control and water for food production, the middle of 1980s to 1997-water for economic development, and 1998 to the present-water for the environmental sustainability and economic development; (3) the reporting of water issues in the People's Daily clearly reflected China's top-down water resources management system, and no "real" public opinions on water were reported during the study period; and (4) the People's Daily is just a wind vane of Chinese mainstream values and policies on water. The findings supported the realist assumption that the societal value changes on water issues in China were triggered by a range of factors including biophysical pressure (floods and droughts), political campaign (the Cultural Revolution), macro-economic reform (Reform and Opening-up), water institutional arrangement (the Water Law), and water management reform (the No. 1 Central Document on water reform). While there are similarities and differences between this study and other studies, important implications for more sustainable water management are a need to strengthen academic specialists' and NGO's voices in the newspaper to create a better informed public, and to stimulate practices toward sustainable water use.


Process evaluation of an integrated, multidisciplinary intervention programme for hand eczema.
BACKGROUND. Over the last decade, few randomized controlled trials of high methodological quality have been carried out to evaluate the effectiveness of interventions for patients with hand eczema. Little to no attention has been paid to the feasibility of these interventions. This process evaluation was carried out to gain insight in the barriers to and facilitators for implementation of an intervention for hand eczema. The aims of this process evaluation were to examine the feasibility and the satisfaction of the patients and the professionals with the integrated care programme, and the perceived barriers to and facilitators for the use of the programme. Eligible for this study were patients with moderate to severe chronic hand eczema who completed the integrated care programme. This programme is an intervention provided by a multidisciplinary team, consisting of a dermatologist, a specialized nurse, and a clinical occupational physician. Data were collected from the patients and the healthcare professionals, by means of semistructured telephone interviews, questionnaires, and a patient tracking system. Implementation, satisfaction and expectations were investigated. Ninety-three patients completed the integrated care programme. Compliance with the integrated care programme was good. The results indicate good satisfaction of both patients and healthcare professionals with the integrated care programme. However, with regard to the process and feasibility of the integrated care programme, there is room for improvement. The clinical occupational physician was only involved in a very limited number of cases, the protocol was not flexible, and the intervention period was too compact. Most of the perceived barriers in the present study are at the organizational level. Satisfaction with the integrated care programme was high among both patients and healthcare professionals. The involvement of the clinical occupational physician in the treatment, when indicated, should be optimized. With the multidisciplinary approach and good communication as a basis for the programme, and a more flexible protocol to avoid unnecessary consultations by the healthcare professionals, integrated care could be a useful treatment from a process evaluation perspective.


Using the Internet as a source of information and support: a discussion paper on the risks and benefits for children and young people with long-term conditions.
Children and young people who have long-term conditions are likely to seek health-related information via the Internet. Because of their continuing contact with children with such conditions, primary care practitioners may be well placed to discuss with them and their families the risks and benefits of accessing information online. This includes not only the relative merits of particular sites but also more general online safety issues. To achieve this, it may be helpful for primary care practitioners to consider how they view risk in general, the risks associated with the Internet and the vulnerabilities of children and young people, particularly those with long-term conditions.


Changes in two-phase emulsion morphology in temperature-amphiphile concentration or fish diagram for ternary amphiphile/oil/water systems.
We examined the morphologies of two-phase emulsions in the ternary 2-butoxyethanol/n-decane/water system at various temperatures and water-to-oil ratios (WORs). The two-phase emulsion morphologies depended on temperature, WOR, and amphiphile concentration, and the results are presented in a temperature-amphiphile concentration coordinate system or a "fish" diagram. The observations made in this work contradict the predictions by the phase-inversion-temperature (PIT) concept. At WOR<1, a vertical inversion line was observed at T<T(lc) (lower critical endpoint temperature), dividing the two-phase region into the subregions of B/T (W/O) and T/B (O/W) emulsions. At T>T(uc) (upper critical endpoint temperature) and at low amphiphile concentrations, only B/T emulsions appeared, irrespective of temperature. At WOR>1, the situation was reversed; T/B emulsions at T<T(lc), T/B and B/T emulsions at T>T(uc), and T/B emulsions at low amphiphile concentrations, irrespective of temperature. At WOR=1, two horizontal inversion lines, one each at T<T(lc) and T>T(uc), were observed. The morphologies of the two-phase emulsions were B/T or T/B emulsions at low amphiphile concentrations, and at higher amphiphile concentrations T/B at T<T(lc) and B/T at T>T(uc). All these findings along with three-phase emulsion data result in complete emulsion morphology diagrams in the temperature-amphiphile concentration space or fish diagram.


Autologous right atrial wall patch for closure of atrial septal defects.
We used the right atrial free wall as a patch to close atrial septal defects (ASD) and report its results. Between July 1998 and April 2006, 87 patients (mean age, 21.9 +/- 13.9 years; range, 7 months to 54 years), underwent closure of ASD with an autologous right atrial free wall patch. The underlying diagnosis were very large secundum ASD in 51 patients, sinus venosus defect in 15, primum ASD in 5, large defect resulting from excision of a left atrial myxoma in 12, complete atrioventricular canal defect in 1, total anomalous pulmonary venous return with ASD in 2, and Ebstein anomaly with a large ASD in 1. Associated surgical procedures were mitral valve repair in 18 patients, repair of total or partial anomalous pulmonary venous drainage in 17, mitral valve replacement in 1, and tricuspid valve repair for Ebstein anomaly in 1. There were two early deaths. One patient with primum defect and preoperative congestive heart failure died 3 weeks postoperatively from refractory ventricular fibrillation. Another patient died from persistent congestive heart failure after undergoing reoperation for residual mitral regurgitation. The remaining patients were discharged after 4 to 9 days. No flow was detected across the septal patch on predischarge echocardiography. At a mean follow up of 53.4 +/- 26.7 months (range, 1 to 103 months), all patients except 1 are in sinus rhythm. One patient underwent reoperation for failed mitral valve repair after 1 month. At reoperation, the patch was intact with normal texture and without any suture dehiscence. Histopathologic examination of the explanted patch revealed viable endothelium and subendothelial muscle on both the surfaces of the patch. Results of Holter monitoring in 9 patients were normal. Electrophysiologic studies in 2 patients recorded normal atrial potentials from the site of the patch. No patch shrinkage, calcification, or thromboembolic complications were noted. The autologous, free, right atrial wall can be safely used as a patch for ASD closure and offers several advantages.


Impairment of recognition memory and hippocampal long-term potentiation after acute exposure to clioquinol.
Clioquinol (CQ) was associated with cases of transient global amnesia and with the neurodegenerative syndrome subacute myelo-optico-neuropathy (SMON) in humans. However, CQ forms lipophilic chelates with cations and has the potential as a scientific and clinical tool used for selective modulation of histochemically reactive zinc pools. The relationship among transient lack of synaptic zinc release, hippocampal long-term potentiation (LTP) induction and cognitive memory is poorly understood. To evaluate the role of synaptic zinc release, in the present study, hippocampal LTP induction and cognitive behavior were examined in young rats after i.p. injection of CQ (30 mg/kg). Intracellular zinc detected by Timm's stain and extracellular (synaptic cleft) zinc detected by ZnAF-2 were significantly decreased in the hippocampus 6 h after CQ injection. The molecular layer of the dentate gyrus, in which perforant path-granule cell synapses exist, was most responsive to CQ injection. Dentate gyrus LTP was induced similarly to the control 2 h after CQ injection, while significantly attenuated 6-24 h after CQ injection. In the training trial of the object recognition memory 2 h after CQ injection, there was no significant difference in learning behavior between the control and CQ-treated rats. In the test trial, CQ-treated rats showed normal recognition memory 1 h after the training, whereas recognition memory deficit 24 h after the training unlike the control rats. These results indicate that acute exposure to CQ impairs long-term (24 h) memory in the hippocampus of young rats. The CQ-mediated attenuation of dentate gyrus LTP, which may be associated with the transient lack of zinc release from zincergic neurons, seems to be involved in the impairment of the long-term memory.


Results of treatment of chronic dorsal fracture-dislocations of the proximal interphalangeal joints of the fingers.
We reviewed 20 cases of chronic dorsal fracture-dislocation of the proximal interphalangeal joint, with a mean follow-up period of 74 months. In patients without comminuted palmar fragments, open reduction and internal fixation or osteotomy of the malunited fragment provided good results. In treating patients with damaged articular cartilage or with comminuted palmar fragments by palmar plate arthroplasty, poor results were obtained because of secondary osteoarthritic changes.


Case Report of Methemoglobinemia: An Illustration That It Is Time to Report all Results with Arterial and Venous Blood Gas Result Reporting.
Methemoglobinemia and carbon monoxide poisoning are potentially life-threatening conditions that can present with nonspecific clinical features. This lack of specificity increases the probability of misdiagnosis or avoidable delays in diagnosis and management. These conditions are both treatable with antidotes of methylene blue and oxygen, respectively. Modern blood gas analyzers have the ability to measure carboxyhemoglobin (COHb) and methemoglobin (MetHb) levels without any additional resources. However, these results, although readily available from the machine used to perform the analysis, are not fully reported by some hospital clinical laboratories. A 49-year-old male presented with shortness of breath and cyanosis after inhaling cocaine via a nasal route ("snorting"). Methemoglobinemia was not initially considered in the differential diagnosis. However, the diagnosis of methemoglobinemia was made once newly routinely reported laboratory results revealed an elevated MetHb level. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Routinely reporting MetHb and COHb levels with arterial and venous blood gas results will facilitate making the diagnoses of these infrequently diagnosed causes of hypoxia more quickly so that early treatment of these uncommon but potentially lethal conditions can be initiated promptly.


Objective evidence of tinnitus in auditory evoked magnetic fields.
The waveforms of the auditory evoked magnetic field in normal-hearing individuals and patients suffering from tinnitus are distinctly different. In tinnitus patients, the magnetic wave M200 (corresponding to the electric wave P200, or P2) is delayed and only poorly developed or even completely missing, while the amplitude of the magnetic wave M100 (corresponding to the electric wave N100, or N1) is significally augmented. A very characteristic feature turned out to be the amplitude ratio of the two waves M200 and M100. Below the age of 50, the amplitude ratio M200/M100 represents a clear-cut criterion to distinguish between tinnitus patients and individuals without tinnitus. In tinnitus patients, the ratio is less than 0.5, independent of age, whereas, in young and middle-aged normal-hearing individuals, it is greater than 0.5. Since in normal-hearing individuals the average amplitude ratio decreases linearly with age, the clusters of amplitude ratios of the two groups begin to overlap beyond the age of 50. The hypothesis is put forward that the decrease of the average amplitude ratio in normal-hearing individuals reflects a degenerative process, probably initiated by multiple exogenous and endogenous factors, which leads to sustained neural activity in the generators of wave M200 and eventually gives rise to the sensation of tinnitus. The absence or poor development of wave M200 is a concomitant phenomenon, resulting from the involved generators being less responsive to external stimuli.


Dissecting CTCF site function in a tense HoxD locus.
In this issue of Genes & Development, Amândio and colleagues (pp. 1490-1509) dissect the function of a cluster of several CTCF binding sites in the HoxD cluster by iterative deletions in mice. They found additive functions for some, and intriguingly found that some sites function as insulators, while others function as anchors for enhancer-promoter interactions. These functions vary depending on developmental context. The work provides new insights into the roles played by CTCF in regulating developmental patterns and 3D chromatin organization.


Aflatoxin B1 and ochratoxin A reduction by Lactobacillus spp. during bread making.
Aflatoxin B1 (AFB1) and ochratoxin A (OTA) are among the most important mycotoxins with common presence in bread and bakery products. Biological detoxification of mould food spoilage and mycotoxin contamination by lactic acid bacteria (LABs) exhibits high potential on a cost-effective and large scale. In this work, the effect of Lactobacillus strains isolated from goat milk whey on reducing AFB1 and OTA during bread making was evaluated by the determination of mycotoxin reduction potential of 12 LAB strains after 72 h incubation in De Man-Rogosa-Sharpe (MRS) broth (37 °C). The most effective LABs were lyophilized and added as ingredient in bread formulation, analysing mycotoxins by high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry after bread fermentation and baking. AFB1 was reduced in MRS broth by seven LABs (11-35%), highlighting Lactobacillus plantarum B3 activity; while all LABs reduced OTA (12-40%) with L. plantarum B3 and Lactobacillus paracasei B10 as the most active strains. Both LABs were lyophilized and added in contaminated bread with and without yeast, reaching AFB1 and OTA reductions up to 27% and 32% respectively in dough and up to 55% and 34% respectively in bread. The selected strains significantly reduced AFB1 and OTA during bread fermentation, pointing to a potential biocontrol strategy for mycotoxins detoxification in bread and bakery products. © 2023 The Authors. Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.


Exploring the role of prolactin in psoriasis.
Prolactin (PRL) is well recognised for its role(s) in mammary gland development and function. Moreover, its role in skin biology, including the potent regulation of human hair growth, is becoming clearer. Less widely appreciated, however, is the potential role of PRL in the pathobiology of psoriasis. While the relationship between PRL and psoriasis remains enigmatic, several recent publications on the PRL-psoriasis connection have demonstrated a reawakening of interest in this conundrum. We take the occasion of these reports to underscore the importance of dissecting the role(s) of PRL in the aetiopathology of psoriasis, not least since this may help to identify novel hormonal treatment strategies in its management.


Different effects on the responses of functional pre- and postsynaptic 5-HT1A receptors by repeated treatment of rats with the 5-HT1A receptor agonist 8-OH-DPAT.
The effects of repeated treatment of rats with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 1.0 mg/kg, subcutaneously, twice daily for 7 days, on the stimulation of post- and presynaptic 5-HT1A receptors were examined. The postsynaptic responses, hypothermia and inhibition of the cage-leaving response, evoked by 0.05 mg/kg 8-OH-DPAT, were measured 48 hr after the final injection. Another postsynaptic response, the 5-HT syndrome (flat body posture and forepaw treading) was observed after the third injection of 8-OH-DPAT (1.0 mg/kg s.c.). One presynaptic response examined was the 8-OH-DPAT-induced decrease in the concentration of 5-hydroxyindoleacetic acid (5-HIAA), that indicates a decrease in turnover of 5-HT, due to stimulation of 5-HT receptors on the cell bodies and measured as the ratio of 5-HIAA to 5-HT in the hippocampus, hypothalamus and medulla oblongata. Another presynaptic response was the 8-OH-DPAT-induced decrease in the accumulation of 5-hydroxytryptophan (5-HTP) in the hippocampus and hypothalamus, after inhibition of L-aromatic amino acid decarboxylase by 3-hydroxybenzylhydrazine (NSD 1015), that is due to stimulation of autoreceptors on the 5-HT cell bodies. The kinetic properties of 5-HT1A receptors in the cerebral cortex and hippocampus, hippocampus alone, hypothalamus and medulla oblongata were determined with [3H]8-OH-DPAT. It was found that the postsynaptic effects were markedly attenuated after the treatment, the hypothermic effect already after a single dose.(ABSTRACT TRUNCATED AT 250 WORDS)


Subclinical cognitive impairment in chronic kidney disease is associated with frailty and reduced quality of life.
Cognitive impairment (CI) in chronic kidney disease (CKD) is highly prevalent and is associated with multiple limitations to patients as well as a higher mortality, more days of hospitalisation and a lower quality of life. Frailty in CKD is associated with adverse health outcomes and is also highly prevalent. The aim of our study was to determine the prevalence and characteristics of CI and relate the findings to frailty, mobility, muscle strength and health-related quality of life (HRQOL). Non-dialysis patients with CKD stages 3-5 were prospectively evaluated for inclusion. Excluded were patients with other cognitive disorders, signs of overt uraemic encephalopathy, severe infection and hyponatraemia. All patients underwent psychometric testing (five different tests): assessments of mobility, strength and frailty and an evaluation of HRQOL. Based on the number of pathological psychometric test results, we established two different definitions of CI: subclinical uraemic encephalopathy 1 (SUE1: one pathological test) and subclinical uraemic encephalopathy 2 (SUE2: two or more pathological test results). Sixty-two patients were included [median age 66 years (interquartile range 57-75), male 55%]. Most patients had CKD stage 3 (48%; stage 4: 32%; stage 5: 19%). CI was highly prevalent (SUE1: 60%; SUE2: 42%) and associated with a higher risk of falls (pathological tandem gait test; SUE1: 50% versus 16%, P = .023; SUE2: 69% versus 15%, P = .001), lower muscle strength (SUE2-pathological: 39% versus 7%, P = .008), frailty (SUE1: 59% versus 28%, P = .038; SUE2: 67% versus 33%, P = .028) and HRQOL. CI is highly prevalent in non-dialysis CKD patients. Even mild CI is associated with decreased mobility, muscle strength and HRQOL and increased frailty.


The isolated 48,000-dalton subunit of yeast DNA primase is sufficient for RNA primer synthesis.
The monoclonal antibody (mAb) 21A6, which specifically inhibits yeast DNA primase activity, has been used to verify whether only one of the two polypeptides of heterodimeric DNA primase (48 and 58 kDa) was responsible for DNA primase function in vitro. Immunoaffinity chromatography of a crude extract from cells of Saccharomyces cerevisiae on a mAb 21A6 protein A-Sepharose 6B column allowed the purification of the p48 primase polypeptide in an isolated form. This polypeptide was not derived through the dissociation of the four-subunit DNA polymerase alpha-primase complex, which can be purified from the same extract by affinity chromatography with a mAb recognizing the DNA polymerase alpha polypeptide. Therefore, free p48 was already present in the yeast extract and, possibly, within the cell. Isolated p48, devoid of any detectable p58 subunit, was sufficient for RNA primer synthesis, although free primase appeared to extend RNA primer-monomers to primer-multimers less efficiently. Primase activity associated with free p48 was highly unstable, indicating that although p48 bears the catalytic site, its association with the other polypeptides of the polymerase-primase complex plays an important role in stabilizing enzyme activity.


Characterization and application of l-methionine γ-lyase Q349S mutant enzyme with an enhanced activity toward l-homocysteine.
l-Methionine γ-lyse (MGL), a pyridoxal 5'-phosphate-dependent enzyme, catalyzes the α,γ-elimination of l-methionine (l-Met) and l-homocysteine (l-Hcy) to produce α-keto acids, thiols, and ammonia. Previously, various mutant enzymes of Pseudomonas putida MGL (PpMGL) were prepared to identify a homocysteine (Hcy)-specific enzyme that would assist the diagnosis of homocystinuria. Among the mutat enzymes the Q349S mutant exhibited high degradation activity toward l-Hcy. In the present study, PpMGL Q349S was characterized; the results suggested that it could be applied to determine the amount of l-Hcy. Compared to the wild-type PpMGL, specific activities of the Q349S mutant with l-Hcy and l-Met were 1.5 and 0.7 times, respectively. Additionally, we confirmed that l-Hcy in plasma samples could be accurately detected using the Q349S mutant by preincubating it with cysteine desulfurase (CsdA). Furthermore, we determined the X-ray crystal structure of PpMGL Q349S l-Met or l-Hcy complexes Michaelis complex, germinal diamine, and external aldimine at 2.25-2.40 Å. These 3D structures showed that the interaction partner of the β-hydroxyl group of Thr355 in the wild-type PpMGL was changed to the carboxyl group of the Hcy-PLP external aldimine in the Q349S mutant. The interaction of Ser349 and Arg375 was different between l-Met and l-Hcy recognition, indicating that it was important for the recognition of the carboxyl group of the substrate.


Meta-analysis of Cardiovascular Events and Related Biomarkers Comparing Survivors Versus Non-survivors in Patients With COVID-19.
Since the emergence of the coronavirus disease 19 (COVID-19), a number of studies have reported the presence of cardiovascular diseases in affected patients and linked them with a higher risk of mortality. We conducted an online search in Medline/PubMed to identify original cohorts comparing data between survivors and non-survivors from COVID-19. The presence of cardiovascular events and related biomarkers were compared between the 2 groups. Data on 1,845 hospitalized patients with COVID-19 were pooled from 12 comparative studies. The overall mortality rate in relation to COVID-19 was 17.6%. Men aged > 50 years old were more likely to die from COVID-19. Significant co-morbidities contributing to mortality were hypertension, diabetes mellitus, smoking, a previous history of cardiovascular disease including chronic heart failure, and cerebrovascular accidents. A significant relationship was observed between mortality and patient presentation with dyspnea, fatigue, tachycardia, and hypoxemia. Cardiovascular disease-related laboratory biomarkers related to mortality were elevated serum level of lactate dehydrogenase, creatine kinase, brain natriuretic peptide, and cardiac troponin I. Adverse cardiovascular disease-related clinical events preceding death were shock, arrhythmias, and acute myocardial injury. In conclusion, severe clinical presentation and elevated biomarkers in COVID-19 patients with established risk factors can predict mortality from cardiovascular causes.


Kinetics and thermodynamics of thermal inactivation for recombinant Escherichia coli cellulases, cel12B, cel8C, and polygalacturonase, peh28; biocatalysts for biofuel precursor production.
Lignocellulosic biomass conversion using cellulases/polygalacturonases is a process that can be progressively influenced by several determinants involved in cellulose microfibril degradation. This article focuses on the kinetics and thermodynamics of thermal inactivation of recombinant Escherichia coli cellulases, cel12B, cel8C and a polygalacturonase, peh 28, derived from Pectobacterium carotovorum sub sp. carotovorum. Several consensus motifs conferring the enzymes' thermal stability in both cel12B and peh28 model structures have been detailed earlier, which were confirmed for the three enzymes through the current study of their thermal inactivation profiles over the 20-80°C range using the respective activities on carboxymethylcellulose and polygalacturonic acid. Kinetic constants and half-lives of thermal inactivation, inactivation energy, plus inactivation entropies, enthalpies and Gibbs free energies, revealed high stability, less conformational change and protein unfolding for cel12B and peh28 due to thermal denaturation compared to cel8C. The apparent thermal stability of peh28 and cel12B, along with their hydrolytic efficiency on a lignocellulosic biomass conversion as reported previously, makes these enzymes candidates for various industrial applications. Analysis of the Gibbs free energy values suggests that the thermal stabilities of cel12B and peh28 are entropy-controlled over the tested temperature range.


Effect of various doses of deoxynivalenol on liver xenobiotic metabolizing enzymes in mice.
DON is one of the major mycotoxic contaminant of cereal grains throughout the world. The purpose of this investigation was to characterize the effects of a range of environmentally relevant doses of DON in mice exposed through a subchronic toxicological assay. Animals received 3 days per week for 4 weeks, 0.014, 0.071, 0.355 or 1.774 mg of toxin/kg b.w. All doses, except 0.014 mg/kg, provoked increases in plasma immunoglobulin A whereas there was no change in plasma biochemical parameters such as alkaline phosphatase, electrolytes or other immunoglobulins. Administration of 0.071 or 0.355 mg/kg doses led to increased liver microsomal pentoxyresorufin depentylase and cytosolic glutathione transferase activities. Examining protein modulation, western blot analyses liver fractions from mice receiving these doses revealed increased levels in both P450 2b, GST alpha and pi isoenzymes without any change in P450 1a expression. A significant competitive inhibition of deoxynivalenol on CDNB conjugation in vitro suggests that the mycotoxin is a putative substrate for glutathione S-transferases. These changes in liver xenobiotic metabolizing enzymes are discussed by considering the structural nature of deoxynivalenol and previous reports on similar effects exerted by other trichothecenes. These results suggest that a subchronic exposure to low doses of deoxynivalenol causes changes in the normal liver metabolism of xenobiotics.


Patterns and Timing of Recurrence following CRS and HIPEC in Colorectal Cancer Peritoneal Metastasis.
Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC) is an established treatment of Colorectal Peritoneal Metastases (CRPM). This study aims to determine the timing and patterns of recurrent disease on imaging following complete CRS/HIPEC. Retrospective analysis of a national peritoneal tumour service database identified CRPM patients with complete CRS/HIPEC(CC0) from 2005 to-2018. Patients with<2 years follow-up or and those where post-operative histology from the CRS/HIPEC procedure did not confirm CRPM from their original colorectal cancer were excluded. Time to recurrence was measured from surgery to first radiologically illustrated recurrence. CT was the primary modality used, supplemented by PET-CT or MRI if required. Outcomes of interest were survival data (including overall survival (OS), disease-free survival (DFS) and peritoneal-recurrence free survival (PRFS)), timing and patterns of recurrent disease. 146 of the 176 patients identified were eligible for inclusion. Median OS for all study patients was 45.2 months (95% CI 38-53 months), median DFS was 11.7 months (95% CI 9-14 months), and median PRFS was 25.2 months (95% CI 14.7-30 months). Recurrent disease was seen in 112 cases (77%), radiologically classified as intraperitoneal in 50 patients (44%), single site systemic in 21 patients (19%) and multi-site in 41 patients (37%). CT detection rate for disease recurrence was 88%. Subgroup analyses showed that PCI ≥12, positive nodal primary disease and synchronous peritoneal disease were associated with worse outcomes. Patients selected for CRS/HIPEC for CRPM have an OS > 45 months, with the majority recurring systemically within a year. Peritoneal recurrence is a later event after several years. Surveillance programs in this group should be most intensive in the first 2 years after surgery, using CT with oral and intravenous contrast.


Entropy production and the Second Law in photosynthesis.
An assertion that the primary photochemistry of photosynthesis can violate the Second Law of thermodynamics in certain efficient systems has been put forward by Jennings et al., who maintain their position strongly despite an argument to the contrary by Lavergne. We identify a specific omission in the calculation of Jennings et al. and show that no violation of the Second Law occurs, regardless of the photosynthetic efficiency.


Association between ratio of γ-glutamyl transpeptidase to high-density lipoprotein cholesterol and prevalence of nonalcoholic fatty liver disease and metabolic syndrome: a cross-sectional study.
Metabolic risk factors including obesity, insulin resistance, dyslipidemia, metabolic syndrome (MS), and diabetes are associated with nonalcoholic fatty liver disease (NAFLD). γ-Glutamyl transpeptidase (GGT) and high-density lipoprotein cholesterol (HDL-C) are associated with insulin resistance, dyslipidemia, oxidative stress, and obesity. We investigated the associations between GGT/HDL-C ratio and prevalence of NAFLD in a Chinese population. The study included 1,813 NAFLD (526 females, 1,287 males) and 4,513 non-NAFLD (3,077 females, 1,436 males) participants. The diagnosis of NAFLD was based on ultrasonography. Participants with NAFLD had higher GGT/HDL-C ratio, BMI, WC, TG, TC, and HOMA-IR, but lower HDL-C than participants without NAFLD. GGT/HDL-C ratio was significantly associated with prevalence of NAFLD. Specifically, for each 1 unit increase in GGT/HDL-C ratio, the prevalence of NAFLD will increase by 0.3%. As GGT/HDL-C ratio quartiles increased, prevalence of NAFLD/MS in Q4 (highest GGT/HDL-C ratio quartile) was 6.362/3.968 times higher than that in Q1 (lowest GGT/HDL-C ratio quartile). The AUC [0.799 (0.788-0.810)] for GGT/HDL-C ratio was significantly higher than those for GGT and HDL-C alone. The present results suggest that GGT/HDL-C ratio can be used as a predictive factor for prevalence of NAFLD after adjustment for confounding variables.


The Body and the Traumatic Real.
The symbol (word) first manifests itself as the killing of the thing…-Jacques Lacan1 This month our books and reviewers challenge us to examine the mental worlds and lived experience of women whose bodies are brutalized, pushed to extremes of overeating and undereating, of wishing to shout yet being unable to say a word. Nathalie Szilagyi reviews writer and feminist Roxane Gay's Hunger, a memoir detailing the author's struggles with self-acceptance and her body in the aftermath of severe trauma. In her review, Szilgayi asks us to imagine how we can help people facing situations like that of Gay, in ways more affirming and effective. Meanwhile, Michael Goldenberg, Kimberly Myers, and Jennifer Aengst examine three graphic memoirs and novels (Ink in Water, Lighter Than My Shadow, Speak: The Graphic Novel). They encourage us to look beyond our patients' speech balloons, affects, and exteriors, imagining the thought bubbles that loom overhead.


Surface modification of activated carbon cloth with calcium silicate and hydroxyapatite: bioactive composite material.
In this study new compounds consisting of activated carbon cloths (ACC) modified with calcium silicate (CaSiO3) were prepared for hydroxyapatite (HAP) generation. ACC samples were oxidized with 8 M HNO3 at different times (15 min and 2 h), to increase oxygenated functional groups. The CaSiO3 fine powders were prepared by chemical coprecipitation using Ca(NO3)2∙4H2O and Si(OC2H5)4, and 5 M NaOH was used as precipitant. The resulting powders were mixed with ethanol by ultrasound stirring and the previously oxidized activated carbon fibers were placed leaving under stirring for 30 min to allow particle dispersion. Once the formed compounds were dried, the samples were immersed in a simulated body fluid (SBF) solution for 21 days in conical tubes at 36.5 °C to allow the HAP formation on the ACC/CaSiO3 composite surface. The results indicated that the increase in oxidation time improves HAP formation on the surface from ACC/CaSiO3 compounds and this bioactive composite may be a potential material for bone regeneration.


Partial purification and some properties of a nucleoside phosphotransferase of chick embryos.
A nucleoside phosphotransferase purified about 40fold from chick embryos utilizes efficiently as phosphate donors deoxyribonucleoside and pyrimidine ribonucleoside monophosphates, whereas the pyrimidine deoxyribonucleoside appear to be the preferred acceptors of phosphate. The enzyme is very unstable to heat, dilution and dialysis. A marked enhancement in the stability is caused by nucleotides and it seems associated with the formation of an aggregated state of the protein.


Familial and social influences on juvenile gambling behavior.
Social learning theory maintains that individuals model, learn and maintain behaviors that are observed, appealing and reinforcing. As such, parents and family members can often serve as significant models for gambling. Four hundred and seventy seven children between the ages of 9 and 14 completed a questionnaire inquiring about their gambling activities, including where and with whom gambling occurs, as well as information concerning their perceptions of their own gambling behavior. Results indicate that 86% of children who gamble regularly reported gambling with family members. Fifty-three percent of students who gambled within the previous 12 months reported gambling with their siblings, 40% gambled with their parents, 46% gambled with other relatives, and 75% gambled in their own homes. Students' responses also indicated gambling with their friends (75%), gambling alone (18%), and with strangers (8%). As children's age increases they tend to gamble more at friend's homes and at school. Prevalence rates indicated that 81% of the total sample had gambled at one point in their lives and 52% of those children reported gambling once a week or more. Eleven percent reported that gambling makes them feel important, 27% feel they gamble more than they desire to do so, and only 10% of the grade 8 students fear being caught gambling, suggesting gambling activities to be a socially acceptable behavior. Several clinical and research questions are addressed.


Lanthanum Doping Enabling High Drain Current Modulation in a p-Type Tin Monoxide Thin-Film Transistor.
Effects of lanthanum (La) loading on the structural, optical, and electrical properties of tin monoxide (SnO) films were examined as a p-type semiconducting layer. La loading up to 1.9 atom % caused the texturing of the tetragonal SnO phase with a preferential orientation of (101), which was accompanied by the smoother surface morphology. Simultaneously, the incorporated La cation suppressed the formation of n-type SnO2 in the La-doped SnO film and widened its optical band gap. These variations allowed the 1.9 atom % La-loaded SnO film to have a high hole mobility and carrier density, compared with the La-free control SnO film. The superior semiconducting property was reflected in the p-type thin-film transistor (TFT). The control SnO TFTs exhibited the field-effect mobility (μSAT) and ION/OFF ratio of 0.29 cm2 V-1 s-1 and 5.4 × 102, respectively. Enhancement in the μSAT value and ION/OFF ratio was observed for the TFTs with the 1.9 atom % La-loaded SnO channel layer: they were improved to 1.2 cm2 V-1 s-1 and 7.3 × 103, respectively. The reason for this superior performance was discussed on the basis of smoother morphology, suppression of disproportionation conversion from Sn2+ to Sn + Sn4+, and reduced gap-state density.


Resolution, purification and characterization of the orthophosphate releasing activities from fracture callus calcifying cartilage.
Callus calcifying cartilage alkaline phosphatase was resolved by DEAE-cellulose column chromatography into two distinct phsophatase activities. The phosphatase activity which was eluted first from the column, (phosphatase I), was active towards a variety of phosphate esters, sodium pyrophosphatase and several linear polyphosphates, while the second phosphatase activity , (phosphatase II), was active toward simple phosphate esters but not towards sodium pyrophosphate and linear oligo or polyphosphates. All the phosphate esters, sodium pyrophosphate and polyphosphates at higher concentrations were inhibitory for phosphatase I. The modulating effects of magnesium, calcium, zinc and other phosphatase modulators have been investigated. Both phosphatases from callus calcifying cartilage were found to be substrates of neuraminidase with sialic acid as the product. Besides the difference in their specificity, the phosphatases were found to be immunologically different and to have different molecular weights, strong indication that they are different enzymes.


Endocrine system dysfunction and chronic heart failure: a clinical perspective.
Chronic heart failure (CHF) leads to an excess of urgent ambulatory visits, recurrent hospital admissions, morbidity, and mortality regardless of medical and non-medical management of the disease. This excess of risk may be attributable, at least in part, to comorbid conditions influencing the development and progression of CHF. In this perspective, the authors examined and described the most common endocrine disorders observed in patients with CHF, particularly in individuals with reduced ejection fraction, aiming to qualify the risks, quantify the epidemiological burden and discuss about the potential role of endocrine treatment. Thyroid dysfunction is commonly observed in patients with CHF, and sometimes it could be the consequence of certain medications (e.g., amiodarone). Male and female hypogonadism may also coexist in this clinical context, contributing to deteriorating the prognosis of these patients. Furthermore, growth hormone deficiency may affect the development of adult myocardium and predispose to CHF. Limited recommendation suggests to screen endocrine disorders in CHF patients, but it could be interesting to evaluate possible endocrine dysfunction in this setting, especially when a high suspicion coexists. Data referring to long-term safety and effectiveness of endocrine treatments in patients with CHF are limited, and their impact on several "hard" endpoints (such as hospital admission, all-cause, and cardiovascular mortality) are still poorly understood.


Vitamin A deficiency and genital viral burden in women infected with HIV-1.
The relation between vitamin A (retinol) deficiency and perinatal transmission of HIV-1, if it exists, might be mediated through an increased viral load in the mother's genital tract. To ascertain whether or not such an association is present, we measured the serum concentration of retinol with high performance liquid chromatography, and correlated the results with concurrent quantified HIV-1 RNA concentrations in cervicovaginal lavage fluid in 301 women infected with the virus. We noted no association between retinol status and genital HIV-1 load. Our findings lend support to those of studies that reported no association between retinol deficiency and perinatal HIV-1 transmission.


Effect of squalene on cyclophosphamide-induced toxicity.
Toxicity due to drugs used for neoplastic disorders is extensively documented. Cyclophosphamide (CYP) is a widely used antineoplastic drug, which could cause toxicity of normal cells due to its toxic metabolites. We evaluated the protective role of squalene (SQ) in the toxicity induced by cyclophosphamide. The activities of serum marker enzymes, clinical chemistry parameters and histopathology studies were done according to the standard procedures in the control and experimental groups of rats. Toxicity of the organs like heart, kidney and liver was evidenced from significant (P<0.05) increases of CK, LDH, AST, ALT, ALP, urea, creatinine and total bilirubin in cyclophosphamide- (150 mg/kg for 2 days) administered rats. Abnormal activities of these enzymes in the organs and serum total protein and cholesterol were also observed. No significant changes were observed in triglycerides in serum. Squalene oral treatment exerted protection towards these organs at a dose of 0.4 ml/day/rat. Histopathological examinations also confirmed the protective efficacy of squalene. Squalene may be efficacious as a cytoprotectant in cyclophosphamide-induced toxicities.


Tests for life chances: CD4 miracles and obstacles in Uganda.
This article discusses the relationship between technologies, socialities and inequities based on case material from a recent study about the first generation of people living with ART - Antiretroviral Therapy - in Uganda. The authors discuss how the diagnostic technologies of HIV tests, 'CD4 counts', and weight measuring produce results and numbers that are appropriated by people living with HIV to reflect upon their lives, bodies and relationships and hence influence their socialities and subjectivities. It is argued that because treatment programmes and especially their associated technologies vary greatly in Uganda, the programmes themselves introduce inequity in the already unequal landscape of HIV patients. In debates about biomedical technology and about HIV/AIDS it has been suggested that new kinds of socialities emerge, which have been conceptualised as 'therapeutic citizenship' and 'bio-sociality'. In the study on which the present article is based, clientship, friendship and kinship are kinds of sociality that play a much larger part in informants' lives than do 'therapeutic citizenship' and 'bio-sociality'. The authors attribute these findings, not only to the Ugandan setting, but to the method of doing extended case studies, which were not institution and programme based, but family and home based.


Mechanobiology-based physical therapy and rehabilitation after orthobiologic interventions: a narrative review.
This review aims to summarize the evidence for the role of mechanotherapies and rehabilitation in supporting the synergy between regeneration and repair after an orthobiologic intervention. A selective literature search was performed using Web of Science, OVID, and PubMed to review research articles that discuss the effects of combining mechanotherapy with various forms of regenerative medicine. Various mechanotherapies can encourage the healing process for patients at different stages. Taping, bracing, cold water immersion, and extracorporeal shockwave therapy can be used throughout the duration of acute inflammatory response. The regulation of angiogenesis can be sustained with blood flow restriction and resistance training, whereas heat therapy and tissue loading during exercise are recommended in the remodeling phase. Combining mechanotherapy with various forms of regenerative medicine has shown promise for improving treatment outcomes. However, further studies that reveal a greater volume of evidence are needed to support clinical decisions.


Reassessment of the Necessity of the Proton Gantry: Analysis of Beam Orientations From 4332 Treatments at the Massachusetts General Hospital Proton Center Over the Past 10 Years.
To retrospectively analyze the beam approaches used in gantry-based proton treatments, and to reassess the practical advantages of the gantry, compared with beam approaches that are achievable without a gantry, in the context of present-day technology. We reviewed the proton therapy plans of 4332 patients treated on gantries at our hospital, delivered by the double scattering technique (n=4228) and, more recently, pencil beam scanning (PBS) (n=104). Beam approaches, relative to the patient frame, were analyzed individually to identify cases that could be treated without a gantry. Three treatment configurations were considered, with the patient in lying position, sitting position, or both. The FIXED geometry includes a fixed horizontal portal. The BEND geometry enables a limited vertical inflection of the beam by up to 20°. The MOVE geometry allows for flexibility of the patient head and body setup. The percentage of patients with head and neck tumors that could be treated without a gantry using double scattering was 44% in FIXED, 70% in 20° BEND, and 100% in 90° MOVE. For torso regions, 99% of patients could be treated in 20° BEND. Of 104 PBS treatments, all but 1 could be reproduced with FIXED geometry. The only exception would require a 10° BEND capability. Note here that the PBS treatments were applied to select anatomic sites, including only 2 patients with skull-base tumors. The majority of practical beam approaches can be realized with gantry-less delivery, aided by limited beam bending and patient movements. Practical limitations of the MOVE geometry, and treatments requiring a combination of lying and sitting positions, may lower the percentage of head and neck patients who could be treated without a gantry. Further investigation into planning, immobilization, and imaging is needed to remove the practical limitations and to facilitate proton treatment without a gantry.


Tracheoesophagogastric anastomosis fistula: a rare complication of esophagectomy.
Fistulas between trachea and esophagogastric anastomosis after esophagectomy are uncommon. We describe 2 patients with such a lesion successfully managed with single-stage repair. The fistula was divided, the tracheal defect was closed directly or with a free pericardial graft, and the esophagogastric anastomosis was redone. A muscle or pleural flap was used to separate the tracheal and digestive suture lines. This treatment of a potentially life-threatening condition yielded excellent results without postoperative complications.


Integrated real-time imaging system, 'IRIS', Kangaroo feeding tube: a guide to placement and image interpretation.
Lung complications occur in 0.5% of the millions of blind tube placements. This represents a major health burden. Use of a Kangaroo feeding tubes with an 'integrated real-time imaging system' ('IRIS' tube) may pre-empt such complications. We aimed to produce a preliminary operator guide to IRIS tube placement and interpretation of position. In a single centre, IRIS tubes were prospectively placed in intensive care unit patients. Characteristics of tube placement and visualised anatomy were recorded in each organ to produce a guide. Of 45 patients having one tube placement, 3 were aborted due to refusal (n=1) or inability to enter the oesophagus (n=2). Of 43 tubes placed beyond 30 cm, 12 (28%) initially entered the respiratory tract but all were withdrawn before reaching the main carina. We identified anatomical markers for the nasal or oral cavity (97.8%), respiratory tract (100%), oesophagus (97.6%), stomach (100%) and intestine (100%). Organ differentiation was possible in 100%: trachea-oesophagus, oesophagus-stomach and stomach-intestine. Gastric tube position was confirmed by aspiration of fluid with a pH <4.0 and/ or X-ray. Trauma was avoided in 13.6% by identifying that the tube remained in the nasal lumen in the presence of a base of skull fracture (n=3) and in the stomach in the presence of recently bleeding polyps or mucosa (n=3). A systematic guide was produced from records of tube placement and interpretation of anatomical images. By permitting real-time confirmation of tube position, direct vision may reduce risk of lung complications. The preliminary operator guide requires validation in larger studies.


The pattern of myelin proteins in triethyltin (TET) intoxication.
Myelin proteins isolated from the brain of Wistar rats intoxicated chronically with triethyltin sulfate (TET) according to the technique of ETO et al. (1971) were investigated. Among the various protein fractions, the Agraval protein happened to be most evidently affected, demonstrating considerably reduced percentages. However the results did not prove that any of the individual myelin proteins was specifically affected by TET intake. The interesting point in chronic TET poisoning was that some clinical symptoms as well as disturbances in myelin proteins demonstrated a clear tendency to retrogression despite of the continued intoxication. These observations indicate obviously that during chronic TET intake, some kind of biochemical adaptation to the noxious action of the poison on the myelin sheath takes place.


Pimobendan directly sensitizes reconstituted thin filament to slide on cardiac myosin.
To elucidate the mechanism of the Ca(2+)-sensitizing action of pimobendan, cardiac thin filaments were reconstituted from actin and tropomyosin-troponin complex and made to slide on a myosin layer. Although filaments showed Brownian movement with a low Ca2+ concentration, they slid at a constant velocity above a certain level of Ca2+ concentration, showing that the sliding was regulated by Ca2+ within a narrow pCa range. Acidosis, addition of inorganic phosphate, and phosphorylation of troponin I increased the threshold Ca2+ concentration. Addition of pimobendan reversed these desensitization effects. These results clearly demonstrated that pimobendan directly increases the Ca2+ sensitivity of thin filament.


Comparison of Clinical Outcomes Stratified by Target Delineation for Patients Undergoing Stereotactic Body Radiotherapy for Spinal Metastases.
Stereotactic body radiotherapy (SBRT) is an effective treatment of spinal metastases in the vertebral body. However, variation has existed between practitioners regarding the appropriate target delineation. As such, we compared the tumor control, rates of compression fractures, and pain control for patients who had undergone SBRT for spinal metastases to either the lesion only (LO) or the full vertebral body (FVB). A total of 126 spinal metastases in 84 patients had received single-fraction SBRT from January 2009 to February 2015. Of the 126 lesions, 36 (29%) were in the FVB group and 90 were in the LO group. The SBRT plans were reviewed to determine the treatment volume. Odds ratios were used to compare the rates of compression fracture and local failure. Regression analysis was performed to identify the predictors of outcome. A total of 5 failures had occurred in the FVB group and 14 in the LO group; however, the difference was not statistically significant (P = 0.5). No difference was found in pain reduction between the 2 groups (P = 0.9). Seven post-treatment compression fractures occurred in the LO group and four in the FVB group; however, the difference was not statistically significant (P = 0.6). The minimum dose to the planning target volume, patient age, and planning target volume size were the only significant factors predicting for local failure, vertebral body fracture, and pain control, respectively. Given that we found no difference in tumor control, pain reduction, or fracture rate between patients treated to the FVB versus the. LO, it might be reasonable to consider SBRT to the LO for select patients.


Relationship Between Post-Traumatic Stress Symptoms and Caregiver Burden In Breast Cancer Patients: The Mediating Role of Anxiety and Depression.
Breast cancer impacts not only the physical and mental health of patients but also the people around them-especially their caregivers. This study examined the relationship between post-traumatic stress symptoms (PTSS) and caregiver burden in breast cancer patients through the mediating pathway of anxiety and depression. A total of 236 breast cancer patients from China completed the Chinese Version of the Posttraumatic Stress Disorder Symptom Scale (PSS), the Chinese version of the Patient Health Questionnaire (PHQ-9), the Chinese version of the General Anxiety Symptoms Scale (GAD-7). In addition, caregivers of these breast cancer patients were surveyed by the Caregiver Self-Assessment Questionnaire (CSAQ). Structural equation model showed that our model fitted well [χ2 /df = 1.966, TLI = 0.959, CFI = 0.994, RMSEA (90% CI) = 0.065 (0-0.12)] and revealed that anxiety, but not depression, mediated the relationship between PTSS in breast cancer patients and caregiver burden. The level of PTSS was positively correlated with anxiety and depression in breast cancer patients, and the level of anxiety and depression was positively related to caregiver burden. The PTSS of patients positively predicted caregiver burden and this relationship appears to be mediated by the patient's anxiety.


Implementation of a PCR assay of Pasteurella pneumotropica to accurately screen for contaminated laboratory mice.
The authors implemented a PCR protocol to rapidly screen for Pasteurella pneumotropica and to accurately identify contaminated laboratory mice in a clinical setting. This protocol was implemented in response to a severe outbreak of P. pneumotropica in their animal facility. Although a sentinel program was in place to routinely screen for P. pneumotropica, it was inadequate for the identification of contaminated animals. As a result, several additional strains of mice were contaminated and developed clinical signs of infection. The authors implemented a screening method using PCR with reported primer pairs previously developed to identify the biotype isolates of P. pneumotropica in laboratory mice. Throat culture swabs were collected from live mice and placed in a bacterial culture. The DNA from these cultures was isolated and screened by PCR. This procedure enabled the authors to eliminate P. pneumotropica from several animal housing rooms. The assay can be easily applied in most animal facilities.


Generation of activated and antigen-specific T cells with cytotoxic activity after co-culture with dendritic cells.
Co-culturing of immunological effector cells with antigen-pulsed DC leads to an increase of cytotoxic activity against antigen-expressing tumour cells. Using this approach, we could detect up to 2.8% antigen-specific CTLs after co-culture with antigen-pulsed DC. However, the required high effector cell numbers remain a major obstacle in immunotherapy. In this study, we show an approach for generating activated and antigen-specific effector cells that enables us to decrease effector to target cell ratios. We used an interferon-gamma secretion assay to enrich activated effector cells after co-culture with antigen-pulsed dendritic cells (DC). Purified immunological effector cells lysed 58.3% of antigen-expressing tumour cells at an effector to target ratio of 1:1. Furthermore, using MHC-IgG complexes, we enriched effector cells expressing antigen-specific T-cell receptor after co-culture with DC. Performing ELISpot, flow cytometry and TCR analysis, we could show a significant increase of activated and specific TCR-expressing effector cells after co-culture with DC.


Regulation and involvement of the ubiquitin ligases in muscle atrophy.
The ability to activate compensatory mechanisms in response to environmental stress is an important factor for survival and maintenance of cellular functions. A system that is often activated both in short and prolonged stress conditions is ubiquitin proteasome system (UPS). UPS is required to clear the cell from dysfunctional and altered proteins and is reported to increase during catabolic conditions. This increase contributes to the loss of contractile proteins and, when is exacerbated, to cachexia. Here I'll present the last data about UPS regulation, the role of UPS in protein turnover in skeletal muscles and the pathogenetic implications of deregulated UPS in muscle disorders.


Acute hypomagnesaemia causing intra-operative lower limb movements in a paraplegic patient, despite full neuromuscular blockade.
Alterations in electrolyte homeostasis associated with major surgery, intravenous fluid therapy, malnutrition, and critical illness are common but usually non-specific. This case report describes the sudden onset of forceful rhythmic flexion movements in both lower limbs during scoliosis surgery in a 12-year-old paraplegic boy with spina bifida. These movements arose despite adequate depth of anaesthesia, complete neuromuscular blockade, and treatment of hypocalcaemia. They persisted post-operatively after reversal of neuromuscular blockade and emergence from anaesthesia. Hypomagnesaemia was identified and treated post-operatively which coincided with cessation of the movements. We deduce hypomagnesaemia to be the aetiology of this unusual clinical presentation. This report underscores the interdependency of Ca2+ and Mg2+ homeostasis in excitable tissues and emphasizes that abnormalities observed in each cation should not be considered independently. In the perioperative care of spinal fusion patients, hypocalcaemia is a well-recognised and understood complication.


Prediction modeling-part 2: using machine learning strategies to improve transplantation outcomes.
Kidney transplant recipients and transplant physicians face important clinical questions where machine learning methods may help improve the decision-making process. This mini-review explores potential applications of machine learning methods to key stages of a kidney transplant recipient's journey, from initial waitlisting and donor selection, to personalization of immunosuppression and prediction of post-transplantation events. Both unsupervised and supervised machine learning methods are presented, including k-means clustering, principal components analysis, k-nearest neighbors, and random forests. The various challenges of these approaches are also discussed.


Frequency power and coherence of electroencephalography are correlated with the severity of Alzheimer's disease: A multicenter analysis in Taiwan.
Slowing of average electroencephalography (EEG) frequency in Alzheimer's disease (AD) is well established, but whether EEG changes are able to reflect the severity of AD is uncertain. We attempt to establish quantitative EEG parameters that are suitable for evaluating AD in clinical practice. Ninety-five patients with newly diagnosed AD at different stages from four neurologic institutes were enrolled for the study. Standard scalp resting EEG data were collected for quantitative analysis. Global band power ratio and interhemispheric alpha band coherence were calculated. Patients with advanced AD had a greater slow-to-fast wave power ratio. Among several power ratio parameters, global theta and delta to alpha and beta band power ratio showed the best correlation with stages of AD (p < 0.05 between any two patient groups). Patients with advanced AD had decreased coherence in multiple brain regions. The phenomenon was most prominent in the centroparietal region (p < 0.05 between any two patient groups). Increased global slow-to-fast power ratio and decreased centroparietal interhemispheric alpha band coherence are strongly correlated with disease progress in AD patients. These two quantitative EEG parameters may help evaluate AD patients in daily clinical practice. Global power ratio changes may suggest a shift of dominant frequency, and decreased interhemispheric alpha band coherence may suggest functional disconnection and corpus callosum abnormalities in AD patients.


Outcomes of passive-active immunoprophylaxis given to infants of mothers infected with hepatitis B virus in Babol, Iran.
Infants born to chronic hepatitis B virus (HBV) infected mothers may be infected in spite of receiving passive-active immunoprophylaxis. The purpose of this study was to assess the outcome of infants born to women actively infected by HBV. From April 2004 to September 2009, infants born to women actively infected by HBV received hepatitis B immune globulin (HBIG) and the first dose of hepatitis B vaccine at birth. The second and third doses of HBV vaccine were administered at 1 and 6 months of age. Post-vaccination tests to detect HBsAg and anti-HBs were assessed between 12 and 15 months of age. Those who had anti-HBs titers<10mIU/ml received the second series of HBV vaccine. Thirty-four and 201 infants were born to HBeAg-seropositive and anti-HBe-seropositive mothers, respectively. HBsAg was detected in 6 (17.6%) infants born to HBeAg-seropositive mothers and in 3 (1.5%) to anti-HBe-seropositive mothers (p=0.0001). Anti-HBs ≥ 10mIU/ml were achieved in 26 (76.5%) and 178 (88.6%) infants of HBeAg-seropositive and anti-HBe-seropositive mothers, respectively (p>0.05). Twenty-two (9.4%) infants were non-responders and 11(50%) of them responded to the second series of HBV vaccine. The results show that infants of HBeAg-seropositive mothers have higher risk of developing of HBV infection. Some HBsAg-seronegative infants may not respond to passive-active immunoprophylaxis and may remain at risk of HBV infection.