Dissociation of exercise tolerance and total myocardial ischemic burden in chronic stable angina pectoris.
Exercise treadmill tests and ambulatory monitoring were used in a double-blind, placebo-controlled, double-dummy crossover comparison of nifedipine (10 mg, 3 times daily) and transdermal nitroglycerin (15 mg). All patients (n = 20) had chronic stable angina with symptomatic and silent events. All patients had 3 episodes of angina/week and 3 episodes of ischemia/24 hr. The protocol was made up of 2 weeks of placebo followed by 2 weeks of active drug, then crossed over for 2 weeks of placebo followed by the other active drug. At the end of each 2-week period, patients had ambulatory monitoring and exercise treadmill testing. All ambulatory monitoring reports were read blind and entered into an independent data base. The results were the following: on transdermal nitroglycerin, the duration of ischemia decreased by 57% from 140 min/24 hr to 60 min/24 hr (p = 0.0054). The exercise time increased by 5.5% from 4.8 to 5.0 minutes (p = 0.16). With nifedipine, the duration of ischemia decreased by 22% from 175 min/24 hr to 137 min/24 hr (p = 0.16). The exercise tolerance time increased by 13% from 4.5 to 5.0 minutes (p = 0.0264). Nifedipine increased exercise time without altering total ischemic time, while transdermal nitroglycerin decreased total ischemic time without increasing exercise time. Thus, changes in exercise time do not necessarily predict changes in total ischemic time.


Uptake and release of tetracycline by cultured carrot cells.
The nature of tetracycline uptake by carrot cell suspension cultures is described. Tetracycline enters the cells by diffusion and the intracellular level of the antibiotic increases with the amount added. Exposure of carrot cells to high levels of tetracycline for a limited time (24 hr) followed by the removal of the drug and the resuspension of the cells in drug-free medium does not affect cell growth and has no inhibitory effect on protein synthesis (14C-leucine incorporation).


[The Veterinary Drug Act, the Veterinary Practice Act and the cattle farmer].
The concept of 'local practising' will disappear in the new legislation. This will render veterinary medicine by mail order possible. From the point of view of the quality of the ultimate product, this development should be strongly rejected. The section will benefit by an expert and payable herd management programme which has as its object a justified use of drugs and a 'clean ultimate product' (healthy animals).


The speed of sound through trabecular bone predicted by Biot theory.
Cancellous bone is a highly porous material filled with fluid. The mechanical properties of cancellous bone determine whether the bone is normal or osteoporotic. Wave propagation can be used to measure the elastic constants of cancellous bone. Recently, poroelasticity theory has been used to predict the elastic constants of cancellous bone from the wave velocities. In this study, it is shown that the fast wave, predicted by the Biot theory, corresponds to the wave penetrating the trabeculae, while the slow wave is determined by the interaction between the trabeculae and the fluid. The trabecular shape does not affect the wave velocity significantly when using the variable, which is determined by the microstructure, and the slow wave velocity decreases after the porosity reaches 80%.


Mutations in the conserved loop of human U5 snRNA generate use of novel cryptic 5' splice sites in vivo.
We have analyzed base pairing interactions between the U5 snRNA and 5' exon sequences during pre-mRNA splicing in a mammalian in vivo system. We constructed synthetic U5 genes with mutations that alter four bases (C3, U4, U5 and U6) within the invariant 9 nt U5 sequence GCCUUUUAC; transient transfection of HeLa cells with these U5 sequences cloned into a U1 expression vector yielded high levels of the mutant snRNAs. To test their function, we cotransfected a rabbit beta-globin gene containing one of two mutations (G1-->A or T2-->A) in the essential GT dinucleotide at the 5' end of the second intron. Certain U5 loop mutants activated novel 5' splice sites only in mutant rabbit beta-globin transcripts. One novel site surprisingly resides in the first exon; its use is invariably coupled to utilization of a particular cryptic 5' splice site in the second exon. All of the newly activated cryptic 5' splice sites exhibit complementarity with the mutant U5 loop in the exon 1-5 nt upstream of the cryptic site, extending previous results in yeast. However, the register of the potential pairing is not identical at the various novel cryptic 5' splice sites, indicating that the interaction between the U5 loop and the 5' exon may be more flexible than previously believed.


The thermoregulatory effects of noradrenaline, serotonin and carbachol injected into the rat spinal subarachnoid space.
1. We have examined the effects on thermoregulation in the rat of noradrenaline bitartrate (NA), 5-hydroxytryptamine hydrochloride (5-HT) and carbamylcholine chloride (CCh) injected into the lumbar spinal subarachnoid space via a chronic indwelling catheter.2. Intrathecal injections of the monoamines and CCh reproducibly affected thermoregulation, whereas injections of control solutions had no effect.3. Intrathecal injections of NA (0.01-0.30 mumol) produced a dose-dependent hypothermia associated with a decrease in tail skin vasomotor tone. Shivering activity was not depressed during the hypothermia and sometimes increased. Intrathecal administration of the alpha-adrenergic agonist clonidine (0.0175-0.070 mumol) elicited changes in T(c) and T(sk) similar to those induced by intrathecal NA.4. Intrathecal 5-HT (0.030-0.90 mumol) elicited a dose-dependent hyperthermia accompanied by increased tail skin vasomotor tone and increased shivering.5. CCh injected intrathecally (0.001-0.06 mumol) evoked a dose-dependent hyperthermia. During the period when core temperature was rising, tail skin vasomotor tone increased and shivering-like activity was present. Once the maximum core temperature had been reached, tail skin vasodilatation occurred. Vasodilatation persisted until core temperature had returned to normal.6. Intravenous injections of 5-HT (0.30 and 0.90 mumol) or CCh (0.006 and 0.03 mumol) caused no thermoregulatory effect. The effects of these agents injected intrathecally were therefore not due to an action in the periphery.7. Intravenous infusions of NA (0.06 and 0.10 mumol) produced hypothermia and transient tail skin vasodilatation. We suggest that an action at peripheral sites may have contributed to the effects produced by intrathecal injection of this monamine.8. These findings suggest that spinal noradrenergic, serotonergic and cholinergic synapses may be importantly involved in the control of body temperature in the rat. The possible functional roles of these synapses and the putative spinal sites of action of the injected substances are discussed.


Klotho recovery by genistein via promoter histone acetylation and DNA demethylation mitigates renal fibrosis in mice.
Renal fibrosis is a common histomorphological feature of renal aging and chronic kidney diseases of all etiologies, and its initiation and progression are substantially influenced by aberrant epigenetic modifications of fibrosis-susceptible genes, yet without effective therapy. "Epigenetic diets" exhibit tissue-protective and epigenetic-modulating properties; however, their anti-renal fibrosis functions and the underlying mechanisms are less understood. In this study, we show that genistein, a phytoestrogenic isoflavone enriched in dietary soy products, exhibits impressive anti-renal fibrosis activities by recovering epigenetic loss of Klotho, a kidney-enriched anti-aging and fibrosis-suppressing protein. Mouse fibrotic kidneys induced by UUO (unilateral ureteral occlusion) displayed severer Klotho suppression and adverse expression of renal fibrosis-associated proteins, but genistein administration markedly recovered the Klotho loss and attenuated renal fibrosis and the protein expression abnormalities. The examination of possible causes of the Klotho recovery revealed that genistein simultaneously inhibited histone 3 deacetylation of Klotho promoter and normalized the promoter DNA hypermethylation by suppressing elevated DNA methyltransferase DNMT1 and DNMT3a. More importantly, genistein's anti-renal fibrosis effects on the renal fibrotic lesions and the abnormal expressions of fibrosis-associated proteins were abrogated when Klotho is knockdown by RNA interferences in UUO mice. Thus, our results identify Klotho restoration via epigenetic histone acetylation and DNA demethylation as a critical mechanism of genistein's anti-fibrosis function and shed new lights on the potentials of epigenetic diets in preventing or treating aging or renal fibrosis-associated kidney diseases. KEY MESSAGES: Genistein prevents renal fibrosis and the associated Klotho suppression in UUO mice. Genistein upregulates Klotho in part by reversing the promoter histone 3 hypoacetylation. Genistein also preserves Klotho via relieving Klotho promoter hypermethylation. Genistein demethylates Klotho promoter by inhibiting aberrant DNMT1/3a expression. Genistein restoration of Klotho is essential for its anti-renal fibrosis function.


Reactive arthritis after the intravesical instillation of BCG.
The intravesical instilation of bacillus Calmette-Guérin (BCG) is a widely used and efficacious procedure for treatment of intermediate to high-grade superficial bladder cancer. The occurrence of osteoarticular side effects is infrequent compared to the number of administrated doses, and reactive arthritis is included within these effects. We present the case of a 54 years old HLA-27 (+) male, who developed reactive arthritis featuring asymmetric olygoarthritis and dactylitis after the second intravesical BCG instillation, which was resolved with administration of Etoricoxib and Isoniazid.


Fast determination of free metronidazole in rat plasma and peritoneal fluid using HPLC-UV method.
Peritonitis refers to the inflammatory reaction of the peritoneum to aggression. In addition, it contributes significantly to sepsis. The presence of free concentrations of antimicrobials above the minimum inhibitory concentration at the site of infection is critical to therapeutic response. Metronidazole (MTZ) is an antimicrobial used to treat peritonitis because of its effectiveness against anaerobic microorganisms. This study investigates free MTZ concentrations in peritoneal microdialysate in Wistar rats. A C18 column (150 × 4.0 mm, 5 μm) was used for the analysis conducted at 40°C under isocratic conditions. The mobile phase consisted of acetonitrile and an aqueous solution of 50-mM monobasic phosphate buffer and 0.1% triethylamine, with pH 3.0 (10:90, v/v). MTZ calibration was linear in the range of 0.5-30.0 μg/ml. The intra- and inter-day precision was satisfactory with relative standard deviation ≤5.67%. The accuracy ranged from 90.64 to 103.77%, and the lower limit of quantification was 0.5 μg/ml. The developed method was successfully applied in a pilot pharmacokinetic study after MTZ administration (30 mg/kg, intravenously) in rats. The main advantage of the employed method is that it does not require sample processing and protein removal steps. This is the first study to be conducted using MTZ in rats.


Opioid Consumption After Knee Arthroscopy.
To prospectively observe opioid consumption in patients undergoing knee arthroscopy and to create an evidence-based guideline for opioid prescription. This prospective multicenter observational study enrolled patients undergoing outpatient knee arthroscopy for meniscal repair, meniscectomy, or chondroplasty. Patients were provided with a pain journal to record postoperative opioid consumption, Numeric Pain Rating Scale (NPRS) pain scores, and Likert scale satisfaction scores for 1 week postoperatively. State databases were reviewed for additional opioid prescriptions. One hundred patients were included in this study. Patients were prescribed a median of 5 pills (37.5 oral morphine equivalent [OME]). Median postoperative opioid consumption was 0 pills, with a mean of 0.6 pills (4.4 OME), and 74% of patients did not consume any opioid medication postoperatively. All patients consumed ≤5 pills (37.5 OME), and no patient required a refill. Patients reported a mean daily NPRS value of 1.9 out of 10 and a mean Likert score of 4.4 out of 5. We found that current opioid prescribing habits exceed the need for postoperative pain management. Overall, all patients consumed ≤5 opioid pills, and 92% of patients discontinued opioids by the second postoperative day. In spite of the low prescription quantity, patients reported high satisfaction rates and low NPRS pain scores and required no refills. Therefore, we recommend that patients undergoing knee arthroscopy are prescribed no more than 5 oxycodone 5-mg pills. II, prospective prognostic cohort investigation.


Involvement of hyperglycemia in deposition of aggregated protein in glomeruli of diabetic mice.
The aim of this study was to clarify the influence of hyperglycemia on the deposition of aggregated protein in the glomeruli of diabetic mice. KK-A(y) mice injected with aggregated bovine serum albumin accumulated more of it in the glomeruli than did ICR mice. There were no histological alterations in the glomeruli of KK-A(y) mice. KK-A(y) mice given voglibose in mouse-chow for 2 weeks had significantly reduced blood glucose, glycated albumin, and hemoglobin A(1C) levels compared with control mice. The voglibose-treated KK-A(y) mice were injected with aggregated bovine serum albumin and accumulated significantly less albumin in the glomeruli than did the control mice. Pioglitazone decreased blood glucose levels compared with the control, and reduced the glomerular deposition of aggregated albumin. Glomerular aggregated bovine serum albumin levels and blood glucose levels were reduced significantly by the injection of insulin. Six times more advanced glycation endproducts were produced from aggregated bovine albumin than from non-aggregated bovine albumin on incubation with glucose and L-lysine in vitro. Glucose-loaded ICR mice generated more advanced glycation endproducts from aggregated albumin, and had more aggregated bovine albumin in the glomeruli. It was suggested that hyperglycemia contributes to an increase in the deposition of aggregated protein in glomeruli even early on in diabetes.


Women's perceived barriers to giving birth in health facilities in rural Kenya: A qualitative evidence synthesis.
In Kenya, uptake of skilled care during birth remains lower in rural areas when compared to urban areas, despite efforts by the government to encourage facility-based births by abolishing maternity fees in public health facilities. To synthesise published and unpublished qualitative research that explores women's perceived barriers to facility-based birth in rural Kenya. Qualitative evidence synthesis DATA SOURCES: Multiple electronic databases (MEDLINE, EMBASE, PsycINFO, POPLINE, CINAHL, Web of Science and ProQuest), grey literature searches, citation chaining and checking of reference lists. Studies were screened by title, abstract and full text, after which a standardised qualitative checklist was used to assess study quality. Synthesis of extracted data followed the 'best-fit' framework method, enhanced with a pathway-based model for the improvement of maternal and newborn care. Sixteen eligible studies were identified. Key themes were: (i) knowledge, attitudes and practices, including past experiences of health facilities and community beliefs about facility services; (ii) insufficient demand for professional care caused by the perceived advantages of seeking alternative care during birth and the disadvantages of facility-based births; (iii) limited access to services, especially in rural areas, because of poor infrastructure; (iv) misconceptions regarding labour characteristics and, (v) poor awareness of labour outcomes. Important factors can be characterised as 'push' factors (those pushing women away from facilities) and 'pull' factors (those related to the relative advantage of facility-based births). However, key to an individual woman's decision are factors relating to knowledge, attitudes and practices and awareness of labour outcomes. While a critical tension exists between government policy and consumer choice, the prevalence of inadequate awareness and the dominance of past experiences and community beliefs offer significant obstacles to a woman in making an informed choice about her preferred place of giving birth.


A randomized EORTC trial comparing intra-arterial infusion with methotrexate vs bleomycin as initial therapy in carcinoma of the oral cavity.
Either intra-arterial infusions of MTX (500 mg over 10 days) or intra-arterial infusions of BLM (95 mg over 13 days) were administered as initial treatment to 85 patients with untreated squamous cell carcinomas of the oral cavity. Tumour regression was assessed 10-15 days after the end of chemotherapy. A sequential analysis was used, and BLM demonstrated a significantly greater local efficacy after the 32nd matched pair was assessed. The same results were observed when tumour response rates were compared, ignoring the matching, on the 85 patients, (P less than 0.001). The response rate for patients with neck nodes was low (10/38). Catheter management problems, toxic effects and lethal reactions were 2.5 times more frequent in the MTX group.


A photocytes-associated fatty acid-binding protein from the light organ of adult Taiwanese firefly, Luciola cerata.
Intracellular fatty acid-binding proteins (FABPs) are considered to be an important energy source supplier in lipid metabolism; however, they have never been reported in any bioluminescent tissue before. In this study, we determined the structural and functional characteristics of a novel FABP (lcFABP) from the light organ of adult Taiwanese firefly, Luciola cerata, and showed anatomical association of lcFABP with photocytes. Our results demonstrated the primary structure of lcFABP deduced from the cDNA clone of light organ shares structural homologies with other insect and human FABPs. In vitro binding assay indicated the recombinant lcFABP binds saturated long chain fatty acids (C₁₄-C₁₈) more strongly than other fatty acids and firefly luciferin. In addition, tissue distribution screening assay using a rabbit antiserum specifically against the N-terminal sequence of lcFABP confirmed the light organ-specific expression of lcFABP. In the light organ, the lcFABP constituted about 15% of total soluble proteins, and was detected in both cytosol and nucleus of photocytes. The specific localization of abundant lcFABP in the light organ suggests that sustained bioluminescent flashes in the light organ might be a high energy demanding process. In photocytes, lcFABP might play a key role in providing long chain fatty acids to peroxisomes for the luciferase-catalyzed long chain acyl-CoA synthetic reaction.


SARS-CoV-2 viral dynamic modeling to inform model selection and timing and efficacy of antiviral therapy.
Mathematical models of viral dynamics have been reported to describe adequately the dynamic changes of severe acute respiratory syndrome-coronavirus 2 viral load within an individual host. In this study, eight published viral dynamic models were assessed, and model selection was performed. Viral load data were collected from a community surveillance study, including 2155 measurements from 162 patients (124 household and 38 non-household contacts). An extended version of the target-cell limited model that includes an eclipse phase and an immune response component that enhances viral clearance described best the data. In general, the parameter estimates showed good precision (relative standard error <10), apart from the death rate of infected cells. The parameter estimates were used to simulate the outcomes of a clinical trial of the antiviral tixagevimab-cilgavimab, a monoclonal antibody combination which blocks infection of the target cells by neutralizing the virus. The simulated outcome of the effectiveness of the antiviral therapy in controlling viral replication was in a good agreement with the clinical trial data. Early treatment with high antiviral efficacy is important for desired therapeutic outcome.


Gaucher and Fabry diseases: from understanding pathophysiology to rational therapies.
Over the past 40 years there has been remarkable development in our understanding of the pathophysiology of lysosomal storage disorders. This review describes the research carried out on the sphingolipid storage disorders from the first demonstration of the underlying metabolic abnormality in Gaucher disease to the development of enzyme replacement therapy for Gaucher and Fabry diseases. Initial developments in gene therapy are also described. The introduction of enzyme replacement therapy has provided a lifeline for patients with Gaucher or Fabry disease. It is anticipated that future developments, including gene therapy, will provide additional therapeutic options.


Sifting fluctuation scattering from microtextured samples.
As the relationship of texture and microtexture to fluctuation X-ray scattering (FXS) has been clarified in detail, key progress is expected in the exploitation of FXS-based structural investigation of matter exhibiting complex order.


Cardiac Registries During the COVID-19 Pandemic: Lessons Learned.
We discuss the role of observational studies and cardiac registries during the COVID-19 pandemic. We focus on published cardiac registries and highlight contributions to the field that have had clinical implications. We included observational studies of COVID-19 patients published in peer-reviewed medical journals with defined inclusion and exclusion criteria, defined study design, and primary outcomes. A PubMed and MEDLINE literature review results in 437 articles, of which 52 include patients with COVID-19 with cardiac endpoints. From July 2020 to December 2021, the average time from last data collected to publication was 8.9 ± 4.1 months, with an increasing trend over time (R = 0.9444, p < 0.0001). Of the 52 articles that met our inclusion criteria, we summarize main findings of 4 manuscripts on stroke, 14 on acute coronary syndrome, 4 on cardiac arrest, 7 on heart failure, 7 on venous thromboembolism, 5 on dysrhythmia, and 11 on different populations at risk for cardiovascular. Registries are cost effective, not disruptive to essential health services, and can be rapidly disseminated with short intervals between last data point collected and publication. In less than 2 years, cardiac registries have filled important gaps in knowledge and informed the care of COVID-19 patients with cardiovascular conditions.


Stimulation of synaptosomal D-[(3)H]aspartate transport by substance P in rat brain.
The effect of the neuropeptide, substance P, on the transport of D-[(3)H]aspartate into rat striatal synaptosomes was studied. Almost 90% of the total transport of D-[(3)H]aspartate was sodium-dependent and the maximum rate (V(max)) of this transport was increased by 34% of control by 2.5 nM substance P (EC(50)=0.52 nM). In contrast, sodium-independent transport was inhibited by substance P. The NK(1) antagonist, L706303 (500 nM) blocked the stimulation of D-[(3)H]aspartate transport by 2.5 nM substance P, but did not alter D-aspartate uptake in the absence of substance P. These results indicate that high affinity glutamate transporters in the brain may be under positive regulation by substance P, and suggest a previously-unidentified mechanism of control of glutamate transport.


Synergistic antitumor activity of camptothecin-doxorubicin combinations and their conjugates with hyaluronic acid.
Combinations of topoisomerase inhibitors I and II have been found to synergistically inhibit cancer cell growth in vitro, yet clinical studies of these types of combinations have not progressed beyond phase II trials. The results of clinical combinations of topoisomerase (top) I and II inhibitors typically fall within one of two categories: little to no improvement in therapeutic efficacy, or augmented toxicity compared to the single drug counterparts. Hence, despite the promising activity of top I and II inhibitor combinations in vitro, their clinical applicability has not been realized. Here, we report the use of polymer-drug conjugates as a means to co-deliver synergistic doses of top I and II inhibitors camptothecin (CPT) and doxorubicin (DOX) to tumors in vivo in a 4T1 breast cancer model. At specific molar ratios, DOX and CPT were found to be among the most synergistic combinations reported to date, with combination indices between 0.01 and 0.1. The identified optimal ratios were controllably conjugated to hyaluronic acid, and elicited significant tumor reduction of murine 4T1 breast cancer model when administered intravenously. This study elucidates a method to identify synergistic drug combinations and translate them to in vivo by preserving the synergistic ratio via conjugation to a carrier polymer, thus opening a promising approach to translate drug combinations to clinically viable treatment regimens.


Inhibition of cell proliferation and induction of apoptosis by ExFABP gene targeting.
Ex-FABP, an extracellular fatty acid binding lipocalin, is physiologically expressed by differentiating chicken chondrocytes and myoblasts. Its expression is enhanced after cell treatment with inflammatory stimuli and repressed by anti-inflammatory agents, behaving as an acute phase protein. Chicken liver fragments in culture show enhanced protein expression after bacterial endotoxin treatment. To investigate the biological role of Ex-FABP, we stably transfected proliferating chondrocytes with an expression vector carrying antisense oriented Ex-FABP cDNA. We observed a dramatic loss of cell viability and a strong inhibition of cell proliferation and differentiation. When chondrocytes were transfected with the antisense oriented Ex-FABP cDNA we observed that Ex-FABP down-modulation increased apoptotic cell number. Myoblasts transfected with the same expression vector showed extensive cell death and impaired myotube formation. We suggest that Ex-FABP acts as a constitutive survival protein and that its expression and activation are fundamental to protect chondrocytes from cell death.


Post-traumatic nonunion of the clavicle in a 4-year-old boy and the importance of vitamin D level testing.
Clavicle fractures in children are common and usually go on to achieve solid union with closed treatment. A limited number of pediatric clavicle fracture nonunion cases have been reported in the literature, none of which were directly associated with hypovitaminosis D. We report the youngest case to our knowledge in a 4-year-old vitamin D-deficient male with a 6-month-old right midshaft clavicle fracture nonunion that was treated successfully with vitamin D supplementation, followed by open reduction and internal fixation with autologus iliac crest bone grafting.


Effects of pregnancy and child birth on urinary symptoms and urodynamics in women with multiple sclerosis.
Our objective was to study the impact of pregnancy and delivery on vesicourethral disorders in patients with multiple sclerosis (MS). We performed a retrospective chart review of records of women diagnosed with MS who were referred to the clinic. A total of 102 women with MS (mean age of 44.7 +/- 11.4 years at the time of the study and mean age of 30.0 +/- 9.6 years at the onset of MS) participated in the study. The mean duration of disease was 15 +/- 10 years. The mean Expanded Disability Status Scale score was 5.4 +/- 1.8. For each patient, demographic data, disease characteristics, urological and obstetrical history and urodynamic data were collected. Urinary disorders were classified as irritative (urinary urgency and frequency) or as obstructive (hesitancy of micturition, reduced or interrupted urinary stream and sensation of incomplete bladder emptying). Urodynamic study consisted of cystometry with continuous recording of urethral sphincter electromyography in 77 (76%) cases. Intravesical and intraurethral pressures were recorded. Bladder dysfunctions were classified into neurogenic detrusor overactivity or detrusor underactivity. Pregnancies and deliveries did not influence symptoms. Moreover, the only statistical difference from a urodynamic point of view was a decrease in maximal urethral closure pressure. No interaction between pregnancy, delivery and urinary symptoms was found in this study. The effects of pregnancy and delivery seemed to be the same in women with MS and in healthy women, with a tendency towards a decrease in urethral pressure in women with MS.


Rubella, rubeola, and mumps in pregnant women: susceptibilities and strategies for testing and vaccinating.
To estimate rubella, rubeola, and mumps (MMR) susceptibilities in pregnant women and determine the percentage not immune to rubeola or mumps, depending on rubella immunity status. A secondary objective was to assess costs of vaccination and testing programs aimed at eliminating these viral susceptibilities to determine an optimal strategy. This was an observational study of women presenting for prenatal care. All women had MMR antibody titers measured. Viral susceptibilities were compared by age, gravidity, parity, and recall of vaccine booster. A logistic regression was performed to assess for predictors of MMR immunity. A cost comparison of different screening and vaccination strategies was performed. Overall, 91 (9.4%) women were susceptible to rubella, 161 (16.5%) to rubeola, and 159 (16.3%) to mumps. Three hundred seventeen (32.6%) were susceptible to at least 1 virus, whereas only 17 (1.7%) were susceptible to all 3. Of the women who were immune to rubella, a large percentage were not immune to either rubeola or mumps (n = 226, 25.6%). Only 74.2% of women who knew they had a booster vaccine were immune to all components of the MMR vaccine. Receiving a booster was predictive of immunity to all 3 viruses. A cost analysis demonstrated that broader screening strategies are more comprehensive and more expensive. The current screening and vaccine program has left many reproductive-aged women susceptible to rubella, rubeola, and mumps infections. Perhaps a more comprehensive viral screening program is needed to ensure immunity.


Potentiation of atracurium toxicity in isolated rat hepatocytes by inhibition of its hydrolytic degradation pathway.
This study tested the hypothesis that the esters of acrylic acid might be responsible for the previously observed cytotoxic effect of atracurium. Rats were pretreated with triorthotolyl phosphate (TOTP), an inhibitor of the hydrolytic degradation of atracurium. Because hydrolysis of acrylates is also inhibited by TOTP and because the hydrolysis represents a detoxification pathway for these esters, we postulated that the leak of lactic dehydrogenase (LDH) induced by atracurium would be enhanced in hepatocytes harvested from rats pretreated with TOTP. Hepatocytes isolated from rats previously treated with TOTP (25 or 50 mg/kg intraperitoneally, 20 hr before induced death) were incubated for 4 hr in the absence of muscle relaxants or in the presence of either atracurium (0.008-0.8 mM) or metocurine (0.015-0.85 mM). Atracurium produced a concentration-dependent leakage of LDH. The leakage out of cells obtained from TOTP-pretreated rats was greater than was the leakage out of hepatocytes harvested from animals pretreated only with corn oil (a vehicle for TOTP). Metocurine did not produce a leak of LDH. It is concluded that the LDH leakage was produced by ester-type products of atracurium degradation. Acrylates appear to be the toxic agent.


An expanding genetic code.
A general method was recently developed that makes it possible to genetically encode unnatural amino acids (UAAs) with diverse physical, chemical or biological properties in Escherichia coli, yeast, and mammalian cells. Over 30 UAAs have been cotranslationally incorporated into proteins with high fidelity and efficiency by means of a unique codon and corresponding tRNA-synthetase pair. A key feature of this methodology is the orthogonality between the new translational components and their endogenous host counterparts. Specifically, the codon for the UAA should not encode a common amino acid; neither the new tRNA nor cognate aminoacyl tRNA synthetase should cross-react with any endogenous tRNA-synthetase pairs; and the new synthetase should recognize only the UAA and not any of the 20 common amino acids. This methodology provides a powerful tool for exploring protein structure and function both in vitro and in vivo, as well as generating proteins with new or enhanced properties.


How familiar are German dermatologists with placebo and nocebo effects and to what extent are these targeted in clinical practice: A survey within the dermatological community.
Every medical treatment inevitably comprises not only physiological, but also psychological components, reflected by placebo and nocebo effects, which significantly affect treatment outcome. However, the extent of knowledge on the mechanisms steering placebo and nocebo effects in the dermatological community in Germany is currently unclear. To assess the state of knowledge about placebo and nocebo effects in the German dermatological community, to evaluate whether this knowledge is already being used in clinical practice, and to investigate whether German dermatologists are interested in learning more about the topic. German Dermatologists, the majority working in their own practice, were asked to fill in an online survey addressing the knowledge about placebo and nocebo effects and the feasibility of special techniques to enhance placebo and minimize nocebo effects within the clinical routine. N = 154 complete (79%) or partial (21%) responses to the survey were recorded in the online database and included in the analysis. All participants reported to know what the placebo effect is and 59.7% (74/124) indicated that they already had experience with prescribing or recommending a treatment without active substances. In contrast, only 62.0% (80/129) stated to know what the nocebo effect is. Participants showed a rather superficial knowledge regarding placebo and nocebo mechanisms. The majority of participants (76.7%, 99/129) expressed their willingness to be further educated about the underlying mechanisms mediating placebo and nocebo effects and the possible application in clinical practice. The current survey offers a so far unique insight into the state of knowledge of German dermatologists on placebo and nocebo effects. The results indicate a need for education about this topic. Encouragingly, however, German dermatologists considered communication strategies to maximize placebo and reduce nocebo effects and expressed motivation to be trained to implement these strategies in everyday clinical practice.


Radiotherapy driven immunomodulation of the tumor microenvironment and its impact on clinical outcomes: a promising new treatment paradigm.
Traditional treatment approaches for advanced malignancies have been associated with limited clinical outcomes necessitating the development of novel therapies. However, the ability of radiotherapy to induce pro-immunogenic changes in tumor immune microenvironment can be leveraged when combined with systemic agents. Radio-immunotherapeutic initiatives employing the use of monoclonal antibodies, genetically engineered T cells, cytokines and virus-vector mediated gene therapies have demonstrated promising potential for the management of various solid malignancies. Future studies incorporating biomarker enrichment strategies and radiobiological variables could pave the way for immune-oncology based personalized medicine approaches to be integrated in standard of care practices for the treatment of challenging clinical populations.


The effect of vitreomacular interface in neovascular age-related macular degeneration treated with intravitreal injection of anti-VEGF.
The purpose of this study is to study the effect of repeated intravitreal injection of anti-vascular endothelial growth factor (anti-VEGF) drugs on vitreomacular interface. Neovascular age-related macular degeneration patients who received intravitreal injections of anti-VEGF drugs were included. Eyes with severe vitreous opacity, uveitis, complicated cataract surgery and previous vitrectomy were excluded. Vitreomacular interface, best corrected visual acuity (BCVA) and central retinal thickness (CRT) assessment were performed once a month for at least 3 months. The nature and time of the change event are recorded. Groups were divided according to whether vitreomacular interface change events occurred. To analyse the risk factors of vitreomacular interface changes and their influence on treatment effect. A total of 87 eyes were evaluated. Vitreomacular interface change event occurred in 9 eyes. Pre-existing vitreomacular interface abnormality (VMIA) was a risk factor for the VMI change (P = 0.033, OR = 16.518, 95% CI: 1.258 to 216.939). 60% of interface events occurred in the first 3 months of treatment. The final BCVA of eyes with vitreomacular interface unchanged was significantly higher than that at baseline (P = 0.001), and the final CRT was also significantly lower than that at baseline (P < 0.001). The final CRT of eyes vitreomacular interface changed was significantly lower than that at baseline (P = 0.015), however, there was no statistical significance in BCVA (P = 0.468). Intravitreal injection of anti-VEGF drugs has a certain probability to cause changes in the vitreomacular interface, and the risk is higher in eyes with pre-existing vitreomacular interface abnormality. The effect of intravitreal injections on the vitreomacular interface was concentrated in the first three injections, and subsequent increases in the number of injections did not significantly increase the risk of vitreomacular interface abnormality. Ophthalmologists should increase attention to the vitreomacular interface in the early stages of anti-VEGF therapy and counsel patients accordingly.


A global map of hemispheric influenza vaccine recommendations based on local patterns of viral circulation.
Both the Northern and the Southern Hemisphere annual WHO influenza vaccine recommendations are designed to ensure vaccine delivery before the winter-time peak of viral circulation in each hemisphere. However, influenza seasonal patterns are highly diverse in tropical countries and may be out of phase with the WHO recommendations for their respective hemisphere. We modelled the peak timing of influenza activity for 125 countries using laboratory-based surveillance data from the WHO's FLUNET database and compared it with the influenza hemispheric recommendations in place. Influenza vaccine recommendations for respectively 25% and 39% of the Northern and Southern Hemisphere countries were out of phase with peak influenza circulation in their corresponding hemisphere (62% and 53%, respectively, when the analysis was limited to the 52 countries in the tropical belt). These results indicate that routine influenza immunization efforts should be closely tailored to local patterns of viral circulation, rather than a country's hemispheric position.


In Vivo DYSF Gene Viral Delivery Provides a Histoprotective Effect in Skeletal Muscle Tissue in Dysferlin-Deficient Mice.
We studied the effects of a dual-vector DYSF gene delivery system based on adeno-associated virus serotype 9 capsids on pathological manifestations of dysferlinopathy in skeletal muscles of Bla/J mice lacking DYSF expression. The mice received intravenous injection of 3×1013 genomic copies of the virus containing the dual-vector system. M. gastrocnemius, m. psoas major, m. vastus lateralis, and m. gluteus superficialis were isolated for histological examination in 3, 6, and 12 weeks after treatment. Healthy wild-type (C57BL/6) mice served as positive control and were sacrificed 3 weeks after injection of 150 μl of 0.9% NaCl into the caudal vein. To detect dysferlin in muscle cryosections, immunohistochemical analysis with diagnostic antibodies was performed; paraffin sections were stained with hematoxylin and eosin for morphometric analysis. After administration of gene-therapeutic constructs, muscle fibers with membrane or cytoplasmic dysferlin location were detected in all examined muscles. The proportion of necrotic muscle fibers decreased, the number of muscle fibers with central location of the nucleus increased, and the mean cross-section area of the muscle fibers decreased.


Comparison of changes in tissue oxidative-stress markers in experimental model of open, laparoscopic, and retroperitoneoscopic donor nephrectomy.
We evaluated the oxidative stress in renal tissue during three types of surgery: open donor nephrectomy (ODN), laparoscopic donor nephrectomy (LDN), and retroperitoneoscopic donor nephrectomy (RDN). The aim was to find out which is the appropriate procedure for harvesting a donor kidney. Twenty-four New Zealand White rabbits were randomized to four groups, each consisting of six rabbits. Group I (control) was subjected to 180 minutes of anesthesia, and transperitoneal nephrectomy was performed without creation of warm ischemia. In group II (ODN), after 180 minutes of anesthesia, warm ischemia was created for 5 minutes, and nephrectomy was performed. Group III (LDN) was subjected to 5 minutes of warm ischemia after 180 minutes of pneumoperitoneum at 12 mm Hg, and the kidney was removed. In group IV (RDN), after pneumoretroperitoneum at 12 mm Hg for 180 minutes, warm ischemia was created for 5 minutes, and nephrectomy was performed. Renal tissues were analyzed to determine malondialdehyde (MDA) and reduced glutathione (GSH) as oxidative-stress markers. Renal tissue GSH levels were decreased, whereas MDA levels were increased in groups II through IV compared with the control group (p<0.05). There was no statistically significant difference between the ODN, LDN, and RDN groups in the renal oxidative-stress markers. No differences were detected in oxidative-stress markers in renal tissue samples between ODN, LDN, and RDN. Therefore, we believe LDN and RDN can be used for live donor kidney harvesting as effectively as ODN without creating greater oxidative stress, which can have deleterious effects on a donor kidney.


From nappe stacking to exhumation: Cretaceous tectonics in the Apuseni Mountains (Romania).
New Ar-Ar muscovite and Rb-Sr biotite age data in combination with structural analyses from the Apuseni Mountains provide new constraints on the timing and kinematics of deformation during the Cretaceous. Time-temperature paths from the structurally highest basement nappe of the Apuseni Mountains in combination with sedimentary data indicate exhumation and a position close to the surface after the Late Jurassic emplacement of the South Apuseni Ophiolites. Early Cretaceous Ar-Ar muscovite ages from structurally lower parts in the Biharia Nappe System (Dacia Mega-Unit) show cooling from medium-grade conditions. NE-SW-trending stretching lineation and associated kinematic indicators of this deformation phase (D1) are overprinted by top-NW-directed thrusting during D2. An Albian to Turonian age (110-90 Ma) is proposed for the main deformation (D2) that formed the present-day geometry of the nappe stack and led to a pervasive retrograde greenschist-facies overprint. Thermochronological and structural data from the Bihor Unit (Tisza Mega-Unit) allowed to establish E-directed differential exhumation during Early-Late Cretaceous times (D3.1). Brittle detachment faulting (D3.2) and the deposition of syn-extensional sediments indicate general uplift and partial surface exposure during the Late Cretaceous. Brittle conditions persist during the latest Cretaceous compressional overprint (D4).


Splenic natural killer-cell activity in mice infected with Leishmania donovani.
Several strains of inbred mice were infected with the protozoan parasite Leishmania donovani, and, at several points during the infection, spleens of groups of these mice were tested for natural killer (NK)-cell activity vs lymphoma target cells in vitro and were evaluated for parasite burdens. Generally, elevated followed by normal (compared to uninfected control mice) or subnormal NK responses occurred as the result of infection. Elevated NK responses were not accompanied by high circulating levels of interferon, yet infected mice responded to an injection of an interferon inducer with interferon production as great as control mice. No consistent correlations among susceptibility phenotype to L. donovani infection, spontaneous NK activity phenotype, and infection-induced NK activation/depression patterns were detected among the various strains of mice.


Lateral Femoral Trochlea Osteochondral Flap Reconstruction of Proximal Pole Scaphoid Nonunions.
The medial femoral trochlea flap has been described as a method of scaphoid proximal pole nonunion reconstruction when the proximal pole is deemed nonsalvageable. The lateral femoral trochlea (LFT) is an alternative donor site providing a comparable vascularized convex osteochondral flap. We describe the technique and outcomes of our first 17 cases of LFT flap reconstruction of the proximal scaphoid pole with a minimum follow-up of 14 months. Seventeen of the first 24 patients who underwent LFT scaphoid reconstruction at 3 institutions were able to be contacted for clinical follow-up and chart reviews. We recorded patient age and sex, duration of nonunion, number of previous surgical procedures, details of surgical technique, achievement of osseous union, complications, additional postoperative procedures, preoperative and postoperative pain, and range of motion. Preoperative and postoperative scapholunate and radiolunate angles were analyzed on x-rays and achievement of osseous union on computerized tomography scans. The average age of patients included was 35 years (range, 16-55 years). Follow-up data were recorded at an average of 33 months (range, 14-62 months). Ten patients had previous procedures (average, 1; range, 0-2). Median duration from trauma to LFT was 3.4 years (range, 8 months-12 years) among patients who had a recognized date of injury. Osseous healing was achieved in 16 of 17 patients and confirmed by computerized tomograpy scan. Twelve patients reported complete pain relief, while 5 reported partial pain relief. Final postoperative range of motion was 59°extension (range, 30°-85°) and 50° flexion (range, 10°-80°), which was comparable to preoperative values. Preoperative (59°) and postoperative (55°) scapholunate angles were similar to normal wrists. Vascularized LFT flaps provide an alternative donor site for vascularized osteochondral reconstruction of proximal pole scaphoid nonunion. Rate of union, range of motion, and pain relief are similar to reported results with medial femoral trochlea flap reconstruction. Therapeutic IV.


V3A processes contour curvature as a trackable feature for the perception of rotational motion.
Contour curvature (CC) is a vital cue for the analysis of both form and motion. Using functional magnetic resonance imaging, we localized the neural correlates of CC for the processing and perception of rotational motion. We found that the blood oxygen level-dependent signal in retinotopic area V3A and possibly also lateral occipital cortex (LOC) varied parametrically with the degree of CC. Control experiments ruled out the possibility that these modulations resulted from either changes in the area of the stimuli, the velocity with which contour elements were actually translating, or perceived angular velocity. We conclude that neurons within V3A and perhaps also LOC process continuously moving CC as a trackable feature. These data are consistent with the hypothesis that V3A contains neural populations that process trackable form features such as CC, not to solve the "ventral problem" of determining object shape but in order to solve the "dorsal problem" of what is going where.


Endovascular embolization techniques in acute thoracic and abdominal bleedings can be technically reproduced and trained in a standardized simulation setting using SLA 3D printing: a 1-year single-center study.
Endovascular embolization techniques are nowadays well established in the management of acute arterial bleedings. However, the education and training of the next generation of interventionalists are still based on the traditional apprenticeship model, where the trainee learns and practices directly at the patient, which potentially affects the patient's safety. The objective of this study was to design and develop a standardized endovascular simulation concept for the training of acute bleeding embolizations, based on real-life cases. An adaptable and cost-effective endovascular simulator was developed using an in-house 3D print laboratory. All thoracic and abdominal acute bleeding embolizations over more than a year with appropriate pre-interventional computed tomography scans were included to manufacture 3D printed vascular models. A peristaltic pump was used to generate pulsatile flow curves. Forty embolization cases were engaged in this study, and 27 cases were fully reproduced in the simulation setting (69.23%). The simulation success was significantly lower in pulmonary embolizations (p = 0.031) and significantly higher in soft tissue (p = 0.032) and coil embolizations (p = 0.045). The overall simulation success was 7.8 out of 10 available points. Using stereolithography 3D printing in a standardized simulation concept, endovascular embolization techniques for treating acute internal hemorrhages in the chest and abdomen can be simulated and trained based on the patient-specific anatomy in a majority of the cases and at a broad spectrum of different causes.


Gut Microbiome Modulation Via Fecal Microbiota Transplant to Augment Immunotherapy in Patients with Melanoma or Other Cancers.
We review emerging evidence regarding the impact of gut microbes on antitumor immunity, and ongoing efforts to translate this in clinical trials. Pre-clinical models and human cohort studies support a role for gut microbes in modulating overall immunity and immunotherapy response, and numerous trials are now underway exploring strategies to modulate gut microbes to enhance responses to cancer therapy. This includes the use of fecal microbiota transplant (FMT), which is being used to treat patients with Clostridium difficile infection among other non-cancer indications. The use of FMT is now being extended to modulate gut microbes in patients being treated with cancer immunotherapy, with the goal of enhancing responses and/or to ameliorate toxicity. However, significant complexities exist with such an approach and will be discussed herein. Data from ongoing studies of FMT in cancer will provide critical insights for optimization of this approach.


k-Carrageenan based magnetic@polyelectrolyte complex composite hydrogel for pH and temperature-responsive curcumin delivery.
The dual stimuli-responsive drug delivery system has attracted a lot of interest in controlled drug delivery to specific sites. The magnetic iron oxide nanoparticles integrated polyelectrolyte complex-based hydrogel (MPEC HG) system was developed in this work. First, magnetic nanoparticles were produced in situ in the synthetic polymer polyhexamethylene guanidine (PHMG). Furthermore, the natural biopolymer k-carrageenan (kCG) was employed to form the polyelectrolyte complex (PEC) through charge-balancing interaction between positively charged guanidine units and negatively charged sulfonate groups. Various characterization approaches were used to characterize the developed magnetic polyelectrolyte complex hydrogel (MPEC HG) system. Curcumin (Cur) was employed as a model bioactive agent to examine the drug loading and stimuli-responsive drug release efficiency of the MPEC HG system. Under the combined pH and temperature stimuli conditions (pH 5.0/42 °C), the developed hydrogel system demonstrated great drug loading efficiency (∼ 68 %) and enhanced drug release. Furthermore, the MPEC HG system's in vitro cytotoxicity behavior was investigated on a human liver cancer (HepG2) cell line, and the results revealed that the MPEC HG system is biocompatible. As a result, the MPEC HG system might be used for dual pH and temperature stimuli-responsive drug delivery applications in cancer therapy.


Two questions for Kounis syndrome: can we use magnetic resonance imaging in the diagnosis and does ST elevation correlates with troponin levels?
Kounis syndrome (KS) is an acute coronary vasospasm after exposure to an allergen due to mast cell degranulation and existing mediators. Various drugs, conditions, and environmental exposures can cause KS. We presented 2 cases, 1 of whom had taken an antiflu drug (containing paracetamol, pseudoephedrine, and dextromethorphan). His electrocardiogram (ECG) showed inferior ST elevations (2 mm) with normal cardiac biomarkers. His cardiac magnetic resonance imaging showed hypokinesis and myocardial hibernation on apical septum and on the left ventricle. The second patient took a pill of naproxen sodium. The ECG showed 1-mm ST elevation in leads DII, V5, and V6. His troponin was markedly elevated. These cases showed that there seems to be no correlation with ECG and troponin levels in KS. In addition, for patients in whom KS type 1 is expected without troponin elevation, noninvasive cardiac magnetic resonance imaging study seems to be appropriate for the diagnosis of KS.


The effect of different acclimation temperatures on the prophenoloxidase system and other defence parameters in Litopenaeus vannamei.
Water temperature changes (higher and lower than 24 degrees C) were shown to have a significant effect on dopamine (DA) concentration, haemocyte count and the proPO system in the white shrimp Litopenaeus vannamei. No significant difference in any of the parameters was observed in the control group. DA concentration in haemolymph in the experimental groups increased to a peak value at 0.5 days; meanwhile serine protease (SP) activity and proteinase inhibitor (PI) activity decreased. Total haemocyte count (THC), differential haemocyte count (DHC) and PO activity were lowest at 1 day. All defence parameters became stable after 1-3 days, while the total haemocyte and large granular cell count stabilized after 6 days. After these stabilized, there was no significant difference in DA concentration and PI activity between the control and experimental groups, as was the case for the THC, DHC, PO and SP activities of shrimp held at higher temperatures. However these latter four parameters in the lower temperature groups were distinctly lower than the control group. alpha(2)-Macroglobulin activity in the experimental groups increased to a peak value after 1 day compared with the control and then stabilized after 6 days when the activity levels in higher temperature groups were higher than the control, while the lower temperature groups had no significant difference from the control. It was therefore concluded that water temperature changes modulated the immune system of L. vannamei.


Soluble guanylate cyclases in the retina.
Soluble guanylate cyclase catalyzes the formation of cyclic GMP using GTP as substrate. It is now well established that soluble guanylate cyclase is highly activated by nitric oxide, and that many of the effects of nitric oxide on various cells and tissues are mediated through increased production of cyclic GMP. This review discusses the evidence for the presence of soluble guanylate cyclases in different classes of cells in vertebrate retina and the role of these enzymes in retinal physiology. It is concluded that the enzyme is present in nearly every class of cells in the retina and that it may be involved in signal transmission between some cells and in the modulation of signal transmission between others.


HIV service delivery in the time of COVID-19: focus group discussions with key populations in India.
There are limited data on the impact of COVID-19-associated disruptions and novel HIV service delivery strategies among key populations (KPs) in low- and middle-income countries. In March 2020, in response to COVID-19, the Government of India revised HIV service delivery policies to include community antiretroviral therapy (ART) distribution and multi-month dispensing (MMD) of ART for all people living with HIV (PLHIV). To assess the acceptability of these adaptations and impact of the pandemic among KPs, we conducted focus groups in November-December 2020 with purposively sampled men who have sex with men (MSM), female sex workers (FSWs) and transgender women (TGW) in Telangana and Maharashtra. Seven discussions were conducted. Topics included HIV service access, risk behaviours, economic security and feedback to ensure service continuity. Inductive coding identified themes across topics. Forty-four individuals aged 20-49 years participated in discussions (13 MSM; 16 FSW; and 15 TGW). Twenty-four participants self-identified as living with HIV. People not living with HIV reported challenges in accessing HIV antibody testing at hospitals due to travel restrictions and fear of contracting COVID-19. Participants accessed HIV antibody testing using transportation arranged by community-based organizations after lockdowns eased. PLHIV reported uninterrupted ART refills and generally consistent adherence; however, there were experiences of delayed CD4 and HIV RNA testing. Participants shared appreciation for MMD as it saved time, money, and reduced exposure to COVID-19. Participants expressed gratitude for home deliveries which enabled ART access, yet shared concerns about home-based services causing confidentiality breaches with family/neighbours. Participants voiced preferences for community-based service provision due to proximity, convenient hours, and welcoming environments compared to public hospitals. Other requests included support for income, employment, nutrient-rich food and more accessible mental health, HIV, and other health services. COVID-19 restrictions had a greater impact on access to HIV antibody, CD4, and RNA testing services compared to ART access. High acceptance of MMD and community-based services support the continued role of differentiated service delivery models to improve KP access to HIV antibody, CD4, RNA testing services, convenient ART retrieval, and integrated services beyond HIV, which may be critical for survival and wellbeing.


Localization of amplified CAD genes on rearranged chromosomes of Chinese hamster cells.
Chinese hamster cell lines carrying an amplified CAD region were selected from V79,B7 cells by their resistance to N-phosphonacetyl-L-aspartate (PALA). In one of the selected cell lines, SP PALA (inf1) (supR) L, an acrocentric chromosome with abnormally elongated q arms was identified as a marker for the PALA-resistant phenotype. The marker chromosome carried a homogeneously staining region close to a telomeric nucleolar organizer region. In the same region, localization of amplified CAD sequences was demonstrated by in situ hybridization. The marker chromosome was found to undergo extensive rearrangements. In particular, dicentric chromosomes, occurring with an unusually high incidence, were found to originate from end-fusion of two homologous marker chromosomes.


Pentoxifylline enhancement of post-thaw motility in cryopreserved semen of spinal cord-injured men.
To investigate the effects of pentoxifylline on cryopreserved human semen of spinal cord injured men, in efforts to enhance post-thaw motility. Semen specimens were collected from: pregnancy-proven donors (n = 10), spinal cord injured (SCI) patients (n = 8), and infertility patients referred for white blood cell (WBC) screening of the semen (n = 18). Following at least 24 hours of freezing in 100% tes and tris-yolk buffer, 0.5-mL semen straws were thawed. Each sample was split into two equal aliquots, one of which was treated with 3.6 mM pentoxifylline. Following incubation, percent motility was recorded manually at 15 minutes, 1 hour, 2 hours, and 24 hours post-thaw. Percent original motility preserved (post-thaw motility/original motility X 100%) was calculated for each specimen. Statistically significant differences (P < .05) were noted in the SCI and WBC patients when samples with and without pentoxifylline were compared at 15 minutes, 1 hour, and 2 hours. No significant difference was noted in the donor population at any time interval, and no difference was seen in any group at 24 hours post-treatment with pentoxifylline. The greatest differential between treatment and control groups was noted at 1 hour in all three populations. Pentoxifylline enhances post-thaw motility of cryopreserved sperm in male infertility patients from 15 minutes to 2 hours post-treatment. Pentoxifylline appears to be most useful at 1 hour post-treatment in the cryopreserved samples of SCI patients obtained by electroejaculation. It does not appear to have any significant effect on the post-thaw motility of pregnancy- proven donors. Pentoxifylline loses its in vitro efficacy prior to 24 hours post-thaw.


Rethinking the cilia hypothesis of hydrocephalus.
Dysfunction of motile cilia in ependymal cells has been proposed to be a pathogenic cause of cerebrospinal fluid (CSF) overaccumulation leading to ventricular expansion in hydrocephalus, primarily based on observations of enlarged ventricles in mouse models of primary ciliary dyskinesia. Here, we review human and animal evidence that warrants a rethinking of the cilia hypothesis in hydrocephalus. First, we discuss neuroembryology and physiology data that do not support a role for ependymal cilia as the primary propeller of CSF movement across the ventricles in the human brain, particularly during in utero development prior to the functional maturation of ependymal cilia. Second, we highlight that in contrast to mouse models, motile ciliopathies infrequently cause hydrocephalus in humans. Instead, gene mutations affecting motile cilia function impact not only ependymal cilia but also motile cilia found in other organ systems outside of the brain, causing a clinical syndrome of recurrent respiratory infections and situs inversus, symptoms that do not typically accompany most cases of human hydrocephalus. Finally, we postulate that certain cases of hydrocephalus associated with ciliary gene mutations may arise not necessarily just from loss of cilia-generated CSF flow but also from altered neurodevelopment, given the potential functions of ciliary genes in signaling and neural stem cell fate beyond generating fluid flow. Further investigations are needed to clarify the link between motile cilia, CSF physiology, and brain development, the understanding of which has implications for the care of patients with hydrocephalus and other related neurodevelopmental disorders.


Repetitive formation of optically-observable planar lipid bilayers by rotating chambers on a microaperture.
Optical observation of a planar lipid bilayer is an effective method of lipid bilayer characterization. However, previous methods for optically observable lipid bilayer formation are unsuitable for repetitive formation of lipid bilayers. In this paper, we propose a system that facilitates repetitive formation of horizontal lipid bilayers via mechanical rotation of the rotating part. We show that multiple bilayers can be observed within a short period, and that the electrical and optical characteristics of a bilayer can be analyzed simultaneously.


Autophagy may protect the brain against prolonged consequences of headache attacks: A narrative/hypothesis review.
To assess the potential of autophagy in migraine pathogenesis. The interplay between neurons and microglial cells is important in migraine pathogenesis. Migraine-related effects, such as cortical spreading depolarization and release of calcitonin gene-related peptide, may initiate adenosine triphosphate (ATP)-mediating pro-nociceptive signaling in the meninges causing headaches. Such signaling may be induced by the interaction of ATP with purinergic receptor P2X 7 (P2X7R) on microglial cells leading to a Ca2+ -mediated pH increase in lysosomes and release of autolysosome-like vehicles from microglial cells indicating autophagy impairment. A search in PubMed was conducted with the use of the terms "migraine," "autophagy," "microglia," and "degradation" in different combinations. Impaired autophagy in microglia may activate secretory autophagy and release of specific proteins, including brain-derived neurotrophic factor (BDNF), which can be also released through the pores induced by P2X7R activation in microglial cells. BDNF may be likewise released from microglial cells upon ATP- and Ca2+ -mediated activation of another purinergic receptor, P2X4R. BDNF released from microglia might induce autophagy in neurons to clear cellular debris produced by oxidative stress, which is induced in the brain as the response to migraine-related energy deficit. Therefore, migraine-related signaling may impair degradative autophagy, stimulate secretory autophagy in microglia, and degradative autophagy in neurons. These effects are mediated by purinergic receptors P2X4R and P2X7R, BDNF, ATP, and Ca2+ . Different effects of migraine-related events on degradative autophagy in microglia and neurons may prevent prolonged changes in the brain related to headache attacks.


Effect of visual restitution training on absolute homonymous scotomas.
The authors examined 16 patients with stable homonymous visual field defects (HVFDs) with static automated perimetry (SAP). Training effect E was defined as difference of the proportions of absolutely defective locations in all test locations, before and after visual restitution training (VRT). E was 0.05 +/- 0.05 (mean +/- SD). The authors observed a relevant training effect (E >or= 0.12) in two subjects, but only monocularly. VRT has little effect on absolute HVFDs in SAP.


Determination of river water composition trends with uncertainty: Seasonal variation of nutrients concentration in Tagus river estuary in the dry 2017 year.
The assessment of long-term trends in river water composition is hampered by river composition heterogeneity, and sampling and sample analysis uncertainty. This work describes a novel methodology for the reliable detection of small river composition trends by taking all relevant uncertainty components into account. The methodology was applied to study the variation of nutrients concentration of Tagus river estuary in the extremely dry 2017 year. Mean nutrient concentrations were determined with an uncertainty that combines sampling and sample analysis uncertainty by the Monte Carlo Method. The nutrient concentration variation observed in two occasions is meaningful if the difference of mean concentrations is metrologically different from zero for a 95% confidence level. The observed meaningful NO2 increase, and SiO2 and NOx variations is justified by dissolved oxygen reduction, decreased freshwater input and algal productivity variations. The developed tool can be applied to the assessment of other composition trends in rivers.


Metabolites and gene expression in the myocardium of fasting rats in an acute hypoxic environment.
With the rising demand for entry to extremely high altitudes (HAs), rapid adaptability to extremely hypoxic environments is a challenge that we need to explore. Fasting was used to evaluate acute hypoxia tolerance at HA and was proven to be an effective method for improving the survival rate at extreme HA. Our experiments also showed that fasting pretreatment for 72 h significantly increased the 24 h survival rate of rats at 7620 m from 10 to 85% and protected the myocardium cells of rats. Here, we compared the metabolites and gene expression in the myocardium of SD rats pretreated with fasting and nonfasting at normal altitude and extreme HA. Our findings demonstrated that the dynamic contents of detected differential metabolites (DMs) between different rat groups were consistent with the expression of differentially expressed genes (DEGs), and DM clusters also showed strong correlations with DEG clusters. DM clusters related to amino acids and lipids were significantly lower in the fasting groups, and the correlated DEG clusters were enriched in mitotic pathways, including CDK1, CDC7, NUF2, and MCM6, suggesting that fasting can attenuate mitotic processes in cardiac tissues and reduce the synthesis of amino acids and lipids. L-Glutamine-related metabolites were particularly low at extreme HA without pretreatment but were normal in the fasting groups. The DEGs in the cluster related to L-glutamine-related metabolites were enriched for T-cell receptor V(D)J recombination, the Hippo signaling pathway, the Wnt signaling pathway, the cGMP-PKG signaling pathway, and the mTOR signaling pathway and were significantly downregulated, indicating that the content of L-glutamine decreased at extreme HA, while fasting increased it to adapt to the environment. Moreover, abundant fatty acids were detected when rats were exposed to extreme HA without pretreatment. Our study revealed the fasting and hypoxic environment-related factors in SD rats and provided new insights into the genetic and molecular characteristics in the myocardium, which is critical to developing more potential rapid adaptation methods to extreme HA.


Intensive care unit admission in patients with T cell lymphomas: clinical features and outcome.
T cell non-Hodgkin lymphomas (T-NHLs) are aggressive malignancies which have a high risk of life-threatening complications. However, their prognosis in the intensive care unit (ICU) setting has not yet been assessed. We conducted a study including 87 ICU patients either with newly diagnosed T-NHLs or those undergoing first-line therapy admitted between January 1, 2000, and December 31, 2014. The primary subtypes were peripheral T cell lymphoma (PTCL) (n = 41, 47%), anaplastic large-cell lymphoma (ALCL) (n = 13, 15%), and adult T-leukaemia/lymphoma (ATLL) (n = 11, 13%). Six in every ten patients had malignancy-related complications (haemophagocytic syndrome 37%, tumour lysis syndrome 18% and hypercalcaemia 9%), while infections accounted for one quarter of ICU admissions. Nine fungal infections were documented, including six invasive aspergillosis. Urgent chemotherapy was started in the ICU in 59% of the patients, and urgent surgery was required in 13%. ICU and day-90 mortality were 22% and 41%, respectively. Multivariate analysis showed that SOFA score at day 1, age, sepsis and haemophagocytic syndrome were independent predictors of day-90 mortality. Compared to 66 ICU-matched controls with non-Hodgkin B cell lymphomas, patients with T-NHLs had a similar ICU survival. Overall survival rates of patients with T cell NHLs and B cell NHLs were 20% and 46%, respectively (hazard ratio for death associated with T cell NHLs 2.00 [1.12-3.58]). Patients with T cell NHLs had a very poor long-term outcome. Although the high rate of short-term survival suggests that an ICU trial is a reasonable option for patients newly diagnosed for the malignancy, extended stay in the ICU or further readmission should be considered only for highly selected patients who respond to the haematological treatment.


Prokaryotic communities and potential pathogens in sewage sludge: Response to wastewaster origin, loading rate and treatment technology.
Sewage sludge features high nitrogen and phosphorous contents encouraging its use as a biosolid in agriculture, but it bears potential chemical and microbiological risks. To tease apart the relative contribution of main factors determining the sludge chemical and microbial features, we analysed 28 treatment plants differing in the wastewater origin (municipal residues, agro-food or chemical industries), organic loading rate and treatment technology (extended aeration, activated sludge or activated sludge followed by anaerobic digestion). We found that the treatment technology and the organic loading rate are main determinants of the sludge chemical properties, including its organic load, nutrient and metal contents, and override the effect of the wastewater origin. Sludge bacterial and archaeal community structure and diversity, characterized through massive sequencing of the 16S rRNA gene, were also mostly determined by the treatment technology partly through shifts in the sludge nutrient load. The same factor conditioned the relative abundance of sequenced bacteria most closely related to potential pathogens, but not that of cultivable Escherichia coli or Salmonella spp. We did not find an effect of the geographic location of the plant on any of the variables at the regional scale of our study. Operational parameters appear as major determinants of the sludge chemical and microbial properties, irrespective of the source of wastewaters, thus leaving a broad management window for improving the agronomic value of sewage sludge.


Growth hormone therapy in children with CKD after more than two decades of practice.
This review focuses on the evidence for the efficacy and safety of recombinant human growth hormone (rhGH) therapy in children with all stages of chronic kidney disease (CKD) and at all ages. It describes the improving height prognosis for our patients both with and without rhGH; explains the underlying hormonal abnormalities that provide the rationale for rhGH use in CKD and the endocrine changes that accompany treatment; and views on who warrants treatment, with what dose, and how long for.


Derivatization of azaspiracid biotoxins for analysis by liquid chromatography with fluorescence detection.
Azaspiracids (AZAs) are an important group of regulated lipophilic biotoxins that cause shellfish poisoning. Currently, the only widely available analytical method for quantitation of AZAs is liquid chromatography-mass spectrometry (LC-MS). Alternative methods for AZA analysis are needed for detailed characterization work required in the preparation of certified reference materials (CRMs) and by laboratories not equipped with LC-MS. Chemical derivatization of the amine and carboxyl groups on AZAs was investigated for the purpose of facilitating analysis by LC with fluorescence detection (FLD). Experiments towards chemical modification of AZA1 at the amine achieved only limited success. Derivatization of the carboxyl group, on the other hand, proved successful using the 9-anthryldiazomethane (ADAM) method previously applied to the okadaic acid (OA) group toxins. Extraction and clean-up methods were investigated for shellfish tissue samples and a post-reaction solid phase extraction procedure was developed for the AZA ADAM derivatives. Chromatographic separations were developed for the LC-FLD analysis of derivatized AZAs alone or in the presence of other derivatized toxins. This new analytical method for analysis of AZAs enabled verification of AZA1-3 concentrations in recently certified reference materials. The method demonstrated good linearity, repeatability and accuracy showing its potential as an alternative to LC-MS for measurement of AZAs.


The Potential of Milk-Derived Exosomes for Drug Delivery.
Exosomes, one of the extracellular vesicles, are widely present in all biological fluids and play an important role in intercellular communication. Due to their hydrophobic lipid bilayer and aqueous hydrophilic core structure, they are considered a possible alternative to liposome drug delivery systems. Not only do they protect the cargo like liposomes during delivery, but they are also less toxic and better tolerated. However, due to the lack of sources and methods for obtaining enough exosomes, the therapeutic application of exosomes as drug carriers is limited. A literature search was performed using the ScienceDirect and PubMed electronic databases to obtain information from published literature on milk exosomes related to drug delivery. Here, we briefly reviewed the current knowledge of exosomes, expounded the advantages of milk-derived exosomes over other delivery vectors, including higher yield, the oral delivery characteristic and additional therapeutic benefits. The purification and drug loading methods of milk exosomes, and the current application of milk exosomes were also introduced. The emergence of milk-derived exosomes is expected to break through the limitations of exosomes as therapeutic carriers of drugs. We hope to raise awareness of the therapeutic potential of milk-derived exosomes as a new drug delivery system.


Is There Scope for a Novel Mycelium Category of Proteins alongside Animals and Plants?
In the 21st century, we face a troubling trilemma of expanding populations, planetary and public wellbeing. Given this, shifts from animal to plant food protein are gaining momentum and are an important part of reducing carbon emissions and consumptive water use. However, as this fast-pace of change sets in and begins to firmly embed itself within food-based dietary guidelines (FBDG) and food policies we must raise an important question-is now an opportunistic time to include other novel, nutritious and sustainable proteins within FBGD? The current paper describes how food proteins are typically categorised within FBDG and discusses how these could further evolve. Presently, food proteins tend to fall under the umbrella of being 'animal-derived' or 'plant-based' whilst other valuable proteins i.e., fungal-derived appear to be comparatively overlooked. A PubMed search of systematic reviews and meta-analytical studies published over the last 5 years shows an established body of evidence for animal-derived proteins (although some findings were less favourable), plant-based proteins and an expanding body of science for mycelium/fungal-derived proteins. Given this, along with elevated demands for alternative proteins there appears to be scope to introduce a 'third' protein category when compiling FBDG. This could fall under the potential heading of 'fungal' protein, with scope to include mycelium such as mycoprotein within this, for which the evidence-base is accruing.


Spin dynamics of the block orbital-selective Mott phase.
Iron-based superconductors display a variety of magnetic phases originating in the competition between electronic, orbital, and spin degrees of freedom. Previous theoretical investigations of the multi-orbital Hubbard model in one-dimension revealed the existence of an orbital-selective Mott phase (OSMP) with block spin order. Recent inelastic neutron scattering (INS) experiments on the BaFe2Se3 ladder compound confirmed the relevance of the block-OSMP. Moreover, the powder INS spectrum revealed an unexpected structure, containing both low-energy acoustic and high-energy optical modes. Here we present the theoretical prediction for the dynamical spin structure factor within a block-OSMP regime using the density-matrix renormalization-group method. In agreement with experiments, we find two dominant features: low-energy dispersive and high-energy dispersionless modes. We argue that the former represents the spin-wave-like dynamics of the block ferromagnetic islands, while the latter is attributed to a novel type of local on-site spin excitations controlled by the Hund coupling.


Method simple: An electronic interactive tool helping nursing students prepare for written and oral presentation.
Developing reflective writing skills is an essential competency in nursing. Nursing schools recognize the importance of promoting scholarly thinking and academic writing amongst their student yet, there is a large gap in the tools and opportunities students receive to help them master these skills during their baccalaureate studies. Method SIMPLE is an innovative and interactive web based tool introduced in first year that can help nursing students prepare university papers both written and oral. To discover how students learn to use the tool, what barriers affect proper use of the tool, and what role faculty plays in ensuring students' successful use of the tool. The study also sought to explore students' perception in regards to the contribution of the tool to improve their academic work. Data was collected using two research methodologies. Method SIMPLE has a built-in satisfaction survey at the end of each of the six modules that provides quantitative and qualitative data about the tool itself. A qualitative descriptive study was chosen to better understand student and faculty's perceptions regarding the tool. Data was collected during three focus groups. Students shared their experiences using the tool and talked at length about the importance Method SIMPLE's section "P" which explains in depth how to submit written papers. Participants recognized the benefits of having a web based tool. Results from the built-in evaluation surveys and descriptive analysis of the focus groups data also helped generate three types of recommendations: ways to enhance the tool itself, ways to enhance students' experience when using the tool and faculty's responsibility in helping students learn how to use the tool.


Adsorption of nanoparticles at the solid-liquid interface.
The adsorption of differently charged nanoparticles at liquid-solid interfaces was investigated by in situ X-ray reflectivity measurements. The layer formation of positively charged maghemite (γ-Fe(2)O(3)) nanoparticles at the aqueous solution-SiO(2) interface was observed while negatively charged gold nanoparticles show no adsorption at this interface. Thus, the electrostatic interaction between the particles and the charged surface was determined as the driving force for the adsorption process. The data analysis shows that a logarithmic particle size distribution describes the density profile of the thin adsorbed maghemite layer. The size distribution in the nanoparticle solution determined by small angle X-ray scattering shows an average particle size which is similar to that found for the adsorbed film. The formed magehemite film exhibits a rather high stability.


A Hill Gastropexy Combined with Nissen Fundoplication Appears Equivalent to a Collis-Nissen in the Management of Short Esophagus.
A Collis gastroplasty combined with a Nissen fundoplication is commonly used when a shortened esophagus is encountered. An alternative combines intra-abdominal fixation of the gastroesophageal junction via a Hill gastropexy with a Nissen fundoplication to maintain length and avoid juxtaposing acid-secreting tissue against the diseased esophagus. A retrospective case-controlled analysis of 106 consecutive patients with short esophagus undergoing Hill-Nissen (HN) or Collis-Nissen (CN) was compared to a cohort of 105 matched patients without short esophagus undergoing primary Nissen fundoplication (NF). At a median follow-up of 27 months, all groups (HN:CN:NF) improved significantly over preoperative baseline with no differences in overall complications (18 vs 16 vs 19%, p = 0.78), DeMeester score (11.1 vs 19.1 vs 14.2, p = 0.49), postoperative PPI use (16 vs 22 vs 15%, p = 0.24), anatomic recurrences (11.7 vs 5.5 vs 7%, p = 0.43), or quality of life (6.8 vs 6.7 vs 6.4, p = 0.3). The management of shortened esophagus with Hill-Nissen is safe and as effective as Collis gastroplasty with Nissen fundoplication. Both options appear to produce similar outcomes to patients requiring only a Nissen fundoplication suggesting a shortened esophagus does not beget an inferior outcome.


Murine pregnancy-associated modulations in lymphocyte reactivity to mitogens: identification of the cell populations affected.
Lymphocytes from the thymus, spleen and inguinal lymph nodes of syngeneically pregnant and non-pregnant mice were compared in their responsiveness to polyclonal stimulation by mitogen. Pregnancy-associated changes in mitogen reactivity were detected, on a cell-per-cell basis, in thymocytes (increased) and spleen cells (decreased) but not in lymph node cells. The hyperreactivity of thymocytes during pregnancy correlated with physiological involution of the thymus occurring through the selective loss of relatively immature, non-mitogen-reactive, Lyt 1+2+ cells. The remaining cells were found largely to be mature Lyt 1+2- T cells with the capacity to respond to mitogenic stimulation. It is most likely the relative increase in the proportion of these Lyt 1+2- cells that causes the hyper-responsiveness of thymocytes to mitogens observed during pregnancy. On the other hand, while spleen cells from pregnant animals gave lower responses to mitogens than those from control virgin females, isolated splenic T cells from the two groups proved equally reactive to T cell mitogens. This supports the contention that at least some aspects of immunity during pregnancy are down-regulated by inhibitory cells within the non-T cell compartment. The results demonstrate the importance of identifying the reactive cell population in studies on changes in lymphocyte responsiveness in pregnancy.


Immunological detection of somatostatin in a primitive hypothalamic mouse cell line, precursor of a neurophysin cell lineage.
A primitive nerve cell line (F7 clone), obtained by SV 40 transformation of mouse fetal hypothalamic cells, has been previously shown to share some properties with a progenitor cell for neurophysin synthesizing neuron. This paper describes the immunological detection, at the light microscope level, of somatostatin in this cell line. A SV 40 transformed neurosecretory clone, synthesizing neurophysin and vasopressin, was used as control.


Low Specificity of Rapid Eye Movement Sleep Behavior Disorder Questionnaires: Need for Better Screening Methods.
Correct diagnosis of rapid eye movement sleep behavior disorder (RBD) is critical due to its link to α-synucleinopathies and risk of injuries and requires video-polysomnography (V-PSG). Usefulness of screening questionnaires outside the context of validation studies is limited. The aim was to assess the performance of three validated RBD screening questionnaires compared with gold-standard V-PSG. In this bicentric prospective study, 400 consecutive subjects referred to a sleep center for the first time filled three RBD questionnaires (RBD Screening Questionnaire, RBD Single Question, and Innsbruck RBD Inventory) in random order before sleep experts' interview. Subjects positive for at least one questionnaire were invited to undergo V-PSG. Data from patients negative for all questionnaires undergoing V-PSG for other reasons were also evaluated. Questionnaire performances were compared to gold-standard V-PSG RBD diagnosis. Three hundred ninety-nine patients (median age: 51 [interquartile range: 37-64] years, 54.9% men) participated. Two hundred thirty-eight (59.6%) were positive for at least one questionnaire, and RBD was diagnosed using V-PSG in 30 patients (7.5%). Questionnaire specificity was 48.1% to 67.4%, sensitivity 80% to 92%, accuracy 51% to 68.3%, negative predictive value 94.2% to 98%, and positive predictive value 14.1% to 20.7%, with no relevant differences in performances among the evaluated questionnaires. RBD questionnaires have low specificity and low positive predictive value and should not be used as a standalone tool for the diagnosis of RBD. Further development of RBD screening methods is needed, particularly for upcoming neuroprotective trials. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Validation of a HPLC method for the determination of p-nitrophenol hydroxylase activity in rat hepatic microsomes.
We report a HPLC-UV method for determination of p-nitrophenol (PNP) hydroxylation to 4-nitrocatechol (4NC) as a marker for CYP2E1 activity in rat hepatic microsomes. Proteins were precipitated by addition of 50 microL phosphoric acid (50%, v/v in water) to 500 microL microsomal suspensions. Following vortex mixing and centrifugation the supernatant (20 microL) was injected onto a Supelcosil C(18) column (150 mm x 4.6 mm, 5 microm), and mobile phase (22% acetonitrile, 0.1% trifluoroacetic acetic acid, 0.5% triethylamine) delivered at 1.0 mL/min produced resolved peaks for internal standard, 4NC, and PNP in < 11 min. Calibration curves were linear (r(2) = 0.999) from 0.1 to 40 microM with intra- and inter-day precision < 12% and accuracy >90%. The method's improved sensitivity (LOQ = 0.1 microM) and minimal sample processing allowed rapid monitoring of PNP hydroxylase activity in fetal, neonatal, juvenile, and adult rat livers.


VLDL best predicts aortic root atherosclerosis in LDL receptor deficient mice.
Hyperlipidemia is a major risk factor for developing atherosclerosis in humans, and epidemiological studies have correlated specific lipoprotein levels with cardiovascular disease risk. Murine models of atherosclerosis rely on the induction of hyperlipidemia for vascular lesions to form, but the pathogenic contributions attributed to different lipoprotein populations are not well defined. To address this issue, we analyzed over 300 LDL receptor (LDLR) deficient mice that have been fed a high-fat diet and for which a full lipoprotein profile and aortic root atherosclerosis values were assessed. Overall, aortic root atherosclerosis is best predicted by plasma VLDL cholesterol levels with less predictive value derived from either LDL or HDL cholesterol. Triglyceride levels are more atherogenic in female mice, especially immune competent females, and depletion of the adaptive immune system leads to a global reduction in plasma lipid levels and aortic root lesion size yet does not appear to alter the atherogenic potential of individual lipoprotein subspecies. In contrast, HDL-cholesterol is a better predictor of aortic root atherosclerosis in apoE-deficient mice. In summary, this large scale analysis of high-fat diet fed LDLR deficient mice highlight the relationship between different plasma lipid components, especially VLDL-cholesterol, and aortic root atherosclerosis.


Bladder Instillation Therapy With Hyaluronic Acid and Chondroitin Sulfate Improves Symptoms of Postradiation Cystitis: Prospective Pilot Study.
After radiotherapy (RT) for prostate cancer (PCa), several patients reported lower urinary tract symptoms (LUTS) due to damage and discontinuation of the glycosaminoglycan layer of the bladder. Instillation of hyaluronic acid and chondroitin sulfate (HA-CS) represents replenishment therapy of the glycosaminoglycan layer. The aim of the study is to evaluate the efficacy and safety of HA-CS in men with symptomatic cystitis after RT for PCa. Eighty consecutive men were treated with RT for PCa; 30 of these (37.5%) reported clinically relevant LUTS and associated bother as measured by the Interstitial Cystitis Symptom Index and Problem Index (ICSI/ICPI) Questionnaire 3 months after RT. Symptomatic patients received instillation therapy with HA-CS weekly for the first month and then at weeks 6, 8, and 12. All patients completed the ICSI/ICPI questionnaire before and after RT and at the end of HA-CS treatment. HA-CS significantly reduced postradiation LUTS (P < .001) and bother (P = .006). Age, Gleason score, and radiation dose were the main determinants of worsening of LUTS after radiation (ICSI score baseline vs. postradiation: P = .047, .043, and .023). In multivariate analysis, only age influenced LUTS worsening after RT (P = .01). Age, radiation dose, and radiation toxicity were related to recovery of LUTS (ICSI score postradiation vs. post-HA-CS P = .041, P = .050, and P = .046). In multivariate analysis, no factor was statistically significant. A remarkable worsening of symptoms and bother was observed after RT. HA-CS instillation is a safe treatment and resulted in an improvement of LUTS irrespective of age and clinical features, with full recovery of urinary bother.


Health inequalities, fundamental causes and power: towards the practice of good theory.
Reducing health inequalities remains a challenge for policy makers across the world. Beginning from Lewin's famous dictum that "there is nothing as practical as a good theory", this paper begins from an appreciative discussion of 'fundamental cause theory', emphasizing the elegance of its theoretical encapsulation of the challenge, the relevance of its critical focus for action, and its potential to support the practical mobilisation of knowledge in generating change. Moreover, it is argued that recent developments in the theory, provide an opportunity for further theoretical development focused more clearly on the concept of power (Dickie et al. 2015). A critical focus on power as the essential element in maintaining, increasing or reducing social and economic inequalities - including health inequalities - can both enhance the coherence of the theory, and also enhance the capacity to challenge the roots of health inequalities at different levels and scales. This paper provides an initial contribution by proposing a framework to help to identify the most important sources, forms and positions of power, as well as the social spaces in which they operate. Subsequent work could usefully test, elaborate and adapt this framework, or indeed ultimately replace it with something better, to help focus actions to reduce inequalities.


Prolonged electrocerebral silent barbiturate coma in intractable seizure disorders.
Barbiturate coma (BC) is a known modality for terminating resistant convulsive status epilepticus. It is usually applied until seizure activity ends. We recently adopted a modified protocol of prolonged, electrocerebral silent BC to treat patients with chronic seizure activity resistant to multiple regimens of antiepileptic drugs. Four patients, aged 4 months to 10 years, with long-standing intractable generalized seizures were treated. Seizure frequency ranged from one to two to numerous times per day. Following BC, one patient has been seizure free during 8 months of follow-up, and another has had only two seizures in 18 months. A 4-month-old infant was seizure-free for 2 weeks after BC and then died from underlying CNS disease. A 10-year-old girl died during BC from shock and hyperpyrexia. The results obtained in our patients indicate that prolonged electrocerebral silent BC may exert a beneficial long-term effect in treatment of intractable seizure disorders. This procedure might also be beneficial in other forms of epilepsy.


Evaluating Firefighter On-Scene Decontamination Practices Using a National Fire Records Management System.
This study describes firefighters' on-scene decontamination procedure use post-working fire and frequency of adherence to best practice. This retrospective analysis of working fires was conducted using records from the ESO Data Collaborative (Austin, TX) national research database from January 1, 2021, to December 31, 2021. Documentation of decontamination procedures was examined among records with smoke or combustion products exposure. Firefighter and incident characteristics were evaluated. Descriptive statistics and univariable odds ratios were calculated. Among the 31,281 firefighters included in the study, 8.0% documented a fire-related exposure. Of those, 82% performed at least one on-scene decontamination procedure; 5% documented all decontamination procedures defined as best practices. The odds of documenting any decontamination procedure were significantly decreased among firefighters responding to incidents in rural areas compared with urban areas (odds ratio, 0.70). Fire personnel may not be taking all necessary decontamination steps post-working fires.


[Screening of binding proteins to interferon-alpha promoter DNA by phage display technique].
To investigate the interferon alpha regulation mechanisms by screening binding proteins of interferon alpha promoter by phage display. PCR product of interferon-alpha promoter was incubated with a phage display cDNA library that expressed a library of human liver proteins on the surface of bacteriophage T7. Unbound phages were washed off and the phages bound to the interferon alpha promoter were amplified. Positive plaques were amplified by PCR and cloned into a pGEM-Teasy vector in order to perform DNA sequence analysis and subsequent computer blasting analysis. Positive phage-displayed proteins binding with interferon alpha promoter were enriched after five rounds of biopanning. We found that the following proteins were relevant to interferon alpha: mitochondrial ribosomal protein, chromosome clone, fibrinogen A alpha polypeptide, enoyl coenzyme A hydratase short chain, eukaryotic translation elongation factor 1 alpha, PI-3-kinase-related kinase SMG-1-like, xeroderma pigmentosum C group, and Homo sapien activity-dependent neuroprotector (ADNP). Many proteins with different functions could bind with interferon alpha promoter.


Radiologic assessment of a self-shield with boron-containing water for a compact medical cyclotron.
The cyclotron at our hospital has a self-shield of boron-containing water. The amount of induced radioactivity in the boron-containing water shield of a compact medical cyclotron has not yet been reported. In this study, we measured the photon and neutron dose rates outside the self-shield during cyclotron operation. We estimated the induced radioactivities of the boron-containing water used for the self-shield and then measured them. We estimated the activation of concrete outside the self-shield in the cyclotron laboratory. The thermal neutron flux during cyclotron operation was estimated to be 4.72 × 10(2) cm(-2) s(-1), and the activation of concrete in a cyclotron laboratory was about three orders of magnitude lower than the clearance level of RS-G-1.7 (IAEA). The activity concentration of the boron-containing water did not exceed the concentration limit for radioactive isotopes in drainage in Japan and the exemption level for Basic Safety Standards. Consequently, the boron-containing water is treatable as non-radioactive waste. Neutrons were effectively shielded by the self-shield during cyclotron operation.