Changing demographics of residents choosing fellowships: longterm data from the American Board of Surgery.
After completing general surgery residency, surgeons may seek focused additional education or fellowships. Longterm data describing the characteristics of residents selecting fellowships are lacking. Credible data could inform decisions about surgical education paradigms and workforce planning. From 1993 to 2005, residents taking the American Board of Surgery In-Training Examination were queried about fellowship plans. Individual and residency program data were collected: gender, postgraduate year level (PGY), medical school location (US/international), residency type (academic/community), residency size, and residency location (Northeast, Southeast, Midwest, Southwest, West). The data were examined for changes in the numbers and characteristics of residents seeking fellowships. Responses from 11,080 postgraduate year level-5 residents were analyzed. The number of women nearly doubled and the number of international medical graduates (IMG) almost tripled. Residency program demographics were static. The percentage choosing fellowships increased from 67% to 77%. Patterns of change from "No Fellowship" to "Any Fellowship" were spread heterogeneously across individual and residency subsets. Increases were greatest for Midwest, Southeast, women, community, small program, and US medical graduates. Temporal patterns of change were also heterogeneous. Specialty top choice patterns varied, leading to disproportionate demographic subgroup representation within some specialties. More general surgery residents are pursuing fellowships. The increase has originated disproportionately from resident and residency demographic subsets and has varied temporally across subgroups. The heterogeneity of change suggests a multifactorial etiology. Future directions in surgical education and workforce planning should reflect these findings.


Immunotoxicity in ascidians: antifouling compounds alternative to organotins - II. The case of Diuron and TCMS pyridine.
Using short-term hemocyte cultures of the colonial ascidian Botryllus schlosseri exposed to various sublethal concentrations of Diuron (3-(3,4-diclorophenyl)-1,1-dimethylurea) and TCMS pyridine (2,3,5,6-tetrachloro-4-(metylsulphonyl)pyridine), we evaluated their immunotoxic effects through a series of cytochemical assays previously used for organotin compounds. At concentrations higher than 250 micro M and 10 micro M for Diuron and TCMS pyridine, respectively, both biocides exerted immunosuppressant effects on Botryllus hemocytes, causing i) deep changes in the cytoskeleton that irreversibly affect cell morphology and phagocytosis, ii) induction of DNA damage, iii) leakage of oxidative and hydrolytic enzymes due to membrane alteration. Unlike organotin compounds, Diuron and TCMS pyridine do not inhibit cytochrome-c-oxidase, and only TCMS pyridine triggers oxidative stress. When co-present, they exert an antagonistic interaction on cytoskeletal components.


Altered Rho GTPase signaling pathways in breast cancer cells.
The Rho family of GTPases have emerged as key players in regulating a diverse set of biological activities including actin organization, focal complex/adhesion assembly, cell motility, cell polarity, gene transcription and cell-cycle progression. Some Rho GTPases and their signaling components are overexpressed and/or are hyperactive in breast cancer and recent studies have shown a requirement for Rho GTPases in breast cancer cell metastasis in vivo. Herein we describe the contribution of Rho GTPase to the malignant phenotype of breast cancer cells and the role of these pathways as potential targets for breast cancer therapy. Rho GTPases promote cell-cycle progression through cyclin D1, and cyclin D1 in turn reduces cellular adhesion and promotes migration, an example of 'inside-out' signaling by cyclin D1. As cyclin D1 overexpression correlates with metastatic cancer, the 'inside-out' signaling function of cyclin D1 to promote cell migration may represent a useful new therapeutic target.


Dynamic voltage threshold adjusted substrate modification technique for complex atypical atrial flutters with varying circuits.
Atypical atrial flutter (AFL) is common in patients with postsurgical atrial scar, with macro- or microscopic channels in the scar acting as substrate for reentry. Heterogeneous atrial scarring can cause varying flutter circuits, which makes mapping and ablation challenging, and recurrences common. We hypothesize that dynamically adjusting voltage thresholds can identify heterogeneous atrial scarring, which can then be effectively homogenized to eliminate atypical AFLs. We studied consecutive patients who presented to Electrophysiology laboratory for atypical AFL ablation with history of atriotomy and included the patients with multiple, varying flutter circuits during mapping in our study. We excluded patients with stable flutter circuit that was sustained and could be localized using traditional entrainment and activation mapping strategy. In the included patients, we performed detailed high-density voltage map of the atrium of interest. We adjusted voltage thresholds as needed to identify heterogeneity and channels in the scarred regions. A thorough scar homogenization was performed with irrigated smart-touch ablation catheter. Re-inducibility of tachycardia, and immediate and long-term outcomes were studied. Of five studied cases, one was female; age 66 ± 10 years. All five had prior surgical substrate. All the patients had multiple flutter morphologies, which varied as we mapped the AFL. After scar homogenization, tachycardia was not inducible in any patient. No recurrence of flutter was noted during a mean follow-up duration of 450 ± 27 days. High-density voltage mapping and homogenization of the scar can be an effective strategy in eliminating complex scar-mediated atypical AFL with multiple circuits.


Improving and monitoring autoclave performance in dental practice.
The sterilisation of instruments is central to the infection control process in the dental surgery, with the autoclave being most frequently used for this process. For effective operation, among other factors, it is essential that the autoclave is loaded correctly and tested regularly to ensure that it is operating at a temperature and pressure which will kill all micro-organisms. Biological indicators are another method of verifying the sterilisation process, since the sterilisation of the bacterial spores within the test ampoule provides a guarantee that sterilising conditions have been achieved.


Enabling technologies for the rapid dechlorination of polychloroarenes and PCBs.
Dielectric heating and acoustic cavitation (ultrasound or high-performance disperser) may all dramatically enhance conversion rates and yields in heterogeneous metal-assisted organic reactions even when low reagent excesses are used. These so called "enabling technologies" bring with them process intensification, safer protocols, cost reduction and energy savings. We herein describe a series of rapid polychlorinated aromatic and PCBs dechlorinations (15min) carried out in a moderate excess of metallic sodium and using non-conventional techniques. We compared the results with those obtained for reactions carried out under conventional heating and with those performed with less reactive metals such as magnesium and zinc. In this comparison, high-intensity ultrasound stands out as the technique of choice.


Ibuprofen degradation by a synergism of facet-controlled MIL-88B(Fe) and persulfate under simulated visible light.
The photocatalysis/persulfate (PS) hybrid system has proven to be a promising method for degrading organic pollutants from aqueous solutions. In this study, three MIL-88B(Fe) iron-based metal-organic framework (MOF) phases with different facet content were prepared and used both as photocatalysts and catalysts for PS activation to remove ibuprofen (IBP). The results showed that there was a close correlation between the exposed facets and the catalytic activity. MIL-88B(Fe)-1 (M88B1) with exposed {100} facets and proportionally more {101} facets showed the best catalytic activity. The optimum PS dosage used in this study was 60 mg/L. The presence of Cl-, SO42-, and NO3- all inhibited the degradation of IBP. X-ray photoelectron spectroscopy (XPS) showed that M88B1 possessed more Fe2+ than the other two MIL-88B(Fe) MOF phases, making it easier to generate active radicals through PS activation. The UV-vis diffuse reflectance spectra (DRS), photoluminescence (PL), and electrochemical analysis indicated that M88B1 possessed the highest light absorption, most active sites, and fastest charge transfer ability. Radical scavenging and electron spin resonance (ESR) experiments demonstrated that SO4-•, •OH, O2-•, and 1O2 species participated in the IBP degradation process. Furthermore, density functional theory (DFT) calculations were performed to identify the crystallographic facets, band structure, and total density of states of MIL-88B(Fe) to further confirm the mechanism of MIL-88B(Fe) as a photocatalyst and a PS activator. This work provides new insights into the synergism between photocatalysis and persulfate activation by facet-controlled MOFs for environmental remediation.


Trimodality therapy (drug/hyperthermia/radiation) with BCNU or mitomycin C.
To develop multimodality treatment combinations with high curative potential in advanced local disease, BCNU (N,N'-bis(2-chloroethyl)-N-nitro-sourea) and mitomycin C were tested with hyperthermia and radiation in the FSaIIC fibrosarcoma system. Growth delay experiments demonstrated that, while neither BCNU nor mitomycin C produced dose modification of the radiation response, and hyperthermia (43 degrees C, 30 min) produced only a moderate dose modification (1.4 +/- 0.2), the combination of BCNU plus hyperthermia resulted in a radiation dose modifying factor (DMF) of 1.9 +/- 0.3, and mitomycin C plus hyperthermia a dose modifying factor of 2.1 +/- 0.4. Tumor cell survival over a range of BCNU doses administered i.p. immediately before hyperthermia resulted in a dose modifying factor of 1.8 +/- 0.2 versus drug alone. With mitomycin C however, giving the drug immediately prior to heating produced a dose modifying factor due to hyperthermia of only 1.2 +/- 0.10. Hoechst 33342 diffusion was used to separate tumor cells into predominately oxic and hypoxic subpopulations. Administration of the single, double and trimodality therapies showed that BCNU was 3.1-fold more toxic to the oxic versus the hypoxic cells whereas mitomycin C was 3.5-fold more toxic to the hypoxic compared to the oxic cells. Hyperthermia was 1.4-fold more toxic to the hypoxic versus the oxic cells whereas 10 Gy of radiation was 2.0-fold more toxic to the oxic compared to the hypoxic cells. The combination of hyperthermia plus radiation increased killing in both Hoechst dye defined subpopulations but relatively more in the hypoxic cells in which killing was 1.8-fold greater than in the oxic cells. When heat was delivered immediately after i.p. administration of the anticancer drugs, hyperthermia increased BCNU killing in the oxic cells by 17.2-fold versus 4.4-fold in the hypoxic cells and increased mitomycin-killing by 2.6-fold in the oxic cells versus 17-fold in the hypoxic cells. Use of the full trimodality treatment, given in the sequence drug (BCNU, 50 mg/kg or mitomycin-C 5 mg/kg)----heat (43 degrees C, 30 min)----radiation (10 Gy) produced a 3 log kill in the oxic cells versus a 2 log kill in the hypoxic cells with BCNU and a 2 log kill in the oxic cells versus a 3 log kill in the hypoxic cells with mitomycin C. These results indicate that the use of selected anticancer drugs with hyperthermia and radiation can produce highly cytotoxic interactions which markedly modify the effect of radiation.(ABSTRACT TRUNCATED AT 400 WORDS)


Exertional Leg Pain.
Exertional leg pain is a common condition seen in runners and the general population. Given the broad differential diagnosis of this complaint, this article focuses on the incidence, anatomy, pathophysiology, clinical presentation, diagnostic evaluation, and management of common causes that include medial tibial stress syndrome, tibial bone stress injury, chronic exertional compartment syndrome, arterial endofibrosis, popliteal artery entrapment syndrome, and entrapment of the common peroneal, superficial peroneal, and saphenous nerves. Successful diagnosis of these conditions hinges on performing a thorough history and physical examination followed by proper diagnostic testing and appropriate management.


[A case of postoperative recurrent breast cancer with multiple lung metastases that completely responded to combination therapy of docetaxel (TXT) and medroxyprogesterone acetate (MPA)].
A 54-year-old female had undergone surgery for breast cancer 5 years ago, after which she developed multiple lung metastases, in spite of treatment with various postoperative chemoendocrine therapies. The patient who had recurrent breast cancer with multiple lung metastases was treated with a combination of docetaxel (TXT) 80 mg/body three cycles, two courses of 40 mg/body four times and medroxyprogesterone acetate (MPA) 600 mg p.o. daily. Six months later, the lung metastases had completely disappeared on chest CT-scan. Complete remission has been maintained for one and half years. The use of combined chemoendocrine therapy with TXT and MPA is considered effective for recurrent breast cancer as second-line therapy.


Teleconsultation in primary ophthalmic emergencies during the COVID-19 lockdown in Paris: Experience with 500 patients in March and April 2020.
This prospective observational cohort study is based on the first 500 patients who requested emergency teleconsultation during the initial days of the COVID-19 lockdown in Paris, France between 20 March and 10 April 2020. It is the first study to assess the utility of emergency teleophthalmology with a simple smartphone application or web browser and a webcam to manage emergency eye care in a population with sudden restricted access to ophthalmologists. In this study, every patient who asked for an ophthalmic emergency consultation in a single specialized center in Paris ('SOS Œil') first had to undergo a teleconsultation appointment to evaluate the indication for a physical consultation to preserve lockdown. Under medical advice only, a physical appointment was given within a day (if necessary). The aim of the study was to describe the population and diagnoses and evaluate the main judgment criteria, defined as the 'ability of teleconsultation to properly indicate a physical consultation for fair diagnosis and treatment in eye emergencies'. This organization has permitted physicians and patients to preserve social distancing while avoiding 3 or 4 physical consultations per person. Notably, 27% of teleconsultations were followed by a physical appointment. There was a mean 4.12-day delay between symptom apparition and consultation, and less than 1 day for traumas, superficial corneal foreign body and neuro-ophthalmological emergencies. There was a 96% sensitivity and 95% specificity to properly evaluate the indication of a physical consultation and only 1.0% misdiagnoses that lead to delayed care. Hence, teleconsultation maintained satisfactory healthcare access to patients with severe ophthalmological disorders while preserving social distancing and sanitary precautions. Therefore, teleconsultation may be seriously considered as a way to efficiently regulate ophthalmic emergencies, especially for patients with limited access to a specialist.


Association study between a functional polymorphism of FK506-binding protein 51 (FKBP5) gene and personality traits in healthy subjects.
Previous studies have shown that the function of hypothalamic-pituitary-adrenal (HPA) axis is involved in the characterization of personality traits. FK506-binding protein 51 (FKBP51 or FKBP5) is a co-chaperone of heat-shock protein 90, and plays an important role in the negative feedback regulation of HPA axis function. It has been reported that a C/T single nucleotide polymorphism in the intron 2 of FKBP5 gene (rs1360780) affects FKBP5 protein levels and cortisol response to dexamethasone and psychological stress tests. Therefore, it is hypothesized that the FKBP5 polymorphism affects personality traits. In the present study, we studied the association between this polymorphism and personality traits in 826 Japanese healthy subjects. Personality traits were assessed by the Temperament and Character Inventory (TCI), and the FKBP5 genotype was detected by a real-time PCR and cycling probe technology for SNP typing. In total subjects, the group with the T allele predictive of impaired negative feedback regulation of the HPA axis had higher scores of harm avoidance (HA) (p=0.043) and lower scores of cooperativeness (CO) (p=0.019) compared to that without the T allele. The T allele was associated with higher scores of HA in females (p=0.020) and lower scores of CO in males (p=0.015). The present study thus suggests that the FKBP5 polymorphism affects HA and CO in healthy subjects, with gender specificity.


Hyaluronic acid synthesis and secretion by rat liver fat storing cells (perisinusoidal lipocytes) in culture.
The ability of rat liver fat storing cells to synthesize and to secrete hyaluronic acid was examined in monolayer cultures. The cells produce [3H] glucosamine-labeled hyaluronic acid, of which about 80% are secreted into the medium. The synthesis rate per cell (mg DNA) of labeled total glycosaminoglycans and hyaluronic acid in the medium increases significantly with culture time, but hyaluronic acid expressed as fraction of total glycosaminoglycans declines from about 0.70 in early cultures (up to the 4th day) down to 0.20 in advanced cultures. Cycloheximide increases and beta-D-xylopyranoside decreases significantly the fraction of hyaluronic acid in the medium, colchicine up to 5 microM was without effect. The synthesis of hyaluronic acid is a newly recognized function of this special type of sinusoidal liver cells. The results suggest that fat storing cells are likely to be a major source of hyaluronic acid in normal and probably also in injured liver.


Clinical predictors of bleeding esophageal varices in the ED.
Some authors have found that thrombocytopenia (<118,000/mm3), splenomegaly, and ascites are useful predictors of large esophageal varices in cirrhotic patients. We decide to see whether these factors could also be used to predict bleeding esophageal varices in patients known to have chronic liver disease in the ED. A case record review was done of all patients admitted to the ED of Changi General Hospital with upper gastrointestinal bleeding from esophageal varices from October 1999 to April 2004. The criteria of thrombocytopenia, splenomegaly, and ascites were applied retrospectively to these patients to see how accurately they performed in predicting bleeding esophageal varices. Only 55% of patients had thrombocytopenia, whereas 45% had splenomegaly, and 27.5% had ascites. Combining thrombocytopenia with the presence of either ascites or splenomegaly did not improve the yield (only 40%), and only 6 patients had all 3 criteria. Twelve patients with bleeding varices did not have any of the criteria. Thrombocytopenia, splenomegaly, or ascites is an unreliable predictor of bleeding esophageal varices. Urgent or emergent endoscopy is still advocated to accurately diagnose bleeding esophageal varices.


Pulmonary fat embolism after reamed and unreamed nailing of femoral fractures.
To determine whether reamed or unreamed intramedullary nailing of femoral fractures results in higher incidence of pulmonary fat embolism, three different methods of intramedullary nailing were compared in sheep. To analyze the presence of bone marrow fat embolism in pulmonary arteries, histological evaluation was undertaken using a quantitative computer-assisted measurement system. In this experimental model of 27 female Swiss alpine sheep, an osteotomy of the proximal femur was conducted in each animal. Then, the animals were divided into three groups according to the method of treatment: two different reamed intramedullary nailing techniques and an unreamed nailing technique were used. In the first group "ER" (experimental reamer; n=9), the nail was inserted after reaming with an experimental reamer; in the second group "CR" (conventional reamer; n=7), the intramedullary nail was inserted after reaming with the conventional AO-reamer. In the third group "UN" (unreamed; n=8) unreamed nailing was performed. During the operation procedure intramedullary pressure was measured in the distal fragment. After sacrificing the animals, quantitative histological analyses of bone marrow fat embolism in pulmonary arteries were done using osmium tetroxide fixation and staining of the fat. The measurement of intramedullary pressure showed significantly lower values for reamed nailing than for the unreamed technique. The quantitative histological evaluation of lung vessels concerning bone marrow fat embolism revealed a statistically significant difference between reamed and unreamed insertion of the nail: 7.77%±6.93 (ER) and 6.66%±5.61 (CR) vs. 16.25%±10.05 (UN) (p<0.05) of the assessed lung vessels were filled with fat emboli. However, no difference was found between the traditional and experimental reamer. Intramedullary nailing after reaming is a safe procedure with low systemic embolisation when compared to the unreamed insertion of the nail.


2D-Layered Ni-MgO-Al2 O3 Nanosheets for Integrated Capture and Methanation of CO2.
CO2 capture is an enabling technology for carbon conversion and storage; however, the high costs of the process have hindered its large-scale application so far. Therefore, new approaches for carbon abatement, particularly from diluted sources, are urgently needed. Herein, based on the adsorption and catalysis bifunctionality of 2D-layered Ni-O-Al2 O3 nanosheets, a two-step "capture and methanation" process is reported for the removal and utilization of CO2 , with no additional energy input for desorption being required. Continuous and nearly 100 % capture of CO2 was demonstrated at low temperatures (≤250 °C) and prolonged cycles. At isothermal conditions, the material could be fully regenerated with the production of methane, showing considerably higher time efficiency than temperature-swing and pressure-swing technologies. This strategy may pave a new way for CO2 reduction, providing a scalable connection between the power grid and the gas grid when H2 is used.


MicroRNA-1 properties in cancer regulatory networks and tumor biology.
Short non-coding microRNAs have been identified to orchestrate crucial mechanisms in cancer progression and treatment resistance. MicroRNAs are involved in posttranscriptional modulation of gene expression and therefore represent promising targets for anticancer therapy. As mircoRNA-1 (miR-1) exerted to be predominantly downregulated in the majority of examined tumors, miR-1 is classified to be a tumor suppressor with high potential to diminish tumor development and therapy resistance. Here we review the complex functionality of miR-1 in tumor biology.


Bell's measure and implementing quantum Fourier transform with orbital angular momentum of classical light.
We perform Bell's measurement for the non-separable correlation between polarization and orbital angular momentum from the same classical vortex beam. The violation of Bell's inequality for such a non-separable classical correlation has been demonstrated experimentally. Based on the classical vortex beam and non-quantum entanglement between the polarization and the orbital angular momentum, the Hadamard gates and conditional phase gates have been designed. Furthermore, a quantum Fourier transform has been implemented experimentally.


There and back again: Intracellular trafficking, release and recycling of matrix metalloproteinases.
Matrix metalloproteinases are a family of zinc-dependent endopeptidases that are involved in a large variety of proteolytic processes in physiological and pathological scenarios, including immune cell surveillance, tissue homeostasis, or tumor cell metastasis. This is based on their ability to cleave a plethora of substrates that include components of the extracellular matrix, but also cell surface-associated and intracellular proteins. Accordingly, a tight regulatory web has evolved that closely regulates spatiotemporal activity of specific MMPs. An often underappreciated mechanism of MMP regulation involves their trafficking to and from specific subcellular sites that require MMP activity only for a certain period. In this review, we focus on the current knowledge of MMP intracellular trafficking, their secretion or surface exposure, as well as their recycling back from the cell surface. We discuss molecular mechanisms that enable these steps, in particular microtubule-dependent motility of vesicles that is driven by molecular motors and directed by vesicle regulatory proteins. Finally, we also point out open questions in the field of MMP motility that may become important in the future.


Analgesic activity of 5-HT3 receptor antagonists.
The effects of 5-HT3 receptor antagonists tropisetron and condensed derivative of benzimidazole (laboratory code 64B) on nociceptive threshold were examined on models with activation of peripheral and central nociceptive mechanisms. The examined substances demonstrated pronounced analgesic effects in peripheral pain.


Sexism and racism in the American health care industry: a comparative analysis.
By drawing on a wide range of material, a picture emerges of extensive abuse, discrimination, and exploitation of women and ethnic minorities at the hands of the American health industry. The numbers of minorities and women in professional schools and among the "elite" strata of the industry remain disproportionately low. As patients, they receive often inferior, insensitive treatment. Overall, there is a remarkable similarity in the situation of women and minorities, a condition which reflects the pervasiveness of racism and sexism in American institutions and ideologies.


A study of light-initiated currents in Limulus lateral eye retinular cells.
Light-initiated currents in Limulus lateral eye retinular cells were studied using the voltage clamp technique. To assess the validity of such current measurements, the isopotentiality of retinular cells was determined on triply impaled cells and the effect of voltage clamping one retinular cell on adjacent retinular cells and on the eccentric cell in the same ommatidium was determined. The results of the experiments are: (1) retinular cells are isopotential at loci 100 micron apart; (2) appreciable steady state current during the clamping episodes leaks into neighboring retinular cells and the eccentric cell; (3) light-initiated currents exhibit two components; (4) there is a dynamic change in the resistance of the photoreceptor membrane during development of the receptor potential; (5) suppression of the rising phase (C1) of the receptor potential does not affect subsequent voltage changes; (6) suppression of the sodium influx which normally produces C1 has only minor effects on subsequent voltage changes; (7) reduced [KC1]out increases and increased [CK1]out decreases the reversal potential of light-initiated currents; and (8) reduced [NaC1]out reduces the magnitude and the reversal potential of light-initiated currents.


Sodium-Glucose Cotransporter Inhibitors Reduce Mortality and Morbidity in Patients With Heart Failure: Evidence From a Meta-Analysis of Randomized Trials.
Recent trials demonstrated the clinical efficacy of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with heart failure (HF), regardless of the presence or absence of type 2 diabetes. These data may allow the use of this innovative drug class in clinical routine for treating these patients. We aimed at further clarifying the role of SGLT2i in patients with diagnosis of HF, capitalizing on pooled sample size and heightened power for clinically relevant safety and efficacy outcomes. We conducted a systematic search of PubMed, reference lists of relevant articles, and Medline database from inception until March 1, 2021. This meta-analysis was completed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched for randomized trials that evaluated the cardiovascular effects of SGLT2i in patients with HF. Three investigators independently assessed study eligibility, extracted the data, and assessed risk of bias. Hazard ratios and 95% confidence intervals (CIs) were pooled and meta-analyzed using a random-effect model. Numbers needed to treat (NNT) with the relative 95% CIs were also calculated. The primary outcome was a composite of HF hospitalization or an urgent visit for worsening HF and cardiovascular death. Three trials were included in the study. Overall, treatment with SGLT2i was associated with a lower risk of the primary composite outcome [hazard ratios 0.73, 95% CI (0.67-0.80), NNT = 11.3]. Similarly, there was a significantly reduced risk of cardiovascular death, all-cause death, HF hospitalization and need for urgent treatment for HF, and HF hospitalization. Therefore, the available evidence supports the routine use of these drugs as standard-of-care, also given the highly favorable NNTs.


Astrovirus infection in hatchling turkeys: histologic, morphometric, and ultrastructural findings.
In three separate experiments, 2- or 5-day-old commercial turkey poults were inoculated orally with astrovirus and examined for clinical signs and for gross and microscopic lesions over a period of 14 days. By day 2 postinoculation (PI), inoculated poults had developed diarrhea, generalized loss of intestinal tone, and dilated ceca that contained light-yellow fluid feces and gas; these changes persisted through day 10 PI. Mild crypt hyperplasia was the only change discernible by light microscopy, and it was first noted in the proximal jejunum on day 1 PI, in the distal jejunum and ileum on day 3 PI, and in the duodenum on day 5 PI. A significant (P < 0.05) increase in crypt depth and area was documented by image analysis on day 3 PI. Ultrastructural evaluation revealed intracytoplasmic aggregates of astrovirus in enterocytes on the sides and base of villi in the ileum and distal jejunum on day 3 PI. Based on the findings, it was concluded that astrovirus caused lesions and replicated in both upper and lower segments of the small intestine in turkey poults.


Interactions of metoclopramide and ergotamine with human 5-HT(3A) receptors and human 5-HT reuptake carriers.
The actions of metoclopramide and ergotamine, drugs which are used as a combined migraine medication, on human (h)5-HT3A receptors and 5-HT reuptake carriers, stably expressed in HEK-293 cells, were studied with patch-clamp- and ([3H]5-HT)-uptake techniques. At clinical concentrations, metoclopramide inhibited peak and integrated currents through h5-HT3A receptors concentration-dependently (IC50 = 0.064 and 0.076 microM, respectively) when it was applied in equilibrium (60 s before and during 5-HT (30 microM) exposure). The onset and offset time constants of metoclopramide action were 1.3 and 2.1 s, respectively. The potency of metoclopramide when exclusively applied during the agonist pulse decreased more than 200-fold (IC50 = 19.0 microM, peak current suppression). Metoclopramide (0.10 microM) did not alter the EC50 of 5-HT-induced peak currents. In contrast to the lack of competitive interaction between metoclopramide and 5-HT in this functional assay, metoclopramide inhibited specific [3H]GR65630 binding to human h5-HT3A receptors in a surmountable manner. This seeming discrepancy between functional studies and radioligand binding experiments may be accounted for by (1) the slow kinetics of inhibition of peak currents by metoclopramide compared with the fast onset and offset kinetics of 5-HT-induced currents and (2) the low efficacy of metoclopramide in inhibiting radioligand binding (e.g. only 20% binding inhibition compared to 79% peak current suppression by 200 nM metoclopramide). At low concentrations (1-10 nM), ergotamine had no effect on 5-HT (30 microM)-induced peak currents. Above clinical concentrations, ergotamine (>3 microM) inhibited them. When both drugs were applied together (0.10 microM metoclopramide +0.001 to 0.01 microM ergotamine), an inhibition of both, peak and integrated current responses was observed. Neither metoclopramide (< or =30 microM) nor ergotamine (< or =30 microM) had an effect on the 5-HT reuptake carrier as they did not alter the citalopram-sensitive [3H]5-HT uptake.


Hereditary cancer syndrome: Part 2.--Psychosocial issues, concerns, and screening--results of a qualitative study.
To describe the feelings and concerns of family members with hereditary cancer syndrome (HCS) and their level of participation in prevention and early detection activities. Qualitative methods; content analysis of interviews. Community, hospital-based cancer screening center with a special program of supportive services for families with HCS. Purposeful theoretical sampling produced a sample (n = 13) of people with HCS. Most were Caucasian women representing a variety of types of HCS. In-depth, unstructured, audiotaped interviews that lasted about 60 minutes. Five themes emerged: (a) issues regarding communication with health professionals, (b) relationships with family members, (c) financial concerns, (d) psychosocial concerns, and (e) participation in screening activities. Individuals from families with HCS live with the knowledge that they have a high risk of developing malignancy. A true understanding of this risk may take time to comprehend. Many members of families with HCS require more education and support regarding cancer screening and prevention activities. Nursing roles include being an educator on risk and early detection measures, a patient advocate, and a resource to all members of the family with HCS. Future nursing research can help identify specific psychosocial needs among different family members and specific psychosocial needs associated with different types of HCS.


Analysis of rapid oscillations of glucose and free fatty acids in plasma.
The authors analyzed rapid oscillations of blood sugar (GL) and free fatty acid levels (FFA) in serum of healthy subjects. They investigated a series of blood samples taken under conditions of absolute rest from the cubital vein at 15-s intervals for a period of 6 min. In addition to common statistical parameters, they calculated the course of autocorrelation and cross-correlation functions and periodograms. The magnitude of oscillations is significantly higher than the error of the biochemical methods. In some sequences periodicities were detected which were statistically significant in 23.8% of GL and in 38.1% of FFA. 24-point series of GL collected in parallel from both arms correlate in 36.3% positively, in 27.3% negatively, and in 36.4% they do not correlate. Series of FFA and GL collected simultaneously from one site correlate mutaually in almost all instances either positively or negatively, frequently with a time shift. The oscillations may be due to (a) feedback regulations of the levels of the two metabolites, (b) permanent mutual interaction between the FFA and glucose level and (c) an uneven concentration of the two metabolites in different parts of the circulation. The above factors may combine, and the list of possible factors may not be complete.


A cell therapy approach to restore microglial Trem2 function in a mouse model of Alzheimer's disease.
Alzheimer's disease (AD) remains one of the grand challenges facing human society. Much controversy exists around the complex and multifaceted pathogenesis of this prevalent disease. Given strong human genetic evidence, there is little doubt, however, that microglia play an important role in preventing degeneration of neurons. For example, loss of function of the microglial gene Trem2 renders microglia dysfunctional and causes an early-onset neurodegenerative syndrome, and Trem2 variants are among the strongest genetic risk factors for AD. Thus, restoring microglial function represents a rational therapeutic approach. Here, we show that systemic hematopoietic cell transplantation followed by enhancement of microglia replacement restores microglial function in a Trem2 mutant mouse model of AD.


Randomized, placebo-controlled trial of the angiotensin-converting enzyme inhibitor, ramipril, in patients with coronary or other occlusive arterial disease. PART-2 Collaborative Research Group. Prevention of Atherosclerosis with Ramipril.
The primary objective of this study was to investigate the effects of the angiotensin-converting enzyme (ACE) inhibitor, ramipril, on carotid atherosclerosis in patients with coronary, cerebrovascular or peripheral vascular disease. Angiotensin-converting enzyme inhibitors have been shown to reduce the risk of coronary events in various patient groups and to prevent the development of atherosclerosis in animal models. It has been hypothesized that the clinical benefits of ACE inhibitors may, therefore, be mediated by effects on atherosclerosis. Six hundred seventeen patients were randomized in equal proportions to ramipril (5-10 mg daily) or placebo. At baseline, two years and four years, carotid atherosclerosis was assessed by B-mode ultrasound, and left ventricular mass was assessed by M-mode echocardiography. Blood pressure (BP) was reduced by a mean of 6 mm Hg systolic and 4 mm Hg diastolic in the ramipril group compared with the placebo group (p<0.001). There was no difference between groups in the changes in common carotid artery wall thickness (p = 0.58) or in carotid plaque (p = 0.93). Left ventricular mass index decreased by 3.8 g/m2 (4%) in the ramipril group compared with the placebo group (2p = 0.04). The results provide no support for the hypothesis that reduced atherosclerosis is responsible for the beneficial effects of ACE inhibitors on major coronary events. It is more likely that the benefits are due to lower BP, reduced left ventricular mass or other factors such as reversal of endothelial dysfunction.


Anxiety, depression, insomnia symptoms & associated factors among young to middle-aged adults during the resurgent epidemic of COVID-19: a cross-sectional study.
The coronavirus disease 2019 (COVID-19) pandemic is a public health emergency of international concern. However, its stress on the mental health of young to middle-aged adults is largely unexplored. This study aimed to evaluate the mental health difficulties during the resurgent phase of COVID-19 among young to middle-aged adults in China. There were 1,478 participants with a median age of 26 years (IQR, 23 - 30), including 535 males (36.2%). The prevalence of anxiety, depression, and insomnia were 8.6%, 11.4%, and 13.7%, respectively. Participants aged 29 - 59 years (OR, 95% CI: 2.46, 1.23 - 4.91) and females (2.49, 1.55 - 4.01) had a higher risk of anxiety. Education status, worried level about the current COVID-19, and the level of COVID-19's impact on life were significantly associated with the prevalence of anxiety. Besides, the level of COVID-19's impact on life was positively related to the prevalence of depression and insomnia. Our study provided novel evidence of psychological difficulties among young to middle-aged adults during the resurgent stage of the COVID-19 epidemic. Psychological intervention should be continuously implemented to prevent long-term psychological comorbidities during the COVID-19 epidemic.


Downregulation of long noncoding RNA NONHSAT037832 in papillary thyroid carcinoma and its clinical significance.
Long noncoding RNA (lncRNA) is a kind of RNA that is longer than 200 nucleotides with limited or no protein-coding potential. Studies have proved that lncRNAs play important regulatory roles in gene expression and contribute to oncogenesis and cancer metastasis. However, the expression level of lncRNAs and their clinicopathologic significance in papillary thyroid carcinoma (PTC) have not been well studied. In this study, we investigated the expression level of a novel lncRNA NONHSAT037832 in PTC and paired noncancerous thyroid tissues as well as some cell lines by quantitative real-time polymerase chain reaction. The association between the expression level of NONHSAT037832 and clinicopathologic characteristics of patients with PTC was further analyzed. Three receiver operating characteristic curves (ROCs) were established to evaluate the diagnostic value of NONHSAT037832. The results suggested that the expression level of NONHSAT037832 was significantly decreased in PTC compared with paired noncancerous tissues (P < 0.01). And, NONHSAT037832 was also significantly downregulated in two PTC cell lines (K1 and IHH-4) compared to normal thyroid follicular epithelial cell line Nthy-ori 3-1 (P < 0.01). Downregulated NONHSAT037832 was significantly associated with lymph node metastasis (P = 0.015) and tumor size (P = 0.032). The ROCs revealed that NONHSAT037832 had a high diagnostic value for differentiating between PTC and noncancerous diseases as well as identifying PTC with lymph node metastasis and larger tumors (≥3 cm). The area under curve was up to 0.897 (95%CI = 0.852-0.942, P = 0.000), 0.641 (95%CI = 0.519-0.762, P = 0.033), and 0.702 (95%CI = 0.567-0.827, P = 0.008), respectively. This study indicated that NONHSAT037832 might serve as a potential biomarker of PTC.


The impact of mariculture on nutrient dynamics and identification of the nitrate sources in coastal waters.
Reclamation along coastal zones is a method that has been used to relieve the problems of strained resources and land. Aquaculture, as one of the major man-made activities in reclamation areas, has an environmental impact on coastal waters. The effluents from aquaculture ponds are known to enrich the levels of nutrients such as nitrogen and phosphate. The goals of the present study are to evaluate the environmental impact of mariculture on coastal waters in the east coast of Laizhou Bay, China, and to identify the nitrate sources. Monitoring the concentrations of dissolved nitrogen and phosphate was used to assess their impact on the water quality of coastal waters. A dual isotope (δ(15)N-NO3(-) and δ(18)O-NO3(-)) approach was used to identify the nitrate sources. Higher dissolved nitrogen concentrations (NH4(+) and NO3(-)) than PO4(3-) concentrations associated with enriched δ(15)N-NO3(-) values were observed in the drainage channels, sea cucumber ponds, and groundwater, which indicated that aquaculture activity has more influence on nitrogen nutrients than on phosphate nutrients. In this coastal area with seawater intrusion, nitrogen released from sea cucumber ponds accumulated in nearshore water and migrated in the offshore direction in groundwater currents. This behavior results in nitrogen enrichment in groundwater within the hinterland. Isotopic data indicate that mixing of multiple nitrate sources exists in groundwater, and nitrogen from mariculture is the main source.


Primary syphilis of the eyelid: case report.
Primary syphilis of the palpebral conjunctiva of the lower eyelid is reported because it is rare, which makes its diagnosis difficult but important.


Methyllycaconitine and (+)-anatoxin-a differentiate between nicotinic receptors in vertebrate and invertebrate nervous systems.
Specific high-affinity binding sites for 125I-alpha-bungarotoxin and (-)-[3H]nicotine have been measured in rat brain and locust (Schistocerca gregaria) ganglia. The binding sites for 125I-alpha-bungarotoxin had similar Kd values of 1.5 x 10(-9) and 0.8 x 10(-9) M for rat and locust preparations, respectively; the corresponding values for the (-)-[3H]nicotine-binding site were 9.3 x 10(-9) and 1.7 x 10(-7) M. Methyllycaconitine (MLA) potently inhibited 125I-alpha-bungarotoxin binding in both rat and locust. MLA was a less effective inhibitor of (-)-[3H]nicotine binding whereas (+)-anatoxin-a was a very potent inhibitor at this site in the rat but not in the locust. These data suggest that (+)-anatoxin-a is a useful probe for the high-affinity nicotine-binding receptor in vertebrate brain, whereas MLA is a preferential probe for the subclass of receptor that binds alpha-bungarotoxin.


Future approaches to the treatment of hypertension in the light of results from recent trials.
In this review approaches to the treatment of hypertension were appraised by considering data from recent trials. Two main questions were asked: at what level of blood pressure is treatment justified, and which drugs should be used? It is now well established that increases in both systolic and diastolic blood pressure are correlated with an increased risk of cardiovascular disease, heart attack or stroke. However, since patients are often asymptomatic, treatment must be justifiable in terms of reversing the risk of cardiovascular disease. The Australian Therapeutic Trial demonstrated that therapy was beneficial in patients whose diastolic pressure was at or above 95 mm Hg before treatment. Three recent large studies (EWPHE, IPPPSH and MRC) have provided interesting data on the level of blood pressure at which to start treatment and the most appropriate drugs to use. In one, treatment in the elderly, which raises particular concern, has been investigated. The MRC trial compared bendrofluazide with propranolol and showed a reduction in the incidence of stroke; however, to prevent 1 stroke, 850 patients would have to be treated for 1 year. Nevertheless, the benefits of therapy were clearly greater when diastolic blood pressure was at the upper end of the range 90-110 mmHg. Myocardial infarctions, which account for more deaths than stroke in mild to moderate hypertensives, do not appear to be reduced by treatment, whether or not this includes a beta-blocker. This is difficult to reconcile with the established 'cardioprotective' action of beta-blockers post-myocardial infarction. Other important factors affecting cardiovascular disease are governed by the patient's life-style, especially whether or not the patient smokes.(ABSTRACT TRUNCATED AT 250 WORDS)


Anti-B- cell-directed immunotherapy (rituximab) in the treatment of refractory pemphigus--an update.
Rituximab is a monoclonal antibody directed against the CD20 surface antigen present on B lymphocytes. Following its application, B cells are rapidly and specifically depleted. Rituximab has been approved for the treatment of relapsed and therapy-refractory non-Hodgkin lymphoma and has been incorporated into numerous chemotherapy regimes with promising results. Eradication of auto-reactive B cell clones is the rationale for its application in a variety of autoimmune disorders including the pemphigus group where B cells are thought to play a critical role in the pathogenesis. Preliminary reports in autoimmune disorders are encouraging. Adverse effects are generally well controlled and although severe infections have been reported following rituximab, the overall risk does not seem to be significantly increased. In the pemphigus group, rituximab has been successfully employed in refractory cases and a recent study suggests that a single course induces long-term remission in this patient group.


Radiation myelitis after pembrolizumab administration, with favorable clinical evolution and safe rechallenge: a case report and review of the literature.
Neurologic complications as myelitis are very rare but extremely deleterious adverse effects of both immunotherapy and radiotherapy. Many recent studies have focused on the possible synergy of these two treatment modalities due to their potential to enhance each other's immunomodulatory actions, with promising results and a safe tolerance profile. We report here the case of a 68-year-old man with metastatic non-small-cell lung cancer (NSCLC) who developed myelitis after T12-L2 vertebral radiotherapy, with motor deficit and sphincter dysfunction, while on treatment with pembrolizumab (an immune checkpoint inhibitor). The spinal abnormalities detected by magnetic resonance imaging (MRI), suggestive of myelitis, faithfully matched the area previously irradiated with 30 Gy in 10 fractions, six and a half months earlier. After immunotherapy discontinuation and steroid treatment, the patient rapidly and completely recovered. On progression, pembrolizumab was rechallenged and, after 8 cycles, the patient is on response and there are no signs of myelitis relapse. The confinement within the radiation field and the latency of appearance are suggestive of delayed radiation myelopathy. Nevertheless, the relatively low dose of radiation received and the full recovery after pembrolizumab discontinuation and steroid therapy plead for the contribution of both radiotherapy and immunotherapy in the causality of this complication, as an enhanced inflammatory reaction on a focal post-radiation chronic inflammatory state. In the three previously described cases of myelopathy occurring after radiotherapy and immunotherapy, a complete recovery had not been obtained and the immunotherapy was not rechallenged. The occurrence of a radiation recall phenomenon, in this case, can not be excluded, and radiation recall myelitis has already been described with chemotherapy and targeted therapy. Safe rechallenges with the incriminated drug, even immunotherapy, have been reported after radiation recall, but we describe it for the first time after myelitis.


Comparison of performance and abnormal cell flagging of two automated hematology analyzers: Sysmex XN 3000 and Beckman Coulter DxH 800.
The purpose was to evaluate the analytical performances of Sysmex XN 3000 and UniCel DxH 800 comparing the obtained results with manual counting and between each other. Also flagging capabilities of abnormal cells were compared for both analyzers. Two thousand one hundred and forty-two whole-blood samples were analyzed for evaluation. The samples flagged due to blast, atypical lymphocyte (AL), immature granulocyte (IG), or nucleated red blood cells (NRBC) were microscopically reviewed (n=102). The within-run and between-day coefficient of variations (CV%) of XN 3000 for hemoglobin, RBC, MCV, WBC, and platelets were lower than 5% and for WBC differentials lower than 10% except monocytes which was 15.6% at low level. The precision results of DxH 800 were also lower than 5.0% except platelets (9.5%) and monocytes (45%) at low level. The comparison of analyzers revealed good agreement (R>.86), except monocytes and basophils. The flagging sensitivities of XN 3000 were higher for IGs, blasts, and ALs than those of DxH 800 and almost similar for NRBC. The XN 3000 and DxH 800 are accurate, highly precise systems and can be used effectively in high-volume laboratories. The flagging sensitivity of XN 3000 was higher in detecting blasts, IGs, and ALs than that of DxH 800. The detection of abnormal cells with high sensitivity may improve laboratory workflow with a reduced slide review and accelerated turnaround time.


Helix 8 of the leukotriene B4 receptor is required for the conformational change to the low affinity state after G-protein activation.
Recent studies have revealed that G-protein-coupled receptors contain a putative cytoplasmic helical domain, helix 8. Leukotriene B4 (LTB4) receptor 1 derivatives with truncated or mutated helix 8 showed much higher LTB4 binding than wild-type (WT) receptors. Similar to the WT receptor, LTB4 promoted guanosine 5'-3-O-(thio)triphosphate (GTPgammaS) binding in these mutants. Unlike the WT receptor, however, the addition of GTPgammaS did not inhibit LTB4 binding to the mutant receptors. Scatchard analyses revealed that mutants maintained high affinity for LTB4, even in the presence of excess GTPgammaS. Consistently, mutant receptors showed a more prolonged Ca2+ mobilization and cellular metabolic activation than the WT receptor. From mutational studies and three-dimensional modeling based on the structure of bovine rhodopsin, we conclude that the helix 8 of LTB4 receptor 1 plays an important role in the conformational change of the receptor to the low affinity state after G-protein activation, possibly by sensing the status of coupling Galpha subunits as GTP-bound.


Unaffected patients with a homozygous absence of the SMN1 gene.
In this report, we present three families in which we identified asymptomatic carriers of a homozygous absence of the SMN1 gene. In the first family, the bialleleic deletion was found in three of four siblings: two affected brothers (SMA type 3a and 3b) and a 25-years-old asymptomatic sister. All of them have four SMN2 copies. In the second family, four of six siblings are affected (three suffer from SMA2 and one from SMA3a), each with three SMN2 copies. The clinically asymptomatic 47-year-old father has the biallelic deletion and four SMN2 copies. In the third family, the biallelic SMN1 absence was found in a girl affected with SMA1 and in her healthy 53-years-old father who had five SMN2 copies. Our findings as well as those of other authors show that an increased number of SMN2 copies in healthy carriers of the biallelic SMN1 deletion is an important SMA phenotype modifier, but probably not the only one.


Successful Management of Neobladder Variceal Bleeding.
Hematuria from a neobladder can occur due to a variety of pathologies including tumors, stones, and fistulas. Variceal bleeding in a neobladder is a very rare condition with only one case reported in literature. We present a case of a patient with cirrhosis and portal hypertension and an ileocolic orthotopic neobladder presenting with hematuria. Computed tomographic angiography showed dilated varices around the neobladder which were successfully embolized. To the best of our knowledge, this is the first report case of variceal bleeding in a neobladder successfully managed with the combination of TIPS (transjugular intrahepatic portosystemic shunt) procedure and embolization.


Increased atherosclerosis and endothelial dysfunction in mice bearing constitutively deacetylated alleles of Foxo1 gene.
Complications of atherosclerosis are the leading cause of death of patients with type 2 (insulin-resistant) diabetes. Understanding the mechanisms by which insulin resistance and hyperglycemia contribute to atherogenesis in key target tissues (liver, vessel wall, hematopoietic cells) can assist in the design of therapeutic approaches. We have shown that hyperglycemia induces FoxO1 deacetylation and that targeted knock-in of alleles encoding constitutively deacetylated FoxO1 in mice (Foxo1(KR/KR)) improves hepatic lipid metabolism and decreases macrophage inflammation, setting the stage for a potential anti-atherogenic effect of this mutation. Surprisingly, we report here that when Foxo1(KR/KR) mice are intercrossed with low density lipoprotein receptor knock-out mice (Ldlr(-/-)), they develop larger aortic root atherosclerotic lesions than Ldlr(-/-) controls despite lower plasma cholesterol and triglyceride levels. The phenotype is unaffected by transplanting bone marrow from Ldlr(-/-) mice into Foxo1(KR/KR) mice, indicating that it is independent of hematopoietic cells and suggesting that the primary lesion in Foxo1(KR/KR) mice occurs in the vessel wall. Experiments in isolated endothelial cells from Foxo1(KR/KR) mice indicate that deacetylation favors FoxO1 nuclear accumulation and exerts target gene-specific effects, resulting in higher Icam1 and Tnfα expression and increased monocyte adhesion. The data indicate that FoxO1 deacetylation can promote vascular endothelial changes conducive to atherosclerotic plaque formation.


The prevalence of chronic obstructive pulmonary disease in Riyadh, Saudi Arabia: a BOLD study.
To estimate the prevalence and associated risk factors of chronic obstructive pulmonary disease (COPD) in Saudi adults aged ⩾40 years using standardised post-bronchodilator spirometry according to the Burden of Obstructive Lung Disease (BOLD) protocol. Saudi men and women aged ⩾40 years were recruited by stratified multistage random sampling in Riyadh, Saudi Arabia. Participants completed questionnaires on respiratory symptoms and exposure to risk factors for COPD. Spirometry was performed according to standard methods. COPD was defined as post-bronchodilator FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ratio <70% (Global Initiative for Obstructive Lung Disease [GOLD]) or less than the lower limit of normal (LLN) (95(th) percentile) of the population distribution for FEV1/FVC. Seven hundred subjects underwent acceptable post-bronchodilator spirometry. The overall prevalence of GOLD COPD was 4.2% (men 5.7%, women 2.5%). The overall prevalence of COPD stage 1 or higher using the LLN was lower than estimates using the GOLD criteria (3.2%). The overall prevalence of GOLD stage 2 or higher COPD was 3.7%. Male sex, increasing age and smoking were significantly associated with COPD diagnosis. The overall prevalence of COPD in Saudi Arabia is 4.2%. Male, increasing age and smoking were the main risk factors for COPD.


Three low molecular weight cysteine proteinase inhibitors of human seminal fluid: purification and enzyme kinetic properties.
The cystatins form a superfamily of structurally related proteins with highly conserved structural folds. They are all potent, reversible, competitive inhibitors of cysteine proteinases (CPs). Proteins from this group present differences in proteinase inhibition despite their high level of structural similarities. In this study, three cysteine proteinase inhibitors (CPIs) of low molecular weight were isolated from human seminal fluid (HSF) by affinity chromatography on carboxymethyl (CM)-papain-Sepharose column, purified using various chromatographic procedures and checked for purity on sodium-dodecyl PAGE (SDS-PAGE). Matrix-assisted laser desorption-ionization-time-of flight-mass spectrometry (MALDI-TOF-MS) identified these proteins as cystatin 9, cystatin SN, and SAP-1 (an N-terminal truncated form of cystatin S). All three CPIs suppressed the activity of papain potentially and showed remarkable heat stability. Interestingly SAP-1 also inhibits the activity of trypsin, chymotrypsin, pepsin, and PSA (prostate specific antigen) and acts as a cross-class protease inhibitor in in vitro studies. Using Surface Plasmon Resonance, we have also observed that SAP-1 shows a significant binding with all these proteases. These studies suggest that SAP-1 is a cross-class inhibitor that may regulate activity of various classes of proteases within the reproductive systems. To our knowledge, this is the first report about purification of CPIs from HSF; the identification of such proteins could provide better insights into the physiological processes and offer intimation for further research.


Effect of AI chatbot emotional disclosure on user satisfaction and reuse intention for mental health counseling: a serial mediation model.
This study explored the effect of chatbot emotional disclosure on user satisfaction and reuse intention for a chatbot counseling service. It also examined the independent and sequential mediation roles of user emotional disclosure intention and perceived intimacy with a chatbot on the relationship between chatbot emotional disclosure, user satisfaction, and reuse intention for chatbot counseling. In total, 348 American adults were recruited to participate in a mental health counseling session with either of the two types of artificial intelligence-powered mental health counseling chatbots. These included a chatbot disclosing factual information only or a chatbot disclosing humanlike emotions. The results revealed that chatbot emotional disclosure significantly increased user satisfaction and reuse intention for a chatbot counseling service. The results further revealed that user emotional disclosure intention and perceived intimacy with a chatbot independently and serially mediates the effect of chatbot emotional disclosure on user satisfaction and chatbot counseling service reuse intention. The results indicate positive effects of artificial emotions and their disclosure in the context of chatbot moderated mental health counseling. Practical implications and psychological mechanisms are discussed.


Global developmental delay and mental retardation or intellectual disability: conceptualization, evaluation, and etiology.
Global developmental delay and mental retardation or intellectual disability offer challenges to the practitioner at several different levels. Accurate recognition of these most common of subtypes of neurodevelopmental disabilities is a central precondition to their correct evaluation and management. Proper evaluation is a time- and labor-intensive process that emphasizes several different goals. Guidelines now exist to assist the practitioner in selecting the appropriate investigation path to be pursued, and these guidelines should be used to inform the selections of investigations made. Although challenging and time consuming, the evaluation of these children offers many professional rewards and is a necessary first step in a family's adaptation to their child's chronic condition.


Anatomic boundaries of the clinical target volume (prostate bed) after radical prostatectomy.
We sought to derive and validate an interdisciplinary consensus definition for the anatomic boundaries of the postoperative clinical target volume (CTV, prostate bed). Thirty one patients who had planned for radiotherapy after radical prostatectomy were enrolled and underwent computed tomography and magnetic resonance imaging (MRI) simulation prior to radiotherapy. Through an iterative process of consultation and discussion, an interdisciplinary consensus definition was derived based on a review of published data, patterns of local failure, surgical practice, and radiologic anatomy. In validation, we analyzed the distribution of surgical clips in reference to the consensus CTV and measured spatial uncertainties in delineating the CTV and vesicourethral anastomosis. Clinical radiotherapy plans were retrospectively evaluated against the consensus CTV (prostate bed). Anatomic boundaries of the consensus CTV (prostate bed) are described. Surgical clips (n = 339) were well distributed throughout the CTV. The vesicourethral anastomosis was accurately localized using central sagittal computed tomography reconstruction, with a mean +/- standard deviation uncertainty of 1.8 +/- 2.5 mm. Delineation uncertainties were small for both MRI and computed tomography (mean reproducibility, 0-3.8 mm; standard deviation, 1.0-2.3); they were most pronounced in the anteroposterior and superoinferior dimensions and at the superior/posterior-most aspect of the CTV. Retrospectively, the mean +/- standard deviation CTV (prostate bed) percentage of volume receiving 100% of prescribed dose was only 77% +/- 26%. We propose anatomic boundaries for the CTV (prostate bed) and present evidence supporting its validity. In the absence of gross recurrence, the role of MRI in delineating the CTV remains to be confirmed. The CTV is larger than historically practiced at our institution and should be encompassed by a microscopic tumoricidal dose.


Facile Synthesis of Hydrophobic Metal-Organic Gels for Volatile Organic Compound Capture.
Exploring a synthesis method for preparing hydrophobic metal-organic gels (MOGs) is highly desirable for air purification. Here, we present a rapid heating-up synthetic route to hydrophobic MOG denoted CAU-3(gel) with hierarchical micro/mesoporosity. CAU-3(gel), which features water and thermal stability, high surface area, and hydrophobicity, exhibits excellent performance for the capture of three representative volatile organic compounds (hexanal, toluene, and p-xylene), higher than BPL activated carbon, zeolite 13X, and some representative metal-organic frameworks including ZIF-8, HKUST-1, MIL-101(Cr), and UiO-66 under wet conditions. Furthermore, CAU-3(gel) could be easily coated on a nonwoven fabric by a simple dip-coating method without using any binder, which exhibits outstanding hexanal removal performance and regenerability at low temperature. Grand canonical Monte Carlo simulations show that hexanal preferentially enters relatively small tetrahedral cages and occupies two adsorption sites at low pressure and then a new site appears in octahedral cages with increasing pressure.


AI and machine learning in resuscitation: Ongoing research, new concepts, and key challenges.
Artificial intelligence (AI) and machine learning (ML) are important areas of computer science that have recently attracted attention for their application to medicine. However, as techniques continue to advance and become more complex, it is increasingly challenging for clinicians to stay abreast of the latest research. This overview aims to translate research concepts and potential concerns to healthcare professionals interested in applying AI and ML to resuscitation research but who are not experts in the field. We present various research including prediction models using structured and unstructured data, exploring treatment heterogeneity, reinforcement learning, language processing, and large-scale language models. These studies potentially offer valuable insights for optimizing treatment strategies and clinical workflows. However, implementing AI and ML in clinical settings presents its own set of challenges. The availability of high-quality and reliable data is crucial for developing accurate ML models. A rigorous validation process and the integration of ML into clinical practice is essential for practical implementation. We furthermore highlight the potential risks associated with self-fulfilling prophecies and feedback loops, emphasizing the importance of transparency, interpretability, and trustworthiness in AI and ML models. These issues need to be addressed in order to establish reliable and trustworthy AI and ML models. In this article, we overview concepts and examples of AI and ML research in the resuscitation field. Moving forward, appropriate understanding of ML and collaboration with relevant experts will be essential for researchers and clinicians to overcome the challenges and harness the full potential of AI and ML in resuscitation.


3',5'-Cyclic AMP inhibits fatty acid synthesis in mitochondria, microsomes and supernatant but does not provoke an enrichment in 3H with regard to 14C as it occurs during fasting after glucose 6-(3)H or 6-(14)C administration. Insulin does not exert any action on "controls" but restores lipogenesis in fasted animals in the examinated fractions and normalises the 3H/(14)C ratio, even that of microsomes. Control of neoglucogenesis by this hormone is more likely than by 3',5'-cyclic AMP.


Extracellular adenosine sensing-a metabolic cell death priming mechanism downstream of p53.
Tumor cells undergo changes in metabolism to meet their energetic and anabolic needs. It is conceivable that mechanisms exist to sense these changes and link them to pathways that eradicate cells primed for cancer development. We report that the tumor suppressor p53 activates a cell death priming mechanism that senses extracellular adenosine. Adenosine, the backbone of ATP, accumulates under conditions of cellular stress or altered metabolism. We show that its receptor, A2B, is upregulated by p53. A2B expression has little effect on cell viability, but ligand engagement activates a caspase- and Puma-dependent apoptotic response involving downregulation of antiapoptotic Bcl-2 proteins. Stimulation of A2B also significantly enhances cell death mediated by p53 and upon accumulation of endogenous adenosine following chemotherapeutic drug treatment and exposure to hypoxia. Since extracellular adenosine also accumulates within many solid tumors, this distinct p53 function links programmed cell death to both a cancer- and therapy-associated metabolic change.


Surgical Treatment of Ameloblastoma: How Does It Impact the Oral Health-Related Quality of Life? A Systematic Review.
This study aimed to analyze the impact of surgical treatment on the quality of life of patients diagnosed with ameloblastoma. We searched PubMed, Science Direct, LILACS, EMBASE, and Web of Science, up to February 2021, with no time restriction. We considered only studies published in English that evaluated patients diagnosed with ameloblastoma who underwent conservative or radical surgical treatments using a quality of life (QOL) instrument. Of the 2155 studies identified, ten were included in our sample. Only studies that analyzed QOL of radical surgical treatment were included. No studies that analyzed QOL after conservative surgical treatment were found. Across all studies, 283 patients (122 females and 161 males; mean age: 28.13 years) were surgically treated for ameloblastoma. A total of 69 complications were reported, with the most frequent being infection in both the donor and recipient site (18 cases) and graft loss (8 cases). Surgical treatment of ameloblastoma was effective in providing reasonable health-related QOL, as most of the assessed dimensions were found to improve.


[Parasitism of the louse fly Lipoptena fortisetosa on cattle].
Parasitism of Lipoptena fortisetosa Maa on cattle was first established. Data on the distribution of this species in the USSR and its abundance on cows in Moldavia are given.


Selective carboxyl methylation of structurally altered calmodulins in Xenopus oocytes.
The eucaryotic protein carboxyl methyltransferase specifically modifies atypical D-aspartyl and L-isoaspartyl residues which are generated spontaneously as proteins age. The selectivity of the enzyme for altered proteins in intact cells was explored by co-injecting Xenopus laevis oocytes with S-adenosyl-L-[methyl-3H]methionine and structurally altered calmodulins generated during a 14-day preincubation in vitro. Control experiments indicated that the oocyte protein carboxyl methyltransferase was not saturated with endogenous substrates, since protein carboxyl methylation rates could be stimulated up to 8-fold by increasing concentrations of injected calmodulin. The oocyte protein carboxyl methyltransferase showed strong selectivities for bovine brain and bacterially synthesized calmodulins which had been preincubated in the presence of 1 mM EDTA relative to calmodulins which had been preincubated with 1 mM CaCl2. Radioactive methyl groups were incorporated into base-stable linkages with recombinant calmodulin as well as into carboxyl methyl esters following its microinjection into oocytes. This base-stable radioactivity most likely represents the trimethylation of lysine 115, a highly conserved post-translational modification which is present in bovine and Xenopus but not in bacterially synthesized calmodulin. Endogenous oocyte calmodulin incorporates radioactivity into both carboxyl methyl esters and into base-stable linkages following microinjection of oocytes with S-adenosyl-[methyl-3H]methionine alone. The rate of oocyte calmodulin carboxyl methylation in injected oocytes is calculated to be similar to that of lysine 115 trimethylation, suggesting that the rate of calmodulin carboxyl methylation is similar to that of calmodulin synthesis. At steady state, oocyte calmodulin contains approximately 0.0002 esters/mol of protein, which turn over rapidly. The results suggest the quantitative significance of carboxyl methylation in the metabolism of oocyte calmodulin.


Elevated ocular pressure reduces voltage-gated sodium channel NaV1.2 protein expression in retinal ganglion cell axons.
Glaucoma is an age-related neurodegenerative disease that is commonly associated with sensitivity to intraocular pressure. The disease selectively targets retinal ganglion cells (RGCs) and constituent axons. RGC axons are rich in voltage-gated sodium channels, which are essential for action potential initiation and regeneration. Here, we identified voltage-dependent sodium channel, NaV1.2, in the retina, examined how this channel contributes to RGC light responses, and monitored NaV1.2 mRNA and protein expression in the retina during progression of modeled glaucoma. We found NaV1.2 is predominately localized in ganglion cell intraretinal axons with dispersed expression in the outer and inner plexiform layers. We showed Phrixotoxin-3, a potent NaV1.2 channel blocker, significantly decreased RGC electrical activity in a dose-dependent manner with an IC50 of 40 nM. Finally, we found four weeks of raised intraocular pressure (30% above baseline) significantly increased NaV1.2 mRNA expression but reduced NaV1.2 protein level in the retina up to 57% (p < 0.001). Following prolonged intraocular pressure elevation, NaV1.2 protein expression particularly diminished at distal sections of ganglion cell intraretinal axons (p ≤ 0.01). Our results suggest NaV1.2 might be a therapeutic target during disease progression to maintain RGC excitability, preserving presynaptic connections through action potential backpropagation.


Knocking out the dopamine reuptake transporter (DAT) does not change the baseline brain arachidonic acid signal in the mouse.
Dopamine transporter (DAT) homozygous knockout (DAT(-/-)) mice have a 10-fold higher extracellular (DA) concentration in the caudate-putamen and nucleus accumbens than do wildtype (DAT(+/+)) mice, but show reduced presynaptic DA synthesis and fewer postsynaptic D(2) receptors. One aspect of neurotransmission involves DA binding to postsynaptic D(2)-like receptors coupled to cytosolic phospholipase A(2) (cPLA(2)), which releases the second messenger, arachidonic acid (AA), from synaptic membrane phospholipid. We hypothesized that tonic overactivation of D(2)-like receptors in DAT(-/-) mice due to the excess DA would not increase brain AA signaling, because of compensatory downregulation of postsynaptic DA signaling mechanisms. [1-(14)C]AA was infused intravenously for 3 min in unanesthetized DAT(+/+), heterozygous (DAT(+/-)), and DAT(-/-) mice. AA incorporation coefficients k* and rates J(in), markers of AA metabolism and signaling, were imaged in 83 brain regions using quantitative autoradiography; brain cPLA(2)-IV activity also was measured. Neither k* nor J(in) for AA in any brain region, or brain cPLA(2)-IV activity, differed significantly among DAT(-/-), DAT(+/-), and DAT(+/+) mice. These results differ from reported increases in k* and J(in) for AA, and in brain cPLA(2) expression, in serotonin reuptake transporter (5-HTT) knockout mice, and suggest that postsynaptic dopaminergic neurotransmission mechanisms involving AA are downregulated despite elevated DA in DAT(-/-) mice.


Diabetes mellitus in the elderly.
Diabetes mellitus is prevalent among the elderly. Although the principles of management of diabetes are fundamentally the same in both the young and elderly, many aspects of the disease and its manifestations are unique to the elderly. Older patients may have atypical presentations of diabetes. Numerous factors may impair adequate nutrition and dietary and exercise compliance in the elderly. Pharmacologic therapy, with either sulfonylureas or insulin, entails a particular risk for hypoglycemia among the elderly, who are more susceptible to hypoglycemia and are more likely to have neuroglycopenic symptoms. Diabetic hyperosmolar coma occurs predominantly in the older type II diabetic population. It requires aggressive hydration and insulin therapy, but most patients can ultimately be managed without insulin. The macrovascular complications (coronary and peripheral vascular disease) are the major source of morbidity and mortality among elderly diabetics, but microvascular complications (nephropathy, retinopathy, neuropathy) also occur and often respond to a variety of therapeutic interventions.


Pyridinylidenaminophosphines: Facile Access to Highly Electron-Rich Phosphines.
Electron-rich tertiary phosphines are valuable species in chemical synthesis. However, their broad application as ligands in catalysis and reagents in stoichiometric reactions is often limited by their costly synthesis. Herein, we report the synthesis and properties of a series of phosphines with 1-alkylpyridin-4-ylidenamino and 1-alkylpyridin-2-ylidenamino substituents that are accessible in a very short and scalable route starting from commercially available aminopyridines and chlorophosphines. The determination of the Tolman electronic parameter (TEP) value reveals that the electron donor ability can be tuned by the substituent pattern at the aminopyridine backbone and it can exceed that of common alkylphosphines and N-heterocyclic carbenes. The potential of the new phosphines as strong nucleophiles in phosphine-mediated transformations is demonstrated by the formation of Lewis base adducts with CO2 and CS2 . In addition, the coordination chemistry of the new phosphines towards CuI , AuI , and PdII metal centers has been explored, and a convenient procedure to introduce the most basic phosphine into metal complexes starting from air-stable phosphonium salt is described.


Structure and function of the nun gene and the immunity region of the lambdoid phage HK022.
The immunity region of the lambdoid phage, HK022, has been sequenced. The HK022 repressor gene, its cognate operators and promoters, and several early phage genes can be discerned. The overall design of the immunity region resembles that of other lambdoid phages. The location of the HK022 nun gene, whose product excludes superinfecting lambda by terminating transcription at (or near) the lambda nut sites, is analogous to that of gene N in lambda. nun is preceded by sequences similar to the lambda nut sites and the lambda pL promoter and is followed by several transcription termination signals. Despite these similarities, Nun is required neither for the lytic nor the lysogenic pathway of phage development. Again, unlike N, Nun is expressed in a prophage, perhaps from a promoter other than pL. We suggest that Nun and N have diverged in evolution and now perform different functions for their respective phages. Although Nun and N compete at the lambda nut sites and interact with the same host Nus proteins, they are only distantly related in predicted amino acid sequence. The presence of transcription terminators in the pL operon suggests that the expression of the HK022 early functions, like those of lambda, entails an antitermination mechanism. However, Nun does not appear to be an essential component of this mechanism. Our most economic model is that the HK022 nutL sequence suppresses pL operon terminators in the absence of a phage-encoded antitermination protein. Striking homologies between the HK022 nutL sequence and related sequences in the Escherichia coli rrn operons support this notion. Alternatively, a phage antitermination gene may be located outside the pL operon.


Inhibition of epidermal growth factor receptor suppresses parathyroid hormone-related protein expression in tumours and ameliorates cancer-associated cachexia.
Lung cancer is the primary cause of cancer deaths worldwide. Activation of epidermal growth factor receptor (EGFR) leads to lung cancer progression and poor prognosis while involuntary weight loss remains a major problem. Tumour-derived parathyroid hormone-related protein (PTHrP) emerged as a potential mediator of cachexia. Here, we investigated the modulatory role of EGFR signalling in PTHrP (encoded by Pthlh) gene expression and the impact of this relationship on cancer cachexia. Global gene expression profiles of Lewis lung carcinoma (LLC) cells were analysed. Pthlh mRNA levels were measured by qRT-PCR in LLC cells treated with EGFR ligands and tyrosine kinase inhibitors (TKIs). LLC tumour-bearing mice received EGFR TKI erlotinib for 7 days via intraperitoneal injection or oral gavage. Tumour Pthlh mRNA, weight of fat/muscle tissue, and grip strength were assessed. RNA-seq data from The Cancer Genome Atlas and gene expression analysis tools were used to characterize expression profiles of PTHLH and EGFR along with correlation analysis of PTHLH with EGFR and transforming growth factor alpha (TGFA) in human lung cancer and head and neck squamous carcinoma (HNSC). Survival of lung squamous cell carcinoma (LUSC) and lung adenocarcinoma (LUAD) patients with EGFR gene alterations was analysed in regard to PTHLH expression. Expression of EGFR ligands, EGFR itself, and PTHrP co-clusters in LLC cells. Activation of EGFR signalling with its ligands significantly increases (3.8-fold, P < 0.0005) while EGFR TKIs significantly decrease (90%, P < 0.0005) Pthlh mRNA levels in LLC cells. Pthlh mRNA drops 65-75% (P < 0.0005) in tumours upon treatment of LLC tumour-bearing mice with erlotinib while their muscle mass and grip strength increase (9.2% P < 0.05, 23% P < 0.005, respectively) compared with tumour-bearing control mice. PTHLH is overexpressed in tumours of LUSC (45.8-fold, P < 0.05) and HNSC (17.5-fold, P < 0.05) compared with normal tissue. PTHLH expression correlates with EGFR and its ligand TGFA in both cancers (LUSC: n = 745, R = 0.32, P < 0.0001 and R = 0.51, P < 0.0001; HNSC: n = 545, R = 0.34, P < 0.001 and R = 0.50, P < 0.001, respectively). High PTHLH mRNA associates with poor overall survival in LUAD patients with activating EGFR mutations (n = 40, log-rank test, P = 0.0451). Epidermal growth factor receptor signalling regulates expression of cachexia mediator PTHrP. EGFR inhibition reduces PTHrP expression in LLC tumours and ameliorates cachexia in LLC tumour-bearing mice.


Psychosocial consequences of allocation to lung cancer screening: a randomised controlled trial.
To examine the psychosocial consequences of being allocated to the control group as compared with the screen group in a randomised lung cancer screening trial. The Danish Lung Cancer Screening Trial, a randomised controlled trial, ran from 2004 to 2010 with the purpose of investigating the benefits and harms of lung cancer screening. The participants in Danish Lung Cancer Screening Trial were randomised to either the control group or the screen group and were asked to complete the questionnaires Consequences Of Screening and Consequences Of Screening in Lung Cancer (COS-LC). The Consequences Of Screening and the COS-LC were used to examine the psychosocial consequences of participating in the study, by comparing the control and the screen groups' responses at the prevalence and at the incidence round. There was no statistically significant difference in socio-demographic characteristics or smoking habits between the two groups. Responses to the COS-LC collected before the incidence round were statistically significantly different on the scales 'anxiety', 'behaviour', 'dejection', 'self-blame', 'focus on airway symptoms' and 'introvert', with the control group reporting higher negative psychosocial consequences. Furthermore, the participants in both the control and the screen groups exhibited a mean increase in negative psychosocial consequences when their responses from the prevalence round were compared with their responses from the first incidence round. Participation in a randomised controlled trial on lung cancer screening has negative psychosocial consequences for the apparently healthy participants-both the participants in the screen group and the control group. This negative impact was greatest for the control group.


In vitro hemodynamics and valve imaging in passive beating hearts.
Due to their high complexity, surgical approaches to valve repair may benefit from the use of in vitro simulators both for training and for the investigation of those measures which can lead to better clinical results. In vitro tests are intrinsically more effective when all the anatomical substructures of the valvular complexes are preserved. In this work, a mock apparatus able to house an entire explanted porcine heart and subject it to pulsatile fluid-dynamic conditions was developed, in order to enable the hemodynamic analysis of simulated surgical procedures and the imaging of the valvular structures. The mock loop's hydrodynamic design was based on an ad-hoc defined lumped-parameter model. The left ventricle of an entire swine heart was dynamically pressurized by an external computer-controlled pulse duplicator. The ascending aorta was connected to a hydraulic circuit which simulated the input impedance of the systemic circulation; a reservoir passively filled the left atrium. Accesses for endoscopic imaging were located in the apex of the left ventricle and in the aortic root. The experimental pressure and flow tracings were comparable with the typical in vivo curves; a mean flow of 3.5±0.1l pm and a mean arterial pressure of 101±2 mmHg was obtained. High-quality echographic and endoscopic video recordings demonstrated the system's excellent potential in the observation of the cardiac structures dynamics. The proposed mock loop represents a suitable in vitro system for the testing of minimally-invasive cardiovascular devices and surgical procedures for heart valve repair.


Cooperative clinical trials and community outreach: the conceptual approach in Northern California.
Despite major advances in cancer treatment, one of the major challenges in oncology is the integration of community oncology and clinical research. A balance needs to be achieved between efforts to increase patient accrual into protocols and education designed to achieve minimal standards of care. The planning efforts in Northern California are one approach to the challenge, but it will take years before answers are available.


Differential acute and chronic effects of burn trauma on murine skeletal muscle bioenergetics.
Altered skeletal muscle mitochondrial function contributes to the pathophysiological stress response to burns. However, the acute and chronic impact of burn trauma on skeletal muscle bioenergetics remains poorly understood. Here, we determined the temporal relationship between burn trauma and mitochondrial function in murine skeletal muscle local to and distal from burn wounds. Male BALB/c mice (8-10 weeks old) were burned by submersion of the dorsum in water (∼ 95 °C) to create a full thickness burn on ∼ 30% of the body. Skeletal muscle was harvested spinotrapezius underneath burn wounds (local) and the quadriceps (distal) of sham and burn treated mice at 3h, 24h, 4d and 10d post-injury. Mitochondrial respiration was determined in permeabilized myofiber bundles by high-resolution respirometry. Caspase 9 and caspase 3 protein concentration were determined by western blot. In muscle local to burn wounds, respiration coupled to ATP production was significantly diminished at 3h and 24h post-injury (P<0.001), as was mitochondrial coupling control (P<0.001). There was a 5- (P<0.05) and 8-fold (P<0.001) increase in respiration in response to cytochrome at 3h and 24h post burn, respectively, indicating damage to the outer mitochondrial membranes. Moreover, we also observed greater active caspase 9 and caspase 3 in muscle local to burn wounds, indicating the induction of apoptosis. Distal muscle mitochondrial function was unaltered by burn trauma until 10d post burn, where both respiratory capacity (P<0.05) and coupling control (P<0.05) were significantly lower than sham. These data highlight a differential response in muscle mitochondrial function to burn trauma, where the timing, degree and mode of dysfunction are dependent on whether the muscle is local or distal to the burn wound.


Influence of gender in pathogenesis of trichomoniasis in congenitally athymic (nude) mice.
Evaluation of abscesses appearing in male and female euthymic and athymic (nude) Balb/c mice after subcutaneous injection of Trichomonas vaginalis in the dorsal region showed that females were more susceptible than males. Female euthymic mice, however, were more susceptible than male athymic mice, and splenectomised athymic males were more susceptible than non-splenectomised athymic males. F1 female athymic mice were the most susceptible, as their abscesses reached a peak size five days earlier than those of athymic homozygous females. F1 male athymic mice, though slightly more susceptible than athymic homozygous males, did not develop abscesses that were similar in size. These results suggest that resistance or susceptibility to T vaginalis infection depends on the gender of the host and on thymus dependent cellular populations.


The 5'-region of the P450XIA1 (P450scc) gene contains a basal promoter and an adrenal-specific activating domain.
The first step to the synthesis of all steroids is catalyzed by P450scc. We constructed nine deletion mutants of the 5'-region of the P450scc gene and connected them to a CAT reporter gene to assay transcriptional activity of the P450scc promoter. A short 145 bp fragment stimulated transcription by two fold. This DNA was active in all cells tested irrespective of their tissue origin and steroidogenic activity. DNA at -145/-573 of the upstream region did not increase transcription any further. DNA including 2500 bp of the upstream region stimulated transcription by 10 fold only in adrenal Y-1 cells. Hence in the -145 region contains a low level P450scc promoter and the 2500 bp DNA possesses an adrenal specific enhancing element.


Characterization of hereditary transthyretin cardiac amyloidosis in Spain.
Hereditary transthyretin amyloidosis (hATTR) is a disease caused by mutations in the transthyretin gene that frequently shows cardiac involvement due to amyloid deposition in the myocardium. Our objective was to identify cardiac involvement in a Spanish cohort. Retrospective multicenter study of patients diagnosed with hATTR with cardiac involvement from Spanish centers. We collected demographic, clinical, and genetic data. A total of 181 patients from 26 centers were included (65.2% men, with a median age at diagnosis of 62 years). The most frequent mutations were Val50Met (67.7%) and Val142Ile (12.4%). The main reason for consultation was extracardiac symptoms (69%), mainly neurological. The mean N-terminal pro-B-type natriuretic peptide level was 2145±3586 pg/mL. The most characteristic electrocardiogram findings were a pseudoinfarct pattern (25.9%) and atrioventricular block (25.3%). Mean ventricular thickness was 15.4±4.1mm. Longitudinal strain was reduced in basal segments by 29.4%. Late diffuse subendocardial enhancement was observed in 58.8%. Perugini grade 2 or 3 uptake was observed in 75% of scintigraphy scans. During follow-up, 24.9% of the patients were admitted for heart failure, 34.3% required a pacemaker, and 31.6% required a liver transplant. One third (32.5%) died during follow-up, mainly due to heart failure (28.8%). The presence of non-Val50Met mutations was associated with a worse prognosis. HATTR cardiac amyloidosis in Spain shows heterogeneous genetic and clinical involvement. The prognosis is poor, mainly due to cardiac complications. Consequently early diagnosis and treatment are vital.


Transseptal Puncture Through an Interatrial Septum With Lipomatous Hypertrophy: A False Perception of Success and Failure.
Transseptal puncture is a standard procedure to access the left atrium during catheter ablation of arrhythmias. It is associated with high success and a meager complication rate in the contemporary era. The potential complications of transseptal puncture include aortic puncture, perforation of the right/left atrial free wall resulting in pericardial effusion/tamponade, and systemic thromboembolism. The dissection of the interatrial septum (IAS) is a rare complication of transseptal puncture, reported in less than 1% of the procedures. We report a case of a dissection of the IAS during an attempted transseptal puncture in a 72-year-old man with lipomatous hypertrophy of the interatrial septum.


Effects of trichloroacetic acid on the nitrogen metabolism of Pinus sylvestris--a 13C/15N tracer study.
Trichloroacetic acid (TCA) can be found in various environmental compartments like air, rain and plants all over the world. It is assumed that TCA is an atmospheric degradation product of volatile chloroorganic hydrocarbons. The herbicide effect of TCA in higher concentrations is well known, but not much is known about the phytotoxic effects in environmentally relevant concentrations. It can be shown in this study by using the 13C/15N stable isotope tracer technique that [13C]TCA is taken up by roots of two-year-old seedlings of Pinus sylvestris L. and transported into the needles. At the same time the effect of the substance on nitrogen metabolism can be analyzed by measuring the incorporation of 15NO3- into different nitrogen fractions of the plant. The more [13C]TCA incorporation, the higher the synthesis of 15N labelled amino acids and proteins is. These effects on the nitrogen metabolism are probably based on the activation of stress- and detoxification metabolism. It has to be assumed that there is an influence on N metabolism of Pinus sylvestris caused by the deposition of environmentally relevant TCA concentrations.


Factors affecting outcome of partial radial head fractures: A Retrospective Cohort Study.
The purpose of this study is to evaluate which factors will affect range of motion (ROM) and function in partial radial head fractures. The hypothesis is that conservative treatment yields better outcomes. This retrospective comparative cohort study included 43 adult volunteers with partial radial head fracture, a minimum 1-year follow up, separated into a surgical and non-surgical group. Risk factors were: associated injury, heterotopic ossification, worker's compensation, and proximal radio ulnar joint (PRUJ) implication. Outcomes included radiographic ROM measurement, demographic data, and quality of life questionnaires (PREE, Q-DASH, MEPS). Mean follow up was 3.5 years (1-7 years). Thirty patients (70%) had associated injuries with decreased elbow extension (-11°, p=0.004) and total ROM (-14°, p=0.002) compared to the other group. Heterotopic ossification was associated with decreased elbow flexion (-9.00°, p=0.001) and fractures involved the PRUJ in 88% of patients. Only worker's compensation was associated with worse scores. There was no difference in terms of function and outcome between patients treated non-surgically or surgically. We found that associated injuries, worker's compensation and the presence of heterotopic ossification were the only factors correlated with a worse prognosis in this cohort of patients. Given these results, the authors reiterate the importance of being vigilant to associated injuries. IV, Retrospective study.


Dye-linked D-amino acid dehydrogenases: biochemical characteristics and applications in biotechnology.
Dye-linked D-amino acid dehydrogenases (Dye-DADHs) catalyze the dehydrogenation of free D-amino acids in the presence of an artificial electron acceptor. Although Dye-DADHs functioning in catabolism of L-alanine and as primary enzymes in electron transport chains are widely distributed in mesophilic Gram-negative bacteria, biochemical and biotechnological information on these enzymes remains scanty. This is in large part due to their instability after isolation. On the other hand, in the last decade, several novel types of Dye-DADH have been found in thermophilic bacteria and hyperthermophilic archaea, where they contribute not only to L-alanine catabolism but also to the catabolism of other amino acids, including D-arginine and L-hydroxyproline. In this minireview, we summarize recent developments in our understanding of the biochemical characteristics of Dye-DADHs and their specific application to electrochemical biosensors.


Implications of Coexisting Aortic Regurgitation in Patients With Aortic Stenosis.
Aortic regurgitation (AR) is a common comorbidity in patients with aortic stenosis (AS), but coexisting AR has often been excluded from major clinical studies on AS. The impact of coexisting AR on the natural history of AS has not been well-described. The authors compared clinical outcomes in medically managed patients with moderate-to-severe AS with or without coexisting AR. Consecutive patients (N = 1,188) with index echocardiographic diagnosis of moderate-to-severe AS (aortic valve area <1.5 cm2) were studied. All patients were medically managed and were divided into those with coexisting AR (at least moderate severity) and those without. Adverse composite clinical outcomes were defined as mortality or admissions for congestive cardiac failure on subsequent follow-up. The authors compared differences in clinical profile and outcomes between the groups. There were 88 patients (7.4%) with coexisting AR and AS. These patients did not differ significantly in age, but had lower body mass index (22.9 ± 3.8 vs 25.3 ± 5.1 kg/m2), lower diastolic blood pressure (68.7 ± 10.7 vs 72.2 ± 12.3 mm Hg), larger end-diastolic volume index (68.8 ± 18.8 vs 60.4 ± 17.8 mL/m2) and larger left ventricular mass index (118.6 ± 36.4 vs 108.9 ± 33.1 g/m2). The prevalence of cardiovascular risk factors did not differ significantly. Coexisting AR was associated with increased incidence of adverse outcomes (log-rank 4.20; P = 0.040). On multivariable Cox regression, coexisting AR remained independently associated with adverse outcomes (HR: 1.36; 95% CI: 1.02-1.82) after adjusting for age, AS severity, left ventricular ejection fraction, and year of study. In patients with AS, coexisting AR was associated with changes in echocardiographic profile and adverse outcomes.


[Health state in women engaged in professional military service in European North].
The authors analysed health state and morbidity of women engaged into professional navy service in North Fleet, age features of health state in these servicewomen, and results of medical stationary examination and checkup results, regular medical examination results and the servicewomen morbidity over 12 years (about 15.5 thousand cases), and 697 reports on the servicewomen diseases according to military medical (navy) commission. The article covers causes of changes in navy fitness category for the servicewomen, analysis of comorbidity, suggestions of new approaches to comorbidity analysis.