Effects of Community Mental Health Service in Subjects with Early Psychosis: One-Year Prospective Follow Up.
The use of a multidisciplinary team approach is essential for increasing the likelihood of recovery among individuals with early psychosis. The aim of the present study was to investigate the effects of community-based mental health services on the symptoms and socio-occupational functioning of subjects with early psychosis. The study included participants who were referred to our Mental Health Promotion Center and who agreed to participate in diverse individual and group programs. During the 1-year follow-up, the medication adherence rate remained high, the recovery rate substantially increased, and the scores on the Positive and Negative Syndrome Scale, Psychotic Symptom Rating Scale-Delusion and Auditory Hallucinations subscales, Global Assessment of Functioning, Interpersonal Sensitivity Measure, and Social Functioning Questionnaire significantly improved over time. The findings suggest that the 1-year outcome of subjects with early psychosis can be improved by diverse community-based psychosocial interventions.


Natural feed additive of Macleaya cordata: safety assessment in rats a 90-day feeding experiment.
Macleaya cordata (Willd.) (Papaveraceae) is used as an active component in the natural feed additive Sangrovit. Sangrovit contains mixture of the intact aerial parts and the fraction of quaternary benzo[c]phenanthridine alkaloids from M. cordata (FQBA). In a 90-day pilot toxicity trial, Sangrovit and the FQBA were tested for safety. Male Wistar rats were fed for 90 days with 100, 7000 or 14000mg of Sangrovit or 600mg of FQBA in 1kg of feed. Body and organ weights, clinical chemistry and hematology markers, oxidative stress parameters, morphological structure of tongue, liver, ileum, kidney and heart samples, and total cytochrome P450 in liver were monitored. The results showed no statistically significant alterations in any parameter between control and treated animals, except for the group treated with 14000ppm Sangrovit that resulted in elevation of reduced glutathione level and superoxide dismutase activity in liver.


Aging-related induction of inducible nitric oxide synthase is vasculo-protective to the arterial media.
Aging associated erectile dysfunction (ED) is primarily caused by the reduction in smooth muscle cells (SMC) and an increase in collagen within the corpora cavernosa, assumed to result from an increase in reactive oxygen species (ROS). This is accompanied by the expression of inducible nitric oxide synthase (iNOS) to produce nitric oxide that scavenges ROS and inhibits collagen deposition. We investigated whether with aging similar processes occur within the arterial media SMC that share some common physiological functions with the cavernosal SMC. Aged (22-24 months) male Brown Norway rats received water with or without an inhibitor of iNOS activity (L-N-(iminoethyl)-lysine acetate [L-NIL], 0.1 g/l), for 3 weeks. Young (3 months) untreated rats were used as control (n=5 per group). Tissue sections from the penis, abdominal aorta, femoral and brachial arteries were stained for collagen, SMC, iNOS, ROS plasminogen activator inhibitor (PAI) and apoptosis, and evaluated by quantitative image analysis. ROS were also determined in fresh tissue and whole blood by the GSH/GSSG ratio. It was observed that most aging-induced changes in the media of the arterial tree from the aorta to the resistance arteries in the penis are similar to what occurs in the corpora cavernosa, i.e. a decrease in the SMC/collagen ratio and an increase in ROS and iNOS, and specifically in the case of the resistance arteries, an increase in SMC apoptosis and PAI. iNOS inhibition by L-NIL further increased ROS and decreased the SMC/collagen ratio in the media. These observations suggest that ED and arteriosclerosis in the aging male may share a common etiology, and that the expression of iNOS by the SMC is an attempt to counteract this fibrosis.


Resuscitation strategies with different arterial pressure targets after surgical management of traumatic shock.
Hypotensive fluid resuscitation has a better effect before and during surgical intervention for multiple trauma patients with haemorrhagic shock. However, it is questionable whether hypotensive fluid resuscitation is suitable after surgical intervention for these patients, and whether resuscitation with different mean arterial pressure (MAP) targets after surgical intervention can obtain different results. The aim of this study was to investigate these questions and to explore the underlying mechanisms. A total of 30 anesthetized piglets were randomly divided into 3 groups (n = 10 per group): low MAP, middle MAP, and high MAP, which had MAP targets of 60, 80, and 100 mmHg, respectively. All animals underwent femur fracture, intestine and liver injury, haemorrhagic shock, early hypotensive resuscitation, and surgical intervention. Then, the animals received fluid resuscitation with different MAP targets as mentioned above for 24 hours. Hemodynamic parameters and vital organ functions were evaluated. Fluid resuscitation in the 80 mmHg MAP group maintained haemodynamic stability, tissue perfusion, and organ function better than that in the other groups. The 60 mmHg MAP group presented with profound metabolic acidosis and organ histopathologic damage. In addition, animals in the 100 mmHg MAP group exhibited severe tissue oedema, organ function failure, and histopathologic damage. In our porcine model of resuscitation, targeting high MAP by fluid administration alone resulted in a huge increase in the infusion volume, severe tissue oedema, and organ dysfunction. Meanwhile, targeting low MAP resulted in persistent tissue hypoperfusion and metabolic stress. Hence, a resuscitation strategy of targeting appropriate MAP might be compatible with maintaining haemodynamic stability, tissue perfusion, and organ function.


Impact of the COVID 19 Pandemic on Radiological Imaging in Germany.
To analyze the impact of the COVID-19 pandemic in 2020 on the radiological imaging volume in Germany. In this retrospective multicenter study, we analyzed CT and MRI examinations of 7 radiology institutes across Germany from January to December 2020. The imaging volume was compared to 2019 (Wilcoxon-Mann-Whitney test). Modality, patient service locations, and examined body parts were assessed in consideration of time periods of the pandemic. In addition, correlation with the incidence of SARS-CoV-2 cases and associated death was performed (Spearman-test). In total, in 2020, imaging volume declined by 4 % (n = 8314) compared with 2019 (p < 0.05). The hard lockdown during the first pandemic wave (calendar week 12-16, March 22 - April 19) revealed the highest decrease with 29 % (n = 894, p < 0.01), with the greatest decrease in CT (36 % vs. MRI 26 %), outpatients (38 %, p < 0.01), and imaging of the spine and extremities (51-72 %, < 0.05 - p < 0.01). Examinations referred from the emergency department (-13 %, p < 0.05) and CT of the chest (-16 %, p < 0.05) were least affected. With the end of the first wave, gradual normalization of the imaging volume was observed and persisted until the end of the observation period. A reduction of imaging volume negatively correlated with the incidence of SARS-CoV-2-positive cases and associated deaths (r = 0.28 and 0.49, p < 0.05 and p < 0.001). The COVID-19 pandemic was associated with a significant temporary decline in imaging volume. After the first lockdown period, a quick recovery was observed with radiologic imaging examinations steadily approaching prior-year figures. · This study assesses the impact of dynamic pandemic activity on radiological imaging in a multicenter analysis in Germany.. · The COVID-19 pandemic was associated with a temporary decline in CT and MRI scans.. · Relaxation of restrictions was associated with fast normalization of imaging volumes to prior-year levels, which persisted until the end of the year.. · Significant catch-up effects were not observed.. · Schmidbauer M, Grenacher L, Juchems MS et al. Impact of the COVID 19 Pandemic on Radiological Imaging in Germany. Fortschr Röntgenstr 2022; 194: 625 - 633.


Occupational therapist home evaluations: inequalities, but doing the best we can?
The purpose of this study was (a) to describe the occupational therapy recommendations provided to patients discharged to inner city homes, and (b) to examine the relationship between patient health insurance and the number and type of occupational therapist recommendations for equipment and home modifications. An archival review was conducted of all referrals to the home evaluation program (n = 755) at a large urban rehabilitation hospital between January 1, 1994, and December 31, 1998. Additional patient demographic data and Functional Independence Measure (FIM) data were obtained in electronic form from the hospital information database. Analysis of results showed that while the pattern of equipment and modification recommendations varied little, publicly insured patients received fewer home modification recommendations compared to privately insured patients (t = 3.7; p < .0005), and were discharged from rehabilitation with significantly lower functional independence (MANOVA F = 3.9; p = .05). Results alert occupational therapists to the relationship between health insurance and treatment recommendations and point to patient advocacy and health policy as potential pathways to desired a achieve social change.


Efficacy of Ablation Therapy for Secondary Hyperparathyroidism by Ultrasound Guided Percutaneous Thermoablation.
The objective of this study was to explore the value of ultrasound-guided percutaneous microwave thermoablation to treat secondary hyperparathyroidism (SHPT). One hundred and thirty-eight parathyroid glands from 56 patients with SHPT were ablated in this study. All the parathyroid glands were evaluated by real-time contrast-enhanced ultrasound before, during and after ablation. Changes in serum parathyroid hormone (sPTH) levels were measured before treatment and at 1 h, 1 wk, 1 mo and 6 mo after thermoablation treatment. All 56 cases had a 1-mo follow-up, and 34 cases had a 6-mo follow-up. The sPTH level of the 54 cases 1 mo after ablation was significantly lower than that before (p < 0.05). In the 34 cases that had a 6-mo follow-up, the sPTH levels were also significantly lower at 6 mo after ablation than before (p < 0.05). Bone pain in patients improved post-operatively (p < 0.05), but itchiness and insomnia did not improve (p > 0.05). Ultrasound-guided percutaneous microwave thermoablation is a feasible and effective non-surgical alternative treatment for SHPT patients.


Resistance training improves single leg stance performance in older adults.
Age-associated losses in muscle mass, or sarcopenia, are marked by accompanying decrements in strength and muscle quality, impairing balance and increasing the risk for falls. Although progressive resistance training has been widely accepted as an appropriate modality for the treatment of sarcopenia, it has yet to offer consistent results in terms of improved balance. The purpose of the present research was to investigate the effects on static balance performance following a 6-week full-body progressive resistance training program in untrained older adults. Evaluation of magnitude-based inferences indicated the progressive resistance training intervention to be likely beneficial for improving static balance performance. These results were likely related to the strengthening of all major muscle groups by the incorporation of both free weights and resistance machines in the exercise regimen. Our findings support the use of progressive resistance training for untrained older adults to improve balance.


Characterization of the bactericidal effect of dietary sphingosine and its activity under intestinal conditions.
Sphingosine is known as a natural antimicrobial agent, protecting the human skin from bacterial colonization and possibly affecting the intestinal microbial community after ingestion. In this study we further investigated the antibacterial spectrum of dietary d-eythro-sphingosine in saline towards three intestinal pathogens and to the health promoting lactobacilli and bifidobacteria. The degree of bactericidal effect was studied using plate counts and Live/Dead analysis combined with flow cytometry. To assess activity under complex intestinal conditions, sphingosine was dosed to the Simulator of the Human Intestinal Microbial Ecosystem (SHIME) for a period of 11 days. Finally, we tried to elucidate the factors influencing the activity and the mode of action of sphingosine. In all performed experiments, high correlation occurred between plate counts and Live/Dead analysis. In saline a strong antibacterial effect was seen to all tested species, Gram-negative and Gram-positive, and sphingosine not selectively acted against pathogens, as health promoting bacteria were also affected. Under simulated intestinal conditions however, no shifts in bacterial concentrations were detected. Experiments with individual medium components thought that the effect of sphingosine is very easily neutralized by BSA, stearic acid and surfactants. Based on our results, d-erythro-sphingosine would only be active when protonated and its mode of action would imply electrostatic attraction to the bacteria and disruption of membrane integrity. In conclusion, the application of sphingosine is limited to specific environments, as activity was very sensitive to inhibition. Yet, because of its broad spectrum membrane disrupting activity, it could be very useful under controlled conditions.


Preoperative portal vein embolization improves prognosis after right hepatectomy for hepatocellular carcinoma in patients with impaired hepatic function.
Percutaneous transhepatic portal vein embolization (PTPE) increases the safety of subsequent major hepatectomy. The aim of this study was to determine the effect of PTPE on long-term prognosis after hepatectomy in patients with hepatocellular carcinoma (HCC). Seventy-one patients with HCC underwent right hepatectomy between 1984 and 1998. Preoperative PTPE was performed in 33 patients (group 1) and was not used in 38 patients (group 2). Outcome after operation was compared between the groups. The patients were further divided according to the median tumour diameter (cut-off 6 cm) and indocyanine green retention rate at 15 min (ICGR15) (cut-off 13 per cent). The cumulative survival rate was significantly higher in group 1 than in group 2 in patients with an ICGR15 of at least 13 per cent. Tumour-free survival rates were similar in both groups. Of patients with tumour recurrence after right hepatectomy, those in group 1 were more frequently subjected to further treatment. Preoperative PTPE improves the prognosis after right hepatectomy for HCC in patients with impaired hepatic function, although it does not prevent tumour recurrence.


Concentrations and origin of polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) in sediments of western Spitsbergen fjords (Kongsfjorden, Hornsund, and Adventfjorden).
Contaminant profiles in sediment cores represent valuable natural archives of environmental contamination, by which contaminant sources and historical changes in contaminant input and cycling may be recognized. In the present study, we discuss the sedimentary profiles and historical trends of organic contaminants - polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) - in three fjords of the Svalbard archipelago differing in environmental conditions and anthropogenic impact. The obtained results revealed no significant differences between the fjords Hornsund and Kongsfjorden, in the average levels of the analyzed contaminants. Levels ranging from 0.05 to 1.47 ng/g d.w. for ∑7 PCBs and from 37.3 to 1973 ng/g d.w. for ∑12 PAHs were measured. The observed spatial and temporal differences in contaminant levels are rather related to local variations in the fjords associated with the location of sampling stations. Higher concentrations of the ∑7 PCBs exceeding 1.00 ng/g d.w. were measured in sediment cores collected in the inner parts of both fjords, which remain under the influence of melting glacier outflows. Important concentrations of these contaminants were noticed in layers deposited recently, suggesting intensive supply of these substances from secondary sources. The observed levels are generally low and well below known established no effect levels. Only the concentration of fluoranthene exceeded the threshold effect level at several sampling stations. Moreover, fluoranthene concentrations in almost all Adventfjorden sediment layer samples were above probable effect levels, which can indicate a risk of adverse effects in exposed benthic organisms. The fluoranthene/pyrene and phenthrene/anthracene ratios, which are used for identification of hydrocarbon sources, suggest a dominance of PAHs of pyrolytic genesis in Kongsfjorden and Hornsund. In Adventfjorden, hydrocarbons of petrogenic origin were predominant. However, other sources like coal dust from stores on land are also possible at this location.


Mechanism of action of the migration stimulating factor produced by fetal and cancer patient fibroblasts: effect on hyaluronic and synthesis.
We have previously demonstrated that confluent fetal fibroblasts migrate into three-dimensional collagen gels to a significantly greater extent than their normal adult counterparts. Recent studies have revealed that this behavioral difference results from the secretion by fetal fibroblasts of a soluble migration-stimulating factor (MSF) which acts on these cells in an autocrine fashion. Adult fibroblasts do not produce MSF but remain responsive to it. Skin fibroblasts from cancer patients resemble fetal fibroblasts (rather than normal adult cells) with respect to their migratory behavior on collagen gels and continued production of MSF. This communication is concerned with elucidating the biochemical basis of MSF activity. Data are presented indicating that a) hyaluronic acid is required for the elevated migratory activity displayed by confluent fetal and breast cancer patient skin fibroblast; b) adult fibroblasts exhibit a bell-shaped dose-response to MSF, with maximal stimulation of migration observed at a concentration of 10 ng/ml; c) the migratory activity of adult fibroblasts pre-incubated with MSF remains high in the absence of additional factor: and d) MSF affects both the quantity and size class distribution of hyaluronic acid synthesized by adult fibroblasts. We have previously speculated that the persistent fetal-like fibroblasts of breast cancer patients play a direct role in disease pathogenesis by perturbing normal epithelial-mesenchymal interactions. The observations reported here suggest that MSF-induced alterations in hyaluronic acid synthesis may contribute to the molecular basis of such perturbations.


Stentless aortic valve reoperations: a surgical challenge.
Stentless aortic valve reoperations may become more common as these bioprostheses reach the limits of their durability. Relatively few studies have examined stentless valve reoperation, and we therefore reviewed our results for these procedures. All patients with stentless valves undergoing redo aortic valve replacement (AVR) at our institution were examined (n = 57). Ten patients had a prior Freestyle valve (Medtronic, Minneapolis, MN), and 47 patients had a Toronto stentless porcine valve (SPV; St. Jude Medical St Paul, MN). Redo AVR was performed 8.4 +/- 3.7 years (range, 0.1 to 16.5 years) after stentless valve implantation. Reoperations were elective in 27 patients (49%), and 30 (51%) underwent urgent or emergency procedures. The indication for redo AVR was structural valve dysfunction in 48 patients (84%), acute endocarditis in 7 (12%), and other in 2 (4%). Aortic insufficiency was present in 47 patients (82%). A total of 36 aortic root replacement operations (63% of patients) were required, of which 19 were secondary to severe adhesions between the stentless valve and the native aortic root. Operative mortality was 11% (n = 6) for the entire group. Mortality was higher in patients undergoing redo AVR less than 1 year after stentless valve implantation versus more than 1 year (67% versus 7%, p = 0.03). Long-term survival at 5 years postoperatively was 79% +/- 7% in all patients, and 81% of survivors were in New York Heart Association class I or II. Reoperation after stentless AVR is a challenging procedure that frequently requires aortic root replacement. Stentless valve reoperation is associated with an increased risk of death, particularly in patients operated on within 1 year of implantation.


High-Quality Draft Genome Sequence of Kallotenue papyrolyticum JKG1T Reveals Broad Heterotrophic Capacity Focused on Carbohydrate and Amino Acid Metabolism.
The draft genome of Kallotenue papyrolyticum JKG1(T), a member of the order Kallotenuales, class Chloroflexia, consists of 4,475,263 bp in 4 contigs and encodes 4,010 predicted genes, 49 tRNA-encoding genes, and 3 rRNA operons. The genome is consistent with a heterotrophic lifestyle including catabolism of polysaccharides and amino acids.


Fetal ethanol exposure activates protein kinase A and impairs Shh expression in prechordal mesendoderm cells in the pathogenesis of holoprosencephaly.
In humans, fetal ethanol exposure can cause holoprosencephaly (HPE), one of the most common birth defects that is characterized by brain, facial, and oral abnormalities. However, the pathogenesis of HPE is not clear. In the present study, we investigated the teratogenic mechanism of ethanol-induced brain and facial malformations in mice. Pregnant C57BL/6J mice were administered ethanol on E7 and facial and brain malformations were characterized on E10.5. We examined the effect of fetal ethanol exposure on Shh expression and activation of protein kinase A (PKA) because mutations in the human Shh gene are the most frequent cause of autosomal-dominant inherited HPE and PKA is a potent endogenous antagonist of Shh signaling. Fetal ethanol exposure on E7 induced severe midline defects characteristic of HPE. Ethanol exposure impaired Shh expression and induced excessive apoptosis only along the anterior edge of the prechordal mesendoderm (PME). In addition, ethanol activated PKA in anterior PME cells. Pretreatment of embryos with antioxidants, such as vitamins C or E, prevented the development of ethanol-induced HPE. Shh expression in PME cells is involved in the pathogenesis of ethanol-induced HPE. Ethanol may impair Shh expression indirectly by activating PKA. The inhibition of excessive apoptosis in PME cells by antioxidants implies that oxidative stress may underlie the teratogenic actions of ethanol. Thus, antioxidant treatment may be a simple preventative measure that could reduce the incidence of HPE following fetal ethanol exposure.


Association between complete right bundle branch block and atrial fibrillation development.
Complete right bundle branch block (CRBBB) is an important predictor of atrial fibrillation (AF) recurrence after pulmonary vein isolation. However, the association between CRBBB and AF development remains unclear. We performed a retrospective study of 2639 patients (male, n = 1549; female, n = 1090; mean age, 58 ± 13 years). CRBBB was defined as a late R (R') wave in lead V1 or V2 with a slurred S wave in lead I and/or lead V6 with a prolonged QRS duration (≥120 ms). Among the 2639 patients, CRBBB was detected in 40 patients (1.5%), and the prevalence of AF was 7.4% (196/2639). The proportion of patients with AF and CRBBB was higher than the proportion of patients with AF without CRBBB (22.5% vs. 7.2%; p = 0.001). In the forward multivariate logistic analysis, CRBBB (odds ratio [OR], 3.329; 95% confidence interval [CI], 1.350-8.211; p = 0.009), complete left bundle branch block (OR, 2.209; 95% CI, 1.238-3.940; p = 0.007), age (OR, 1.020; 95% CI, 1.005-1.035; p = 0.009), valvular heart disease (OR, 2.332; 95% CI, 1.531-3.552; p < 0.001), left atrial diameter (OR, 1.133; 95% CI, 1.104-1.163; p < 0.001), left ventricular ejection fraction (OR, 1.023; 95% CI, 1.006-1.041; p = 0.007), and class I or III anti-arrhythmic drug use (OR, 10.534; 95% CI, 7.090-15.651; p < 0.001) were associated with AF. Complete right bundle branch block was significantly associated with AF development in hospitalized patients with cardiovascular diseases.


Exophiala campbellii causing a subcutaneous palmar cyst in an otherwise healthy UK resident.
Exophiala is a ubiquitous genus encompassing more than forty species, a number of which have been associated with superficial or systemic infections in humans, and other hot- or cold-blooded animals. Here we report a human case of subcutaneous mycotic cyst caused by Exophiala campbellii. To our knowledge, this is only the third reported human infection caused by E. campbellii, all three of which involved subcutaneous nodules in patients who had resided in the United Kingdom.


The mechanism of the NFAT transcription factor family involved in oxidative stress response.
As a transcriptional activator widely expressed in various tissues, nuclear factor of activated T cells (NFAT) is involved in the regulation of the immune system, the development of the heart and brain systems, and classically mediating pathological processes such as cardiac hypertrophy. Oxidative stress is an imbalance of intracellular redox status, characterized by excessive generation of reactive oxygen species, accompanied by mitochondrial dysfunction, calcium overload, and subsequent lipid peroxidation, inflammation, and apoptosis. Oxidative stress occurs during various pathological processes, such as chronic hypoxia, vascular smooth muscle cell phenotype switching, ischemia-reperfusion, and cardiac remodeling. Calcium overload leads to an increase in intracellular calcium concentration, while NFAT can be activated through calcium-calcineurin, which is also the main regulatory mode of NFAT factors. This review focuses on the effects of NFAT transcription factors on reactive oxygen species production, calcium overload, mitochondrial dysfunction, redox reactions, lipid peroxidation, inflammation, and apoptosis in response to oxidative stress. We hope to provide a reference for the functions and characteristics of NFAT involved in various stages of oxidative stress as well as related potential targets.


The amino acid's backup bone - storage solutions for proteomics facilities.
Proteomics methods, especially high-throughput mass spectrometry analysis have been continually developed and improved over the years. The analysis of complex biological samples produces large volumes of raw data. Data storage and recovery management pose substantial challenges to biomedical or proteomic facilities regarding backup and archiving concepts as well as hardware requirements. In this article we describe differences between the terms backup and archive with regard to manual and automatic approaches. We also introduce different storage concepts and technologies from transportable media to professional solutions such as redundant array of independent disks (RAID) systems, network attached storages (NAS) and storage area network (SAN). Moreover, we present a software solution, which we developed for the purpose of long-term preservation of large mass spectrometry raw data files on an object storage device (OSD) archiving system. Finally, advantages, disadvantages, and experiences from routine operations of the presented concepts and technologies are evaluated and discussed. This article is part of a Special Issue entitled: Computational Proteomics in the Post-Identification Era. Guest Editors: Martin Eisenacher and Christian Stephan.


Mirror symmetry breaking in biochemical evolution.
The problem of origination of molecular asymmetry in biochemical evolution is discussed. The theoretical analysis shows that chiral purity of biomolecules has the biological significance for self-reproduction of organisms. The models of spontaneous symmetry-breaking in molecular systems are given. The aspects of various stages of biochemical evolution associated with the development of chiral polarization are analysed.


Properties of monoclonal antibodies to thyroliberin (TRH) induced by different immunogens: comparison with pituitary TRH receptor.
Thyroliberin E-H-P-NH2 (TRH) is a small neuropeptide pGlu-His-Pro-NH2 widely distributed in neural sites. The aim of this work was to obtain an antibody molecule with the nearest properties to that of TRH-receptor in GH3 cells. Different TRH-protein conjugates were prepared and utilized to induce monoclonal antibodies in mice. Several monoclonal antibodies were obtained using E-H-P-NH2 (TRH) coupled either to the histidyl residue (immunogen I) or to the prolyl residue (immunogen II). Antibodies generated using immunogen I and immunogen II were characterized in a radioimmunoassay system and an enzyme immunoassay system respectively. Their selectivities regarding a series of TRH related peptides were compared to those of rabbit polyclonal antibodies using three differently labelled TRH (tritiated-TRH, mono-iodinated-TRH and TRH-OH-acetyl-cholinesterase) as tracers and to prolactin secreting cells TRH receptors using 3H-TRH. Whatever the immunogen, the stereospecificity of monoclonal antibodies tested were found more different from TRH receptor characteristics than rabbit polyclonal antibodies.


Basics of the virology of HIV-1 and its replication.
Human immunodeficiency virus is undoubtedly the causative agent of AIDS. The understanding of HIV-1 pathogenesis is essential to develop and maintain antiretroviral treatment and vaccination. Since the first isolation of HIV-1 in cell culture, thousands of publications dealing with HIV and/or AIDS per year were released. In this review we give a basic overview of the virology of HIV-1 including the functions of the different HIV-1 proteins required for effective viral replication. Moreover, we summarize the interactive processes between HIV-1 and its target cells. Finally, the HIV-1 specific immune response and the current status of antiretroviral therapy are briefly described in this review.


Oral squamous cell carcinoma in post-transplant patients.
Patients on immunosuppressant therapy after transplantation have an increased risk of developing cutaneous squamous cell carcinomas. The risk of developing solid tumors of the upper aerodigestive tract in this population has been less defined. We present five patients that subsequently developed oral squamous cell carcinoma after transplantation. Retrospective chart review and literature review. Three bone marrow and two heart transplant patients were subsequently diagnosed with oral (oral cavity or oropharynx) carcinoma. The timing of diagnosis of oral cancer after transplant ranged from 18 months to 17 years post-transplantation. Patients with a history of transplantation should be routinely assessed for the potential development of oral neoplastic lesions. Oral squamous cell carcinoma in transplant patients can be more aggressive and clinically mistaken for chronic graft versus host disease. It is therefore reasonable to consider early biopsy in these patients to guide the need for intervention.


Chronic cerebral hypoperfusion shifts the equilibrium of amyloid β oligomers to aggregation-prone species with higher molecular weight.
Epidemiological studies have shown that atherosclerotic risk factors accelerate the pathological process underlying Alzheimer's disease (AD) via chronic cerebral hypoperfusion. In this study, we aimed to clarify the mechanisms by which cerebral hypoperfusion may exacerbate AD pathology. We applied bilateral common carotid artery stenosis (BCAS) to a mice model of AD and evaluated how the equilibrium of amyloid β oligomers respond to hypoperfusion. BCAS accelerated amyloid β (Aβ) convergence to the aggregation seed, facilitating the growth of Aβ plaques, but without changing the total Aβ amount in the brain. Furthermore, Aβ oligomers with high molecular weight increased in the brain of BCAS-operated mice. Considering Aβ is in an equilibrium among monomeric, oligomeric, and aggregation forms, our data suggest that cerebral hypoperfusion after BCAS shifted this equilibrium to a state where a greater number of Aβ molecules participate in Aβ assemblies to form aggregation-prone Aβ oligomers with high molecular weight. The reduced blood flow in the cerebral arteries due to BCAS attenuated the dynamics of the interstitial fluid leading to congestion, which may have facilitated Aβ aggregation. We suggest that cerebral hypoperfusion may accelerate AD by enhancing the tendency of Aβ to become aggregation-prone.


Inflammatory, vascular, and infectious myelopathies in children.
Acute nontraumatic myelopathies of childhood include inflammatory, infectious, and vascular etiologies. Inflammatory immune-mediated disorders of the spinal cord can be categorized as idiopathic isolated transverse myelitis, neuromyelitis optica, and multiple sclerosis. In recent years, human T-cell lymphotropic virus type 1, West Nile virus, enterovirus-71, and Lyme disease have been increasingly recognized as infectious etiologies of myelopathy, and poliomyelitis remains an important etiology in world regions where vaccination programs have not been universally available. Vascular etiologies include vasculopathies (systemic lupus erythematosus, small vessel primary angiitis of the central nervous system), arteriovenous malformations, and spinal cord infarction (fibrocartilaginous embolism, diffuse hypoxic ischemia-mediated infarction). Vascular myelopathies are less common than inflammatory and infectious myelopathies, but are more likely to lead to devastating clinical deficits. Current therapeutic strategies include acute anti-inflammatory treatment and rehabilitation. Stem cell transplantation, nerve graft implantation, and stimulation of endogenous repair mechanisms represent promising strategies for spinal cord repair.


Pluronic F-127: An Efficient Delivery Vehicle for 3-(1'-hexyloxy)ethyl-3-devinylpyropheophorbide-a (HPPH or Photochlor).
To determine the impact of delivery vehicles in photosensitizing efficacy of HPPH, a hydrophobic photosensitizer was dissolved in various formulations: 1% Tween 80/5% dextrose, Pluronic P-123 and Pluronic F-127 in 0.5%, 1% and 2% phosphate buffer solutions (PBS). HPPH was also conjugated to Pluronic F-127, and the resulting conjugate (PL-20) was formulated in PBS. Among the different delivery vehicles, only Pluronic P-123 displayed significant vehicle cytotoxicity, whereas Pluronic F127 was nontoxic. Compared to PL-20, HPPH formulated in Tween80 and Pluronic F-127 showed higher cell-uptake, but lower long-term retention in Colon26 cell compared to PL-20. The higher retention of PL-20 was similarly observed during in vivo uptake with BALB/c mice baring Ct26 tumors. In contrast to the in vitro uptake experiments, PL-20 showed slightly higher uptake compared to HPPH formulated in Tween or Pluronic-F127. A significant difference in pharmacokinetic profile was also observed between the HPPH-Pluronic formulation and PL-20. Under similar in vivo treatment parameters (drug dose 0.47 µmol kg-1 , light dose: 135 J cm-2 at 24 h post-injection of PS), HPPH formulated either in Tween or Pluronic F-127 formulation showed similar in vivo PDT efficacy (20-30% tumor cure on day 60), whereas PL-20 showed 40% tumor cure (day 60).


Isolation and characterization of filamentous fungi capable of degrading the mycotoxin patulin.
Patulin is a toxic secondary metabolite synthesized by various fungal strains. This mycotoxin is generally toxic to microorganisms as well as mammals due to its reactivity with the important cellular antioxidant glutathione. In this study, we explored the presence of microorganisms capable of degrading patulin. Microorganisms were screened for the ability to both grow in culture medium containing patulin and reduce its concentration. Screening of 510 soil samples resulted in the isolation of two filamentous fungal strains, one of which, Acremonium sp. TUS-MM1 was characterized in detail. Liquid chromatography-mass spectrometry and nuclear magnetic resonance analyses revealed that TUS-MM1 cells degraded patulin to desoxypatulinic acid. In addition, extracellular components of strain TUS-MM1 also exhibited patulin-transforming activity. High-performance liquid chromatography analysis revealed that the extracellular components generated several products from patulin. Disc diffusion assay using Escherichia coli cells revealed that the patulin-transformation products by the extracellular components are less toxic than patulin. We also demonstrated that a thermostable, low-molecular-weight compound within the extracellular components was responsible for the patulin-transforming activity. These results suggest that strain TUS-MM1 transforms patulin into less-toxic molecules by secreting a highly reactive compound. In addition, once patulin enters the cells, strain TUS-MM1 can transform it into desoxypatulinic acid to reduce its toxicity.


Intracranial granuloma caused by Aspergillus fumigatus.
A case is reported of intracranial granuloma caused by Aspergillus fumigatus involving the anterior cranial fossa and the frontal lobe. In this case, clinical symptoms developed about 5 years before the diagnosis was made. The final diagnosis was made by a craniotomy. The patient was treated with an extensive excision and chemotherapy, but finally he failed to respond to these treatments. We compile a summary of reported cases with a tabulation of pertinent information and discuss the pathogenesis, prognosis, and difficulty in treating this infection.


Dissociation versus posttraumatic stress: cortisol and physiological correlates in adults highly exposed to the World Trade Center attack on 9/11.
Nine months on average after the World Trade Center (WTC) attack, 21 highly exposed adults and 10 healthy controls without major exposure did not differ in cortisol and physiologic measures. Dissociation and posttraumatic stress symptoms were quantified in the exposed group. Dissociation was associated with greater peritraumatic dissociation and, marginally, childhood trauma, lower plasma cortisol levels at 08.00h, and blunted heart rate reactivity to psychosocial stress. Posttraumatic stress was associated with exposure, peritraumatic distress, and early posttraumatic stress, and marginally associated with peritraumatic dissociation; it was not associated with cortisol or physiologic measures. Urinary cortisol differed significantly in its relationship to dissociation versus posttraumatic stress. This small study emphasizes the importance of dissecting the neurobiology of posttraumatic stress versus dissociative traumatic responses.


Retracted: The Efficacy of Psychological Care and Chinese Herbal Decoction in Postoperative Chemotherapy Patients with Endometrial Cancer.
[This retracts the article DOI: 10.1155/2022/5700637.].


Fps/Fes and Fer protein-tyrosinekinases play redundant roles in regulating hematopoiesis.
The highly related protein-tyrosine kinases Fps (also called Fes) and Fer are sole members of a subfamily of kinases. In this study, knock-in mice harboring kinase-inactivating mutations in both fps and fer alleles were used to assess functional redundancy between Fps and Fer kinases in regulating hematopoiesis. Mice harboring kinase-inactivating mutations in fps and fer alleles were generated previously. Compound homozygous mice were bred that lack both Fps and Fer kinase activities and progeny were analyzed for potential defects in viability and fertility. Potential differences in hematopoiesis were analyzed by lineage analysis of bone marrow cells, peripheral blood counts, and hematopoietic progenitor cell colony-forming assays. Mice devoid of both Fps and Fer kinase activities were viable and displayed reduced fertility. Circulating levels of neutrophils, erythrocytes, and platelets were elevated in compound mutant mice compared to wild-type controls, suggesting that hematopoiesis is deregulated in the absence of Fps and Fer kinases. Compound mutant mice also showed reduced overall bone marrow cellularity, and lineage analysis revealed elevated CD11b(hi)Ly-6G(lo) myeloid cells, which may reflect increased granulocyte progenitors. Although no differences in the overall number of granulocyte/monocyte colony-forming progenitors were observed, qualitative differences in myeloid colonies from compound mutant mice suggested a role for Fps and Fer kinases in regulating cell-cell adhesion or a skewing in cellularity of colonies. Mice lacking both Fps and Fer kinase activities develop normally, show reduced fertility, and display defects in hematopoiesis, thus providing evidence for functional redundancy between Fps and Fer kinases in regulating hematopoiesis.


The relationship of workplace violence and nurse outcomes: Gender difference study on a propensity score matched sample.
To investigate workplace violence and nurse outcomes by comparing gender differences. A secondary analysis of cross-sectional survey data. Workplace violence was measured by four items from the International Hospital Outcome Study. Nurse outcomes were measured by tools including burnout, job satisfaction and intention to stay. We used propensity score matching to generate a sociodemographic balanced dataset of 108 male and 288 female nurses. A hypothetical relationship model was derived from the affective events theory. Comparative statistics and multi-group structural equation modelling were conducted to analyze gender differences. Data were collected in China from December 2013 - August 2014. Male nurses reported more workplace violence from staff and less intention to stay than females. Besides finding the mediation of burnout sharing with female nurses consistent with the affective events theory, workplace violence was directly linked to less intention to stay in male nurses. Male nurses experience more workplace violence by staff than female nurses. Besides responding emotionally to workplace violence like female nurses, male nurses also respond behaviourally. What problem did the study address? Gender differences in workplace violence and its relationship to nurse outcomes. What were the main findings? Male nurses experienced more workplace violence than female nurses, linked directly to less intention to stay. Workplace violence linked to less job satisfaction and intention to stay in nurses was mediated by burnout. Where and on whom will the research have impact? Gender-based prevention of and coping with workplace violence should be included in nursing training.


Lactic acidosis, neurological deterioration and compromised cellular pyruvate oxidation due to a defect in the reoxidation of cytoplasmically generated NADH.
Two patients, one dying at 25 days and one at 20 months had 'chronic' lactic acidaemia with a high lactate to pyruvate ratio. Both showed EEG abnormalities and seizure activity and both died of respiratory failure. Investigation of cultured skin fibroblasts from these patients revealed normal pyruvate dehydrogenase and pyruvate carboxylase activities but the cells showed a decreased ability to oxidase pyruvate which was returned to normal on the addition of methylene blue. Subsequent investigations revealed that the mitochondria from the patients' cells could oxidase pyruvate normally but that the cells had an abnormal NAD to NADH ratio under standard conditions of incubation. It was concluded that both children had a redox disequilibrium in the cytoplasmic compartment due to a problem in transporting reducing equivalents from the cytoplasmic to the mitochondrial compartments.


Designing a resilience model for pharmaceutical supply chain during crises: a grounded theory approach.
During disasters or crises, the traditional models of supply chain encounter failure and skewedness under the inevitable and unknown pressures. The procurement and transformation of required equipment to the involved areas is considered as one of the main triggers of decreasing damages and losses during crisis. In this regard, a breakdown in pharmaceutical supply chain can lead to intensive, undesired consequences. This was a qualitative study applying a grounded theory approach. The study was conducted with attending of 32 informant participants who were qualified in supply chain during natural disasters and crisis. In order to collect the data, deep semi-structured interviews were applied along with investigating the documents, observation, field notes and theoretical memos. For data analysis, a continuous comparison was used according to Corbin and Strauss method. Results of the study were categorized in 8 main categories as the main themes. "Wasting" appeared as the main factor of the resilience of pharmaceutical and consumable medical equipment supply chain. Wasting included two subthemes of loss of resources and wasting time. In order to make resilience in pharmaceutical and consumable medical equipment during disasters, it is necessary to reinforce the various dimensions of the resilience model to increase the rate of supply chain responsiveness. This study particularly contributes to broadening and deepening our understanding of how to mitigate the risk of undesirable outcomes of pharmaceutical supply chain during the disasters or crises.


Maisonneuve fracture: case report of a missed diagnosis.
We report the case of a Maisonneuve fracture of the fibula in which the diagnosis was initially missed. The patient presented with a chief complaint of medial ankle pain. Rentograms of the ankle were unremarkable, and the proximal fibula was not examined. He returned four days later with increased pain, at which time examination revealed tenderness along the proximal fibula and medial ankle. Roentgenograms showed widening of the medial joint space of the ankle and an oblique crush of the proximal fibula. The patient underwent open reduction and internal fixation of the syndesmosis and repair of the deltoid ligament, and recovered uneventfully. Physical examination of ankle injuries should include the proximal fibula.


Low pH effects on reactive oxygen species and methylglyoxal metabolisms in Citrus roots and leaves.
Limited data are available on the responses of reactive oxygen species (ROS) and methylglyoxal (MG) metabolisms to low pH in roots and leaves. In China, quite a few of Citrus are cultivated in acidic soils (pH < 5.0). 'Xuegan' (Citrus sinensis) and 'Sour pummelo' (Citrus grandis) (C. sinensis were more tolerant to low pH than C. grandis) seedlings were irrigated daily with nutrient solution at a pH of 2.5, 3 or 5 for nine months. Thereafter, we examined low pH effects on growth, and superoxide anion production rate (SAP), malondialdehyde (MDA), MG, antioxidants, and enzymes related to ROS and MG detoxification in roots and leaves in order to (a) test the hypothesis that low pH affected ROS and MG metabolisms more in roots than those of leaves, and (b) understand the roles of ROS and MG metabolisms in Citrus low pH-tolerance and -toxicity. Compared with control, most of the physiological parameters related to ROS and MG metabolisms were greatly altered at pH 2.5, but almost unaffected at pH 3. In addition to decreased root growth, many fibrous roots became rotten and died at pH 2.5. pH 2.5-induced changes in SAP, the levels of MDA, MG and antioxidants, and the activities of most enzymes related to ROS and MG metabolisms were greater in roots than those of leaves. Impairment of root ascorbate metabolism was the most serious, especially in C. grandis roots. pH 2.5-induced increases in MDA and MG levels in roots and leaves, decreases in the ratios of ascorbate/(ascorbate+dehydroascorbate) in roots and leaves and of reduced glutathione/(reduced+oxidized glutathione) in roots were greater in C. grandis than those in C. sinensis. Low pH affected MG and ROS metabolisms more in roots than those in leaves. The most seriously impaired ascorbate metabolism in roots was suggested to play a role in low pH-induced root death and growth inhibition. Low pH-treated C. sinensis roots and leaves had higher capacity to maintain a balance between ROS and MG production and their removal via detoxification systems than low pH-treated C. grandis ones, thus contribute to the higher acid-tolerance of C. sinensis.


Stability assessment of tamsulosin and tadalafil co-formulated in capsules by two validated chromatographic methods.
The advent of a new pharmaceutical formulation evokes the need for examining the chemical stability of their constituents and establishing proper stability-indicating methods. Herein, the stability of the newly co-formulated Tamsulosin and Tadalafil were examined under different stress conditions. The acidic degradation of Tamsulosin yielded its sulfonated derivative, while Tadalafil was susceptible to both acidic and basic degradation. Two stability-indicating chromatographic methods, namely; high-performance thin-layer chromatography and high-performance liquid chromatography, have been developed. Significant high-performance thin-layer chromatography-fractionation could be achieved by utilizing a stationary phase of silica gel 60 F254 and a mobile phase composed of ethyl acetate/toluene/methanol/ammonia (4:2:4:0.6, by volumes) with densitometric recording at 280 nm over a concentration range of 0.5-25 μg/band for both drugs. The HPLC-separation could be reached on XBridge® C18 column isocraticaly by using a mobile phase having acetonitrile/phosphate buffer, pH 6.0 (45:55, v/v) pumped at a flow rate of 1.7 mL/min and applying diode array ultraviolet-detection at 210 nm over a linearity range of 3-70 μg/mL for each drug. Specificity of the two methods was additionally assured via peak purity assessment. Moreover, the methods were distinctly exploited for evaluating the drugs' stability in accelerated stability-studied samples of Tamplus® capsules.


Reinfection and reactivation of equine herpesvirus-1 in the mouse.
Balb/c mice were inoculated with equine herpesvirus-1 (EHV-1) by the intranasal (i.n.) route. Mice developed respiratory signs; virus replication occurred in the respiratory tract and viraemia was detected; some mice died. Recovered mice were given a second inoculation with the same strain 5 months later. Following the second infection no mice died, however, virus replication was again observed in the respiratory tract and viraemia was detected once more. Administration of an antiviral agent during the acute infection prevented mice from developing severe clinical signs and all survived. These mice, and some that had survived an acute infection without chemotherapy, were given a variety of stimuli, for example X-irradiation or corticosteroid injection. Reappearance of infectious virus was detected in approx. 1/3 animals in either the respiratory tract or blood. We speculate on the possible sites of latency in the model.


1'-Acetylferrocene-1-carboxylic acid: an instance of hydrogen bonding in the rare dimeric acid-to-ketone mode.
The title compound, [Fe(C(6)H(5)O(2))(C(7)H(7)O)], adopts a conformation involving partial staggering of its rings and aggregates in the solid as acid-to-ketone hydrogen-bonding dimers [O.O = 2.720(4)A and O-H...O = 164 degree] having centrosymmetrically related components. Close intermolecular C-H...O contacts were found to both carboxyl O atoms.


Methionine oxidation in human growth hormone and human chorionic somatomammotropin. Effects on receptor binding and biological activities.
The oxidation of the methionine residues of human growth hormone (hGH) and human chorionic somatomammotropin (hCS) to methionine sulfoxide by hydrogen peroxide has been studied. The kinetics of oxidation of individual methionine residues has been measured by reverse-phase high pressure liquid chromatography tryptic peptide mapping. Met-170 is completely resistant to oxidation in both hormones. The other 3 methionine residues in hCS (Met-64, Met-96, and Met-179) have markedly different reaction rates. Oxidation of the methionine residues does not appear to cause gross conformational changes in either hGH or hCS, as judged by CD and 1H NMR spectroscopy. Oxidation of Met-14 and Met-125 in hGH has little effect on affinity of the hormone for lactogenic receptors or on its potency in the Nb2 rat lymphoma in vitro bioassay for lactogenic hormones. The oxidation of Met-64 and/or Met-179 in hCS reduces profoundly both its affinity for lactogenic receptors and its in vitro biological potency. It is inferred by induction that residues 64 and/or 179 are critical for the binding of both hGH and hCS to lactogenic receptors and the expression of lactogenic biological activity.


Upregulation of HIV-1 expression in cocultures of chronically infected promonocytes and human brain cells by dynorphin.
Using cocultures of human fetal brain cells and a chronically human immunodeficiency virus-1 (HIV-1)-infected promonocytic line U1, we investigated the effect of dynorphin, an endogenous opioid peptide found in the CNS, on upregulation of HIV-1 expression. Dynorphin and the synthetic kappa receptor agonist U50,488 promoted HIV-1 expression with a bell-shaped concentration-response relationship in which maximal effects were observed at 10(-13) and 10(-11) M, respectively. Pretreatment for 30 min with the kappa receptor antagonist nor-binaltorphimine completely blocked the stimulatory effect of dynorphin and U50,488. The involvement of cytokines on HIV-1 expression was tested. Dynorphin-induced upregulation of HIV-1 in the cocultures was largely blocked by antibodies to tumor necrosis factor (TNF)-alpha and interleukin (IL)-6 but not by antibodies to IL-10. Also, dynorphin stimulated TNF-alpha and IL-6 in the brain cell cultures at both mRNA and protein levels, suggesting the involvement of these cytokines in opioid-induced HIV-1 expression. These findings suggest that endogenous opioid peptides such as dynorphin may have an immunomodulatory function in the CNS and could act as a cofactor in the neuropathogenesis of HIV-1.


Advantages of short-time ureteric stenting for prevention of urological complications in kidney transplantation: an 18-year experience.
We retrospectively studied the incidence of urological complications in a consecutive series of 590 patients (group B) who received a kidney transplant (KT) with a ureteral stent from January 1994 to December 2002. The ureteral stent was sewn to the bladder catheter during the surgical procedure and left in situ for a mean time of 10 days (range 8 to 12 days). The results were compared to a consecutive series of 414 patients who received a KT from March 1986 to December 1993 without a ureteral stent (group A). The two groups were comparable in terms of donor and recipient gender, ischemia time, delayed graft function, and chronic rejection incidence, but differed in mean donor age (44.1 vs 36.0 years), mean recipient age (45.4 vs 39.1 years), living/cadaveric donor rate (19.8% vs 11.9%), arterial lesions and bench reconstruction rate (11.1 vs 3.5%), as well as acute rejection episodes (11.7% vs 29.2%). Complications were seen in nine patients in group B (1.5%) and 17 patients in group A (4.1%) (P < .0001). Urinary leaks presented in two patients in group B (0.3%) and 11 patients in Group A (2.6%; P < .0001), while stenosis was present in six patients in group B (1.5%) and 7 in group A (1.2%) (P = NS). Urological complications such as urinary tract infection and macroscopic hematuria were similar in both groups. Time to presentation of a leak was within 2 weeks from KT in 10 patients (92.3%), while stenosis presented early in four patients (one in group B and four in group A). Of the stenoses, 69.3% presented late (beyond 12 weeks) in five patients in group B and three in Group A. In conclusion, our data suggest that routine use of double pigtail ureteral stent significantly decreased the incidence of leaks and early stenoses, but it did not modify late stenosis incidence. In the last decade, risk factors for urological complications have been increasing over time, namely, older donors and older recipients, living donation, length of dialysis, and the use of grafts with arterial lesions. Therefore we believe that a ureteral stent should be routinely considered to afford the advantage to protect the urinary anastomosis in the early postoperative period when the incidence of complications is highest, without the need of cystoscopy for its removal.


Evaluation of Singh index for assessment of osteoporosis using digital radiography.
Evaluation of Singh index (SI) as a simple means for estimating bone mass on radiographs has been subject of numerous studies. All of these studies used plain film radiographs for assessment of SI. Digital radiography may improve validity and reliability of SI assessment. Aim of this study was to evaluate SI gradings assessed on digital radiographs. Digital pelvic radiographs of 100 patients were graded using SI by five independent observers (two radiologists, three traumatologists) blinded to dual energy X-ray absorptiometry (DXA) results and re-graded by all observers for assessment of intraobserver agreement. SI was correlated with DXA measurements and after grouping the patients according to World Health Organisation (WHO) criteria (osteoporosis, osteopenia, normal). Logistic regression analysis was performed in order to identify influential parameters on the SI grading process. Mean intraobserver agreement was 0.648+/-0.18 (Kendall's Tau) and 0.43+/-0.28 (kappa). Mean interobserver agreement was 0.488+/-0.193 (Kendall's Tau) and 0.199+/-0.248 (kappa). Mean correlation between SI and trochanteric BMD and T scores was 0.219+/-0.04 and 0.210+/-0.05 (Spearman's coefficient). Only one observer (senior radiologist) reached the significance level after grouping the patients' DXA results according to WHO criteria and correlating the results with SI gradings. Logistic regression analysis revealed a significant influence of trochanteric T score in two observers while other variable parameters failed to reach the significance level. Even though we found reasonable intraobserver agreement assessment of SI is highly subjective and interobserver agreement is generally poor. Moreover, using digital radiography could not improve correlation with DXA measurements.


Down-regulation of microRNA-21 reduces inflammation and podocyte apoptosis in diabetic nephropathy by relieving the repression of TIMP3 expression.
Several miRNAs including miR-21 have emerged as important regulators in the development of diabetic nephropathy (DN). However, the molecular mechanism of miR-21 underlying DN pathogenesis remains to be further discussed. Streptozotocin (STZ)-induced DN rats and high glucose (HG)-induced podocytes were used as the in vivo and in vitro models of DN. miR-21 level was detected by qRT-PCR assay. Inflammatory cytokine levels were assessed by ELISA. Kidney injury of rats was evaluated by blood glucose, serum creatinine and blood urine nitrogen concentrations and periodic acid schiff (PAS) staining. Apoptosis in kidney tissues and podocytes was determined by TUNEL and flow cytometry analyses, respectively. Western blot analysis was applied to measure the protein levels of tissue inhibitors of metalloproteinase 3 (TIMP3), Bax and Bcl-2. The relationship between TIMP3 and miR-21 was confirmed by luciferase reporter assay. miR-21 expression was upregulated in serum and kidney tissues of DN patients, kidney tissues of STZ-induced DN rats, and HG-treated podocytes. miR-21 depletion inhibited pro-inflammatory factor (IL-1β, TNF-α) secretions and alleviated kidney damages in STZ-induced DN rats. Moreover, TIMP3 was a target of miR-21 in HG-treated podocytes. Additionally, TIMP3 overexpression abated HG-induced inflammatory responses and podocyte apoptosis. Furthermore, the inhibitory effects of TIMP3 on inflammatory responses and podocyte apoptosis were alleviated by increased miR-21. The down-regulation of miR-21 inhibited the progression of DN by targeting TIMP3 in STZ-induced DN rats and HG-treated podocytes, elucidating a novel regulatory mechanism of miR-21 in DN progression and offering a potential target for DN therapy.


Increased self-efficacy: the experience of high-intensity exercise of nursing home residents with dementia - a qualitative study.
There has been increasing interest in the use of non-pharmacological interventions, such as physical exercise, to improve the well-being of nursing home residents with dementia. For reasons regarding disease symptoms, persons with dementia might find it difficult to participate in exercise programs. Therefore, it is important to find ways to successfully promote regular exercise for patients in residential care. Several quantitative studies have established the positive effects of exercise on biopsychosocial factors, such as self-efficacy in older people; however, little is known regarding the qualitative aspects of participating in an exercise program among older people with dementia. From the perspective of residents, we explored the experiences of participating in a high-intensity functional exercise program among nursing home residents with dementia. The participants were eight elderly people with mild-to-moderate dementia. We conducted semi-structured interviews one week after they had finished a 10-week supervised high-intensity exercise program. We analyzed the data using an inductive content analysis. Five overreaching and interrelated themes emerged from the interviews: "Pushing the limits," "Being invested in," "Relationships facilitate exercise participation," "Exercise revives the body, increases independence and improves self-esteem" and "Physical activity is a basic human necessity--use it or lose it!" The results were interpreted in light of Bandura's self-efficacy theory. The exercise program seemed to improve self-efficacy through several mechanisms. By being involved, "being invested in" and having something expected of them, the participants gained a sense of empowerment in their everyday lives. The importance of social influences related to the exercise instructor and the exercise group was accentuated by the participants. The nursing home residents had, for the most part, positive experiences with regard to participating in the exercise program. The program seemed to increase their self-efficacy through several mechanisms. The instructor competence emerged as an important facilitating factor. The participants emphasized the importance of physical activity in the nursing home.


Radiology information systems, picture archiving and communication systems, teleradiology--overview and design criteria.
Information technology (IT), long taken for granted in commercial settings, is now being utilized for health-care applications. Medical imaging has lagged comparatively due to the extremely vast data content of each frame; thus, the requirement for expensive high-end components. Further, IT in radiology has evolved from two distinctly separate camps--information systems, known as RIS (radiology information systems) and PACS (picture archiving and communications systems). Both RIS and PACS applications have migrated to the PC environment, enabling cost-effective implementation, but from two backgrounds: RIS from vendors using conventional information systems platforms and products, and PACS from radiographic film and modality vendors. The radiology department at Texas Tech University has assembled a seamlessly integrated, enterprise-wide RIS/PACS/teleradiology intranet. The design criteria include user-friendliness, flexibility to respond to changing needs, and open modular architecture to assure interoperability, cost-effectiveness, and future-proofing of investment. Since no single venor could provide an integrated system meeting our specifications, we decided to assume the burden of constructing our own system. As the system integrator, we embrace open architecture, thus enabling the incorporation of industry-standard-compliant, COTS (commercially off the shelf) products as modules. Microsoft Windows NT operating system, Visual C++ programming language, TCP/IP (transmission control protocol/internetworking protocol), relational SQL (structured query language) database, ODBC (open database connectivity), HL-7 (health level seven) and DICOM (digital imaging and communications in medicine) interfaces are utilized. The usage of COTS components reduces the cost to very affordable levels. With this approach, any module in our system can be replaced when outmoded, without affecting other modules in our system, making it truly future-proof. Construction and evolution of our system (TECHRAD) is reviewed.


Usefulness of ultrasonography and MRI for diagnosis of fetal pulmonary agenesis: case report and review of the literature.
A pregnant Japanese female was referred to our hospital due to intrauterine fetal growth restriction. A prenatal diagnosis of right pulmonary agenesis could be made using ultrasonography and fetal magnetic resonance imaging, and a Caesarian section was performed at 34 weeks of gestation. The infant developed a respiratory disorder immediately, received systemic management in the neonatal intensive care unit (NICU), and was discharged at age of 103 days without any severe sequelae.


[Clinically significant drug-drug and drug-food interactions associated with calcium channel blockers].
Calcium channel blockers have been widely used for treatment of hypertension, angina pectoris, arrhythmia, and other heart diseases. Nowadays, combination therapy is widely common for these diseases. However, combination therapy is associated with increasing risks of pharmacokinetic or pharmacodynamic drug-drug interaction, and therefore clinicians should pay attention to prevent it. Furthermore, in addition to drug-drug interactions, we need to be cautions for drug interaction with food and drink including health-food and supplement.


Neurotransmitter receptor histochemistry: the contribution of in situ hybridization.
Molecular cloning of neurotransmitter receptors has enabled the application of in situ hybridization histochemistry to the study of the regional distribution and cellular localization of receptor mRNAs with an unprecedented degree of selectivity. This has resulted in a large body of information including detailed maps of the distribution of receptor subtype transcripts, the establishment of neurotransmitter phenotype and connectivity of receptor-expressing cells, and the relationship between receptor transcripts and binding sites. In this minireview, we discuss and illustrate with a number of examples the contributions of in situ hybridization histochemistry to the study of receptor distribution in brain tissue.


Effects of tributyltin on barrier functions in human intestinal Caco-2 cells.
The effect of tributyltin (TBT) on human intestinal epithelial cell functions was investigated by using human intestinal Caco-2 cell monolayers. We paid particular attention to the effect of TBT on two barrier functions: the tight junction as a physical barrier and MDR1/P-glycoprotein as a biological barrier. A loss of monolayer integrity was apparent from the TBT treatment and the paracellular permeability was increased by TBT. On the other hand, the activity of P-glycoprotein, which was examined by measuring the accumulation of Rhodamine-123 and daunomycin, was increased by prolonged TBT treatment in a concentration-dependent manner (1-100 nM). Furthermore, it was clarified by Western and Northern blots that this increase was accompanied by the increased expression of MDR1 mRNA and protein. The activation of a multidrug resistance transporter P-glycoprotein by TBT would cause a disorder of the human intestines by changing the drug pharmacokinetics.


Bilateral sudden sensorineural hearing loss caused by alcohol abuse and heroin sniffing.
Objective. Acute or chronic heroin abuse has been associated with various central neurologic pathologies and, occasionally, with peripheral nervous system damage. The effect of heroin on hearing has not been adequately documented, although several cases with sudden hearing loss owed to heroin abuse have been reported. We present a young male with bilateral sudden sensorineural hearing loss, following heroin sniffing and alcohol consumption. Methods. Our patient underwent a detailed clinical and audiological evaluation, including auditory brainstem responses and otoacoustic emission. Routine laboratory blood tests and imaging studies were performed. Results. The patient was treated with corticosteroids and magnesium, resulting in complete restoration of hearing after one month. Conclusion. Sudden hearing loss owed to heroin abuse is usually curable, following adequate treatment.


Myocardial uptake of thallium 201 and technetium 99m-labeled sestamibi after ischemia and reperfusion: comparison by quantitative dual-tracer autoradiography in rabbits.
Myocardial scintigraphy with 99mTc-labeled sestamibi (99mTc-sestamibi) or 201Tl is used to assess regional perfusion in acute coronary syndromes associated with metabolic or functional abnormalities, such as acute coronary thrombosis with reperfusion and ischemia at rest. However, the initial uptake of these agents may be affected by a recent ischemic insult because the myocardial retention of these tracers depends on cellular metabolism. Accordingly, 99mTc-sestamibi and 201Tl were injected simultaneously in rabbits after transient brief (10 to 15 minutes, group I) or prolonged (45 to 60 minutes, group II) coronary occlusion. Accumulated subendocardial and subepicardial 99mTc-sestamibi and corresponding 201Tl activity were determined from autoradiographs of 30 microns short-axis slices comounted with serial tissue standards. Circumferential 99mTc-sestamibi and 201Tl activity profiles closely overlapped in both groups. The initial global and segmental myocardial activity per unit blood flow within the ischemic zone did not differ from unity for either tracer regardless of the duration of the ischemic insult. The initial myocardial uptake of both 99mTc-sestamibi and 201Tl after an acute ischemic insult reflected predominantly coronary blood flow, independent of myocardial viability. Thus this study supports the use of both 99mTc-sestamibi and 201Tl as perfusion probes in acute coronary syndromes characterized by acute occlusion and reperfusion.


Transient oculomotor nerve palsy due to non-aneurysmal neurovascular compression.
Acute oculomotor nerve palsy requires urgent exclusion of aneurysmal compression. We report a 62year old man with a transient right third nerve palsy with pupillary involvement, who was found to have neurovascular compression of the cisternal oculomotor nerve as it curved over a duplicated superior cerebellar artery on high resolution MR imaging. Direct vascular compression should be considered in patients with isolated cranial neuropathies in whom other pathologies have been excluded.


Urinary incontinence in the dog and cat.
In small animals, urinary incontinence is mainly a problem of dogs, particularly bitches. The following descriptions relate to canine incontinence although comparisons will be made, where appropriate, to similar conditions in the cat. The investigative procedures commonly employed have been summarized previously but contrast radiographic techniques are essential.


Systems-level identification of PKA-dependent signaling in epithelial cells.
G protein stimulatory α-subunit (Gαs)-coupled heptahelical receptors regulate cell processes largely through activation of protein kinase A (PKA). To identify signaling processes downstream of PKA, we deleted both PKA catalytic subunits using CRISPR-Cas9, followed by a "multiomic" analysis in mouse kidney epithelial cells expressing the Gαs-coupled V2 vasopressin receptor. RNA-seq (sequencing)-based transcriptomics and SILAC (stable isotope labeling of amino acids in cell culture)-based quantitative proteomics revealed a complete loss of expression of the water-channel gene Aqp2 in PKA knockout cells. SILAC-based quantitative phosphoproteomics identified 229 PKA phosphorylation sites. Most of these PKA targets are thus far unannotated in public databases. Surprisingly, 1,915 phosphorylation sites with the motif x-(S/T)-P showed increased phosphooccupancy, pointing to increased activity of one or more MAP kinases in PKA knockout cells. Indeed, phosphorylation changes associated with activation of ERK2 were seen in PKA knockout cells. The ERK2 site is downstream of a direct PKA site in the Rap1GAP, Sipa1l1, that indirectly inhibits Raf1. In addition, a direct PKA site that inhibits the MAP kinase kinase kinase Map3k5 (ASK1) is upstream of JNK1 activation. The datasets were integrated to identify a causal network describing PKA signaling that explains vasopressin-mediated regulation of membrane trafficking and gene transcription. The model predicts that, through PKA activation, vasopressin stimulates AQP2 exocytosis by inhibiting MAP kinase signaling. The model also predicts that, through PKA activation, vasopressin stimulates Aqp2 transcription through induction of nuclear translocation of the acetyltransferase EP300, which increases histone H3K27 acetylation of vasopressin-responsive genes (confirmed by ChIP-seq).


Mechanism of action of bimatoprost, latanoprost, and travoprost in healthy subjects. A crossover study.
To study the effects of 3 prostaglandin analogs, bimatoprost, latanoprost, and travoprost, on aqueous dynamics in the same subjects and to compare techniques of assessing outflow facility. Experimental study (double-masked, placebo-controlled, randomized paired comparison, 4-period crossover). Thirty healthy adult subjects. Bimatoprost, latanoprost, travoprost, or a placebo was administered to the left eye once a day in the evening for 7 days, after a minimum 4-week washout period between each session. Tonographic outflow facility was measured by Schiøtz tonography and pneumatonography on day 7. On day 8, the aqueous humor flow rate and fluorophotometric outflow facility were measured by fluorophotometry. Uveoscleral outflow was calculated from the aqueous humor flow rate and outflow facility using the Goldmann equation. Facility of outflow, aqueous humor flow rate, intraocular pressure (IOP), and calculation of uveoscleral outflow. All medications lowered IOP relative to a placebo. None of the drugs affected aqueous humor production. All medications increased outflow facility compared with placebo when measured by Schiøtz and 2-minute pneumatonography (P< or =0.02); the apparent increase of outflow facility measured with fluorophotometry and 4-minute pneumatonography did not reach statistical significance. In contrast, uveoscleral outflow was significantly increased by all medications when calculated from 4-minute pneumatonography data, and fluorophotometry and Schiøtz data at higher episcleral venous pressures. The apparent increase found with 2-minute pneumatonography did not reach statistical significance. These differing results in the same patients indicate that differences in measurement techniques, and not differences in mechanism of action, explain previous conflicting published reports on the mechanism of action of the prostaglandins. Bimatoprost, latanoprost, and travoprost have similar mechanisms of action. All 3 drugs reduce IOP without significantly affecting the aqueous production rate. All drugs increase aqueous humor outflow, either by enhancing the pressure-sensitive (presumed trabecular) outflow pathway or by increasing the pressure-insensitive (uveoscleral) outflow, but the assessment of the amount of flow through each pathway depends upon the measurement technique.


Characteristics of gay and bisexual men who drop out of a web survey of sexual behaviour in the UK.
An invitation to take part in a web survey of sexual behaviour appeared on two popular websites for gay men in the UK in May and June 2003. As soon as men began the survey, their responses were recorded. If they quit before the end, the point at which they stopped was identified. Men clicked into the survey a total of 4,271 times and 2,752 (64%) respondents completed it. The median last question reached by respondents who dropped out was question number 20 out of 158. Multivariate analysis indicated that drop out was related to ethnic group, openness about sexual orientation and age. The results suggest that MSM who use the Internet to seek sexual partners may be younger, more likely to be from an ethnic minority and less open about their sexuality than web surveys indicate. This has implications for the development of online HIV and STI interventions.


Using the full Raman depolarisation in the determination of the order parameters in liquid crystal systems.
The depolarisation ratio for the Raman-active phenyl stretching mode has been measured over the whole of the mesophase range, and the orientational order parameters deduced, in the uniaxial nematic liquid crystal octylcyanobiphenyl (8CB). Linearly polarised light was incident normally on a homogeneously aligned sample and a chi(2) minimisation routine performed on the 360 degrees depolarisation ratio profile. The order parameters (P(200)) and (P(400)), together with the differential polarisability ratio, r , are used as fitting parameters and measured as a function of temperature. Interestingly, we show that the value for r , conventionally measured in the isotropic phase and assumed to remain constant, has a clear temperature dependence, ranging from -0.032 + or - 0.008 in the isotropic phase through to -0.245 + or - 0.015 at the nematic-to-smectic A phase transition. The measured order parameters (P(200)) and (P(400)) varied from 0.35-0.55 + or - 0.02 and 0.180-0.245 + or - 0.02, respectively, across the 8 degrees C wide nematic phase range. The values of both (P(200)) and (P(400)) are in excellent agreement with theory, but it is noteworthy that (P(400)) shows a much better quantitative match than has been reported in previous work. Crucially the temperature dependence of r is shown to be a contributing factor in the low (P(400)) values that have been conventionally reported from Raman scattering measurements. The potential for fitting the entire angular depolarisation ratio distribution in liquid crystalline systems that are described by more order parameters, specifically biaxial materials, is discussed.


The satisfaction of elderly people with elderly caring social organizations and its relationship with social support and anxiety during the COVID-19 pandemic: a cross-sectional study.
With the deepening of China's aging population, higher demands have been placed on the supply of elderly care services. As one of the main sources of providing elderly care services, the quality of service provided by elderly caring social organizations (SOs) directly affects the quality of life of the elderly. In recent years, mental health issues among the elderly have become increasingly prominent, especially with the onset of the COVID-19 pandemic. Necessitating the need to pay much more attention to the social support and mental health of this population. This study, therefore, explores the mediating role of institutional satisfaction between the social support and anxiety levels of elderly people in Chongqing's elderly caring SOs. This study employed a multi-stage stratified random sampling method to survey 1004 service recipients in elderly caring social organizations from July to August 2022. The self-made sociodemographic questionnaire, institutional satisfaction questionnaire, MSPSS, and GAD-7 were used to collect data on sociodemographic characteristics, institutional satisfaction, social support, and anxiety levels of older adults. Exploratory Factor Analysis and Cronbach's alpha were used to test construct validity and scale reliability, respectively. Data features were described with One-Way Analysis of Variance, while Multiple Linear Regression and Structural Equation Modeling were used to evaluate relationships between social support, institutional satisfaction, and anxiety levels. The average institutional satisfaction score for elderly people in elderly caring SOs was 48.14 ± 6.75. Specifically, the satisfaction score for environmental quality and the satisfaction score for service quality were 16.63 ± 2.56 and 31.52 ± 4.76, respectively. In terms of socio-demographic variables, the presence of visits from relatives, personal annual average income, and self-rated health status all have significant effects on anxiety. Elders who receive visits from relatives have lower levels of anxiety compared to those who do not. Personal annual average income and self-rated health status are negatively correlated with anxiety levels. Social support had significant positive effect on institutional satisfaction, while institutional satisfaction had significant negative effect on anxiety. Institutional satisfaction partially mediated the relationship between social support and anxiety. Our research demonstrates that improving the quality of organizational services in elderly caring SOs and increasing institutional satisfaction among the elders has significant potential for reducing anxiety levels among the elderly. Additionally, the social support by visits from family members cannot be overlooked. We encourage increasing the frequency of family visits through various means to enhance the support provided to elderly individuals.


FPGA-based burst-error performance analysis and optimization of regular and irregular SD-LDPC codes for 50G-PON and beyond.
We evaluate the burst-error performance of the regular low-density parity-check (LDPC) code and the irregular LDPC code that has been considered for ITU-T's 50G-PON standard via experimental measurements in FPGA. By using intra codeword interleaving and parity-check matrix rearrangement, we demonstrate that the BER performance can be improved under ∼44-ns-duration burst errors for 50-Gb/s upstream signals.


Comparing the influence of selenite (Se4+) and selenate (Se6+) on the inhibition of the mercury (Hg) phytotoxicity to pak choi.
Selenite (Se (IV)) and selenate (Se (IV)) have recently been demonstrated to be equally effective in inhibiting mercury (Hg) phytotoxicity to plants. This assertion is still unclear. In this study, we aimed to explore the potential effects of Se species (Se4+ and Se6+) on the inhibition of the mercury (Hg) bioavailability to pak choi in dry land. Pot experiments with exposure to different dosages of mercuric chloride (HgCl2) and selenite (Na2SeO3) or selenate (Na2SeO4) were treated. To compare the influence of Se (IV) and Se (VI) on the bioaccumulation and bioavailability of Hg, the levels of total Hg in different pak choi (Brassica chinensis L.) tissues (roots and shoots) and the distribution changes of Hg fractions in soil before planting and after harvest were determined as well as the Hg IR values in soils (relative binding intensity) were analyzed. Results showed that application Se (IV) reduced the concentrations of Hg in pak choi roots more than Se (VI). Hg concentrations were also decreased in pak choi shoots in Se (IV) treatments, while which notably increased in Se (VI) treatments. Thus, Se (IV) plays a more important role than Se (VI) in limiting the absorption and bioaccumulation of Hg in pak choi. Moreover, this inhibition may only significantly occur when Se (IV) is at an appropriate level (2.5mg/kg). In addition, the good correlations between the proportions of mobile Hg fractions (soluble and exchangeable fractions), IR values with the Hg concentrations in plants were observed. This affirmed the importance of the Hg fractions transformation and the IR indicator of Hg in the assessment of their bioavailability. Our findings regarding the importance of Se (IV) influence in reducing Hg bioaccumulation not only provided the correct appraisal about the effect of Se species on the inhibition of the Hg phytotoxicity to pak choi in dry land, but also be a good reference for selecting Se fertilizer forms (Se4+ or Se6+).


Oral glutamine challenge is a marker of altered ammonia metabolism and predicts the risk of hepatic encephalopathy.
The current therapies for hepatic encephalopathy (HE) are not completely effective in all patients, probably due to the physiopathological heterogeneity and the different conditions underlying the bout of HE. We hypothesized that oral glutamine challenge (OGC) is able to predict the risk of HE through the identification of various features and types of HE. We included 238 cirrhotic patients (198 without and 40 with a previous HE episode) that underwent OGC, obtaining baseline and 60 minutes post-load ammonia levels. Combined evaluation of baseline hyperammonemia (>78 mcg/dL) and impaired OGC (Δ >32 mcg/dL) defined low-, intermediate- and high-risk groups. Patients were censored at HE, liver transplantation and death or 6 years of follow-up. The 28.3% (56/198) of the main cohort suffered from HE during the follow-up. In the competing risk analysis, both intermediate- (subhazard ratio (sHR) 2.01 (95% CI 1.00-4.14); P = .048) and high-risk groups (sHR 4.67 (95% CI 2.19-9.98); P = .0001) were associated with the first HE episode, together with age and albumin. Similar results were found for repeated HE events. The cumulative incidence for HE of the high-risk group was two and four times greater than the intermediate- and low-risk groups, respectively. The HE grade was also higher in individuals with the greatest risk (P = .035). The most common precipitant factor was diuretics in the high-risk group, while infections and electrolyte imbalance predominated in the rest of patients. Oral glutamine challenge identified patients at risk of HE and defined specific features of the episodes. This tool could be useful in the decision-making process for the adequate management of HE.


Effects of chronic ethanol administration on the composition of membrane lipids in the mouse.
The relative proportions of the phospholipid fatty acids of erythrocyte membranes in mice were changed by chronic ethanol treatment and were not related to effects of the drug on nutrition, body temperature or experimental stress. Similar changes were observed using two different routes of ethanol administration and they did not reflect the metabolic effects of ethanol seen in the phospholipid fatty acids of whole liver. The observed increased content of saturated fatty acids and decreased content of polyunsaturated acids support the concept of adaptive changes taking place in the membrane during tolerance development to compensate for an increased membrane fluidity caused by ethanol. However, an increased content of the mono-unsaturated acid, octadecenoic (oleic), was found and there was no change in the cholesterol/phospholipid ratio. Other contrasting types of plasma membrane in mice showed different patterns of change in their phospholipid fatty acids during chronic ethanol administration. It is suggested that changes in membrane lipid composition could only partly account for an adaptation to ethanol-induced membrane disordering.


Oligodactyly and multiple synostoses of the extremities: two cases in sibs. A variant of Cenani-Lenz syndactyly.
Two sibs with a rare phenotype of oligodactyly with metacarpal, carpal, radioulnar, and metatarsal synostoses and shortening of the forearms were born of healthy parents. Genetic counselling with regard to future children of one of these sibs was given on the assumption of an autosomal recessive inheritance, which is highly probable, judging from the other rare familial cases found in the literature.


Cardiotoxicity of diazepam in cultured heart cells.
The responses of primary cultures of rat myocardial cells to diazepam (Valium) were evaluated. The cells were exposed to 4, 16 or 32 microgram/ml of diazepam for 1, 4 or 24 h. The cultures were evaluated for changes in beating activity and morphology and for cytotoxic effects. After the 1-h treatment exposure, the cultures exhibited tachycardia which was dose-dependent. The longer durations of treatment either produced arrhythmias or caused a loss of beating. Major morphological alterations observed were the formation pseudopodia and increased cytoplasmic granulation. Cytotoxicity was measured quantitatively by leakage of lactic dehydrogenase (LDH) from the cells into the media and by cell viability. Moderate amounts of LDH were leaked from the cells after exposure to diazepam for 4 h. After 24 h of treatment with the higher concentrations of diazepam, cell viability was greatly reduced.


Construction of myoglobin-amphiphilic alginate caprylamide-graphene composite modified electrode for the direct electron transfer between redox proteins and electrode and electrocatalysis of myoglobin.
To achieve the dispersion of the hydrophobic graphene (GR), the amphiphilic alginate caprylamide (ACA) was synthesized to fabricate electroactive Nafion/Mb-ACA-GR/CILE for the accurate determination of trichloroacetic acid (TCA). SEM observation, FT-IR and UV-Vis spectroscopic analysis indicated that ACA could tightly immobilize Mb and GR on the electrode surface by constructing biointerfaces, which not only provided Mb a suitable microenvironment to maintain its biological activity, but also shortened the distances between the active centers of Mb with carbon ionic liquid electrode (CILE), thus promoting the electron transfer rate. The electrochemical characterization of Nafion/Mb-ACA-GR/CILE showed that the direct electron transfer of Mb was realized on the modified electrode, which was attributed to the high electrical conductivity and excellent electrocatalytic activity of GR and good biocompatibility of ACA. Moreover, Nafion/Mb-ACA-GR/CILE exhibited good electrocatalytic activity towards TCA with the linear range from 2.5 to 47.3 mmol L-1 and lower K M app value of 8.3 mmol L-1. Moreover, the modified electrode also revealed good stability, reproducibility and accurate detection of tap-water, exhibiting great potential for the applications as the third-generation electrochemical biosensors.


Real-world safety and effectiveness of retreatment of Egyptian chronic hepatitis C patients not responding to NS5A inhibitor-based therapies.
The aim of this study was to assess the efficacy and safety of two protocols for retreatment of a cohort of Egyptian patients with chronic hepatitis C (CHC) who relapsed after NS5A inhibitor-based therapy. We conducted a prospective cohort study to assess the safety and efficacy of 12 weeks' retreatment with either combination of sofosbuvir/daclatasvir/simeprevir plus ribavirin (SOF/DCV/SMV/RBV, n = 45) or sofosbuvir/ombitasvir/paritaprevir/ritonavir plus ribavirin (SOF/OBV/PTV/r/RBV, n = 163) in patients who had previously failed NS5A inhibitors-based regimens. The primary end point was SVR 12 weeks after the end of treatment (SVR12). Safety follow-up data were recorded for 60 weeks after the end of treatment. Two hundred-eight patients were included in the study. Of them, 53.4% of patients were females and 40.4% had liver cirrhosis. The most common prior drug combinations were sofosbuvir/daclatasvir (n = 94) and sofosbuvir/daclatasvir plus ribavirin (n = 109). The overall SVR12 rates were 98.1%. In SOF/DCV/SMV/RBV group, 95.6% achieved SVR12, while in SOF/OBV/PTV/r/RBV group, the SVR12 rates were 98.8%. SVR12 was higher in cirrhotic patients (84/84) than noncirrhotic (120/124), P value = .0149. Regarding the safety outcomes, anaemia and fatigue were significantly higher in SOF/OBV/PTV/r/RBV group. Hepatocellular carcinoma (HCC) was reported in eight (3.8%) patients (four in each group). Of them, death was confirmed in four patients. Retreatment of Egyptian CHC relapsed patients with either sofosbuvir/daclatasvir/simeprevir plus ribavirin or sofosbuvir/ombitasvir/paritaprevir/ritonavir plus ribavirin is highly effective and well-tolerated for both noncirrhotic and compensated cirrhotic patients. Incidental de novo HCC and hepatic decompensation are comparable in the two groups.


In vivo study assessed meropenem and amikacin combination therapy against carbapenem-resistant and carbapenemase-producing Enterobacteriaceae strains.
Carbapenem-resistant Enterobacteriaceae (CRE), especially for carbapenemase-producing Enterobacteriaceae (CPE), is an emerging cause that pose a significant threat to public health. However, efficient therapy has not been established. We assessed the antimicrobial efficacy of meropenem (MEPM) and amikacin (AMK) combination therapy. Total eight isolates of Escherichia coli or Klebsiella pneumoniae, including CRE and/or CPE have carbapenemase genes were used. The relationship between phenotype and in vivo efficacy was assessed in neutropenic murine thigh infection model. Efficacy was determined using the change in bacterial density and survival rate. The combination therapy showed enhanced antimicrobial activities against CRE+/CPE+ and CRE+/CPE-K. pneumoniae isolates than MEPM monotherapy (0.63 ± 0.04 vs. 2.56 ± 0.24 ⊿log10 cfu/mL, p < 0.05; -1.05 ± 0.15 vs. -0.48 ± 0.30 ⊿log10 cfu/mL, p < 0.05). Likewise, the combination therapy showed enhanced antimicrobial activities against CRE+/CPE+ and CRE+/CPE-E. coli isolates than MEPM monotherapy (0.90 ± 0.68 vs. 1.86 ± 0.23 ⊿log10 cfu/mL, p < 0.05; -1.81 ± 0.06 vs. -0.88 ± 0.23 ⊿log10 cfu/mL, p < 0.05). Also, combination therapy group showed similar to higher survival rates in CRE + E. coli infection mice, compared to MEPM monotherapy group. Our results are the first supportive data to threat CRE infections with combination therapy of MEPM and AMK with in vivo model. The current results verify the promising utility of the combination therapy with MEPM and AMK against CRE isolates with a wide range of MEPM MICs.


Subtype-specific differences in the intracellular sorting of G protein-coupled receptors.
We have examined the subcellular distribution of three subtypes of adrenergic receptor by immunocytochemical localization of wild-type and epitope-tagged proteins expressed in Cos-7 and K293 cells. Two subtypes (beta 2 and M alpha 2-10H) are localized in the plasma membrane at steady state in untreated cells, while another subtype (M alpha 2-4H) is found both in the plasma membrane and in a population of intracellular vesicles. Within 15 min following the addition of adrenergic agonists, beta 2 and M alpha 2-10H receptors are differentially sorted; beta 2 receptors are selectively internalized to intracellular vesicles, which are distinct from those containing M alpha 2-4H receptors, while M alpha 2-10H receptors remain in the plasma membrane. Subtype-specific sorting suggests a new class of functional properties that may differentiate the signaling and regulation of homologous G protein-coupled receptors.


Thyroid cancer MR molecular imaging via SHP2-targeted nanoparticles.
Molecular imaging has generated a great demand to develop targeted contrast agents for MR imaging. In this study, we synthesized Src homology 2-containing phosphotyrosine phosphatase 2 (SHP2)-targeted and polylactic-co-glycolic acid--based nanoparticles (NPs), which encapsulated perfluoropentane and being chelated with gadolinium (Gd3+) as an efficient molecular probe for targeting MR imaging on thyroid carcinoma. These NPs displayed practical properties and favorable biocompatibility in vitro. Furthermore, they showed abilities to specifically target thyroid cancer and enhance MRI as a contrast agent in both in vitro and in vivo experiments. This novel MR molecular imaging based on this SHP2-targeted contrast agent provides a useful and non-invasive method for the early detection of thyroid carcinoma.


The value of the seagrass Posidonia oceanica: a natural capital assessment.
Making nature's value visible to humans is a key issue for the XXI century and it is crucial to identify and measure natural capital to incorporate benefits or costs of changes in ecosystem services into policy. Emergy analysis, a method able to analyze the overall functioning of a system, was applied to reckon the value of main ecosystem services provided by Posidonia oceanica, a fragile and precious Mediterranean seagrass ecosystem. Estimates, based on calculation of resources employed by nature, resulted in a value of 172 € m(-2)a(-1). Sediment retained by meadow is most relevant input, composing almost the whole P. oceanica value. Remarks about economic losses arising from meadow regression have been made through a time-comparison of meadow maps. Suggested procedure represents an operative tool to provide a synthetic monetary measure of ecosystem services to be employed when comparing natural capital to human and financial capitals in a substitutability perspective.


Cytomorphological comparison of mechanical and chemical defoaming of a yeast culture.
Defoaming of the medium by a rotating turbine during yeast cultivation, in contrast to defoaming by oil, results in fading away of cells of higher age categories and in an increase of dead cells proportion in the population. The negative effect of the mechanical defoaming device did not manifest itself in the amount of biomass obtained but in the cell numbers observed.


Two Distinct Hippocampal Astrocyte Morphotypes Reveal Subfield-Different Fate during Neurodegeneration Induced by Trimethyltin Intoxication.
Astrocytes comprise a heterogenic group of glial cells, which perform homeostatic functions in the central nervous system. These cells react to all kind of insults by changing the morphology and function that result in a transition from the quiescent to a reactive phenotype. Trimethyltin (TMT) intoxication, which reproduces pathological events in the hippocampus similar to those associated with seizures and cognitive decline, has been proven as a useful model for studying responses of the glial cells to neurodegeneration. In the present study, we have explored morphological varieties of astrocytes in the hippocampal subregions of ovariectomized female rats exposed to TMT. We have demonstrated an early loss of neurons in CA1 and DG subfields. Distinct morphotypes of protoplasmic astrocytes observed in CA1/CA3 and the hilus of control animals developed different responses to TMT intoxication, as assessed by GFAP-immunohistochemistry. In CA1 subregion, GFAP+ astrocytes preserved their domain organization and responded with typical hypertrophy, while the hilar GFAP+ astrocytes developed atrophy-like phenotype and increased expression of vimentin and nestin 7 days after the exposure. Both reactive and atrophied-like astrocytes expressed Kir4.1 in CA1/CA3 and the hilus of DG, respectively, indicating that these cells did not change their potential for normal activity at this time point of pathology. Together, the results demonstrate the persistence of two protoplasmic morphotypes of astrocytes, with distinct appearance, function, and fate after TMT-induced neurodegeneration, suggesting their pleiotropic roles in the hippocampal response to neurodegeneration.