Management of aneurysmal subarachnoid haemorrhage with intracerebral hematoma: Is there an indication for coiling first? Study of 44 cases.
Aneurysmal subarachnoid haemorrhage (ASH) with intracerebral hematoma (ICH) has a poor prognosis. The treatment is to secure the aneurysm and do an ICH evacuation. The aim of the study was to determine if aneurysm coiling followed by ICH evacuation is a viable alternative treatment compared to exclusive surgery, regardless of the clinical or paraclinical presentations. A retrospective study was conducted between 2004 and 2014, which included 44 patients. The patients were divided up in four groups. Two were principal groups: The clipped group (aneurysm clipping with ICH evacuation) and the coiled group (aneurysm coiling, followed by ICH evacuation); and two were subgroups of the latter: Aneurysm coiling with ICH evacuation after 24 hours and ICH evacuation followed by aneurysm coiling. We studied the demographic and radiologic characteristics, and the 3-month outcome. We included 17 patients in the coiled group: The outcome was better for the patients with World Federation of Neurosurgery (WFNS) scores of 1, 2 and 3; compared to the patients with WFNS scores 4 and 5. We included 16 patients in the clipped group: The outcome was better, compared the coiled group, for those patients with WFNS scores 4 and 5. Six patients were treated with aneurysm coiling, followed by ICH evacuation after 24 hours: 33% had a good outcome. Five patients were treated by ICH evacuation, followed by aneurysm coiling: None had a good outcome. It was necessary to realise a prospective study to compare the outcomes of patients with WFNS scores of 1, 2 or 3; between those with aneurysm coiling followed by ICH evacuation and aneurysm clipping with ICH evacuation, to determine the potential of using the coiling first, for these patients.


Differential roles of thought suppression and dispositional mindfulness in posttraumatic stress symptoms and craving.
Exposure to traumatic events often results in severe distress which may elicit self-medication behaviors. Yet, some individuals exposed to trauma do not develop post-traumatic stress symptoms and comorbid addictive impulses. In the wake of traumatic events, psychological processes like thought suppression and mindfulness may modulate post-traumatic stress and craving for substances. We examined the differential roles of mindfulness and suppression in comorbid post-traumatic stress and craving among a sample of 125 persons with extensive trauma histories and psychiatric symptoms in residential treatment for substance dependence. Results indicated that thought suppression, rather than extent of trauma history, significantly predicted post-traumatic stress symptom severity while dispositional mindfulness significantly predicted both post-traumatic stress symptoms and craving. In multiple regression models, mindfulness and thought suppression combined explained nearly half of the variance in post-traumatic stress symptoms and one-quarter of the variance in substance craving. Moreover, multivariate path analysis indicated that prior traumatic experience was associated with greater thought suppression, which in turn was correlated with increased post-traumatic stress symptoms and drug craving, whereas dispositional mindfulness was associated with decreased suppression, post-traumatic stress, and craving. The maladaptive strategy of thought suppression appears to be linked with adverse psychological consequences of traumatic life events. In contrast, dispositional mindfulness appears to be a protective factor that buffers individuals from experiencing more severe post-traumatic stress symptoms and craving.


Astrocytic VEGFA: An essential mediator in blood-brain-barrier disruption in Parkinson's disease.
The integrity of blood-brain-barrier (BBB) is essential for normal brain functions, synaptic remodeling, and angiogenesis. BBB disruption is a common pathology during Parkinson's disease (PD), and has been hypothesized to contribute to the progression of PD. However, the molecular mechanism of BBB disruption in PD needs further investigation. Here, A53T PD mouse and a 3-cell type in vitro BBB model were used to study the roles of α-synuclein (α-syn) in BBB disruption with the key results confirmed in the brains of PD patients obtained at autopsy. The A53T PD mouse studies showed that the expression of tight junction-related proteins decreased, along with increased vascular permeability and accumulation of oligomeric α-syn in activated astrocytes in the brain. The in vitro BBB model studies demonstrated that treatment with oligomeric α-syn, but not monomeric or fibrillar α-syn, resulted in significant disruption of BBB integrity. This process involved the expression and release of vascular endothelial growth factor A (VEGFA) and nitric oxide (NO) from oligomeric α-syn treated astrocytes. Increased levels of VEGFA and iNOS were also observed in the brain of PD patients. Blocking the VEGFA signaling pathway in the in vitro BBB model effectively protected the barrier against the harmful effects of oligomeric α-syn. Finally, the protective effects on BBB integrity associated with inhibition of VEGFA signaling pathway was also confirmed in PD mice. Taken together, our study concluded that oligomeric α-syn is critically involved in PD-associated BBB disruption, in a process that is mediated by astrocyte-derived VEGFA.


Changes in quality parameters of orange juice deacidified by ion exchange resins.
In this study, the effectiveness of five different ion exchange resins (Amberlite-IRA96,-FPA51,-FPA53,-FPA54 and Lewatit-S4528) in reducing the acidity of Valencia orange juice and effects on juice quality were determined. The greatest decrease in titratable acidity (65%) and increase (23%) in pH were determined in the juices deacidified using Amberlite-FPA51. The greatest color change (ΔE*=4.89) was identified by treatment of Lewatit-S4528. Ascorbic acid contents were decreased between 12 and 28% by deacidification. Changes ((-4.43)-(+8.18)%) in the carotenoid contents were also assessed in juices treated with different resins. The changes in amount of hydroxycinnamic, hydroxybenzoic acids, flavanones, flavonol and flavone were determined. The largest decrease (ca.28%) in total phenolics was observed with Amberlite-FPA54. The most abundant organic acids in juices were citric acid followed by quinic, malic, ascorbic, tartaric, succinic and oxalic acid, which were decreased after deacidification. Lowest color change and highest carotenoid content were obtained with Amberlite-FPA54.


Alterations of gait in neuromuscular disease.
Individuals affected with neuromuscular disorders have multisystem pathologies. Among the systems most affected are those involving muscle function and integration of moving leading to both subtle and obvious changes in the individual's gait. An ability to recognize the characteristic changes in gait of many neuromuscular problems is helpful in recognizing these disorders leading to improved referrals and timely diagnoses. The characteristic gait changes of neuromuscular and neurologic diseases is reviewed.


[Personal experiences of a physician with legal proceedings].
According to the author's experience with a judicial inquiry, the borderline between the right of the prosecutor to get an insight into the patients file and the right of the physician to refuse the disclosure of the patient's medical history is very much blurred. Even if the inquiry is directed just against an unknown person, a physician should be aware that the Department of Public Prosecution might take stiffening procedural steps to enforce its demand. At any rate, the physician's position to keep the patient's data secret is very weak in such a situation.


Compliance with hormone therapy.
The analysis of compliance with hormonal replacement therapy in postmenopausal women must take into account the physician's knowledge of and willingness to prescribe such treatment and the patient's acceptance of the risks and benefits. Studies have shown that most women receiving oral therapy take their medication only sporadically, and those who discontinue treatment usually do so because of the fear of endometrial cancer. Both physicians and patients should be made aware that the addition of progestogen can greatly lessen this risk. Estrogen therapy has been shown to offer significant benefits, notably a reduction in the incidence of osteoporosis-related fractures. Epidemiologic models can be useful in showing both physicians and patients that hormonal treatment is safe and effective. Noncompliance, stemming from side effects or the problem of forgetting to take medications, can be improved through the use of the transdermal estrogen formulation. This product has been associated with excellent tolerability; local and systemic adverse reactions have been minimal, and any problems with unscheduled bleeding or hyperplasia can be circumvented through the addition of progestogens.


Efficacy and safety of subanesthetic doses of esketamine combined with propofol in painless gastrointestinal endoscopy: a prospective, double-blind, randomized controlled trial.
Painless gastrointestinal endoscopy is widely used for the diagnosis and treatment of digestive diseases. At present, propofol is commonly used to perform painless gastrointestinal endoscopy, but the high dose of propofol often leads to a higher incidence of cardiovascular and respiratory complications. Studies have shown that the application of propofol combined with ketamine in painless gastrointestinal endoscopy is beneficial to reduce the dosage of propofol and the incidence of related complications. Esketamine is dextrorotatory structure of ketamine with a twice as great anesthetic effect as normal ketamine but fewer side effects. We hypothesized that esketamine may reduce the consumption of propofol and to investigate the safety of coadministration during gastrointestinal endoscopy. A total of 260 patients undergoing painless gastrointestinal endoscopy (gastroscope and colonoscopy) were randomly divided into P group (propofol + saline), PK1 group (propofol + esketamine 0.05 mg/kg), PK2 group (propofol + esketamine 0.1 mg/kg), and PK3 group (propofol + esketamine 0.2 mg/kg). Anesthesia was achieved by 1.5 mg/kg propofol with different doses of esketamine. Propofol consumption per minute was recorded. Hemodynamic index, pulse oxygen saturation, operative time, induction time, awakening status, orientation recovery time, adverse events, and Mini-Mental State Examination (MMSE) were also recorded during gastrointestinal endoscopy. Propofol consumption per minute was 11.78, 10.56, 10.14, and 9.57 (mg/min) in groups P, PK1, PK2, and PK3, respectively; compared with group P, groups PK2 and PK3 showed a decrease of 13.92% (P = 0.021) and 18.76% (P = 0.000), respectively. In all four groups, systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), but not pulse oxygen saturation (SpO2) significantly decreased (P = 0.000) immediately after administration of induction, but there were no significant differences between the groups. The induction time of groups P, PK1, PK2, and PK3 was 68.52 ± 18.394, 64.83 ± 13.543, 62.23 ± 15.197, and 61.35 ± 14.470 s, respectively (P = 0.041). Adverse events and psychotomimetic effects were observed but without significant differences between the groups. The combination of 0.2 mg/kg esketamine and propofol was effective and safe in painless gastrointestinal endoscopy as evidenced by less propofol consumption per minute, shorter induction time, and lower incidence of cough and body movement relative to propofol alone. The lack of significant differences in hemodynamic results, anesthesia-related indices, adverse events, and MMSE results showed the safety to apply this combination for painless gastrointestinal endoscopy. Trial registration This study was registered with China Clinical Trial Registration on 07/11/2020 (registration website: chictr.org.cn; registration numbers: ChiCTR https://clinicaltrials.gov/ct2/show/2000039750 ).


Expression and purification of mouse TIMP-1 from E. coli.
Tissue inhibitors of metalloproteinases (TIMPs) constitute a family of secreted glycoproteins involved in regulating extracellular matrix degradation in both normal and malignant tissues. We have expressed a cDNA clone of mouse TIMP-1 as a 22-kDa protein with 12 cysteine residues in E. coli and purified protein that shows inhibitory activity against collagenase following renaturation by chemical means. The low specific activity and circular dichroism measurements suggest, however, that the renaturation of the mouse recombinant (non-glycosylated) protein is not efficient under the conditions we have used, indicative of either thermodynamic instability or the transition to kinetic intermediates which have very low in vitro refolding rates.


Perineural and lymphovascular invasion in squamous cell carcinoma of the tongue.
Perineural invasion (PNI) and lymphovascular invasion (LVI) may be adverse prognostic indicators in squamous cell carcinoma (SCC) of the tongue. The percentages of histological PNI and LVI were determined in 335 patients with tongue SCC. Sixty tumours originally reported as negative for these features were tested to determine how many more were positive with "immunohistochemical enhancement." PNI was found in 141 (42.1%) and LVI in 51 (15.2%) patients. 79.4% of the 141 patients who had PNI and 72.6% of the 51 with LVI had a T3 or T4 tumour. Lymph node metastasis was identified in 145 (51.2%) of the 280 patients who had undergone neck dissection; 58.2% of the 141 patients with PNI and 80.4% of the 51 patients with LVI had lymph node metastasis. There was a highly statistically significant correlation between PNI with increasing pT (P < .00001) and pN (P < .0001) stage, and a statistically significant correlation between LVI and pT stage (P < .001), the association of LVI with pN status could not be reliably tested statistically. Immunohistochemistry for S100 identified five further cases of PNI, but review of the original H&E showed the feature was present in four and had been missed at original reporting. CD31 identified three further possible cases of LVI and D2-40 none. The endothelium of some vascular channels was positive for both CD31 and D2-40 and cross-reactivity with other cells compromised interpretation. Histological identification of PNI and LVI per se remains of uncertain prognostic significance. "Immunohistochemical enhancement" offered little benefit.


Dilational rheology of oil/water interfaces covered by amphiphilic polysaccharides derived from dextran.
This work studied the adsorption at dodecane/water interface of amphiphilic polysaccharides derived from dextran (a nonionic bacterial polysaccharide) by random attachment of phenoxy groups along the chains (between 10 and 20 attached phenoxy groups per 100 glucose repeat units). The long-time kinetics of interfacial tension decrease was satisfactorily described assuming diffusion-limited adsorption of hydrophobic units (over 4h). Dilational rheology of dodecane/water interface was studied for the first time with that kind of amphiphilic polysaccharides and evidenced a significant elastic component. For all dextran derivatives, experimental results were conveniently described using Lucassen-van den Tempel model which assumed diffusion-limited of surface active species. The characteristic frequency increased with the number of attached phenoxy groups and its order of magnitude (10-3-10-2rad.s-1) was consistent with estimations based on the previous model. Experimental results were compared to those obtained with commercial stabilizers like Pluronics (L64, P105, F68 and F127) and Tween 80.


Outcomes after Thrombectomy for Minor Stroke: A Meta-Analysis.
To determine the outcomes after mechanical thrombectomy (MT) versus medical management in patients with minor stroke symptomatology. A meta-analysis was performed for studies reporting outcomes after MT, either as stand-alone therapy or with intravenous thrombolysis in patients with minor stroke and large-vessel occlusion. Fourteen studies with 2134 patients met the selection criteria and were included. Two studies compared immediate thrombectomy versus best medical management (with rescue thrombectomy) and the odds ratios of excellent outcomes, good outcomes, mortality and incidence of symptomatic intracranial hemorrhage (sICH) after immediate thrombectomy versus best medical management were 1.07 (95% confidence interval [CI] 0.93-1.22%), 1.15 (95% CI 1.05-1.25), 0.65 (95% CI 0.30-1.38), and 2.89 (95% CI 0.82-10.13), respectively. Among the 8 studies that compared MT outcomes versus medical management (without thrombectomy), odds ratios of excellent outcomes, good outcomes, mortality, and incidence of sICH after MT versus medical management were 0.98 (95% CI 0.89-1.07), 0.94 (95% CI 0.89-1.00), 1.61 (95% CI 1.08-2.41), and 2.59 (95% CI 1.35-4.96), respectively. Among all 14 studies, pooled proportions of excellent outcomes, good outcomes, mortality, and sICH after thrombectomy were 58.7%, 76.2%, 6.82%, and 3.23%, respectively. Our study shows significant selection bias and heterogeneity in the literature with differences in baseline characteristics (age, stroke severity, prestroke modified Rankin Scale score, side of infarct, vessel and site of occlusion, use of intravenous thrombolysis, criteria for clinical deterioration, and selection bias for rescue MT and rates of reperfusion), emphasizing the need for a randomized controlled trial.


The fate of DNA satellites I, II, III and ribosomal DNA in a familial dicentric chromosome 13:14.
In a family with a stable dicentric 13:14 translocation chromosome, the distribution of DNA sequences complementary to satellite DNAs I, II and III and ribosomal RNA were studied. The translocation chromosome showed a loss of sequences complementary to all three satellite DNAs, located in the short arms of the acrocentric chromosomes, but slightly more of the sequences complementary to satellite I were retained than of the other two satellite DNAs. The fact that material was lost from all three satellites indicates that they are not present as single discrete blocks in these chromosomes, when we would expect to find the distal sequences lost and the proximal ones retained, but consist of interspersed blocks with each sequence represented by more than one, and probably several blocks. There was a total loss of ribosomal DNA from the nucleolar organiser regions of the chromosomes involved in the 13:14 translocation, but an interesting finding was the presence of extra ribosomal DNA and satellite DNAs I, II and III in one chromosome 22 which was found in seven out of nine individuals of the family with the 13:14 translocation, and in only one of five individuals without the translocation. There may be a compensatory mechanism present when certain sequences are elminated during chromosomal rearrangements. The relationship of such mechanisms to reproductive fitness is discussed.


Reprogramming the tumor microenvironment to enhance adoptive cellular therapy.
The frontiers of cancer immunotherapy are extending in terms of both the range of cancer types that can potentially be targeted and the types of therapeutics that are in clinical development. The use of adoptive cellular therapy (ACT) and its derivative, chimeric antigen receptor (CAR) T cells, is currently limited to hematological malignancies and immunogenic cancers such as melanoma and renal cell carcinoma. Although ACT utilizing ex vivo expanded tumor-infiltrating lymphocytes (TIL) or engineered CAR/TCR T cells have undergone clinical trials for other solid cancers, their efficacy to date has been limited. This may be due, in part, to the immunosuppressive nature of the tumor microenvironment. The development of novel combination approaches which target the immunosuppressive network engineered by tumors has raised the possibility of using ACT for a broader range of cancers. This review summarizes the potential of such strategies and outlines the clinical relevance of these observations.


Glucocorticoid effects on bone strength in children with renal diseases.
Glucocorticoids (GC) are essential medicines for idiopathic steroid-sensitive nephrotic syndrome (ISSNS) and IgA nephropathy (IgAN), with good clinical results. However, they cause bone fragility. The aim of this study was to elucidate GC effects on bone strength assessed as bone mineral density (BMD) and bone quality, using bone turnover markers (BTM), in children with ISSNS or IgAN. Eleven children with ISSNS and 13 with IgAN were included. All the patients received GC treatment according to each protocol. The BMD and BTM-serum alkaline phosphatase (S-ALP), tartrate-resistant acid phosphatase 5b (S-TRACP-5b), and undercarboxylated osteocalcin (S-ucOC)-were measured from the initiation of steroid treatment (STx) to the end of STx in both groups. In ISSNS, S-ALP and S-ucOC levels were decreased significantly at 1 month. BMD and S-TRACP-5b levels showed no significant change through this observation period. In IgAN, BMD and S-ALP levels were decreased significantly at 1 and 3 months, respectively, and recovered to baseline at 10 months after the initiation of GC dosage reduction. S-TRACP-5b levels were decreased significantly at 3 months and remained lower than at baseline through the observation period. In both groups, S-ucOC levels did not directly reflect bone strength. This study clarified the following three points regarding GC effects on bone strength in children with ISSNS or IgAN: first, S-ALP is a more sensitive bone quality marker than S-TRACP-5b; second, BMD loss was observed only when both S-ALP and S-TRACP-5b levels decreased, and third, S-ucOC levels do not directly reflect bone strength.


Evaluation of a mobile phone-based, advanced symptom management system (ASyMS) in the management of chemotherapy-related toxicity.
To evaluate the impact of a mobile phone-based, remote monitoring, advanced symptom management system (ASyMS) on the incidence, severity and distress of six chemotherapy-related symptoms (nausea, vomiting, fatigue, mucositis, hand-foot syndrome and diarrhoea) in patients with lung, breast or colorectal cancer. A two group (intervention and control) by five time points (baseline, pre-cycle 2, pre-cycle 3, pre-cycle 4 and pre-cycle 5) randomised controlled trial. Seven clinical sites in the UK; five specialist cancer centres and two local district hospitals. One hundred and twelve people with breast, lung or colorectal cancer receiving outpatient chemotherapy. A mobile phone-based, remote monitoring, advanced symptom management system (ASyMS). Chemotherapy-related morbidity of six common chemotherapy-related symptoms (nausea, vomiting, fatigue, mucositis, hand-foot syndrome and diarrhoea). There were significantly higher reports of fatigue in the control group compared to the intervention group (odds ratio = 2.29, 95%CI = 1.04 to 5.05, P = 0.040) and reports of hand-foot syndrome were on average lower in the control group (odds ratio control/intervention = 0.39, 95%CI = 0.17 to 0.92, P = 0.031). The study demonstrates that ASyMS can support the management of symptoms in patients with lung, breast and colorectal cancer receiving chemotherapy.


Best international practices for road safetyRoad transportation is not only a vital component of how cities grow and how society functions, but it is also a significant factor that can affect the frequency of serious accidents and traumas. Human failure is not omitted, addressing it at the system level, involving the prevention of fatal and severe accidents, reducing mortality, and the cost itself. With the aim of outlining the best ways to improve road traffic, and prevent road trauma we have observed the experience of different countries in this regard. As materials and methods, we used Pubmed and Google Academic databases to identify and analyze in detail each strategy or plan with the period included in the study 2010- 2022, in 10 countries. The results show that each of the countries researched followed the example of the Global Plan and implemented respective strategies. Each country focused on particular errors in the country and formed different methods of improvement. As a suggestion for developing the updated strategy, it would be effective to establish the current gaps in their own system more clearly. In conclusion, road safety is a shared responsibility, recognizing the role of policymakers as well as planners and public health professionals, all parts of the system need to be strengthened to multiply their effects so that if one part fails, people are still protected.


Genetic ablation of PRAS40 improves glucose homeostasis via linking the AKT and mTOR pathways.
Alterations in PI3K-AKT-mTOR signaling have been implicated in diabetes. This study assessed whether disruption of PRAS40, a substrate of AKT and component of mTORC1, would alter glucose homeostasis and prevent hyperglycemia in the streptozotocin (STZ)-induced diabetes mouse model. PRAS40 ablation resulted in a mild lowering of blood glucose levels and glycated hemoglobin (HbA1C), a lowered insulin requirement, and improved glucose tolerance in untreated PRAS40 gene knockout (PRAS40(-/-)) as compared to wild-type (PRAS40(+/+)) mice. Diabetes was then induced in these mice using STZ at 50mg/kg/day over five days. Following STZ-treatment, PRAS40(-/-) mice exhibited significantly lower blood glucose and HbA1C levels than PRAS40(+/+) mice. Liver tissue of PRAS40(-/-) mice and shPRAS40 Hep3B cells showed increased activation of AKT (p-AKT T308) and mTORC1 (p-p70S6K) signaling as well as decreased p-AKT (S473) and increased p-IRS1 (S612) protein levels. Altered tissue gene expression of several glucose transporters (GLUT) and increased hepatic GLUT4 protein levels were observed in PRAS40(-/-) as compared to PRAS40(+/+) mice. In summary, PRAS40 deletion significantly attenuates hyperglycemia in STZ-induced PRAS40(-/-) mice through increased hepatic AKT and mTORC1 signaling, a lowered serum insulin requirement, and altered hepatic GLUT4 levels.


Does alpha-lipoic acid-loaded nanostructured lipid carriers improve post-thawed sperm quality and ameliorate apoptosis-related genes of rooster sperm?
Oxidative stress could be prevented by antioxidant-loaded nanoparticles. The purpose of this study was to assess the effects of 10 (A10), 20 (A20), 30 (A30), 40 (A40), and 50 (A50) μM alpha-lipoic acid and alpha-lipoic acid nanostructured lipid carriers (ALN) at 10 (ALN10), 20 (ALN20), 30 (ALN30), 40 (ALN40), and 50 (ALN50) μM on post-thawed sperm quality, fertility, and apoptosis-related genes of rooster sperm. The extender supplemented with ALN30 led to higher total and progressive motility, straight-line velocity, and linearity in comparison to the control group. The ALN30 resulted in higher percentage of mitochondria activity and glutathione peroxidase level compared with control (P < 0.05). The extender supplemented with ALN30 led to lower percentage of apoptotic sperm, when compared with the control. CASPASE 3 expression in ALN30 was lower (P < 0.05) than the other groups. The results showed that BCL-2 mRNA expression of sperm was significantly (P < 0.05) higher in ALN30 compared with the other groups (P < 0.05). Higher percentages of fertility and hatchability rates were observed in ALN30 group. The results indicate that ALN30 could be regarded as a novel potential cryoprotectant for the cryopreservation of rooster semen. Therefore, nanostructured lipid carriers improve not only the active compound (such as alpha-lipoic acid) of biomedical applicability but also the potential for industrial application in sperm cryopreservation.


Three-Dimensional Live Imaging of Filamentous Fungi with Light Sheet-Based Fluorescence Microscopy (LSFM).
We describe a method for the three-dimensional live imaging of filamentous fungi with light sheet-based fluorescence microscopy (LSFM). LSFM provides completely new opportunities to investigate the biology of fungal cells and other microorganisms with high spatial and temporal resolution. As an example, we study the established aging model Podospora anserina. The protocol explains the mounting of the live fungi for the light sheet imaging, the imaging procedure and illustrates basic image processing of data.


Miniaturizing the laparoscope: current applications of micro- and minilaparoscopy.
Technological advancements have enabled miniaturization of the endoscope without significant compromise to either diagnostic or operative abilities. With a complement of instruments <5 mm in diameter, newer minimally invasive techniques have been developed to decrease the pain and trauma associated with surgical procedures. These advancements involve additional options for peritoneal access as well as facilitating diagnostic evaluation of the pelvis. Although the robustness and durability of the smaller instruments is an area of concern, a thorough understanding of the clinical advantages and disadvantages has the potential to improve patient outcomes.


A theory analysis of Mastery Learning and Self-Regulation.
This analysis examines the applicability of Mastery Learning and Self-Regulation theories as a combined approach to nursing education. The conclusion may serve as a foundation for an innovative, evidence-based approach to teaching nurses resulting in improved patient care and outcomes. Mastery Learning promotes a teaching approach that supports achievement of content taught. Self-Regulation describes individual student's actions or behaviors that promote learning. The effectiveness of Mastery Learning has been documented in current healthcare literature. Research on Self-Regulation, primarily conducted among students from middle-school through graduate education, confirms that Self-Regulation strategies can enhance skill development and promote job performance. The evidence is void of analysis of the two theories. Literature reviewed was retrieved from ERIC, CINAHL, PubMed, PsycINFO and Sage Premier, for the years 1968-2014. Search terms included: mastery learning, self-regulation and nursing education. Walker and Avant's (2011) Strategies for Theory Construction in Nursing was used as the framework for the analysis. This analysis supports the applicability of both Mastery Learning and Self-Regulation Theories to nursing education. Conducting educational research on the application of Mastery Learning theory and its influence on Self-Regulating practices might reveal a new approach for how nurses are educated resulting in improved patient care outcomes.


Enhanced biodegradation of hexachlorocyclohexane (HCH) isomers by Sphingobium sp. strain D4 in the presence of root exudates or in co-culture with HCH-mobilizing strains.
Lindane and other 1,2,3,4,5,6-hexachlorocyclohexane (HCH) isomers are persistent organic pollutants highly hydrophobic, which hampers their availability and biodegradation. This work aimed at (i) investigating genes encoding enzymes involved in HCH degradation in the bacterium Sphingobium sp. D4, (ii) selecting strains, from a collection of environmental isolates, able to mobilize HCHs from contaminated soil, and (iii) analysing the biodegradation of HCHs by strain D4 in co-culture with HCH-mobilizing strains or when cultivated with root exudates. Fragments of the same size and similar sequence to linA and linB genes were successfully amplified. Two isolates, Streptomyces sp. M7 and Rhodococcus erythropolis ET54b able to produce emulsifiers and to mobilize HCH isomers from soil were selected. Biodegradation of HCH isomers by strain D4 was enhanced when co-inoculated with HCH mobilizing strains or when cultivated with root exudates. The degrader strain D4 was able to decompose very efficiently HCHs isomers, reducing their concentration in soil slurries by more than 95% (from an average initial amount of 50 ± 8 mg HCH kg-1 soil) in 9 days. The combination of HCH-degrading and HCH-mobilizing strains can be considered a promising inoculum for future soil bioremediation studies using bioaugmentation techniques or in combination with plants in rhizodegradation assays.


Primary right ventricular osteosarcoma.
A 41-year-old man suffering from dyspnea on exertion was found to have a mass located on the right ventricle. Resection of the tumour required reconstruction of the right ventricular outflow tract and replacement of the pulmonary valve. Histopathology confirmed the diagnosis of high-grade osteosarcoma.


Prevalence, diagnosis, and pharmacological treatment of mood disorders in HIV disease.
Human immunodeficiency virus seropositive (HIV+) individuals are at a heightened risk of developing mood disorders and related syndromes. Over the past several decades, increased rates of mood disorders, including depression and mania, have been reported among HIV+ individuals. Because alterations in mood may impact on quality of life and perhaps reduce adherence to antiretroviral treatment regimens that are critical for preventing disease progression, recognition and effective treatment of mood disorders is essential. There are accumulating data showing that antidepressants and mood stabilizers, as well as other novel agents, might benefit HIV+ individuals suffering from a concomitant mood disturbance. This review highlights the relevant studies that have examined prevalence rates of mood disorders in HIV+ individuals, characteristics of HIV disease that influence the diagnosis and psychopharmacologic treatment of mood disorders, including complex interactions with antiretroviral medications, as well as the available evidence regarding the efficacy of agents used to treat depression and mania in the context of HIV disease.


New Middle Permian palaeopteran insects from Lodève Basin in southern France (Ephemeroptera, Diaphanopterodea, Megasecoptera).
Three new palaeopteran insects are described from the Middle Permian (Guadalupian) of Salagou Formation in the Lodève Basin (South of France), viz. the diaphanopterodean Alexrasnitsyniidaefam. n., based on Alexrasnitsynia permianagen. etsp. n., the ParelmoidaePermelmoa magnificagen. etsp. n., and Lodevohymen lapeyrieigen. etsp. n. (in Megasecoptera or Diaphanopterodea, family undetermined). In addition the first record of mayflies attributed to family Syntonopteridae (Ephemeroptera) is reported. These new fossils clearly demonstrate that the present knowledge of the Permian insects remains very incomplete. They also confirm that the Lodève entomofauna was highly diverse providing links to other Permian localities and also rather unique, with several families still not recorded in other contemporaneous outcrops.


Octreotide in patients with active ulcerative colitis treated with high dose corticosteroids (OPUS 1).
In ulcerative colitis the intestinal somatostatin content is reduced. Somatostatin has several immune-inhibitory effects. In vitro it diminishes activity of intestinal lymphocytes and peripheral blood monocytes. Its long-acting analogue octreotide has beneficial effects on mucosal damage in acute experimental acetic acid colitis in rats. To determine the potential benefits of octreotide as a treatment for patients with severe ulcerative colitis treated with high dose corticosteroids. Forty-two patients with severe ulcerative colitis (more than 10 points on the Powell-Tuck scoring system and mucosal disease Heatly grade III or IV). In a multi-centre, double blind, placebo-controlled trial all patients were treated with oral 5-ASA (1.6-2.4 g daily) and high dose corticosteroids (tapering off from 60 to 80 mg daily). They were randomly assigned to receive subcutaneous placebo (n = 22) or octreotide 500 microg (n = 20) thrice daily during 21 days. Clinical and endoscopic disease activity, histology and laboratory parameters were obtained during the study period. Clinical disease activity for both octreotide and placebo were not significantly different at baseline and after 21 days of treatment. Endoscopic disease activities (mean +/- SD) changed from 12.5 +/- 4.7 to 7.2 +/- 5.3 for octreotide, and from 11.5 +/- 5.0 to 5.0 +/- 3.4 for placebo (NS). Seven patients from both groups received additional treatment (colectomy (n = 6), cyclosporin (n = 1)). Adverse events occurred equally in both groups. Subcutaneous administration of octreotide 500 microg thrice daily is not of additional benefit as adjuvant therapy to high dose corticosteroids in severe ulcerative colitis.


Making contact.
Gay men can notify ex-partners of sexually transmitted infections through a messaging service being piloted at seven clinics.


Molecular events associated with Macrovipera lebetina obtusa and Montivipera raddei venom intoxication and condition of biomembranes.
Studies on the interaction of snake venom and organized lipid interfaces have been conducted using a variety of systems, including BLMs, SUVs and GUVs. The present study was undertaken to elucidate how the plastic properties (namely, its microviscosity, thickness, permeability) of model membranes from native lipids of different tissues of rats change in the course of Macrovipera lebetina obtusa (MLO), Montivipera raddei (MR) and Naja kaouthia (NK) venoms processing. The presence of viper venom in organism leads to increasing of the electrical resistance of BLMs from liver and muscle lipids approximately on a sequence, while the BLMs from brain lipids have not shown noticeable differences of plastic properties compared to the control. Giant unilamellar vesicles (GUVs) with a mean diameter of 30μm have a minimum curvature and mimic cell membranes in this respect. Snake venom was added to the sample chamber before the vesicles were formed. The membrane fluorescence probes, ANS and pyrene, were used to assess the state of the membrane and specifically mark the phospholipid domains. Fluorescent spectra were acquired on a Varian fluorometer instrument. ANS and pyrene allow us to quantify the fluidity changes in the membrane by measuring of the fluorescence intensity. The presence of viper venom in GUVs media reveals a noticeable decreasing of membrane fluidity compared to the control, while the binding of fluorophores with GUVs modified by venom leads to the appearance of channel activity. These studies also emphasize the importance of a membrane surface curvature for its interaction with enzymatic components of venom.


Role of kinins in the renoprotective effect of angiotensin-converting enzyme inhibitors in experimental chronic renal failure.
The aim of this study was to investigate whether the renoprotective effect of angiotensin-converting enzyme inhibitors (ACEIs) following 5/6 renal mass reduction is due in part to the potentiation of kinins. Three groups of rats with 5/6 renal mass reduction were studied during the 14 weeks following surgery. One group received no therapy (control); the second group was treated from the beginning with the ACEI ramipril (1 mg/kg/day) added to the drinking water, and the last group received ramipril plus a beta2-bradykinin antagonist, HOE 140 (500 microg/kg/day) via osmotic minipumps. Plasma creatinine did not change in any group during the study. Urinary protein excretion rose in the controls from 9.18+/-1.6 to 45.0+/-5.6 mg/24 h at the end of the study. In ramipril group proteinuria was prevented (initial 7.5+/-1.0 and final 8.6+/-0.8 mg/24h). The effect of ramipril was abolished by HOE 140 (initial 11.6+/-2.0 and final 38.9+/-11 mg/ 24 h). The systolic blood pressure of the controls increased from 106+/-2 to 144+/-5 mm Hg at the 14th week. Ramipril abolished the increase in systolic blood pressure. The effect of ramipril was reverted by HOE 140 (initial 108+/-2 and final 140+/-9 mmHg). Control rats had more severe histopathologic changes. Those animals receiving ramipril + HOE 140 displayed less severe glomerular changes, while rats treated only with ramipril had mild alterations. Thus the glomerular injury score was 2.11+/-0.32 for controls, 1.53+/-0.52 for rats treated with ramipril + HOE 140, and 0.06+/-0.04 for rats treated only with ramipril. The glomerular area was 20,886+/-1,410, 19,693+/-2,200 and 14,352+/-3,200 microm2, respectively, for the 3 groups. These results suggest that the protective effect of ACEIs in the development of chronic renal failure is partially mediated by kinins.


Patient perspectives on telemedicine use in rheumatology during the COVID-19 pandemic: survey results from the COVID-19 Global Rheumatology Alliance.
The COVID-19 pandemic resulted in rapid adoption of telemedicine in rheumatology. We described perspectives of patients with rheumatic diseases related to telemedicine use. An anonymous online survey for people with rheumatic diseases was launched in January 2021. We collected data on reasons for telemedicine use, perceived benefits, disadvantages and obstacles of telemedicine, perceived telemedicine effectiveness for different clinical tasks, level of satisfaction with telemedicine use, and future preferences for telemedicine. We summarized results with descriptive statistics and identified themes in free text responses to describe perspectives of telemedicine qualitatively. We received 596 complete responses (85% female and 47% 41-60 years old). During the COVID-19 pandemic, 78% (467/596) of respondents used telemedicine, and 61% (283/467) of telemedicine users reported that telemedicine was as effective or more effective than an in-person visit. Younger participants and those in North America reported effectiveness and satisfaction with telemedicine at higher frequencies. Participants reported similar effectiveness to in-person visits for making medication changes and discussing disease symptoms or complications. Most respondents found telemedicine at least as effective as in-person visits. Participants found telemedicine to be effective for specific scenarios, such as making medication changes and discussion of disease activity. Telemedicine may continue to be of importance in the care of patients with rheumatic diseases post pandemic, but likely for specific subsets of patients for specific visit indications. Key Points • Most patients with rheumatic disease found telemedicine as effective as in-person visits, particularly for some indications.


Influence of various temperatures, seed priming treatments and durations on germination and growth of the medicinal plant Aspilia africana.
For millennia, Aspilia africana has been used across Africa to treat various diseases including malaria, wounds, and diabetes. In this study, temperature influenced the in vitro germination of A. africana with highest final germination percentage (FGP) and germination index (GI) of 65.0 ± 7.64% and 2.26 ± 0.223, respectively, at 19.8 °C. Priming seeds with H2O, KNO3, and GA3 (gibberellic acid 3) improved both in vitro germination and ex vitro emergence of A. africana seeds. Seed priming with [Formula: see text] M GA3 produced overall highest in vitro FGP (from 90.0 ± 4.08% to 100 ± 0.00%) and GI (from 2.97 ± 0.385 to 3.80 ± 0.239) across all priming durations. Seeds primed with KNO3 had better germination parameters for 6 and 12 h compared to 18 and 24 h. Furthermore, the highest in vitro FGP (100 ± 0.00%) was observed in seeds primed for 12 h with [Formula: see text] M GA3. Ex vitro A. africana seed emergence was significantly enhanced by GA3 priming. Priming A. africana seeds with H2O, KNO3, and GA3 improved their growth after 3 months, with the overall best growth for seeds primed with [Formula: see text] M GA3. Seed priming of A. africana is a feasible approach for improving germination and seed emergence, and enhancing plant growth.


External validation of NTCP-models for radiation pneumonitis in lung cancer patients treated with chemoradiotherapy.
Normal tissue complication probability (NTCP) models can be used to estimate the risk of radiation pneumonitis (RP). The aim of this study was to externally validate the most frequently used prediction models for RP, i.e., the QUANTEC and APPELT models, in a large cohort of lung cancer patients treated with IMRT or VMAT. [1-2] METHODS AND MATERIALS: This prospective cohort study, included lung cancer patients treated between 2013 and 2018. A closed testing procedure was performed to test the need for model updating. To improve model performance, modification or removal of variables was considered. Performance measures included tests for goodness of fit, discrimination, and calibration. In this cohort of 612 patients, the incidence of RP ≥ grade 2 was 14.5%. For the QUANTEC-model, recalibration was recommended which resulted in a revised intercept and adjusted regression coefficient (from 0.126 to 0.224) of the mean lung dose (MLD),. The APPELT-model needed revision including model updating with modification and elimination of variables. After revision, the New RP-model included the following predictors (and regression coefficients): MLD (B = 0.250), age (B = 0.049, and smoking status (B = 0.902). The discrimination of the updated APPELT-model was higher compared to the recalibrated QUANTEC-model (AUC: 0.79 vs. 0.73). This study demonstrated that both the QUANTEC- and APPELT-model needed revision. Next to changes of the intercept and regression coefficients, the APPELT model improved further by model updating and performed better than the recalibrated QUANTEC model. This New RP-model is widely applicable containing non-tumour site specific variables, which can easily be collected.


The use of DNA flow cytometry in the diagnosis of triploidy in human abortions.
The ploidy of placental tissue from 59 abortions was determined using DNA flow cytometry. The specimens were also screened histologically for features considered to be characteristic of a partial mole. Triploidy was found in six cases; three of these cases presented histologically as partial moles. From the four specimens histologically classified as partial moles, three appeared to be triploid. The most specific histologic features of triploidy were cystic change of the placental villi and trophoblastic hyperplasia with vacuolation of the syncytiotrophoblast; however, these changes were also found in some of the nontriploid abortions. Irregularity of villous contours was less specific.


GuiLu-ErXian Glue extract promotes mesenchymal stem cells (MSC)-Induced chondrogenesis via exosomes release and delays aging in the MSC senescence process.
The treatment of osteoarthritis (OA) patients is a challenging problem. Mesenchymal stem cells (MSCs) are multipotent cells and play key roles in regenerative medicine for cartilage degeneration. GuiLu-ErXian Glue (GLEXG) is an herbal remedy widely used in traditional Chinese medicine to treat joint pain and disability in elderly OA patients. However, the mechanisms of how GLEXG affects MSCs-induced chondrogensis remains to be elucidated. The aim of this study was to investigate the effects of GLEXG on MSC-derived chondrogenesis, both in vitro and in vivo and its potential mechanisms. Using human MSC (hMSCs) as in vitro model, the effects of HPLC-profiled GLEXG water extract on chondrogenic differentiation were investigated by 3D spheroid cultures under chondrogenesis-inducing medium (CIM) condition. The chondrogenesis process was evaluated by measuring the sphere sizes, chondrogenesis-related genes expression by reverse transcription real-time PCR that targeted type II/X collagens, SOX9, aggrecan, and protein expression by immunostaining. Anti-TGF-β1 neutralization antibody was used for mechanistic study. Mono-iodoacetate (MIA) induced OA joint was used to evaluate the effects of GLEXG on in vivo model. MSCs-derived exosomes were purified for proteomics study and senescence process was evaluated by cumulative population doublings and senescence-associated β-Galactosidase staining. The results showed that GLEXG enhanced hMSCs chondrogenesis and upregulated RNA expression of type II/X collagen, SOX9 and aggrecan at 0.1 μg/mL, 0.3 μg/mL in vitro. In vivo, GLEXG at the dose of 0.3 μg intraarticular (i.a.) injection rescued the MIA-induced cartilage defect. Proteomics and ingenuity pathway analysis obtained from MSCs-released exosomes suggested that senescence pathway was less activated in GLEXG group than in vehicle group. Besides, GLEXG was able to increase cumulative population doubling and delayed hMSCs senescence process after four passages in cultures. we conclude that GLEXG promotes in vitro MSC-induced chondrogenesis possibly via exosomes release and delays aging in the MSC senescence process and that treatment with GLEXG (0.3 μg, i.a.) rescued cartilage defects in rat OA knee model.


Comparison of SARS-CoV-2 molecular detection in nasopharyngeal swab, saliva, and gargle samples.
The nasopharyngeal swab is a gold standard for detecting SARS-CoV-2. However, the inconvenience of this method compelled us to compare its efficiency with saliva and gargle samples, which we collected sequentially from 229 individuals. Saliva outperformed gargle samples, constituting a reliable RNA viral source with similar performance to nasopharyngeal samples.


NanoARPES of twisted bilayer graphene on SiC: absence of velocity renormalization for small angles.
The structural and electronic properties of twisted bilayer graphene (TBG) on SiC(000) grown by Si flux-assisted molecular beam epitaxy were investigated using scanning tunneling microscopy (STM) and angle-resolved photoelectron spectroscopy with nanometric spatial resolution. STM images revealed a wide distribution of twist angles between the two graphene layers. The electronic structure recorded in single TBG grains showed two closely-spaced Dirac π bands associated to the two stacked layers with respective twist angles in the range 1-3°. The renormalization of velocity predicted in previous theoretical calculations for small twist angles was not observed.


Sodium cyanide antagonism of the vasodilator action of sodium nitroprusside in theisolated rabbit aortic strip.
Resistance to sodium nitroprusside (SNP) is uncommon, but its occurrence has led to massive overdoses of SNP and sometimes death. To examine the mechanism responsible for resistance, aortic smooth muscle strips were prepared and dose-response curves for norepinephrine (NE) obtained. SNP alone caused a shift of the dose-response curve for NE to the right. However, this shift was less when the strips were exposed to both SNP and sodium cyanide (CN-). When CN- alone was added to the aortic strips, the response to NE was unchanged. In a further group of aortic muscle strips first contracted with NE and then relaxed with SNP, the addition of CN- caused the muscles to contract again. It is concluded that CN- antagonizes the action of SNP in vitro, and that this antagonism is specific for SNP.


Discovery of natural estrogen receptor modulators with structure-based virtual screening.
Eleven compounds were identified as estrogen receptor modulators from an in-house natural product database (NPD) by structure-based virtual screening for ERα and ERβ. Among them, 3 compounds were confirmed as ER agonists and 8 compounds were confirmed as ER antagonists by yeast two-hybrid (Y2H) assay, with EC50 values ranging from several micromolar to 100 micromolar. In this study, a novel series of cycloartane triterpenoids isolated from Schisandra glaucescens Diels was found to have ER antagonistic effect, the most potent antagonist of which exhibited activity with EC50 value of 2.55 and 4.68 μM for ERα and ERβ, respectively. Moreover, the types of modulation and subtype selectivity were also investigated through molecular docking simulation.


Case study methodology in tissue viability. Part 2: A study to determine the levels of knowledge of nurses providing care for patients with leg ulcers in an acute hospital setting.
One of the main components of the clinical governance framework is a comprehensive programme of quality improvement activity that includes the implementation of evidence-based, everyday clinical practice. This paper addresses the challenges surrounding the implementation of one area of evidence-based practice, the management of leg ulcers in an acute hospital trust. The aim of the study was to distinguish the levels of knowledge of nurses providing care for patients with leg ulcers within an acute hospital setting. The design used was that of a collective case study. Each 'case' was a patient with a leg ulcer and the nurses who cared for that patient. They were studied in order to provide insight into the nurses' understanding of leg ulcer management. A number of themes were identified as being common to all the cases. They are: evidence-based practice, nursing skills, quality of life, patient understanding of their ulcer and pain. Each of these themes identified areas of knowledge deficit in the nurses. As part of the implementation of a leg ulcer policy an education programme is being developed to address these deficits.


The comfort assessment in healthy adults during constant-flow mode in noninvasive ventilator.
From the point of view of machine construction and hydrodynamics, this paper innovatively proposes that the essence of high-flow nasal cannula (HFNC) is a constant-flow mode in noninvasive ventilator (NIVCFM). This study enrolled healthy adults as study subjects to assess the subjective comfort assessed by visual analog scoring scale of NIVCFM/HFNC and objective comfort measured by the noise level generated by NIVCFM/HFNC, aiming to provide a scientific basis for the rational clinical application of NIVCFM/HFNC. Forty-four healthy adults participated in this study. The noise generated by NIVCFM/HFNC is measured, and the comfort is evaluated during NIVCFM delivery at flow rates of 0, 5, 10, 15, 20, 25, 30, 35, 40, 45, 50, 55, and 60 L/min. When the ventilator flow rate is 60 L/min, the maximum noise is 65.9 dB, increasing noise by 23.7 dB from a baseline of 42.2 dB at the flow rate of 0 L/min. There was a strong nonlinear positive correlation between the noise level and the flow rates. The median score for dry mouth, nose or throat, dysphagia, sore throat, and other discomfort was 0. The median score for dyspnea was 0 at 0-30 L/min, 1 at 35-55 L/min, and 2 at 60 L/min. The grater the flow rate, the greater the noise generated by NIVCFM/HFNC (<65.9 dB). The maximum flow rate that most healthy adults can able to tolerate is 30 L/min, and the main discomfort is dyspnea.


Effect of the duration of prone position in ARDS patients during the SARS-CoV-2 pandemic.
To describe the characteristics of patients with acute respiratory distress syndrome (ARDS) due to bilateral COVID-19 pneumonia on invasive mechanical ventilation (IMV), and to analyze the effect of prone position >24 h (prolonged) (PPP) compared to prone decubitus <24 h (PP). A retrospective observational descriptive study was carried out, with uni- and bivariate analyses. Department of Intensive Care Medicine. Hospital General Universitario de Elche (Elche, Alicante, Spain). Patients with SARS-CoV-2 pneumonia (2020-2021) on IMV due to moderate-severe ARDS, ventilated in prone position (PP). IMV. PP maneuvers. Sociodemographic characteristics, analgo-sedation, neuromuscular blockade (NMB), PD duration, ICU stay and mortality, days of IMV, non-infectious complications, healthcare associated infections. Fifty-one patients required PP, and of these, 31 (69.78%) required PPP. No differences were observed in terms of patient characteristics (gender, age, comorbidities, initial severity, antiviral and antiinflammatory treatment received). Patients on PPP had poorer tolerance to supine ventilation (61.29% vs 89.47%, p = 0.031), longer hospital stay (41 vs 30 days, p = 0.023), more days of IMV (32 vs 20 days, p = 0.032), longer duration of NMB (10.5 vs 3 days, p = 0.0002), as well as a higher percentage of episodes of orotracheal tube obstruction (48.39% vs 15%, p = 0.014). PPP was associated with greater resource use and complications in patients with moderate-severe ARDS due to COVID-19.


Novel SERPING1 gene mutations and clinical experience of type 1 hereditary angioedema from North India.
There is paucity of literature on long-term follow-up of patients with hereditary angioedema (HAE) from developing countries. This study was carried out to analyze the clinical manifestations, laboratory features, and genetic profile of 32 patients (21 male and 11 female) from 23 families diagnosed with HAE between January 1996 and December 2019. Data were retrieved from medical records of Paediatric Immunodeficiency Clinic, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Median age at onset of symptoms was 6.25 years (range 1-25 years), and median age at diagnosis was 12 years (range 2-43 years). Serum complement C4 level was decreased in all patients. All patients had low C1-esterase inhibitor (C1-INH) quantitative level (type 1 HAE). SERPING1 gene sequencing could be carried out in 20 families. Of these, 11 were identified to have a pathogenic disease-causing variant in the SERPING1 gene. While 2 of these families had a previously reported mutation, remaining 9 families had novel pathogenic variants in SERPING1 gene. Because of non-availability of C1-INH therapy in India, all patients were given long-term prophylaxis (attenuated androgens or tranexamic acid (TA) or a combination of the 2). Life-threatening episodes of laryngeal edema were managed with fresh-frozen plasma (FPP) infusions. We recorded one disease-related mortality in our cohort. This happened in spite of long-term prophylaxis with stanozolol and TA. We report largest single-center cohort of patients with HAE from India. Attenuated androgens, fibrinolytic agents, and FPP may be used for management of HAE in resource-limited settings.


Thulium:YAG VapoEnucleation of the prostate in large glands: a prospective comparison using 70- and 120-W 2-µm lasers.
This study compared the efficacy of 70- and 120-w 2-µm thulium:YAG VapoEnucleation of the prostate (ThuVEP) for patients with benign prostatic obstruction (BPO). A prospective analysis of 84 patients with symptomatic BPO and prostatic enlargement (≥60 ml) who underwent either 70-w (n=44) or 120-w ThuVEP (n=40) non-randomly was carried out. Patient demographics and perioperative and 12-month follow-up data were analysed. The mean prostate volume was 79.90±27.49 ml in patients who had received 70-w ThuVEP, which was less than in those who had received 120-w ThuVEP (88.53±25.10; P=0.033). The mean enucleation (resected weight/laser time, 2.16±1.21 g min(-1) vs. 1.23±0.60 g min(-1); P=0.013), operation efficiency (resected weight/total operation time, 0.76±0.35 g min(-1) vs. 0.42±0.27 g min(-1); P=0.000) and percentage of resected tissue (66.93%±22.79% vs. 45.41%±23.33%; P=0.000) were higher with 120-w treatment compared to 70-w ThuVEP. One patient (1.2% of total patients) (in the 120-w group) required a blood transfusion postoperatively. Sixty-one patients (73%) were available for review at the 12-month follow-up time point. The quality of life (QoL), International Prostate Symptom Score (IPSS), maximum urinary flow rate (Q(max)), postvoiding residual urine (PVR) and prostate volume improved significantly after treatment (P≤0.035) and were not significantly different between those treated with the different devices (70- and 120-w). The median prostate volume reduction was 81.70% and 82.19% with 70- and 120-w ThuVEP, respectively. The incidence of complications was low and did not differ between groups treated with the different devices. Two patients (2.4%) (one per group) had a bladder neck contracture at the follow-up. ThuVEP is a safe and efficacious procedure for the treatment of symptomatic BPO. The incidence of complications was low with both devices. The 120-w thulium:YAG device enhances the effectiveness of ThuVEP with regard to the percentage of resected tissue and the enucleation/operation efficiency.


Predatory behavior in a necrophagous bee Trigona hypogea (Hymenoptera; Apidae, Meliponini).
Although most bees feed on nectar and pollen, several exceptions have been reported. The strangest of all is the habit found in some neotropical stingless bees, which have completely replaced pollen-eating by eating animal protein from corpses. For more than 20 years, it was believed that carrion was the only protein source for these bees. We report that these bees feed not only off dead animals, but on the living brood of social wasps and possibly other similar sources. Using well developed prey location and foraging behaviors, necrophagous bees discover recently abandoned wasps' nests and, within a few hours, prey upon all immatures found there.


Identification and characterization of Dichelobacter nodosus serogroup H from ovine footrot in India.
A total of 56 foot swabs were collected from inter digital spaces of sheep with footrot lesions were screened for 16 rRNA of Dichelobacter nodosus by PCR. Out of the 56 samples, 38(67.85%) were found to be positive. All the positive samples were subjected to multiplex PCR targeting fimA gene for identification of serogroups of D. nodosus. Serogroup H was found along with serogroup B in 12 (55.26%) samples and with serogroup I in 8 (22.2%) samples. The serogroup H was identified for the first time from the Indian subcontinent. The phylogenetic analysis of the present sequence with the available serogroup H sequences of GenBank revealed to be in close association with the serotype H1.


Detection of Mycobacterium avium subsp. paratuberculosis in bulk tank milk by combined phage-PCR assay: evidence that plaque number is a good predictor of MAP.
Conventional culture and a rapid phage-PCR method were used to detect Mycobacterium avium subsp. paratuberculosis (MAP) in bulk tank milk (BTM) samples. Only two of 225 samples (0.9%) were found to contain MAP by culture whereas 50 (22%) MAP-positive samples were identified using the phage-PCR assay, including both samples that were MAP-culture positive. Results using the phage-based method for independently tested duplicate samples indicated that the assay is very reproducible (r(2)=0.897), especially when low levels of mycobacteria are present. A relationship was established between plaque number and the presence of MAP in a sample. A cut-off value was determined allowing identification of MAP-positive samples based on plaque number alone (90% sensitivity, 99% specificity; area under the curve=0.976). These results indicate that the assay is a robust method for screening BTM, providing results within 24 h.


Ion-pairs in proteins.
A "working definition" for an ion-pair has been derived based upon analysis of the distance distributions for like- and oppositely charged groups in 38 proteins. Ion-pairs defined according to this criterion (less than or equal to 4 A between charged groups) have been analysed in respect of: (1) the frequencies of different pair types; (2) the residue separations and secondary structural locations of the residues involved; (3) the flexibility of the side-chains involved; (4) their conformation; (5) their environment (accessibility to solvent and proximity to active site or ligand binding regions); and (6) their conservation in related proteins. The results obtained indicate that on average one-third of the charged residues in a protein are involved in ion-pairs and 76% of these are concerned with stabilizing the tertiary (rather than the secondary) structure. Only 17% of ion-pairs are buried, and conservation of the interactions is generally low unless the residues involved have more specific functions to perform. In the light of the results obtained, the role of ion pairs in globular proteins is discussed.


Changes in Patient Experiences of Hospital Care During the COVID-19 Pandemic.
It is important to assess how the COVID-19 pandemic was adversely associated with patients' care experiences. To describe differences in 2020 to 2021 patient experiences from what would have been expected from prepandemic (2018-2019) trends and assess correlates of changes across hospitals. This cohort study compared 2020 to 2021 data with 2018 to 2019 data from 3 900 887 HCAHPS respondents discharged from 3381 HCAHPS-participating US hospitals. The data were analyzed from 2022 to 2023. The primary outcome was an HCAHPS summary score (HCAHPS-SS), which averaged 10 HCAHPS measures. The primary analysis estimated whether HCAHPS scores from patients discharged from 2020 to 2021 differed from scores that would be expected based on quarterly and linear trends from 2018 to 2019 discharges. Secondary analyses stratified hospitals by prepandemic overall star ratings and staffing levels. Of the 3 900 887 HCAHPS 2020 to 2021 respondents, 59% were age 65 years or older, and 35% (11%) were in the surgical (maternity) service lines. Compared with trends expected based on prepandemic (2018-2019) data, HCAHPS-SS was 1.2 percentage points (pp) lower for quarter (Q) 2/2020 discharges and -1.9 to -2.0 pp for Q3/2020 to Q1/2021, which then declined to -3.6 pp by Q4/2021. The most affected measures (Q4/2021) were staff responsiveness (-5.6 pp) and cleanliness (-4.9 pp); the least affected were discharge information (-1.6 pp) and quietness (-1.8 pp). Overall rating and hospital recommendation measures initially exhibited smaller-than-average decreases, but then fell as much as the more specific experience measures by Q2/2021. Quietness did not decline until Q2/2021. The HCAHPS-SS fell most for hospitals with the lowest prepandemic staffing levels; hospitals with bottom-quartile staffing showed the largest decrements, whereas top-quartile hospitals showed smaller decrements in most quarters. Hospitals with better overall prepandemic quality showed consistently smaller HCAHPS-SS drops, with effects for 5-star hospitals about 25% smaller than for 1-star and 2-star hospitals. The results of this cohort study of HCAHPS-participating hospitals found that patient experience scores declined during 2020 to 2021. By Q4/2021, the HCAHPS-SS was 3.6 pp lower than would have been expected, a medium effect size. The most affected measures (staff responsiveness and cleanliness) showed large effect sizes, possibly reflecting high illness-associated hospital workforce absenteeism. Hospitals that were lower performing and less staffed prepandemic may have been less resilient to reduced staff availability and other pandemic-associated challenges. However, by Q4/2021, even prepandemic high-performing hospitals had similar declines.


Appetite as a predictor of malnutrition in end-stage renal disease patients in Saudi Arabia.
Patients with chronic kidney disease (CKD) undergoing hemodialysis (HD) are at high risk for malnutrition. This study aimed to 1) Investigate the prevalence of malnutrition among CKD patients undergoing maintenance HD; 2) Assess level of knowledge and appetite among patients; 3) Identify potential predictors of malnutrition. This cross-sectional study included 71 CKD patients on HD who were recruited from two principal outpatient dialysis centers located in Jeddah, Saudi Arabia. Data were collected using an interviewer-administered questionnaire which included sociodemographic and health characteristics, nutritional status (assessed using the Patient-Generated Subjective Global Assessment [PG-SGA]), biochemical data, nutritional knowledge, and appetite status (assessed using Council of Nutrition Appetite Questionnaire [CNAQ]). Forty-four percent of patients included in this study were malnourished, and over half of the patients had limited nutritional knowledge and appetite. Hemoglobin level and the CNAQ score were found to be independently negatively associated with the PG-SGA score (B: -1.03 [95% confidence interval (CI): -1.99, - 0.08] and B: -0.37 [95% CI: -0.64, -0.11], respectively). Renal healthcare professionals should assess the nutritional status of HD patients and identify barriers to adequate nutrition. Patients with poor appetite should specifically be targeted for nutrition-focused evaluation and management.


Dopamine neurotoxicity: age-dependent behavioral and histological effects.
The oxidative stress (OS) theory has implicated the involvement of reactive oxygen species (ROS) in both aging and age-dependent neurodegenerative diseases. The dopaminergic system is particularly vulnerable to ROS, and dopamine (DA) itself can be an endogenous source of ROS. The present study evaluated the hypothesis that DA-induced toxicity is age-dependent, and tested the behavioral and histological correlates of DA neurotoxicity in aging. Young (6 months) and middle-aged (15 months) rats were chronically treated with DA in the substantia nigra (SN, 1 micromol/2 microl vehicle per side/day/5 days) and were subsequently examined for changes in motor function and histology. The neurotoxic effect of DA treatment was an age-dependent effect, as middle-aged animals that received DA infusions in the SN were more impaired than their age-matched controls, especially on tasks that involved greater sensory-motor coordination, whereas young animals that received DA behaved similarly to their age-matched controls. The behavioral effects noted were accompanied by a loss of the tyrosine hydroxylase phenotype in substantia nigra. However, selective neurodegeneration was not noted in the SN of the treated animals, nor was a selective iron deposition noted at the site of injection. These results suggest that a neurochemical deficit and not cell loss per se within the nigrostriatal system underlies the motor behavioral deficits observed in the middle-aged rats.


Tuberculosis of transverse testicular ectopic testis associated with persistent mullerian duct syndrome.
A 10-month-old male infant presented with bilateral inguinal hernia and left un-descended testis. During right herniotomy, both gonads were found on same side with mullerian duct structures. On naked eye examination, both gonads were normal looking. Excision of mullerian duct remnant and fixation of ectopic testis was made. Histopathological examination revealed that gonads were testicles. Presence of multiple granulomas composed of Langhans cells and epithelioid cells in ectopic testicle suggested tuberculosis. Patient was kept on antituberculous therapy and was on regular follow-up without any complication.


Arsenic species determination in human scalp hair by pressurized hot water extraction and high performance liquid chromatography-inductively coupled plasma-mass spectrometry.
Analytical methods for the determination of total arsenic and arsenic species (mainly As(III) and As(V)) in human scalp hair have been developed. Inductively coupled plasma-mass spectrometry (ICP-MS) and high performance liquid chromatography (HPLC) coupled to ICP-MS have been used for total arsenic and arsenic species determination, respectively. The proposed methods include a "green", fast, high efficient and automated species leaching procedure by pressurized hot water extraction (PHWE). The operating parameters for PHWE including modifier concentration, extraction temperature, static time, extraction steps, pressure, mean particle size, diatomaceous earth (DE) mass/sample mass ratio and flush volume were studied using design of experiments (Plackett-Burman design PBD). Optimum condition implies a modifier concentration (acetic acid) of 150 mM and powdered hair samples fully mixed with diatomaceous earth (DE) as a dispersing agent at a DE mass/sample mass ratio of 5. The extraction has been carried out at 100°C and at an extraction pressure of 1500 psi for 5 min in four extraction step. Under optimised conditions, limits of quantification of 7.0, 6.3 and 50.3 ng g(-1) for total As, As(III) and As(V), respectively were achieved. Repeatability of the overall procedure (4.4, 7.2 and 2.1% for total As, As(III) and As(V), respectively) was achieved. The analysis of GBW-07601 (human hair) certified reference material was used for validation. The optimised method has been finally applied to several human scalp hair samples.


A comparison between knotted and knotless medial row of suture bridge technique in arthroscopic rotator cuff repair surgery: a meta-analysis.
The shoulder arthroscopic suture bridge technique is currently very popular, but scientific evidence relating to the clinical outcomes of the medial row with or without knots has not been systematic reviewed. The purpose of this study was to compare the clinical outcomes of knotted versus knotless double-row suture bridges for rotator cuff repairs. Meta-analysis. Five databases that contain literature in English were searched (Medline, PubMed, Embase, Web of Science, and the Cochrane Library), with a focus on works published between 2011 and 2022. Clinical data relating to arthroscopic rotator cuff repair with the suture bridge approach was examined and the outcomes of medial row knotting contrasted with that of the knotless technique. The search phrase used was: (double row) AND (rotator cuff) AND (repair), and the search method is subject term plus free word search. Literature quality evaluation was performed using the Cochrane "risk of bias" tool 1.0 and the Newcastle-Ottawa scale quality assessment instrument. One randomized controlled trial, four prospective cohort studies, and five retrospective cohort studies were included in this meta-analysis. Data pertaining to 1146 patients was drawn from these ten original papers and analyzed. Meta-analyses that were performed on 11 postoperative outcomes revealed that none of the differences were statistically significant (P > 0.05) and that the publications were unbiased (P > 0.05). Postoperative retear rate and postoperative retear categorization were the outcomes assessed. Scores on postoperative pain, forward flexion, abduction, and external rotation mobility were collated and evaluated. The University of California, Los Angeles scoring systems in the first year following surgery, the American Shoulder and Elbow Surgeons score and Constant scales in the first and second years after surgery were the secondary outcomes spotlighted in this study. The clinical outcomes of shoulder arthroscopic rotator cuff repair with the suture bridge technique with or without a knotted medial row was proven to be equivalent. These outcomes are about postoperative retear, postoperative retear classification, postoperative shoulder function score, postoperative shoulder mobility, and postoperative pain, respectively. It should be noted that the conclusions are based on short-term clinical follow-up data.


Behavioural and morphological changes in ciliates induced by the predator Amoeba proteus.
The predator Amoeba proteus induced behavioural and morphological changes in ciliates of the genus Euplotes. The frequency of avoidance behaviour in E. octocarinatus increased from 16±5% to 84±5% (SD) after 14 h of coexistence with the predator. The ciliate's width increased from 59±3 μm to 77±4 μm (SDM) within 48 h. Similar behavioural, but not morphological, change was induced in E. daidaleos, but neither morphological nor behavioural responses occurred in E. aediculatus. E. octocarinatus and E. daidaleos populations survived in the presence of A. proteus, whereas E. aediculatus populations became extinct by predation. Induced behavioural response seemed to be the reason for the low predation risk of E. octocarinatus and E. daidaleos. The results suggest that Euplotes ciliates have evolved specific defence mechanisms to various predators. Defensive changes are induced by a chemical substance released from A. proteus. This "kairomone" has a molecular weight between 5000 and 10000 Da. Proteolytic digestion of its activity indicated that the avoidance-inducing substance is a peptide. After the turbellarian Stenostomum sphagnetorum had induced a defensive morphology in E. octocarinatus or E. aediculatus, neither of these ciliates immediately avoided Amoeba proteus. Thus, Euplotes ciliates with a defensive morphology do not have behavioural defences in reaction to all predators.


Surfactant therapy in neonates with respiratory failure due to haemorrhagic pulmonary oedema.
We studied the clinical and biochemical factors associated with surfactant dysfunction and factors affecting the responsiveness to exogenous surfactant among 27 neonates with haemorrhagic pulmonary oedema (HPE). HPE was defined as the presence of a large amount of blood-stained lung effluent and respiratory failure which was difficult to differentiate from respiratory distress syndrome. Among the neonates, 33% had very low birth weight, 96% were preterm, 70% were delivered by caesarean section, and 44% had delivery room intubation. The onset of HPE was at 1.5+/-0.1 h (mean +/- SEM) after birth. In 26 cases, surfactant was administered at 3.0+/-1.3 h after the onset of HPE. The concentrations of surfactant protein A (SP-A), disaturated phosphatidylcholine (DSPC), and albumin in the epithelial lining fluid were determined using the first lung effluent from the patients. The level of inhibitory activity against pulmonary surfactant in the effluent was determined in vitro. Surfactant inhibitory activity was associated with lower birth weight, earlier gestational age, delivery room intubation, earlier onset of HPE, and lower SP-A or DSPC concentration. A good response to exogenous surfactant, which was defined as ventilatory index <0.047 at 1 h after surfactant administration, was seen in 82% of cases, and was associated with lower serum albumin, lower birth weight, and earlier gestational age. Cases with higher DSPC concentration prior to surfactant administration and shorter interval between the onset of HPE and surfactant administration showed an immediate response to surfactant, followed by no increase in ventilatory index for 24 h after surfactant administration. exogenous surfactant appeared to be a useful adjunctive therapy for overcoming surfactant inhibition and normalising the respiratory status of infants with haemorraghic pulmonary oedema. Surfactant treatment for this indication awaits further investigations including a randomised controlled study.


An observational study to investigate the relationship between plasma glucosylsphingosine (lyso-Gb1) concentration and treatment outcomes of patients with Gaucher disease in Japan.
Gaucher disease (GD) is an autosomal recessive disease caused by GBA1 mutations resulting in glucosylceramide accumulation in macrophages. GD is characterized by hepatosplenomegaly, anemia, thrombocytopenia, bone complications, and neurological complications. Glucosylsphingosine (lyso-Gb1), a deacylated form of glucosylceramide, has been identified as a promising biomarker for the diagnosis and treatment response in GD. The aim of this study was to examine the relationship between plasma lyso-Gb1 and therapeutic goals for GD (improvements in hepatomegaly, splenomegaly, anemia, thrombocytopenia, bone pain, and bone crisis), as well as disease type and GBA1 mutation type, in Japanese patients with GD receiving velaglucerase alfa, an enzyme replacement therapy (ERT). Furthermore, this study compared the plasma lyso-Gb1 concentration observed in Japanese patients included in this study with that observed in a previous non-Japanese clinical study. This non-interventional, open-label, multicenter observational cohort study (October 2020 to March 2021) included a total of 20 patients (of any age) with GD (type 1: n = 8; type 2: n = 9; type 3: n = 3) treated with velaglucerase alfa for ≥ 3 months. Median (minimum-maximum) duration of velaglucerase alfa treatment was 49.5 (3-107) months. A total of 14 (70.0%) patients achieved all therapeutic goals (i.e., 100% achievement; improvements in hepatomegaly, splenomegaly, anemia, thrombocytopenia, bone pain, and bone crisis). Overall, median (minimum-maximum) lyso-Gb1 concentration was 24.3 (2.1-150) ng/mL. Although not statistically significant, numerically lower plasma lyso-Gb1 concentrations were observed in patients with 100% achievement compared with those without; no statistically significant difference in plasma lyso-Gb1 concentration was observed between patients with different disease type or mutation type. Furthermore, lyso-Gb1 concentrations observed in Japanese patients were numerically lower than that observed in a previous study of non-Japanese patients with GD receiving ERT. In this study, high achievement rates of therapeutic goals with low lyso-Gb1 concentration were observed, demonstrating a correlation between therapeutic goals and lower plasma lyso-Gb1 concentration in Japanese patients with GD treated with velaglucerase alfa. This study further suggests that plasma lyso-Gb1 concentration may be a useful biomarker for treatment response in patients with GD.


Low prolactin response to fenfluramine in impulsive aggression.
To examine the prolactin (prl) response to d,l-fenfluramine in a large sample of personality disorder patients with impulsive aggression. Patients were screened from clinics at the Bronx VAMC and the Mount Sinai Medical Center and from press releases. One hundred and forty-six personality disorder patients (90M;56F) and 23 normal controls (15M;8F) underwent oral d,l-fenfluramine challenge. The peak change in prolactin(deltapkprl) was calculated by subtracting baseline prolactin from peak response following fenfluramine administration (3 h). Analysis of variance and regression analysis were used to detect group differences in deltapkprl. Deltapkprl in impulsive aggressive men, but not women, with personality disorders was blunted compared with controls. Men with suicide histories also had a blunted deltapkprl compared with those without, which was not accounted for by depression. This study represents a replication of previous studies, in a much larger sample, showing a blunted PRL response to fenfluramine of male patients with personality disorder in relation to impulsive aggression and to suicide attempts.


Follicle loss after laparoscopic treatment of ovarian endometriotic cysts.
To evaluate follicle loss and its associated factors during laparoscopic cystectomy for ovarian endometrioma. Between October 2008 and December 2009, 140 patients with ovarian cysts undergoing laparoscopic cystectomy at Peking Union Medical Hospital were enrolled: 74 had ovarian endometrioma with no preoperative hormonal therapy (group A), 40 had ovarian endometrioma pretreated with GnRHa (group B), and 26 had non-endometriotic cysts (group C). Pre-, peri- , and postoperative clinical data were collected, and cyst specimens were evaluated histologically. The number of capsules showing follicles and the mean number of follicles per capsule were lower in group C than in group A or B (P<0.05). Fewer type IIC than type IIB endometriomas showed follicles (P<0.05). The number of follicles per cyst was related negatively to disease duration but positively to pain severity. Women in group A with unilateral endometrioma had a lower mean dysmenorrhea score after the surgery (P<0.05), but no change in basal follicle-stimulating hormone (FSH). The type of cyst, disease duration, and severity of dysmenorrhea were associated with ovarian follicle loss during laparoscopic excision of endometrioma. Laparoscopic unilateral cystectomy for endometrioma was effective in relieving pain but had little effect on serum FSH, which might reflect the remaining ovarian reserve.


Correction: Li et al. Novel Therapies for Tongue Squamous Cell Carcinoma Patients with High-Grade Tumors. Life 2021, 11, 813.
Yinghua Li was not included as an author in the original publication [...].


Spectrum of fungal infection in a neurology tertiary care center in India.
There is a paucity of studies on spectrum of fungal infections in neurology care. This study reports clinical, MRI and outcome of patients with central nervous system (CNS) fungal infections. 39 patients with CNS fungal infections treated in neurology service during the last 3 years were included and a detailed medical history and clinical examination were undertaken. Cranial MRI including paranasal sinuses were carried out and the location and nature of abnormalities were noted. Fungal infection was confirmed by CSF examination or histopathology. Death during hospital stay was noted. The median age was 37 (8-72) years and 8 were females. The clinical features included altered sensorium in 31, focal motor deficits in 13, visual loss in 12, seizures in 10, diplopia in 7, and papilledema in 9 patients. 28 patients had the following predisposing conditions: HIV in 15, diabetes in 8, corticosteroid in 2 and alcohol, immunosuppression, neutropenia and analgesic abuse in 1 patient each. On CT or MRI scan, 5 patients had meningeal enhancement, 7 sinusitis, 10 each granuloma and infarction, 4 hydrocephalous and 1 cerebral venous sinus thrombosis. 28 patients had cryptococcal meningitis, 7 zygomycosis, 2 aspergillosis and 1 each candida and phaeohyphomycosis. Death was related to the type of fungal infection; all patients with zygomycosis and candida infection died. Rhinocerebral form of fungal infection due to zygomycetes has poorer survival compared to meningitis group which was mainly due to cryptococcal infection.


Expression of a fusion protein containing human epidermal growth factor and the collagen-binding domain of Vibrio mimicus metalloprotease.
Human epidermal growth factor (hEGF) is a polypeptide of 53 amino acids, is an important autocrine/paracrine factor in the human body, and is used in the pharmaceutical and cosmetics industries. We constructed a fusion hEGF protein with a collagen-binding domain (CBD) composed of 33 amino acids from Vibrio mimicus metalloprotease (VMCBD). The CBD segment of the metalloprotease was fused at the C terminus of the hEGF protein. The recombinant fusion protein was expressed in Escherichia coli and purified. The purified hEGF protein promoted greater growth of human/A-431 cells than did the control hEGF. The fusion EGF protein also showed collagen-binding activity with type I collagen. In contrast, hEGF did not bind to type I collagen. These results suggest that recombinant hEGF protein fused to VMCBD may be able to remain for a long period at injured epidermal tissue acting as a healing agent.


Identification of RNA-binding regions on the P and V proteins of human parainfluenza virus type 2.
We have shown that the P and V proteins of human parainfluenza virus type 2 (hPIV-2) bind to genomic RNA by using Northwestern blot analysis. To identify the RNA-binding regions on the P and V proteins, we used a set of deletion mutants produced in Escherichia coli. One region required for the RNA-binding was found in the P-V common domain (aa 1-82). Others were found in the P protein-specific region (aa 249-354) and the V protein-specific region (aa 176-225). In addition, we have shown that substitutions of some basic residues with alanines in these regions abrogate RNA-binding by the P or V proteins. Intriguingly, the P and V proteins of hPIV2 can selectively bind to the viral RNA under our experimental conditions.


Influence of long-range transboundary transport on atmospheric water vapor mercury collected at the largest city of Tibet.
Monsoon circulation is an important process that affects long-range transboundary transport of anthropogenic contaminants such as mercury (Hg). During the Indian monsoon season of 2013, a total of 92 and 26 atmospheric water vapor samples were collected at Lhasa, the largest city of the Tibet, for Hg and major ions analysis, respectively. The relatively low pH/high electronic conductivity values, together with the fact that NH4(+) in atmospheric water vapor was even higher than that determined in precipitation of Lhasa, indicated the effects of anthropogenic perturbations through long-range transboundary atmospheric transport. Concentrations of Hg in atmospheric water vapor ranged from 2.5 to 73.7ngL(-1), with an average of 12.5ngL(-1). The elevated Hg and major ions concentrations, and electronic conductivity values were generally associated with weak acidic samples, and Hg mainly loaded with anthropogenic ions such as NH4(+). The results of principal component analysis and trajectory analysis suggested that anthropogenic emissions from the Indian subcontinent may have largely contributed to the determined Hg in atmospheric water vapor. Furthermore, our study reconfirmed that below-cloud scavenging contribution was significant for precipitation Hg in Lhasa, and evaluated that on average 74.1% of the Hg in precipitation could be accounted for by below-cloud scavenging.


Elevated Cytoplasmic Free Zinc and Increased Reactive Oxygen Species Generation in the Context of Brain Injury.
Intracellular zinc release and the generation of reactive oxygen species (ROS) have been reported to be common ingredients in numerous toxic signaling mechanisms in neurons. A key source for intracellular zinc release is its liberation from metallothionein-III (MT-III). MT-III binds and regulates intracellular zinc levels under physiological conditions, but the zinc-binding thiols readily react with certain ROS and reactive nitrogen species (RNS) to result in intracellular zinc liberation. Liberated zinc induces ROS and RNS generation by multiple mechanisms, including the induction of mitochondrial ROS production, and also promotes ROS formation outside the mitochondria by interaction with the enzymes NADPH oxidase and 12-lipoxygenase. Of particular relevance to neuronal injury in the context of ischemia and prolonged seizures, the positive feedback cycle between ROS/RNS generation and increasing zinc liberation will be examined.


Progesterone, but not 17-alpha-hydroxyprogesterone caproate, inhibits human myometrial contractions.
The aim was to determine whether progesterone (P4) or 17-alpha-hydroxyprogesterone caproate (17P) directly inhibit human uterine contractility in vitro and thereby clarify their mechanisms of action. Myometrial tissues were suspended in organ chambers and exposed for 2 to 20 hours to varying concentrations of P4 or 17P or solvent. Contractile activity was registered, stored, and analyzed. Dose response curves were then generated for P4 or 17P at various times. P4 significantly inhibited spontaneous contractility dose dependently. The inhibition was not blocked by RU486 but was reversible after washing. Surprisingly, 17P dose dependently stimulated contractility. HPLC and GC-MS methods were used to determine the detectable concentrations of progestins in the baths. P4, at concentrations equivalent to those present in the placenta and uterus, inhibit spontaneous myometrial contractility in vitro by nongenomic mechanisms.


Effect of laparoscopic liver resection versus the open technique on hepatocyte regenerating activity in the rat.
Laparoscopic liver resection offers a safe and feasible option primarily for the excision of hepatic neoplasms. Timely recovery of liver volume is a key factor for improving prognosis and post-operative mortality of patients undergone liver resection. The aim of the present study was to compare liver regeneration after laparoscopic over open partial hepatectomy. Wistar rats were subjected to laparoscopic 70% hepatectomy (group LAP-HEP), open 70% hepatectomy (group HEP), sham operation (group Sham) or no intervention (group Control). At various timepoints following operation (1 h-2 weeks), the liver was excised to assess relative liver weight, thiobarbituric acid reactive substances (TBARS) levels, mitotic activity, tissue expression of Nuclear Factor-κB (NFκB), Intercellular Adhesion Molecule-1 (ICAM-1) and Vascular Cell Adhesion Molecule-1 (VCAM-1) and the histopathologic profile. No differences were seen in relative liver weight between hepatectomy groups. Mitotic index was increased in all operative study groups, being higher in group LAP-HEP than in group HEP. TBARS levels were higher in group LAP-HEP compared to group HEP. NFκB and VCAM-1 tissue expression scores were increased in all operative study groups with VCAM-1 being higher in group HEP, while ICAM-1 was overexpressed only in hepatectomy groups. Mild histopathologic lesions were noted in hepatectomy groups with the histopathologic score being higher in group HEP (24 h). Laparoscopic liver resection enhanced hepatocyte mitotic activity which was accompanied by mild oxidative stress and a less pronounced local inflammatory response and tissue injury to that of the open technique.


Heparan sulphate proteoglycans: the sweet side of development.
Pattern formation during development is controlled to a great extent by a small number of conserved signal transduction pathways that are activated by extracellular ligands such as Hedgehog, Wingless or Decapentaplegic. Genetic experiments have identified heparan sulphate proteoglycans (HSPGs) as important regulators of the tissue distribution of these extracellular signalling molecules. Several recent reports provide important new insights into the mechanisms by which HSPGs function during development.


The Relationship between S. aureus and Branched-Chain Amino Acids Content in Composite Cow Milk.
The early diagnosis of mastitis is an essential factor for the prompt detection of the animal for further actions. In fact, if not culled, infected cows must be segregated from the milking herd and milked last, or milked with separate milking units. Besides microbiological analysis, the somatic cell count (SCC) commonly used as predictor of intramammary infection, frequently lead to a misclassification of milk samples. To overcome these limitations, more specific biomarkers are continuously evaluated. The total amino acid content increases significantly in mastitic milk compared to normal milk. S. aureus requires branched-chain amino acids (BCAAs-isoleucine, leucine, and valine) for protein synthesis, branched-chain fatty acids synthesis, and environmental adaptation by responding to their availability via transcriptional regulators. The increase of BCAAs in composite milk has been postulated to be linked to mammary infection by S. aureus. The aim of this work is to demonstrate, by a direct ion-pairing reversed-phase method, based on the use of the evaporative light-scattering detector (IP-RP-HPLC-ELSD), applied to 65 composite cow milk samples, a correlation between the concentration of isoleucine and leucine, and S. aureus load. The correlation coefficient, r, was found to be 0.102 for SCC (p = 0.096), 0.622 for isoleucine (p < 0.0001), 0.586 for leucine (p < 0.0001), 0.013 for valine (p = 0.381), and 0.07 for tyrosine (p = 0.034), standing for a positive correlation between S. aureus and isoleucine and leucine concentration. The link between the content of BCAAs, isoleucine and leucine, and udder infection by S. aureus demonstrated with our study has an important clinical value for the rapid diagnosis of S. aureus mastitis in cows.


The effect of chelating agent on the separation of Fe(III) and Ti(IV) from binary mixture solution by cation-exchange membrane.
The competitive transport of Fe(III) and Ti(IV) ions and the effect of chelating agents on separation from binary mixture solutions through charged polysulfone cation-exchange membrane (SA3S) has been studied under Donnan dialysis conditions. The amount of chelating agent was taken as an equimolar of Fe(III) ion in the feed phase. In this process, the membrane separated two electrolyte solutions: the feed solution, initially containing metal salts (Fe, Ti), or metal salts solution, containing a chelating agent, and the other side (receiver solution) being HCl solution. An external potential field is not applied. It was observed that the chelating agents affect the metal transport; the transport of Fe(III) is decreased and the transport of Ti(IV) is increased.


Ultrasound-Assisted Crystallization Enables Large-Area Perovskite Quasi-Monocrystalline Film for High-Sensitive X-ray Detection and Imaging.
In recent years, halide perovskites have shown great application potential in X-ray detection due to their superior optoelectronic properties and high X-ray attenuation coefficient. However, large-area perovskite fabrication for high performance X-ray detectors remains extremely challenging. Herein, ultrasound-assisted crystallization combined with the hot-pressing method is proposed to prepare large-area (10 cm × 10 cm) and high-quality quasi-monocrystalline thick film of a mixed-cation perovskite MA0.42 FA0.58 PbI3 . The rapid ultrasound-assisted crystallization provides more homogeneous nucleation, which is essential to the fabrication of large-area and uniform perovskite microcrystalline film. Furthermore, the post hot-pressing treatment is implemented to fuse the crystal boundaries, rearrange the crystal grains, and eliminate the voids between crystals, resulting in a quasi-monocrystalline film. After the hot-pressing treatment, the carrier mobility and the carrier mobility-lifetime product increased about 13-fold (from 1.8 to 23.5 cm2 s-1 V-1 ) and 18 times (from 8.4 × 10-6 to 1.5 × 10-4 cm2 V-1 ), respectively. As a result, a high-performance MA0.42 FA0.58 PbI3 quasi-monocrystalline X-ray detector is achieved with an impressively high sensitivity (1.16 × 106 µC Gyair -1 cm-2 ) and low detection limit (37.4 nGyair s-1 ), demonstrating the potential of the ultrasound-assisted crystallization and hot-pressing strategy from an industrial perspective.