Roles and regulation of quorum sensing in anaerobic granular sludge: Research status, challenges, and perspectives.
Anaerobic granular sludge (AnGS) has a complex and important internal microbial communication system due to its unique microbial layered structure. As a concentration-dependent communication system between bacterial cells through signal molecules, QS (quorum sensing) is widespread in AnGS and exhibits great potential to regulate microbial behaviors. Therefore, the universal functions of QS in AnGS have been systematically summarized in this paper, including the influence on the metabolic activity, physicochemical properties, and microbial community of AnGS. Subsequently, the common QS-based AnGS regulation approaches are reviewed and analyzed comprehensively. The regulation mechanism of QS in AnGS is analyzed from two systems of single bacterium and mixed bacteria. This review can provide a comprehensive understanding of QS functions in AnGS systems, and promote the practical application of QS-based strategies in optimization of AnGS treatment process.


Bariatric surgery and obstructive sleep apnea: a systematic review and meta-analysis.
Several studies evaluated the effect of bariatric surgery on obstructive sleep apnea (OSA) but findings have been inconsistent. The aim of this study was to conduct an updated systematic review and meta-analysis to investigate the effect of bariatric surgery on OSA. The databases for PubMed, CENTRAL, and Scopus were searched up to the 1st of December, 2021. Studies were included if they were cohort or case-control in design, included patients with diagnosis of OSA, the patients underwent any bariatric surgery, and the study performed postoperative polysomnography. The total number of the included patients was 2310 patients with OSA from 32 studies. Our analysis showed that bariatric surgery was associated with significant reduction in BMI (WMD = - 11.9, 95%CI: - 13.4, - 10.4), apnea-hypopnea index (AHI) (WMD = - 19.3, 95%CI: - 23.9, - 14.6), and respiratory disturbance index (RDI) (WMD = - 33.9, 95%CI: - 42.1, - 25.7). The rate of OSA remission after the surgery was 65% (95%CI: 0.54, 0.76). Our results suggest that bariatric surgeries are effective in reducing obesity among patients with OSA in addition to OSA severity measures. However, the low rate of OSA remission suggests that the main etiology of OSA is not only obesity but also includes other important variables such as the anatomy of the jaw.


The role of endogenous opioids in footshock-induced hyperthermia.
Either opioid or nonopioid forms of stress-induced analgesia can be elicited depending on the intensity or duration of the stressor. Several forms of stress have also been shown to cause hyperthermia in the rat. The present study investigated whether opioid and nonopioid forms of such stress-induced hyperthermia can be elicited in the rat as a function of footshock current intensity. Rats were given footshock after pretreatment with saline or naltrexone, or chronic morphinization. Footshock produced hyperthermia, the degree of which was found to be a function of current intensity. While the peak rise in temperature was not affected by naltrexone or chronic morphine administration, the rate of return to baseline temperature was slowed by these treatments. Thus, the endogenous opioid system appears to be involved in the return to normal body temperature following footshock, but not in the footshock-induced rise in temperature.


Spectroscopic and computational investigation of the interaction between the new anticancer agent enasidenib and human serum albumin.
Enasidenib (EDB) is a new therapeutic agent for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation. This research aimed at utilizing experimental and theoretical approaches to characterize the binding mechanism between EDB and human serum albumin (HSA). Formation of an EDB-HSA static complex was demonstrated by quenching of the HSA intrinsic fluorescence by EDB. Using well known mathematical relations (e.g. Stern-Volmer and Lineweaver-Burk equations), the recorded EDB-HSA fluorescence data were interpreted and revealed binding constants in the magnitude order of 104 M-1 for the different investigated temperatures. These determined results were taken into further mathematical calculations to reveal the thermodynamic properties of EDB-HSA binding. Results demonstrated that spontaneous EDB and HSA binding takes place led by electrostatic forces. Computational docking studies have further confirmed the latter finding showing that EDB fits into the HSA Sudlow site I. Molecular dynamic simulation was performed to calculate the root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg) and hydrogen bond parameters for the EDB-HSA complex.


In vivo sustained dermal delivery and pharmacokinetics of interferon alpha in biphasic vesicles after topical application.
Biphasic vesicles, a novel nanostructured lipid-based delivery system show potential for topical application of interferon alpha (IFN α) for the treatment of human papillomavirus (HPV) infections (anogenital warts). Dermal delivery of IFN α encapsulated in biphasic vesicles (BPV-IFN α), applied topically to the skin, was characterized in a guinea pig model. BPV-IFN α (1g, 2 MIU/g) was topically applied either as a single or multiple treatments on the skin of guinea pigs. As a comparison with currently used regimens, IFN α solution was administered intravenously or intradermally. Skin and serum samples were collected over 96 h, IFN α levels were determined by an antiviral assay, and half-life (t₁/₂) and elimination (k) rates were calculated. Topical BPV-IFN α treatment resulted in maximum skin levels (about 100,000 U/100 cm(2)) of IFN α within 6h and maintained for 72-96 h. Clearance from the skin after intradermal injections was initially fast (t₁/₂ 0.62 h, k 1.1179 h(-1)), followed by a slower steady decrease after 6h. After intravenous and intradermal administration, IFN α was rapidly cleared from the serum, t₁/₂ 0.75 h, k 0.9271 h(-1) and t₁/₂ 1.28 h, k 0.5421 h(-1), respectively, whereas after topical application, IFN α levels remained below 100 U/mL. Topical application of BPV- IFN α resulted in sustained delivery of biologically active IFN α locally into skin with minimal systemic exposure.


Frequencies of D19S433 silent alleles in a Japanese population of 1501 individuals and their effect on likelihood ratios calculated in kinship tests.
Although silent alleles in D19S433 typing using the GlobalFiler PCR Amplification Kit have been reported, the exact frequency of the D19S433 silent alleles in population data of 1501 Japanese individuals, which are widely used for the assessment of Japanese STR typing results, is unclear. In this study, we examined the exact D19S433 silent allele frequency in this population data. We newly observed the G32A variant causing silent alleles at D19S433 in five samples. Combining them with data including 30 samples with the variant reported previously, we determined that the total frequency of the silent alleles (i.e. the frequency of the G32A variant) in the 1501 Japanese samples was 0.0117 (35/3002). Using the D19S433 allele frequency data, we evaluated the effect of presence/absence information for the D19S433 silent allele on kinship tests. Likelihood ratios (LRs) were calculated for both simulated parent-child and full sibling cases, revealing that the LR may change by approximately 10-2 to 103 fold when the presence/absence of the D19S433 silent allele is revealed in a kinship test. Therefore, if a sufficiently large or small LR is obtained, there is little need to determine the presence/absence of the D19S433 silent allele in Japanese kinship tests using GlobalFiler. This study will be beneficial for the assessment of Japanese human identification and kinship test results using GlobalFiler.


Probing trace Hg2+ in a microfluidic chip coupled with in situ near-infrared fluorescence detection.
A novel microfluidic chip coupled with near-infrared (NIR) fluorescence detection set-up was established for specific analysis of trace Hg(2+). Based on the NIR fluorescence changes caused by Hg(2+)-induced dissolution and aggregation of label-free single-strand DNA (ssDNA) wrapped single-walled carbon nanotubes (SWNTs), Hg(2+) in aqueous solution were detected sensitively and specifically in the microfluidic chips system. Due to the small device dimension effect as well as the high efficiency of microfluidic chips, the reagent volume reduced from 500 μL to 9 μL and the minimum reaction time reaching the plateau was shortened from 60 min to 30 min, while the detection limit for Hg(2+) decreased from 10.5 nM to 1.5 nM, compared with that of measured in regular Eppendorf tube. The idea of detecting NIR fluorescence spectra in microfluidic systems opens new avenues to optical analysis and bioassays in probing trace species.


Discovery of novel salicylaldehyde derivatives incorporating an α-methylene-γ-butyrolactone moiety as fungicidal agents.
Plant diseases caused by phytopathogenic fungi and oomycetes pose a serious threat to ensuring crop yield and quality. Finding novel fungicidal candidates based on natural products is one of the critical methods for developing effective and environmentally friendly pesticides. In this study, a series of salicylaldehyde derivatives containing an α-methylene-γ-butyrolactone moiety were designed, synthesized, and their fungicidal activities were evaluated. The bioassay studies indicated that compound C3 displayed an excellent in vitro activity against Rhizoctonia solani with a half-maximal effective concentration (EC50 ) value of 0.65 μg/mL, higher than that of pyraclostrobin (EC50 = 1.44 μg/mL) and comparable to that of carbendazim (EC50 = 0.33 μg/mL). For Valsa mali and Phytophthora capsici, compound C3 also showed good fungicidal activities with EC50 values of 0.91 and 1.33 μg/mL, respectively. In addition, compound C3 exhibited promising protective in vivo activity against R. solani (84.1%) at 100 μg/mL, which was better than that of pyraclostrobin (78.4%). The pot experiment displayed that compound C3 had 74.8% protective efficacy against R. solani at 200 μg/mL, which was comparable to that of validamycin (78.2%). The antifungal mode of action research indicated that compound C3 could change the mycelial morphology and ultrastructure, increase cell membrane permeability, affect respiratory metabolism by binding to complex III, and inhibit the germination and formation of sclerotia, thereby effectively controlling the disease. The present study provides support for the application of these salicylaldehyde derivatives as promising potential pesticides with remarkable and broad-spectrum fungicidal activities against phytopathogenic fungi and oomycetes in crop protection. © 2023 Society of Chemical Industry.


Clinical and pathologic evidence of corticobasal degeneration and progressive supranuclear palsy in familial tauopathy.
Corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) are neurodegenerative tauopathies. Sporadic and familial cases of PSP and CBD have been noted, but both have not been reported in a single family. To describe the clinical, oculomotor, balance, functional imaging, histopathologic, and genetic studies in a family with CBD and PSP. A report of the clinical and pathological features in a familial tauopathy. University of Minnesota. Patients We evaluated 2 siblings and clinically assessed 20 additional family members. Demonstration of salient features in deceased and living family members. Histopathologically confirmed CBD in one sibling and PSP in another deceased sibling were demonstrated; both had clinical features of corticobasal syndrome. In addition, 3 siblings had probable PSP by clinical criteria. Genetic studies of 4 affected family members demonstrated the H1/H1 haplotype but did not reveal pathogenic tau mutations. The family history revealed consanguinity. This is the first report, to our knowledge, of CBD and PSP in 2 individuals in a single family who presented with corticobasal syndrome and had other affected siblings with clinical PSP. Despite clinical and pathologic heterogeneity, a unifying genetic etiology appears likely in this familial tauopathy.


Legionella pneumophila seen in Gram stains of respiratory secretions and recovered from conventional blood cultures.
We report a fatal case of Legionnaires' disease in which Legionella pneumophila was easily visible in large numbers in Gram stains of clinical material and was recovered from conventional blood cultures after seven days incubation. The presence of many readily seen Gram-negative, pleomorphic bacilli in direct Gram stains of respiratory secretions should support a possible diagnosis of Legionnaires' disease.


A multichannel microspectrophotometer for visual pigment investigations.
The microspectrophotometer described replaces the photomultiplier of conventional scanning systems with a multichannel detector. By eliminating scanning-related artifacts, particularly those associated with mechanical vibrations, this system makes possible ship-based microspectrophotometric studies of visual pigments of marine organisms too fragile for live transport to shore-based laboratories. The performance of the multichannel microspectrophotometer is compared with that of conventional scanning systems and absorbance spectra taken at sea on isolated rhabdoms from Euphausia pacifica are presented. Difference spectra gave a lambda max for rhodopsin of 483 nm and a lambda max for metarhodopsin of 489 nm.


Antibody directed targeting of methotrexate-containing small unilamellar vesicles.
The potential of antibody-linked SUVs containing MTX in anticancer therapy was investigated. The SUVs, mean diameter 50 +/- 20 nm, were prepared by probe sonication of MTX-containing MLVs and were covalently linked either to a RAMG or NRG. After incubation with M21 melanoma cells for 2 h, RAMG-linked SUVs showed 2 and 4 times more binding than NRG-linked MTX-containing SUVs or MTX-containing SUVs unlinked to any Ig. Furthermore, on incubating M21 melanoma cells with RAMG-linked 3H MTX-containing SUVs for 2, 4, and 8 h at 4 degrees C or 37 degrees C, a higher radioactivity was associated with cells at 37 degrees C than at 4 degrees C. Membrane immunofluorescence revealed aggregation of and cap formation by RAMG-linked SUVs after 2 h (37 degrees C) and endocytosis at 4 and 8 h at 37 degrees C. Electron microscopic and autoradiographic studies confirmed aggregation of 3H MTX-containing SUVs around and on the surface of M21 cells. Electron microscopy also revealed these SUVs inside invaginations of and under the plasma membrane of melanoma cells. A colony inhibition assay showed that RAMG-linked, MTX-containing SUVs were 60 times, 8 times, and 4.5 times more growth inhibitory than free MTX, NRG-linked MTX-containing SUV, and MTX-containing SUVs unlinked to any Ig, but not toxic to a human kidney cancer line (that did not react with RAMG).


Small ubiquitin-like Modifier (SUMO) modification inhibits GLI2 protein transcriptional activity in vitro and in vivo.
The Gli transcription factors are key downstream mediators of the Hedgehog (Hh) signaling pathway. How the activities of Gli transcription factors are regulated by upstream Hh signaling events and protein modifications are not fully understood. Here we show that GLI2 is conjugated by small ubiquitin-like modifier (SUMO) at lysine residues 630 and 716 in the cell. The level of GLI2 sumoylation is reduced by either mutations in six serine residues that are normally phosphorylated by protein kinase A (PKA) or stimulation by HH. This suggests that PKA phosphorylation enhances GLI2 sumoylation, whereas HH signaling inhibits it. In addition, mutation of these two lysines into arginine residues significantly increases GLI2 transcriptional activity in a cell-based reporter assay. The same mutations in the GLI2 locus also result in an increase in GLI2 activity in the mouse. Interestingly, GLI2 can interact with HDAC5 (histone deacetylase 5), but the GLI2 mutant cannot. Taken together, our results suggest that SUMO modification inhibits GLI2 transcriptional activity by recruiting HDAC5.


[Support of isolated foreign minors: patients' journeys].
People of all ages leave their own country to migrate to France. Isolated foreign minors are received and assisted by France Terre d'Asile an association promoting human rights and providing support to people in need of protection. This article looks back on the experience of two young minors.


Different Cabergoline Effect on Metabolic and Anthropometric Parameters in Female Prolactinoma Patients Versus Idiopathic Hyperprolactinemia Patients.
Hyperprolactinemia can lead to weight gain, insulin resistance, abnormal glucose homeostasis and dyslipidemia. Reversibility of these changes after normalization of prolactin with dopamine agonists is still controversial and needs more clarification. We aimed to: 1) evaluate and compare metabolic and anthropometric profile in female with newly diagnosed prolactin-secreting adenoma versus female idiopathic hyperprolactinemic patients; 2) compare the effects of one year cabergoline therapy on the metabolic profile and anthropometric parameters (by using visceral adiposity index as index for evaluation of adipose tissue dysfunction) in females with prolactinoma to female idiopathic hyperprolactinemic patients. We enrolled 40 female patients with newly diagnosed prolactinoma and 40 female patients with idiopathic hyperprolactinemia, who were matched according to: age; weight; BMI; waist; and prolactin levels. We enrolled the participants in this study at the time of diagnosis before therapy and they were followed up for 12 months. Cabergoline therapy had significant favorable effects on metabolic and anthropometric parameters, visceral adiposity index and in all patients (apart from HDLc in prolactinoma patients). Cabergoline therapy was significantly more effective in patient with idiopathic hyperprolactinemia than prolactinoma patients with regard to BMI, waist circumference, HDLc and visceral adiposity index despite normalization of prolactin levels in both groups. 12 months of Cabergoline treatment improved most of the anthropometric and metabolic parameters, and visceral adiposity index as a marker for adipose tissue dysfunction in both idiopathic hyperprolactinemia and prolactinoma patients. However, Cabergoline treatment was more effective in idiopathic hyperprolactinemic than prolactinoma patients.


In vitro activity of doripenem alone and in multi-agent combinations against extensively drug-resistant Acinetobacter baumannii and Klebsiella pneumoniae.
Carbapenems are increasingly needed to treat infections caused by drug-resistant gram-negative bacilli (GNB), but carbapenem resistance is increasing. We evaluated the activity of doripenem by broth microdilution against 96 extensively drug-resistant (XDR) Acinetobacter baumannii and Klebsiella pneumoniae isolates from patients with hospital-associated infections. All isolates were non-susceptible to doripenem, but ≥ 1 doripenem combination demonstrated synergy (fractional inhibitory concentration index: ≤ 0.5 for 2 agents, ≤ 0.75 for 3 agents) against 7 (15%) A. baumannii and 23 (48%) K. pneumoniae isolates; doripenem with rifampin and/or polymyxin B were most active. As doripenem has unique potential for use in prolonged infusions, suggested pharmacodynamic (PD) breakpoints range from 2-8 μg/mL; synergistic activity was found for higher proportions of XDR-GNB at higher PD breakpoints with doripenem with amikacin or with rifampin. The clinical utility of these observations requires further study, as treatment options for XDR-GNB infections are limited.


Thoracic trauma: presentation and management outcome.
To determine the presentation and management outcome of thoracic trauma in a tertiary care setting. Case series study. The study was carried out in the Department of Surgery, Pakistan Institute of Medical Sciences (PIMS), Islamabad from January to December 2005. A total of 143 patients, who presented with chest trauma, were included in the study. All the patients were assessed by the history, physical examination and ancillary investigations. Appropriate managements were instituted as required. Data was described in percentages. Out of 143 patients, 119 (83%) were males and 24 (17%) were females. Most of the patients belonged to the age group of 21-50 years. Ninety seven (66%) patients were admitted for indoor management. Blunt injury was found in 125 (87.4%) patients, while penetrating injuries in only 18 (12.6%) patients. Road Traffic Accidents (RTAs) were the commonest cause of trauma (n=103, 72%). Rib fracture was the commonest chest injury (74% patients). Head injury was the most frequently associated injury (18% of the patients). Tube thoracostomy was the commonest intervention undertaken in 65 (45%) patients. Seventeen (11.88%) patients were managed with mechanical ventilation. There were 17 deaths with a mortality rate of 11.88%. Thoracic trauma is an important cause of hospitalization, morbidity and mortality in the younger population. RTAs constitute the leading cause of thoracic trauma in our setup. Tube thoracostomy is the most frequent and at times the only invasive procedure required as a definitive measure in thoracic trauma patients. A policy of selective hospitalization helps to avoid unnecessary hospital admissions.


A Bioenergetics Approach to Understanding the Population Consequences of Disturbance: Elephant Seals as a Model System.
Using long-term empirical data, we developed a complete population consequences of acoustic disturbance (PCAD) model and application for northern elephant seals. We assumed that the animals would not successfully forage while in a 100-km-diameter disturbance region within their foraging and transit paths. The decrease in lipid gain due to exposure was then translated to changes in birth rate and pup survival. Given their large foraging range, elephant seals were resilient to such a disturbance, showing no population-level effects. However, similar track analysis showed that given their more coastal nature, California sea lions were within a 25-km-diameter region of disturbance more often.


The human vocal cord surface.
The epithelium of the vocal cord from children and adults is analysed with SEM and TEM. Scanning micrographs show that the apical cell membrane is furnished with microvilli and microridges of various patterns. The function of microridges is discussed in relation to the distribution and retention of mucus on the vocal cord.


Methods to Visualize the Actin Cytoskeleton During Plant Cell Division.
Cell division in plants consists of separating the mother cell in two daughter cells by the centrifugal growth of a new wall. This process involves the reorganization of the structural elements of the cell, namely the microtubules and actin cytoskeleton which allow the coordination, the orientation, and the progression of mitosis. In addition to its implication in those plant-specific structures, the actin cytoskeleton, in close association with the plasma membrane, exhibits specific patterning at the cortex of the dividing cells, and might act as a signaling component. This review proposes an overview of the techniques available to visualize the actin cytoskeleton in fixed tissues or living cells during division, including electron, fluorescent, and super-resolution microscopy techniques.


Stability and function of glycosaminoglycans in porcine bioprosthetic heart valves.
Glycosaminoglycans (GAGs) are important structural and functional components in native aortic heart valves and in glutaraldehyde (Glut)-fixed bioprosthetic heart valves (BHVs). However, very little is known about the fate of GAGs within the extracellular matrix of BHVs and their contribution to BHV longevity. BHVs used in heart valve replacement surgery have limited durability due to mechanical failure and pathologic calcification. In the present study we bring evidence for the dramatic loss of GAGs from within the BHV cusp structure during storage in saline and both short- and long-term Glut fixation. In order to gain insight into role of GAGs, we compared properties of fresh and Glut-fixed porcine heart valve cusps before and after complete GAG removal. GAG removal resulted in significant morphological and functional tissue alterations, including decreases in cuspal thickness, reduction of water content and diminution of rehydration capacity. By virtue of this diminished hydration, loss of GAGs also greatly increased the "with-curvature" flexural rigidity of cuspal tissue. However, removal of GAGs did not alter calcification potential of BHV cups when implanted in the rat subdermal model. Controlling the extent of pre-implantation GAG degradation in BHVs and development of improved GAG crosslinking techniques are expected to improve the mechanical durability of future cardiovascular bioprostheses.


Embolization-driven occlusion of the abdominal aortic aneurysmal sac as the basis of prevention of endoleaks in a new swine model.
To assess the effect of a new polymer in embolization of endoleaks using an animal model. A modified aortic stent-graft was placed in 20 pigs. Embolization was performed at the time of graft insertion with non-cytotoxic n-butyl-2-cyanoacrylate-metacryloxysulpholane and lipiodol (0.2:0.8ratio, 2 ml). Angiography, scanning electron microscopy and immuno-histochemistry were obtained at day 0, 1 week and 3 months. In control animals both type I and II endoleaks were demonstrated. In treated animals, neither type-I nor type-II endoleaks were observed and a fibro-proliferative response was demonstrated within the aneurysm thrombus. Host vascular responses govern the fate of the excluded aneurysm. Embolization of the sac and feeding arteries with non-cytotoxic glue sealed all occlusions by stimulating a massive restenosis-like process.


Management and obstetric outcome of ovarian hyperstimulation syndrome.
To describe the management and obstetric outcome, in terms of take home baby rate, of Ovarian Hyperstimulation Syndrome (OHSS). Case series. Baqai University Hospital, Nazimabad and Baqai Institute of Reproduction and Developmental Sciences, from January 1998 to December 2002. All patients undergoing in vitro fertilization and intracytoplasmic sperm injection from 5th January 1998 till 12th December 2002 were selected for the study. The infertile couple were interviewed, after informed consent, examined and investigated. Ovulation induction agents were prescribed to the female, if all the investigations were normal. In vitro fertilization was reserved for blocked fallopian tubes, endometriosis and abnormal semen parameters. Intracytoplasmic sperm injection was indicated for cases with few normal sperms. All the patients, who had developed mild ovarian hyperstimulation syndrome were excluded from the study. The patients who had developed moderate and severe ovarian hyperstimulation syndrome were included in the study. Out of 30 patients who developed OHSS, 23 had moderate OHSS, 7 patients had developed severe OHSS. Polycystic ovaries were present in 21 cases. Clinical pregnancy rate in the study was 40% and the take-home baby rate was 21.7%. Patients with polycystic ovarian disease were identified as the main reason for subfertility and were identified as the main reason for adverse foetal outcome. A remarkable pregnancy rate was achieved, but the take-home baby rate was comparatively low. But even then, the results were comparable in terms of take-home baby rate to the results reported in international literature.


Meningitis in mixed connective tissue disease complicated by herpes virus infection: case report.
The authors report a rare case of a female patient diagnosed with mixed connective tissue disease (MCTD). After a few years in remission, the patient acquired herpes zoster infection followed by a disease flare. Disease activity was accompanied by the development of meningitis. To determine whether the meningitis was caused by the previous herpes virus infection or was aseptic meningitis associated with the activity of MCTD raised important differential diagnostic issues. Repeated laboratory assessments of the patient's sera and cerebrospinal fluid revealed leukocytopenia, high anti-U1 ribonucleoprotein autoantibody level, increased immune complex, and decreased complement concentrations. The administration of corticosteroids resulted in rapid improvements in clinical symptoms and laboratory indicators.


Newborn screening programmes in Europe; arguments and efforts regarding harmonization. Part 2. From screening laboratory results to treatment, follow-up and quality assurance.
In a survey conducted in 2010/2011 data from the 28 EU member states, four EU candidate states (Croatia, FYROM, Iceland, Turkey), three potential EU candidate states (Bosnia Herzegovina, Montenegro, Serbia), and two EFTA states (Norway and Switzerland) were collected. The status and function of newborn screening (NBS) programmes were investigated from the information to prospective parents and the public via confirmation of a positive screening result up to decisions on treatment. This article summarises the results from screening laboratory findings to start of treatment. In addition we asked about the existence of feedback loops reporting the conclusions of confirmation of screening results to the screening laboratory and communication of long-term outcome to diagnostic units and possibly existing central registries. Parallel to the description of actual practices of where, how and by whom the different steps of the programmes are executed, we also asked for the existence of guidelines or directives regulating the screening programmes, material to support information of parents about diagnoses and treatment and training facilities for professionals involved in the programmes. This survey gives a first comprehensive overview of the steps following a positive screening result in European NBS programmes. The 37 data sets reveal substantial variation of national screening panels, but also a lot of similarities. Analysis across all countries revealed that actual practice is often organised but not regulated by guidelines. Material to inform patients is available more often for explaining treatment (69 %) than explaining the necessity of confirmatory diagnostics (41 %). Training of professionals is rarely regulated by a guideline (2 %), but is offered for paediatricians (40 %) and dieticians (29 %) and only rarely for other professions (e.g. geneticists, clinical nurse specialists, psychologists). Registry-based evaluation of long-term outcome is as yet almost nonexistent (3 %).


Deformable hard tissue with high fatigue resistance in the hinge of bivalve Cristaria plicata.
The hinge of bivalve shells can sustain hundreds of thousands of repeating opening-and-closing valve motions throughout their lifetime. We studied the hierarchical design of the mineralized tissue in the hinge of the bivalve Cristaria plicata, which endows the tissue with deformability and fatigue resistance and consequently underlies the repeating motion capability. This folding fan-shaped tissue consists of radially aligned, brittle aragonite nanowires embedded in a resilient matrix and can translate external radial loads to circumferential deformation. The hard-soft complex microstructure can suppress stress concentration within the tissue. Coherent nanotwin boundaries along the longitudinal direction of the nanowires increase their resistance to bending fracture. The unusual biomineral, which exploits the inherent properties of each component through multiscale structural design, provides insights into the evolution of antifatigue structural materials.


Unusual chemistries in fungal meroterpenoid biosynthesis.
Meroterpenoids are polyketide and terpenoid hybrid natural products with remarkable biological activities. Recent progress in fungal meroterpenoid biosynthesis has revealed several unusual enzyme reactions and novel enzymes, including unique terpene cyclization reactions by a novel family of membrane-bound terpene cyclases and post-cyclization modification reactions by oxygenases, such as non-heme iron-dependent dioxygenases, flavin adenine dinucleotide-dependent monooxygenases, and cytochrome P450 monooxygenases. They contribute to the structural diversification and increase in complexity of fungal meroterpenoids. Structure-function studies of these enzymes provide strategies for engineering the biosynthetic machinery to create novel molecular scaffolds for drug discovery.


Effects of CO2-mediated changes in paper birch and white pine chemistry on gypsy moth performance.
We examined the effects of CO2-mediated changes in the foliar chemistry of paper birch (Betula papyrifera) and white pine (Pinus strobus) on performance of the gypsy moth (Lymantria dispar). Trees were grown under ambient or enriched CO2 conditions, and foliage was subjected to plant chemical assays and insect bioassays. Enriched CO2 atmospheres reduced foliar nitrogen levels and increased condensed tannin levels in birch but not in pine. Foliar carbohydrate concentrations were not markedly altered by CO2 environment. Gypsy moth performance was significantly affected by CO2 level, species, and the CO2 x species interaction. Under elevated CO2 conditions, growth was reduced for larvae fed birch, while development was prolonged for larvae fed pine. Although gypsy moths performed better overall on birch than pine, birch-fed larvae were influenced more by CO2-mediated changes in host quality.


Shifting Perspectives on the Challenges of Shared Decision Making in Mental Health Care.
Although shared decision making (SDM) has become the most preferable way in doctor-patient communication, it is not fully implemented in mental health care likely due to the complex nature of psychiatric syndromes and treatments. In this review we provide a systematic overview of all perceived and reported barriers to SDM in the literature, acknowledging field-specific challenges, and offering perspectives to promote its wider use. We conducted a systematic search of the wider literature in different databases and included all publications mentioning specified barriers to SDM in psychiatric care. Relevant data and opinions were categorised into micro-, meso- and macro-level themes and put into clinical perspective. We derived 20 barriers to SDM from 100 studies and reports. Eight were on micro-level care delivery, seven involved meso-level issues, five concerned macro-level themes. The multitude of perceived and actual barriers to SDM underline the challenges its implementation poses in mental health care, some of which can be resolved while others are inherent to the nature of the care, with its long-term relationships, complex dynamics, and social consequences, all requiring a flexible approach. We present four perspectives to help change views on the potential of SDM in mental health care.


Activation of protein kinase D3 by signaling through Rac and the alpha subunits of the heterotrimeric G proteins G12 and G13.
PKD is the founding member of a novel protein kinase family that also includes PKD2 and PKD3. PKD has been the focus of most studies up to date, but little is known about the mechanisms that mediate PKD3 activation. Here, we show that addition of aluminum fluoride to COS-7 cells cotransfected with PKD3 and Galpha13 or Galpha12 induced PKD3 activation, which was associated with a transient plasma membrane translocation of cytosolic PKD3. Treatment with Clostridium difficile toxin B blocked PKD3 activation induced by either bombesin or by aluminum fluoride-stimulated Galpha12/13 but did not affect Galphaq-induced PKD3 activation. Furthermore, PKD3 immunoprecipitated from cells cotransfected with a constitutively active Rac (RacV12) exhibited a marked increase in PKD3 basal catalytic activity. In contrast, cotransfection with active Rho (RhoQ63L), Cdc42 (Cdc42Q61L), or Ras (RasV12) did not promote PKD3 activation. Expression of either COOH-terminal dominant-negative fragment of Galpha13 or dominant negative Rac (Rac N17) attenuated bombesin-induced PKD3 activation. Treatment with protein kinase C (PKC) inhibitors prevented the increase in PKD3 activity induced by RacV12 and aluminum fluoride-stimulated Galpha12/13. The catalytic activation of PKD3 in response to RacV12, alpha12/13 signaling or bombesin correlated with Ser-731/Ser-735 phosphorylation in the activation loop of this enzyme. Our results indicate that Galpha12/13 and Rac are important components in the signal transduction pathways that mediate bombesin receptor-induced PKD3 activation.


Neuron-specific and state-specific differences in calcium homeostasis regulate the generation and degeneration of neuronal architecture.
Many stimuli (e.g., neurotransmitters and electrical activity) regulate neuromorphogenesis by changing intracellular calcium. The ionophore A23187 was employed as a receptor-independent method to investigate neuronal calcium homeostasis. Distinctive neuron-specific (B5 versus B19) and state-specific (growing versus non-growing) differences in calcium homeostasis were observed in cultured identified Helisoma neurons. Fura-2 studies revealed that A23187 induced a transient rise in intracellular calcium in growing neurons B5 but a sustained rise in growing neurons B19. In stable-state (non-growing) cells A23187 evoked only a transient calcium rise. Both neuron-specific and state-specific differences in calcium homeostasis were dependent on extracellular sodium. Morphological studies also indicated that such differences in calcium-regulatory capacity can have profound consequences on the generation and degeneration of neuronal architecture.


Experience-based teaching of therapeutics and clinical pharmacology of antiepileptic drugs. Sudden unexplained death in epilepsy: do antiepileptic drugs have a role?
The contents of this paper have been written to be used in a teaching program specifically designed for medical postgraduate education of resident physicians and fellows in training interested in the clinical pharmacology of antiepileptic drugs and their role in the treatment of epilepsy and/or in the prevention of sudden unexpected death associated with this disease. With some modifications, such as a specific lecture to provide an overview of the numerous concepts presented in the text, the article could be used when teaching fourth-year medical students. The format of the paper is a combination of didactic review and eight case reports in a self-learning format. A quiz for self-assessment is included at the end of the article (see Appendix). This material was covered in part in the 1992 Board Review Course for Clinical Pharmacology sponsored by the American College of Clinical Pharmacology. The format or setting of instruction for this material could include small learning groups composed of 10 to 15 students. When used in combination with other topics prepared in similar formats, this could become a take home course for those preparing to take the Boards in Clinical Pharmacology. Each instructor could select specific publications from the reference list for assigned readings depending upon the material emphasized by the instructor. The questions included at the end of the text could be used as either a closed or an open book quiz to assess student learning.


A systematic review of robotic surgery: From supervised paradigms to fully autonomous robotic approaches.
From traditional open surgery to laparoscopic surgery and robot-assisted surgery, advances in robotics, machine learning, and imaging are pushing the surgical approach to-wards better clinical outcomes. Pre-clinical and clinical evidence suggests that automation may standardise techniques, increase efficiency, and reduce clinical complications. A PRISMA-guided search was conducted across PubMed and OVID. Of the 89 screened articles, 51 met the inclusion criteria, with 10 included in the final review. Automatic data segmentation, trajectory planning, intra-operative registration, trajectory drilling, and soft tissue robotic surgery were discussed. Although automated surgical systems remain conceptual, several research groups have developed supervised autonomous robotic surgical systems with increasing consideration for ethico-legal issues for automation. Automation paves the way for precision surgery and improved safety and opens new possibilities for deploying more robust artificial intelligence models, better imaging modalities and robotics to improve clinical outcomes.


Effects of Monoacyltrehalose Fraction of Rhodococcus Biosurfactant on the Innate and Adaptive Immunity Parameters In Vivo.
The biosurfactant monoacyltrehalose fraction isolated from Rhodococcus ruber IEGM 231 actinobacterium suppresses antibody production, bactericidal potential, and production of IL-1β by mouse peritoneal cells after intraperitoneal and intramuscular injection and stimulates the production of IL-10 after intraperitoneal injection. The data of in vitro experiments attest to an important role of bacterial glycolipids in the regulation of the functions of splenocytes and peritoneal macrophages.


Severe hypernatremia complicating urinary tract obstruction.
Severe hypernatremia and hyperosmolar dehydration developed in a patient with partial urinary tract obstruction. The urine was initially hypotonic, and there was no response to exogenous vasopressin. These abnormalities resolved with relief of the urinary tract obstruction and replacement of the water deficit. This case documents lower urinary tract obstruction as a cause of nephrogenic diabetes insipidus and severe hypernatremia and illustrates its reversible nature.


Overexpression of Orai1 and STIM1 proteins alters regulation of store-operated Ca2+ entry by endogenous mediators.
Orai1 and STIM1 have been identified as the main determinants of the store-operated Ca(2+) entry (SOCE). Their specific roles in SOCE and their molecular interactions have been studied extensively following heterologous overexpression or molecular knockdown and extrapolated to the endogenous processes in naïve cells. Using molecular and imaging techniques, we found that variation of expression levels of Orai1 or STIM1 can significantly alter expression and role of some endogenous regulators of SOCE. Although functional inhibition of Ca(2+)-independent phospholipase A(2) β (iPLA(2)β or PLA2g6A), or depletion of plasma membrane cholesterol caused a dramatic loss of endogenous SOCE in HEK293 cells, these effects were attenuated significantly when either Orai1 or STIM1 were overexpressed. Molecular knockdown of iPLA(2)β impaired SOCE in both control cells and cells overexpressing STIM1. We also discovered important cross-talk between expression of Orai1 and a specific plasma membrane variant of iPLA(2)β but not STIM1. These data confirm the role of iPLA(2)β as an essential mediator of endogenous SOCE and demonstrate that its physiological role can be obscured by Orai1 and STIM1 overexpression.


Changes in the secretion of inhibin and steroid hormones during induced follicular atresia after hypophysectomy in the rat.
Sequential changes in the function of antral follicles during the period of follicular atresia were investigated after hypophysectomy (Hypox) at 1100 hr on proestrus. Within 6 hours after Hypox, concentrations of progesterone (P), testosterone (T) and estradiol-17 beta (E) decreased abruptly in ovarian venous plasma (OVP) and follicles showed a reduced ability to ovulate. Six hours after Hypox, ovulation was still induced by human chorionic gonadotropin (hCG) in all animals but with significantly fewer number of oocytes compared to the group given hCG at 1100 hr on the day of proestrus. Nine hours after Hypox, several granulosa cells of all large follicles (greater than 400 microns in diameter) exhibited morphological signs of atresia. Twelve hours after Hypox, all large and medium sized (200-400 microns in diameter) follicles showed advanced stages of atresia and almost all follicles failed to ovulate in response to hCG. Inhibin activity in OVP declined more slowly compared to the profiles of steroid hormones and 53% of the initial inhibin activity was still maintained at 18 hours after the operation. Inhibin activity further decreased to 7% of the initial level at 24 hours and was undetectable by 48 hours after Hypox. These results suggest that fully developed Graafian follicles gradually lose their ability to secrete inhibin in contrast to the rapid decrease in secretion of steroid hormone during the process of atresia.


DAS28: a useful instrument to monitor infliximab treatment in patients with rheumatoid arthritis.
The Disease Activity Score using 28 joint counts (DAS28) has been developed in a cohort of patients with rheumatoid arthritis in which only conventional anti-rheumatic treatments were used. It has extensively been validated to monitor disease activity in daily clinical practice as well as in clinical trials. The study of Vander Cruyssen and colleagues showed that the DAS28 correlated best with the decisions of rheumatologists to increase the infliximab dose because of insufficient response. This result once more confirms the validity of the DAS28 to monitor disease activity in patients with rheumatoid arthritis and to titrate treatment with biologicals.


Incidence and risk factors of delirium in multi-center Thai surgical intensive care units: a prospective cohort study.
Delirium in intensive care units increases morbidity and mortality risk. The incidence and risk factors of delirium vary among studies. This study therefore aimed to determine the incidence and risk factors of delirium in Thai university-based surgical intensive care units. A multi-center, prospective cohort study was conducted. All patients who had been admitted to surgical intensive care units (SICU) between April 2011 and January 2012 were enrolled. Delirium was diagnosed using the Intensive Care Delirium Screening Checklists (ICDSC). The univariable and multivariable risk regression analyses were analyzed and presented as risk ratio (RR) and 95 % confidence interval (CI). The overall incidence of delirium was 3.6 % (162 of 4450, 95 % CI 3.09-4.19 %) whilst the incidences of delirium for patients being admitted ≤48 and >48 h were 0.7 % (21 of 2967, 95 % CI 0.41-1.01 %) and 8.3 % (141 of 1685, 95 % CI 7.04-9.68 %), respectively. The incidence of delirium on each study site was significantly different (range between 0 and 13.9 %, P < 0.001). Delirious patients had a significantly higher age (65.3 ± 15.6 versus 61.8 ± 17.3 years, P = 0.013), higher Acute Physiology and Chronic Health Evaluation II score (APACHE II score) (16 (12-23) versus 10 (7-15), P < 0.001), and higher sequential organ failure assessment score (5 (2-8) versus 2 (1-5), P < 0.001). The median duration of delirium was 3 (1-5) days. Delirious patients had significantly longer duration of ICU stay (8 (5-19) versus 2 (1-4), P < 0.001) and higher ICU mortality rate (23.5 versus 8.1 %, P < 0.001). Sepsis (RR = 3.70, 95 % CI 2.33-5.90, P < 0.001), exposure to sedative medications (RR = 3.54, 95 % CI 2.13-5.87, P < 0.001), higher APACHE II score (RR = 2.79, 95 % CI 1.98-3.95, P < 0.001), thoracic surgery (RR = 1.74, 95 % CI 1.09-2.78, P = 0.021), and emergency surgery (RR = 1.70, 95 % CI 1.09-2.65, P = 0.019) were independent risk factors of delirium in SICU. Sepsis, exposure to sedative medications, higher APACHE II score, thoracic surgery, and emergency surgery were independent risk factors of delirium in Thai university-based surgical intensive care units.


Softball injuries treated in US EDs, 1994 to 2010.
Softball is a popular participant sport in the United States. This study investigated the epidemiology of softball injuries with comparisons between children and adults. Data from the National Electronic Injury Surveillance System for patients 7 years and older treated in an emergency department (ED) for a softball injury from 1994 through 2010 were analyzed. An estimated 2107823 (95% confidence interval [CI], 1736417-2479229) patients were treated in US EDs for a softball injury during the 17-year study period. The annual number of injuries decreased by 23.0% from 1994 to 2010 (P < .001); however, during the last 6 years of the study, injuries increased by 11.7% (P = .008). The annual rate of softball injuries increased significantly during the study period (P = .035). The most commonly injured body regions were the hand/wrist (22.2%) and face (19.3%). Being hit by a ball was the most common mechanism of injury (52.4%) and accounted for most of face (89.6%) and head (75.7%) injuries. Injuries associated with running (relative risk, 2.36; 95% CI, 1.97-2.82) and diving for a ball (relative risk, 4.61; 95% CI, 3.50-6.09) were more likely to occur among adult than pediatric patients. To our knowledge, this is the first study to investigate softball injuries using a nationally representative sample. Softball is a common source of injury among children and adults. Increased efforts are needed to promote safety measures, such as face guards, mouth guards, safety softballs, and break-away bases, to decrease these injuries.


Volume changes and potential artifacts of epithelial cells of frog skin following impalement with microelectrodes filled with 3 m KCl.
Cells of isolated frog skin epithelium were observed microscopically during impalement with standard microelectrodes of 5 to 20 Momega resistance, filled with 3 m KCl. Impaled cells, as well as some neighboring cells, were seen to swell 10 to 100 sec after impalement, while the negative potential recorded by the microelectrode depolarized (open circuit conditions). Apparently, osmotic swelling of small epithelial cells may be caused by diffusion of KCl from such electrodes. This conclusion is supported by calculations quoted from the literature of KCl loss from microelectrodes. Intracellular recordings from epithelia with destructed cellular membranes gave negative "pre-tip potentials" of up to mV. The potentials could be altered by electrode movement, by decreasing the ambient pH or the tip-pH and by modifying the fixed charges of the tissue chemically. It is shown that even a moderate loss of KCl, which will not result in appreciable swelling, can produce negative potentials in front of the electrode tip if the protoplasm has a high density of negative fixed charges. We suggest the use of 3 m KCl electrodes with resistances above 30 Momega if after impalement compression of intracellular material by the tip can be avoided. Where such compression cannot be avoided, it is best to fill the microelectrode with an isotonic solution which mimics the electrolyte composition of the cytosol.


Vulnerability to alcohol consumption, spiritual transcendence and psychosocial well-being: test of a theory.
to demonstrate the relations among vulnerability, self-transcendence and well-being in the young adult population and the effect of each of these variables on the adoption of low-risk consumption conducts. quantitative and cross-sectional correlation study using structural equations analysis to test the relation among the variables. an inverse relation was evidenced between vulnerability to alcohol consumption and spiritual transcendence (β-0.123, p 0.025) and a direct positive relation between spiritual transcendence and psychosocial well-being (β 0.482, p 0.000). the relations among the variables spiritual transcendence, vulnerability to alcohol consumption and psychosocial well-being, based on Reed's Theory, are confirmed in the population group of young college students, concluding that psychosocial well-being can be achieved when spiritual transcendence is enhanced, as the vulnerability to alcohol consumption drops. demonstrar as relações entre vulnerabilidade, autotranscendência e bem-estar na população adulta jovem e o efeito de cada uma destas variáveis na adoção de condutas de baixo risco de consumo. estudo quantitativo, transversal do tipo correlacional que utilizou a análise estatística de Equações Estruturais para comprovar a relação entre as variáveis. evidenciou-se uma relação inversa entre a vulnerabilidade ao consumo do álcool e a transcendência espiritual (β-0.123, p 0.025) e uma relação direta positiva entre a transcendência espiritual e o bem-estar psicossocial (β 0.482, p 0.000). Conclusões: as relações das variáveis transcendência espiritual, vulnerabilidade ao consumo do álcool e bem-estar psicossocial, fundamentadas na Teoria de Reed, são confirmadas no grupo populacional de jovens adultos universitários, concluindo que é possível alcançar o bem-estar psicossocial quando se incrementa a transcendência espiritual, enquanto a vulnerabilidade ao consumo do álcool se reduz. demostrar las relaciones entre vulnerabilidad, autotrascendencia y bienestar en la población adulta joven y el efecto de cada una de estas variables en la adopción de conductas de bajo riesgo de consumo. estudio de abordaje cuantitativo, trasversal de tipo correlacional que utilizó el análisis estadístico de Ecuaciones Estructurales para la comprobación de la relación entre las variables. se evidenció relación inversa entre la vulnerabilidad al consumo de alcohol y la trascendencia espiritual (β-0.123, p 0.025) y una relación directa positiva entre la trascendencia espiritual y el bienestar psicosocial (β 0.482, p 0.000). las relaciones de las variables trascendencia espiritual, vulnerabilidad al consumo de alcohol y bienestar psicosocial, fundamentadas en la Teoría de Reed, son confirmadas en el grupo poblacional de adultos jóvenes universitarios, concluyendo que es posible alcanzar el bienestar psicosocial cuando se incrementa la trascendencia espiritual, en tanto que la vulnerabilidad al consumo de alcohol se reduce.


Predictive values of procalcitonin for coinfections in patients with COVID-19: a systematic review and meta-analysis.
To assess the ability of procalcitonin (PCT)-a promising marker for coinfections-to predict coinfections in patients with COVID-19. In this systematic review and meta-analysis, PubMed, Embase, Web of Science, Cochrane, the China National Knowledge Infrastructure (CNKI), and Wanfang were searched to identify eligible studies (up to August 30, 2021). Articles that reported the predictive value of PCT for coinfections in patients with COVID-19 were included. Individual and pooled sensitivities and specificities were reported, and I2 was used to test heterogeneity. This study was prospectively registered on the International Prospective Register of Systematic Reviews (PROSPERO) database (registration number: CRD42021283344). Five studies involving a total of 2775 patients reported the predictive value of PCT for coinfections in patients with COVID-19. The sensitivity, specificity, and area under the curve of PCT in predicting coinfections in the pooled studies were 0.60 (95% CI 0.35-0.81, I2 = 88.85), 0.71 (95% CI 0.58-0.81, I2 = 87.82), and 0.72(95% CI 0.68-0.76) respectively. Although PCT has limited predictive value for coinfections in patients with COVID-19, lower PCT levels seem to indicate a decreased probability of having a coinfection.


Is trimodality approach better then bimodality in stage IIIA, N2 positive non-small cell lung cancer?
Neoadjuvant treatment followed by surgery is currently being investigated for locally advanced non-small cell lung cancer (NSCLC). This study reports efficacy, toxicity and feasibility of neoadjuvant chemotherapy with concurrent radiotherapy (CCRT) in stage IIIA, N2 positive NSCLC. From March 2001 to February 2004, 52 patients with histologically confirmed stage IIIA, N2 positive NSCLC were registered. Patients received preoperative CCRT that consisted of weekly paclitaxel plus platinum chemotherapy and concurrent radiotherapy followed by surgery. Overall response rate was 76.9% (95% CI, 64-88%). The major grade 3-4 toxicities were radiation esophagitis (15.4%) and neutropenia (11.5%), and treatment-related mortality rate was 1.9%. Forty-two of 52 patients (80.8%) subsequently underwent surgical resection and 35 of 52 patients (67.3%) underwent complete resection. Among them, pathological complete response was obtained in 4.8%. Pathological downstaging rate to N0-1 and stage 0-II at surgery were 69.0% and 66.7%, respectively. The perioperative major morbidity rate was 23.8% and perioperative mortality was 2.4%. At a median follow-up of 33.9 months (range: 16.4-49.9), the median progression-free survival and overall survival were 16.5 months (95% CI, 6.2-26.8) and 25.6 months (95% CI, 14.6-36.6), respectively. Multivariate analyses identified that patients achieved mediastinal nodal clearance (downstage to pathological N0 or N1) after CCRT (p=0.02) and age at diagnosis<60 years (p=0.01) showed significantly improved survival. Neoadjuvant CCRT showed a high overall response rate with tolerable toxicity profile. Downstaging after CCRT may increase the rate of complete tumor resection and result in survival benefit in stage IIIA, N2 positive NSCLC patients.


Gene expression profile in human late radiation enteritis obtained by high-density cDNA array hybridization.
Late radiation enteritis is a sequela of radiation therapy to the abdomen. The pathogenic process is poorly understood at the molecular level. cDNA array analysis was used to provide new insights into the pathogenesis of this disorder. Gene profiles of six samples of fibrotic bowel tissue from patients with radiation enteritis and six healthy bowel tissue samples from patients without radiation enteritis were compared using membrane-based arrays containing 1314 cDNAs. Results were confirmed with real-time RT-PCR and Western blot analysis. Array analysis identified many differentially expressed genes involved in fibrosis, stress response, inflammation, cell adhesion, intracellular and nuclear signaling, and metabolic pathways. Increased expression of genes coding for proteins involved in the composition and remodeling of the extracellular matrix, along with altered expression of genes involved in cell- to-cell and cell-to-matrix interactions, were observed mainly in radiation enteritis samples. Stress, inflammatory responses, and antioxidant metabolism were altered in radiation enteritis as were genes coding for recruitment of lymphocytes and macrophages. The Rho/HSP27 (HSPB1)/zyxin pathway, involved in tissue contraction and myofibroblast transdifferentiation, was also altered in radiation enteritis, suggesting that this pathway could be related to the fibrogenic process. Our results provide a global and integrated view of the alteration of gene expression associated with radiation enteritis. They suggest that radiation enteritis is a dynamic process involving constant remodeling of each structural component of the intestinal tissue, i.e. the mucosa, the mesenchyme, and blood vessels. Functional studies will be necessary to validate the present results.


Fish IKKα from Japanese eel (Anguilla japonica) can activate NF-κB, AP1, and type I IFN signaling pathways.
Inhibitor of nuclear factor kappa-B kinase subunit alpha (IKKα) plays a pivotal role in the activation of nuclear factor kappa-B (NF-κB) pathway in response to pathogens infections in mammals, but the information about IKKα in the regulation of immune responses is still limited in teleost fishes. In the present study, the full-length cDNA of an IKKα homologue, AjIKKα, was cloned by 5' and 3' SMART RACE from Japanese eel, and its characteristics of expression in response to various PAMPs and A. hydrophila infection were investigated both in vivo and in vitro using quantitative real-time polymerase chain reaction (qRT-PCR). In addition, the subcellular localization of AjIKKα GFP fusion protein and the induction of AjIKKα in the activation of NF-κB, type I IFN and AP1 performed using Dual-Glo luciferase assay system were also detected. Sequence comparison analysis revealed that AjIKKα has typical conserved domains, including an N-terminal kinase domain, an ubiquitin-like domain, a scaffold dimerization domain, and a C-terminal NEMO-binding domain. The predicted three-dimensional structure of AjIKKα is similar to that of human IKKα. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed a broad expression for AjIKKα in a wide range of tissues, with the highest expression in the liver, followed by the intestine, gills, and spleen, and with a lower expression in the muscle and heart. The AjIKKα expressions in the liver and kidney were significantly induced following injection with the viral mimic poly I:C and Aeromonas hydrophila infection, whereas the bacterial mimic LPS down-regulated the expression of AjIKKα in the spleen. In vitro, the AjIKKα transcripts of Japanese eel liver cells were significantly enhanced by the treatment of LPS, poly I:C, CpG-DNA, and PGN or the stimulation of different concentration of Aeromonas hydrophila (1 × 106 cfu/mL, 1 × 107 cfu/mL, and 1 × 108 cfu/mL). Luciferase assays demonstrated that AjIKKα expression could significantly induce NF-κB, AP-1 and type I IFN promoter activation in a dose-dependent manner. Additionally, subcellular localization studies showed that AjIKKα was evenly distributed in the cytoplasm in the natural state, but AjIKKα was found to aggregate into spots in the cytoplasm after the stimulation of LPS and poly I:C. These results collectively indicated that AjIKKα plays an important role in innate immunity of host against antibacterial and antiviral infection likely via the activation of NF-κB, AP1and type I IFN signaling pathway.


A multilayer dynamic perturbation analysis method for predicting ligand-protein interactions.
Ligand-protein interactions play a key role in defining protein function, and detecting natural ligands for a given protein is thus a very important bioengineering task. In particular, with the rapid development of AI-based structure prediction algorithms, batch structural models with high reliability and accuracy can be obtained at low cost, giving rise to the urgent requirement for the prediction of natural ligands based on protein structures. In recent years, although several structure-based methods have been developed to predict ligand-binding pockets and ligand-binding sites, accurate and rapid methods are still lacking, especially for the prediction of ligand-binding regions and the spatial extension of ligands in the pockets. In this paper, we proposed a multilayer dynamics perturbation analysis (MDPA) method for predicting ligand-binding regions based solely on protein structure, which is an extended version of our previously developed fast dynamic perturbation analysis (FDPA) method. In MDPA/FDPA, ligand binding tends to occur in regions that cause large changes in protein conformational dynamics. MDPA, examined using a standard validation dataset of ligand-protein complexes, yielded an averaged ligand-binding site prediction Matthews coefficient of 0.40, with a prediction precision of at least 50% for 71% of the cases. In particular, for 80% of the cases, the predicted ligand-binding region overlaps the natural ligand by at least 50%. The method was also compared with other state-of-the-art structure-based methods. MDPA is a structure-based method to detect ligand-binding regions on protein surface. Our calculations suggested that a range of spaces inside the protein pockets has subtle interactions with the protein, which can significantly impact on the overall dynamics of the protein. This work provides a valuable tool as a starting point upon which further docking and analysis methods can be used for natural ligand detection in protein functional annotation. The source code of MDPA method is freely available at: https://github.com/mingdengming/mdpa .


Electro-deposit polyaniline on carbon electrode for voltammetric detection of lipase.
Normally, the pancreatic digestive enzymes are created and carried into the duodenum in an inactive form. During pancreatitis attacks, these enzymes are inhibited from reaching the duodenum, become activated while still in the pancreas, and begin to autodigest and destroy the pancreas. In order to accurately detect lipase within seconds, a square wave technique was explored without immobilizing enzyme and any other biomolecules over the electrode surface. The cyclic voltammetric (CV) technique was used to coat a carbon electrode with a thin layer of polyaniline. This modified electrode proved to be highly sensitive and specific to detect lipase between 0 and 225 IU/L, which is well within the normal physiological range. The consistency and reliability of this technique proved to be a very formidable detector of lipase present in abnormal quantities due to pancreatitis and other pathological disorders. The interference test has been performed to detect the lipase in the presence of amylase 50, 100, and 150 IU/L to understand the interference phenomenon with lipase detection. There is no significant effect of the amylase concentration over lipase detection resulting from using a modified carbon electrode. The response time of the modified carbon electrode is approximately 5s and the electrode has shown to be stable for 4 weeks at room temperature without special storage condition.


Exploring and Understanding the Biochemical Diversity of the Human Microbiota.
Recent studies have illuminated a remarkable diversity and abundance of microbes living on and within the human body. While we are beginning to appreciate associations of certain bacteria and genes with particular host physiological states, considerable information is lacking about the relevant functional activities of the human microbiota. The human gut microbiome encodes tremendous potential for the biosynthesis and transformation of compounds that are important for both microbial and host physiology. Implementation of chemical knowledge and techniques will be required to improve our understanding of the biochemical diversity of the human microbiota. Such efforts include the characterization of novel microbial enzymes and pathways, isolation of microbial natural products, and development of tools to modulate biochemical functions of the gut microbiota. Ultimately, a molecular understanding of gut microbial activities will be critical for elucidating and manipulating these organisms' contributions to human health and disease.


Long-range charge transport through double-stranded DNA mediated by manganese or iron porphyrins.
Guanine oxidation by electron transfer results in the formation of a guanine radical cation, which is at the origin of long-range charge transport through double-stranded DNA. It is possible to observe guanine lesions at a long distance from the oxidative reagent covalently bound to DNA owing to the migration of the positive hole in the DNA pi-stacks. This phenomenon of long-range hole transport is classically studied in the literature with photosensitizers used as one-electron oxidants. It is shown in the present work that the process of long-range charge transport and the concomitant formation of guanine lesions at a long distance can be observed also in the case of two-electron oxidants. This is the signature of the formation of a transient guanine radical cation in the course of the two-electron abstraction process and consequently evidence of the separated one plus one electron abstraction steps. Long-range charge transport is likely to be a universal mechanism for any two-electron oxidant acting by electron abstraction provided that the second electron abstraction is slower than hole transfer.


Asthma and smoking status in a population-based study of California adults.
Because they experience respiratory symptoms, adults with asthma might be expected to avoid cigarette smoking. However, previous studies have not adequately addressed whether adults with asthma have a lower prevalence of smoking than the general population. The authors sought to determine whether adult asthmatics are less likely to smoke cigarettes than members of the general population. The authors used data from a random sample of 2,902 California adults ages 18 years or older,with oversampling of African Americans, Asian/Pacific Islanders, adults with disabilities, and adults aged 45 to 70 years. Sampling weights were used in all analyses. In this cross-sectional study, 217 participants (7.5%) reported a physician diagnosis of asthma. The prevalence of "ever smoking" was similar among adults with asthma (48.3%) and those without asthma (43.0%) (risk difference 5.3%; 95% CI -1.6%, 12.2%). There was also no difference in the prevalence of "current smoking" among adults with asthma (20.2%) compared with the non-asthmatic subjects (18.8%) (risk difference 1.4%; 95% CI -4.2%, 6.9%). After controlling for age, gender, race, and education, there was no evidence that adults with asthma were less likely to ever smoke. Although the confidence intervals did not exclude "no association," asthma was actually associated with an increased risk of ever smoking (OR 1.3; 95% CI 1.0, 1.8). There was also no association between asthma and the risk of current smoking after controlling for covariates (OR 1.1; 95% CI 0.8, 1.6). Moreover, there were no differences in "age of smoking initiation," "duration of smoking," or "intensity of smoking" after adjusting for demographic characteristics. Redefining the referent group to exclude respondents with other chronic lung diseases did not appreciably change study conclusions. Adults with asthma do not appear to selectively avoid cigarette smoking. Specific smoking prevention and cessation efforts should be targeted to adults with asthma.


[Curative effect of percutaneous microwave coagulation therapy for hepatocellular carcinoma].
To observe the curative effect of percutaneous microwave coagulation therapy (PMCT) with 2450 MHz microwave antenna for hepatocellular carcinoma. Under local or epidural anesthesia, a thin percutaneous microwave antenna was introduced with ultrasound guidance into the tumor in the liver for thermo-coagulation. Among the 97 hepatic cancer lesions in 52 patients, 61(62.9%) with phi < 3 cm were coagulated once. In follow-up of 6-12 months of these lesions, 57(93.4%) showed no recurrence by CT or MRI. Thirty-six (37.1%) with 3 cm < phi < 5 cm coagulated twice showed that 27 (75.0%) gave CR and 9 (25.0%) gave PR by CT or MRI in follow up of 6 months. There were no serious clinical side effects or complications in the PMCT patients. Percutaneous microwave coagulation therapy gives good curative effect on liver tumor with phi < 3 cm. It is partly effective on lesions 3 cm < phi < 5 cm.


Pelvic inflammatory disease complicated by massive helminthic hyperinfection.
Strongyloidiasis is a potentially life-threatening condition which, when appropriately diagnosed early in its course, is easily eradicated. When severe, it may mimic other disease processes including appendicitis or severe pelvic inflammatory disease. The diagnosis of parasitic infestation should be considered in any individual who has lived in an endemic area and presents with diarrhea regardless of attendant conditions and superimposed disease processes. A minimum workup consisting of stool examination for ova and parasites should be performed on all such individuals. Thiabendazol is the treatment of choice in nonpregnant patients; however, piperazine tartrate has established safety and efficacy in pregnancy and is therefore preferable in the pregnant patient.


Anesthesia for cardiac transplantation: experience from a single center.
Cardiac transplantation has become the established therapeutic modality in patients with end-stage heart failure. This article presents our institution's clinical experience in the anesthetic management of patients who underwent cardiac transplantation between February 1998 and August 2012. In our institution, 175 patients (136 males and 39 females) diagnosed as having end-stage heart failure have undergone cardiac transplantation between February 1998 and August 2012. A retrospective review performed on this series of patients sought to analyze elements of perioperative anesthetic care, including preoperative characteristics, general anesthia, and blood product usage. The patients were diagnosed as having either nonischemic cardiomyopathy (n = 128; 73%) or ischemic cardiomyopathy (n = 47; 27%). Seventy-three of them had undergone previous cardiac surgery. Invasive arterial, central venous, and pulmonary arterial pressures were monitored as well as intraoperative transesophageal echocardiography. Etomidate was used as the induction agent in 158/175 patients (average dose, 18.67 ± 1.91 mg). The average intraoperative fentanyl dose was 898.85 ± 211.65 μg. Anesthesia was maintained with either end-tidal 2%-4% sevoflurane (n = 132) or 4%-6% desflurane (n = 43). Dopamine, dobutamine, and epinephrine were used after weaning from cardiopulmonary bypass and continued upon exiting the operating room in 168, 159, and 143 patients, respectively. Inhaled nitric oxide (20-40 ppm) was used in 37 patients (21%). The total amount of perioperative blood, fresh frozen plasma, and thrombocyte suspension transfusions were 2.95 ± 2.05 (range, 1-15), 1.29 ± 0.97 (range, 0-6), and 1.23 ± 2.29 (range; 0-12) units, respectively. On average, patients were extubated 16 hours after arrival in the intensive care unit where they remained to day 6. A total of 67 patients (38%) died during the follow-up; infection and right ventricular failure were the most common causes. Anesthesia for cardiac transplantation requires an appreciation of heart failure pathophysiology, invasive monitoring, and skillful anesthetic and postoperative care.


Racial and Ethnic Disparities in Total Joint Arthroplasty Care: A Contemporary Systematic Review and Meta-Analysis.
Total joint arthroplasty (TJA) is one of the most common surgical procedures in the United States; however, racial and ethnic disparities in utilizations and outcomes have been well documented. This systematic review and meta-analysis investigated associations between race/ethnicity and several metrics in total hip arthroplasty (THA) and total knee arthroplasty (TKA). In August 2021, PubMed, Scopus, CINAHL, and SPORTDiscus databases were queried. Sixty three studies investigating racial/ethnic disparities in TJA utilizations, complications, mortalities, lengths of stay (LOS), discharge dispositions, readmissions, and reoperations were included. Study quality was assessed using a modified Newcastle-Ottawa Scale. A majority of studies demonstrated disparities in TJA utilizations and outcomes. Black patients exhibited higher rates of 30-day complications (THA odds ratio [OR] 1.18, 95% confidence interval [CI] 1.08-1.29; TKA OR 1.20, 95% CI 1.10-1.31), 30-day mortality (THA OR 1.27, 95% CI 1.08-1.48), prolonged LOS (THA mean difference [MD] +0.27 days, 95% CI 0.21-0.33; TKA MD +0.30 days, 95% CI 0.20-0.40), nonhome discharges (THA OR 1.47, 95% CI 1.37-1.57; TKA OR 1.65, 95% CI 1.38-1.96), and 30-day readmissions (THA OR 1.13, 95% CI 1.08-1.19; TKA OR 1.19, 95% CI 1.16-1.21) than White patients. Rates of complications (THA 1.18, 95% CI 1.03-1.36), prolonged LOS (TKA MD +0.20 days, 95% CI 0.17-0.23), and nonhome discharges (THA OR 1.26, 95% CI 1.10-1.45; TKA OR 1.37, 95% CI 1.22-1.53) were also increased among Hispanic patients, while Asian patients experienced longer LOS (TKA MD +0.09 days, 95% CI 0.05-0.12) but fewer readmissions. Outcomes among American Indian-Alaska Native and Pacific Islander patients were infrequently reported but similarly inequitable. Racial and ethnic disparities in TJA utilizations and outcomes are apparent, with minority patients often demonstrating lower rates of utilizations and worse postoperative outcomes than White patients. Continued research is needed to evaluate the efficacy of recent efforts dedicated to eliminating inequalities in TJA care. IV.


Resection and total femoral prosthesis reconstruction treatment of massive femoral hemophilic pseudotumor: A case report.
Hemophilic pseudotumor is a rare and serious complication of hemophilia, often occurring in the long bones and muscle tissue of the extremities, with an incidence of about 1-2%. However, there is no effective surgical treatment for massive hemophilia pseudotumors of the extremities. Therefore, we would like to report this case to provide new ideas and methods for the treatment of massive hemophilic pseudotumors of the extremities through resection and total femoral prosthesis reconstruction. After admission, the patient first underwent a month-long coagulation factor replacement therapy to maintain the patient's factor IX level at approximately 100%. Then, extensive resection of hemophilic pseudotumor and total femoral prosthesis reconstruction was performed in collaboration with several departments, and we collected the patient's preoperative, intraoperative and postoperative data for analysis. After coagulation factor replacement therapy the patient's factor IX level was significantly increased and approached 100%. The surgical procedure was uneventful, and postoperative X-ray suggested a well-positioned prosthesis with postoperative pathological features consistent with a hemophilic pseudotumor. The patient was able to move around with the assistance of a walker 14 days after surgery, and there was no recurrence after one year of follow-up. For treat the massive hemophilic pseudotumors of the extremities, extensive resection and prosthetic replacement with coagulation factor replacement therapy is a safe and effective treatment that can significantly improve the prognosis and quality of life of patients.


Influence of mechanical tail-detachment techniques of schistosome cercariae on the production, viability, and infectivity of resultant schistosomula: a comparative study.
Two decaudation methods used by Schistosoma mansoni cercariae for the production of schistosomula by in vitro transformation were comparatively tested. Both low-pressure syringe passage and vortex mixing of the cercariae produced schistosomula of similar percentages of viability, and the levels of worm recovery following subcutaneous injection in mice were also comparable, though low. By all criteria tested, including simplicity and time requirement, the two methods are equally efficient and are well applicable for mass production of schistosomula.


Spatio-temporal patterns of mortality in Pemphigus populicaulis and P. populitransversus on cottonwoods.
Galls of the aphid species Pemphigus populitransversus and P. populicaulis from a single cottonwood in Clinton, New York were censused for mortality approximately every ten days during the summer of 1978. P. populitransversus had significantly higher survival than P. populicaulis. Both species of aphid showed considerably elevated mortality later in the season. Mortality was not spatially random, but neighboring galls had a tendency to die at close to the same time. This tendency to spatially autocorrelated mortality varied from time to time, being more pronounced earlier in the season than later. Later in the season, galls on the outer portions of branches tended to have a higher mortality rate than galls closer to the main trunk of the tree. This effect was highly significant in P. populicaulis, but only suggestive in P. populitransversus.The proportion of dead galls in samples of the two species taken at other times and places was consistent with the data from the censuses. In addition, the potential of two common predators, Anthocoris sp. and Leucopis sp., for producing autocorrelated mortality in Pemphigus was assessed in these collections. There was some association of Leucopis with regions of higher mortality, but this was not the case in Anthocoris. Leucopis tended to be found in galls of P. populicaulis more frequently than in P. populitransversus unlike Anthocoris, suggesting that some of the differential mortality between P. populitransversus and P. populicaulis might be due to this dipteran predator.


Congenital triangular bones in the hand.
From the literature we found reports of 105 patients whom we judged had a triangular deformity of one of the bones of the hand or foot. We found 49 patients of our own with 84 delta-shaped phalanges limited strictly to the hand. This represents an incidence of 3.5% of our congenital abnormalities of the upper extremity. The deformity is associated with many abnormalities: syndactyly, polydactyly, symphalangism, triphalangeal thumb, cleft hand, and hypoplastic hand are the most frequent Triangular deformity of the bone of the index finger usually is associated with Apert's syndrome. Triangular deformity of the proximal phalanx of the ring finger often is found with central polydactyly. Our average follow-up time on these 49 patients was 14 years, giving us a chance to establish some guidelines and general rules about the natural history and treatment of the delta bone.


CT imaging with fistulography for perianal fistula: does it really help the surgeon?
To prospectively evaluate the relative accuracy of computed tomography (CT) fistulography for preoperative assessment of fistula in ano. Ethical committee approval and informed consent were obtained. A total of 22 patients (15 male and 7 female, age 21-58 years) who were suspected of having fistula in ano underwent preoperative CT fistulography (CTF). The CT images of 0.6 mm were obtained respectively before and after fistulography; contrast-enhanced CT scan was also performed in 22 patients. CTF images were evaluated by two expert radiologists to assess the fistulas in the following respects: (a) the volume-rendered imaging; (b) the extensions of active inflammatory tissue; (c) the internal opening and external opening; (d) the hidden areas of tract or abscess; and (e) the deep abscess adjacent to fistula. CT findings in 18 patients were compared with surgical findings or exam under anesthesia. The CTF findings in 18 cases were basically in accordance with the surgical findings and/or examination findings under anesthesia. Both coronal and transverse planes were useful in assessing the location and direction of tracts or abscesses. Complicated spatial information within the perianal soft tissue about the fistula with secondary ramifications or abscesses can be easily demonstrated to the surgeons. Contrast-enhanced images were useful in assessing the inflammatory lesion activity and infiltrated area. CTF exquisitely depicts the perianal anatomy and shows the fistulous tracks with their associated ramifications, enables selection of the most appropriate surgical treatment, and therefore minimizes all chances of recurrence.


Proposal of a parametric imaging method for quantitative diagnosis of liver fibrosis.
Coming up with a quantitative diagnosis method for liver fibrosis using ultrasound would be highly significant. To permit tissue characterization using the characteristics of the echo signal such as power spectrum, texture parameters, local attenuation, and statistical characteristics, the relation between complicated scatterer structures and the echo signal must be understood. In this study, we analyzed the property of the echo amplitude envelope using computer-simulated scatterer models. These models mimicked various liver conditions to evaluate our quantitative parametric imaging methods. Statistical echo characteristics changed with the density of the heterogeneous scatterer buried in a speckle. The new analysis method for a medium in which some tissues are embedded was proposed in consideration of analysis results from computer simulations. In the new method, it is possible to eliminate the influence of a cyst or veins and to detect the existence of fibers more clearly than in previous methods.


Telomeres, aging and cancer: in search of a happy ending.
Telomeres are distinctive structures, composed of a repetitive DNA sequence and associated proteins, that cap the ends of linear chromosomes. Telomeres are essential for maintaining the integrity and stability of eukaryotic genomes. In addition, under some circumstances, telomeres can influence cellular gene expression. In mammals, the length, structure, and function of telomeres have been proposed to contribute to cellular and organismal phenotypes associated with cancer and aging. Here, we discuss what is known about the basis for the links between telomeres, aging and cancer, and some of the known and proposed consequences of telomere dysfunction and maintenance for mammalian cells and organisms.


Berberine protects against diabetic kidney disease via promoting PGC-1α-regulated mitochondrial energy homeostasis.
Disordered lipid metabolism and disturbed mitochondrial bioenergetics play pivotal roles in the initiation and development of diabetic kidney disease (DKD). Berberine is a plant alkaloid, used in Chinese herbal medicine. It has multiple therapeutic actions on diabetes mellitus and its complications, including regulation of glucose and lipid metabolism, improvement of insulin sensitivity, and alleviation of oxidative damage. Here, we investigated the reno-protective effects of berberine. We used samples from DKD patients and experiments with models of DKD (db/db mice) and cultured podocytes, to characterize energy metabolism profiles using metabolomics. Molecular targets and mechanisms involved in the regulation of mitochondrial function and bioenergetics by berberine were investigated, along with its effects on metabolic alterations in DKD mice. Metabolomic analysis suggested altered mitochondrial fuel usage and generalized mitochondrial dysfunction in patients with DKD. In db/db mice, berberine treatment reversed the disordered metabolism, podocyte damage and glomerulosclerosis. Lipid accumulation, excessive generation of mitochondrial ROS, mitochondrial dysfunction, and deficient fatty acid oxidation in DKD mouse models and in cultured podocytes were suppressed by berberine. These protective effects of berberine were accompanied by activation of the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) signalling pathway, which promoted mitochondrial energy homeostasis and fatty acid oxidation in podocytes. PGC-1α-mediated mitochondrial bioenergetics could play a key role in lipid disorder-induced podocyte damage and development of DKD in mice. Restoration of PGC-1α activity and the energy homeostasis by berberine might be a potential therapeutic strategy against DKD.


Early and midterm outcome after off-pump and on-pump surgery in Beating Heart Against Cardioplegic Arrest Studies (BHACAS 1 and 2): a pooled analysis of two randomised controlled trials.
Although no randomised controlled trial has assessed the midterm effects of coronary-artery bypass surgery on the beating heart, this technique is being used in more and more patients. We did two randomised trials to compare the short-term morbidity associated with off-pump and on-pump myocardial revascularisation. Our aim was to pool the results to assess midterm outcomes. From March, 1997, to November, 1999, we randomly allocated 200 patients to off-pump and 201 to on-pump coronary surgery. In Beating Heart Against Cardioplegic Arrest Study (BHACAS) 1, we excluded patients who had had myocardial infarction in the past month or who required grafting of the circumflex artery distal to the first obtuse marginal branch. In BHACAS 2, we included such patients. Primary outcomes were all-cause mortality and cardiac-related events at midterm follow-up (1-3 years). Analysis was by intention to treat. Analyses of combined data from both trials showed the following risk differences with off-pump compared with on-pump surgery: atrial fibrillation -25% (95% CI -33% to -16%); chest infection -12% (-19% to -5%); inotropic requirement -18% (-25% to -10%); transfusion of red blood cells -31% (-41 to -21); and hospital stay longer than 7 days -13% (-21 to -5). Mean follow-up was 25 0 months (SD 9.1) for BHACAS 1 and 13.7 months (5 5) for BHACAS 2. Four (2%) of 200 patients in the off-pump groups died from any cause, compared with seven (3%) of 201 in the on-pump group (hazard ratio 0.57, 95% CI 0.17-1.96). 33 (17%) of 200 patients in the off-pump group died or had a cardiac-related event, compared with 42 (21%) of 201 in the on-pump group (0.78, 0 49-1.22). Off-pump coronary surgery significantly lowers in-hospital morbidity without compromising outcome in the first 1-3 years after surgery compared with conventional on-pump coronary surgery.


Effectiveness of a group intervention using pain neuroscience education and exercise in women with fibromyalgia: a pragmatic controlled study in primary care.
Very positive effects have been described in the application of pain neuroscience education (PNE) to chronic pain and migraine. However, there are few data on the applicability of this therapeutic approach in actual clinical practice in a primary care (PC) setting. The aim of this study was to explore the efficacy in fibromyalgia (FM) of an intervention based on PNE and exercise compared to treatment as usual (TAU). Pragmatic nonrandomised controlled trial set in 5 healthcare centres and one physiotherapy centre in PC. Fifty-three women with FM (2010 American College of Rheumatology Diagnostic Criteria for Fibromyalgia) were studied, 35 in the intervention group (IG) and 18 in the control group (CG). The women in the IG were interviewed individually and then received 6 weekly sessions plus one review session (1 month later): those in the CG received their TAU. The subject assignation to the CG or the IG was determined according to their availability to attend the sessions. They all filled in several questionnaires (prior to and 1 year after the intervention) to evaluate the impact of FM in their daily lives, catastrophism, anxiety and depression, severity and impact of pain in daily personal performance and functional capacity. The reductions (improvements) in the scores of all tests (baseline-final) were greater in the IG (p < 0.05) when adjusted for age and baseline values, with moderate or high effect size. After 1 year, 20% (CI - 1 to 42%) more women in the IG, compared to the CG, had a FIQ score < 39 (mild functional impairment). 17/38 (49%) women in the IG no longer met FM criteria at the end of follow-up. An intervention based on PNE and exercise in patients with FM is feasible and seems effective in PC. The study was retrospectively registered at ClinicalTrials.gov (Trial Registration NCT04539171 ), on 04/09/2020.


Renal lymphangioma.
Lymphangioma cavernosum of the kidney is a benign tumor. Metastasis has not been found in any of the 20 cases reported to date. The sex ratio of patients is 1.5 to 1, favoring female subjects. Average patient age is 33.7 years. Treatment has consisted of nephrectomy in 18 patients, since the possibility of a malignant tumor could not be eliminated preoperatively.


Knowledge and attitude of donating and using cord blood for transfusion among patients attending Nnamdi Azikiwe University Teaching Hospital, Nnewi, South East Nigeria.
Allogeneic blood for transfusion is in short supply in most parts of the developing world. Cord blood for transfusion can be a significant source of blood supply to our health institutions. This study aims to investigate the knowledge and attitude to the donation and use of umbilical cord blood (UCB) for transfusion among the patients receiving services in a tertiary health institution in South-East Nigeria. This was a cross-sectional study; an anonymous structured questionnaire was used. A total of 549 consenting patients randomly selected from the antenatal, postnatal, sickle cell clinics, and wards were the subjects. Statistical analysis of the data was done using SPSS version 20.0. The mean age of the participants was 31.9 ± 9.5 years. The majority were females (77.2%), married (86.4%). About 26.2% of the respondents were willing to accept UCB for transfusion to them or their child. Following counseling, the acceptance rate increased to 71.5%. Most of the respondents (80.0%) were willing to donate the UCB of their baby; or be tested for HIV (93.3%), if necessary. Educational level was significantly associated with knowledge of UCB. After logistic regression, occupation, and gender were significantly associated with acceptance of UCB for transfusion. Up to 52% belonged to low income family background, approximately 150 US dollars monthly family income (50,000 naira). The knowledge and acceptance of UCB for transfusion are low in our environment. However, proper counseling and public enlightenment could change this attitude.


Therapeutic effects of herbal medicines in different types of retinopathies: A systematic review.
Retinopathy is an ocular manifestation of systemic diseases such as diabetes and vascular diseases. Herbal drugs have been considered as an effective therapeutic option with minimal side effects for the treatment of retinopathy by reducing the symptoms and improving visual acuity. The purpose of this systematic review was to collect studies on the effectiveness of medicinal plants in the treatment or prevention of retinopathy. A systematic literature search was performed in PubMed, Scopus, Google Scholar, and other databases in April 2021 using "herbal products" and "Retinopathy" with all their equivalent and similar terms. For this purpose, human clinical trials with the English language were included and articles with subject irrelevancy were excluded from further evaluation. Overall, 30 articles with 2324 patients were studied for possible effects of herbal therapy on retinopathy. From 30 included articles, different herbal products had been evaluated. Out of 30 selected articles, 11 articles were for the treatment of age-related macular degeneration (AMD), 14 articles covered patients with diabetic retinopathy, and the other five studies were for other retinal disorders. The outcomes in majority of the studies include changes in visual acuity (VA), fundus performance, best-corrected visual acuity (BCVA), central macular thickness (CMT), focal electroretinogram (fERG), supplements and adjuvant medications appeared to be more beneficial in patients with AMD and diabetic maculopathy. Herbal therapy can be considered as a potential candidate in the adjuvant and complementary therapies of retinopathy. However, further studies are required to verify such efficiency.


Sinus venosus atrial septal defect associated with partial anomalous pulmonary venous drainage: surgical repair.
This report descrbies a new technique for the repair of sinus venosus atrial septal defect associated with partial anomalous pulmonary venous drainage. A right atrial wall flap is used both to deflect the anaomalous venous blood into the left atrium and to close the atrial septal defect. Then an atrioplasty is performed. This method does not employ any foreign materials, avoids injury to the sinoatrial node and internodal tracts, and minimizes the risk of obstruction of the ostia of the anomalous pulmonary veins and superior vena cava.


Sex differences in fetal rabbit pulmonary surfactant production.
Male infants have a higher risk of respiratory distress syndrome than females at concurrent gestations. Recent evidence in humans has linked fetal sex with differences in amniotic fluid indices of lung maturation. We tested the hypothesis that the late gestation surge in pulmonary surfactant production occurs later in the male fetus than in the female fetus in the rabbit model. We measured saturated phosphatidylcholine and total phosphatidylcholine in lung lavage at 26, 28, and 30 days gestation and in amniotic fluid at 24, 26, 28, and 30 days gestation (term = 31 days). The saturated phosphatidylcholine/sphingomyelin ratios were 158 and 55% higher in female fetal lung lavage at 26 and 28 days, respectively, and 75% higher in amniotic fluid at 28 days (P less than 0.05). The total phosphatidylcholine/sphingomyelin ratios were 39% higher in female fetal lung lavage and 35% higher in female amniotic fluid at 28 days (P less than 0.05). Significant differences were not detected in the very immature (24 day) or the mature (30 day) fetuses. This provides clear evidence of a biochemical difference according to fetal sex in the maturation of pulmonary surfactant production.


["The right of nurses to prescribe vaccinations should be extended to other vaccines."]
The year 2021 was marked by the opening of the prescription right to nurses in the framework of the vaccination against COVID-19. Vaccination is an important public health tool that seeks on a collective level a protective effect of vaccinated individuals and contributes to reducing the circulation of the infectious agent within the population. Patrick Chamboredon, President of the National Order of Nurses, discusses the skills of nurses in the service of vaccination.


Activity concentrations of 137Cs, 40K, and 210Pb radionuclides in selected medicinal herbs from Central Serbia and their effective dose due to ingestion.
Specific activity of 137Cs, 40K, and 210Pb radionuclides in fifteen selected medicinal herbs from three locations in Central Serbia (two mountains, Kopaonik and Zlatar, and a valley, Sokobanja) was measured using two semiconductor HPGe spectrometer systems. The obtained values are in intervals (<0.3 ÷ 9.7) Bq/kg, (<0.2 ÷ 24.7) Bq/kg, and (<0.2 ÷ 5.7) Bq/kg for 137Cs; in intervals (125 ÷ 1100) Bq/kg, (104 ÷ 872) Bq/kg, and (103 ÷ 954) Bq/kg for 40K, and in intervals (3.6 ÷ 49.0) Bq/kg, (3.9 ÷ 57.9) Bq/kg, and (2.8 ÷ 103) Bq/kg for 210Pb, for herbs from Kopaonik, Sokobanja and Zlatar, respectively. The highest activity measured in individual herbs was: 24.7 Bq/kg for 137Cs (Sokobanja valley), 1100 Bq/kg for 40K (Mt. Kopaonik) and 103 Bq/kg for 210Pb (Mt. Zlatar). The corresponding individual annual effective doses due to ingestion calculated from the measured activity concentrations, of the radionuclides are: in intervals (<1.7 ÷ 82.9) nSv, (<1.4 ÷ 211) nSv, and (<1.1 ÷ 48.7) nSv for 137Cs; in intervals (0.76 ÷ 4.5) μSv, (0.64 ÷ 4.4) μSv, and (0.63 ÷ 4.9) μSv for 40K, and in intervals (1.1 ÷ 18.2) μSv, (1.3 ÷ 21.6) μSv, (0.9 ÷ 38.3) μSv for 210Pb, respectively. The specific activity concentration values of 137Cs and 40K obtained for the investigated herbs are similar to the literature data, while no information was found in literature about specific activity concentration of 210Pb. The all values obtained for individual annual effective dose due to ingestion are less than 100 μSv, which means that the daily use of 200 mL of herbal infusion during a year made from the investigated herbs does not represent a radiological risk for health. However, a high individual annual effective dose of ingestion of 210Pb obtained for some herbs indicate that their consumption in larger amounts 2-3 cups of infusion daily over a year could make the dose to exceed the recommended level, and points to necessity for extensive investigation of 210Pb activity concentration worldwide.