Syntheses and biological activity of bisdaunorubicins.
To study the length and flexibility of the linkers between two monomers of bisdaunorubicins for their activity against cancer cells, seven bisdaunorubicins were rationally designed and synthesized through click chemistry. Their cytotoxicity was tested in leukemia cells with MTS assay. The results showed that the compounds with short linkers exhibited higher activity than the compounds with long linkers, while the flexibility of the linker also contributed to their activity. These results indicated that the length and flexibility of the linkers between two monomers in bisdaunorubicins are very critical to maintain their activity against cancer cells.


Performance evaluation of ozonation for removal of antibiotic-resistant Escherichia coli and Pseudomonas aeruginosa and genes from hospital wastewater.
The performance of ozonation for the removal of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) using Escherichia coli and Pseudomonas aeruginosa carrying ARGs from hospital wastewaters was evaluated in this study. Bacterial inactivation was determined using plate count methods and real time PCR for ARG damage (Sul1, blatem, blactx, blavim and qnrS). The reduction rate of bacterial cells and ARGs was increased by different amounts of transferred ozone dose from 11 to 45 mg/L. The concentration of 108 cfu/ml bacteria was reduced to an acceptable level by ozone treatment after a 5 min contact time, Although the removal rate was much higher for concentrations of 106 cfu/ml and 104 cfu/ml bacteria. Overall, the tendency of gene reduction by ozonation from more to less was 16S rRNA > sul1 > blatem > blactx > qnrS > blavim. Given that plasmid-borne ARGs can potentially be transferred to other bacteria even after the disinfection process, our results can provide important insights into the fate of ARGs during hospital wastewater ozonation.


Early randomized intervention with high-frequency jet ventilation in respiratory distress syndrome.
To determine whether early use of high-frequency jet ventilation reduces neonatal mortality or pulmonary morbidity rates, we randomly selected 42 infants with clinical and radiographic evidence of severe respiratory distress syndrome to receive either high-frequency jet ventilation or conventional ventilation. Separate sequential analyses (two-sided, alpha = 0.05, power = 0.95 to detect 85:15 advantage) were performed for mortality rates, air leaks, bronchopulmonary dysplasia, intraventricular hemorrhage, and assignment crossover, and a combined analysis was performed, with death overriding other outcome variables. Enrollment was completed when the combined analysis reached the sequential design boundary indicating no treatment difference. Mortality rates (19% among infants receiving high-frequency jet ventilation vs 24% among infants receiving conventional ventilation), the incidence of air leaks (48% vs 52%), bronchopulmonary dysplasia (39% vs 41%), and intraventricular hemorrhage (33% vs 43%), and assignment crossovers (14% vs 24%) did not differs significantly between the treatment groups. We conclude that early use of high-frequency jet ventilation does not prevent or substantially reduce mortality or morbidity rates associated with assisted ventilation.


Copper-Catalyzed Aerobic Enantioselective Cross-Dehydrogenative Coupling of N-Aryl Glycine Esters with Terminal Alkynes.
A copper-catalyzed enantioselective cross-coupling of a Csp3-H moiety (N-aryl glycine ester) with a Csp-H component (terminal alkyne) using molecular oxygen as the terminal oxidant is described for the first time. The sustainable method provides an efficient and environmentally friendly approach to rapidly prepare a diverse array of optically active non-natural α-amino acids.


A case of Mycobacterium chelonae mediastinitis and acute humoral rejection after heart transplantation.
Mediastinitis is one of the life-threating complications that can occur after cardiac surgery. However, to the best of our knowledge, there has been no report of mediastinitis caused by Mycobacterium chelonae, which is one of the rapidly growing nontuberculous mycobacteria species. As far as we know, our case is the first case describing the curative management for mediastinitis caused by M. chelonae after heart transplantation.


Epidermal nicotinamide adenine dinucleotides in psoriasis during treatment with dithranol.
Epidermal nicotinamide adenine dinucleotides were measured in subcorneal and basal epidermal layers in patients with psoriasis and in healthy controls during a 2-week period in which they were treated once a day with 0.15% dithranol in white petrolatum. Lowry's microtechniques utilizing enzymatic cycling were used. In the controls the total NAD contents decreased 25% during the treatment period. The total NADP content did not change, nor did the proportions of NADH and NADPH. In the psoriatic patients effects of the treatment were seen only in the epidermis of the lesions. Both the total NAD and NADP displayed an initial increase on the second day, followed by a steady decrease to the levels found in the non-involved skin. During the first week of treatment parakeratosis was still evident in the lesions. In spite of variation in the total NAD contents during this period, a significant reduction of the percentage of NADH was found. Concomitant with the appearance of an orthokeratotic horny layer, both NAD+ and NADH returned to normal. The percentage contribution of NADPH did not change during these events.


Changes of albumin concentrations in the first morning urine according to age and sex in 2990 healthy children and adults.
This study was performed to clarify the changes in urinary albumin excretion according to age and sex in healthy subjects, for the appropriate judgment of microalbuminuria in insulin-dependent diabetes mellitus (IDDM). Concentrations of albumin in the first morning urine from 2990 healthy individuals (1713 males, 1277 females) aged from 6 to 39 years were measured by turbidimetry immunoassay. Reference values of the concentrations for each age group were obtained from the 95% confidence limits from the distribution simulated by the chi 2-test (k = 1). Reference values were 1.3-2.2 mg/dl in children aged 6-11 years. Values for females increased significantly from 22 mg/dl at age 11 years to 3.9 mg/dl at age 12 years (P < 0.0001) and those of males increased gradually from 1.7 mg/dl at age 11 years to 3.9 mg/dl at age 16 years. There were significant differences between males and females at the ages of 12 (P < 0.0001), 13 (P < 0.0001), and 14 (P < 0.0007). After 17 years, the values decreased from 3.9 mg/dl to 3.3 mg/dl in females, and to 2.9 mg/dl in males. We conclude that reference values of urinary albumin excretion change according to age and sex, which should be taken into consideration in the assessment of diabetic nephropathy in IDDM.


Performance evaluation and ranking of regional primary health care and public health Systems in Iran.
The present study has been undertaken with the aim to evaluate performance and ranking of various universities of medical sciences that are responsible for providing public health services and primary health care in Iran. Four models; Weighted Factor Analysis (WFA), Equal Weighting (EW), Stochastic Frontier Analysis (SFA), and Data Envelopment Analysis (DEA) have been applied for evaluating the performance of universities of medical sciences. This study was commenced based on the statistical reports of the Ministry of Health and Medical Education (MOHME), census data from the Statistical Center of Iran, indicators of Vital Statistics, results of Multiple Indicator of Demographic and Health Survey 2010, and results of the National Survey of Risk Factors of non-communicable diseases. The average performance scores in WFA, EW, SFA, and DEA methods for the universities were 0.611, 0.663, 0.736 and 0.838, respectively. In all 4 models, the performance scores of universities were different (range from 0.56-1, 0.53-1, 0.73-1 and 0.83-1 in WFA, EW, SFA and DEA models, respectively). Gilan and Rafsanjan universities with the average ranking score of 4.75 and 41 had the highest and lowest rank among universities, respectively. The universities of Gilan, Ardabil and Bojnourd in all four models had the highest performance among the top 15 universities, while the universities of Rafsanjan, Ahvaz, Kerman and Jiroft showed poor performance in all models. The average performance scores have varied based on different measurement methods, so judging the performance of universities based solely on the results of a model can be misleading. In all models, the performance of universities has been different, which indicates the need for planning to balance the performance improvement of universities based on learning from the experiences of well-performing universities.


Muscarinic receptor binding in the rat adrenal medulla.
Muscarinic receptor binding sites are present in rat adrenal gland andare associated primarily with the medulla. A Scatchard analysis using the ligand [3H]-quinuclidinyl benzylate (eH-QNB) revealed a KD of 0.064 nM and a Bmax of 66 fmol/mg prot. Denervation of the adrenal gland had no significant effect on 3H-QNG binding. The presence of muscarinic receptor binding sites in the adrenal medulla is consistent with reports that muscarinic receptors play a role in the release of adrenal catecholamines and modulation of cycle 3',5'-guanosine monophosphate.


Abrupt loss of dependence of retinopetal neurons on their target cells, as shown by intraocular injections of kainate in chick embryos.
We have examined the capacity of neurons in the chick isthmo-optic nucleus (ION) to survive when their target neurons in the contralateral retinal are destroyed by intraocular injections of kainate (KA) at different stages in development. The retinal vulnerability to KA builds up progressively from embryonic day 10 (E10) until a plateau is reached at E15 (see accompanying paper); and the effects on the ION increase in parallel, almost all the ION neurons being rapidly lost after the E15 injections. KA injection before E15 lesioned only part of the retina and caused degeneration only in the topographically corresponding region of the ION. Near the end of the natural cell death period in the ION (E17), this initial dependence on the target cells is rapidly lost. Already at E16 the injections kill less ION neurons, and by E19 they kill none of them. The ION neurons have become completely insensitive to the KA injections and appear normal more than 4 months later, although axotomy (by eye removal) at a similar age would by then have killed them. The ectopic ION neurons, scattered outside the ION but projecting to the retina, are never affected by KA injections at any age.


Presence of sarcopenia identifies a special group of lean NAFLD in middle-aged and older people.
Sarcopenia, the age-related loss of muscle mass and function, is closely associated and frequently concomitant with non-alcoholic fatty liver disease (NAFLD). We aimed to investigate the clinical features of the sarcopenic NAFLD patients from middle-aged and older people. A total of 1305 patients with NAFLD from the Shanghai Changfeng Study were included for analysis. Sarcopenia was diagnosed based on the height-adjusted appendicular skeletal muscle mass (ASM/height2). We comprehensively analyzed the metabolic phenotype, carotid artery condition, liver fibrosis score, and serum metabolomic profile of each participant. Among the middle-aged and older population, 68.1% of patients with sarcopenia and NAFLD were lean. Sarcopenia was independently associated with increased risk of carotid plaque (OR, 2.22; 95%CI 1.23-4.02) and liver fibrosis (OR, 2.07; 95%CI 1.24-3.44), and the sarcopenic lean NAFLD patients were characterized by a higher risk of carotid plaque (p = 0.008) and liver fibrosis (p = 0.001) than the non-sarcopenic lean NAFLD patients, despite their lower BMI and similar prevalence of metabolic syndrome and diabetes. Further serum metabolomic examination indicated that the sarcopenic lean NAFLD patients presented a distinct metabolomic profile prone to carotid plaque and liver fibrosis, with upregulated serum valine, N-acetylneuraminyl-glycoproteins, lactic acid, small LDL triglycerides and VLDL5 components, and reduced components of HDL4. A sarcopenic characterization score based on above metabolites was established and could also predict increased risk of carotid plaque and liver fibrosis. The presence of sarcopenia identifies a special subgroup of lean NAFLD with increased risk of cardiovascular disease and liver fibrosis clinically.


Genomic analysis of sequence variation in tandemly repeated DNA. Evidence for localized homogeneous sequence domains within arrays of alpha-satellite DNA.
As a model to examine the local distribution of sequence variation within large arrays of tandemly repeated DNA in complex genomes, the long-range organization of alpha-satellite DNA from human chromosome 17 was investigated. Three individual chromosomes, representing different alpha-satellite haplotypes, were segregated into mouse and human somatic cell hybrids and their arrays sized by pulse-field gel electrophoresis. An inventory of the higher-order repeat units found in multiple separate regions of these megabase arrays was obtained using cosmid mapping and two-dimensional gel electrophoresis, a technique that combines the large-scale resolution of pulsed-field gel electrophoresis with the small-scale resolution of conventional gel electrophoresis. These analyses show that alpha-satellite arrays are characterized by the presence of localized homogeneous domains containing only one distinct type of repeat unit. These domains, which consist of sequence variants and/or higher-order repeat length variants, can be up to at least several hundred thousands of bases in length. Both abundant and rare variant repeat units can be localized in these distinct domains, which may correspond to transition states in the evolution of tandem multicopy DNA families. This description of the organization of large arrays of tandem repeats provides insight into mechanisms involved in their homogenization.


Directed mutagenesis of the transmembrane domain of the PsbL subunit of photosystem II in Synechocystis sp. PCC 6803.
The PsbL protein is one of three low-molecular-weight subunits identified at the monomer-monomer interface of photosystem II (PSII) [Ferreira et al. (2004) Science 303:1831-1838; Loll et al. (2005) Nature 438:1040-1044]. We have employed site-directed mutagenesis to investigate the role of PsbL in Synechocystis sp. PCC 6803 cells. Truncation of the C-terminus by deleting the last four residues (Tyr-Phe-Phe-Asn) prevented association of PsbL with the CP43-less monomeric sub-complex and therefore blocked PSII assembly resulting in an obligate photoheterotrophic strain. Replacement of these residues with Ala created four photoautotrophic mutants. Compared to wild type, the F37A, F38A, and N39A strains had reduced levels of assembled PSII centers and F37A and F38A cells were readily photodamaged. In contrast, Y36A and Y36F mutants were similar to wild type. However, each of these strains had elevated levels of the CP43-less inactive monomeric complex. Mutations targeting a putative hydrogen bond between Arg-16 and sulfoquinovosyldiacylglycerol resulted in mutants that were also highly susceptible to photodamage. Similarly mutations targeting a conserved Tyr residue (Tyr-20) also destabilized PSII under high light and suggest that Tyr-20-lipid interactions or interactions of Tyr-20 with PsbT influence the ability of PSII to recover from photodamage.


Treating to target patients with primary hyperlipidaemia: comparison of the effects of ATOrvastatin and ROSuvastatin (the ATOROS study).
In a 24-week, open-label, randomized, parallel-group study, we compared the efficacy and metabolic effects, beyond low density lipoprotein cholesterol (LDL-C)-lowering, of atorvastatin (ATV) and rosuvastatin (RSV) in cardiovascular disease-free subjects with primary hyperlipidaemia, treated to an LDL-C target (130 mg/dL). After a 6-week dietary lead-in period, patients were randomized to RSV 10 mg/day (n = 60) or ATV 20 mg/day (n = 60). After 6 weeks on treatment the dose of the statin was increased (to RSV 20 mg/day or ATV 40 mg/day) if the treatment goal was not achieved. A control group of healthy volunteers (n = 60) was also included for the validation of baseline serum and urinary laboratory parameters. The primary outcome was the percentage of patients reaching the LDL-C goal; secondary outcomes were changes in lipid and non-lipid metabolic parameters. A total of 45 patients (75.0%) in the RSV-treated group and 43 (71.7%) in the ATV-treated group achieved the treatment target at the initial dose. Both regimens were generally well tolerated and there were no withdrawals due to treatment-related serious adverse events. Similar significant reductions in total cholesterol, LDL-C, apolipoprotein (apo) B, triglycerides, apoB/apoA1 ratio, fibrinogen and high-sensitivity C-reactive protein levels were seen. RSV had a significant high density lipoprotein cholesterol (HDL-C)-raising effect and showed a trend towards increasing apoA1 levels. Glycaemic control and renal function parameters were not influenced by statin therapy. ATV, but not RSV, showed a significant hypouricaemic effect. RSV and ATV were equally efficacious in achieving LDL-C treatment goals in patients with primary hyperlipidaemia at the initial dose and following dose titration. RSV seems to have a significantly higher HDL-C-raising effect, while ATV lowers serum uric acid levels.


Restoration of forearm rotation following malunited fractures: Baldwin's operation.
The technique and results of a series of 38 Baldwin's operations (excision of the ulnar neck) are described. This is a simple and effective procedure to restore forearm rotation following malunited fractures of the distal forearm.


CD15 focus score: Infection diagnosis and stratification into low-virulence and high-virulence microbial pathogens in periprosthetic joint infection.
The aim of the work was to validate the CD15 focus score for the infection pathology of periprosthetic joint infection in a large group and to clarify whether a stratification into low-virulence and high-virulence microbial pathogens is possible by means of the CD15 focus score (quantification of CD15 positive granulocytes). The histopathology of 275 synovial tissue samples taken intraoperatively during revision operations (n=127 hip, n=141 knee, n=2 shoulder, n=5 ankle) was evaluated according to the SLIM consensus classification (SLIM=synovial-like interface membrane). Neutrophilic granulocytes (NG) were quantified by the CD15 focus score on the basis of the principle of focal maximum infiltration (focus) with evaluation of one field of vision (about 0.3mm2). The quantification values were compared with the microbiological diagnoses taking into consideration the virulence groups of low-virulence and high-virulence microbial pathogens and mixed infection. The patients with positive microbiological findings (n=160) had significantly (p<0.001, Mann-Whitney U test) higher CD15 focus score values than patients with negative microbiological findings (n=115), the cut-off value being 39 cells per high power field (HPF). The CD15 focus score values of low-virulence microbial pathogens (n=94) were significantly lower (p<0.001, Mann-Whitney U test) than the values of high-virulence microbial pathogens (n=55), the cut-off value being 106 cells per HPF. Based on the microbiological diagnosis the sensitivity with respect to a microbial infection is 0.91, the specificity 0.92 (PPV=0.94; NPV=0.88; accuracy: 0.92; AUC=0.95). Based on the differentiation of the CD15 focus score values between low-virulence and high-virulence microbes the sensitivity is 0.70 and the specificity 0.77 (PPV=0.63; NPV=0.81; accuracy=0.74; AUC=0.74). As a result of the high sensitivity and specificity, the easy to use CD15 focus score is a diagnostically valid score for microbial periprosthetic infection. A differentiation between low-virulence and high-virulence microorganism of sufficiently high diagnostic quality is additionally possible as a result of the defined quantification of CD15 positive granulocytes (the CD15 focus score) histopathological diagnosis of microbial infections is possible, which on the one hand supports the microbiological diagnosis and on the other hand by the stratification into low-virulence and high-virulence microbial pathogens could represent an additional basis for a pathogen-specific antibiotic treatment in the event of unclear constellations of findings.


Mechanism of inactivation of gamma-aminobutyric acid aminotransferase by (S,E)-4-amino-5-fluoropent-2-enoic acid.
Evidence for an enamine mechanism of inactivation of pig brain gamma-aminobutyric acid (GABA) aminotransferase by (S,E)-4-amino-5-fluoropent-2-enoic acid is presented. apo-GABA aminotransferase reconstituted with [3H]pyridoxal 5'-phosphate is inactivated by (S,E)-4-amino-5-fluoropent-2-enoic acid and the pH is raised to 12. All of the radioactivity is released from the enzyme as an adduct of the cofactor; no [3H]pyridoxamine 5'-phosphate is generated.


Label-free impedance detection of oligonucleotide hybridisation on interdigitated ultramicroelectrodes using electrochemical redox probes.
The direct detection of oligodeoxynucleotide (ODN) hybridisation using electrochemical impedance spectroscopy was made on interdigitated array (IDA) gold (Au) ultramicroelectrodes manufactured by silicon technology. The immobilisation of single stranded ODNs (ssODNs) was accomplished by self-assembling of thiol-modified ODNs onto an Au-electrode surface. Faradaic impedance was measured in the presence of K(3)[Fe(CN)(6)]. Double strand formation was identified by a decrease of approximately 50% in impedance in the low frequency region in the presence of K(3)[Fe(CN)(6)], compared to the spectrum of single stranded ODN. The frequency dependent diffusion of Fe(CN)(6)(3-) ions through defects in the ODN monolayer determines the impedance of Au-ssODN surface. The influence of DNA intercalator methylene blue on the impedance of both, single and double strands, was examined along with K(3)[Fe(CN)(6)] and confirmed by cyclic voltammetry. The layer densities and the hybridisation have been further corroborated by chronoamperometric redox recycling of para-aminophenol (p-AP) in ELISA like experiments. It can be concluded, that a performed impedance spectroscopy did not change the layer density. The impedance spectroscopy at ultramicroelectrodes combined with faradaic redox reactions enhances the impedimetric detection of DNA hybridisation on IDA platforms.


Spectrogram decomposition of ultrasonic guided waves for cortical thickness assessment using basis learning.
Due to its multimode and dispersive nature, ultrasonic guided waves (UGWs) usually consist of overlapped wave packets, which challenge accurate bone characterization. To overcome this obstacle, a classic idea is to separate individual modes and to extract the corresponding dispersion curves. Reported single-channel mode separation algorithms mainly focused on offering a time-frequency representation (TFR) where the energy distributions of individual modes were apart from each other. However, such approaches are still limited to identifying the modes without significant overlapping in time-frequency domain. In this study, a spectrogram decomposition technique was developed based on a combination strategy of generalized separable nonnegative matrix factorization (GS-NMF) and adaptive basis learning, towards the automatic mode extraction under severe overlapping and low signal-to-noise ratio (SNR). The extracted modes were further used for cortical thickness estimation. The method was verified using broadband simulated and experimental datasets. Experiments were conducted on a bone-mimicking plate and bovine cortical bone plates. For simulated data, the relative errors between extracted and theoretical dispersion curves are 1.33% (SNR = ∞), 1.43% (SNR = 10 dB) and 0.88% (SNR = 5 dB). The root-mean-square errors of the estimated thickness for 3.10 mm-thick bone-mimicking plate, 3.83 mm- and 4.00 mm-thick bovine cortical bone plates are 0.039 mm, 0.049 mm, and 0.052 mm, respectively. It is demonstrated that the proposed method is capable of separating multimodal UGWs even under significantly overlapping and low SNR conditions, further facilitating the UGW-based cortical thickness assessment.


Impaired exercise capacity, but unaltered mitochondrial respiration in skeletal or cardiac muscle of mice lacking cellular prion protein.
The studies of physiological roles for cellular prion protein (PrP(c)) have focused on possible functions of this protein in the CNS, where it is largely expressed. However, the observation that PrP(c) is expressed also in muscle tissue suggests that the physiological role of PrP(c) might not be limited to the central nervous system. In the present study, we investigated possible functions of PrP(c) in muscle using PrP(c) gene (Prnp) null mice (Prnp(0/0)). For this purpose, we submitted Prnp(0/0) animals to different protocols of exercise, and compared their performance to that of their respective wild-type controls. Prnp(0/0) mice showed an exercise-dependent impairment of locomotor activity. In searching for possible mechanisms associated with the impairment observed, we evaluated mitochondrial respiration (MR) in skeletal or cardiac muscle from these mice during resting or after different intensities of exercise. Baseline MR (states 3 and 4), respiratory control ratio (RCR) and mitochondrial membrane potential (DeltaPsi) were evaluated and were not different in skeletal or cardiac muscle tissue of Prnp(0/0) mice when compared with wild-type animals. We concluded that Prnp(0/0) mice show impairment of swimming capacity, perhaps reflecting impairment of muscular activity under more extreme exercise conditions. In spite of the mitochondrial abnormalities reported in Prnp(0/0) mice, our observation seems not to be related to MR. Our results indicate that further investigations should be conducted in order to improve our knowledge about the function of PrP(c) in muscle physiology and its possible role in several different neuromuscular pathologies.


Structures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers reveal new dimerization modalities in the bHLH-PAS transcription factor family.
Neuronal PER-ARNT-SIM (PAS) domain protein 4 (NPAS4) is a protective transcriptional regulator whose dysfunction has been linked to a variety of neuropsychiatric and metabolic diseases. As a member of the basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) transcription factor family, NPAS4 is distinguished by an ability to form functional heterodimers with aryl hydrocarbon receptor nuclear translocator (ARNT) and ARNT2, both of which are also bHLH-PAS family members. Here, we describe the quaternary architectures of NPAS4-ARNT and NPAS4-ARNT2 heterodimers in complexes involving DNA response elements. Our crystallographic studies reveal a uniquely interconnected domain conformation for the NPAS4 protein itself, as well as its differentially configured heterodimeric arrangements with both ARNT and ARNT2. Notably, the PAS-A domains of ARNT and ARNT2 exhibit variable conformations within these two heterodimers. The ARNT PAS-A domain also forms a set of interfaces with the PAS-A and PAS-B domains of NPAS4, different from those previously noted in ARNT heterodimers formed with other class I bHLH-PAS family proteins. Our structural observations together with biochemical and cell-based interrogations of these NPAS4 heterodimers provide molecular glimpses of the NPAS4 protein architecture and extend the known repertoire of heterodimerization patterns within the bHLH-PAS family. The PAS-B domains of NPAS4, ARNT, and ARNT2 all contain ligand-accessible pockets with appropriate volumes required for small-molecule binding. Given NPAS4's linkage to human diseases, the direct visualization of these PAS domains and the further understanding of their relative positioning and interconnections within the NPAS4-ARNT and NPAS4-ARNT2 heterodimers may provide a road map for therapeutic discovery targeting these complexes.


Antitumoral cyclic peptide analogues of chlamydocin.
A series of cyclic tetrapeptides bearing the bioactive alkylating group on an epsilon-amino-lysyl function have been examined for their antitumoral activity on L1210 and P388 murine leukemia cell lines. One analogue belonging to the chlamydocin family and bearing a beta-chloroethylnitrosourea group was found to be potent at inhibiting L1210 cell proliferation and had a higher therapeutic index than the reference compound bis-beta-chloroethylnitrosourea (BCNU) on the in vivo P388-induced leukemia model.


Non-venereal sclerosing lymphangitis of the penis following herpes progenitalis.
Two patients are described in which non-venereal sclerosing lymphangitis of the penis occurred immediately after a herpes simplex infection. The possibility of a causal relationship between these two conditions is discussed.


A comparison of an evidence based regime with the standard protocol for monitoring postoperative observation: a randomised controlled trial.
Monitoring patients' vital signs is an important component of postoperative observations. To compare the safety and efficacy of the current standard practice for monitoring postoperative observations in one hospital with an experimental protocol. Patients who were classified as American Society of Anaesthesiologists (ASA) Class 1 or 2 and who met the inclusion criteria were randomised to one of two groups. Following their return to the ward from the recovery unit, these patients were monitored according to either the standard practice (n=96) or the experimental protocol (n=93). Data collected included patient demographics, medical and surgical history, the postoperative observations and the number and type of untoward events. The findings indicated that there was no statistically significant difference in the incidence of abnormal vital signs between the groups in the first four hours as well as within the 24 hours following return to the ward from the recovery unit. Additionally, none of the patients required either transfer to the intensive care unit /high dependency unit or management by the intensive care team. Patients in both groups were successfully discharged within 24 hours following surgery. This study provides evidence to inform clinicians of a safe and cost effective regime in the management of the patient in the postoperative period following discharge from the recovery to the ward. Clinicians, however, must utilise clinical judgement to determine which patients require close monitoring during the postoperative period.


The efficacy and safety of diuretics on extracorporeal shockwave lithotripsy treatment of urolithiasis: A systematic review and meta analysis.
The aim of this systematic review and meta-analysis was to demonstrate the efficacy and safety of diuretics on extracorporeal shockwave lithotripsy (SWL) treatment of urolithiasis. The databases MEDLINE, EMBASE, and the Cochrane Controlled Trial Register of Controlled Trials from January 1980 until November 2019 were searched to identify randomized controlled trials that referred to the use of diuretics on extracorporeal SWL treatment of urolithiasis. Six randomized controlled trials containing 1344 patients were included in this meta-analysis, which compared diuretics with placebo on extracorporeal SWL treatment of urolithiasis. In the analysis, we found that diuretics on extracorporeal SWL treatment were more effective for the management of urinary stones. Compared with placebo, patients who received diuretics during extracorporeal SWL treatment had significantly higher successful stone clearance rate (Odds ratio; 1.73, 95% confidence interval (CI); 1.35 to 2.21, P < .0001), higher stone fragmentation rate (odds ratio; 2.83, 95% CI; 1.30 to 6.16, P = .009), less average number of sessions per stone (mean difference; -0.13; 95% CI, -0.25 to -0.01, P = .03) and similar average number of shocks per stone (mean difference; -126.89; 95% CI, -394.53 to 140.76, P = .35). This systematic review and meta-analysis indicates that diuretics during extracorporeal SWL was effective in the management of urolithiasis with lower risk of complications.


Virtual Learning Collaborative Compared to Technical Assistance as a Strategy for Implementing Health Promotion in Routine Mental Health Settings: A Hybrid Type 3 Cluster Randomized Trial.
Despite widespread use of learning collaboratives, few randomized trials have evaluated their effectiveness as a strategy for implementing evidence based practices. This randomized trial evaluated the effectiveness of a virtual learning collaborative (VLC) in the implementation of a health promotion program for persons with serious mental illness (SMI) aimed at reducing cardiovascular risk reduction in routine mental health settings, compared to routine technical assistance (TA). Fifty-five mental health provider organizations were recruited to participate in a Hybrid Type 3 cluster randomized implementation-effectiveness trial of the InSHAPE health promotion program for persons with SMI. Sites were stratified by size and randomized prior to implementation to an 18-month group-based VLC with monthly learning sessions or individual site TA with four scheduled conference calls over 18 months. Primary implementation and service outcomes were InSHAPE program fidelity, participation, and reach. Primary clinical outcomes were weight loss, cardiorespiratory fitness, and cardiovascular risk reduction (≥ 5% weight loss or > 50 m increase on the 6-Minute Walk Test). Program fidelity was assessed at 6, 12, and 24 months; program participation and participant-level outcomes were assessed at 3, 6, 9, and 12 months. VLC (N = 27) and TA (N = 28) sites were similar in organizational characteristics (all p > 0.05). At 12-month follow-up mean program fidelity score was higher in VLC compared to TA (90.5 vs. 79.1; p = 0.002), with over double the proportion with good fidelity (VLC = 73.9% vs. TA = 34.8%; p = 0.009). Over half of individuals in both VLC and TA achieved cardiovascular risk-reduction at 6-month follow-up (VLC: 51.0%; TA: 53.5%; p = 0.517) and at 12-month follow-up (62% VLC and TA; p = 0.912). At 12-month follow-up VLC compared to TA was associated with greater participation (VLC 69.5% vs. TA 56.4% attending at least 50% of sessions, p = 0.002); larger caseloads (VLC = 16 vs. TA = 11; p = 0.024); greater reach consisting of 45% greater number of participants receiving InSHAPE (VLC = 368 vs. TA = 253), and 58% greater number of participants achieving cardiovascular risk reduction (VLC = 150 vs. TA = 95). Virtual learning collaboratives compared to routine technical assistance as an implementation strategy for evidence-based health promotion promote greater intervention fidelity, greater levels of intervention participation, greater reach, and a greater number of participants achieving clinically significant risk reduction outcomes, while achieving similarly high levels of intervention effectiveness for participants who completed at least 6 months of the program.


[Step by step: differential indication and specialized in-door psychotherapy as implemented in a psychiatric-psychotherapeutic state hospital].
Different patients need different treatment, when in-door psychotherapy is the indication. Also, in the course of psychotherapeutic treatment a change of setting might be useful or necessary. It is shown how this knowledge can be put into work in a psychiatric-psychotherapeutic state hospital with obligatory service, using an integrated group of several specialized wards.


Stem cell donor registry activities during the COVID-19 pandemic: a field report by DKMS.
The COVID-19 pandemic has serious implications also for patients with other diseases. Here, we describe the effects of the pandemic on unrelated hematopoietic stem cell donation and transplantation from the perspective of DKMS, a large international donor registry. Especially, we cover the development of PBSC and bone marrow collection figures, donor management including Health and Availability Check (HAC), transport and cryopreservation of stem cell products, donor recruitment and business continuity measures. The total number of stem cell products provided declined by around 15% during the crisis with a particularly strong decrease in bone marrow products. We modified donor management processes to ensure donor and product safety. HAC instead of confirmatory typing was helpful especially in countries with strict lockdowns. New transport modes were developed so that stem cell products could be safely delivered despite COVID-19-related travel restrictions. Cryopreservation of stem cell products became the new temporary standard during the pandemic to minimize risks related to transport logistics and donor availability. However, many products from unrelated donors will never be transfused. DKMS discontinued public offline donor recruitment, leading to a 40% decline in new donors during the crisis. Most DKMS employees worked from home to ensure business continuity during the crisis.


Microalgal system for treatment of effluent from poultry litter anaerobic digestion.
The potential of mixotrophic microalgae to utilize poultry litter anaerobic digester (AD) effluent (PLDE) as nutritional growth medium was evaluated. Three algal strains viz. Chlorella minutissima, Chlorella sorokiniana and Scenedesmus bijuga and their consortium showed significant biomass productivity in 6% (v/v) concentration of PLDE in deionized water. Multiple booster dosage of PLDE supported better growth relative to a single dose PLDE. The maximum biomass productivity of 76 mg L(-1) d(-1) was recorded. The biomass was rich in protein (39% w/w) and carbohydrates (22%) while lipids (<10%) were low, making it most suitable as an animal feed supplement. The mixotrophic algae showed sustainable growth against variations in PLDE composition in different AD batches, thus proving to be a suitable candidate for large scale wastewater treatment with concomitant production of renewable biomass feedstock for animal feed and bioenergy applications.


The number and composition of work hours for attending physicians in Taiwan.
Long work hours among physicians is a worldwide issue in the healthcare arena. Previous studies have largely focused on the work hours of resident physicians rather than those of attending physicians. The purpose of this study was to investigate total work hours and the composition of those work hours for attending physicians across different hospital settings and across different medical specialties through a nationwide survey. This included examining differences in physician workload and its composition with respect to different hospital characteristics, and grouping medical specialties according to the work similarities. A cross-sectional self-reported nationwide survey was conducted from June to September of 2018, and the two questionnaires were distributed to all accredited hospitals in Taiwan. The number of physician work hours in different types of duty shifts were answered by medical specialty in each surveyed hospital. Each medical specialty in a hospital filled only one response for its attending physicians. The findings reveal that the average total work hours per week of an attending physician is around 69.1 h, but the total work hours and their composition of different duty shifts varied among hospital accreditation levels, geographic locations, emergency care responsibilities, and medical specialties. Because of the variance in the number and composition of attending physicians' work hours, adjusting physician work hours to a reasonable level will be a major challenge for health authority and hospital managers.


Preparation and properties of tritiated human beta-endorphin with high specific radioactivity.
Tritiated human beta-endorphin, specifically labelled at Tyr27, has been prepared with 50 Ci/mmol. Various physicochemical investigations indicated that tritiated peptide is identical with the native betah-endorphin. In addition, opiate activity of the tritiated product possesses the same potency as the native peptide.


X-linked mental deficiency.
Ten percent of cases of intellectual deficiency in boys are caused by genes located on the X chromosome. X-linked mental retardation (XLMR) includes more than 200 syndromes and 80 genes identified to date. The fragile X syndrome is the most frequent syndrome, due to a dynamic mutation with a CGG triplet amplification. Mental retardation is virtually always present. Phonological and syntactic impairments are often combined with pragmatic language impairment and visuospatial reasoning difficulties. A minority fulfill the criteria for autism. In girls, the clinical expression of the complete mutation varies according to the X chromosome inactivation profile. Several XLMR occur as severe early onset encephalopathies: Lowe oculocerebrorenal syndrome, ATR-X syndrome (alpha thalassemia/mental retardation X-linked), Allan-Herdon-Dudley syndrome (MCT8 gene). Two genes, ARX (X-LAG; Partington syndrome) and MECP2 (Rett syndrome in females; mild MR with spastic diplegia/psychotic problems in males) are associated with various phenotypes, according to the mutation involved. Oligophrenine 1 (OPHN-1) gene mutations lead to vermal dysplasia. PQBP1 gene mutations (Renpenning syndrome) are responsible for moderate to severe mental deficiency, microcephaly, and small stature. Although some forms of XLMR are not very specific and the phenotype for each given gene is somewhat heterogeneous, a clinical diagnostic strategy is emerging.


Autologous Muscle-Derived Nerve Wrap for Prevention of Symptomatic Microneuromas in Primary Nerve Repair.
Regeneration of peripheral nerves after repair is incomplete. Painful microneuromas may form at the site of an appropriately performed primary microsurgical nerve repair leading to a persistent Tinel's sign and hypersensitivity in that location. Here, we describe an autologous option using a free muscle-derived nerve wrap with the intent to capture axonal escape at the site of primary nerve coaptation. We demonstrate this technique on a patient undergoing primary nerve repair of a laceration to the superficial branch of the radial nerve using extensor digitorum communis muscle as a donor graft. This has become our preferred technique over commercially available nerve wraps as the muscle wrap is autologous, not limited by cost, and has the potential to limit microneuroma formation at the coaptation site.


Analysis of anabolic steroids in the horse: development of a generic ELISA for the screening of 17alpha-alkyl anabolic steroid metabolites.
Due to the potential for misuse of a wide range of anabolic steroids in horse racing, a screening test to detect multiple compounds, via a common class of metabolites, would be a valuable forensic tool. An enzyme-linked immunosorbent assay (ELISA) has been developed to detect 17alpha-alkyl anabolic steroid metabolites in equine urine. 16beta-Hydroxymestanolone (16beta,17beta-dihydroxy-17alpha-methyl-5alpha-androstan-3-one) was synthesised in six steps from commercially available epiandrosterone (3beta-hydroxy-5alpha-androstan-17-one). Polyclonal antibodies were raised in sheep, employing mestanolone (17beta-hydroxy-17alpha-methyl-5alpha-androstan-3-one) or 16beta-hydroxymestanolone conjugated to human serum albumin, via a 3-carboxymethyloxime linker, as antigens. Antibody cross-reactivities were determined by assessing the ability of a library of 54 representative steroids to competitively bind the antibodies. Antibodies raised against 16beta-hydroxymestanolone showed excellent cross-reactivities for all of the 16beta,17beta-dihydroxy-17alpha-methyl steroids analysed and an ELISA has been developed to detect these steroid metabolites. Using this 16beta-hydroxymestanolone assay, urine samples from horses administered with stanozolol (17alpha-methyl-pyrazolo[4',3':2,3]-5alpha-androstan-17beta-ol), were analysed raw, following beta-glucuronidase hydrolysis, and following solid-phase extraction (SPE) procedures. The suppressed absorbances observed were consistent with detection of the metabolite 16beta-hydroxystanozolol. Positive screening results were confirmed by comparison with standard LCMS analyses. Antibodies raised against mestanolone were also used to develop an ELISA and this was used to detect metabolites retaining the parent D-ring structure following methandriol (17alpha-methylandrost-5-ene-3beta,17beta-diol) administration. The ELISA methods developed have application as primary screening tools for detection of new and known anabolic steroid metabolites.


Novel risk model based on angiogenesis-related lncRNAs for prognosis prediction of hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death due to early metastasis or recurrence. Tumor angiogenesis plays an essential role in the tumorigenesis of HCC. Accumulated studies have validated the crucial role of lncRNAs in tumor angiogenesis. Here, we established an angiogenesis-related multi-lncRNAs risk model based on the machine learning for HCC prognosis prediction. Firstly, a total of 348 differential expression angiogenesis-related lncRNAs were identified by correlation analysis. Then, 20 of these lncRNAs were selected through univariate cox analysis and used for in-depth study of machine learning. After 1,000 random sampling cycles calculating by random forest algorithm, four lncRNAs were found to be highly associated with HCC prognosis, namely LUCAT1, AC010761.1, AC006504.7 and MIR210HG. Subsequently, the results from both the training and validation sets revealed that the four lncRNAs-based risk model was suitable for predicting HCC recurrence. Moreover, the infiltration of macrophages and CD8 T cells were shown to be closely associated with risk score and promotion of immune escape. The reliability of this model was validated by exploring the biological functions of lncRNA MIR210HG in HCC cells. The results showed that MIR210HG silence inhibited HCC growth and migration through upregulating PFKFB4 and SPAG4. Taken together, this angiogenesis-related risk model could serve as a reliable and promising tool to predict the prognosis of HCC.


[Determination of deoxynivalenol and deepoxy-deoxynivalenol in milk].
A HPLC method with UV/diode array detection for the determination of deoxynivalenol (DON) and deepoxy-deoxynivalenol (DOM-1) in milk was developed. Milk was incubated with β-glucuronidase and then defatted. After purification by immunoaffinity chromatography, DON and DOM-1 were separated on a C18 reversed phase column with acetonitril/water (10/90) as the mobile phase and detected at 218 nm. Limits of quantification were 1 μg/l for both toxins, with mean recoveries (1-10 μg/l) of 97% (DON) and 84% (DOM-1), respectively. Milk samples (pasteurized, UHT; n=32) from German retail shops were analysed by this method. Neither DON/DOM-1 nor their glucuronides were found in any sample. These results are consistent with published studies indicating that in lactating cows, DON and DOM-1 are mostly eliminated through urine, and that the carry-over into milk is negligible.


Limited dispersal and its effect on population structure in the milkweed beetle Tetraopes tetraophthalmus.
The movement patterns of adult milkweed beetles, Tetraopes tetraphthalmus, were monitored via a mark-recapture technique. Movement or dispersal patterns were studied in two natural populations, one in which the host plant, Asclepias syriaca, was nearly continuously distributed over a 250×90 m area and another where Asclepias was distributed in 17 small discrete patches. In both populations dispersal distances resulting from the flight patterns of the adult beetles were quite short, averaging less than 40 m from the point of first encounter 10 days after marking. Males were shown to be more vagile than females. The distribution of dispersal distances collected from one of the populations was fit to three statistical distributions cited in the literature as expected from dispersal by many small-scale movements or observed in other species. It was found that an equation describing an exponential decay gave the best statistical fit to the data collected here for milkweed beetles. The data is discussed in the context of the effects of the limited dispersal power of the beetles and the distribution of suitable habitat on the population structure of Tetraopes.


Two redundant ubiquitin-dependent pathways of BRCA1 localization to DNA damage sites.
The tumor suppressor BRCA1 accumulates at sites of DNA damage in a ubiquitin-dependent manner. In this work, we revisit the role of RAP80 in promoting BRCA1 recruitment to damaged chromatin. We find that RAP80 acts redundantly with the BRCA1 RING domain to promote BRCA1 recruitment to DNA damage sites. We show that that RNF8 E3 ligase acts upstream of both the RAP80- and RING-dependent activities, whereas RNF168 acts uniquely upstream of the RING domain. BRCA1 RING mutations that do not impact BARD1 interaction, such as the E2 binding-deficient I26A mutation, render BRCA1 unable to accumulate at DNA damage sites in the absence of RAP80. Cells that combine BRCA1 I26A and mutations that disable the RAP80-BRCA1 interaction are hypersensitive to PARP inhibition and are unable to form RAD51 foci. Our results suggest that in the absence of RAP80, the BRCA1 E3 ligase activity is necessary for recognition of histone H2A Lys13/Lys15 ubiquitylation by BARD1, although we cannot rule out the possibility that the BRCA1 RING facilitates ubiquitylated nucleosome recognition in other ways.


Phenomenological aspects of hypnotic interactions: the effect of kinship.
This study analyzes the relationship of various measures of hypnosis as a function of kinship. Subjects with varying degrees of kinship (mono- and dizygotic twins, siblings, and parent-child pairs) participated. The Stanford Hypnotic Susceptibility Scale, Form A (SHSS:A), as well as other measures-including the Dyadic Interactional Harmony (DIH) and the Phenomenology of Consciousness Inventory (PCI)-were used with both subjects and hypnosis practitioners. Findings indicated that the phenomenological experience of hypnosis is not determined genetically. The subjects apparently evaluated the session as related to the degree of kinship. MZ twins-on the basis of reactive interactional pattern-evaluate the hypnotic interaction similarly. This was not true for SHSS:A scores or the phenomenological aspects of the state (PCI). These findings were interpreted within the sociopsychobiological model of hypnosis.


LncRNA HCG18 Promotes Osteosarcoma Cells Proliferation, Migration, and Invasion in by Regulating miR-34a/RUNX2 Pathway.
Osteosarcoma (OS) is a type of tumor with high malignant behaviors. Increasing investigates have confirmed that long non-coding RNA HLA complex group 18 (lncRNA HCG18) acted as a tumor-promoting factor in multiple tumors. Nevertheless, the underlying mechanism of HCG18 on OS remains largely unclear. HCG18, miR-34a, and runt-related transcription factor 2 (RUNX2) expressions were detected by quantitative real-time PCR (RT-qPCR) or western blotting assays, respectively. The underlying tumorigenic phenotypes were detected by MTT, wound healing, transwell invasion, western blotting assays. Molecular interactions were verified by dual-luciferase report assay. HCG18 and RUNX2 were notably enhanced, whereas miR-34a was decreased in OS tumor tissues and cell lines. Functional experiments uncovered that HCG18 silencing significantly inhibited the capabilities of proliferation, migration, and invasion, while overexpression of HCG18 play the opposite roles. Furthermore, HCG18 directly bound to miR-34a, and miR-34a was confirm to be a negative regulator of RUNX2. Interestingly, the anti-tumor effects of HCG18 silencing were attenuated by miR-34a inhibitor and RUNX2 overexpression. Taken together, the present study suggested that HCG18 promoted the malignant biological behaviors of OS through regulating the miR-34a/RUNX2 pathway, implying HCG18 might serve as a new target for OS treatment.


Caspase-11 cleaves gasdermin D for non-canonical inflammasome signalling.
Intracellular lipopolysaccharide from Gram-negative bacteria including Escherichia coli, Salmonella typhimurium, Shigella flexneri, and Burkholderia thailandensis activates mouse caspase-11, causing pyroptotic cell death, interleukin-1β processing, and lethal septic shock. How caspase-11 executes these downstream signalling events is largely unknown. Here we show that gasdermin D is essential for caspase-11-dependent pyroptosis and interleukin-1β maturation. A forward genetic screen with ethyl-N-nitrosourea-mutagenized mice links Gsdmd to the intracellular lipopolysaccharide response. Macrophages from Gsdmd(-/-) mice generated by gene targeting also exhibit defective pyroptosis and interleukin-1β secretion induced by cytoplasmic lipopolysaccharide or Gram-negative bacteria. In addition, Gsdmd(-/-) mice are protected from a lethal dose of lipopolysaccharide. Mechanistically, caspase-11 cleaves gasdermin D, and the resulting amino-terminal fragment promotes both pyroptosis and NLRP3-dependent activation of caspase-1 in a cell-intrinsic manner. Our data identify gasdermin D as a critical target of caspase-11 and a key mediator of the host response against Gram-negative bacteria.


Psychological effects of Tai Chi Chuan.
This article reviews the scientific studies which have been carried out at the international level on the psychological benefits that Tai Chi Chuan (TCC) brings to those who practice it. It analyzes the framework in which the research was performed, the real benefits that this activity achieves and their causes. The present article brings a new analytical perspective to the reviews carried out to date in regard to classifying and analyzing the psychological variables involved in the practice of TCC and offers a homogeneous framework within which to develop research in this field based on the model proposed by Spirduso et al. (2005).


Insights into the fatty acid chain length specificity of the carboxylesterase PA3859 from Pseudomonas aeruginosa: A combined structural, biochemical and computational study.
The open reading frame PA3859 of Pseudomonas aeruginosa encodes an intracellular carboxylesterase belonging to a group of microbial enzymes (EC 188.8.131.52) that catalyze the hydrolysis of aliphatic and aromatic esters with a broad substrate specificity. With few exceptions, for this class of enzymes, belonging to the α/β-hydrolase fold superfamily, very little information is available regarding their biochemical activity and in vivo function. The X-ray crystal structure of recombinant PA3859 has been determined for two crystal forms (space groups P2(1) and P2(1)2(1)2). The kinetic properties of the enzyme were studied using p-nitrophenyl esters as substrates and data fitted to a surface dilution mixed micelle kinetic model. Enzymatic assays and computational docking simulations, pinpointed the enzyme's preference for esters of palmitic and/or stearic acids and provided insights into the enzyme-substrate favorable binding modes.


Study of Endogenous CRAC Channels in Human Mast Cells Using an Adenoviral Delivery System to Transduce Cells with Orai-Targeting shRNAs or with cDNAs Expressing Dominant-Negative Orai Channel Mutations.
We describe two methods to study CRAC channel function in human lung mast cells. Both methods involve suppression of endogenous channel function. In the first we use Orai-targeting shRNAs to knock down Orai channel mRNA transcripts. In the second we overexpress dominant-negative mutants of the three members of the Orai channel family. To overcome the poor transfection efficiency of mast cells, we employ an adenoviral delivery system for cell transduction. Knockdown of CRAC channel transcripts is assessed initially using quantitative RT-PCR. We describe an assay for β-hexosaminidase release as a measure of mast cell degranulation to assess the effect of overexpression of dominant-negative mutants.


Quantitative electron energy loss spectroscopy in biology.
The potential for applying electron energy loss spectroscopy (EELS) in biology is assessed. Some recent developments in instrumentation, spectrometer design, parallel detection and elemental mapping are discussed. Quantitation is demonstrated by means of the spectrum from DNA which gives an elemental ratio for N:P close to the expected value. A range of biologically important elements that can be usefully analyzed by EELS is tabulated and some possible applications for each are indicated. Detection limits and the effects of radiation damage are illustrated by spectra from the protein, insulin, and from the fluorinated amino-acid, histidine. Calcium detectability under optimum conditions may be as low as 1 mmol/kg dry weight. The application of EELS to analysis of cryosectioned adrenomedullary (chromaffin) cells is described in order to help determine the composition of the secretory granule. Water content can be determined from the amount of inelastic scattering as measured by the low-loss spectrum. The nitrogen/phosphorus ratio can be measured to provide information about the relative concentrations of ATP, chromogranin, and catecholamines. Quantitative EELS elemental maps are obtained in the STEM mode from chromaffin cells in order to measure the distribution of light elements.


Adsorption of azithromycin in agricultural soils of the Bogotá savanna, Colombia.
Azithromycin is one of the most widely used macrolide antibiotics in medical treatment. However, there is little information on studies of the ecotoxicity, persistence and mobility of this type of compounds in the environment, although their presence in surfaces and wastewater has already been detected (Hernández et al., 2015). Based on this approach, the present research performs an analysis of the behavior of the adsorption process of azithromycin in soils of different textural classes, with the intention of establishing a first approach to assess the destination and transport of such substances in the biosphere. From the results of the evaluation of the conditions of adsorption of azithromycin, it is established that the Langmuir model has a better fit for clay soils with correlation coefficients R2 between 0.998 and 0.961. In contrast, the Freundlich model fits the soil with higher sand fraction with a higher correlation, R2 of 0.9892. Finally, based on a correlation analysis between the clay content, the percentage of organic matter and the adsorption coefficient K, it was evident that the adsorption of azithromycin is mainly related to the inorganic fraction of the soil.


Does the frequency of soft sonographic aneuploidy markers vary by fetal sex?
To determine whether the frequency of soft sonographic aneuploidy markers varies by fetal sex. We identified all singleton fetuses with known sex undergoing genetic sonography at 17 weeks' to 21 weeks 6 days' gestation in a single perinatal center from January 1, 2000, to December 31, 2003. Markers studied were biparietal diameter/femur length, transcerebellar diameter, ear length, echogenic bowel, femur length, humerus length, absent middle fifth phalanx, nuchal fold, renal pelvis dilatation, echogenic cardiac focus, and choroid plexus cysts. Additional information extracted from the prospectively ascertained database included maternal age, referral indications, and chromosomal analyses. Multiple gestations and fetuses with structural or chromosomal abnormalities were excluded. The study received exempt review status by the Institutional Review Board. Dichotomous variables were compared by the chi(2) or Fisher exact test; continuous variables were compared by the unpaired t test. In total, 4057 eligible fetuses, 2103 male and 1954 female, were examined at 18.9 +/- 0.9 weeks (mean +/- SD). Referral indications included maternal age of 35 years or older (n = 2983), abnormal second-trimester serum screen results (n = 610), soft marker on sonography (n = 583), prior aneuploid offspring (n = 24), and other (n = 125). More than 1 referral indication was possible for a given fetus. Overall, male fetuses exhibited echogenic fetal bowel (odds ratio, 1.76; 95% confidence interval [CI], 1.14-2.72; P = .009) and renal pelvis dilatation (odds ratio, 2.00; 95% CI, 1.30-3.09; P = .001) significantly more often than female fetuses. However, when fetuses were evaluated for single isolated markers, only male predominance of renal pelvis dilatation persisted (odds ratio, 2.32; 95% CI, 1.32-4.09; P = .003). No markers had increased frequency in female offspring. Male fetuses exhibit a significantly increased frequency of renal pelvis dilatation compared with female fetuses. Sex-specific adjustment of sonographically derived aneuploidy risk does not appear to be indicated. However, a larger series of fetuses with trisomy 21 and pyelectasis is required to assess sex-specific risk adjustment for this marker.


HDAC-mediated suppression of histone turnover promotes epigenetic stability of heterochromatin.
Heterochromatin causes epigenetic repression that can be transmitted through multiple cell divisions. However, the mechanisms underlying silencing and stability of heterochromatin are not fully understood. We show that heterochromatin differs from euchromatin in histone turnover and identify histone deacetylase (HDAC) Clr3 as a factor required for inhibiting histone turnover across heterochromatin domains in Schizosaccharomyces pombe. Loss of RNA-interference factors, Clr4 methyltransferase or HP1 proteins involved in HDAC localization causes increased histone turnover across pericentromeric domains. Clr3 also affects histone turnover at the silent mating-type region, where it can be recruited by alternative mechanisms acting in parallel to H3K9me-HP1. Notably, the JmjC-domain protein Epe1 promotes histone exchange, and loss of Epe1 suppresses both histone turnover and defects in heterochromatic silencing. Our results suggest that heterochromatic-silencing factors preclude histone turnover to promote silencing and inheritance of repressive chromatin.


Gepants - a long way to cure: a narrative review.
Calcitonin gene-related peptide (CGRP) is probably the most potent vasodilator in cerebral circulation. Forty years after its discovery, the new CGRP-targeted therapy monoclonal antibodies, and the small molecule gepants, are now available for clinical practice. While randomized controlled trials and real-world experience consistently demonstrated the high efficacy and tolerability of monoclonal antibodies, limited evidence is available to characterize gepants fully. Depending on pharmacokinetics, these CGRP receptor antagonists can be used for acute (ubrogepant, rimegepant, and the not yet approved zavegepant) or preventive (atogepant and rimegepant) migraine treatment. Randomized placebo-controlled trials demonstrated gepants efficacy in treating acute attacks to obtain 2 h pain freedom in about 20% of patients and pain relief in about 60%, while up to 60% of treated patients with episodic migraine may experience a 50% reduction in monthly migraine days. The most common treatment-related emergent adverse events were gastrointestinal (nausea, constipation) for the acute or preventive use. No vascular or hepatic concerns have emerged so far. More studies are ongoing to investigate gepant tolerability and safety also if associated with monoclonal antibodies targeting CGRP and other therapeutic classes. Gepants are also under investigation to treat other painful and non-painful conditions. Real-life studies are necessary to confirm the trials' findings and investigate more practical clinical aspects.


Genome Sequences of Three Strains of Lactobacillus paracasei of Different Origins and with Different Cholate Sensitivities.
We report here the draft genome sequences of three strains of Lactobacillus paracasei (NRIC 0644, NRIC 1781, and NRIC 1917) isolated from different sources. The three genomes range from 2.95 to 3.15 Mb with a G+C content of 46% and contain approximately 2,700 protein coding sequences.


Inhibitory effects of Thai plants beta-glycosides on Trichomonas vaginalis.
Trichomoniasis is now an important health problem in developing countries. Although metronidazole has so far been widely used to treat this disease, the prevalence of metronidazole-resistant protozoa and unpleasant adverse effects have been found. In this study, natural products purified from Thai plants were, therefore, investigated for their effectiveness against Trichomonas vaginalis. The minimal inhibitory concentrations for all beta-glycosides against Trichomonas vaginalis at 24 h were in a range of 6.25-12.5 microM. In addition, torvoside A and H were found to be more potent than their corresponding aglycones, deglucosylated torvoside A and H, while other beta-glycosides were generally as active as their corresponding aglycones. The cytotoxicity of these compounds was also determined. Except for dalcochinin, none of the tested compounds showed cytotoxicity against Vero and cancer cell lines (KB and MCF-7), having IC(50) values greater than 50 microg/ml. In conclusion, beta-glycosides and several aglycones showed selective inhibition against Trichomonas vaginalis without harmful effect to mammalian cells.


Plasma vitamin E, apolipoprotein B and HDL-cholesterol in middle-aged men from southern Italy.
Plasma vitamin E, HDL-cholesterol, apolipoprotein B and triglycerides were measured in an apparently healthy, male, random population sample (n = 74) from Southern Italy. Plasma vitamin E concentration was positively correlated to that of serum cholesterol, non-HDL cholesterol, triglycerides and apolipoprotein B (all P less than 0.001). The results of partial correlation analysis showed that apo B, the apolipoprotein constituent of LDL, was related to vitamin E independently of serum triglycerides, a fairly accurate marker of VLDL. On the other hand, triglycerides were related to vitamin E independently of apo B. Both correlations were much weaker if an adjustment was performed for non-HDL-cholesterol. No independent relationship was demonstrated between plasma vitamin E and HDL-cholesterol.


Clinical benefits of telemetered electrograms in assessment of DDD function.
The advent of telemetry of the endocardial electrogram is a new capability. It must be convenient to use if it is to gain acceptance. Our experience is still growing but already it is confirming information that was either deduced or previously only available by active invasive procedures. The potential value of the technology has only been touched upon in this presentation. We are convinced that it will grow and that its value will be further established as more physicians have an opportunity to use it and gain additional experience.


Effect of a policy to reduce user fees on the rate of skilled birth attendance across socioeconomic strata in Burkina Faso.
In Sub-Saharan Africa, maternal and neonatal morbidity and mortality rates are associated with underutilization of skilled birth attendance (SBA). In 2007, Burkina Faso introduced a subsidy scheme for SBA fees. The objective of this study was to evaluate the effect of Burkina Faso's subsidy policy on SBA rate across socioeconomic status (SES) strata. We used a quasi-experimental design. The data sources were two representative surveys (n = 1408 and n = 1403) of women from Houndé and Ziniaré health districts of Burkina Faso, and a survey of health centres assessing structural quality of care. Multilevel Poisson regression models were used with robust variance estimators. We estimated adjusted rate ratios (RR) and rate differences (RD) as a function of time and SES. For lowest-SES women, immediately upon the introduction of the subsidy policy, the rate of SBA was 45% higher (RR = 1.45, 95% confidence interval (CI): 1.19-1.77) than expected in the absence of subsidy introduction. The results indicated a sustained effect after introduction of the subsidy policy, based on RR estimate (95% CI) of 1.48 (1.21-1.81) at 2 years. For middle-SES women, the RR estimates were 1.28 (1.09-1.49) immediately after introduction of the subsidy policy and 1.30 (1.11-1.51) at 2 years, respectively. For highest-SES women, the RR estimates were 1.19 (1.02-1.38) immediately after subsidy introduction and 1.21 (1.06-1.38) at 2 years, respectively. The RD (95% CI) was 14% (3-24%) for lowest-SES women immediately after introduction of the policy, and the effect was sustained at 14% (4-25%) at 2 years. Our study suggests that the introduction of a user-fee subsidy in Burkina Faso resulted in increased rates of SBA across all SES strata. The increase was sustained over time and strongest among the poorest women. These findings have important implications for evidence-informed policy making in Burkina Faso and other countries in Sub-Saharan Africa.


PheASR2, a novel stress-responsive transcription factor from moso bamboo (Phyllostachys edulis), enhances drought tolerance in transgenic rice via increased sensitivity to abscisic acid.
Abscisic acid, stress and ripening (ASR) transcription factors comprise a small family of proteins that play a key role in stress responses in plants. ASR genes involved in drought tolerance in moso bamboo (Phyllostachys edulis) are largely unknown. In our study, an ASR gene, PheASR2, was isolated and characterized. The expression of PheASR2 was up-regulated under various abiotic stresses, including drought, salt and abscisic acid (ABA). PheASR2 was localized in the nucleus in tobacco cells, and displayed transactivation activity in yeast. Ectopic expression of PheASR2 in rice conferred enhanced tolerance to drought stress, as determined through physiological analyses of germination rate, plant height, water loss and survival rate. The PheASR2-overexpressing transgenic plants showed an increase in reactive oxygen species (ROS), electrolyte leakage and malondialdehyde levels, reduced enzyme (CAT and SOD) activities, and higher expression of genes encoding ROS-scavenging enzymes. Consequently, the transgenic plants exhibited increased tolerance to oxidative stress compared with wild-type plants. Moreover, following ABA treatment, the seed germination rate and plant height of the PheASR2-overexpressing lines were inhibited, and stomatal closure was reduced. The expression of marker genes, including, OsAREB, OsP5CS1, OsLEA, and OsNCED2, was up-regulated in the PheASR2-overexpressing lines when subjected to drought treatment. Together, these results indicate that PheASR2 functions in drought stress tolerance through ABA signaling.


Structure and function of immunoglobulin domains. VII. Studies on the structural requirements of human immunoglobulin G for granulocyte binding.
The ability of various fragments of human myeloma IgG1 to inhibit rosette formation between human anti-D-coated human red blood cells and human polymorphonuclear leukocytes has been investigated. Although IgG and Fc showed a dose-dependent inhibition of rosettes and Fc showed a dose-dependent inhibition of rosettes at equimolar concentrations, neither of the fragments corresponding to the Cgamma2 and Cgamma3 homology regions obtained by acid-tryptic cleavage of Fc was able to inhibit rosette formation. The pepsin fragment of Fc, pFc', which represents the complete Cgamma3 domain, was also unable to prevent rosette formation. Reduction and alkylation of IgG or Fc markedly diminished cytophilic activity as measured by this system. These data indicate that the site in human IgG1 bound by granulocytes is dependent on the full quaternary structure of Fc, a requirement in marked contrast to that noted for binding by macrophages and monocytes.


Longer Prehospitalization and Preintubation Periods in Intubated Non-survivors and ECMO Patients With COVID-19: A Systematic Review and Meta-Analysis.
Purpose: There is no clear consensus on the clinical course of critical COVID-19 patients. We examined the clinical course among intubated survivors, non-survivors, and extracorporeal membrane oxygenation (ECMO) patients to reveal the standard clinical course and the difference among critical COVID-19 patients. Methods: In this systematic review and meta-analysis, we searched PubMed, Web of Science, and Scopus for original studies published until December 11, 2020, including case accumulation and clinical course reporting. Pregnant patients and children were excluded. We followed PRISMA guidelines and registered them with PROSPERO (CRD42021235534). Results: Of the 11,716 studies identified, 94 met the selection criteria, and 2,549 cases were included in this meta-analysis. The times from intubation to extubation and death were 12.07 days (95% confidence interval 9.80-14.33 days) and 10.14 days (8.18-12.10 days), respectively, and the ECMO duration was 14.72 days (10.57-18.87 days). The time from symptom onset to hospitalization (prehospitalization period) of intubated survivors, non-survivors, and ECMO patients was 6.15 (4.61-7.69 days), 6.45 (4.55-8.34 days), and 7.15 days (6.48-7.81 days), and that from symptom onset to intubation (preintubation period) was 8.58 (7.36-9.80 days), 9.14 (7.26-11.01 days), and 10.54 days (9.18-11.90 days), respectively. Sensitivity analysis showed that the time from intubation to extubation and death was longer in the US and Europe than in East Asia. Conclusion: For COVID-19, we hypothesize that prehospitalization and preintubation periods are longer in intubated non-survivors and ECMO patients than in intubated survivors. These periods may serve as a predictor of disease severity or death and support therapeutic strategy determination.


Outcomes of Aspirex®S thrombectomy system combined with catheter-directed thrombolysis for treating bilateral lower extremity deep venous thrombosis.
Pharmacomechanical catheter-directed thrombolysis (PCDT) is rarely reported in treating bilateral lower extremity deep venous thrombosis (LEDVT). This study was aimed to investigate the safety, patency, and mid-term outcomes of the Aspirex®S thrombectomy system combined with catheter-directed thrombolysis (CDT) in treating symptomatic bilateral LEDVT. The clinical data of 45 consecutive patients with acute or subacute bilateral LEDVT (60.00% male; mean age, 53.8 ± 16.5 years) who received endovascular treatment with PCDT between January 2015 and June 2019 were retrospectively analyzed in this study. The clinical efficacy of thrombolysis (≥50% thrombolysis), complications, primary patency, valvular function, and cumulative prevalence of post-thrombotic syndrome (PTS) were retrospectively analyzed. PCDT was performed in all 45 patients successfully. No serious procedure-related complication or death was observed. The average urokinase dosage was 4.1 ± 1.5 million IU, and the average thrombolysis time was 5.3 ± 1.3 days. The mean length of hospital stay was 9.9 ± 2.5 days. The primary patency was 100% after lysis. The clinical efficacy of thrombolysis was 86.7% (39/45). Deep venous thrombosis recurrence was observed in six (13.3%) patients within 12 months after discharge. The primary patency at 1-, 3-, 6-, 9-, and 12-month follow-up was 97.8%, 93.3%, 88.9%, 82.2%, and 73.3%, respectively. The cumulative prevalence of PTS was 24.4% (11/45) throughout the follow-up period, whereas the prevalence of moderate and severe PTS was only 6.7% (3/45). PCDT for treating bilateral LEDVT is feasible, effective, and safe.


Clinical efficacy of high frequency jet ventilation during extracorporeal shock wave lithotripsy of renal and ureteral calculi: a comparison with conventional mechanical ventilation.
The use of high frequency jet ventilation compared to conventional mechanical ventilation during general anesthesia for extracorporeal shock wave lithotripsy of renal or ureteral calculi can reduce stone movement. This decrease in stone movement theoretically lessens the total shock and energy requirements for stone fragmentation and perirenal tissue damage. To assess these theoretical advantages of high frequency jet ventilation, we studied patients undergoing extracorporeal shock wave lithotripsy to determine differences in stone movement during high frequency jet and conventional mechanical ventilation (30 patients), and in total shock requirements (1,174 patients). Mean stone movement in the 30 patients was 34.3 +/- 4.3 mm. during conventional mechanical ventilation compared to 4.1 +/- 1.9 mm. during high frequency jet ventilation (p less than 0.001). Mean total shocks were 1,542 +/- 212 (452 patients) during conventional mechanical ventilation compared to 1,217 +/- 165 (722 patients) during high frequency jet ventilation (p less than 0.001). Only 1 patient in the study had clinically significant perirenal tissue damage. We conclude that high frequency jet ventilation when compared to conventional mechanical ventilation results in clinically and economically beneficial decreases in total shocks for extracorporeal shock wave lithotripsy fragmentation of renal or ureteral calculi.


Prompt treatment-seeking behaviour varies within communities among guardians of children with malaria-related fever in Malawi.
In Malawi, malaria is responsible for 40% of hospital deaths. Prompt diagnosis and effective treatment within 24 h of fever onset is critical to prevent progression from uncomplicated to severe disease and to reduce transmission. As part of the large evaluation of the malaria vaccine implementation programme (MVIP), this study analysed survey data to investigate whether prompt treatment-seeking behaviour is clustered at community-level according to socio-economic demographics. From 4563 households included in the survey, 4856 children aged 5-48 months were enrolled. Out of 4732 children with documented gender, 52.2% were female and 47.8% male. Among the 4856 children, 33.8% reported fever in the two weeks prior to the survey. Fever prevalence was high in communities with low socio-economic status (SES) (38.3% [95% CI: 33.7-43.5%]) and low in areas with high SES (29.8% [95% CI: 25.6-34.2%]). Among children with fever, 648 (39.5%) sought treatment promptly i.e., within 24 h from onset of fever symptoms. Children were more likely to be taken for prompt treatment among guardians with secondary education compared to those without formal education (aOR:1.37, 95% CI: 1.11-3.03); in communities with high compared to low SES [aOR: 2.78, 95% CI: 1.27-6.07]. Children were less likely to be taken for prompt treatment if were in communities far beyond 5 km to health facility than within 5 km [aOR: 0.44, 95% CI: 0.21-0.92]. The high heterogeneity in prevalence of fever and levels of prompt treatment-seeking behaviour underscore the need to promote community-level malaria control interventions (such as use of long-lasting insecticide-treated nets (LLINs), indoor residual spraying (IRS), intermittent preventive therapy (IPT), presumptive treatment and education). Programmes aimed at improving treatment-seeking behaviour should consider targeting communities with low SES and those far from health facility.


Endometrial and plasma concentrations of pregnancy-associated plasma protein-A (PAPP-A).
Pregnancy-associated plasma protein-A (PAPP-A), oestradiol and progesterone levels have been measured by radioimmunoassay in plasma and in endometrial homogenates of 20 women undergoing hysterectomy. Results were grouped according to the histological stages of the endometrium. In plasma, oestradiol and progesterone concentrations changed from proliferative to secretory stages in the well-established pattern of the menstrual cycle, but PAPP-A levels did not change. In endometrium, oestradiol levels were high during the proliferative stage and low in inactive and secretory endometrium. Endometrial PAPP-A and progesterone concentrations increased from inactive to secretory stages, but only the increase in PAPP-A was statistically significant. A positive correlation observed between endometrial PAPP-A concentrations and plasma oestradiol/progesterone ratio suggests a possible hormonal control for the presence of PAPP-A in the uterus.


Human cytomegalovirus persists in cells treated with interferon. Brief report.
Human cytomegalovirus disappeared from cultures continuously exposed to interferon. When interferon was removed, high titers of virus reappeared. Cytomegalovirus was thus able to persist in potentially infectious form in cells protected by interferon.


A Primed Neutrophil Subset Predicts the Risk of Bloodstream Infections in Allogeneic Hematopoietic Stem-Cell Transplant Patients: A Prospective Study.
Bloodstream infections (BSIs) are the most common infectious complication in patients who receive allogeneic hematopoietic stem-cell transplants (allo-HSCTs). Polymorphonuclear neutrophils (PMNs) are quantified to monitor the susceptibility to BSIs; however, their degree of activation is not. We previously identified a population of primed PMNs (pPMNs) with distinct markers of activation representing approximately 10% of PMNs in circulation. In this study, we investigate whether susceptibility to BSIs is related to the proportion of pPMNs rather than strictly PMN counts. In this prospective observational study, we used flow cytometry to assess pPMNs in blood and oral rinse samples collected from patients receiving an allo-HSCT over the course of their treatment. We used the proportion of pPMNs in the blood on day 5 post-transplant to categorize patients into a high- or a low-pPMN group (>10% or <10% pPMNs). These groups were then used as a predictor of BSIs. A total of 76 patients were enrolled in the study with 36 in the high-pPMN group and 40 in the low-pPMN group. Patients in the low-pPMN group had lower expression of PMN activation and recruitment markers and displayed a delay in PMN repopulation of the oral cavity after the transplant. These patients were more susceptible to BSIs compared with patients in the high-pPMN group with an odds ratio of 6.5 (95% confidence interval, 2.110-25.07; P = .002). In patients who receive an allo-HSCT, having <10% pPMNs early in the post-transplant phase can be an independent predictor of BSI in allo-HSCT patients.


Transcriptomic and metabolomic analyses revealed epiboly delayed mechanisms of 2,5-dichloro-1, 4-benuinone on zebrafish embryos.
2,5-Dichloro-1,4-benzenediol (2,5-DCBQ) is a putative disinfection by-product that belongs to the halogenated benzoquinone class. However, its developmental toxicity and related mechanism remained unclarified. In our study, we used zebrafish embryos as the model and exposed them to graded concentrations of 2,5-DCBQ (100, 200, 300, 400 μg/L). We found that the rate of epiboly abnormalities increased significantly in a concentration-dependent manner. The results of whole-mount in situ hybridization (WISH) indicated that the expression patterns and levels of chordin (dorsoventral marker), foxa2 (endodermal marker), eve1 (ventral mesodermal marker), and foxb1a (ectodermal marker) were altered, suggesting that 2,5-DCBQ might affect the germ layer development of zebrafish embryos. Integrated transcriptomic and metabolomic analyses were adopted to explore the molecular mechanisms of embryonic developmental delays. The results showed that 2,5-DCBQ exposure induced 1163 differentially expressed genes (DEGs) and 37 differential metabolites (DEMs). Bioinformatic analysis enriched the most affected molecular pathways (Wnt signaling pathway, cell adhesion molecules, actin cytoskeleton regulation) and metabolic pathways (purine metabolism, aminoacyl-tRNA biosynthesis, arginine and proline metabolism) in zebrafish embryos. To summarize, our findings broadened the molecular mechanisms of 2,5-DCBQ embryotoxicity through multi-omics and bioinformatic analyses.


Inhibitor of apoptosis proteins as intracellular signaling intermediates.
Inhibitor of apoptosis (IAP) proteins have often been considered inhibitors of cell death due to early reports that described their ability to directly bind and inhibit caspases, the primary factors that implement apoptosis. However, a greater understanding is evolving regarding the vital roles played by IAPs as transduction intermediates in a diverse set of signaling cascades associated with functions ranging from the innate immune response to cell migration to cell-cycle regulation. In this review, we discuss the functions of IAPs in signaling, focusing primarily on the cellular IAP (c-IAP) proteins. The c-IAPs are important components in tumor necrosis factor receptor superfamily signaling cascades, which include activation of the NF-κB transcription factor family. As these receptors modulate cell proliferation and cell death, the involvement of the c-IAPs in these pathways provides an additional means of controlling cellular fate beyond simply inhibiting caspase activity. Additionally, IAP-binding proteins, such as Smac and caspases, which have been described as having cell death-independent roles, may affect c-IAP activity in intracellular signaling. Collectively, the multi-faceted functions and complex regulation of the c-IAPs illustrate their importance as intracellular signaling intermediates.


Percutaneous ablation of renal tumors versus surgical ablation and partial nephrectomy: Medicare trends and reimbursement cost comparison from 2010 to 2018.
The purpose of this study is to analyze trends in Medicare volume and reimbursement for percutaneous and surgical ablation as well as laparoscopic and open partial nephrectomy for treatment of small renal tumors from 2010 to 2018. Claims from the Medicare Part B Physician/Supplier Procedure Summary from 2010 to 2018 were extracted using CPT codes for percutaneous and surgical renal ablation and surgical and laparoscopic partial nephrectomy. Facility reimbursement and relative value units (RVUs) were obtained using the Centers for Medicare & Medicaid Services physician fee schedule look-up tool. Volume of percutaneous ablation increased from 2539 to 4571 procedures (80.0%). Specifically, percutaneous cryoablation became the dominant technique, increasing from 1434 to 2981 procedures (107.9%). Overall, volume of partial nephrectomy also increased by 40.4%, driven by an increase in laparoscopic partial nephrectomy from 3227 to 7770 procedures (140.8%) with a decrease in open partial nephrectomy from 3489 to 1661 (- 52.4%). Volume of surgical ablations also decreased 72.7% from 1260 to 344 procedures. In 2018, reimbursement was $358.56 for percutaneous radiofrequency ablation, $481.32 for percutaneous cryoablation, $1216.43 for surgical radiofrequency ablation, $1269.35 for surgical cryoablation, $1381.67 for open partial nephrectomy, and $1552.66 for laparoscopic partial nephrectomy. There has been a trend toward minimally invasive techniques for treatment of small renal tumors among Medicare patients. Laparoscopic partial nephrectomy has become the dominant treatment. In the setting of evidence showing comparable outcomes with surgery as well as lower costs to insurers, the volume of percutaneous ablation has also markedly increased.


NAVIO RATKA shows similar rates of hemoglobin-drop, adverse events, readmission and early revision vs conventional TKA: a single centre retrospective cohort study.
Despite widespread adoption of NAVIO robotic-assisted total knee arthroplasty (NAVIO RATKA) in clinical practice, clinical outcome in terms of adverse events and complications remains unclear. The purpose of this study was to compare adverse events, length of stay, surgical time, hemoglobin drop, early readmission rate and revision rate between conventional TKA (CTKA) and NAVIO RATKA. This single-centre retrospective cohort analysis compared 230 NAVIO RATKA patients to 489 CTKA patients with a minimal follow-up of 12 months. Baseline demographic and comorbidity parameters were collected, as well as length of stay, revision rate and reason for revision, early readmission rate (< 6w) and reason for readmission, post-operative hemoglobin levels, adverse events, surgical time and operating room time. Data were compared using Mann-Whitney U test for continuous data without normal distribution and ordinal data, categorical variables were compared using the Chi-square or Fisher exact test. There were no clinically relevant baseline demographic or comorbidity differences between groups. CTKA had shorter length of stay than NAVIO RATKA (5.0 days vs 5.4 days, p = 0.010) but trended towards a higher reoperation rate (4.1% vs 1.7%, p = .144, n.s). No differences were found in hemoglobin drop, readmission rate or overall incidence of adverse events, but CTKA showed more hematoma formation (1.6% vs 0%, p = .044) and higher incidence of periprosthetic joint infection (PJI) (1% vs 0%, p = n.s.), whilst NAVIO RATKA showed more periprosthetic fractures and persistent wound drainage (0.4% vs 2.2%, p = .038 and 0.6% vs 4.3%, p = .001, respectively). Surgical time remained significantly longer in NAVIO RATKA during all 230 cases (87 min vs 67.6 min) and showed a continuous downward trend. This study further validates the usage of NAVIO RATKA as a safe method to perform TKA, with comparable short term outcomes to CTKA in terms of early revisions and adverse events. Surgeons should be mindful of the differing adverse event profile in NAVIO RATKA and adjust their patient selection accordingly to ensure optimal outcomes. In addition, surgeons using NAVIO RATKA should expect a linear learning curve and a surgical time exceeding that of CTKA. Level III (therapeutic retrospective cohort study).


PROMIS fatigue, pain intensity, pain interference, pain behavior, physical function, depression, anxiety, and anger scales demonstrate ecological validity.
Ecological validity refers to the degree to which instruments faithfully capture information in respondents' natural environments. We examined the ecological validity of eight instruments from the Patient Reported Outcomes Measurement Information System (PROMIS), most of which use 7-day reporting periods, by comparing PROMIS scores with daily diary data as a standard. Five groups of approximately 100 respondents each completed daily diaries and weekly PROMIS instruments for 4 consecutive weeks: community residents; osteoarthritis patients; women experiencing premenstrual syndrome; men undergoing hernia surgery; and breast cancer patients receiving chemotherapy. The last three groups experienced events (menses, surgery, or chemotherapy, respectively) at standardized times in the protocol to examine symptom changes attributable to these events. We examined the ability of the PROMIS scales to replicate between-group differences in diaries, to replicate week-to-week changes in diaries, and the correlation between diary and PROMIS scales. As a secondary aim, we examined known-group differences with the PROMIS measures. All three types of ecological validity were strongly confirmed, as was known-group validity for the PROMIS recall scales. This study adds to the growing literature supporting the reliability and validity of the family of PROMIS instruments.


Human umbilical cord mesenchymal stem cell-derived extracellular vesicles improve ovarian function in rats with primary ovarian insufficiency by carrying miR-145-5p.
Stem cell/exosome therapy is a novel strategy for primary ovarian insufficiency (POI). This paper is to examine the role of human umbilical cord mesenchymal stem cell-derived extracellular vesicles (hUCMSC-EVs) in POI. hUCMSC-EVs were extracted and identified. POI rats were induced by cyclophosphamide for 15 days and treated with EV or GW4869 every 5 days and euthanized 28 days later. Vaginal smears were observed for 21 days. Serum hormone levels (FSH/E2/AMH) were measured by ELISA. Ovarian morphology, follicle numbers, and granulosa cell (GC) apoptosis were observed by HE and TUNEL staining. GCs extracted from Swiss albino rats were cyclophosphamide-induced to establish the POI cell model, followed by oxidative injury and apoptosis evaluation with the help of DCF-DA fluorescence, ELISA, and flow cytometry. The relation between miR-145-5p and XBP1 was predicted on StarBase and validated by dual-luciferase assay. miR-145-5p and XBP1 levels were measured by RT-qPCR and Western blot. EV treatment reduced irregular estrus cycle incidence since day 7, increased E2 and AMH levels and all-stage follicle numbers, reduced FSH level, GC apoptosis, and atretic follicle numbers in POI rats. EV treatment diminished GC oxidative injury and apoptosis in vitro. miR-145-5p knockdown in hUCMSC-EVs partly abolished hUCMSC-EV-mediated effects on GCs and ovarian function in vivo and on GC oxidative injury and apoptosis in vitro. Silencing XBP1 partially negated miR-145-5p knockdown-exerted effects on GCs in vitro. miR-145-5p carried by hUCMSC-EVs attenuates GC oxidative injury and apoptosis and thus extenuates ovarian injury and improves ovarian function in POI rats.


Starting up anammox system with high efficiency nitrogen removal at low temperatures: Performance optimization, sludge characterization and microbial community analysis.
Anaerobic ammonia oxidation (anammox) has potential advantages for nitrogen removal when operating at medium temperatures, but the increased operation costs of heating limit its application. It would be advantageous to start and operate anammox at low temperatures, the feasibility of which was studied here on a lab scale. Two identical expanded granular sludge bed (EGSB) reactors were inoculated at 35 ± 1 °C (Amed) and 15 ± 3 °C (Alow). Results showed that anammox was successful after 138 d for Alow, only 7 d longer than Amed. Stable operation to 194 d in Alow, the nitrogen loading rate (NLR) increased to 1.01 kg m-3·d-1, giving a high nitrogen removal efficiency (NRE) of 85%, which was only slightly lower than that of Amed (90%). More extracellular polymeric substance (EPS) was produced by the microbes of Alow compared to Amed, which prevented anaerobic ammonia oxidizing bacteria (AnAOB) against low temperature stress. Microbial community revealed presence of Candidatus Jettenia in Amed with relative abundance 7.4%, while the "cold-tolerant" Candidatus Kuenenia with 4% was the dominant anammox bacteria in Alow. The anammox granules adapted well to low temperatures and demonstrated high efficiency in anammox process without heating. Therefore, constructing an energy-saving and cost-effective anammox system in high latitudes or high altitudes can be considered.


Simultaneous determination of fosinopril and hydrochlorothiazide in pharmaceutical formulations by spectrophotometric methods.
Three new spectrophotometric procedures for the simultaneous determination of fosinopril and hydrochlorothiazide are described. The first method, derivative-differential spectrophotometry, comprised of measurement of the difference absorptivities derivatized in the first-order (DeltaD(1)) of a tablet extract in 0.1 N NaOH relative to that of an equimolar solution in methanol at wavelengths of 227.6 and 276.4 nm, respectively. The second method, depends on the application ratio spectra derivative spectrophotometric method to resolve the interferance due to spectral overlapping. The analytical signals were measured at 237.9, 243.8 nm for fosinopril and 262.4, 269.3 and 278.6 nm for hydrochlorothiazide in the binary mixture, in the first derivative of the ratio spectra of the mixture solutions in methanol. Calibration graphs were established for 4.0-50.0 microg ml(-1) fosinopril and 2.0-14.0 microg ml(-1) hydrochlorothiazide in binary mixture. The third method, absorbance ratio method, the determination of fosinopril and hydrochlorothiazide was performed by using the absorbances read at 210.0, 219.5 and 271.7 nm in the zero-order spectra of their mixture. The developed methods were compared with absorbance ratio method. Application of the suggested procedures were successfully applied to the determination of this compound in synthetic mixtures and in pharmaceutical preparations, with high percentage of recovery, good accuracy and precision.


Predicting factors for complications in peripheral intravenous catheters in the pediatric population.
To characterise the association between peripheral intravenous catheter (PIVC) gauge (G), the patient's age, insertion site and complication incidence. This prospective study was performed in Hadassah Medical Center, Jerusalem, Israel, between June 2018 and March 2019. Children with PIVC admitted to the paediatric departments were included. PIVCs were evaluated daily. A total of 113 children with 132 PIVCs were included in the study. The most common site of insertion was the antecubital fossa (43.9%). PIVCs were most commonly used for intravenous (IV) antibiotics (46.6%). Complications were observed for 40.9% PIVCs. Dislodgement was the most common complication. The complication rate was higher for the lower limbs (60%) and external jugular veins (100%) p = 0.002. In infants younger than 12 months, the complication rate was higher for 22 G PIVCs or larger (58.7% versus 27.5%; p = 0.05). In contrast, for the 1-6 years age group, PIVCs smaller than 24 G had a higher complication rate (p = 0.004). Patients with comorbidities had a higher complication rate (p = 0.003). Risk factors for complications are comorbidities and sites of insertion other than the upper limbs. In infants, 24 G PIVC or smaller should be inserted, whereas 22 G PIVC or larger are superior for 1- to 6-year-old children.