The experiences of interval appendectomy for inflammatory appendiceal mass.
Interval appendectomy (IA) is a common treatment of acute appendicitis (AA) with inflammatory appendiceal mass (IAM). However, the management of patients with IAM is still controversial. The aim of this study was to assess the outcomes in patients with this condition. We retrospectively evaluated 244 patients with AA for their clinical characteristics and outcomes. Forty-three patients had IAM at the first medical examination. The mean age was significantly younger and the C-reactive protein level significantly higher (12.6 vs 3.1 mg/dL) in patients with IAM. Thirty-four patients received IA, and nine received emergency appendectomy (EA). In the IA group, the diameter of the abscess was larger than in the EA group (31.4 vs 16.1 mm). The total length of hospitalization was longer in the IA group than the EA group (20.6 vs 7.0 days), although the operative time was longer in the EA group because of adhesion (101.1 vs 192.1 min). Furthermore, most IA patients received a reduced-port appendectomy (74% vs 11%). Recurrence occurred in approximately 15% of patients awaiting IA. There were no complications in either group. Although each treatment approach has its advantages and disadvantages, both IA and EA can be the first option for the treatment of AA with IAM.


Multimillimetre-large superlattices of air-stable iron-cobalt nanoparticles.
Self-organization of nanoparticles into two- and three-dimensional superlattices on a large scale is required for their implementation into nano- or microelectronic devices. This is achieved, generally after a size-selection process, through spontaneous self-organization on a surface, layer-by-layer deposition or the three-layer technique of oversaturation, but these techniques consider superlattices of limited size. An alternative method developed in our group involves the direct formation in solution of crystalline superlattices, for example of tin nanospheres, iron nanocubes or cobalt nanorods, but these are also of limited size. Here, we report the first direct preparation in solution of multimillimetre-sized three-dimensional compact superlattices of nanoparticles. The 15-nm monodisperse FeCo particles adopt an unusual short-range atomic order that transforms into body-centred-cubic on annealing at 500 degrees C. The latter process produces an air-stable material with magnetic properties suitable for radiofrequency applications.


LW-FQZip 2: a parallelized reference-based compression of FASTQ files.
The rapid progress of high-throughput DNA sequencing techniques has dramatically reduced the costs of whole genome sequencing, which leads to revolutionary advances in gene industry. The explosively increasing volume of raw data outpaces the decreasing disk cost and the storage of huge sequencing data has become a bottleneck of downstream analyses. Data compression is considered as a solution to reduce the dependency on storage. Efficient sequencing data compression methods are highly demanded. In this article, we present a lossless reference-based compression method namely LW-FQZip 2 targeted at FASTQ files. LW-FQZip 2 is improved from LW-FQZip 1 by introducing more efficient coding scheme and parallelism. Particularly, LW-FQZip 2 is equipped with a light-weight mapping model, bitwise prediction by partial matching model, arithmetic coding, and multi-threading parallelism. LW-FQZip 2 is evaluated on both short-read and long-read data generated from various sequencing platforms. The experimental results show that LW-FQZip 2 is able to obtain promising compression ratios at reasonable time and memory space costs. The competence enables LW-FQZip 2 to serve as a candidate tool for archival or space-sensitive applications of high-throughput DNA sequencing data. LW-FQZip 2 is freely available at http://csse.szu.edu.cn/staff/zhuzx/LWFQZip2 and https://github.com/Zhuzxlab/LW-FQZip2 .


Erratum: Sinonasal Symptoms in COPD: Burden and Associations with Clinical Markers of Disease [Corrigendum].
[This corrects the article DOI: 10.2147/COPD.S372991.].


Neuronal types in the striatum of man.
Nerve cells of the human striatum were investigated with the use of a newly developed technique that reveals the pattern of pigmentation of individual nerve cells by means of transparent Golgi impregnations of their cell bodies and processes. Five types of neurons are distinguished: Type I is a medium-sized spine-laden neuron with an axon giving off a great number of collateral branches. The vast majority of the cells in the striatum belong to this type. Numerous intensely stained lipofuscin granules are contained in one pole of the cell body and may also extend into adjacent portions of a dendrite. Type II is a medium-sized to large neuron with long intertwining dendrites decorated with spines of uncommon shape. A distinguishing feature of this cell type is the presence of somal spines. This cell type is devoid of pigment or contains only a few tiny lipofuscin granules. Type III is a large multipolar neuron. The cell body generates a few rather extended dendrites that are very sparsely spined. The finely granulated pigment is evenly dispersed within a large portion of the cytoplasm. Type IV is a large aspiny neuron with rounded cell body and richly branching tortuous dendrites. The axon branches frequently in the vicinity of the parent soma. Large pigment granules are concentrated within a circumscribed part of the cell body close to the cell membrane. Type V is a small to medium-sized aspiny neuron. The dendrites break up into a swirling mass of thin branches. More than one axon may be given off from the soma. The axons branch close to the soma into terminal twigs. Cells of this type contain numerous large and well-stained lipofuscin granules. Each of the cell types has a characteristic pattern of pigmentation. The different varieties of nerve cells in the striatum can therefore be distinguished not only in Golgi impregnations but also in pigment-Nissl preparations.


Intrinsic sexual dimorphism in the placenta determines the differential response to benzene exposure.
Maternal immune activation (MIA) by environmental challenges is linked to severe developmental complications, such as neurocognitive disorders, autism, and even fetal/maternal death. Benzene is a major toxic compound in air pollution that affects the mother as well as the fetus and has been associated with reproductive complications. Our objective was to elucidate whether benzene exposure during gestation triggers MIA and its impact on fetal development. We report that benzene exposure during pregnancy leads MIA associated with increased fetal resorptions, fetal growth, and abnormal placenta development. Furthermore, we demonstrate the existence of a sexual dimorphic response to benzene exposure in male and female placentas. The sexual dimorphic response is a consequence of inherent differences between male and female placenta. These data provide crucial information on the origins or sexual dimorphism and how exposure to environmental factors can have a differential impact on the development of male and female offspring.


Intelligent multichannel stimulator for the study of cardiac arrhythmias.
An intelligent multichannel stimulator (IMS) has been designed and built for use in a cardiac research environment. The device is capable of measuring and responding to cardiac electrophysiological phenomena in real time with carefully timed and placed electrical stimuli. The system consists of 16 channels of sense/stimulation electronics controlled by a digital signal processor (DSP) data acquisition card and a host computer and can be expanded to include more channels. The DSP allows for powerful and flexible algorithms to be implemented for real-time interaction with the cardiac tissue. Although a number of possible uses can be conceived for such a device, the initial motivation was to improve upon attempts to terminate fibrillation by pacing. The IMS was tested in an open-chest animal model, both in sinus rhythm and during fibrillation. It was shown to be an effective research tool by demonstrating the ability to measure and respond to cardiac activations in real time using complex numerical algorithms and appropriately timed stimuli.


Effects of phenol on extracellular polymeric substances and microbial communities from aerobic granular sludge treating low strength and salinity wastewater.
The effects of phenol on aerobic granular sludge including extracellular polymeric substances (EPS) and microbial community were investigated for low strength and salinity wastewater treatment. Elevated phenol over 20 mg/L stimulated biological phosphorus removal mainly via co-metabolism with nearly complete phenol degradation, whereas resulted in significant accumulation of nitrate around 4 mg/L. Aerobic granules kept structural stability via enhancing production of extracellular polymeric substances (EPS), especially folds of polysaccharides (PS) and varying functional groups identified through EEM, FTIR and XPS spectral characterizations at increasing phenol loads. Illumina MiSeq sequencing results indicated that elevated phenol decreased the bacterial diversity and richness, and caused remarkable variations in structural and compositions of microbial population. Multiple halophilic bacteria including Stappia, Luteococcus, and Formosa laid the biological basis for stability of aerobic granules and efficient biological nutrients and phenol removal. Redundancy analysis (RDA) suggested the key role of phenol in shaping the relative abundances and predominant genera. This study proved that aerobic granular sludge was feasible for low-saline and phenol-laden low-strength wastewater treatment.


Comparison of MI-oriented versus CBT-oriented adjunctive treatments: impacts on therapeutic alliance and patient engagement during hospital treatment for an eating disorder.
Our aim was to compare MI-oriented versus CBT-oriented adjunctive treatments to test whether an MI approach is superior in terms of improving therapeutic alliance and engagement among individuals with an eating disorder. The current study was a pilot randomized controlled trial with random allocation to either MI-oriented or a CBT-oriented adjunctive treatment group completed concurrently with a hospital-based group program for adults. Both adjunctive treatment conditions consisted of three individual therapy sessions and a self-help manual. Sixty-five outpatients receiving hospital treatment for a diagnosed eating disorder were randomly assigned to a treatment group. Measures of working therapeutic alliance, engagement, treatment completion, and clinical impairment were completed at preadmission, mid-treatment, and at the end of treatment. Working alliance increased equivalently in both conditions over time in treatment. Similarly, there were no differences between conditions in terms of engagement. Regardless of therapy orientation, greater use of the self-help manual predicted lowered eating disorder risk; stronger patient ratings of therapeutic alliance predicted decreased feelings of both ineffectiveness and interpersonal problems. This pilot RCT provides further evidence that both alliance and engagement are important for treatment of an eating disorder; however, there was no clear advantage of MI over CBT as an adjunctive treatment approach to improving alliance or engagement. ClinicalTrials.gov ID #NCT03643445 (proactive registration).


Simultaneous green extraction of fat and bioactive compounds of cocoa shell and protein fraction functionalities evaluation.
This work aimed to verify the feasibility of using alcoholic solvents under atmospheric pressure for the simultaneous extraction of fat and bioactive compounds from cocoa shell (CS), a byproduct of the cocoa industry, as well as to determine the influence of processing on the characteristics of defatted solids (DS). To this end, CS fat (CSF) extraction kinetics using ethanol or isopropanol as solvents were determined at 75 and 90 °C. Relative extraction yields of flavanols and alkaloids were determined, and protein functionalities such as the nitrogen solubility index were evaluated. CSF extraction yields from 36 to 70% were obtained with the highest figures related to absolute solvents. Conversely, hydrated alcohols were suitable to extract bioactive compounds, especially alkaloids, with extraction yields up to 73%. The best values of DS functionalities were obtained with the use of isopropanol, with a foaming capacity of (34 ± 2)% and stability of (57 ± 3)%; regarding emulsifying capability, the highest value was (126 ± 2) m2/g with a stability of (53 ± 4) min. CSF with a fatty acid composition similar to that of cocoa butter and DS with interesting protein functionalities were achieved, indicating that CS can be applied in food systems.


Characterization of estrogen-responsive epithelial cell lines and their infectivity by genital Chlamydia trachomatis.
Chlamydial attachment and infectivity in vitro and ascending disease and sequelae in vivo have been reported to be enhanced/modulated by estrogen. Endometrial carcinoma cell lines Ishikawa and HEC-1B and the breast cancer lines MCF-7 and HCC-1806 were examined for Chlamydia trachomatis E infectivity. Estrogen receptor (ER) presence was confirmed by Western blot and qRT-PCR analyses. FACS analysis was used to determine the percent of plasma membrane-localized ERs (mERs), and their activity was tested by estrogen binding and competitive estrogen antagonists assays. Chlamydiae grew in all cell lines with HEC (90%) >> MCF-7 (57%)>Ishikawa (51%) >> HCC-1806 (20%). The cell line ER isoform composition was re-defined as: ERalpha + ERbeta + for MCF-7, HCC-1806 and Ishikawa; and ERbeta only for HEC-1B. HeLa cells were also tested and found to express ERbeta, but not ERalpha. A small percentage of both ERs were surface-exposed and functionally active. The endometrium-predominant ERbeta isoform was found in all cell lines, including those most representative of the common sites of C. trachomatis infection. Thus, the role of chlamydial attachment/infectivity will now be analyzed in ERbeta+and-isogenic HEC-1B cells.


Studies on the kinetics and renal excretion of low and high molecular weight dextrans in preterm babies, newborns and young infants.
Administration of low and high molecular weight dextrans in the initial phase of shock is no longer controversial. The special conditions in newborns, however, have been insufficiently considered in planning therapy. This investigation aimed at determining the biological half-lives of dextran 40 (Rheomacrodex) and dextran 60 (Macrodex) in this age group. The half-life of dextran 40 was found to be 60 min and that of dextran 60 3 h. Preterm babies and newborns excrete up to 25% less dextran 40 and 60 in 24 h than infants and adults. Normal adult values for excretion are only reached towards the end of the first year of life.


Neural envelope encoding predicts speech perception performance for normal-hearing and hearing-impaired adults.
Peripheral hearing impairment cannot fully account for speech perception difficulties that emerge with advancing age. As the fluctuating speech envelope bears crucial information for speech perception, changes in temporal envelope processing are thought to contribute to degraded speech perception. Previous research has demonstrated changes in neural encoding of envelope modulations throughout the adult lifespan, either due to age or due to hearing impairment. To date, however, it remains unclear whether such age- and hearing-related neural changes are associated with impaired speech perception. In the present study, we investigated the potential relationship between perception of speech in different types of masking sounds and neural envelope encoding for a normal-hearing and hearing-impaired adult population including young (20-30 years), middle-aged (50-60 years), and older (70-80 years) people. Our analyses show that enhanced neural envelope encoding in the cortex and in the brainstem, respectively, is related to worse speech perception for normal-hearing and for hearing-impaired adults. This neural-behavioral correlation is found for the three age groups and appears to be independent of the type of masking noise, i.e., background noise or competing speech. These findings provide promising directions for future research aiming to develop advanced rehabilitation strategies for speech perception difficulties that emerge throughout adult life.


Beneficial effects of urine-derived stem cells on fibrosis and apoptosis of myocardial, glomerular and bladder cells.
Urine-derived stem cells (USCs) are isolated from voided urine and display high proliferative activity and multiple differentiation potentials. The applicability of USCs in the treatment of bladder dysfunction and in cell-based urological tissue engineering has been demonstrated. Whether they could serve as a potential stem cell source for the treatment of diabetes mellitus (DM) and its complications has not been investigated. Here, we report the repairing and protective effects of USCs on pancreatic islets, the myocardium, the renal glomerulus and the bladder detrusor in diabetic rat models. Type 2 diabetic rat models were induced by means of a high fat diet and intraperitoneal injection with streptozotocin. USCs isolated from voided urine were administered via tail veins. The functional changes of pancreatic islets, left ventricle, glomerulus and bladder micturition were assessed by means of insulin tolerance tests, echocardiography, urine biochemical indexes and cystometry. The histologic changes were evaluated by hematoxylin and eosin staining, Masson's trichrome staining and TUNEL staining. Treatment with USCs significantly alleviated the histological destruction and functional decline. Although the USC treatment did not decrease fasting blood glucose to a significantly different level, the fibrosis and apoptosis of the myocardium, glomerulus and detrusor were significantly inhibited. This study indicates that administration of USCs may be useful for the treatment of the complications of DM.


Phytochemicals: A potential therapeutic intervention for the prevention and treatment of cachexia.
Cachexia, a multifactorial and often irreversible wasting syndrome, is often associated with the final phase of several chronic disorders. Although cachexia is characterized by skeletal muscle wasting and adipose tissue loss, it is a syndrome affecting different organs, which ultimately results in systemic complications and impaired quality of life. The pathogenesis and underlying molecular mechanisms of cachexia are not fully understood, and currently there are no effective standard treatments or approved drug therapies to completely reverse cachexia. Moreover, adequate nutritional interventions alone cannot significantly improve cachexia. Other approaches to ameliorate cachexia are urgently needed, and thus, the role of medicinal plants has received considerable importance in this respect due to their beneficial health properties. Increasing evidence indicates great potential of medicinal plants and their phytochemicals as an alternative and promising treatment strategy to reduce the symptoms of many diseases including cachexia. This article reviews the current status of cachexia, the molecular mechanisms of primary events driving cachexia, and state-of-the-art knowledge that reports the preventive and therapeutic activities of multiple families of phytochemical compounds and their pharmacological mode of action, which may hold promise as an alternative treatment modality for the management of cachexia. Based on our review of various in vitro and in vivo models of cachexia, we would conclude that phytochemicals may have therapeutic potential to attenuate cachexia, although clinical trials are required to unequivocally confirm this premise.


Trajectories of sickness absence and disability pension days among 189,321 white-collar workers in the trade and retail industry; a 7-year longitudinal Swedish cohort study.
1) identify different trajectories of annual mean number of sickness absence (SA) and disability pension (DP) days among privately employed white-collar workers in the trade and retail industries and 2) investigate if sociodemographic and work-related characteristics were associated with trajectory membership. A longitudinal population-based cohort register study of all white-collar workers in the trade and retail industry in 2012 in Sweden (N = 189,321), with SA and DP data for 2010-2016. Group-based trajectory analysis was used to identify groups of individuals who followed similar trajectories of SA/DP days. Multinomial logistic regression was used to determine associations between sociodemographic and work-related factors and trajectory membership. We identified four trajectories of SA/DP days. Most individuals (73%) belonged to the trajectory with 0 days during all seven years, followed by a trajectory of few days each year (24%). Very small minorities belonged to a trajectory with increasing SA/DP days (1%) or to constantly high SA/DP (2%). Men had a lower risk of belonging to any of the three trajectories with SA/DP than women (OR Low SA/DP 0.42, 95% CI 0.41-0.44; Increasing SA/DP 0.34, 0.30-0.38; High SA/DP 0.33, 0.29-0.37). Individuals in occupations with low job control had a higher risk of belonging to the trajectory High SA/DP (OR low demands/low control 1.51; 95% CI 1.25-1.83; medium demands/low control 1.47, 1.21-1.78; high demands/low control 1.35, 1.13-1.61). Most white-collar belonged to trajectories with no or low SA/DP. Level of job control was more strongly associated with trajectory memberships than level of job demands.


Association between type D personality and prognosis in patients with cardiovascular diseases: a systematic review and meta-analysis.
Since 1995, the association of type D personality and mortality in patients with cardiovascular diseases has been increasingly investigated. The aim of this meta-analysis was to integrate conflicting results and to examine possible moderators of this association. Prospective studies assessing type D personality and hard endpoints were selected and pooled in meta-analyses. Cardiovascular diagnosis, type and quality of adjustment, and publication date were examined in moderator analyses. Twelve studies on patients with cardiovascular diseases (N = 5,341) were included. Pooled crude and adjusted effects demonstrated a significant association of type D personality and hard endpoints (odds ratio (OR) of 2.28 (95% CI [1.43-3.62]), adjusted hazard ratio (HR) of 2.24 (95% CI [1.37-3.66])). The OR decreased over time (OR 5.02 to OR 1.54). There was no association in congestive heart failure patients. More recent methodologically sound studies suggest that early type D studies had overestimated the prognostic relevance.


Scleroderma-like fibrosing disorders.
Many conditions presenting with clinical hard skin and tissue fibrosis can be confused with systemic sclerosis (scleroderma). These disorders have very diverse etiologies and often an unclear pathogenetic mechanism. Distinct clinical characteristics, skin histology, and disease associations may allow one to distinguish these conditions from scleroderma and from each other. A prompt diagnosis is important to spare patients from ineffective treatments and inadequate management. This article highlights nephrogenic systemic fibrosis (nephrogenic fibrosing dermopathy), eosinophilic fasciitis (Shulman's syndrome), scleromyxedema, and scleredema. These often are detected in the primary care setting and referred to rheumatologists for further evaluation. Rheumatologists must be able to promptly recognize them to provide valuable prognostic information and appropriate treatment options for affected patients.


A non-haem iron centre in the transcription factor NorR senses nitric oxide.
Nitric oxide (NO), synthesized in eukaryotes by the NO synthases, has multiple roles in signalling pathways and in protection against pathogens. Pathogenic microorganisms have apparently evolved defence mechanisms that counteract the effects of NO and related reactive nitrogen species. Regulatory proteins that sense NO mediate the primary response to NO and nitrosative stress. The only regulatory protein in enteric bacteria known to serve exclusively as an NO-responsive transcription factor is the enhancer binding protein NorR (refs 9, 10-11). In Escherichia coli, NorR activates the transcription of the norVW genes encoding a flavorubredoxin (FlRd) and an associated flavoprotein, respectively, which together have NADH-dependent NO reductase activity. The NO-responsive activity of NorR raises important questions concerning the mechanism of NO sensing. Here we show that the regulatory domain of NorR contains a mononuclear non-haem iron centre, which reversibly binds NO. Binding of NO stimulates the ATPase activity of NorR, enabling the activation of transcription by RNA polymerase. The mechanism of NorR reveals an unprecedented biological role for a non-haem mononitrosyl-iron complex in NO sensing.


Protected stent-assisted carotid angioplasty in the management of late post-endarterectomy restenosis.
The high complication rate associated with the surgical treatment of post-carotid endarterectomy restenosis has led several investigators to propose stent-assisted angioplasty as the treatment of choice for this condition. Late restenosis is very infrequent and mainly due to atherosclerotic progression. The aim of this study is to evaluate the potential risk of intraprocedural embolic stroke during stent-assisted angioplasty with cerebral protection devices in these patients. We describe our recent experience in the endovascular treatment of 10 patients presenting late carotid restenosis by means of stent-assisted angioplasty with the aid of a filter cerebral protection device. Mean elapsed time from surgery to angioplasty was 92+/-31 months (range 48-144 months). Procedural success was obtained in all the cases. Pre-dilation was performed in six cases, post-dilation in all the cases. The mean percentage stenosis was reduced from mean 77+/-12% (range 60-95%) to 6.3+/-6.7% (range 0-17%). Bradycardia while inflating the balloon was mild-to-moderate in seven cases and severe in two. No patient sustained stroke or transient ischemic attack (TIA) during the procedure or during hospital stay. On follow-up, two patients presented with moderate asymptomatic restenosis and were managed conservatively. Carotid angioplasty with cerebral protection can be performed safely in late carotid restenosis with a high technical success rate. No clinical embolic complications occurred in this subset of patients. With recent innovations and improvements in angioplasty technique, previous indications for angioplasty in these patients will have to be redefined. Carotid angioplasty seems to be a valuable treatment alternative to conventional surgery in this subset of patients.


The mechanism of metals precipitation by biologically generated alkalinity in biofilm reactors.
Microbial strains, characterized by increased tolerance and ability to grow in metal bearing wastewaters as well as by effective metal sequestering capability by both active (bioaccumulative) and passive (biosorptive) processes, were tested as inoculum for metal laden wastewater treatment systems. Their capacity to grow in metal bearing wastewater, using an easily available and inexpensive carbon source such as acetate, was studied in batch experiments. Two principal conclusions were drawn: (1). Growth was observed for all the strains examined suggesting that the strains can be acclimated to metals bearing wastewaters. (2). Solution pH increased from neutral to alkaline values during growth (pH(initial)=7, pH(final)=10). The later was observed systematically for all strains. Metal precipitation, due to the metabolically generated alkalinity is expected as a result.Supporting evidence for this hypothesis was provided during the operation of two pilot moving bed sand filters treating two different metal bearing wastewaters. Acetate was used as carbon source to support the growth and maintenance of microbial biomass on the sand grains of the filters. The characteristics of the sludge produced from the operation of the pilot plants were subsequently studied in the laboratory. Both sludges were significantly loaded with large amounts of metals.A mechanism of metal precipitation induced by the metabolically generated alkalinity, when acetate is used as carbon source, could be proposed as the main process responsible for the metals sequestering inside the moving bed sandfilter reactor.


Acute 2,3,7,8-Tetrachlorodibenzo-p-dioxin exposure in adult mice does not alter the morphology or inflammatory response of cortical microglia.
Microglia, the immune cells of the brain, have a canonical role in regulating responses to neurological disease or injury, but have also recently been implicated as regulators of neurophysiological processes such as learning and memory. Given these dual immune and physiological roles, microglia are a likely mechanism by which external toxic stimuli are converted into deficits in neuronal circuitry and subsequently function. However, while it is well established that exposure to environmental toxicants negatively affects the peripheral immune system, it remains unknown whether and how such exposure causes neuroinflammation which, in turn, may negatively impact microglial functions in vivo. Here, we examined how acute 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in adulthood, which negatively impacts immune cells in the periphery, affects microglial characteristics in the cortex of the mouse. We found that microglia density, distribution, morphology, inflammatory signaling, and response to a secondary, pathological activation were unaffected by acute TCDD exposure. These results suggest that acute, peripheral TCDD exposure in adulthood is not sufficient to induce an overt inflammatory phenotype in cortical microglia.


Effect of hydrodynamics on the transformation of nitrogen in river water by regulating the mass transfer performance of dissolved oxygen in biofilm.
Biofilms drive crucial ecosystem processes in rivers. This study provided the basis for overall quantitative calculations about the contribution of biofilms to the nitrogen cycle. At the early stage of biofilm formation, dissolved oxygen (DO) could penetrate the biofilms. As the biofilm grew and the thickness increased, then the mass transfer of DO was restricted. The microaerobic layer firstly appeared in biofilm under the turbulent flow conditions, with the appearance of the microaerobic and anaerobic layer, the nitrification and denitrification reaction could proceed smoothly in biofilm. And the removal efficiency of total nitrogen (TN) increased as the biofilm matured. Under the turbulent flow conditions, mature biofilms had the smallest thickness, but the highest proportion the anaerobic layer to the biofilm thickness, the highest density, and the highest nitrogen removal efficiency. However, the nitrogen removal efficiency of biofilm was the lowest under laminar flow conditions. The difference of layered structure of biofilm and the DO flux in biofilm explained the difference of nitrogen migration and transformation in river water under different hydrodynamic conditions. This study would help control the growth of biofilm and improve the nitrogen removal capacity of biofilm by regulating hydrodynamic conditions.


Fear, ambivalence, and liminality: key concepts in refusal to donate an organ after brain death.
The refusal to donate an organ is a phenomenon in need of exploration and explanation. This article refers to the major fear of becoming an organ donor in relation to a global culture perspective and to the Halacha (Jewish law). A theoretical critique about the ambivalence demonstrated by health care providers and families will discuss these concepts in relation to brain death, from the stages of hospitalization, through the period prior to the assertion of brain death, ending with brain death, and its perspective as a liminal situation.Finally, we conclude that nursing practices during the care of the "brain dead" patient, and toward the patient's family, should convey an unequivocal message. That is, brain death describes irreversible cessation of all brain function, and therefore, the patient becomes a dead body and can be treated as a potential organ donor.


Trajectories of alcohol consumption up to 30 years before and after the diagnosis of cardiovascular diseases: a longitudinal case-control study of 12 502 participants.
To examine the longitudinal trajectories of alcohol consumption prior to and following the diagnosis of cardiovascular diseases (CVD). We conducted a case-control study of 2501 incident cases of angina, myocardial infarction or stroke and 10 001 matched controls without the condition. Repeated measures of alcohol were centred on the date of diagnosis, spanning up to 30 years before and after CVD onset. Mean trajectories of weekly consumption were estimated using growth curve models. For trajectories prior to diagnosis, mean volume of alcohol consumed among male cases increased over time, peaking at around 8 years before diagnosis at 95 (95% CI 60 to 130) g/week and declining afterwards. Trajectories following diagnosis showed mean consumption in male cases dropped from 87 (95% CI 54 to 120) g/week to 74 (95% CI 45 to 102) g/week after the date of diagnosis and then slightly rose to 78 (95% CI 40 to 116) g/week at the subsequent 3.5 years, before gradually declining to 31 (95% CI 2 to 61) g/week at 30 years after diagnosis. Mean consumption among female cases remained stable prior to diagnosis (at about 30 g/week), fell marginally to 25 (95% CI 20 to 30) g/week after the date of diagnosis and kept decreasing afterwards. Similar trajectories were obtained in cases and controls. This is the first attempt to show how patients with CVD change their drinking volume over such a wide time span. Future research needs to establish insight into drinking behaviour in other ways (such as frequency and context) and address the impact of changes in drinking on patients with CVD.


A novel application of In2S3 for visible-light-driven photocatalytic inactivation of bacteria: Kinetics, stability, toxicity and mechanism.
Photocatalytic bacterial inactivation under visible light emerges as a new alternative to control microbial contamination by utilizing free and renewable sunlight. However, the exploration of highly effective and safe visible-light-driven (VLD) photocatalysts remains an important step toward accessing this new technology. Herein, an eco-friendly photocatalyst, namely Indium Sulfide (In2S3), was fabricated through a facile hydrothermal method for VLD photocatalytic inactivation of bacteria. The energy band gap of the as-prepared In2S3 was measured as 2.25 eV. As expected, the obtained In2S3 photocatalyst showed remarkable inactivation efficiency toward E. coli under fluorescent tubes irradiation. The photocatalytic inactivation kinetic was perfectly fitted by a mathematical model for bacteria inactivation. In addition, In2S3 exhibited high stability and could be reused. The leakage of In3+ was not significant and showed no toxic effect to the bacteria. Based on the results of scavenger study and ESR technology, the dominant reactive species causing In2S3 VLD photocatalytic bacterial inactivation were proposed as O2-, h+, H2O2 and e-, rather than OH. The SEM study suggested that the damages to the intracellular components occurred prior to the destruction of cell wall. This study provides novel application of In2S3 for VLD photocatalytic inactivation of bacteria as well as comprehensive insight into the inactivation mechanism.


Electronmicroscopical investigations of the effects of heparin upon the structural elements of the rat glomerulus.
In this study the ultrastructure of the renal glomeruli was investigated 30 minutes after the intraperitoneal administration of heparin. It was observed that the matrix and fibrillary structure became more abundant in the mesangial cells and also in the epicytes; it was noted that the Golgi apparatus was active and the granular endoplasmic reticulum was very enlarged, partially containing structures of a particular shape. Furthermore, there was a general thickening and a dense accumulation of matter in the basement membrane. It was thought that this was due to the migration of structural elements of the mesangial cells and epicytes to the basement membrane and not because of heparin storage. Therefore we have postulated that these structural changes observed in the glomeruli were not associated with the extrarenal effects (antiinflammatory; anticoagulating and anticomplementary activities) of heparin but that they could be related to its cyto-hormonal action upon the epicytes and mesangial cells.


[Prospective, comparative study of a infrared spectroscopic blood culture system (Bactec NR-660)].
The automatic Bactec NR-660 system was compared with a conventional blood culture system - Septi-Check, La Roche (RSC). Out of a total of 962 blood cultures 157 isolates were detected: 123 in RSC and 104 in Bactec 6A. If only clinical relevant strains were considered the isolation rate was nearly equal in both systems, being 75% in RSC and 77% in Bactec 6A, respectively. The RSC-system was more frequently contaminated (3.3% vs 1.0%). Positive blood cultures were detected 12 hrs earlier by the Bactec system.


Tracing of false negative results in phenotypic methods for identification of carbapenemase by Real-time PCR.
Carbapenemase production causes multi antibiotics resistant in Gram-negative bacteria. A simple rapid and accurate phenotypic test for detection of Gram-negative carbapenemase-producing bacteria is useful for the treatment of infections. The aim of this study was to track the negative results in carbapenemase phenotypic test by Real-time PCR. In this study, 161 imipenem resistant Gram-negative bacteria were surveyed. Modified Hodge Test (MHT), boronic acid (BA), EDTA and dipicolinic acid were used for detection of Klebsiella pneumoniae carbapenemase (KPC) and metallo-beta-lactamase (MBLs). Different phenotypic methods and PCR confirmation followed by Real-time PCR for determination of phenotypic false-negative results were used. Our results indicated that 85, 51 and 112 strains were MHT, BA and dipicolinic acid positive, respectively. No synergistic effect was observed between imipenem and EDTA. Sixty-nine strains were confirmed as carbapenemase-producers according to the results of molecular tests. All of the isolates carried the gene and expressed carbapenemase. Comparison between the results of phenotypic and genotypic methods showed that the phenotypic methods could be used as the primary screening and the PCR remains as the gold standard for detection of carbapenemase positive strains.


Behavioral and neurochemical effects on rat offspring after prenatal exposure to ethanol.
The work studied behavioral and neurochemical alterations in 21-day-old pups, from both sexes (26 g on average) born from female Wistar rats administered daily with ethanol (0.5 or 4.0 g/kg, p.o.), for 30 days before mating, and throughout their gestational period. Ethanol administration continued from delivery up to weaning. The open field, elevated plus maze and forced swimming tests were used to evaluate effects of ethanol on locomotion, anxiety and depression, respectively. Binding assays were used to identify dopaminergic (D1- and D2-like) and muscarinic (M1 plus M2) receptors. Results of the plus maze test indicated significant and dose-dependent increases in the number of entrances in the open arms and in the time of permanence in the open arms, in the prenatally ethanol-exposed offspring, as compared to controls, indicating an anxiolytic effect. In the open field test, this group presented decreases in spontaneous locomotor activity as well as in the occurrences of rearing and grooming. Offspring also showed dose-dependent increases in their immobility time in the forced swimming test, characterizing despair behavior. Decreases in the hippocampal (D2: 32%; D1: 25%) and striatal (D2: 30%; D1: 52%) dopaminergic binding were detected in ethanol-exposed offspring. On the other hand, significant increases were observed in muscarinic binding in the hippocampus (40%) as well as in the striatum (42%). This study shows evidence that in utero ethanol exposure produces a long-lasting effect on development and pharmacological characteristics of brain systems that may have important implications in behavioral and neurochemical responsiveness occurring in adulthood.


Capacitive deionization coupled with microbial fuel cells to desalinate low-concentration salt water.
A new technology (CDI-MFC) that combined capacitive deionization (CDI) and microbial fuel cell (MFC) was developed to treat low-concentration salt water with NaCl concentration of 60mg/L. The water desalination rate was 35.6mg/(Lh), meanwhile the charge efficiency was 21.8%. Two desorption modes were investigated: discharging (DC) mode and short circuit (SC) mode. The desalination rate in the DC mode was 200.6±3.1mg/(Lh), 47.8% higher than that in the SC mode [135.7±15.3mg/(Lh)]. The average current in the DC mode was also much higher than that of the SC mode. The energy stored in the CDI cell has been reused to enhance the electron production of MFC by the discharging desorption mode (DC mode), which offers an approach to recover the electrostatic energy in the CDI cell.


Magnetic Resonance Fingerprinting of the Pediatric Brain.
Magnetic resonance fingerprinting (MRF) is increasingly being used to evaluate brain development and differentiate normal and pathologic tissues in children. MRF can provide reliable and accurate intrinsic tissue properties, such as T1 and T2 relaxation times. MRF is a powerful tool in evaluating brain disease in pediatric population. MRF is a new quantitative MR imaging technique for rapid and simultaneous quantification of multiple tissue properties.


An eight-month clinical study of LA-2575 30.0 mg: a new 4-month, subcutaneous delivery system for leuprolide acetate in the treatment of prostate cancer.
To investigate the safety, efficacy, and pharmacokinetics of a new 4-month subcutaneous depot of leuprolide acetate in patients with prostate cancer. Ninety patients diagnosed with adenocarcinoma of the prostate were enrolled in an open-label, multicenter study. LA-2575 30.0 mg was administered subcutaneously once every 4 months for 8 months. The primary efficacy parameter was a serum testosterone level of 50 ng/dL or less. The pharmacokinetics of leuprolide acetate were analyzed in the first 24 enrolled patients. The values are reported as the mean +/- standard error. Of 90 enrolled patients, 82 (91%) completed the 8-month study. Eight patients voluntarily withdrew from the study for the following reasons: nonmedical reasons (n = 3), treatment-related adverse events (n = 3), disease progression (n = 1), and cardiovascular disease (n = 1). By day 28, 85 (94%) of the 90 patients had achieved a serum testosterone level less than 50 ng/dL. At study completion, 88 (98%) of the 90 patients had a testosterone value less than the castrate level (mean 12.4 +/- 0.8 ng/dL), with 81 (90%) at less than 20 ng/dL. From baseline to month 6, the mean luteinizing hormone level had decreased from 7.51 +/- 0.69 mIU/mL to 0.12 +/- 0.02 mIU/mL. The mean prostate-specific antigen level had decreased 90% from 13.2 +/- 2.0 ng/mL at baseline to 1.3 +/- 0.3 ng/mL at 8 months. No clinically significant flare reactions were observed. The most common treatment-related adverse event was mild hot flashes. LA-2575 30.0-mg depot consistently produced and maintained safe and effective suppression of serum testosterone, with total serum testosterone concentrations well below the medical castrate level of less than 50 ng/dL.


Symptomatic spinal epidural lipomatosis after a single local epidural steroid injection.
Spinal epidural lipomatosis is a rare disorder that can manifest with progressive neurological deficits. It is characterized by abnormal accumulation of unencapsulated epidural fat commonly associated with the administration of exogenous steroids associated with a variety of systemic diseases, endocrinopathies, and Cushing syndrome (Fogel et al. Spine J 5:202-211, 2005). Occasionally, spinal epidural lipomatosis may occur in patients not exposed to steroids or in patients with endocrinopathies, primarily in obese individuals (Fogel et al. Spine J 5:202-211, 2005). However, spinal lumbar epidural lipomatosis resulting from local steroid injection has rarely been reported. We report the case of a 45-year-old diabetic man with claudication that was probably due to symptomatic lumbar spinal lipomatosis resulting from a single local epidural steroid injection.


Field experiments of Anopheles gambiae attraction to local fruits/seedpods and flowering plants in Mali to optimize strategies for malaria vector control in Africa using attractive toxic sugar bait methods.
Based on recent studies in Israel demonstrating that attractive toxic sugar bait (ATSB) methods can be used to decimate local anopheline and culicine mosquito populations, an important consideration is whether the same methods can be adapted and improved to attract and kill malaria vectors in Africa. The ATSB approach uses fruit or flower scent as an attractant, sugar solution as a feeding stimulant, and an oral toxin. The ATSB solutions are either sprayed on vegetation or suspended in simple bait stations, and the mosquitoes ingesting the toxic solutions are killed. As such, this approach targets sugar-feeding female and male mosquitoes. This study examines the attractiveness of African malaria vectors to local fruits/seedpods and flowering plants, key biological elements of the ATSB approach for mosquito control. Three field experiments were conducted at sites in Mali. The attraction of Anopheles gambiae s.l. to 26 different local fruits and seedpods was determined at a site in the semi-arid Bandiagara District of Mali. Wire mesh glue traps with fruits/seedpods suspended on skewers inside were set along a seasonal lagoon. Seven replicates of each fruit/seedpod species were tested, with a water-soaked sponge and a sugar-soaked sponge as controls. The attraction of An. gambiae s.l. to 26 different types of flowering plants was determined at a site near Mopti in Mali. The flowering plants held in a water-filled buried container were tested using the same glue traps, with controls including water only and sugar solution. Six replicates of each selected plant type were tested on transects between rice paddies. Additional studies using CDC light traps were done to determine the relative densities and periodicity of An. gambiae s.l. attraction to branches of the most highly attractive flowering plant, branches without flowers, human odor, and candescent light. Of the 26 fruits and seedpods tested, 6 were attractive to An. gambiae s.l. females and males, respectively. Guava (Psidium guajava) and honey melon (Cucumis melo) were the two most attractive fruits for both females and males. Of the 26 flowering plants tested, 9 were significantly attractive for females, and 8 were attractive for males. Acacia macrostachya was the most attractive flowering plant. Periodicity studies using this plant showed peaks of An. gambiae s.l. attraction between 1930 and 2200 h and 0400-0500 h, which differed considerably from the response to human odors, which expectedly peaked at around midnight. These field experiments in Mali highlight that female and male An. gambiae s.l. have pronounced differences in attraction for diverse types of indigenous fruits/seedpods and flowering plants. The identification of attractive fruits and seedpods shows that a variety of indigenous and locally abundant natural products could potentially be used as juices to make ATSB solution for mosquito control. As well, the simple methods used to identify the most attractive flowering plants provide valuable insights into the natural history of sugar feeding for An. gambiae s.l. These observations can be used to guide future strategies for employing ATSB methods for malaria vector control in Africa. They also provide a basis for subsequent chemical analysis and development of attractive baits for mosquito control.


Effects of EPHX1 and CYP3A4*22 genetic polymorphisms on carbamazepine metabolism and drug response among Tunisian epileptic patients.
The aim of this study was to evaluate the impact of polymorphisms in the EPHX1 (c.416A > G, c.337T > C) and CYP3A4*22 genes involved in carbamazepine (CBZ) metabolism and pharmacoresistance among 118 Tunisian patients with epilepsy under maintenance dose of CBZ. These genetic polymorphisms were analyzed by PCR-RFLP. Associations between plasma CBZ concentration, CBZ-E concentration, maintenance doses and metabolic ratio (CBZ-E:CBZ, CBZ-D:CBZ-E) were analyzed with each polymorphism. Both variants of EPHX1 c.416A > G and c.337T > C are significantly associated with higher metabolic ratio CBZ-E:CBZ and seem to decrease the activity of the epoxide hydrolase. The CYP3A4*22 variant allele is significantly associated with lower CBZ-D:CBZ-E ratio and seems also to be associated with less activity of the cytochrome. Our data suggest that certain polymorphisms of metabolizing enzyme genes could influence inter-individual variability of CBZ metabolism.


The Giants (biologicals) against the Pigmies (small molecules), pros and cons of two different approaches to the disease modifying treatment in rheumatoid arthritis.
Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease that, if untreated, can lead to disability and reduce the life expectancy of affected patients. Over the last two decades the improvement of knowledge of the pathogenetic mechanisms leading to the development of the disease has profoundly changed the treatment strategies of RA through the development of biotechnological drugs (bDMARDs) directed towards specific pro-inflammatory targets involved in the RA network. To date, the therapeutic armamentarium for RA includes ten bDMARDs able to produce the depletion B-cells, the blockade of three different pro-inflammatory cytokines (tumour necrosis factor alpha, interleukin-6 and interleukin-1), or the inhibition of T-cell co-stimulation. The introduction of these new compounds has dramatically improved outcomes in the short and long term, although still a significant proportion of patients are unable to reach or maintain the treatment target over time. The identification of the fundamental role of Janus kinases in the process of transduction of the inflammatory signal within the immune cells has recently provided the opportunity to use the new pharmacological class of small molecules for the therapy of RA, further increasing the number of treatment options. In this review the PROS and CONS of these two drug classes will be discussed, trying to provide the evidence currently available to make the right choice based on the analysis of the efficacy and safety profile of the different drugs on the market and close to marketing.


Maximum oxygen uptake corrected for skeletal muscle mass accurately predicts functional improvements following exercise training in chronic heart failure.
Skeletal muscle mass and peak oxygen uptake are important predictors of functional status and outcome in patients with stable chronic heart failure. To assess changes in skeletal muscle mass and peak oxygen uptake following an exercise training program. Thirty-six patients with moderate stable chronic heart failure were randomly allocated to either a bicycle ergometer (bike) or functional electrical muscle stimulators (FES) applied to quadriceps and gastrocnemius muscles to be used daily for six weeks. Dual-energy X-ray absorptionometry (DEXA) scanning was performed before and after training along with symptom limited cardiopulmonary exercise test, quadriceps strength and fatigue resistance, and 6-min walk test. Both exercise modalities resulted in improvements in treadmill exercise time, leg strength, 6-min walk test and peak oxygen uptake per kilogram of skeletal muscle. Despite significant improvements in functional capacity, there were no significant changes in body composition for total skeletal muscle mass, leg muscle mass or total body fat content. Skeletal muscle mass was strongly predictive of maximum oxygen uptake at baseline (r=0.61, p<0.001) and after exercise training (r=0.68, p<0.001). In moderate stable chronic heart failure, exercise training using bicycle ergometer or FES results in favourable qualitative rather than quantitative changes in skeletal muscle. Correction of maximum oxygen uptake for skeletal muscle mass rather than total body mass is a more sensitive measure of changes associated with exercise training.


[Analysis of genetic heterogenicity of seed embryos in trees characterized by different seed productivity in Crimean population of Pinus pallasiana D. Don].
A comparative analysis of allozyme variability has been conducted for 10 polymorphic loci of samples of seeds and maternal plants characterized by significant differencies in productivity of empty and full-grained seeds in Pinus pallasiana D. Don population in Crimea. It has been determined that allele diversity is fully reproduced in seed progeny of plants of distinguished samples. However, their genetic structure is deviated because of heterozygote deficiency.


Laser interferometry analysis of ciprofloxacin and ampicillin diffusion from liposomal solutions to water phase.
The paper presents experimental investigations of diffusion of antibiotics (ciprofloxacin or ampicillin) into the water phase from mixtures of neutral or negatively charged liposomes, and antibiotic-liposome interactions. Using the laser interferometry technique, the amounts and fluxes of released antibiotics, concentration field evolution, and the velocity of the concentration boundary layer's "growth" were determined. To avoid the limitations of membranes, a measurement system without the artificial boundary of phases with a free water-solution interface has been proposed. It was found that the diffusion of anionic and neutral liposomes into the water phase was insignificant and mainly the diffusion of antibiotics was measured. Differences in the diffusion kinetics of ciprofloxacin and ampicillin from liposomal solutions to the water phase were observed. Ampicillin diffused more efficiently than ciprofloxacin regardless of the liposomal solution type. Moreover, the amount of ampicillin and ciprofloxacin released from the anionic liposomal phase was higher than that from the neutral one. Our results confirm that ciprofloxacin at neutral pH shows little tendency to bind neutral liposomes. Additionally, it was also observed that ciprofloxacin disrupts negatively charged liposomes as a final effect of antibiotic-lipid interactions.


The global burden of sudden infant death syndrome from 1990 to 2019: a systematic analysis from the Global Burden of Disease study 2019.
Sudden infant death syndrome (SIDS) still remains one of the leading causes of infant death worldwide, especially in high-income countries. To date, however, there is no detailed information on the global health burden of SIDS. To characterize the global disease burden of SIDS and its trends from 1990 to 2019 and to compare the burden of SIDS according to the socio-demographic index (SDI). Systematic analysis based on the Global Burden of Disease (GBD) 2019 data. Epidemiological data of 204 countries from 1990 to 2019 were collected via various methods including civil registration and vital statistics in the original GBD study. Estimates for mortality and disease burden of SIDS were modeled. Crude mortality and mortality rates per 100 000 population were analyzed. Disability-adjusted life years (DALYs) and DALY rates were also assessed. In 2019, mortality rate of SIDS accounted for 20.98 [95% Uncertainty Interval, 9.15-46.16] globally, which was a 51% decrease from 1990. SIDS was most prevalent in Western sub-Saharan Africa, High-income North America and Oceania in 2019. The burden of SIDS was higher in males than females consistently from 1990 to 2019. Higher SDI and income level was associated with lower burden of SIDS; furthermore, countries with higher SDI and income had greater decreases in SIDS burden from 1990 to 2019. The burden of SIDS has decreased drastically from 1990 to 2019. However, the improvements have occurred disproportionately between regions and SDI levels. Focused preventive efforts in under-resourced populations are needed.


Quality and readability assessment of online patient information on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.
We aim to assess the quality and readability of online information available to patients considering cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). The top three search engines (Google, Bing, and Yahoo) were searched in March 2022. Websites were classified as academic, hospital-affiliated, foundation/advocacy, commercial, or unspecified. Quality of information was assessed using the JAMA benchmark criteria (0-4) and DISCERN tool (16-80), and the presence of a Health On the Net code (HONcode) seal. Readability was evaluated using the Flesch Reading Ease score. Fifty unique websites were included. The average JAMA and DISCERN scores of all websites were 0.72 ± 1.14 and 39.58 ± 13.71, respectively. Foundation/advocacy websites had significantly higher JAMA mean score than commercial (p = 0.044), academic (p < 0.001), and hospital-affiliated websites (p = 0.001). Foundation/advocacy sites had a significantly higher DISCERN mean score than hospital-affiliated (p = 0.035) and academic websites (p = 0.030). The HONcode seal was present in 4 (8%) websites analyzed. Readability was difficult and at the level of college students. The overall quality of patient-oriented online information on CRS-HIPEC is poor and available resources may not be comprehensible to the general public. Patients seeking information on CRS-HIPEC should be directed to sites affiliated with foundation/advocacy organizations.


Machine learning to predict dynamic changes of pathogenic Vibrio spp. abundance on microplastics in marine environment.
Microplastics are widely found in the marine environment. Recent studies have shown that pathogenic microorganisms can hitchhike on microplastics, which might act as a vector for the spread of pathogens. Vibrio spp. are known to be pathogenic to humans and can cause serious foodborne diseases. In this study, using datasets from an estuary and a mariculture zone in China, five machine learning models were established to predict the relative abundance of Vibrio spp. on microplastics. The results showed that deep neural network (DNN) model and RandomForest algorithm achieved the best predictive performance. Different data sources, data sampling, and processing methods had a little impact on the prediction performance of DNN and RandomForest models. SHapley Additive exPlanations (SHAP) indicated that salinity and temperature are the primary factors affecting the relative abundance of Vibrio spp. The prediction performances of the five machine learning models were further improved by feature selection, providing information to support future experimental research. The results of this study could help establish a long-term and dynamic monitoring system for the relative abundance of Vibrio spp. on microplastics in response to environmental factors as well as provide useful information for assessing the potential health impacts of microplastics on marine ecology and humans.


Interplay between hydrophilic and hydrophobic interactions in the self-assembly of a gemini amphiphilic pseudopeptide: from nano-spheres to hydrogels.
The formation of soluble nano-spheres or stable hydrogels through the self-assembling of a simple gemini amphiphilic pseudopeptide can be controlled by the tuning of the hydrophilic/hydrophobic interactions in aqueous medium.


Advances in testing for sample manipulation in clinical and forensic toxicology - Part A: urine samples.
In many countries, adherence testing is used to monitor consumption behavior or to prove abstinence. Urine and hair are most commonly used, although other biological fluids are available. Positive test results are usually associated with serious legal or economic consequences. Therefore, various sample manipulation and adulteration strategies are used to circumvent such a positive result. In these critical review articles on sample adulteration of urine (part A) and hair samples (part B) in the context of clinical and forensic toxicology, recent trends and strategies to improve sample adulteration and manipulation testing published in the past 10 years are described and discussed. Typical manipulation and adulteration strategies include undercutting the limits of detection/cut-off by dilution, substitution, and adulteration. New or alternative strategies for detecting sample manipulation attempts can be generally divided into improved detection of established urine validity markers and direct and indirect techniques or approaches to screening for new adulteration markers. In this part A of the review article, we focused on urine samples, where the focus in recent years has been on new (in)direct substitution markers, particularly for synthetic (fake) urine. Despite various and promising advances in detecting manipulation, it remains a challenge in clinical and forensic toxicology, and simple, reliable, specific, and objective markers/techniques are still lacking, for example, for synthetic urine.


A model system for assessing physicochemical factors affecting calcium absorbability from the intestinal tract.
An in vitro model system was utilized to critically examine physicochemical factors that could play a role in determining the amount of potentially absorbable ionic calcium as well as soluble complexes in the proximal jejunum following ingestion of tricalcium dicitrate, calcium carbonate, or tricalcium diphosphate. The solubility of calcium salts (500 mg calcium each) was tested in 300 ml water containing varying amounts of hydrochloric acid (0, 0.72, 2.4, 7.26, and 24.2 mEq) intended to mimic achlorhydric to peak acid secretory states. Whereas 20% of calcium citrate dissolved in the absence of hydrochloric acid, a negligible amount of calcium carbonate and calcium phosphate underwent dissolution. In solutions containing 0.72-7.26 mEq hydrochloric acid, calcium citrate was more than twofold soluble than calcium carbonate, and calcium phosphate had intermediate solubility. At simulated peak acid secretion, all three salts were completely soluble, or nearly so. To simulate pancreatic bicarbonate secretion, the filtrates obtained from solubility studies were titrated to pH 5, 6, and 7 with sodium hydroxide. Reprecipitation of calcium citrate and calcium carbonate did not occur. However, substantial calcium phosphate reprecipitation took place especially at high pH and in filtrates derived from high hydrochloric acid content. In filtrates derived from reprecipitation experiments (at pH 6 and 7), anionic complexation of calcium was calculated in order to estimate the amount of ionic and complexed calcium. Considerable amount of calcium from dissolved calcium citrate was complexed (60-65%), principally as soluble CaCit-, whereas calcium complexation was negligible in the calcium carbonate and calcium phosphate systems.


Possible physiological significance of the initial step in the catabolism of noradrenaline in the central nervous system of the rat.
The hypothalamus, the cerebral cortex and the cerebellar cortex of the rat were labelled in vitro with 3H-noradrenaline (3H-NA) and the metabolism of the tritiated transmitter was studied during spontaneous outflow and under conditions of release elicited by exposure to 20 mM K+. In the three areas of the central nervous system of the rat 3H-NA accounted for approximately 40% of the total radioactivity in spontaneous outflow while the 3H-O-methylated deaminated fraction (3H-OMDA) and 3H-3,4-dihydroxyphenylglycol (3H-DOPEG) were the main metabolites. Exposure to the reserpine-like agent, Ro 4-1284 induced a selective increase in the spontaneous outflow of 3H-DOPEG, while the contribution of the 3H-OMDA metabolites to the release induced by Ro 4-1284 was very small. During 3H-transmitter release elicited by exposure to 20 mM K+, approximately 80% of the radioactivity was collected as unmetabolized 3H-NA, while 3H-DOPEG was the main metabolite formed under these experimental conditions. Exposure to cocaine prevented 3H-DOPEG formation from 3H-NA released by K+, indicating that 3H-DOPEG was formed after neuronal reuptake of the transmitter released by K+. After in vitro labelling with 3H-NA, the unmetabolized transmitter represented approximately 70% of the total radioactivity retained in the tissue. However, when 3H-NA was administered in vivo, by intraventricular injection, only 30% of the total radioactivity retained by the tissue was accounted for by 3H-NA, and 60% of the radioactivity corresponded to the 3H-OMDA fraction, most of which was retained as 3H-MOPEG sulfate. When the rats were pretreated with pyrogallol, free 3H-DOPEG accounted for nearly 50% of the radioactivity retained in the three areas of the central nervous system after in vivo labelling with 3H-NA. When monoamine oxidase was inhibited by pargyline and 3H-NA was administered by intraventricular injection, 3H-NMN accounted for approximately 50% of the total radioactivity retained in the three areas of the central nervous system of the rat. The results obtained are compatible with the view that formation of the deamined glycol is the first step in the metabolism of 3H-NA in the rat central nervous system. In addition, it is concluded that the determination of the levels of some NA metabolites retained in the central nervous system does not necessarily represent an accurate reflection of the degree of central noradrenergic activity or of selective metabolic pathways. Consequently, in studies on the metabolism of NA it is important to take into account not only the transmitter and its metabolites in the tissue but also in the outflow from the structures studied either under in vivo or in vitro conditions.


Family behavior theory-based intervention via mobile messaging to improve oral health of adolescents: study protocol for a cluster randomized controlled trial.
Due to some unique physical, social and psychological features in the adolescent population, adolescents can be a time of heightened caries activity and periodontal disease. Oral health-related behaviors can be modified to improve oral health status. The family networks and the built environment can promote or inhibit health behaviors. The aim of this study is to implement and evaluate a behavior theory-based, integrated family intervention via mobile messaging to improve oral health of adolescents. This is a three-arm parallel-design cluster-randomized controlled trial. This trial will allocate 12 local secondary schools (clusters) in Hong Kong to three test or comparison groups with a ratio 1:1:1. The enrolled Form II to IV students (ages 12 to 15) will be eligible for participation. The intervention to three study groups will be (i) Health Belief Model (HBM)-based mobile messaging to the adolescents and their parents, which will consist of several blocks of HBM-based messages and reinforcement during 24 weeks; (ii) same HBM-based messaging to adolescents only; and (iii) delivering e-version of oral health education pamphlets to adolescents. The primary outcome will be caries increment 2 years post-intervention. Changes in oral health self-efficacy and behaviors, oral hygiene, and gingival status will be the secondary outcomes. No school dental care service is available to secondary school students in Hong Kong. This study will be the first to test a theory-driven and family-engaged preventive intervention among adolescents in Hong Kong. Findings will contribute to developing a low-cost, feasible, and efficient oral health preventive program for adolescents. ClinicalTrials.gov NCT05448664 . Registered on 7 July 2022.


Long-term outcomes of ulcerative interstitial cystitis after complete transurethral resection with therapeutic hydrodistention.
We analyzed the long-term efficacy of simultaneous transurethral resection (TUR) and therapeutic hydrodistention in patients with ulcerative interstitial cystitis (IC) who did not experience recurrence on long-term follow-up. We studied 132 female patients (mean age = 56.45 ± 11.56 years) who underwent TUR followed by hydrodistention to treat ulcerative IC between January 2010 and January 2017, and who were available for follow-up, for more than 36 months (mean = 52.3 ± 10.51 months). Of the 132 patients, those who did not suffer recurrence within 36 months after surgery were allocated to group I and those who had a recurrence within the same period were assigned to group II. Preoperative factors, including age, were compared between the groups. In group I, improvements in pain and voiding symptoms were recorded using a 10-point visual analog pain scale (VAS) and a 3-day micturition chart. A global response assessment (GRA) was used to evaluate patient satisfaction. In group II, the maximum functional bladder capacity (FBC) was smaller, and voiding frequency was higher, than in group I. Follow-up of patients in group I for more than 3 years showed that pain decreased after surgery. The 10-point VAS scores were 9.68 before surgery, and 1.54, 0.93, 0.55, and 0.46 at 1, 6, 12, and 36 months after surgery (p < 0.001), respectively. Maximum FBCs were 174.82 mL before surgery and 237.14, 250.71, and 254.46 mL at 1, 12, and 36 months after surgery (p < 0.001), respectively; thus, FBC increased after surgery. Urination frequency decreased significantly after surgery; the number of daily urinations was 12.77 before surgery, and 9.88, 9.21, and 9.25 at 1, 12, and 36 months after surgery (p < 0.001), respectively. Overall patient satisfaction improved after surgery; the GRA scores were 2.39, 2.71, and 2.8 points at 1, 12, and 36 months after surgery (p < 0.001), respectively. Upon simultaneous performance of TUR and therapeutic hydrodistention in patients with ulcerative IC, 49.2% showed favorable outcomes for 3 years.


Contextualising missed care in two healthcare inquiries using a socio-ecological systems approach.
To examine missed care within two patient safety public inquiries using a socio-ecological model. Missed care is a care which has been omitted or rendered incomplete. Possible outcomes of missed care have been identified including poor patient outcomes such as higher mortality rates, reduced care quality and lower patient satisfaction, job dissatisfaction, staff burnout and higher attrition rates. A qualitative design, specifically document analysis, was used to review two serious case reviews. Between August-December 2018, two public patient safety inquiries were examined using a document analysis method. Both inquiries are based in acute hospital care settings of nursing (UK) and midwifery (Ireland). The Standards for Reporting Qualitative Research checklist provided a framework to report the study methods, context, findings, analysis and interpretation. Findings highlighted instances of missed care related to practice which contributed to poor patient outcomes. Missed care was located within contingency factors, such as unintended negative patient health and safety outcomes in multiple system levels which resulted in care deficits. A socio-ecological model enabled consideration of how multi-system deficits combine to impact nursing and midwifery care delivery. To tackle current and future practice challenges, broader contextual issues that influence front-line cases should be identified and addressed before they create conditions which result in substandard care. This paper adds to the scholarship on missed care by incorporating a greater contextual lens. Findings suggest that some factors contributing to missed care events may be systemic in origin. Practice, policy, research and education should foster nurses' and midwives' review of the totality of influencing factors impacting missed care and care deficits. Consequently, early warning signs and proactive responses at a system level should be inherent in all settings that nurses' and midwives' practice.


Novel dications with unfused aromatic systems: trithiophene and trifuran derivatives of furimidazoline.
We report the synthesis, interaction with DNA, topoisomerase II inhibition, and cytotoxicity of two novel unfused aromatic dications derived from the antimicrobial agent furimidazoline. The central diphenylfuran core of furimidazoline has been replaced with a trithiophene (DB358) or a trifuran (DB669) unit and the terminal imidazoline groups were preserved. The strength and mode of binding of the drugs to nucleic acids were investigated by complementary spectroscopic techniques including spectrophotometric, surface plasmon resonance, circular and linear dichroism measurements. The trifuran derivative forms intercalation complexes with double-stranded DNA, whereas the mode of binding of the trithiophene derivative varies depending on the drug/DNA ratio, as independently confirmed by NMR spectroscopic studies performed with (A-T)7 and (G-C)7 oligomers. Two-dimensional NMR data provided a molecular model for the binding of DB358 within the minor groove of the AATT sequence of the decanucleotide d(GCGAATTCGC)(2). DNase I footprinting experiments confirmed the sequence-dependent binding of DB358 to DNA. The trithiophene derivative interacts preferentially with AT-rich sequences at low concentrations, but can accomodate GC sites at higher concentrations. DNA relaxation assays revealed that DB358 stimulated DNA cleavage by topoisomerase II, in contrast to DB669. The substitution of N-alkylamidines for the imidazoline terminal groups abolished the capacity of the drug to poison topoisomerase II. At the cellular level, flow cytometry analysis indicated that DB358, which is about six times more cytotoxic than the trifuran analogue, induced a significant accumulation of HL-60 human leukemia cells in the G2/M phase. The incorporation of thiophene heterocycles appears as a convenient procedure to limit the strict AT selectivity of dications containing an extended unfused aromatic system and to design cytotoxic DNA intercalating agents acting as poisons for human topoisomerase II.


Microbial community structure and dynamics during anaerobic digestion of various agricultural waste materials.
The influence of the feedstock type on the microbial communities involved in anaerobic digestion was investigated in laboratory-scale biogas reactors fed with different agricultural waste materials. Community composition and dynamics over 2 months of reactors' operation were investigated by amplicon sequencing and profiling terminal restriction fragment length polymorphisms of 16S rRNA genes. Major bacterial taxa belonged to the Clostridia and Bacteroidetes, whereas the archaeal community was dominated by methanogenic archaea of the orders Methanomicrobiales and Methanosarcinales. Correlation analysis revealed that the community composition was mainly influenced by the feedstock type with the exception of a temperature shift from 38 to 55 °C which caused the most pronounced community shifts. Bacterial communities involved in the anaerobic digestion of conventional substrates such as maize silage combined with cattle manure were relatively stable and similar to each other. In contrast, special waste materials such as chicken manure or Jatropha press cake were digested by very distinct and less diverse communities, indicating partial ammonia inhibition or the influence of other inhibiting factors. Anaerobic digestion of chicken manure relied on syntrophic acetate oxidation as the dominant acetate-consuming process due to the inhibition of aceticlastic methanogenesis. Jatropha as substrate led to the enrichment of fiber-degrading specialists belonging to the genera Actinomyces and Fibrobacter.


[Demonstration of air inclusions in human hair by light and UV microscopy (author's transl)].
Cranial hairs of 47 randomly selected probands were examined for the presence of air inclusions by conventional light microscopy and by short-wave ultraviolet-light microscopy. The air inclusions seen in UV light stand out as brightly luminous regions against the surrounding hair substance. Two sorts of air inclusions were observed-strips-like or cleft-like regions running parallel to the longitudinal axis localized inthe cortex of the hair and air containing pores on the hair surface. The presence and amount of the air inclusions is independent of the hair colour.


Adsorption therapy in critically ill with septic shock and acute kidney injury: a retrospective and prospective cohort study.
Haemoadsorption has been described as an effective way to control increased pro- and anti-inflammatory mediators ("cytokine storm") in septic shock patients. No prospective or randomised clinical study has yet confirmed these results. However, no study has yet prospectively specifically investigated patients in severe septic shock with sepsis-associated acute kidney injury (SA-AKI). Therefore, we aimed to examine whether haemoadsorption could influence intensive care unit (ICU) and hospital mortality in these patients. Furthermore, we examined the influence of haemoadsorption on length of stay in the ICU and therapeutic support. Retrospective control group and prospective intervention group design in a tertiary hospital in central Europe (Germany). Intervention was the implementation of haemoadsorption for patients in septic shock with SA-AKI. 76 patients were included in this analysis. Severity of illness as depicted by APACHE II was higher in patients treated with haemoadsorption. Risk-adjusted ICU mortality rates (O/E ratios) did not differ significantly between the groups (0.80 vs. 0.83). We observed in patients treated with haemoadsorption a shorter LOS and shorter therapeutic support such as catecholamine dependency and duration of RRT. However, in multivariate analysis (logistic regression for mortality, competing risk for LOS), we found no significant differences between the two groups. The implementation of haemoadsorption for patients in septic shock with acute renal failure did not lead to a reduction in ICU or hospital mortality rates. Despite univariate analysis delivering some evidence for a shorter duration of ICU-related treatments in the haemoadsorption group, these results did not remain significant in multivariate analysis. Trial registration CytoSorb® registry https://clinicaltrials.gov/ct2/show/NCT02312024 . December 9, 2014. https://www.cytosorb-registry.org/ (registration for content acquisition is necessary).


Silver-promoted oxidative sulfonylation and ring-expansion of vinylcyclopropanes with sodium sulfinates leading to dihydronaphthalene derivatives.
Silver-promoted sulfonylation and ring-expansion of vinylcyclopropanes with sodium sulfinates is established for the construction of 1-sulfonylmethylated 3,4-dihydronaphthalenes. This sulfonylation process involves a radical pathway, including sulfonyl radical formation, radical addition, ring-opening and cyclization. The 1-sulfonylmethylated 3,4-dihydronaphthalenes can be converted into other useful products.


Combination of immunomagnetic separation with flow cytometry for detection of Listeria monocytogenes.
Listeria monocytogenes can grow at the low temperature commonly used in the storage and transportation of food, and the number of cases of food poisoning caused by L. monocytogenes has increased recently in the US and Europe. Several methods of detecting L. monocytogenes cells have been proposed; however, all existing methods require approximately 48 h incubation. In this study, we attempted rapid detection of L. monocytogenes using flow cytometry (FCM). The method is based on measuring the number of L. monocytogenes cells by using a combination of FCM and immunomagnetic separation (IMS). First, polyclonal antibodies (anti-L. monocytogenes rabbit IgG-FITC) conjugated with fluorescein isothiocyanate (FITC) were reacted with L. monocytogenes cells, and then FCM was applied. The cell numbers were determined by FCM using a traditional colony-counting method in the range of 10(4)-10(8) cells ml(-1). Tetrameric antibody complexes (TAC) were used because they can recognize both magnetic and FITC molecules on the FITC-conjugated antibodies. FITC-labeled L. monocytogenes cells were reacted with a secondary antibody (TAC) bound to magnetic beads. Then, IMS was used. The method is suitable for detection in the range of 10(2)-10(8)cells ml(-1). The FCM assay enumerated the cells within 1 min and the total assay time, including sample preparation, was less than 2 h.


(1-->6)-Beta-D-glucan as the cell wall binding site for Debaryomyces hansenii killer toxin.
The aims of this study were to characterize the cell wall binding site of Debaryomyces hansenii killer toxin to provide a simple purification method and to determine some characteristics of this toxin. Various linear (1-->6)-beta-D-glucans of different origins were effective competitive inhibitors of the toxin action. Periodate oxidation and 1H-NMR was used to determine the receptor nature. Affinity chromatography on pustulan-Sepharose column was used to purify D. hansenii killer toxin, probably a 23-kDa protein. The killer toxin character was cureless. The investigation revealed that the killer toxin was mainly adsorbed by (1-->6)-beta-D-glucans. This is a low molecular weight protein, probably encoded by chromosomal genes. The specificity of the killer toxin for its receptor provides an effective means to purify the killer toxin. This study is the first to identify the cell wall binding site of this killer toxin, a toxin with properties of industrial relevance.


A computer-aided design tool for biomedical OBT sensor tuning in cell-culture assays.
The biomedical engineering must frequently develop sensor designs by including information from performance of bio-samples (cell cultures or tissues), technical specifications of transducers, and constrains from electronic circuits. A computer program for real-time cell culture monitoring system design is developed; analyzing, modelling and integrating into the program design flow the electrodes, cell culture and test circuit's influences. The computer tool, first, generates an equivalent electric circuit model for the cell-electrode bio-systems based on the area covered by cells, which also considers the cell culture dynamics. Second, proposes an Oscillation Based Test (OBT) parameterized circuit, for Electrical Cell-Substrate Sensing (ECIS) measurements of the cell culture system bioimpedance. Third, simulates electrically the full system to define the best system parameter values for the sensor. Reported experimental results are based on commercial gold electrodes and the AA8 cell line. Characteristics of the cell lines, as time-division or cell size, are incorporated into the program design flow, showing that for a given assay, the optimal OBT circuit parameters can be selected with the help of the computer tool. The electrical simulations of the full system demonstrate that the can be correctly predicted the output frequency and amplitude ranges of the voltage response, obtaining accurate results when cell culture approaches to confluence phase. It is proposed a computer program for system design of biosensors applied to monitoring cell culture dynamics. The program allows obtaining confident system information by electrical stimulation. All system components (electrodes, cell culture and test circuits) are properly modelled. The employed procedure can be applied to any other 2D electrode layout or alternative circuit technique for ECIS test. Finally, deep insight information on cell size, number, and time-division can be extracted from the comparison with real cell culture assays in the future.


Ultra-high frequency ultrasound for digital arteries: improving the characterization of vasculopathy in systemic sclerosis.
To provide a full characterization of proper palmar digital arteries (PPDA) in systemic sclerosis (SSc) with ultra-high frequency ultrasound (UHFUS), and to investigate possible relationships between digital macroangiopathy and microangiopathy. SSc patients without active digital ulcers and healthy controls (HC) were enrolled. Each subject underwent UHFUS 70 MHz evaluation of PPDA from II to V fingers bilaterally, searching for vessel occlusion and measuring the thickness of the three arterial layers and the systolic-diastolic excursion range. Microcirculation was investigated with capillaroscopy and laser speckle contrast analysis (LASCA). Forty-six SSc patients (87% female, mean age 55.5 years) and 15 HC comparable for age and sex were enrolled. UHFUS in SSc revealed the occlusion of 124 (16.8%) PPDA, whereas in HC they were all patent. Considering a finger with at least one PPDA occluded as ultrasonographically pathological, 67.4% patients presented ≥1 pathological fingers. All three arterial layers were significantly thicker and excursion range significantly reduced in SSc than in HC (p<0.001 for all). Seventy-three percent of fingers previously affected by digital ulcers, were ultrasonographically pathological. Disease duration was directly correlated to the thickness of all three arterial layers. No significant correlations emerged between capillaroscopy or LASCA findings and UHFUS features. UHFUS allows the characterization of vasculopathic involvement of PPDA in SSc, also showing subclinical vasculopathy. The lack of correlations between UHFUS and capillaroscopy or LASCA likely mirrors non-overlapping vasculopathic processes. UHFUS evaluation of PPDA emerges as complementary to microcirculation assessment for a more accurate and complete characterization of SSc vasculopathy.


Single molecule mtDNA fiber FISH for analyzing numtogenesis.
Somatic human cells contain thousands of copies of mitochondrial DNA (mtDNA). In eukaryotes, natural transfer of mtDNA into the nucleus generates nuclear mitochondrial DNA (NUMT) copies. We name this phenomenon as "numtogenesis". Numtogenesis is a well-established evolutionary process reported in various sequenced eukaryotic genomes. We have established a molecular tool to rapidly detect and analyze NUMT insertions in whole genomes. To date, NUMT analyses depend on deep genome sequencing combined with comprehensive computational analyses of the whole genome. This is time consuming, cumbersome and cost prohibitive. Further, most laboratories cannot accomplish such analyses due to limited skills. We report the development of single-molecule mtFIBER FISH (fluorescence in situ hybridization) to study numtogenesis. The development of mtFIBER FISH should aid in establishing a role for numtogenesis in cancers and other human diseases. This novel technique should help distinguish and monitor cancer stages and progression, aid in elucidation of basic mechanisms underlying tumorigenesis and facilitate analyses of processes related to early detection of cancer, screening and/or cancer risk assessment.


Inadequate antioxidant nutrient intake and altered plasma antioxidant status of rheumatoid arthritis patients.
Elevated free radical generation in inflamed joints and impaired antioxidant system have been implicated in rheumatoid arthritis (RA). The present study was performed to evaluate dietary nutrient intake and plasma oxidant/antioxidant status in RA patients. RA patients (n = 97) and their age, gender-matched controls (n = 97) participated in this cross-sectional case-control study. Nutrient intake was estimated using a semi-quantitative food frequency questionnaire. Twenty subjects from each group provided blood samples, and plasma concentrations of alpha-tocopherol and malondiadehyde (MDA) were measured. Also, plasma activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were measured. The mean calorie intake of RA patients was lower than that of the healthy controls. Energy-adjusted intake of fat, vitamin A and beta-carotene were significantly lower in patients than those of the control subjects. RA patients had a decreased mean plasma alpha-tocopherol level. The activity of plasma SOD and GPx in patients was significantly lower than that in control subjects. These results suggest proper antioxidant nutrient intake management may reduce free radical generation and improve antioxidant status in RA patients.


Pharmacokinetics and clinical use of parenteral phenytoin, phenobarbital, and paraldehyde.
Intravenous phenytoin, phenobarbital, and paraldehyde are effective and safe for the treatment of acute seizures such as status epilepticus. All of these drugs should be infused in a diluted solution and at a slow rate to minimize the occurrence of adverse effects.


Outpatient visits before and after Lyme disease diagnosis in a Maryland employer-based health plan.
Insurance claims data have been used to inform an understanding of Lyme disease epidemiology and cost of care, however few such studies have incorporated post-treatment symptoms following diagnosis. Using longitudinal data from a private, employer-based health plan in an endemic US state, we compared outpatient care utilization pre- and post-Lyme disease diagnosis. We hypothesized that utilization would be higher in the post-diagnosis period, and that temporal trends would differ by age and gender. Members with Lyme disease were required to have both a corresponding ICD-9 code and a fill of an antibiotic indicated for treatment of the infection within 30 days of diagnosis. A 2-year 'pre- diagnosis' period and a 2-year 'post-diagnosis period' were centered around the diagnosis month. Lyme disease-relevant outpatient care visits were defined as specific primary care, specialty care, or urgent care visits. Descriptive statistics examined visits during these pre- and post-diagnosis periods, and the association between these periods and the number of visits was explored using generalized linear mixed effects models adjusting for age, season of the year, and gender. The rate of outpatient visits increased 26% from the pre to the post-Lyme disease diagnosis periods among our 317-member sample (rate ratio = 1.26 [1.18, 1.36], p < 0.001). Descriptively, care utilization increases appeared to persist across months in the post-diagnosis period. Women's care utilization increased by 36% (1.36 [1.24, 1.50], p < 0.001), a significantly higher increase than the 14% increase found among men (1.14 [1.02, 1.27], p = 0.017). This gender difference was mainly driven by adult members. We found a borderline significant 17% increase in visits for children < 18 years, (1.17 [0.99, 1.38], p = 0.068), and a 31% increase for adults ≥ 18 years (1.31 [1.21, 1.42], p < 0.001). Although modest at the population level, the statistically significant increases in post-Lyme diagnosis outpatient care we observed were persistent and unevenly distributed across demographic and place of service categories. As Lyme disease cases continue to grow, so will the cumulative prevalence of persistent symptoms after treatment. Therefore, it will be important to confirm these findings and understand their significance for care utilization and cost, particularly against the backdrop of other post-acute infectious syndromes.


Factors influencing the clinical decision-making of midwives: a qualitative study.
Although midwives make clinical decisions that have an impact on the health and well-being of mothers and babies, little is known about how they make those decisions. Wide variation in intrapartum decisions to refer women to obstetrician-led care suggests that midwives' decisions are based on more than the evidence based medicine (EBM) model - i.e. clinical evidence, midwife's expertise, and woman's values - alone. With this study we aimed to explore the factors that influence clinical decision-making of midwives who work independently. We used a qualitative approach, conducting in-depth interviews with a purposive sample of 11 Dutch primary care midwives. Data collection took place between May and September 2015. The interviews were semi-structured, using written vignettes to solicit midwives' clinical decision-making processes (Think Aloud method). We performed thematic analysis on the transcripts. We identified five themes that influenced clinical decision-making: the pregnant woman as a whole person, sources of knowledge, the midwife as a whole person, the collaboration between maternity care professionals, and the organisation of care. Regarding the midwife, her decisions were shaped not only by her experience, intuition, and personal circumstances, but also by her attitudes about physiology, woman-centredness, shared decision-making, and collaboration with other professionals. The nature of the local collaboration between maternity care professionals and locally-developed protocols dominated midwives' clinical decision-making. When midwives and obstetricians had different philosophies of care and different practice styles, their collaborative efforts were challenged. Midwives' clinical decision-making is a more varied and complex process than the EBM framework suggests. If midwives are to succeed in their role as promoters and protectors of physiological pregnancy and birth, they need to understand how clinical decisions in a multidisciplinary context are actually made.


How can we reduce hepatic veno-occlusive disease-related deaths after allogeneic stem cell transplantation?
Hepatic veno-occlusive disease (VOD) is a common and potentially devastating complication of hematopoietic stem cell transplantation. Confirmative diagnosis of this disorder can prove difficult early post hematopoietic stem cell transplantation, as a broad differential diagnosis exists and no definitive diagnostic test is available. Incidence of VOD has decreased in recent years, with especially dramatic declines in severe and fatal VOD. This improvement is attributed to less toxic and reduced-intensity conditioning regimens, and more appropriate patient selection. When severe VOD does occur, current treatments have been largely ineffective. Prevention remains the primary tool in the clinician's arsenal for managing VOD. Our institution pursues aggressive preventative measures for VOD, including appropriate conditioning regimen selection, avoiding hepatotoxic drugs, early prophylactic use of ursodiol, and aggressive fluid management. With appropriate management steps, we believe the incidence of VOD and related deaths can be further decreased.


Monitoring for micronutrient deficiency after bariatric surgery-what is the risk?
Bariatric surgery may increase the risk of micronutrient deficiencies; however, confounders including preoperative deficiency, supplementation and inflammation are rarely considered. To examine the impact of bariatric surgeries, supplementation and inflammation on micronutrient deficiency. Two public hospitals, Australia. Participants were recruited to an observational study monitoring biochemical micronutrient outcomes, supplementation dose, inflammation and glycaemic control, pre-operatively and at 1-3, 6 and 12 months after gastric bypass (GB; Roux-en-Y Gastric Bypass and Single Anastomosis Gastric Bypass; N = 66) or sleeve gastrectomy (SG; N = 144). Participant retention at 12 months was 81%. Pre-operative micronutrient deficiency was common, for vitamin D (29-30%), iron (13-22%) and selenium (39% GB cohort). Supplement intake increased after surgery; however, dose was <50% of target for most nutrients. After SG, folate was vulnerable to deficiency at 6 months (OR 13 [95% CI 2, 84]; p = 0.007), with folic acid supplementation being independently associated with reduced risk. Within 1-3 months of GB, three nutrients had higher deficiency rates compared to pre-operative levels; vitamin B1 (21% vs. 6%, p < 0.01), vitamin A (21% vs. 3%, p < 0.01) and selenium (59% vs. 39%, p < 0.05). Vitamin B1 deficiency was independently associated with surgery and inflammation, selenium deficiency with improved glycaemic control after surgery and inflammation, whilst vitamin A deficiency was associated with inflammation only. In the setting of prophylactic post-surgical micronutrient prescription, few nutrients are at risk of de novo deficiency. Although micronutrient supplementation and monitoring remains important, rationalising high-frequency biochemical testing protocols in the first year after surgery may be warranted.