Kyphoplasty in patients with multiple myeloma a retrospective comparative pilot study.
This retrospective study of 73 myeloma patients with painful vertebral lesions compares clinical and radiomorphological outcomes up to 2 years after additional kyphoplasty, radiation therapy or systemic treatment only. We assessed pain, disability and radiomorphological parameters by visual analogue scale (VAS 0-100), Oswestry Disability Index and by re-evaluating available follow-up X-rays, respectively, in patients that were treated according to a clinical pathway. After 2 years the VAS score was reduced in all groups by 66 ± 8.2 (kyphoplasty), 35 ± 10.5 (radiation therapy) and 38 ± 20.5 (systemic therapy only). Only after kyphoplasty we observed a significantly reduced Oswestry Disability Index after 1 year (P < 0.001). Vertebral height remained stable after kyphoplasty (P = 0.283), in contrast to a progressive height loss in the other groups (P = 0.013 and P = 0.015 for radiation and systemic therapy only, respectively). Two years after kyphoplasty and radiotherapy the overall vertebral fracture incidence was significantly decreased as compared to the group after systemic therapy only (9.7% of all thoracic and lumbar vertebrae had new vertebral fractures after systemic therapy only, 2% after kyphoplasty (P < 0.001), 4.8% after radiation (P = 0.032)). Additional kyphoplasty was more effective than additional radiation or systemic therapy in terms of pain relief, reduction of pain associated disability and reduction of fracture incidence of the entire lumbar and thoracic spine.


Variability of serial CT scans in subacute necrotizing encephalomyelopathy (Leigh disease).
Computed tomographic (CT) brain scans of patients with subacute necrotizing encephalomyelopathy (SNE) may reveal focal lesions that correspond to sites of anatomic involvement of the disease. Three patients with SNE were followed with serial CT brain scans. In two patients radiographic abnormalities appeared well after the onset of clinical symptoms. In all three patients the radiographic lesions changed with time. This variability seen with serial scanning is an important feature of SNE.


A modified procedure for determination of metallothionein-like proteins in animal tissues.
1. The effect of low-molecular-weight substances interfering with determination of metallothionein is eliminated by precipitation of 203Hg-thionein by tannic acid. 2. In animals not exposed to metals, the mean values for metallothionein content in liver and kidney are, respectively, 0.10 and 0.18 mg/g in rats, 0.06 and 0.07 in mice and 0.12 and 0.29 in guinea-pigs, i.e. are 2-3 times lower as compared with the values obtained by the procedure not involving treatment with tannic acid.


Complete genome sequencing of SARS-CoV-2 strains: A pilot survey in Palestine reveals spike mutation H245N.
SARS-CoV-2, severe respiratory syndrome coronavirus-2, is an RNA virus that emerged from China sweeping the globe in the form of a pandemic that became an international public health concern. This pilot study aimed to describe the genetic variation and molecular epidemiology of SARS-CoV-2 in Palestine in fall 2020. To achieve these aims, whole genome sequencing of SARS-CoV-2, phylogenetic analysis, haplotype networking and genetic diversity analysis were performed. These analyses revealed a unique spike mutation H245N that has never been reported before. The phylogenetic analysis depicted that three clusters existed in Palestinian SARS-CoV-2 genome sequences, in which cluster-I comprised the majority of clusters by 90%. Congruently, the haplotype network analysis depicted the same three clusters with a total of 39 haplotypes. The genetic diversity analysis showed that Cluster-I is highly diverse as confirmed by statistically significant mutation rate indices, Tajima's D and Fu-Li's-F tests (- 2.11 and 2.74, respectively), highest number of mutations (Eta = 120), highest number of haplotypes (h = 17), and highest average number of nucleotide differences between any two sequences (S = 118). The study confirmed the high genetic diversity among the Palestinian of SARS-CoV-2 which possessed high number of mutations including one which was reported for the first time.


Decreasing the required lumbar extensor moment induces earlier onset of flexion relaxation.
Flexion relaxation (FR) is characterized by the lumbar erector spinae (LES) becoming myoelectrically silent near full trunk flexion. This study was designed to: (1) determine if decreasing the lumbar moment during flexion would induce FR to occur earlier; (2) characterize thoracic and abdominal muscle activity during FR. Ten male participants performed four trunk flexion/extension movement conditions; lumbar moment was altered by attaching 0, 5, 10, or 15lb counterweights to the torso. Electromyography (EMG) was recorded from eight trunk muscles. Lumbar moment, lumbar flexion and trunk inclination angles were calculated at the critical point of LES inactivation (CPLES). Results demonstrated that counterweights decreased the lumbar moment and lumbar flexion angle at CPLES (p<0.0001 and p=0.0029, respectively); the hypothesis that FR occurs earlier when lumbar moment is reduced was accepted. The counterweights did not alter trunk inclination at CPLES (p=0.1987); this is believed to result from an altered hip to spine flexion ratio when counterweights were attached. Lumbar multifidus demonstrated FR, similar to LES, while thoracic muscles remained active throughout flexion. Abdominal muscles activated at the same instant as CPLES, except in the 15lb condition where abdominal muscles activated before CPLES resulting in a period of increased co-contraction.


Efficient biogenesis of Cu2O nanoparticles using extract of Camellia sinensis leaf: Evaluation of catalytic, cytotoxicity, antioxidant, and anti-human ovarian cancer properties.
At the moment, metallic nanoparticles especially copper nanoparticles are administrated for the cure of different disorders, such as tumor and cancer. In recent years, many chemotherapeutic supplements have been formulated by copper nanoparticles. In the present study, copper nanoparticles were prepared and synthesized in aqueous medium using Camellia sinensis leaf extract. The as-prepared Cu2O nanoparticles was thoroughly characterized using XRD, FT-IR, FESEM, EDX, TEM and X-ray elemental mapping techniques. The as-synthesized Cu2O/C. sinensis NPs applied as novel nanocatalyst for the synthesis of annulated fused pyrano[2,3-d]pyrimidinones via a one-pot, three-component condensation of a barbituric acid, aromatic aldehydes, and malonitrile or ethylcyanoacetate under mild condition at 25 °C. Main properties of this facile method are the involves an easy work-up procedure, avoidance of hazardous or polluting chemicals, significant yields under mild conditions, and one-pot reaction. We assessed the anti-human ovarian cancer potentials of these nanoparticles against Caov-3, SW-626, and SK-OV-3 cell lines. For investigating the antioxidant activities of CuCl2⋅2H2O, C. sinensis, and copper nanoparticles, the DPPH free radical test was used. For the determining of anti-human ovarian cancer properties of CuCl2⋅2H2O, Camellia sinensis leaf aqueous extract, copper nanoparticles, and Carboplatin (Standard positive control), MTT assay was used on normal (HUVECs) and human ovarian cancer (Caov-3, SW-626, and SK-OV-3) cell lines. Copper nanoparticles had high cell death and anti-human ovarian cancer properties against Caov-3, SW-626, and SK-OV-3 cell lines. Among the above cell lines, the best result was gained in the cell line of SW-626. According to the above findings, it looks copper nanoparticles green-synthesized by Camellia sinensis leaf aqueous extract have the potential to be used as a chemotherapeutic material for human ovarian cancers.


Spectroscopic and ionization properties of N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-labeled lipids in model membranes.
The spectroscopic and ionization properties of various lipids labeled with the 7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) group have been studied in model membranes using fluorescence, absorbance and electrophoretic mobility measurements. Electrophoretic measurements show that the NBD group is uncharged at neutral pH. However, at high pH, hydroxyl addition or deprotonation occurs with a pKa, depending upon conditions, of 11.5-11.8 for the NBD group of headgroup-labeled phosphatidylethanolamine (NBD-PE) and 11.1-11.5 for NBD labels placed at the end of one fatty acyl chain of a phosphatidylcholine (6-NBD-PC and 12-NBD-PC). This type of behavior is not observed in the case of a methylated NBD label placed in the flexible 'tail' of cholesterol (NBD-cholesterol). The similarity in pKa for NBD-PE and NBD-PCs suggests that in these cases the NBD group is at a similar depth in the membrane. This was examined further by comparison of the fluorescence emission maximum of the NBD group in model membranes with that in solvents of varying polarity. The apparent polarity experienced by NBD groups in model membranes indicates that for NBD-PE and 12-NBD-PC they are located at the polar region whereas the NBD group of NBD-cholesterol is deeply buried in a nonpolar region of the membrane. This conclusion is supported further by fluorescence quenching experiments measuring NBD exposure to the aqueous quencher Co2+. The results of this study confirm the tentative conclusions of our previous fluorescence quenching studies on the location of NBD groups in model membranes.


Recurrent cerebellar ischemic infarctions and stereotyped peri-ictal sympathetic responses in a near-SUDEP patient with cardiovascular risk factors.
We report a 60-year-old woman who presented to the emergency department after experiencing a witnessed unknown onset bilateral tonic clonic seizure (GTCS) that culminated in cardiac arrest. A neurology consultant uncovered a years-long history of frequent episodic staring followed by confusion and expressive aphasia, which strongly suggested that she suffered from epilepsy. Thus, her cardiac arrest and subsequent resuscitation met criteria for a near-sudden unexpected death in epilepsy (SUDEP) diagnosis. Serial bloodwork demonstrated transient troponin I elevations and leukocytoses, while a brain MRI revealed global cerebral anoxic injury and a small acute right cerebellar ischemic infarction. A review of her medical record uncovered a hospitalization sixteen months earlier for a likely GTCS whose workup showed similar troponin I elevations and leukocytoses, and surprisingly, a different small acute right cerebellar ischemic infarction in the same vascular territory. To our knowledge, this is the first report of subcortical ischemic infarctions occurring concurrently with GTCSs in a near-SUDEP patient. Aside from illustrating the key role of inpatient neurologists in the diagnosis of near-SUDEP, this manuscript discusses the potential significance of postictal ischemic infarctions, transient asymptomatic troponin elevations, and transient non-infectious leukocytoses in epilepsy patients with cardiovascular risk factors.


Evaluation of the QuEChERS and magnetic micro dispersive solid-phase extraction of brominated flame retardants in red fruits with determination by GC/MS.
A sample preparation method, QuEChERS extraction combined with a magnetic micro dispersive solid phase extraction (MµdSPE), was optimized and evaluated for the trace analysis of 9 brominated flame retardants in red fruit samples (strawberries, blueberries, and raspberries) using gas chromatography-mass spectrometry. Magnetic nanomaterials were used as sorbents providing an extraction of the target compounds. Linearity was established for all the analytes (from 10 to 200 µg kg-1). Seven concentration levels were analyzed with three measurements at each concentration. Linear responses (R2 > 0.99) were obtained, recoveries of all target analytes were within the range of 65-141%, relative standard deviations were <20% at all three spiking levels, while intraday and interday precisions were below 20%. This study demonstrated that the new sample preparation with magnetic nanoparticles could potentially be expanded to extract and pre-concentrate the BFRs in different red fruit samples. The method has been successfully applied to study BFRs in 12 samples from conventional and organic farming.


p85β regulatory subunit of class IA PI3 kinase negatively regulates mast cell growth, maturation, and leukemogenesis.
We show that loss of p85α inhibits the growth and maturation of mast cells, whereas loss of p85β enhances this process. Whereas restoring the expression of p85α in P85α(-/-) cells restores these functions, overexpression of p85β has the opposite effect. Consistently, overexpression of p85β in WT mast cells represses KIT-induced proliferation and IL-3-mediated maturation by inhibiting the expression of Microphthalmia transcription factor. Because p85α and p85β differ in their N-terminal sequences, chimeric proteins consisting of amino or carboxy-terminal of p85α and/or p85β do not rescue the growth defects of p85α(-/-) cells, suggesting cooperation between these domains for normal mast cell function. Loss of p85β impaired ligand induced KIT receptor internalization and its overexpression enhanced this process, partly because of increased binding of c-Cbl to p85β relative to p85α. In vivo, loss of p85β resulted in increased mast cells, and bone marrow transplantation of cells overexpressing p85β resulted in significant reduction in some tissue mast cells. Overexpression of p85β suppressed the growth of oncogenic KIT-expressing cells in vitro and prolonged the survival of leukemic mice in vivo. Thus, p85α and p85β differentially regulate SCF and oncogenic KIT-induced signals in myeloid lineage-derived mast cells.


Interleukin-6 plasma levels are modulated by a polymorphism in the NF-κB1 gene and are associated with outcome following rituximab-combined chemotherapy in diffuse large B-cell non-Hodgkin lymphoma.
Peripheral blood cytokines are known prognostic parameters in diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy, but their role after the introduction of rituximab is unknown. Seven polymorphisms in the promoter regions of IL-6, IL-10 and NF-κB1 genes were assessed in 167 patients with DLBCL and 99 controls and correlated with interleukin-6 (IL-6) and IL-10 plasma levels. Outcome was analyzed in 137 patients treated with rituximab-based chemotherapy. The NF-κB1 - 94ATTG deletion was associated with increased IL-6 and IL-10 in DLBCL. High IL-6 concentration correlated with unfavorable prognostic factors included in the international prognostic index (IPI) and predicted for inferior progression-free (p = 0.007) and overall survival (p = 0.02). IL-6 levels remained a significant outcome predictor also including IPI as a covariate (p = 0.006 for progression-free survival). Our data suggest that the NF-κB1 genetic background influences IL-6 production in DLBCL, and that high IL-6 concentration is an independent prognostic factor also in the "rituximab era."


Outbreak of Hypervirulent Multidrug-resistant Klebsiella variicola Causing High Mortality in Neonates in Bangladesh.
We report a clonal outbreak of multidrug-resistant (MDR) Klebsiella variicola (sequence type [ST] 771) in a Bangladeshi neonatal unit from October 2016 to January 2017, associated with high mortality (54.5%). During the outbreak, K. variicola ST771 acquired an MDR plasmid harboring blaNDM-1, linked to high exposure to ceftriaxone and amikacin.


Apathy in schizophrenia: clinical correlates and association with functional outcome.
Apathy is considered one of the negative symptoms of schizophrenia, but its natural history and relationship to other clinical characteristics have not been systematically studied. The purpose of this cross-sectional study was to measure the level of apathy in schizophrenia and its relation to other symptoms and functional outcome. Twenty-eight patients with schizophrenia, and receiving antipsychotic treatment, were assessed with the Apathy Evaluation Scale (AES). The mean level of apathy of patients with schizophrenia, as rated by the AES, was significantly higher than that of matched healthy control subjects. In the patients, apathy was not significantly correlated with positive symptoms or depressive symptoms. It was significantly correlated with the item "emotional withdrawal" on the negative subscale of the Positive and Negative Syndrome Scale (PANSS), but was not correlated with the overall negative subscale score. Apathy was more highly associated with functional outcome than were other symptom measures, and it was independently associated with functional outcome above and beyond other negative symptoms. It was not associated with observed interest in playing a video game or performance on a simulated clerical task.


[Doctor Knock lives at Wall Street. The new targets of pharmaceutical industry].
The aim of this paper is to inform clinicians about some new commercial practices of the pharmaceutical industry. Drug promotion nowadays involves sophisticated marketing strategies, in which the prescribing physician is not necessarily a central actor. Pharmaceutical advertising is more and more directed towards the general public (consumers), contributes to define and popularise disease categories, and encourages the medicalisation of everyday life. Doctors should be aware of the consequences of these new commercial strategies.


Isolation, Structure Characterization, Total Synthesis and Biological Evaluation of Cinnamic Acid Derivatives from Tinospora sagittata.
Thirteen cinnamic acid derivatives (1-13), including six formerly unreported hybrids incorporating different short-chain fatty acid esters (1-6), have been obtained and structurally elucidated from an ethnological herb Tinospora sagittata. The structures of them have been established by spectroscopic data analyses and NMR comparison with known analogs, while those of 1, 2, 4 and 6 have been further supported by total synthesis, and it is the first report of this type of metabolites from the title species. All the isolates have been assessed in an array of bioassays encompassing cytotoxic, antibacterial, anti-inflammatory, antioxidant, as well as α-glucosidase and HDAC1 inhibitory models. Compound 7 showed significant inhibitory activity against α-glucosidase, and half of the isolates also displayed moderate antiradical effect.


Post treatment care in photodynamic therapy (PDT) of large facial port-wine stain (PWS) birthmarks.
Photodynamic therapy (PDT) has been proved to be an effective and safe treatment for port-wine stain (PWS) birthmarks in China, especially for lager facial lesions. However, excessive treatment, improper nursing and human errors can cause serious adverse reactions that might result in high risks of infection, thick scabs and scar formation. The understanding and implementing of good post treatment care play a critical role in preventing and minimizing adverse reactions. This article will discuss details of good practice for the post treatment care in PDT of PWS birthmarks.


A comparison of populations self-selected and randomly selected for coronary risk factor screening.
Levels of coronary risk factors in 3,090 adults who sought screening over a 2-year period in Perth, Western Australia, were compared with those in 722 subjects who were selected at random to attend the screening center. Self-referred (SR) subjects were less likely than random-sample (RS) subjects to have suffered from, or be on treatment for, heart disease, hypertension, gout, or diabetes but were more likely to have a family history of premature heart disease. They were less likely to be current smokers and overweight (women only) but more likely to be sedentary at work and have higher mean serum cholesterol levels. SR also had more knowledge about coronary heart disease (CHD) and its causes and were more likely to believe that this knowledge had influenced their behavior, but were less likely than RS to be satisfied with their knowledge level. Smokers among SR were more likely to express a wish to give up smoking than smokers in the RS. These findings are consistent with previous observations. The differences, although statistically significant, were generally small and did not clearly favor one group with respect to total risk of CHD. Therefore the effectiveness of risk factor modification following screening should not be greatly affected by self-selection for screening. Effectiveness may be greater in self-selected subjects because of their apparently greater motivation toward risk factor change.


High affinity insulin binding by soluble insulin receptor extracellular domain fused to a leucine zipper.
Insulin receptors (IRs) that are truncated at the end of the ectodomain form dimers that bind insulin with different characteristics to wild type receptors. These soluble IRs have lowered affinity for insulin compared with full-length IR, and exhibit linear Scatchard plots in contrast to the curvilinear plots obtained with full-length IR, IR truncated at the C-terminus of the transmembrane region and IR ectodomains fused to the self-associating constant domains from Fc or lambda immunoglobulins. In this report, we have fused the IR ectodomain to the 33 residue leucine zipper from the transcriptional activator GCN4 of Saccharomyces cerevisiae. This fusion protein binds insulin with high affinity in a manner comparable to native receptor. The respective dissociation constants were Kd1 8.2 X 10(-11) M and Kd2 1.6 x 10(-8) M for hIRedZip and Kd1 5.7 x 10(-11) M and Kd2 6.3 x 10(-9) M for membrane-anchored, native receptor.


The risk of being bitten by a dog is higher on hot, sunny, and smoggy days.
Humans commit more violent crimes when temperature and air pollution is higher. Here, we investigate if also the day-to-day rates of dogs biting humans is influenced by environmental factors. 69,525 reports of dogs biting humans, sourced from public records on animal control requests and from ER records, were analyzed. The impact of temperature and air pollutants were evaluated with a zero-inflated Poisson generalized additive model, while controlling for regional and calendar effects. Exposure-response curves were used to assess the association between outcome and major exposure variables. We find that the rates of dogs biting humans increases with increasing temperature and ozone, but not PM2.5 exposure. We also observed that higher UV irradiation levels were related to higher rats of dog bites. We conclude that dogs, or the interactions between humans and dogs, are more hostile on hot, sunny, and smoggy days, indicating that the societal burden of extreme heat and air pollution also includes the costs of animal aggression.


Reports of anesthesia-related adverse events.
A case report involving an anesthesia adverse event that was received in the FDA database was used to demonstrate postmarket reporting of medical devices by the manufacturers and the FDA. Even common, everyday adverse events are evaluated and used to improve the safety and efficacy of medical products. Instructions for accessing the FDA MedWatch forms and coding manual are provided, and readers are referred to additional resources on the FDA website.


Metabolic drug targets of the cytosine metabolism pathways in the dromedary camel (Camelus dromedarius) and blood parasite Trypanosoma evansi.
Trypanosomiasis is a major illness affecting camels in tropical and subtropical regions. Comparisons of camel and Trypanosoma evansi genomes can lead to the discovery of new drug targets for treating Trypanosoma infections. The synthesis pathways of cytosine, cytidine, cytidine monophosphate (CMP), cytidine diphosphate (CDP), cytidine triphosphate (CTP) deoxycytidine, deoxycytidine monophosphate (dCMP), deoxycytidine diphosphate (dCDP), and deoxycytidine triphosphate (dCTP) were compared in the dromedary camel (Camelus dromedarius) and T. evansi. None of the enzymes involved in cytosine pathway were detected in camels and T. evansi. Notably, cytidine kinase (CK) and 5'-nucleotidase, which interconverts cytidine to CMP, were not detected in T. evansi but were present in camels. UMP/CMP kinase was not predicted in T. evansi. Therefore, the presence of enzymes involved in the CTP synthesis cascade was not predicted in T. evansi. CMP synthesis might also be encoded by other enzymes, e.g., purine nucleotides kinases. Both camel and T. evansi share an efficient enzyme system for converting CDP to CTP. In conclusion, CTP synthase is important for homeostasis of cytosine nucleotides in T. evansi and could be a potential drug target against the parasite. In addition, the inhibition of UMP synthesis might contribute to parasite death as it is a shared source for CTP synthesis.


Anaphylaxis to penicillin in a frozen dinner.
A case of violent anaphylaxis apparently due to penicillin "hidden" in a frozen dinner is described. Steps helpful in investigating such cases are briefly discussed.


Effect of pyrolysis temperatures and times on the adsorption of cadmium onto orange peel derived biochar.
The mechanism and capacity of adsorption of cadmium (Cd) on orange peel (OP)-derived biochar at various pyrolysis temperatures (400, 500, 600, 700 and 800°C) and heating times (2 and 6 h) were investigated. Biochar was characterized using proximate analysis, point of zero charge (PZC) analysis, Fourier transform infrared spectroscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy and X-ray diffraction. Equilibrium and kinetic experiments of Cd adsorption on biochar were performed. The results indicated that the pH value at PZC of biochar approached 9.5. Equilibrium can be reached rapidly (within 1 min) in kinetic experiments and a removal rate of 80.6-96.9% can be generated. The results fitted the pseudo-second-order model closely. The adsorption capacity was estimated using the Langmuir model. The adsorption capacity of Cd on biochar was independent of the pyrolysis temperature and heating time (p>0.01). The maximum adsorption capacity of Cd was 114.69 (mg g(-1)). The adsorption of Cd on biochar was regarded as chemisorption. The primary adsorption mechanisms were regarded as Cπ-cation interactions and surface precipitation. Cadmium can react with calcite to form the precipitation of (Ca,Cd)CO3 on the surface of biochar. The OP-derived biochar can be considered a favourable alternative and a new green adsorbent for removing Cd(2+) ions from an aqueous solution.


Treatment failure sites according to irradiation technique and histology in patients with endometrial cancer.
Three hundred and seventy-two patients with endometrial cancer treated from 1948 through 1969 and having complete follow-up were reviewed. All patients completed definitive therapy with preoperative irradiation and surgery or irradiation alone and have separated into two main groups: 1) those treated with irradiation by radium alone or 2) those treated with external irradiation plus diminished amounts of radium. Pathology material from each patient was reviewed by one pathologist. Treatment by radium alone led to fewer pelvic failures than did external irradiation plus diminished amounts of radium, when evaluated by stage, grade, and specific histology. Both irradiation modalities led to about the same incidence of failures due to distant metastasis only.


What they didn't tell you about limit cycles.
The paper examines the numerous assumptions involved in theories of predator-prey limit cycles. Predatorprey theories should incorporate the environmental fluctuations appropriate to each specific case.


Determination of methylmercury in environmental samples using static headspace gas chromatography and atomic fluorescence detection after aqueous phase ethylation.
A rapid and automated method for the determination of monomethylmercury (MMHg) in environmental samples was developed using headspace gas chromatography with atomic fluorescence detection in combination with aqueous phase ethylation. Sample preparation steps were optimized for sediments, biological samples, and water samples using certified reference materials and real samples with a broad range of MMHg concentrations. Different extraction procedures were compared for both sediments and biological samples. The methods were applied in the intercomparison exercises for the certification of MMHg in sediments (IAEA 405) and in Oyster tissue (BCR 710) and the results were accepted for certification. The detection limits for MMHg are 0.002 ng Hg/g for sediments and biological samples and 0.01 ng Hg/L for water samples. The method was tested for methylation artifacts; no artifact was observed in the sediment samples and CRMs tested.


Decomposition of CO2 to carbon and oxygen under mild conditions over a zinc-modified zeolite.
An electron-rich zinc-modified zeolite Y material shows substantial activity for the decomposition of CO(2) to carbon with the release of O(2) at about 300 °C. It is elucidated that electrons delocalized in the vicinity of zinc cations in the zeolite material play an essential role in the decomposition reaction.


Mixed effect of increasing outflow of medical patients from an emergency department.
Since 2014, the annual number of patients entering our emergency department (ED) has increased significantly. These were primarily Internal Medicine (IM) patients, and of these, 25-30% were admitted. The present governmental policy presents a deterrent to adding IM beds for these patients, and Emergency and IM departments cope with ever-increasing number of IM patients. We describe a quality improvement intervention to increase outflow of IM patients from the ED to the IM departments. We conducted a quality improvement intervention at the Shaare Zedek Medical Center from 2014 to 2018. The first stage consisted of an effort to increase morning discharges from the IM departments. The second stage consisted of establishing a process to increase the number of admissions to the IM departments from the ED. Implementation of the first stage led to an increased morning discharge rate from a baseline of 2-4 to 18%. The second stage led to an immediate mean (± SD) morning transfer of 35 ± 7 patients to the medical departments (8-12 per department), providing significant relief for the ED. However, the additional workload for the IM departments' medical and nursing staff led to a rapid decrease in morning discharges, returning to pre-intervention rates. Throughout the period of the new throughput intervention, morning admissions increased from 30 to > 70%, and were sustained. The number of patients in each department increased from 36 to 38 to a new steady state of 42-44, included constant hallway housing, and often midday peaks of 48-50 patients. Mean length of stay did not change. IM physician and nurse dissatisfaction led to increased number of patients being admitted during the evening and night hours and fewer during the morning. We describe a quality improvement intervention to improve outflow of medical patients from the ED in the morning hours. The new ED practices had mixed effects. They led to less ED crowding in the morning hours but increased dissatisfaction among the IM department medical and nursing staff due to an increased number of admissions in a limited number of hours. The present governmental reimbursement policy needs to address hospital overcrowding as it relates to limited community healthcare beds and an aging population.


Compartmentalized isozyme genes and the origin of introns.
Both the mouse cytosolic malate dehydrogenase gene and its mitochondrial counterpart contain eight introns, of which two are present at identical positions between the isozyme genes. The probability that the two intron positions coincide by chance between the two genes has been shown to be significantly small (= 1.3 x 10(-3), suggesting that the conservation of the intron positions has a biological significance. On the basis of a rooted phylogenetic tree inferred from a comparison of these isozymes and lactate dehydrogenases, we have shown that the origins of the conserved introns are very old, possibly going back to a date before the divergence of eubacteria, archaebacteria, and eukaryotes. In the aspartate aminotransferase isozyme genes, five of the introns are at identical places. The origins of the five conserved introns, however, are not obvious at present. It remains possible that some or all of the conserved introns have evolved after the divergence of eubacteria and eukaryotes.


Prevalence of human papillomavirus (HPV) infection in Basque Country women using slot-blot hybridization: a survey of women at low risk of developing cervical cancer.
Cervical smears from 1,178 women with cytologically normal cervices and 67 women with cervical intra-epithelial neoplasia (CIN) or cervical carcinoma were analyzed for the presence of HPV 6, 11, 16 and 18 DNA by slot-blot hybridization. HPV DNA was detected in 17% (95% CI: 14%-19%) of the women with a normal smear; 11% of infected women harboured HPV 16 and 18 (95% CI: 9%-13%, each). HPV DNA was detected in 54% (95% CI: 41%-66%) of patients with abnormal smear; the most prevalent virus type in this group was HPV 16 (45%; 95% CI: 32%-38%). In order to verify the slot-blot results, a proportion of the samples was also investigated by PCR. There was 88% correlation between the 2 tests. The high prevalence of HPV 16 and 18 infection demonstrated in our low-cervical-cancer-risk area further support the role of as yet unidentified co-factors as determinants of the different geographic rates of cervical-cancer incidence.


Sperm adenylyl cyclase in young and middle-aged men.
The present report is an extension of a previous study of the accessory sex gland function in normal young (20-25 years) and middle-aged (50-55 years) men. In the same individuals, the basal and in vitro stimulated activities of the sperm adenylyl cyclase were determined. A high degree of individual variation existed in both basal and Gpp(NH)p-, forskolin- and acetate-stimulated sperm adenylyl cyclase, and no significant difference could be demonstrated between the means of the age groups. Furthermore, no significant correlation existed between the concentrations of the glandular secretory products (prostatic acid phosphatase, citric acid, zinc, spermine, spermidine, putrescine, fructose and prostaglandin E) in the ejaculate and the activity of the sperm adenylyl cyclase. Furthermore, the number of morphologically abnormal sperm cells in the ejaculate did not influence the activity of the enzyme. No inverse correlation existed between the magnitude of basal activity and the relative response to Gpp(NH)p, forskolin or acetate suggesting that the variation in the enzyme could not be explained by its partial desensitization by seminal plasma constituents during the liquefaction period. A lack of correlation between the response of the enzyme to Gpp(NH) p and forskolin on the one hand and acetate on the other, implied that these drugs activate the enzyme through different mechanisms.


Safety and effectiveness of lumbar cerebrospinal fluid drainage to prevent delayed cerebral ischemia after Fisher grade 3 subarachnoid hemorrhage with minimal intraventricular hemorrhage.
Lumbar drainage (LD) of cerebrospinal fluid (CSF) is a simple way of clearing subarachnoid hemorrhage (SAH) and reducing the risk of delayed cerebral ischemia (DCI). We focused on Fisher grade 3 SAH with or without minimal intraventricular hemorrhage (IVH; Graeb score ≤5), which has a lower risk of cerebellar tonsillar herniation during LD. The aim of this study was to test the efficacy of LD with respect to reducing the risk of DCI in this patient group. The authors retrospectively reviewed the medical records of 107 patients with Fisher grade 3 SAH with or without minimal IVH, admitted to two hospitals from 2013 to 2019. Patients were retrospectively divided into two groups: study group receiving standard therapy plus LD, or control group receiving standard therapy alone. Primary outcome measures were efficient in preventing DCI. One hundred and seven subjects were allocated to the control (n=79) or study (n=28) groups. Incidence of DCI was 28% (n=22) and 18% (n=5), respectively (P=0.448). Subgroup analysis for HH grade 3+4 (n=68) showed incidence of DCI of 24% (n=19) in the control group (n=50) and 7% (n=2) in the study group (n=18) (P=0.040). There were no LD-related complications. This study could not draw a meaningful conclusion about the overall efficacy of LD on DCI reduction due to small sample size. However, there was a significant reduction of DCI by LD in the HH 3+4 subpopulation. Larger-scale studies are required to confirm our results.


Classification and Morphological Variation of the Frontalis Muscle and Implications on the Clinical Practice.
Forehead aesthetics have a major contribution to the youthful appearance of the face. Restoration of the upper facial aesthetics is important to counteract the changes related to the ageing process. The interaction between the frontalis and its antagonists' muscles contributes to the overall aesthetic balance of the forehead. In this study, we evaluated the gross anatomy of the frontalis and classified the muscle according to the morphological appearance. 26 cadavers of Caucasian and South East Asian origin were dissected. The frontalis muscle was dissected without mobilisation, and the gross anatomy and variations were analysed on the backdrop of gender and ethnicity. Our dissection studies revealed three main variations of the muscle based on the extent of interdigitation between the two bellies in the midline. The average length of the muscle was 10.9 cm in males and 9.1 cm in females. The width of the muscle in females was 4 cm at the origin and 6.5 cm at the insertion and in males 4.4 cm at the origin and 5.8 cm at the insertion. In six specimens, the muscle attached only up to the medial two-thirds of the eyebrows. This was predominantly observed in the Caucasians cadavers and may contribute to the constitutional downward slanting eyebrows in some individuals. This study provides an in-depth analysis and classification of the frontalis muscle. Understanding the morphological variation of the muscle helps to amend clinical application and treatment protocols. Evaluation of the patterns of decussation of the frontalis muscle may assist with non-surgical interventions using botulinum toxin in the treatment of forehead rhytids. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Bioconjugation of CdTe quantum dot for the detection of 2,4-dichlorophenoxyacetic acid by competitive fluoroimmunoassay based biosensor.
Quantum dots (QD) are semiconductor fluorescent nanoparticles, which can be made use of for environmental monitoring with high sensitivity. In view of the alarming levels of pesticides and herbicides being used in agriculture practices, there is a need for their rapid, sensitive and specific detection in food and environmental samples, as pesticides and herbicides are harmful to living beings even at trace levels. Present study was carried out to develop a reliable and rapid method for analysis and detection of 2,4-D (herbicide) using cadmium telluride quantum dot nanoparticle (CdTe QD). Fluoroimmunoassay based on the fluorescent property of quantum dot was used along with immunoassay to detect 2,4-D. CdTe capped with mercaptopropionic acid, was conjugated using N-(3-dimethylaminopropyl)-N-ethylcarbodiimide hydrochloride (EDC) and a coupling reagent like N-hydroxysuccinimide (NHS) to alkaline phosphatase (ALP) which was in turn conjugated to 2,4-D molecule. Anti 2,4-D-IgG antibodies were immobilized in an immunoreactor column using Sepharose CL-4B as an inert matrix. The detection of 2,4-D was carried out by fluoroimmunoassay-based biosensor using competitive binding between conjugated 2,4-D-ALP-CdTe and free 2,4-D with immobilized anti 2,4-D antibodies in an immunoreactor column. It was possible to detect 2,4-D upto 250pgmL(-1). Present study also emphasizes on the resonance energy transfer between ALP and CdTe QD as a result of bioconjugation, which can be used for future biosensor development based on quantum dot-biomolecular interactions.


Effect of pentylenetetrazole and sound stimulation induced single and repeated convulsive seizures on the MDA, GSH and NO levels, and SOD activities in rat liver and kidney tissues.
the aim of our study was to evaluate the activity of superoxide dismutase (SOD) and the levels of glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) in liver and kidney tissues in a rat model of convulsive seizure induced by single and repeated doses of pentylenetetrazole (PTZ) and sound stimulation with key ringing. male Wistar adult rats (n=48), were used in the experiment. The animals were divided into six groups: (1) Single Seizure Control Group (SS-Control; n=8), (2) Repeated Seizures Control Group (RS-Control; n=8), (3) PTZ induced Single Seizure Group (SS-PTZ Group; n=8), (4) PTZ induced Repeated Seizures Group (RS- PTZ Group; n=8), (5) Key-Ringing Induced Single Seizure Group (SS-KEY Group; n=8), (6) Key-Ringing Induced Repeated Seizures Group (RS-KEY Group; n=8). Following injections rats were observed for seizure activity for 30 min. Animals were sacrificed 24h after induced seizure (single or last seizure) or saline administration. MDA, NO, GSH levels and SOD activities were determined in liver and kidney tissues. there was no significant difference between SS-Control and RS-Control groups, SS-PTZ and SS-KEY groups, and RS-PTZ and RS-KEY groups (p>0.05) in none of the examined 4 parameters in liver and kidney tissues. The liver and kidney levels of MDA and NO in SS-PTZ group were found to be significantly higher than the SS-Control group (p<0.05). In SS-KEY group, the liver and kidney levels of MDA and NO were found to be significantly higher and GSH levels were significantly lower than the SS-Control group (p<0.05). While liver and kidney levels of MDA in RS-PTZ group and RS-KEY group were found to be significantly higher than the RS-Control group (p<0.05), liver and kidney GSH levels were significantly lower (p<0.05). The liver levels of NO in RS-PTZ group and RS-KEY group were found to be significantly higher than the RS-Control group (p<0.05). Kidney SOD activities in RS-PTZ group and RS-KEY group were found to be significantly lower than the RS-Control group (p<0.05). When RS-PTZ group is compared with the SS-PTZ group, the liver SOD activity and kidney NO level were found to be significantly lower in the RS-PTZ group (p<0.05). While the liver NO level and GSH level in RS-KEY group were significantly higher than the SS-KEY group, SOD activity was significantly lower in the RS-KEY group (p<0.05). When RS-KEY group was compared with SS-KEY group, the kidney NO level and SOD activity were found to be significantly lower in the RS-KEY group (p<0.05). in conclusion, key-ringing or PTZ induced single and repeated seizures result in increased oxidative damage and lipid peroxidation, and decreased antioxidant defense mechanisms.


Double-sided psoas abscess in a young infant: sonographic and radiographic findings.
Psoas abscess is rare in children and is exceptional in the neonatal period. A sonographically and radiographically well-documented case of double-sided primary psoas abscess in a few-week-old infant is presented. To our knowledge this is the first description of a case of double-sided psoas abscess in a neonate.


Bracket Transfer Accuracy with the Indirect Bonding Technique-A Systematic Review and Meta-Analysis.
To investigate the bracket transfer accuracy of the indirect bonding technique (IDB). Systematic search of the literature was conducted in PubMed MEDLINE, Web of Science, Embase, and Scopus through November 2021. In vivo and ex vivo studies investigating bracket transfer accuracy by comparing the planned and achieved bracket positions using the IDB technique were considered. Information concerning patients, samples, and applied methodology was collected. Measured mean transfer errors (MTE) for angular and linear directions were extracted. Risk of bias (RoB) in the studies was assessed using a tailored RoB tool. Meta-analysis of ex vivo studies was performed for overall linear and angular bracket transfer accuracy and for subgroup analyses by type of tray, tooth groups, jaw-related, side-related, and by assessment method. A total of 16 studies met the eligibility criteria for this systematic review. The overall linear mean transfer errors (MTE) in mesiodistal, vertical and buccolingual direction were 0.08 mm (95% CI 0.05; 0.10), 0.09 mm (0.06; 0.11), 0.14 mm (0.10; 0.17), respectively. The overall angular mean transfer errors (MTE) regarding angulation, rotation, torque were 1.13° (0.75; 1.52), 0.93° (0.49; 1.37), and 1.11° (0.68; 1.53), respectively. Silicone trays showed the highest accuracy, followed by vacuum-formed trays and 3D printed trays. Subgroup analyses between tooth groups, right and left sides, and upper and lower jaw showed minor differences. The overall accuracy of the indirect bonding technique can be considered clinically acceptable. Future studies should address the validation of the accuracy assessment methods used.


Epithelioid dedifferentiated liposarcoma: A clinicopathological and molecular study of 6 cases.
In this study, we present six cases of epithelioid dedifferentiated liposarcoma to further characterize its clinical and pathological features. The patients are all adult men with age at presentation ranging from 46 to 64 years (median 58.5 years). The patients presented with nonspecific symptoms of retroperitoneal mass, intermittent dull pain or discomfort. None of the patients had any prior history of a primary tumor. Radiological examinations revealed the presence of ill-demarcated heterogenous mass located in the deep soft tissue, including retroperitoneum (4 cases), pelvis and trunk (1 case each). Grossly, they appeared as solid tumors with focal areas of necrosis being presented in 2 cases. Histologically, all tumors were characterized by sheets of epithelioid cells that displayed marked cellular atypia and brisk mitotic activity. Variable portion of atypical lipomatous tumor/well-differentiated liposarcoma was present in 3 cases. By immunohistochemistry, the high-grade epithelioid component in all 6 cases showed strong and diffuse nuclear staining of MDM2, CDK4 and P16, with partial expression of AE1/AE3 in 3 cases. Fluorescence in situ hybridization analysis revealed high-level amplification of MDM2 in all 6 cases, with co-amplification of CDK4 in 3 cases. Follow up information showed that two patients died of the disease within one year despite multidisciplinary treatment. Due to the striking epithelioid appearance, this rare variant of dedifferentiated liposarcoma may be confused with undifferentiated epithelioid sarcoma, poorly differentiated carcinoma, mesothelioma or other malignancies with epithelioid phenotype. The study presented herein further highlights the aggressive clinical behavior of this unique tumor type. For patients with advanced disease, CDK4 inhibitor may provide an optional targeted treatment.


Thyroid function and the intraocular pressure response to topical corticosteroids.
Baseline thyroxine, thyrotropin (TSH), and triiodothyronine (T3) resin uptake levels were measured in patients classified according to their topical intraocular response to corticosteroids. Results of thyroid studies were similar in patients with primary open-angle glaucoma and noncorticosteroid responsive (NN, intraocular pressure less than 20 mmHg after six weeks of topical 0.1% dexamethasone eyedrops) subjects. Primary open-angle glaucoma was not associated with the increased prevalence of low thyroid function values. The TSH suppression induced by oral dexamethasone was similar in NN subjects and patients with primary open-angle glaucoma. Patients with primary open-angle glaucoma did not demonstrate an increased glucocorticoid sensitivity as related to thyroid function. Thus, the adenohypophysial thyrotropic cell, the major site of dexamethasone inhibition of TSH secretion, does not appear to share the enhanced corticosteroid sensitivity of the eye, the hypothalamus, and the lymphocyte in patients with primary open-angle glaucoma.


Follow-up study of patients admitted to the pediatric emergency department for chest pain.
Chest pain is a relatively common cause of admission to the Emergency Department, being related in most of the cases to benign conditions with only a minority of the cases affected by heart disease. Limited data are available about the follow up of these patients in terms of risk of recurrence of symptoms, Emergency Department re-admissions, level of impairment, and school absenteeism. We identified 761 children who visited our ED with the chief complaint of chest pain, equal to 0.68% of all admissions. Twenty-four patients were excluded for a previous history of cardiac disease. Eight (1%) patients were determined to have chest pain of cardiac origin. Ninety-seven percent of patients were successfully contacted by telephone: 69% agreed to answer the questionnaire. Of these, 33% experienced recurrent chest pain, up to 41% was forced to be absent from school, about 20% was limited in its daily activities, and about 20% repeated a cardiologic evaluation.Conclusion: Chest pain is mainly due to benign causes and is a recurrent symptom in a high percentage of patients, associated with re-admission and school absenteeism.What is Known:• Chest pain is a relatively common cause of admission to the Emergency Department.• It is mainly due to benign causes and is among the most common reasons for referral to the pediatric cardiologist.What is New:• Chest pain is a recurrent symptom associated with re-admission and school absenteeism.• As a family history of cardiac disease or exertional symptoms are a well-known red flag for chest pain of cardiac origin, school absenteeism should be considered a red flag for symptoms related to psychological distress in patients with non-cardiac chest pain.


Two-dimensional materials for high density, safe and robust metal anodes batteries.
With a high specific capacity and low electrochemical potentials, metal anode batteries that use lithium, sodium and zinc metal anodes, have gained great research interest in recent years, as a potential candidate for high-energy-density storage systems. However, the uncontainable dendrite growth during the repeated charging process, deteriorates the battery performance, reduces the battery life and more importantly, raises safety concerns. With their unique properties, two-dimensional (2D) materials, can be used to modify various components in metal batteries, eventually mitigating the dendrite growth, enhancing the cycling stability and rate capability, thus leading to safe and robust metal anodes. In this paper, we review the recent advances of 2D materials and summarize current research progress of using 2D materials in the applications of (i) anode design, (ii) separator engineering, and (iii) electrolyte modifications by guiding metal ion nucleation, increasing ion conductivity, homogenizing the electric field and ion flux, and enhancing the mechanical strength for safe metal anodes. The 2D material modifications provide the ultimate solution for obtaining dendrite-free metal anodes, realizes the high energy storage application, and indicates the importance of 2D materials development. Finally, in-depth understandings of subsequent metal growth are lacking due to research limitations, while more advanced characterizations are welcome for investigating the metal deposition mechanism. The more facile and simplified preparation of 2D materials possess great prospects in high energy density metal anode batteries, and thus fulfils the development of EVs.


L-tryptophan: effects on daytime sleep latency and the waking EEG.
The effects of L-tryptophan (4 g) on the waking EEG and daytime sleep were studied in a group of 20 normal adults. Subjects were assigned to a morning or afternoon group, and data were collected on two occasions, after L-tryptophan and after placebo, assigned in a counterbalanced order. L-Tryptophan significantly reduced sleep latency without altering nap sleep stages and elevated plasma total and free tryptophan levels. EEGs were digitized on-line and later analyzed for changes in 5 frequency bands: 16-40 c/sec (beta), 13.0-15.5 c/sec (sigma), 8.0-12.5 c/sec (alpha), 4.0-7.5 c/sec (theta) and 0.5-3.5 c/sec (delta). During waking EEGs, L-tryptophan significantly increased alpha time, theta time, and theta intensity and significantly decreased alpha frequency. No wave bands were altered during sleep. L-Tryptophan is an effective daytime hypnotic which can facilitate sleep onset at clock times which do not coincide with biological sleep times. The hypnotic effects may be mediated by lowering arousal level during the awake state, thus setting the stage for more rapid sleep onset.


Somnogenic activity of immune response modifiers.
Sleepiness is a presenting symptom in nearly all infectious diseases. James Krueger describes how microbial products, such as muramyl peptides, lipid A and double-stranded RNA, as well as endogenous products elicited by these substances, such as interleukin 1, modulate sleep. The altered sleep during infection seems to result from an exaggerated activation of physiological sleep mechanisms, since normal sleep is controlled by a wide range of substances including many of these immune response modifiers.


Radiobiological results from the Bacillus subtilis Biostack experiments within the Apollo and the ASTP space flights.
In order to check the results of earlier Biostack experiments, new experimental techniques were developed for the Biostack III experiment in the Apollo-Soyuz test project (ASTP). These techniques resulted in an increased accuracy of localization down to 0.2 micrometers for the determination of the impact parameter, accompanied by an increase in the sample size available for biological investigation. In addition, colony forming ability, metabolic mutations, and mutations affecting UV- and x-ray sensitivity were rendered observable by these methods. The biological and physical results obtained so far from the evaluation of the Bacillus subtilis experiment within Biostack III confirm and extend the findings of the previous Biostack experiments. They also add to the questions about the mechanisms of action of the radiation field under investigation, since the observed effects cannot be interpreted in terms of standard concepts.


Investigation of vacuum pumping on the dose response of the MAGAS normoxic polymer gel dosimeter.
The effect of vacuum pumping on the dose response of the MAGAS polymer gel dosimeter has been investigated. A delay of several days post-manufacture before irradiation was previously necessary due to the slow oxygen scavenging of ascorbic acid. The MAGAS polymer gel dosimeter was vacuum pumped before gelation to remove dissolved oxygen. The MAGAS polymer gel dosimeter was poured into glass screw-top vials, which were irradiated at various times, post-manufacture to a range of doses. Magnetic resonance imaging techniques were used to determine the R2-dose response and R2-dose sensitivity of the MAGAS polymer gel. The results were compared with a control batch of MAGAS polymer gel that was not vacuum pumped. It was shown that vacuum pumping on the MAGAS polymer gel solution immediately prior to sealing in glass screw-top vials initially increases the R2-dose response and R2-dose sensitivity of the dosimeter. An increase in the R2-dose response and R2-dose sensitivity was observed with increasing time between manufacture and irradiation. Over the range of post-manufacture irradiation times investigated, the greatest R2-dose response and R2-dose sensitivity occurred at 96 hours.


Occurrence and persistence of organic emerging contaminants and priority pollutants in five sewage treatment plants of Spain: two years pilot survey monitoring.
This work summarized all results obtained during almost two-years of a monitoring programme carried out in five municipal sewage treatment plants (STPs) located in the north, centre and south-east of Spain. The study evaluated the occurrence and persistence of a group of 100 organic compounds belonging to several chemical groups (pharmaceuticals, personal care products, pesticides and metabolites). The average removal efficiencies of the STPs studied varied from 20% (erythromycin) to 99% (acetaminophen). In analysed samples, we identified a large number of compounds at mean range concentrations between 7-59,495 ng/L and 5-32,720 ng/L for influent and effluent samples, respectively. This study also identified 20 of the mostly detected and persistent compounds in wastewater effluent, of which hydrochlorothiazide, atenolol, gemfibrozil, galaxolide and three metabolites (fenofibric acid, 4-AAA and 4-FAA), presented the highest average contribution percentages, in relation to the total load of contaminants for the different STPs effluent studied.


Clinically suspected heparin-induced thrombocytopenia during extracorporeal membrane oxygenation.
Patients receiving extracorporeal membrane oxygenation (ECMO) are at risk for thrombocytopenia including heparin-induced thrombocytopenia (HIT). The purpose of this study was to determine the frequency of suspected HIT in patients receiving ECMO and unfractionated heparin (UFH). We conducted a retrospective review in adult patients on ECMO. Patients were included if they received ECMO for at least 5 days and concomitant UFH. There were 119 patients who met inclusion criteria. Twenty-three patients (19%) had a heparin-platelet factor 4 immunoassay performed. Patients with suspected HIT had a significantly lower platelet count within the first 3 days of ECMO, 69×10(9)/L (22-126×10(9)/L) vs 87.5×10(9)/L (63-149×10(9)/L); P=.04. The lowest platelet count on the day of HIT testing was 43×10(9)/L (26-73), representing a 71% reduction from baseline. Twenty patients (87%) had an optical density score less than 0.4, and all patients had a score less than 1.0. A functional assay was performed in 7 patients (30%), with only 1 patient having laboratory-confirmed HIT. The evaluation of HIT occurred in a small percentage of patients, with HIT rarely being detected. Patients who had heparin-platelet factor 4 immunoassay testing exhibited lower platelet counts with a similar duration of ECMO and UFH exposure.


Satisfaction from surgical treatment and its influence on the wellbeing of patients with Recklinghausen disease - preliminary report.
Background: Neurofibromatosis type 1 (NF-1) is one of the most common autosomal dominant disorders. Multiple benign dermal neurofibromas, café au lait spots, axillary and inguinal freckling are the hallmarks of NF-1.
Aim: The aim of this paper is to verify if surgical treatment performed in patients with NF-1 is satisfactory to them and to describe demographic factors characteristic for patients with Recklinghausen disease.
Methods: A special questionnaire was prepared for the study, which contained 45 questions. Seventeen patients with neurofibromatosis type 1 agreed to fill in the questionnaire aged from 22 to 61 years.
Results: Surgical treatment in patients was started between 6 and 45 years of age. All patients declared their will to continue surgical treatment. After treatment patients felt more comfortable, more self-confident and sociable. The first symptoms of neurofibromatosis were seen at about 13 years of life in most patients. All women who gave birth noticed progression of the disease during pregnancy.
Conclusions: Performed surgical treatment raises life comfort and increases self-confidence in patients with neurofibromatosis type 1. Due to visible skin changes in neurofibromas it is worth referring patients to Plastic Surgery Departments. Doctors dealing with patients with NF-1 should inform them about the potential heredity of the disease and that puberty and pregnancy intensify the process of skin neurofibroma development.


Oral rapamycin inhibits growth of atherosclerotic plaque in apoE knock-out mice.
Inflammatory and immunological responses of vascular cells are known to play significant roles in atherosclerotic plaque development. Rapamycin with antiinflammatory, immunosuppressive and antiproliferative properties has been shown to reduce neointima formation when coated on stents. This study is designed to test the potential of oral rapamycin to inhibit atherosclerotic plaque development. Eight-week-old apoE knock-out mice were fed with 0.25% cholesterol supplemented diet (control diet), control diet containing 50 microg/kg rapamycin (low-dose rapamycin) or 100 microg/kg rapamycin (high-dose rapamycin) for 4 or 8 weeks. Subsets of mice from each group (n=10) were weighed and euthanized. Whole blood rapamycin levels were determined using HPLC-MS/MS, and histological analyses of atherosclerotic lesions in the aortic root were performed. Mice fed with high-dose rapamycin did not gain weight (18.5+/-1.5 vs. 20.6+/-0.9 g, P=.01). Blood levels of rapamycin 117+/-7 pg/ml were detected in the blood of mice fed with high-dose rapamycin for 8 weeks. The plaque area in mice fed with high dose oral rapamycin is significantly less as compared to control (0.168+/-0.008 vs. 0.326+/-0.013 mm2, P=.001 at 4 weeks; 0.234+/-0.013 vs. 0.447+/-0.011 mm2, P=.001 at 8 weeks). Lumen area was inversely proportional to the plaque area. The results indicate that oral rapamycin is effective in attenuating the progression of atherosclerotic plaque in the mice.


Beyond BMI: The Next Chapter in Childhood Obesity Management.
Pediatric obesity treatment has traditionally focused on body mass index (BMI) and has had limited success. Recent research has suggested new ways to approach this topic that focuses more on holistic measures of health and inclusion of a larger population of children. This paper discusses new evidence in the prevention of chronic disease and treatment of obesity that has a body positive and mental health lens as well as integrating research from several areas of health, including the prevention of chronic disease. Practical medical and mental health assessments tools are suggested for clinical use. Implications for an individualized, positive treatment future are presented.


Structure of the mercury(II) mixed-halide (Br/Cl) complex of 2,2'-(5-tert-butyl-1,3-phenyl-ene)bis-(1-pentyl-1H-benzo[d]imidazole).
The mercury(II) complex of 2,2'-(5-tert-butyl-1,3-phenyl-ene)bis-(1-pentyl-1H-benz-imidazole), namely catena-poly[[dihalogenido-mercury(II)]-μ-2,2'-(5-tert-butyl-1,3-phenyl-ene)bis-(1-pentyl-1H-benzimidazole)-κ2N3:N3'], [HgBr1.52Cl0.48(C34H42N4)], 2, has a polymeric structure bridging via the N atoms from the benzimidazole moieties of the ligand. The compound crystallizes in the ortho-rhom-bic space group Pca21 and is a racemic twin [BASF = 0.402 (9)]. The geometry around the HgII atom is distorted tetra-hedral, with the HgII atom coordinated to two N atoms, one Br atom, and a fourth coordination site is occupied by a mixed halide (Br/Cl). For the two ligands in the asymmetric unit, there is disorder with one of the two tert-butyl groups and benzimidazole moieties showing twofold disorder, with occupancy factors of 0.57 (2):0.43 (2) for the tert-butyl group and 0.73 (3):0.27 (3) for the benzimidazole group. In addition, there is threefold disorder for two of the four n-pentyl groups, with occupancy factors of 0.669 (4):0.177 (4):0.154 (4) and 0.662 (4):0.224 (4):0.154 (4), respectively. The mol-ecules form a one-dimensional helical polymer propagating in the b-axis direction. The helices are held together by intra-strand C-H⋯Br and C-H⋯Cl inter-actions. Each strand is further linked by inter-strand C-H⋯Br and C-H⋯Cl inter-actions. In addition, there are weak C-H⋯N inter-strand inter-actions which further stabilize the structural arrangement.


Branchi-oculo-facial syndrome: a case report to highlight recent genetic considerations.
Branchio-oculo-facial syndrome (BOFS) is a rare entity described during the last century which has been recently linked to mutations of the gene encoding for the transcription factor named 'TFAPA2'. We report here a sporadic case of BOFS with a partial phenotype caused by a de novo mutation of this gene and discuss recent genetic findings.


Foliar spraying with a mixture of transpiration inhibitor-rhamnolipid reduces the Cd content in rice grains.
A field experiment was conducted to investigate the effectiveness and mechanisms of foliar spraying of transpiration inhibitor (TI) and different amounts of rhamnolipid (Rh) on the Cd content in rice grain. The contact angle of TI on the rice leaves was significantly reduced when it was combined with one critical micelle concentration of Rh. The Cd concentration in the rice grain in the presence of TI, TI + 0.5Rh, TI + 1Rh, and TI + 2Rh significantly decreased by 30.8 %, 41.7 %, 49.4 %, and 37.7 % respectively, compared with the control treatment. Specifically, the Cd content with TI + 1Rh was as low as 0.182 ± 0.009 mg/kg, which meets the national food safety requirements (< 0.2 mg/kg). The rice yield and plant biomass of TI + 1Rh were highest compared to the other treatments, possibly because of the alleviation of oxidative stress due to Cd. The hydroxyl and carboxyl concentrations in the soluble components in the leaf cells for the TI + 1Rh treatment were the highest compared to the other treatments. Our results demonstrated that the foliar spraying of TI + 1Rh is an efficient method to reduce Cd accumulation in rice grain. It holds potential for the future development of safe food production in soils polluted with Cd.


A study of hepatic mitochondrial respiration and microsomal cytochrome P450 content in mice infected with the liver fluke Fasciola hepatica.
Previous studies of the effects of infection of Wistar rats with the common liver fluke, Fasciola hepatica, on liver bioenergetic and drug metabolism have demonstrated a loss of respiratory control in isolated mitochondria and reduced microsomal cytochrome P450 content, respectively, from 2 weeks post-infection throughout the acute phase of the infection. In the present study male Balb/c mice infected with F. hepatica showed a loss of respiratory control in isolated liver mitochondria only at 4 weeks post-infection. A similar time course was demonstrated for a reduction in hepatic microsomal cytochrome P450 content. Preparations from infected CBA mice showed similar changes to Balb/c mice but mitochondrial respiration in preparations from infected Swiss outbred mice was normal. A host difference between strains of mice and between mice and rats is therefore evident in the timing and extent of liver mitochondrial dysfunction and in the timing of the decrease in the cytochrome P450 content of hepatic microsomes. This difference between hosts may be related to the reported differences in cellular inflammatory responses to the migrating juvenile flukes in the livers of rats and mice.


Validation of a surgical workspace scale during robot-assisted surgery.
A sufficient surgical workspace is crucial to avoid complications. Within classic laparoscopy, many subjective surgical rating scales (SRSs) have previously been used to evaluate the surgical workspace. This study aimed to validate a modified version of the 5-point SRS during robot-assisted radical nephrectomy (RARN). Thirty-two intra-operative videos of intraperitoneal spaces were recorded from eight patients who underwent RARN. To attain the visualisation of different types of workspaces, we recorded 20 s panoramic videos of different pneumoperitoneum, namely 3, 5, 7 and 12 mmHg. The videos were randomised and presented two times to eight experienced robotic surgeons to evaluate the workspace using our modified 5-point SRS. Both inter-and intra-rater reliabilities were tested. The results of the validation study showed moderate inter-rater and good to excellent intra-rater reliability. This is a valid tool that can be confidently used by future researchers in the field of robot-assisted surgery.


A new aspect of tri-modal therapy with superselective intra-arterial chemotherapy in maxillary sinus carcinoma.
This superselective intra-arterial intervention technique enabled us to administer a higher dose of cisplatinum to the local lesion with a lower incidence of adverse issues by use of neutralizer, compared with the conventional methods. A wide variety of modalities, including surgery, radiotherapy, and chemotherapy, alone or in combination, have been reported for the treatment of maxillary sinus cancer. However, there is still much controversy with regard to the optimum treatment to obtain better local control and acceptable preservation of shape and function. Since 2001, we have performed superselective intra-arterial infusion chemotherapy in combination with radiotherapy and surgery aiming at a higher local control rate. This was a review of prospective collected data. The therapeutic design consisted of weekly intra-arterial infusion of high dose CDDP with concomitant radiotherapy and planned surgery performed during chemo-radiation therapy. From June 2001 to January 2004, 14 patients with squamous cell carcinoma of maxillary sinus underwent this treatment procedure at the University of Tokyo Hospital. The local response rate with this combined therapy was 85.7%. Overall survival rates at 1 and 2 years were 78.6% and 56.2%, respectively, with median follow-up of 25.5 months.


Insights into characteristics of light absorbing carbonaceous aerosols over an urban location in Southeast Asia.
Light absorbing carbonaceous aerosols (LACA) consisting of black carbon (BC) and brown carbon (BrC) have received considerable attention because of their climate and health implications, but their sources, characteristics and fates remain unclear in Southeast Asia (SEA). In this study, we investigated spatio-temporal characteristics of LACA, their radiative properties and potential sources in Singapore under different weather conditions. Hourly BC concentrations, measured from May 2017 to March 2018, ranged from 0.31 μg/m3 to 14.37 μg/m3 with the mean value being 2.44 ± 1.51 μg/m3. High mass concentrations of BC were observed during the south-west monsoon (SWM, 2.60 ± 1.56 μg/m3) while relatively low mass concentrations were recorded during the north-east monsoon (NEM, 1.68 ± 0.96 μg/m3). There was a shift in the Absorption Ångström exponent (AAE) from 1.1 to 1.4 when the origin of LACA changed from fossil fuel (FF) to biomass burning (BB) combustion. This shift is attributed to the presence of secondary BrC in LACA, derived from transboundary BB emissions during the SWM. Lower AAE values were observed when local traffic emissions were dominant during the NEM. This explanation is supported by measurements of water-soluble organic carbon (WSOC) in LACA and the corresponding AAE values determined at 365 nm using a UV-vis spectrophotometer. The AAE values, indicative of the presence of brown carbon (BrC), showed that photochemically aged LACA contribute to an enhancement in the light absorption of aerosols. In addition, spatio-temporal characteristics of BC in the intra-urban environment of Singapore were investigated across diverse outdoor and indoor microenvironments. High variability of BC was evident across these microenvironments. Several air pollution hotspots with elevated BC concentrations were identified. Overall, the results stress a need to control anthropogenic emissions of BC and BrC in order to mitigate near-term climate change impacts and provide health benefits.


Valorization of date palm (Phoenix dactylifera) fruit processing by-products and wastes using bioprocess technology - Review.
The date palm Phoenix dactylifera has played an important role in the day-to-day life of the people for the last 7000 years. Today worldwide production, utilization and industrialization of dates are continuously increasing since date fruits have earned great importance in human nutrition owing to their rich content of essential nutrients. Tons of date palm fruit wastes are discarded daily by the date processing industries leading to environmental problems. Wastes such as date pits represent an average of 10% of the date fruits. Thus, there is an urgent need to find suitable applications for this waste. In spite of several studies on date palm cultivation, their utilization and scope for utilizing date fruit in therapeutic applications, very few reviews are available and they are limited to the chemistry and pharmacology of the date fruits and phytochemical composition, nutritional significance and potential health benefits of date fruit consumption. In this context, in the present review the prospects of valorization of these date fruit processing by-products and wastes' employing fermentation and enzyme processing technologies towards total utilization of this valuable commodity for the production of biofuels, biopolymers, biosurfactants, organic acids, antibiotics, industrial enzymes and other possible industrial chemicals are discussed.


Long-term followup of endoscopic management of urethral strictures in children.
The long-term followup of 31 children with urethral strictures managed by an endoscopic technique was reviewed. Four children could not be managed endoscopically and required urethroplasty, yielding an over-all success rate of 87 per cent. Repeat endoscopic procedures were needed in approximately a third of the patients and intralesional steroids enhanced the change of success. The initial favorable short-term results with endoscopic management of urethral strictures in children are confirmed in this expanded series.


No difference in stem cell somatic mutation between the background mucosa of right- and left-sided sporadic colorectal carcinomas.
Epidemiological, morphological, and molecular differences exist between carcinomas of the right and left sides of the large bowel. To investigate whether this is reflected in differences in somatic mutation frequency in the background mucosa, mutation of the neutral O-acetyltransferase gene (oat) was quantified in histologically normal resection margins from 20 informative (heterozygous) patients with caecal or ascending colon cancer (11 males, median age 75 years) and 20 with sigmoid colon or rectal cancer (10 males, median age 70 years). Mutant discordant crypts lacking O-acetyltransferase activity were visualized by mPAS staining and classified as wholly or partially involved by the mutant phenotype; median frequencies (x10(-4) were compared (Mann-Whitney U-test) after assessing a sample of more than 10,000 crypts per case. No significant difference was found between the frequencies of wholly involved mPAS-positive crypts in background mucosa of left- and right-sided cancers (p = 0.4569), indicating that tumours on both sides of the colon are associated with similar levels of lifetime-accumulated stem cell mutational load. However, partially involved mPAS-positive crypts were significantly more frequent in mucosa from left-sided cancers (p < 0.04), indicating increased mutational activity during the previous 12 months. Analysis of mucosa proximal and distal to left-sided cancers showed that this increase was due to a statistically higher frequency of partially involved crypts in proximal mucosa, which probably resulted from the obstructive effects of the tumour causing increased exposure of the proximal mucosa to luminal carcinogens and/or epithelial regeneration in response to low-grade inflammation or ischaemia. The findings indicate that although left-sided colonic cancer is commoner than right-sided cancer in the British population, carcinomas on both sides of the large bowel arise in a background of similar levels of stem cell mutational activity.


Hepatic blood flow changes in chronic hepatitis C measured by duplex Doppler color sonography: relationship to histological features.
Our aim was to determine if portal vein and hepatic artery blood flow indices are a noninvasive index of severity of liver disease in chronic hepatitis C. The effect of interferon-alpha treatment on liver blood flow was also studied. Liver blood flow measurements were recorded by duplex Doppler color sonography in 39 patients with chronic hepatitis C, 50 healthy controls, and a single patient with hepatocellular carcinoma. Doppler perfusion index (DPI) (calculated as the ratio of hepatic artery flow to total hepatic flow) and the congestive index of the portal vein (area/velocity) were calculated. Liver biopsies were scored for hepatic inflammation and fibrosis. Hepatic arterial flow (415.7+/-329.1 ml/min vs 195.1+/-103.5 ml/min) and DPI (0.27+/-0.14 vs. 0.17+/-0.06) were elevated in chronic hepatitis C patients compared to controls (P = 0.0002 and 0.0003, respectively) while portal vein flow and total hepatic flow were similar. Portal vein congestive index was similar in chronic hepatitis C (0.106+/-0.05) compared to controls (0.125+/-0.08) P 0.52. Hepatic blood flow indices were not related to the grade of hepatic inflammation or the stage of hepatic fibrosis. Twelve weeks of treatment with interferon-alpha had no effect on liver blood flow. In conclusion, patients with chronic hepatitis C have elevated hepatic artery blood flow. Hepatic blood flow indices have no relationship to the severity of histological liver injury in chronic hepatitis C, and these flow indices are unaffected by a 12-week course of interferon-alpha.


The influence of diagnosis, intra- and inter-person variability on serum and plasma Abeta levels.
Evidence suggests that high peripheral beta-amyloid (Abeta)(1-40) levels and low ratios of Abeta(1-42)/Abeta(1-40) are associated with increased risk for Alzheimer's disease (AD). In this cross-sectional design, serum and plasma samples from 67 AD patients and 146 controls (similar in age and gender) were evaluated using Abeta(1-40) and Abeta(1-42) ELISA. Coefficient of variance was calculated for intra- and inter-person variability of Abeta(1-40) and Abeta(1-42). Abeta(1-40) correlated with age, MMSE and their Abeta(1-42)/Abeta(1-40) ratios (p<0.05). Significantly higher Abeta(1-40) levels were observed in AD patients than controls (p<0.05) but no difference was observed for Abeta(1-42) (p>0.05). Serum Abeta(1-42)/Abeta(1-40) ratios were also significantly lower in AD patients than controls (p<0.05). Lower intra-person than inter-person variability was observed for serum and plasma Abeta(1-40) and Abeta(1-42) and these were higher in controls than in AD patients. The intra-person variability of serum Abeta(1-40) did not influence the group differences observed between AD patients and controls. Significant interaction was observed between diagnosis and intra-person variability for serum Abeta(1-40) levels (p<0.05) and was supported by our finding of higher intra-person variability for serum Abeta(1-40) in controls (26.97%) than in AD patients (18.35%). We confirm the previously observed differences in blood Abeta levels between AD and control groups. In addition, we now report the presence of high intra- and inter-person variability possibly due to factors that influence peripheral Abeta levels and warrant further investigation before the potential use of Abeta as an AD biomarker can be fully exploited.


Ulcerative colitis patients in clinical remission demonstrate correlations between fecal immunochemical test results, mucosal healing, and risk of relapse.
To assess the risk of relapse in ulcerative colitis (UC) patients in clinical remission using mucosal status and fecal immunochemical test (FIT) results. The clinical outcomes of 194 UC patients in clinical remission who underwent colonoscopy were based on evaluations of Mayo endoscopic subscores (MESs) and FIT results. Patients with an MES of 0 (n = 94, 48%) showed a ten-fold lower risk of relapse than those with an MES of 1-3 (n = 100, 52%) (HR = 0.10, 95%CI: 0.05-0.19). A negative FIT result (fecal hemoglobin concentrations ≤ 100 ng/mL) was predictive of patients with an MES of 0, with a sensitivity of 0.94 and a specific of 0.76. Moreover, patients with a negative FIT score had a six-fold lower risk of clinical relapse than those with a positive score (HR = 0.17, 95%CI: 0.10-0.28). Inclusion of the distinguishing parameter, sustaining clinical remission > 12 mo, resulted in an even stronger correlation between negative FIT results and an MES of 0 with respect to the risk of clinical relapse (HR = 0.11, 95%CI: 0.04-0.23). Negative FIT results one year or more after remission induction correlate with complete mucosal healing (MES 0) and better prognosis. Performing FIT one year after remission induction may be useful for evaluating relapse risk.


Genetic change may be caused by interference with protein-protein interactions.
Several aprotic polar solvents were shown to induce mitotic aneuploidy in yeast: diethyl ketone, gamma-valerolactone, pyridine, pivalinic acid nitrile, phenylacetonitrile and fumaric acid dinitrile. Only fumaric acid dinitrile also strongly induced other types of genetic effects including mitotic crossing-over, mitotic gene conversion and point mutation. The other substances only induced aneuploidy and this only over a very narrow dose range. The treatment protocol used suggested that these chemicals acted via interference with tubulin assembly and disassembly causing a malfunctioning of spindle fiber microtubules. This hypothesis was tested using twice recycled porcine brain tubulin. Diethyl ketone, gamma-valerolactone, pyridine and phenylacetonitrile inhibited GTP-promoted assembly of porcine brain tubulin in vitro in the concentration range needed for the induction of mitotic aneuploidy in yeast. Pivalinic acid nitrile accelerated tubulin aggregation whereas fumaric acid dinitrile had no effect even at concentrations 18 times higher than the lowest tested concentration effective in yeast. The in vitro experiments with porcine brain tubulin further suggest that genetic change can result from interference with specific protein-protein interactions. Fumaric acid dinitrile was the only exception since it did induce aneuploidy but had no effects on the assembly of porcine brain tubulin. This could be caused either by interference with protein-protein interactions other than between molecules during assembly and disassembly of microtubules or species-specific differences in susceptibility between yeast spindle and porcine brain tubulin.


Retinal-cell-conditioned medium prevents TNF-alpha-induced apoptosis of purified ganglion cells.
Retinal ischemic processes occurring in glaucoma or diabetic retinopathy induce the secretion of tumor necrosis factor (TNF)-alpha. This cytokine was reported to be either toxic to or protective of retinal ganglion cells (RGCs). In the present study, its effect on RGCs was analyzed in different culture conditions. Adult rat RGCs were prepared in mixed retinal cell cultures and in purified cultures. They were incubated in normoxic or ischemic conditions, in the presence or absence of TNFalpha and/or conditioned media isolated from rat retinal glial cell cultures and from adult mixed retinal cell cultures. In mixed retinal cell culture, RGCs were insensitive to TNF-alpha, whereas it induced their degeneration in purified adult RGC cultures. This TNFalpha-elicited toxicity was suppressed by TNFalpha-R1-neutralizing antibodies or caspase 8/10 inhibitors. Analyses of mRNA and protein content in purified RGCs revealed a time-dependent reduction in the expression of the inhibitor of caspase-8, c-FLIP. c-FLIP mRNA was also undetectable after 5 days of culture in the presence of TNFalpha. The retinal cell-conditioned medium protected the RGCs from TNFalpha-induced death and prevented the decrease in c-FLIP mRNA and protein in purified cultures. This medium promoted NF-kappaB translocation in purified RGCs, whereas an NF-kappaB inhibitor induced RGC death in mixed retinal cells. The results confirm that TNFalpha can induce RGC death by TNF-R1 activation. They indicate, however, that other retinal cells can release a molecule that promotes NF-kappaB translocation in RGCs, the synthesis of the anti-caspase-8, c-FLIP, and thereby prevents TNFalpha-mediated RGC death.


Melanism and diel activity of alpine Colias (Lepidoptera: Pieridae).
The hypothesis that increased melanism provides a benefit in prolonging diel activity through more efficient absorption of solar radiation was tested in the field on a population of alpine Colias sulphur butterflies. A marked increase in the duration of flight and feeding behaviour existed for melanistic individuals when compared to lighter individuals under cool temperatures and low intensity solar radiation. More melanistic butterflies moved longer distance per day, and emigrated from the population at a faster rate. At high temperature and high radiant load lighter coloured individuals appeared more active. This is the first field demonstration of the advantage of melanism for increasing activity of ectotherms in cold environments.


HDL-cholesterol concentration and its association with coronary artery calcification: a systematic review and meta-analysis.
Coronary artery calcification (CAC) is a potential risk marker of coronary atherosclerosis that has high specificity and sensitivity. However, the association between high-density lipoprotein cholesterol (HDL-C) concentration and CAC incidence and progression is controversial. PubMed, Embase, Web of Science, and Scopus were systematically searched to identify relevant observational studies up to March 2023 and assessed the methodological quality using Newcastle-Ottawa Scale (NOS) scale. Random-effects meta-analysis was used to estimate pooled odds ratios (OR) and 95% confidence interval considering heterogeneity across studies. Of the 2,411 records, 25 cross-sectional (n = 71,190) and 13 cohort (n = 25,442) studies were included in the systematic review. Ten cross-sectional and eight cohort studies were not eligible and were omitted from the meta-analysis. A total of 15 eligible cross-sectional studies (n = 33,913) were included in the meta-analysis and pooled results revealed no significant association between HDL-C and CAC > 0, CAC > 10, or CAC > 100 [pooled OR: 0.99 (0.97, 1.01)]. Meta-analysis of the 5 eligible prospective cohort studies (n = 10,721) revealed no significant protective effect of high HDL-C against CAC > 0 [pooled OR: 1.02 (0.93, 1.13)]. According to this analysis of observational studies, high HDL-C levels were not found to predict protection against CAC. These results suggest HDL quality rather than HDL quantity is important for certain aspects of atherogenesis and CAC. CRD42021292077.


First Indian study to establish safety of immediate-spin crossmatch for red blood cell transfusion in antibody screen-negative recipients.
The US Food and Drug Administration and American Association of Blood Banks approved the type and screen approach in 1980s, long after antibody screen (AS) was introduced in 1950s. The present study omits conventional anti-human globulin (AHG) crossmatch and replaces it with immediate-spin (IS) crossmatch as part of pretransfusion testing in AS-negative patients to study the safety and effectiveness of IS crossmatch in recipients. This prospective longitudinal study was conducted on over 5000 red cell units transfused to AS-negative patients admitted to the hospital. Pretransfusion testing comprised blood grouping and AS followed by IS crossmatch, at the time of issue of red cell unit. The patients were transfused IS compatible red cell units. AHG crossmatch was performed posttransfusion for all red cell units. Any incompatible AHG crossmatch was followed up as suspected transfusion reaction. A total of 5023 red cell units were transfused to 2402 patients with negative AS. 99.7% IS compatible red cell units were also compatible on posttransfusion AHG crossmatch. Anti-P1 alloantibody was identified in one patient who was transfused two IS crossmatch compatible units but later both units were incompatible on AHG crossmatch. There was no clinical or serological sign of hemolysis in the patient. In AS-negative patients, IS crossmatch is as safe as conventional AHG crossmatch and can, therefore, replace conventional AHG crossmatch protocol.


A rare ocular complication of septicemia: a case series report and literature review.
Septicemia that leads to ocular involvement mostly presents as endophthalmitis or panophthalmitis. Contrarily, septicemia without intraocular involvement, known as hematogenous orbital cellulitis (HOC), involves only the orbit and is an extremely rare complication of septicemia and a rare type of orbital cellulitis. Four male patients with septicemia presented with orbital involvement without intraocular infection were described in this study. They were 22 (case 1), 15 (case 2), 79 (case 3), and 30 (case 4) years old, with a mean age of 29.75 years. All patients were immunocompromised except for case 2. Cases 1 and 3 had a history of steroid use, whereas case 4 was in a post-chemotherapy myelosuppression phase. Septicemia in case 1 was community-acquired, cases 3 and 4 were hospital-acquired, and case 2 was secondary to acne squeezing. Blood cultures from cases 1, 2, and 3 were positive for Candida albicans, methicillin-resistant Staphylococcus aureus, and Klebsiella pneumoniae, respectively. Case 4 had negative cultures; however, next-generation sequencing reported the presence of Enterococcus faecalis and Rhizopus oryzae. Case 1 had right eye involvement, and both eyes were involved in the other three cases. According to Chandler's classification, case 1 was type 2, case 2 was type 2 (OD) and type 4 (OS), and cases 3 and 4 were type 1 orbital infections. All patients had eyelids erythema, and cases 1 and 2 had mildly decreased visual acuity, proptosis, and painful and restricted ocular motility. Hospital stays ranged from 13 to 43 days (mean, 24 days). All patients received systemic antibiotic therapy based on drug sensitivity and next-generation sequencing results, in combination with multidisciplinary treatment, resulting in complete recovery of ocular and systemic signs and symptoms; no ocular surgical interventions were performed. Extraocular muscle palsy was the last symptom to resolve. HOC is predominantly seen in immunocompromised individuals with a high proportion of hospital-acquired infections and positive cultures for pathogens. Infection control using systemic antibiotics targeted at the causative organism guarantees a favorable prognosis.


The effect of COVID-19 lockdowns on exercise and the role of online exercise in Australians with multiple sclerosis.
Regular exercise is beneficial for people with Multiple Sclerosis (MS), regardless of disability level. The previously reported differential effect of COVID-19-related lockdowns on exercise levels in this population remains unexplained. We examined effects of lockdowns on exercise in Australians with MS according to disability levels, lockdown severity and health technology use. A cross-sectional survey of people with MS in Australia (22 April-23 September 2021) collected demographic and clinical information as well as exercise patterns before and during lockdowns. Mann-Whitney was used to compare ordinal data and Likelihood Ratio to compare dichotomous data. 151 people completed the survey. 72.2% had mild disability and 25.2% moderate disability. Extended lockdowns were associated with significantly decreased sedentary behaviour (31.5% to 25.9%) but also with decreased exercise frequency in frequent exercisers (≥3 times/week; 53.7% to 22.2%). The latter occurred significantly more in those with mild disability (-22.7%) than with moderate disability (-3.5%). More people with mild disability walked for exercise pre-pandemic (LR 8.6, p=.004) and during lockdowns (LR 6.6, p=.010). Walking during lockdowns was positively associated with working from home. People with moderate disability were more likely to engage in home exercise both pre-pandemic (LR 5.5, p=.019) and during lockdown (LR 5.2, p=.023). Engagement in home exercise rose for both groups during lockdowns and was facilitated by on-line exercise classes. Lockdowns differentially affected exercise patterns according to disability level. The proportion of people achieving exercise recommendations decreased more in those with mild but not moderate disability. Incidental physical activity was disproportionately impacted in people with moderate disability.


Immunomodulation with human recombinant autoantigens.
The loss of beta cells in type 1 diabetes is the consequence of a T cell-dependent autoimmune attack. Autoantibodies against GAD65 (Mr 65.000 isoform of glutamic acid decarboxylase), IA-2 (insulinoma-associated protein IA-2) or insulin, alone or in combination, predict disease. Preclinical studies in spontaneously diabetic rodents suggest that immunomodulation with autoantigens might alter the course of autoimmune diabetes. Oral insulin reduces the development of diabetes in risk subjects with high insulin autoantibody levels. Giving alum-formulated GAD65 to patients classified with latent autoimmune diabetes of the adult (LADA) is safe and suggests possible immunomodulating effects of GAD65. Future immunomodulation trials might better ascertain subjects based on HLA genetic risk factors, the level of insulin that is still produced or by combining autoantigens with, for example, anti-CD3 antibodies, to induce antigen-specific tolerance and thereby a long-lasting protection for beta cells.


Assessment of the potential of phage-antibiotic synergy to induce collateral sensitivity in Salmonella Typhimurium.
This study was designed to evaluate the synergistic effect of phage and antibiotic on the induction of collateral sensitivity in Salmonella Typhimurium. The synergistic effects of Salmonella phage PBST32 combined with ciprofloxacin (CIP) against S. Typhimurium KCCM 40253 (STKCCM) were evaluated using a fractional inhibitory concentration (FIC) assay. The CIP susceptibility of STKCCM was increased when combined with PBST32, showing 16-fold decrease at 7 log PFU/mL. The combination of 1/2 × MIC of CIP and PBST32 (CIP[1/2]+PBST32) effectively inhibited the growth of STKCCM up to below the detection limit (1.3 log CFU/mL) after 12 h of incubation at 37 °C. The significant reduction in bacterial swimming motility was observed for PBST32 and CIP[1/4]+PBST32. The CIP[1/4]+PBST32 increased the fitness cost (relative fitness = 0.57) and decreased the cross-resistance to different classes of antibiotics. STKCCM treated with PBST32 alone treatment exhibited the highest coefficient of variation (90%), followed by CIP[1/4]+PBST32 (75%). These results suggest that the combination of PBST32 and CIP can be used to control bacterial pathogens.


Systematic classification of unknown metabolites using high-resolution fragmentation mass spectra.
Metabolomics using nontargeted tandem mass spectrometry can detect thousands of molecules in a biological sample. However, structural molecule annotation is limited to structures present in libraries or databases, restricting analysis and interpretation of experimental data. Here we describe CANOPUS (class assignment and ontology prediction using mass spectrometry), a computational tool for systematic compound class annotation. CANOPUS uses a deep neural network to predict 2,497 compound classes from fragmentation spectra, including all biologically relevant classes. CANOPUS explicitly targets compounds for which neither spectral nor structural reference data are available and predicts classes lacking tandem mass spectrometry training data. In evaluation using reference data, CANOPUS reached very high prediction performance (average accuracy of 99.7% in cross-validation) and outperformed four baseline methods. We demonstrate the broad utility of CANOPUS by investigating the effect of microbial colonization in the mouse digestive system, through analysis of the chemodiversity of different Euphorbia plants and regarding the discovery of a marine natural product, revealing biological insights at the compound class level.


Inadequate Expression and Activation of Mineralocorticoid Receptor Aggravates Spatial Memory Impairment after Traumatic Brain Injury.
The administration of glucocorticoids (GCs) for the treatment of traumatic brain injury (TBI) is controversial. Both protective and deleterious effects of GCs on the brain have been reported in previous studies, while the mechanisms are unclear. Most experimental studies have reported glucocorticoid receptor (GR)-mediated deleterious effects after TBI. Sufficient mineralocorticoid receptor (MR) activation was reported to be indispensable for normal function and survival of hippocampal neurons, but changes in MR expression and activation and the roles of MRs in the survival of neurons after TBI remain unclear. We hypothesized that inadequate MR expression and activation caused by TBI aggravates posttraumatic hippocampal apoptosis but that restoration by restoring MRs promotes the survival of neurons. Using a rat controlled cortical impact model, we examined plasma corticosterone, MR expression and activation, neuronal apoptosis in the hippocampus, and spatial memory on day 3 after injury with and without fludrocortisone (1 mg/kg) treatment. Plasma corticosterone levels were significantly reduced after TBI. In addition, both MR expression and activation were inhibited. Fludrocortisone treatment significantly increased both the expression and activation of MRs, reduced the number of apoptotic neurons and cell loss in the ipsilateral hippocampus, and subsequently improved spatial memory. Its protective effects were counteracted by the MR antagonist spironolactone. The results suggest that adequate expression and activation of MRs is crucial for the survival of neurons after TBI and that fludrocortisone protects hippocampal neurons via promoting MR expression and activation.


Prenatal Care during and after Breast Cancer Treatment.
Cancer associated with pregnancy is defined by diagnosis during pregnancy, lactation, or the first year after delivery. The decision about type of treatment depends on the cancer stage and gestational age. Termination of pregnancy does not seem to modify the maternal prognosis for breast cancers. Interdisciplinary meetings and discussions are needed to evaluate and balance the maternal and fetal risks. In this chapter, we discuss about how to prevent or treat maternal and fetal complications of surgery and chemotherapy in pregnancy-associated breast cancer.