Statistical and theoretical considerations for the platform re-location water maze.
The Morris water maze is a commonly employed method to investigate learning and memory. The task demands experimental subjects use distal spatial cues in navigating to a hidden escape platform while swimming in a pool of opaque water. Since its primary description thirty years ago, several modifications have emerged. For example, part-way through the experiment, the target platform can be re-located, thus requiring subjects re-learn spatial aspects of the task. This procedure demands sequential memory encoding of highly similar events and can be selectively impaired by genetic and pharmacological methods affecting cognitive flexibility. While the primary reasons for employing re-locating platform tasks are to study aspects of cognitive flexibility, the paradigms also demonstrate a potential for reducing within-treatment group variation by enabling within-subject analysis. We tested this hypothesis using the C57BL/6 mouse line, a commonly chosen subject for behavioral experiments, and demonstrate that a within-subject comparison approach is both valid and effective in reducing variability. Interestingly, the within-subject statistical advantage is most pronounced for performance measures of short-term memory. In addition, we find that subject naivety, but not experimental inter-phase interval or subcutaneous saline injections, has a significant effect on variation in performance. We also found repeated training in the Morris water maze improved short-term memory without enhancing long-term memory. Together, the data suggest platform re-location tasks can help alleviate within-group variability, a major conundrum in behavioral neuroscience, and provide valuable insight into the general sources of variability underlying performance in cognitive tasks.


Accelerated Longitudinal Weight Gain Among Infants With In Utero COVID-19 Exposure.
Since the initial outbreak of coronavirus disease 2019 (COVID-19), a novel population of children with in utero exposure to maternal infection has emerged whose health outcomes are largely unknown. To compare longitudinal growth trajectories among infants with vs without in utero COVID-19 exposure. We conducted a longitudinal cohort study leveraging a prospectively enrolled perinatal biorepository among 149 infants with in utero COVID-19 exposure and 127 unexposed controls. Weight, length, and body mass index (BMI) were abstracted from health records at 0, 2, 6, and 12 months and standardized using World Health Organization growth charts. Analyses were adjusted for maternal age, ethnicity, parity, insurance, and BMI as well as infant sex, birthdate, and breastfeeding. Infants with in utero COVID-19 exposure vs controls exhibited differential trajectories of weight and BMI, but not length, z-score over the first year of life (study group × time interaction, P < .0001 for weight and BMI). Infants born to mothers with prenatal COVID-19 had lower BMI z-score at birth (effect size: -0.35, 95% CI -0.66 to -0.03) and greater gain in BMI z-score from birth to 12 months (effect size: 0.53, 95% CI 0.06 to 0.99). Birth weight z-score mediated a significant proportion of the relationship between COVID-19 exposure and postnatal growth (estimate ± SE, 32 ± 14%, P = .02). Infants with in utero COVID-19 exposure exhibited lower birth weight and accelerated weight gain in the first year of life, which may be harbingers of downstream cardiometabolic pathology. Further studies are needed to delineate cardiometabolic sequelae among this emerging global population.


The influence of oligodeoxyribonucleotide phosphorothioate pyrimidine strands on triplex formation.
Analogues of the homopyrimidine oligonucleotide dT15 that contained phosphorothioate bonds of a mixture of diastereoisomers or one of the two stereoisomers (either Rp or Sp) were synthesized. The analogues were mixed under conditions conducive to the formation of triple-stranded assemblies. The mixtures were characterized by their thermal stabilities (Tm values), CD spectra, and gel electrophoresis pattern. The 34-mer duplexes containing 15 central purines on one strand and 15 complementary pyrimidines on the other strand gave no detectable triple helix upon combination with dT15S14. On the other hand, 34-bp duplexes with dT15S1, having Rp or Sp, formed triple helixes. This suggests that a steric factor plays an important role in triple helix formation.


Extent and variation of omeprazole prescribing in an elderly population of Ontario.
To determine the extent of omeprazole prescribing in the senior population of Ontario over a 1-year period; the variation in omeprazole prescribing for this population according to age group, gender, and geographic region: and the extent of inappropriate prescribing of omeprazole for this population. Retrospective drug utilization review of prescription drug insurance claims. The Ontario Drug Benefit (ODB) program claims database. The following outcomes were measured: the proportion of seniors in Ontario who received a prescription for omeprazole from April 1, 1992 to March 31, 1993: effects of age group, gender, and geographic region of residence on omeprazole prescribing; and the extent of inappropriate omeprazole prescribing according to the ODB criteria for use. Prescribing of omeprazole was defined as inappropriate if a first-line antiulcer drug (i.e., histamine2-receptor antagonist) was not prescribed within 1-6 months of the first prescription claim for omeprazole. A total of 29,936 seniors in Ontario received omeprazole from April 1, 1992 to March 31, 1993 (2.53 recipients per 100 eligible population). The age-gender group most frequently prescribed omeprazole was women 65-74 years, followed by women and men 75 years or older, and then men 65-74 years. Omeprazole prescribing varied widely among the 48 provincial counties (range of 1.66 recipients per 100 eligible population to 4.52 recipients per 100 population, p < 0.001). There was no evidence of a clustering effect in omeprazole prescribing at the county level. Prescribing of omeprazole was considered to be inappropriate for 80.5% of recipients. This study demonstrated the ineffectiveness of the ODB limited-use program in controlling omeprazole prescribing. Further study should be done to examine determinants of variation in prescribing by geographic region.


Comparison of Peripheral Nerve Regeneration with Side-to-side, End-to-side, and End-to-end Repairs: An Experimental Study.
The present study was conducted to find out a tool to enable improved functional recovery with proximal nerve injury. In this experimental study, nerve regeneration was compared between side-to-side (STS), end-to-side (ETS), and end-to-end repairs. The walk track analysis was used as an outcome of functional recovery. Nerve regeneration was studied with morphometry and histology 6 or 26 weeks postoperatively. All 3 repair techniques showed regeneration of the nerve. From 12 weeks onward, the functional results of the 3 intervention groups were significantly better compared with the unrepaired control group. End-to-end repair was significantly better when compared with the STS and ETS groups. At 26 weeks, the functional and morphometric results and histologic findings did not differ between the STS and ETS groups. The functional results correlated with the morphometric findings in all groups. STS neurorrhaphy showed nerve regeneration, and the end results did not differ from clinically widely used ETS repair. Further studies are warranted to optimize the neurorrhaphy technique and examine possible applications of STS repair in peripheral nerve surgery.


[Pharmacist's interview with type 2 diabetes: Development of a follow-up form].
Type 2 diabetes is a major public health concern because of its prevalence, the severity of complications and the financial implications. Compliance and patient's autonomy in medications intake play key roles in the success of treatment. Pharmacists' interviews ensure an optimized and individual follow-up. Type 2 diabetes is not one of the targeted diseases to perform pharmacists' interviews on under Health Insurance. We thus judged useful to contribute to their development. We applied a cross-disciplinary methodological process in order to define the specifications of the follow-up form useful to conduct the pharmacist's interview 1 by focusing on the identification of a non-compliance and its origins. A feasibility study was carried out in order to check its workability to the pharmacy practice. The follow-up form, associated with a pharmacist practical guide, includes 3 parts: (1) General informations, (2) Survey establishing patient's knowledge, (3) Summary including a level of knowledge assessment grid. Outcomes provide a long but appropriate-felt duration, few difficulties to conduct the interview and a proven usefulness in 90% of all cases that make the follow-up form suitable to the pharmacy practice. This tool could serve as a model for the pharmacist to conduct his future interviews for the type 2 diabetes patients, thus improving patient care, together with other health professionals.


The effect of Laminaria japonica polysaccharides on the recovery of the male rat reproductive system and mating function damaged by multiple mini-doses of ionizing radiations.
To evaluate the radiation-protect effects of Laminaria japonica polysaccharides (LJP) on male reproductive system damage and mating dysfunction induced by multiple mini-dose ionizing radiations, male rats were administrated with radiation and/or LJP. Results showed that mating function (such as erection, mount and ejaculation), sperm count and survival rate in LJP group were significantly better than the corresponding model group after the radiation. The testis organ coefficient, GSH (glutathione) content, serum sex hormones (luteinizing hormone, follicle-stimulating hormone, testosterone and estradiol) levels improved while MDA (malondialdehyde) content decreased. In addition, SOD (superoxide dismutase), GSH-PX (glutathione peroxidase), LDH (lactate dehydrogenase) activities were enhanced while testicular tissue damage was reduced, 14 days after the cessation of radiation; all indicators in the LJP group were similar to the control group. Our results suggest that, LJP has some promoting effects on the recovery of the reproductive system and mating dysfunction induced by radiation.


When there's smoke there's…scleroderma: evidence that patients with scleroderma should stop smoking.
There is no treatment for the autoimmune disease scleroderma (systemic sclerosis, SSc), a multisystem disorder characterized by vascular damage and fibrosis. In particular, SSc can severely affect the lung, resulting in pulmonary arterial hypertension and fibrosis. Smoking is well-known to affect pulmonary health, and a recent report (Hudson et al., Arthritis Rheum, in press Oct 8) provides convincing evidence that stopping smoking improves disease outcome in SSc patients. This commentary discusses this recent publication which suggests that physicians should encourage SSc patients to stop smoking immediately.


Determination of Ruboxistaurin analysis in rat plasma utilizing LC-MS/MS technique.
Ruboxistaurin (RBX) used to treat retinopathy in diabetic patients which caused by microvascular damage and leakage which contributes to visual loss. There are no published studies on the use of liquid chromatography-tandem mass spectrometry for development and validation of a simple, sensitive, and accurate method for measuring RBX in rat plasma. Chromatographic separation of RBX was achieved using ultra-performance liquid chromatography. Multiple-reaction monitoring quantification used RBX [M + H] + ion at m/z 469.18 and daughter ions at m/z 84, 58.12, and 98.10. Atorvastatin was used as internal standard (IS), has a single daughter ion, and was identified using m/z 559.6 → 249.9. Validation of the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for RBX in rat plasma for linearity (greater than0.997) was carried out at 25-1000 ng/mL. In rat plasma, the accuracy was within 3.4%, and the intra- and inter-day precision was within 11.8%. Stability, recovery, and matrix effect were all within acceptable limits. The drug retention time (0.85 ± 0.03 min) was remarkably short. The method developed in the current study is suitable to quantify RBX in plasma or bulk doses.


Leveraging manifold learning techniques to explore white matter anomalies: An application of the TractLearn pipeline in epilepsy.
An accurate description of brain white matter anatomy in vivo remains a challenge. However, technical progress allows us to analyze structural variations in an increasingly sophisticated way. Current methods of processing diffusion MRI data now make it possible to correct some limiting biases. In addition, the development of statistical learning algorithms offers the opportunity to analyze the data from a new perspective. We applied newly developed tractography models to extract quantitative white matter parameters in a group of patients with chronic temporal lobe epilepsy. Furthermore, we implemented a statistical learning workflow optimized for the MRI diffusion data - the TractLearn pipeline - to model inter-individual variability and predict structural changes in patients. Finally, we interpreted white matter abnormalities in the context of several other parameters reflecting clinical status, as well as neuronal and cognitive functioning for these patients. Overall, we show the relevance of such a diffusion data processing pipeline for the evaluation of clinical populations. The "global to fine scale" funnel statistical approach proposed in this study also contributes to the understanding of neuroplasticity mechanisms involved in refractory epilepsy, thus enriching previous findings.


The antishock effect of anisodamine requires the upregulation of α7 nicotine acetylcholine receptors by IL-10.
Although anisodamine, a muscarinic acetylcholine receptor antagonist, has been used in China for treating various shocks for many years, the mechanisms are not well understood. Our previous studies have demonstrated anisodamine exerts its cholinergic anti-inflammatory action through indirectly activating α7 nicotinic acetylcholine receptors (α7 nAChR). Because IL-10 is a critical anti-inflammatory factor, we investigated its potential role in the antishock action of anisodamine. C57BL/6 and IL-10 -/- mice were intraperitoneally administered LPS and/or anisodamine, and the 24h survival rate, cytokine production and α7 nAChR expression were examined. In addition, RAW264.7 cells were stimulated with LPS, anisodamine and/or IL-10, and cytokine production and α7 nAChR expression were investigated. Anisodamine dose-dependently increased the 24h survival rate of C57BL/6 mice treated with LPS. The antishock role of anisodamine was significantly attenuated in IL-10 -/- mice. Anisodamine significantly decreased TNF-α and IL-1β production in LPS-treated RAW264.7 cells and C57BL/6 mice. However, it did not increase the level of IL-10 in the same experiments. In RAW264.7 cells, IL-10 treatment increased α7 nAChR expression, which was further augmented in the presence of anisodamine. Spleens from IL-10 -/- mice expressed significantly lower α7 nAChRs levels compared to IL-10 +/+ mice. Although anisodamine markedly increased the expression of α7 nAChRs in spleens from LPS-treated IL-10 +/+ mice, it only induced a marginal increase of the receptor in spleens from LPS-treated IL-10 -/- mice. These findings demonstrate that IL-10 plays an important role in the antishock action of anisodamine. It acts through upregulating α7 nAChR synergistically with anisodamine.


Relationship of DRD5 and MAO-B VNTR polymorphisms with paranoid and antisocial personality disorders in polydrug users.
Although multiple studies have shown the role genetics plays in personality disorders and in addictions, few have studied the genetic aspects of their comorbidity. Here, we carried out a cross-sectional study in a sample comprising 303 Caucasian polydrug-consuming patients. The presence of personality disorders was evaluated using the International Personality Disorder Examination, and genes related to dopamine, serotonin and monoamine oxidase (MAO) were genotyped. A significant relationship was observed between the bp 279 DRD5 variable number of tandem repeat (VNTR) polymorphism and paranoid personality disorder OR 95 % CI = 2.186 1.074 ; 4.449 ; p = 0.006 . The bp 182 OR 95 % CI = 0.407 0.178 ; 0.931 ; p = 0.033 and bp 184 OR 95 % CI = 0.391 0.188 ; 0.813 ; p = 0.012 alleles of the MAOB VNTR were also associated with antisocial personality disorder. Among patients with addictions, paranoid personality disorder should also be considered in addition to the importance of antisocial and borderline personality disorders. The higher frequency of the bp 279 DRD5 VNTR allele found in patients with paranoid personality disorder, as well as the associations between alleles of the MAOB VNTR and antisocial personality disorder, support the monoaminergic bases of these personality disorders, especially when dealing with patients with addictions.


Space-resolved average kinetic energy of ion swarms in a uniform electric field.
A pulse of noninteracting charged particles in an unbounded gas, exposed to a low, constant, homogeneous electric field, was studied in both space and time using a Monte Carlo simulation technique. The difference in electrical potential between the leading and trailing edges of the swarm results in the space-resolved average ion kinetic energy becoming a linearly increasing function of space. This Letter analyzes whether the average ion kinetic energy at the leading edge reaches a stationary value during the spatiotemporal evolution of the swarm, as has been considered so far. When the swarm's mean kinetic energy reaches a steady-state value, indicating that an energy balance is established over time, the gains (from the field) and losses (due to collisions) are nonuniform across space. The local power balance is negative at the front of the swarm and positive at the tail. Cooling the ions at the front and heating the ions at the tail results in a decrease in the average ion kinetic energy at the front and an increase at the tail. Thus, it can be concluded that stationary values of average ion kinetic energy do not exist at the leading and trailing edges during the evolution. Instead, they tend to approach the swarm's mean kinetic energy as t→∞.


Monitoring of styrene oligomers as indicators of polystyrene plastic pollution in the North-West Pacific Ocean.
Styrene oligomers (SOs) as global contaminants are an environmental concern. However, little is known on the distribution of SOs in the ocean. Here, we show the distribution of anthropogenic SOs generated from discarded polystyrene (PS) plastic monitored from the coastal ocean surface waters (horizontal distribution) and deep seawaters (vertical distribution) in the North-West Pacific Ocean. SOs concentrations in surface seawater and deep seawater ranged from 0.17 to 4.26 μg L-1 (total mean: 1.48 ± 1.23 μg L-1) and from 0.31 to 4.31 μg L-1 (total mean: 1.32 ± 0.87 μg L-1), respectively. Since there is no significant difference in the mean concentrations, SOs seems to be spread across marine environment selected in this study. Nevertheless, regional SOs appears to persist to varying degrees with their broad horizontal and vertical distribution in the ocean. Each horizontal and vertical distribution of SOs differs by approximately 1.95-2.57 times, probably depending on the events of weather and global ocean circulation. These results provide the distribution pattern of SOs for assessing environmental pollution arising from PS plastic.


Assessment of occupational exposure from shielded and unshielded syringes for clinically relevant positron emission tomography (PET) isotopes-a Monte Carlo approach using EGSnrc.
18F has been the most widely used radionuclide in positron emission tomography (PET) facilities over the last few decades. However, increased interest in novel PET tracers, theranostics and immuno-PET has led to significant growth in clinically used positron-emitting radionuclides. The decay schemes of each of these radioisotopes are markedly different from18F, with different endpoint energies for the emitted positrons and, in some cases, additional high energy gamma radiation. This has implications for the occupational exposure of personnel involved in the manipulation and dispensing of PET radiopharmaceuticals. The EGSnrc Monte Carlo simulation software was used to estimate the doses to extremities in contact with unshielded and shielded syringes containing64Cu,18F,11C,13N,15O,68Ga and89Zr, respectively. Dose rates at various distances from the syringe were also modelled, with dose rates reported in terms of eye (Hp(3)), skin equivalent (Hp(0.07)) and deep (Hp(10)) doses. The composition and geometry of the simulated syringe shields were based on a selection of commercially available PET shields. Experimental dose rate measurements were performed for validation purposes where possible. Contact skin dose rates for all isotopes, except for64Cu, were found to be higher than18F for the unshielded syringe. The addition of a shield resulted in approximately equal contact skin dose rates for nearly all isotopes, for each shield type, with the exception of89Zr which was notably higher. Dose rate constants (µGy/MBq.hr) for a range of PET isotopes and shields are presented and their significance discussed.


Nitrogenous chemicals generated from acidification of saliva influence transient lower oesophageal sphincter relaxations.
Saliva contains high concentrations of nitrite derived from the enterosalivary recirculation of dietary nitrate and its reduction by buccal bacteria. Acidic gastric juice converts the swallowed nitrite to varying proportions ofnitrous acid and nitric oxide (NO) depending upon ascorbic acid availability. Neuronally generated NO is the key in the pathway of transient lower oesophageal sphincter relaxations in vivo. Furthermore, in vitro NO and nitrous acid relax the smooth muscle of the stomach, lower oesophageal sphincter (LOS) and oesophageal body. The objective of this article was to determine whether luminal administration of NO or nitrous acid affects the generation of transient LOS relaxations following a meal. Fifteen healthy subjects were studied on three separate days. A manometry catheter was used to record oesophageal, LOS and gastric pressures, and two oesophageal pH probes were used to record reflux. One of three solutions was infused each day into the cardia after a standardized meal: 1) control solution ofhydrochloric acid pH 1.0, 2) nitrous acid and 3) nitrous acid plus ascorbic acid to generate NO. The solutions were randomized and double-blinded. The frequency of transient LOS relaxations was increased by the NO-generating solution at 5.2/h compared with both the control (3.5, p <0.01) and nitrous acid solution (3.1, p <0.0001). The NO-generating solution also increased oesophageal acid exposure to 62.2%, compared with both the control (37.5%, p <0.03) and nitrous acid solution (36.6%, p <0.002). Luminal NO at the gastro-oesophageal junction increases the generation of transient LOS relaxations following a meal. Chemicals generated by the acidification of salivary nitrite may contribute to gastro-oesophageal motility disorders.


Binding of ADP and ATP analogs to cross-linked and non-cross-linked acto X S-1.
We previously determined the binding constants of ADP, adenylyl imidodiphosphate (AMP-PNP), and inorganic pyrophosphate (PPi) to acto . myosin subfragment 1 (acto X S-1) by measuring the dissociation of acto X S-1 as a function of ATP analog concentration (Greene, L.E., and Eisenberg, E. (1980) J. Biol. Chem. 255, 543-548). In the present study, we reinvestigated this question by measuring the extent to which these ATP analogs inhibit the acto X S-1 ATPase activity using both cross-linked actin X S-1 and non-cross-linked proteins. No significant difference was found between the cross-linked and non-cross-linked acto X S-1 complexes in their affinity for either ADP or AMP-PNP. The binding constant of ADP to acto X S-1 determined by the inhibition method was in excellent agreement with that obtained previously by the dissociation method, both techniques giving values of about 7 X 10(3) M-1. However, this was not the case for AMP-PNP and PPi, with the inhibition method giving about 10-fold weaker binding constants than those determined previously by the dissociation method. Upon redoing our dissociation experiments over a wider range of actin concentrations than we used previously, we now find that the dissociation method gives much weaker values for the binding constants of PPi and AMP-PNP to acto X S-1, i.e. values on the order of 4 X 10(2) M-1. The very weak binding of these ATP analogs to acto X S-1 makes it difficult to obtain these values with great accuracy. Nevertheless, they seem to be in good agreement with the binding constants determined by the inhibition method. The weak binding of AMP-PNP and PPi to acto X S-1 is consistent with the recent fiber studies of Pate and Cooke (Pate, E., and Cooke, R. (1985) Biophys. J. 47, 773-780) and Schoenberg and Eisenberg (Schoenberg, M., and Eisenberg, E. (1986) Biophys. J. 48, 863-872).


Expression of GC clusters in the yeast mitochondrial var 1 gene. Transcription into stable RNAs.
We have determined whether two 46-base pair (bp) GC-rich clusters present in the coding region of the yeast mitochondrial var 1 gene are transcribed and retained in the putative mRNA for the var 1 protein. One GC cluster is found in all var 1 alleles, while the other is optional; both are identical in sequence and, when present together in var 1, are arranged in opposite orientation 158 bp apart. Because of their dyad symmetry, these GC clusters would form stem and loop structures if present in RNA. We have exploited this potential for secondary structure to show that these GC clusters are transcribed. Using a 46-bp RsaI-MboI var 1 restriction fragment as primer and 16 S RNA (the putative var 1 mRNA (Farrelly, F., Zassenhaus, H. P., and Butow, R. A. (1982) J. Biol. Chem. 257, 6581-6587) purified from strains whose var 1 allele contains one or both of these GC clusters as template for AMV reverse transcriptase, we find the accumulation of a major class of cDNAs whose size is consistent with an impediment of reverse transcription at the predicted positions of the GC clusters in the RNA template. Moreover, depending upon the RNA template, we find that the small fraction of full length cDNA molecules made in the reaction contain one or two SstII sites. Because of fold-back, these sites are predicted to be present in the otherwise single-stranded cDNAs if the GC clusters are transcribed.


Self-powered molecular imprinted photoelectrochemical sensing platform of sialic acid employing WO3/Bi2S3 photoanode and CuInS2 photocathode.
A dual-photoelectrode molecular imprinted photoelectrochemical (PEC) sensor is first built for the determination of sialic acid (SA) without additional energy supply. Specifically, WO3/Bi2S3 heterojunction behaves as a photoanode to provide amplified and stable photocurrent for the PEC sensing platform, which is attributed to the matched energy levels of WO3 and Bi2S3 promoting the electron transfer and improving photoelectric conversion properties. CuInS2 micro-flowers functionalized by molecularly imprinted polymers (MIPs) are served as photocathode to recognize SA, avoiding the deficiency of high production cost and poor stability from biological enzymes, aptamers, or antigen-antibodies. The inherent deviation between the Fermi level of the photoanode and the photocathode guarantees a spontaneous power supply for the PEC system. Benefiting from the photoanode and recognition elements, the as-fabricated PEC sensing platform has a strong anti-interference ability and high selectivity. Moreover, the PEC sensor displays a wide linear range of 1 nM-100 μM and a low detection limit of 7.1 × 10-10 M (S/N = 3) based on the relationship between photocurrent signal and SA concentration. Accordingly, this research provides a new and valuable approach to detecting various molecules.


Bioactive peptides from fisheries residues: A review of use of papain in proteolysis reactions.
Papain is a cysteine endopeptidase of vegetal origin (papaya (Carica papaya L.) with diverse applications in food technology. In this review we have focused our attention on its application in the production of bio-peptides by hydrolysis of proteins from fish residues. This way, a residual material, that can become a contaminant if dumped without control, is converted into highly interesting products. The main bioactivity of the produced peptides is their antioxidant activity, followed by their nutritional and functional activities, but peptides with many other bioactivities have been produced. Thera are also examples of production of hydrolysates with several bioactivities. The enzyme may be used alone, or in combination with other enzymes to increase the degree of hydrolysis.


Human macrophages contain a stretch-sensitive potassium channel that is activated by adherence and cytokines.
A variety of stimuli, including cytokines and adhesion to surfaces and matrix proteins, can regulate macrophage function, in part through changes in Ca(2+)- dependent second messengers. While fluctuation in intracellular Ca2+ is an important modulator of cellular activation, little attention has been paid to the roles of other ions whose cytoplasmic concentrations can be rapidly regulated by ion channels. To examine the role of ion channels in macrophage function, we undertook patch clamp studies of human culture-derived macrophages grown under serum-free conditions. The major ionic current in these cells was carried by an outwardly rectifying K+ channel, which had a single-channel conductance of 229 pS in symmetrical K(+)-rich solution and macroscopic whole-cell conductance of 9.8 nS. These channels opened infrequently in resting cells but were activated immediately by (i) adhesion of mobile cells onto a substrate, (ii) stretch applied to isolated membrane patches in Ca(2+)-free buffers, (iii) intracellular Ca2+ (EC50 of 0.4 microM), and (iv) the cytokine IL-2. Furthermore, barium and 4-aminopyridine, blockers of this channel, altered the organization and structure of the cytoskeletal proteins actin, tubulin and vimentin. These cytoskeletal changes were associated with reversible alteration to the morphology of the cells. Thus, we have identified an outwardly rectifying K+ channel that appeared to be involved in cytokine and adherence-mediated macrophage activation, and in the maintenance of cytoskeletal integrity and cell shape.


A pair-wise meta-analysis highlights circular RNAs as potential biomarkers for colorectal cancer.
Circular RNAs (circRNAs) have emerged as a special subset of endogenous RNAs that are implicated in tumorigenesis and cancer progression. Herein we aim to carry out a meta-analysis to evaluate the clinicopathologic, diagnostic and prognostic significance of circRNA expression in colorectal cancer (CRC). A systematic search of online databases was performed for original articles published in English, which investigated the diagnostic accuracy, prognostic utility, and clinicopathologic association of circRNA(s) in CRC. Data were strictly extracted and study bias was judged using the Quality Assessment for Studies of Diagnostic Accuracy II (QUADAS II) and Newcastle-Ottawa Scale (NOS) checklists. A total of 13 studies, involving 1430 patients with CRC, were included in the meta-analysis. The clinicopathologic study showed that abnormally expressed circRNAs were correlated with tumor diameter (P = 0.0350), differentiation (P = 0.0038), lymphatic metastasis (P = 0.0119), distant metastasis (P < 0.0001), TNM stage (P = 0.0002), and depth of invasion (P = 0.001) in patients with CRC. The summary area under the curve (AUC) of circRNA for the discriminative efficacy between patients with and without CRC was estimated to be 0.79, corresponding to a weighted sensitivity of 0.77 [95% confidence interval (CI): 0.74-0.79], specificity of 0.67 (95%CI: 0.64-0.70), and diagnostic odds ratio (DOR) of 7.52 (95%CI: 4.66-12.12). Survival analysis showed that highly expressed circRNAs were correlated with significantly worse overall survival (OS) [hazard ratio (HR) = 2.66, 95%CI: 2.03-3.50, P = 0.000; X2 = 4.34, P = 0.740, I2 = 0.0%], whereas lower expression of circRNAs was associated with prolonged OS (weighted HR = 0.30, 95%CI: 0.17-0.53, P = 0.000; X2 = 1.34, P = 0.909, I2 = 0.0%). Stratified analysis in circRNA expression status, and test matrix also showed robust results. Abnormally expressed circRNAs may be auxiliary biomarkers facilitating CRC diagnosis, and promising prognostic biomarkers in predicting the survival of CRC patients.


Usefulness of Interleukin-18 as a Diagnostic Biomarker to Differentiate Adult-Onset Still's Disease With/Without Macrophage Activation Syndrome From Other Secondary Hemophagocytic Lymphohistiocytosis in Adults.
Interleukin (IL)-18 is markedly elevated in systemic inflammatory diseases that cause the 'cytokine storm' such as adult-onset Still's disease (AOSD) and hemophagocytic lymphohistiocytosis (HLH). The differences in IL-18 between AOSD and HLH, especially in adults, is uncertain. Macrophage activation syndrome (MAS), a form of secondary HLH, is often difficult to differentiate cases of AOSD that include MAS from other secondary HLH. In this case-control study, we investigated whether serum IL-18 levels could be a useful biomarker for the differential diagnosis of AOSD with or without MAS (AOSD group) and other secondary HLH in adults (adult HLH group). We enrolled 46 patients diagnosed with AOSD including 9 patients with MAS and 31 patients in the adult HLH group, which excluded AOSD-associated MAS. The clinical features and laboratory data were compared between the AOSD and adult HLH groups. In addition, we subdivided the AOSD group (with or without MAS) and the adult HLH group (whether lymphoma-associated or not) and compared the four groups. A logistic regression analysis was used to identify factors with high efficacy in differentiating the two groups, followed by a receiver operating characteristic (ROC) curve analysis to evaluate the differential diagnostic ability of IL-18. We analyzed the correlation between IL-18 and various laboratory parameters in the AOSD group. Serum IL-18 levels of patients in the AOSD groups were significantly higher than those of the adult HLH groups, and were closely correlated with ferritin, soluble interleukin-2 receptor (sIL-2R), and other laboratory data. Univariate and multivariate logistic regression analyses revealed that IL-18, sIL-2R, and 'arthralgia or arthritis' are independent factors useful in the differential diagnosis of AOSD from adult HLH. In the differential diagnosis of both groups, the area under the curve obtained from the ROC curve of IL-18 with a cutoff value of 18,550 pg/mL was 0.91 (95% confidence interval 0.83-1.00; sensitivity 90.3%, specificity 93.5%), and the differential diagnosis ability of IL-18 was superior to that of other laboratory data. IL-18 could be a useful biomarker for the differential diagnosis of AOSD and adult HLH.


A head-to-head comparison of the intra- and interobserver agreement of COVID-RADS and CO-RADS grading systems in a population with high estimated prevalence of COVID-19.
To evaluate the inter- and intraobserver agreement of COVID-RADS and CO-RADS reporting systems among differently experienced radiologists in a population with high estimated prevalence of COVID-19. Chest CT scans of patients with clinically-epidemiologically diagnosed COVID-19 were retrieved from an open-source MosMedData data set, randomised, and independently assigned COVID-RADS and CO-RADS grades by an abdominal radiology fellow, thoracic imaging fellow and a consultant cardiothoracic radiologist. The inter- and intraobserver agreement of the two systems were assessed using the Fleiss' and Cohen's κ coefficients, respectively. A total of 200 studies were included in the analysis. Both systems demonstrated moderate interobserver agreement, with κ values of 0.51 [95% confidence interval (CI): 0.46-0.56] and 0.55 (95% CI: 0.50-0.59) for COVID-RADS and CO-RADS, respectively. When COVID-RADS and CO-RADS grades were dichotomised at cut-off values of 2B and 4 to evaluate the agreement between grades representing different levels of clinical suspicion for COVID-19, the interobserver agreement became substantial with κ values of 0.74 (95% CI: 0.66-0.82) for COVID-RADS and 0.73 (95% CI: 0.65-0.81) for CO-RADS. The median intraobserver agreement was considerably higher for CO-RADS reaching 0.81 (95% CI: 0.43-0.76) compared with 0.60 (95% CI: 0.43-0.76) of COVID-RADS. COVID-RADS and CO-RADS showed comparable interobserver agreement, which was moderate when grades were compared head-to-head and substantial when grades were dichotomised to better reflect the underlying levels of suspicion for COVID-19. The median intraobserver agreement of CO-RADS was, however, considerably higher compared with COVID-RADS. This paper provides a comprehensive review of the newly introduced COVID-19 chest CT reporting systems, which will help radiologists of all sub-specialties and experience levels make an informed decision on which system to use in their own practice.


Androgens, oestrogens, and progesterone concentrations in wastewater purification processes measured with capillary electrophoresis.
A novel analytical-scale concept to improve reliability of detection and analysis of natural and processed wastewater samples from a purification plant was developed. A sequential sample clean-up system of polymer-based octadecyl and silane-based quaternary amine sorbents were used for concentrating human based steroid hormones and their metabolites and detecting them by UV absorption with capillary electrophoresis (CE). The water samples were collected from influent and effluent processes of the water purification plant in Helsinki, Finland.The CE methods were partial-filling micellar electrokinetic chromatography and capillary zone electrophoresis. The analysis times and method concentration levels were optimized with eight steroids at the range of 0.5-10 mg/L. Since in CE the detectable quantities were higher than the existing amounts in the process waters, the real samples needed matrix removal combined with steroid enrichment. After 20,000-fold concentration testosterone-glucoside, androstenedione, progesterone, and estradiol-glucoside could be determined in the process water samples. The amounts of individual steroids in influent and effluent waters were 0-429 and 0-207 ng/L, respectively. Correspondently, their total amounts were 735 and 212 ng/L with excellent in day and inter-day repeatability. The RSD values were less than 1, 9.7, and 19% in repeated analyses, calculated from 60 analyses during 24 h, and from 130 analyses during 15 months, respectively. The steroid removal in purification process was 65% on average. The solid particles separated in three steps during the water clean-up concept contained 9.8-45 ng/g steroids in combined dry precipitates.


Less is not necessarily more: low-dose corticosteroid therapy and long-term prognosis in generalized myasthenia gravis after thymectomy.
We investigated the efficacy of low-dose prednisolone (PSL) regimen in patients with generalized myasthenia gravis (MG) post-thymectomy and its correlation with long-term outcome. This is a 2-year observational study. The subjects were aged 16-75 years, a Myasthenia Gravis Foundation of America (MGFA) clinical classification of II to IV, generalized MG after thymectomy. We selected a low-dose (5 mg/day) initiation and slowly incrementing (10 mg every 4 weeks) PSL therapy regimen. We collected the clinical characteristics, treatment-related data, and 2-year clinical outcomes of MG patients, and analyzed the effect of various factors on the achievement of the treatment target. Sixty-three generalized MG were recruited in our study. After 2 years of observation, 52 patients (82.5%) of generalized MG achieved treatment goal. Based on the maximum daily dose of PSL received, the MG patients were divided into 20 mg, 30 mg, and ≥ 40 mg groups. Subgroup analysis showed that the 20 mg group had the highest rate of achieving the treatment target (94.9%), followed by the 30 mg group (73.3%) and the lowest rate was among the ≥ 40 mg group (44.4%). Using a multivariate logistic regression analysis, we identified that the maximum daily dose of PSL 20 mg was the only positive, independent predictor of treatment goal achievement after 2 years. Low-dose initiation, slowly incrementing PSL therapy is feasible for generalized MG patients after thymectomy. Early response to low-dose PSL therapy may predict better long-term outcomes.


A two-year drinking-water study of dichloromethane in rodents. II. Mice.
To investigate its carcinogenic potential, dichloromethane (DCM) was administered at levels of 0, 0, 60, 125, 185 and 250 mg/kg body weight/day to a total of 1000 B6C3F1 mice in deionized drinking-water for 104 wk. The high-dose male and female mice showed a transitory increase in mean leucocyte counts. Treatment-related toxic changes were noted in both male and female livers at the highest dose. There was a slight elevation of proliferative hepatocellular lesions in the treated males but no dose-related trend was apparent and the effect was absent in the females. Neoplastic lesions observed in the study were homogeneous among all groups and were within the range of incidence in historical controls. The results of this study demonstrated a toxicological no-observable-effect level (NOEL) for DCM of 185 mg/kg body weight/day in both sexes.


Women Have More Recurrences of Atrial Fibrillation than Men after Thoracoscopic Ablation and Suffer More from Established Risk Factors.
Atrial fibrillation (AF) is more prevalent in men than in women. However, women with AF are more symptomatic, have a worse quality of life, a higher stroke risk and may therefore benefit most from ablation. In this study we aim to identify the risk of recurrent AF after thoracoscopic ablation, and assess the differential impact of the risk factors for recurrence between women and men. This is a single center cohort study, including patients undergoing thoracoscopic ablation for advanced AF between 2008 and 2019. All patients were clinically followed up for two years with quarterly 24 h Holter monitoring and ECGs for the detection of recurrent AF. Left atrial appendage (LAA) tissue was collected for collagen analysis. We included 571 patients, of whom 143 (25%) were women. Women were older than men (63 ± 8.3 y vs. 59 ± 8.5, p < 0.001), but had fewer cardiovascular risk factors, myocardial infarctions (1.4% vs. 6.5%, p = 0.03) and, in particular, vascular disease (7.0% vs. 16.1%, p = 0.01). Women suffered more from AF recurrence, driven by more atrial tachycardias, and sex was an independent risk factor for recurrence (HR1.41 [1.04-1.91], p = 0.028]). The presence of vascular disease was associated with an increased risk for AF recurrence in women, but not in men. In LAA histology, women had more collagen than men, as had patients with persistent compared to paroxysmal AF. Women had 15% more recurrences, driven by more atrial tachycardias, which may be explained by a more fibrotic atrial substrate. What's new? Women undergoing thoracoscopic AF ablation have a higher risk of recurrent AF, driven by more atrial tachycardias. Among patients with left atrial enlargement or persistent AF, women have worse outcomes than men. Vascular disease was a risk factor for recurrence in women, but not in men. In a histopathologic analysis of the left atrial appendage, women had more collagen than men, as had patients with persistent compared to paroxysmal AF.


Triosephosphate isomerase tyrosine nitration induced by heme-NaNO2 -H2 O2 or peroxynitrite: Effects of different natural phenolic compounds.
Peroxynitrite and heme peroxidases (or heme)-H2 O2 -NaNO2 system are the two common ways to cause protein tyrosine nitration in vitro, but the effects of antioxidants on reducing these two pathways-induced protein nitration and oxidation are controversial. Both nitrating systems can dose-dependently induce triosephosphate isomerase (TIM) nitration, however, heme-H2 O2 -NaNO2 was less destructive to protein secondary structures and led to more nitrated tyrosine residue than 3-morpholinosydnonimine hydrochloride (SIN-1, a peroxynitrite donor). Both of desferrioxamine and catechin could inhibit TIM nitration induced by heme-H2 O2 -NaNO2 and SIN-1 and protein oxidation induced by SIN-1, but promoted heme-H2 O2 -NaNO2 -induced protein oxidation. Moreover, the antagonism of natural phenolic compounds on SIN-1-induced tyrosine nitration was consistent with their radical scavenging ability, but no similar consensus was found in heme-H2 O2 -NaNO2 -induced nitration. Our results indicated that peroxynitrite and heme-H2 O2 -NaNO2 -induced protein nitration was different, and the later one could be a better model for anti-nitration compounds screening.


CD21low B cells are predictive markers of new digital ulcers in systemic sclerosis.
The objective of this study was to evaluate the predictive role of CD21low B cells as markers of new digital ulcers in systemic sclerosis patients. Peripheral blood B cell subpopulations and clinical assessments have been evaluated in 74 systemic sclerosis patients at baseline and after a 12-month follow-up. After a 12-month follow-up, 23 (31.1%) systemic sclerosis patients developed new digital ulcers. The median percentage of CD21low B cells was significantly higher in patients with than without new digital ulcers [10.1 (4.3-13.6) versus 4.8 (3.5-7.4); p < 0.01]. The 10% cut-off shows good diagnostic accuracy [area under the curve (AUC) = 0.732, confidence interval (CI) = 0.587-0.878; P = 0.01]. Kaplan-Meier curves show a significantly reduced free survival from new digital ulcers in systemic sclerosis patients with CD21low B cells ≥ 10% (p < 0.0001). In multivariate analysis, CD21low B cells ≥ 10%, modified Rodnan skin score (mRSS) and systolic pulmonary arterial pressure (sPAP) are associated with the development of new digital ulcers. We hypothesize that CD21low B cells are a predictive marker of new digital ulcers in systemic sclerosis patients.


Recurrence and survival after neck dissections in cutaneous head and neck melanoma.
An important prognostic factor in head and neck melanoma is the status of the regional lymph nodes since the presence of metastatic disease in the nodes greatly aggravates the prognosis. There is no consensus on the surgical treatment algorithm for this group. Our aim was to study if there is a difference in nodal recurrence and survival after radical, modified or selective neck dissection. A total of 57 patients treated for regional meta-stases of head and neck melanoma were analysed retrospectively with respect to type of neck dissection, use of sentinel node biopsy, nodal recurrence and survival. After a median 127-month (range: 22-290) follow-up period, we showed that there was no significant difference in nodal recurrence between three different dissection groups (11% for radical node dissection, 24% for modified radical node dissection and 23% for selective node dissection, p > 0.05). No significant difference in five-year survival was observed between the dissection types (56% for radical node dissection, 61% for modified radical node dissection and 48% for selective node dissection, p = 0.613). Multivariate and univariate analysis revealed that patients with metastatic deposits in sentinel nodes had a better survival than patients with clinically palpable nodes (five-year survival rate: 70% versus 36%, p = 0.008). The extent of neck dissection does not significantly influence the rate of recurrence or survival. This study indicates that there is a survival benefit for patients who undergo completion lymph node dissection following a positive sentinel node biopsy. not relevant. not relevant.


Palliative Care, Patient-Reported Measures, and Outcomes in Hospitalized Patients With Cirrhosis.
Studies of palliative care (PC) in hospitalized patients with cirrhosis have been retrospective, with limited evaluation of patient-reported measures and outcomes. To examine the relationship between PC, patient-reported measures (quality of life and functional status), and outcomes. We performed a prospective cohort study of patients with cirrhosis hospitalized from 2014 to 2019. We recorded PC consultation details, quality of life (chronic liver disease questionnaire), and functional status (functional status questionnaire). Patients were followed for 90 days to assess readmissions, costs, and mortality. Seventy-four of 679 patients saw PC, often later in the hospitalization (median hospital day 8; IQR 4-16). Those who saw PC had greater Charlson comorbidity index (mean 6.8 vs. 5.9), MELD (mean 25 vs. 20), and prior 30-day admission (47% vs. 35%). Compared to those who did not see PC, PC patients had greater impairments in intermediate activities of daily living (83% vs. 72%), social activity (72% vs. 59%), quality of interactions (49% vs. 36%), abdominal symptoms (mean score 3.1 vs. 3.6), activity (mean 3.3 vs. 3.6), and overall quality of life (mean 3.6 vs. 3.8). PC was associated with fewer transfusions and upper endoscopies and with greater completion of advanced directives. After multivariable adjustment, PC was not associated with intensive care, 30-day readmissions, 90-day costs, or mortality. PC occurs infrequently and late in those with more severe liver disease and functional impairment. PC may be associated with reduction in utilization and greater completion of advanced directives. Randomized trials are needed to evaluate PC for this population.


Medical cannabinoids: a pharmacology-based systematic review and meta-analysis for all relevant medical indications.
Medical cannabinoids differ in their pharmacology and may have different treatment effects. We aimed to conduct a pharmacology-based systematic review (SR) and meta-analyses of medical cannabinoids for efficacy, retention and adverse events. We systematically reviewed (registered at PROSPERO: CRD42021229932) eight databases for randomized controlled trials (RCTs) of dronabinol, nabilone, cannabidiol and nabiximols for chronic pain, spasticity, nausea /vomiting, appetite, ALS, irritable bowel syndrome, MS, Chorea Huntington, epilepsy, dystonia, Parkinsonism, glaucoma, ADHD, anorexia nervosa, anxiety, dementia, depression, schizophrenia, PTSD, sleeping disorders, SUD and Tourette. Main outcomes and measures included patient-relevant/disease-specific outcomes, retention and adverse events. Data were calculated as standardized mean difference (SMD) and ORs with confidence intervals (CI) via random effects. Evidence quality was assessed by the Cochrane Risk of Bias and GRADE tools. In total, 152 RCTs (12,123 participants) were analysed according to the type of the cannabinoid, outcome and comparator used, resulting in 84 comparisons. Significant therapeutic effects of medical cannabinoids show a large variability in the grade of evidence that depends on the type of cannabinoid. CBD has a significant therapeutic effect for epilepsy (SMD - 0.5[CI - 0.62, - 0.38] high grade) and Parkinsonism (- 0.41[CI - 0.75, - 0.08] moderate grade). There is moderate evidence for dronabinol for chronic pain (- 0.31[CI - 0.46, - 0.15]), appetite (- 0.51[CI - 0.87, - 0.15]) and Tourette (- 1.01[CI - 1.58, - 0.44]) and moderate evidence for nabiximols on chronic pain (- 0.25[- 0.37, - 0.14]), spasticity (- 0.36[CI - 0.54, - 0.19]), sleep (- 0.24[CI - 0.35, - 0.14]) and SUDs (- 0.48[CI - 0.92, - 0.04]). All other significant therapeutic effects have either low, very low, or even no grade of evidence. Cannabinoids produce different adverse events, and there is low to moderate grade of evidence for this conclusion depending on the type of cannabinoid. Cannabinoids are effective therapeutics for several medical indications if their specific pharmacological properties are considered. We suggest that future systematic studies in the cannabinoid field should be based upon their specific pharmacology.


[Studies into bacterial gynecological infections, with particular reference to anaerobic and micro-aerophile germs (author's transl)].
Reported in this paper are 50 pyogenic infections, with anaerobic germs being cultured in 40,7 per cent of the cases, as well as 105 examinations of patients with flour, with Haemophilus vaginalis having been isolated in 20 cases. Widespread occurrence of such pathogens and severity of infections caused by such bacteria call for close cooperation between clinical practitioners and microbiologists, as no safe diagnosis is practicable without involvement of the latter. Reference is made to possible therapies, using chloremphenicol and metronidazole.


Sodium transport by isolated bullfrog small intestine. Effect of prostaglandin E1.
Addition of 446 micron prostaglandin E1 (PGE1) to the serosal medium of isolated short-circuited bullfrog small intestine elicited small increases transmural potential difference and short-circuit current while addition of PGE1 to the mucosal medium caused no change in the electrical parameters. Addition of 100 micron indomethacin to the mucosal medium inhibited both potential difference and short-circuit current with a resultant increase in steady-state tissue resistance. In the presence of mucosal 100 micron indomethacin, serosal 60 micron PGE1 markedly stimulated transmural potential difference and short-circuit current with a resultant decrease in steady-state tissue resistance. Serosal arachidonic acid (330 micron) stimulated transmural potential difference and short-circuit current and this effect was abolished by the addition of 100 micron indomethacin to the mucosal medium. Serosal 60 micron PGE1 only stimulated the M (mucosa) leads to S (serosa) unidirectional flux of sodium. These results strongly suggest that the PGE1 action is mediated either via a series of metabolic reactions which possibly increase the permeability of the mucosal membrane to sodium or via direct stimulation of rheogenic sodium pump activity.


Tension-type headache: classification and diagnosis.
Tension-type headache (TTH) is the most prevalent form of primary headache in the general population. In this article, the diagnostic challenges of TTH are discussed. The classification of these headaches according to the second edition of the International Classification of Headache Disorders (ICHD-2) and the main differences between the ICHD-2 and the first edition of the classification (ICHD-1, 1988) are discussed. The typical features of TTH also are highlighted. Finally, the differential diagnosis of episodic and chronic TTH, emphasizing the situations more likely to raise doubts, is discussed. The wide clinical spectrum of TTH frequently challenges the physician's diagnostic acumen. A structured approach to the patient and a better comprehension of this variability of presentation should translate into better quality of care and a more specific diagnosis for TTH sufferers.


Analysis of antiproliferative effect of Chamerion angustifolium water extract and its fractions on several breast cancer cell lines.
To evaluate the antiproliferative effect of the aerial part of Chamerion angustifolium (L.) Holub. (Onagraceae) extract and its fractions in vitro. This is the first study on the anti-proliferative effect of C. angustifolium on 3 distinct breast cancer cell lines. Breast cancer cell lines MCF7, MDA-MB-468 and MDA-MB-231 were exposed to different concentrations of the water extract of C. angustifolium, where DPPH radical scavenging activity was 0.018-0.443mg/ml, expressed in rutin equivalents. Cell growth was analyzed after 24, 48 and 72h of incubation. Solid-phase extraction was applied for the fractionation of C. angustifolium water extract and MDA-MB-468 cell line growth was tested using different fractions. The concentrations corresponding to radical scavenging activity of 0.117 and 0.266mg/ml caused MCF7 cells growth inhibition, while in the samples exposed to the highest concentration (0.355 and 0.443mg/ml) no proliferation was register, suggesting cell death. MDA-MB-468 cell analysis showed similar responses. MDA-MB-231 demonstrated cell growth inhibition following the exposure to all analyzed high extract doses (0.117-0.443mg/ml). MDA-MB-468 cells were selected to evaluate the effect of fractions. In the samples exposed to the fraction containing the highest amount (91%) of oenothein B, at the concentration of 0.117mg/ml a pronounced cell growth inhibition while at higher concentrations (0.266 and 0.443mg/ml) no cell proliferation was observed. The consumption of C. angustifolium herb can be advantageous, alongside with conventional breast cancer treatment.


Efficacy of Probiotics in Rheumatoid Arthritis and Spondyloarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
We aimed to provide a systematic review and meta-analysis of randomized controlled trials assessing the effect of probiotics supplementation on symptoms and disease activity in patients with chronic inflammatory rheumatic diseases (rheumatoid arthritis (RA), spondylarthritis (SpA), or psoriatic arthritis). A systematic literature review and meta-analysis from RA and SpA randomized controlled trials were conducted searching for articles in MEDLINE/PubMed and abstracts from recent international rheumatology meetings. The control group was a placebo or another dietary intervention. The risk of bias of the selected studies was evaluated using the Cochrane Collaboration tool and the Jadad scale. The initial search yielded 173 articles. Of these, 13 studies were included in the qualitative synthesis, 8 concerning a total of 344 RA patients and 2 concerning a total of 197 SpA patients. Three meta-analyses were also analyzed. Probiotic strains and quantities used were different among trials (5 studies using Lactobacillus sp., 1 trial Bacillus coagulans and the others a mix of different probiotic strains). Time to assess response ranged from 8 weeks to one year. Two studies associated probiotic supplementation with a dietary intervention. Meta-analysis showed a statistically significant decrease of C-reactive protein (CRP) concentration (mean difference (MD)) -3.04 (95% CI -4.47, -1.62) mg/L, p < 0.001; I2 = 20%, n patients = 209) with probiotics in RA. However, after excluding high-risk-of-bias trials of meta-analysis, there was no difference between probiotics and placebo on DAS28 (standard MD -0.54; 95% CI -1.94 to 0.85, p = 0.45, I2 93%, n patients = 143). The two studies on SpA patients showed no efficacy of probiotics. Probiotic supplementation might decrease RA activity with a moderate decrease effect on CRP, but lack of evidence and studies' heterogeneity do not allow us to propose them to patients with inflammatory arthritis to control their disease. Further RCTs are required in the future to determinate the efficacy of probiotics and the optimal administration design.


KRAS-dependent cancer cells promote survival by producing exosomes enriched in Survivin.
Mutations in KRAS frequently occur in human cancer and are especially prevalent in pancreatic ductal adenocarcinoma (PDAC), where they have been shown to promote aggressive phenotypes. However, targeting this onco-protein has proven to be challenging, highlighting the need to further identify the various mechanisms used by KRAS to drive cancer progression. Here, we considered the role played by exosomes, a specific class of extracellular vesicles (EVs) derived from the endocytic cellular trafficking machinery, in mediating the ability of KRAS to promote cell survival. We found that exosomes isolated from the serum of PDAC patients, as well as from KRAS-transformed fibroblasts and pancreatic cancer cells, were all highly enriched in the cell survival protein Survivin. Exosomes containing Survivin, upon engaging serum-starved cells, strongly enhanced their survival. Moreover, they significantly compromised the effectiveness of the conventional chemotherapy drug paclitaxel, as well as a novel therapy that combines an ERK inhibitor with chloroquine, which is currently in clinical trials for PDAC. The survival benefits provided by oncogenic KRAS-derived exosomes were markedly reduced when depleted of Survivin using siRNA or upon treatment with the Survivin inhibitor YM155. Taken together, these findings demonstrate how KRAS mutations give rise to exosomes that provide a unique form of intercellular communication to promote cancer cell survival and therapy resistance, as well as raise interesting possibilities regarding their potential for serving as therapeutic targets and diagnostic markers for KRAS-dependent cancers.


Rapid detection of cadmium ions in meat by a multi-walled carbon nanotubes enhanced metal-organic framework modified electrochemical sensor.
This work presents an electrochemical device based on a composite modification of amine functionalized Zr(IV) metal-organic framework (UiO-66-NH2) and multi-walled carbon nanotubes (MWCNTs) for voltammetry determination of cadmium ions (Cd2+). The UiO-66-NH2@MWCNTs composites were prepared by one-pot hydrothermal reaction. The prepared sensor performs excellent performance, which was attributed to the synergism between UiO-66-NH2 with a special octahedral structure and enlarged surface area and MWCNTs with outstanding conductivity. Under optimal experiment condition, the fabricated sensor showed good linear relationship from 0.5 to 170 μg/L, with a detection limit of 0.2 μg/L. Finally, the sensor was successfully applied to detect Cd2+ in meat samples (N = 21) with relative standard deviation (RSD) lower than 4.5% and recovery of 95.1-107.5%, and the results were compared with certified method, there was no statistical significance difference between the developed sensor and certified method at a 95% confidence level.


Inhibition of gliding movement by calcium in doublet microtubules on Tetrahymena ciliary dyneins in vitro.
We examined the effects of Ca ions on the gliding movement of Tetrahymena ciliary doublet microtubules induced by 14S or 22S dyneins in an in vitro motility assay system. The doublet microtubule appeared as circular-arc in solution, about 5 to 6 microns in length [1]. The doublet microtubules glided distal-end first on a 14S or 22S dynein-coated glass surface either clockwise or counterclockwise following the addition of ATP. The diameter of the circular path changed according to Ca concentration in the solution. Gliding velocity was from 1 to 5 microns/s. The addition of 0.1% Nonidet P-40 was necessary to induce the gliding movement on 22S dynein. This movement on 22S dynein was strongly inhibited above 0.5 mM ATP in the presence of 10(-9) M Ca, and at 0.05 to 1 mM ATP in the presence of 10(-3) M Ca. Many studies have indicated that Ca ions regulate ciliary movement [2-8] in which dyneins and doublet microtubule in the axoneme may play an essential role. The inhibition of the gliding movement of doublet microtubule on dyneins at appropriate concentrations of Ca and ATP as observed in this study may be the key for understanding Ca regulation of ciliary motility.


Time domain double slit interference of electron produced by XUV synchrotron radiation.
We present a new realization of the time-domain double-slit experiment with photoelectrons, demonstrating that spontaneous radiation from a bunch of relativistic electrons can be used to control the quantum interference of single-particles. The double-slit arrangement is realized by a pair of light wave packets with attosecond-controlled spacing, which is naturally included in the spontaneous radiation from two undulators in series. Photoelectrons emitted from helium atoms are observed in the energy-domain under the condition of detecting them one by one, and the stochastic buildup of the quantum interference pattern on a detector plane is recorded.


The influence of elevated levels of C-reactive protein and hypoalbuminemia on survival in patients with advanced inoperable esophageal cancer undergoing palliative treatment.
Inflammation perpetuates individual tumor progression resulting in decreased survival in cancer patients. The aim of our study was to evaluate the influence of elevated levels of C-reactive protein (CRP) as well as low levels of albumin on patients with inoperable esophageal carcinoma. The data of 218 patients with advanced esophageal cancer, who were treated at a single center within 12 years, were evaluated retrospectively. Patient's age, gender, body weight, dysphagia, plasma levels of CRP and albumin, the Glasgow Prognostic Score (GPS) combining both indicators, and survival were assessed for statistical evaluation. Thirty-nine (18.2%) had hypoalbuminemia and 161 (73.9%) had elevated CRP levels. Patients with hypoalbuminemia (P = 0.001) as well as patients with increased CRP levels (P = 0.001) showed a significantly shorter survival. Weight loss was correlated to elevated plasma CRP (P = 0.022), to diarrhea (P = 0.021), and to dysphagia (P = 0.008). Increasing GPS was significantly associated with poor survival (P = 0.001). Elevated CRP levels and hypoalbuminemia are significantly associated with reduced survival and are considered to be an appropriate predictor for poor outcome in advanced esophageal carcinoma. The GPS provides additional detailed prognostication and should be therefore taken into consideration when the individual palliative strategy has to be scheduled.


Calcium regulation in heart cells. The interaction of mitochondrial and sarcoplasmic reticulum with troponin-bound calcium.
A study has been carried out of the interaction of dog heart mitochondria and sarcoplasmic reticulum with Ca2+ bound to troponin or to its Ca2+-binding component (troponin-C). Both organelles are able to release more than 80% of the Ca2+ bound to the two proteins. However, sarcoplasmic reticulum is only able to do so in the presence of oxalate, whereas mitochondria are active also in the absence of permeant Ca-complexing anions. On the other hand, calcium uptake in heart mitochondria is severely inhibited by Mg2+. The results are discussed with reference to the problem of the control of Ca2+ in heart sarcoplasm.


The sympatomatic treatment of carcinoma of the bronchus using combination chemotherapy.
A study was made of chemotherapy for inoperable carcinoma of the bronchus. Only patients with symptoms directly due to the tumour or with evidence of rapid tumour growth were selected for treatment. Half the patients selected in this way responded and in these patients survival may have been prolonged. The regimen chosen caused the minimum of interference with the patient's life and, by relief of symptoms, appeared to offer an improvement in the quality of life.


Association of GST genotypes with age of onset and lymph node metastasis in oral squamous cell carcinoma.
Environment-gene interaction in oral carcinogenesis is well demonstrated by phase I and II enzymes that are involved in the metabolism of carcinogens. This study investigated the association of glutathione S-transferase (GST)T1 and GSTM1 genotypes of phase II enzyme genes with risk for, age of onset, and neck lymph node metastasis (LNM) in areca-associated oral squamous cell carcinoma (OSCC). A total of 114 OSCC male patients and 100 male controls were recruited. All subjects were areca users and tobacco smokers. DNA was obtained from peripheral blood samples. Genotyping of GSTT1 (non-null/null) and GSTM1 (non-null/null) was determined by polymerase chain reaction (PCR) analysis using specific primers that only amplify non-null alleles. No association was found between GST genotype and the risk of OSCC based on case-controls. Patients with the GSTT1 null genotype were older at onset (P = 0.03). Those with the GSTM1 null genotype had a higher incidence of neck LNM than those with the GSTM1 non-null genotype (P = 0.01). Patients with the GSTM1/GSTT1 null genotype appeared to have later onset and a higher incidence of neck LNM than those carrying the opposite genotype. The GST genotypes may be important markers for the age of onset and risk of metastasis in OSCC. The data also suggest that the various GST isoforms may be differentially involved in development or progression of OSCC.


Low charge density cationic polymers for gene delivery: exploring the influence of structural elements on in vitro transfection.
A series of end-functionalized poly(trimethylene carbonate) DNA carriers, characterized by low cationic charge density and pronounced hydrophobicity, is used to study structural effects on in vitro gene delivery. As the DNA-binding moieties are identical in all polymer structures, the differences observed between the different polymers are directly related to the functionality and length of the polymer backbone. The transfection efficiency and cytotoxicity of the polymer/DNA complexes are thus found to be dependent on a combination of polymer charge density and functionality, highlighting the importance of such structural considerations in the development of materials for efficient gene delivery.


Levels of human immunodeficiency virus type 1 RNA in cerebrospinal fluid correlate with AIDS dementia stage.
The relationship between the presence and severity of AIDS dementia complex (ADC) and the levels of human immunodeficiency virus type 1 (HIV-1) RNA in cerebrospinal fluid (CSF) were assessed. Nineteen patients with ADC (stages 1-3), 6 without ADC (group 1), and 10 (group 2) without ADC but with cryptococcal meningitis or progressive multifocal leukoencephalopathy were studied. There was a significant relationship between increasing CSF virus burden and ADC severity (P = .0006) but not with plasma burden and ADC severity. In group 2, CSF HIV-1 RNA levels in patients with cryptococcal meningitis were elevated. These results show that CSF HIV-1 RNA concentrations correlate well with ADC severity but may also be increased by central nervous system infections, such as cryptococcal meningitis.


Prolonged Microgravity Affects Human Brain Structure and Function.
Widespread brain structural changes are seen following extended spaceflight missions. The purpose of this study was to investigate whether these structural changes are associated with alterations in motor or cognitive function. Brain MR imaging scans of National Aeronautics and Space Administration astronauts were retrospectively analyzed to quantify pre- to postflight changes in brain structure. Local structural changes were assessed using the Jacobian determinant. Structural changes were compared with clinical findings and cognitive and motor function. Long-duration spaceflights aboard the International Space Station, but not short-duration Space Shuttle flights, resulted in a significant increase in total ventricular volume (10.7% versus 0%, P < .001, n = 12 versus n = 7). Total ventricular volume change was significantly associated with mission duration (r = 0.72, P = .001, n = 19) but negatively associated with age (r = -0.48, P = .048, n = 19). Long-duration spaceflights resulted in significant crowding of brain parenchyma at the vertex. Pre- to postflight structural changes of the left caudate correlated significantly with poor postural control; and the right primary motor area/midcingulate correlated significantly with a complex motor task completion time. Change in volume of 3 white matter regions significantly correlated with altered reaction times on a cognitive performance task (bilateral optic radiations, splenium of the corpus callosum). In a post hoc finding, astronauts who developed spaceflight-associated neuro-ocular syndrome demonstrated smaller changes in total ventricular volume than those who did not (12.8% versus 6.5%, n = 8 versus n = 4). While cautious interpretation is appropriate given the small sample size and number of comparisons, these findings suggest that brain structural changes are associated with changes in cognitive and motor test scores and with the development of spaceflight-associated neuro-optic syndrome.


Public Perceptions About Smart Cities: Governance and Quality-of-Life in Hong Kong.
This study analyzes public perceptions about the impact of 'smart cities' programs on governance and quality-of-life. With smart city scholarship focusing primarily on technical and managerial issues, political legitimacy remains relatively underexplored-particularly in non-Western contexts. Drawing on a Hong Kong-based survey of over 800 residents conducted in 2019, this study analyzes the results of probit regressions on dependent variables for governance (participation, transparency, public services, communication, and fairness) and quality-of-life (buildings, energy-environment, mobility-transportation, education, and health). Findings show more optimism about the impact of smart cities on quality-of-life than on governance. Awareness about the smart city concept associates positively with expectations about smart city benefits, but the effect is sensitive to education level and income. This study deepens understandings about the political legitimacy of smart cities, at a time when urban governments are accelerating investments in related technologies. More broadly, it adds contextual nuance to research about state-society relations and, at a practical level, supports policy recommendations to strengthen information and awareness campaigns, better articulate smart city benefits, and openly acknowledge limitations.


Long-term serum creatinine values after radical nephrectomy.
Both pre- and postnephrectomy levels of serum creatinine were measured in 52 consecutive patients who underwent radical nephrectomy for localized renal cell carcinoma between 1971 and 1976. At the time of follow-up, 17 patients were alive and 35 had died, 14 of renal cell carcinoma and 21 of other causes. Follow-up lasted a minimum of 115.5 months (mean 151.1 months, median 141.1, range 115.5-211.3 months) for 16 of the 17 patients who were alive. In this group only 2 patients had elevations in the serum creatinine level above 1.6 mg/dL-1.9 mg/dL and 2.4 mg/dL, respectively. The patient whose value was 2.4 mg/dL was a diabetic who required insulin. No serious renal failure, renal disease, or tumors in the contralateral kidney occurred among the total group of 52 patients. These data indicate that renal function remains adequate in patients who have a normal contralateral kidney and are treated by radical nephrectomy.


Quantitation and characterization of human megakaryocyte colony-forming cells using a standardized serum-free agarose assay.
Human progenitors of the megakaryocyte (Mk) lineage were detected by their ability to generate colonies-containing from 3 to > 100 Mk, detectable as glycoprotein IIb/IIIa+ cells in APAAP-stained whole mount agarose cultures. Optimal growth conditions were achieved through the use of a defined serum substitute and a suitable cocktail of recombinant cytokines. Under these culture conditions, the smallest Mk-containing colonies (CFC-Mk) were detectable within a week followed by colonies containing larger numbers of Mk over the ensuing 2 weeks. The total number of CFC-Mk at 18-21 d was linearly related to the number of cells plated. Variation in the cytokines added showed that thrombopoietin (TPO) or IL-3 alone would support the formation of large numbers of CFC-Mk. However, optimal yields of colonies containing cells of both Mk and non-Mk lineages required the addition of other growth factors, of which a combination of IL-3, IL-6, GM-CSF and Steel factor (SF) +/- TPO was the best of those tested. The further addition of erythropoietin to this combination reduced the number of large "pure' Mk colonies seen and in their place a corresponding number of mixed erythroid-Mk colonies became detectable. Flt3-ligand alone was unable to support the growth of CFC-Mk nor did it enhance their growth when combined with other factors. Plating of FACS-sorted sub-populations of CD34+ marrow cells in both serum-free agarose and methylcellulose assays demonstrated that most CFC-Mk are generated from CD34+ cells that are CD45RA- and CD71+, approximately half of which are CD41+. Thus, CFC-Mk are more similar to primitive clonogenic erythroid progenitors than to their granulopoietic counterparts in their expression of CD34, CD45RA and CD71. Taken together, these findings support the concept that some erythroid and Mk progenitors may share a common developmental pathway. The availability of sensitive and reproducible procedures for isolating and detecting human Mk progenitors should facilitate future investigations of their biology and role in a variety of haematological conditions.


Multi-omics study reveals associations among neurotransmitter, extracellular vesicle-derived microRNA and psychiatric comorbidities during heroin and methamphetamine withdrawal.
Despite decades of research in the field of substance withdrawal, molecular biomarkers and related mechanistic study have generally been lacking. In addition to known neurotransmitters, circulating miRNAs are found in small vesicles known as exosomes within blood that have diagnostic potential and are known to contribute to psychiatric disorders. The aim of this work was to characterize the changes in neurotransmitter and exosomal miRNA profiles during heroin and methamphetamine withdrawal using a cross-sectional study design, and to determine their associations to psychiatric comorbidities in a large group of patients with substance use disorders (SUDs). Using weighted gene co-expression network analysis, a series of known, conserved, and novel exosomal miRNAs were identified as being associated with the severity of anxiety and depression, as well as the concentrations of neurotransmitters GABA, choline, and serotonin. Bioinformatics analyses established that the differences in the miRNA profile target signaling pathways are significantly associated with developmental and intellectual abnormalities. Notably, a set of dysregulated miRNA signatures including hsa-mia-451a and hsa-mir-21a resulted in an AUC of 0.966 and 0.861, respectively, for predicting the patients with SUDs. Furthermore, hsa-miR-744a-5p was positively correlated with serotonin, and its important role in maintaining neuronal development and function was revealed using an in vitro human induced pluripotent stem cells derived neuronal model. Our results suggest that the miRNA content of circulating exosomes represent a biomolecular "fingerprint" of the progression of substance withdrawal and may uncover the putative mechanism of how these exosomal miRNAs contribute to psychiatric symptoms.


Chronic necrotizing pulmonary aspergillosis mimicking bronchocentric granulomatosis.
We present a case of slowly progressive Aspergillus infection occurring in a partially immunocompromised host. The histologic pattern mimicked bronchocentric granulomatosis as seen in allergic bronchopulmonary aspergillosis, but the clinical history, spread of disease in the face of steroid therapy, peculiar granulomatous response to the organisms, and large numbers of organisms present suggest that this was really a case of chronic necrotizing pulmonary aspergillosis. These entities must be distinguished because their therapy, prognosis, and clinical significance are totally different.


Exploring the dynamic nature of divalent metal ions involved in DNA cleavage by CRISPR-Cas12a.
CRISPR-Cas12a has been widely used in genome editing and nucleic acid detection. In both of these applications, Cas12a cleaves target DNA in a divalent metal ion-dependent manner. However, when and how metal ions contribute to the cleavage reaction is unclear. Here, using a single-molecule FRET assay, we reveal that these metal ions are necessary for stabilising cleavage-competent conformations and that they are easily exchangeable, suggesting that they are dynamically coordinated.


Engineering of bionic Fe/Mo bimetallene for boosting the photocatalytic nitrogen reduction performance.
The "FeMo cofactors" in biological nitrogenase play a decisive role in nitrogen reduction. Herein, a novel bionic Fe/Mo bimetallene was applied in photocatalytic nitrogen reduction. The surface coating Fe/Mo bimetallene of Bi2Mo0.3W0.7O6 (BMWO) nanocrystals could effectively promote the separation and transportation of photogenerated carriers by multi-electron redox reactions and deliver 2.8 times longer photo-carrier lifetime. Consequently, the nitrogen fixation activity of Fe/Mo bimetallene-coated BMWO nanocrystal photocatalyst was obviously enhanced (218.93 μmol g-1h-1), which was about 4.8 times that of unmodified BMWO nanocrystals. This work provides a novel approach to design bionic Fe/Mo bimetallene-modified inorganic semiconductor photocatalysts for nitrogen reduction.


An enhancement to the Maddox Wing test for the reliable measurement of horizontal heterophoria.
To attempt to improve the reliability of the Maddox Wing (MW) test for the measurement of horizontal heterophoria at near. Horizontal heterophoria measurements at 30 cm using the MW instrument were made on a group of 58 normally-sighted binocular young adult subjects. The procedures were repeated at each of five weekly visits. The standard tangent scale card provided by the instrument's manufacturer was used as the control condition vs four alternative cards designed to enhance accommodative stimulation and improve operational reliability. A statistically-similar mean near phoria value was recorded using each of the five cards. However one of the alternative card designs produced a small but statistically significantly less variable result than the others: this design featured a much smaller typeface (4pt) than that used for the digits on the standard card, and the horizontal row of numbers was flanked by two periods of a low spatial frequency (< 2 c deg(-1)) square wave grating. It is suggested that for improved reliability of near phoria measurement when using the MW instrument a more appropriately detailed design of tangent card would promote enhanced accommodation, an operational consideration likely to be especially relevant when examining children.


Autophagy in neuroinflammatory diseases.
Autophagy is a metabolically-central process that is crucial in diverse areas of cell physiology. It ensures a fair balance between life and death molecular and cellular flows, and any disruption in this vital intracellular pathway can have consequences leading to major diseases such as cancer, metabolic and neurodegenerative disorders, and cardiovascular and pulmonary diseases. Recent pharmacological studies have shown evidence that small molecules and peptides able to activate or inhibit autophagy might be valuable therapeutic agents by down- or up-regulating excessive or defective autophagy, or to modulate normal autophagy to allow other drugs to repair some cell alteration or destroy some cell subsets (e.g. in the case of cancer concurrent treatments). Here, we provide an overview of neuronal autophagy and of its potential implication in some inflammatory diseases of central and peripheral nervous systems. Based on our own studies centred on a peptide called P140 that targets autophagy, we highlight the validity of autophagy processes, and in particular of chaperone-mediated autophagy, as a particularly pertinent pathway for developing novel selective therapeutic approaches for treating some neuronal diseases. Our findings with the P140 peptide support a direct cross-talk between autophagy and certain central and peripheral neuronal diseases. They also illustrate the fact that autophagy alterations are not evenly distributed across all organs and tissues of the same individual, and can evolve in different stages along the disease course.


A comparison of 6-month outcomes between periacetabular osteotomy with concomitant hip arthroscopy to isolated hip arthroscopy for femoroacetabular impingement.
To compare early outcomes of periacetabular osteotomy (PAO) with concomitant hip arthroscopy to isolated hip arthroscopy for femoroacetabular impingement (FAI) and chondrolabral pathology using patient-reported outcomes measurement information system (PROMIS). Consecutive patients scheduled for PAO with concomitant hip arthroscopy (PAO + HA) or isolated hip arthroscopy (HA) between the ages of 15 and 30 years old were prospectively included in the study. Based on power analysis, subjects were recruited until there were 22 subjects in the PAO + HA group. These subjects were then gender matched to the HA group. The PROMIS, with six subscales and two global health measures, were completed during preoperative and 6-month follow-up visits. One-way ANOVA was performed to compare intake information of age, symptom duration, body mass index, and Beighton scores as well as preoperative and 6-month postoperative PROMIS scores between the PAO + HA and HA. 22 consecutive subjects undergoing PAO + HA were all females (average age 20.0 years) and matched to 22 consecutive females (average age 22.6) in the HA group. ANOVA did not find a significant difference between the two groups when comparing intact information, with exception of age (p = 0.04). A significant difference was also not identified (p ≥ 0.05) between the two groups on preoperative or 6-month postoperative PROMIS scores. The largest difference in 6-month postoperative scores between the two groups was 4.4 points on physical function subscale. Outcomes at 6 months were not significantly different when comparing PAO + HA to HA for FAI and chondrolabral pathology in females under 30 years of age. The more extensive surgery with a prolonged protective period associated with PAO do not seem to negatively impact outcomes at 6 months when compared to HA. These finding support the use of PAO + HA, particularly if the patient and/or surgeon were concerned about prolonged disability, metal health issues, and/or higher pain levels that might be associated with the PAO procedure.


Diffuse Cerebral Vasospasm After Removal of a Posterior Fossa Hemangioblastoma in a 62-Year-Old Woman.
The development of diffuse cerebral vasospasm after the removal of a brain tumor is extremely rare. We report a case of cerebral vasospasm after the removal of a posterior fossa hemangioblastoma. A 62-year-old woman presented with a 1-month history of vertigo and nausea. Neurologic examination revealed that she was alert, with no paresis, and a mild left-sided cerebellar ataxia. Contrast-enhanced magnetic resonance imaging showed a cystic lesion with a strongly enhancing nodule, measuring 20 × 26 mm in diameter, in the cerebellar dorsal vermis. Angiography revealed that the lesion had feeding arteries from the left posterior inferior cerebellar artery. A diagnosis of hemangioblastoma was suspected and surgery was performed. On the first postoperative day, paresis of the right-sided extremities occurred. Diffusion-weighted imaging showed a high-intensity area in the medial side of the left frontal lobe. Magnetic resonance angiography indicated diffuse cerebrovascular stenosis. Considering these findings to be caused by vasospasm, we started the treatment used for vasospasm secondary to aneurysmal subarachnoid hemorrhage. Magnetic resonance angiography on the 13th postoperative day revealed an improvement in the cerebrovascular stenosis. In this case, it appears that the cause of vasospasm was intraoperative spillage of the contents of the cyst. Although the occurrence of diffuse cerebral vasospasm after the removal of brain tumors in the posterior fossa is rare, this complication should be noted as a potential postoperative complication after tumor removal; this should lead to earlier diagnosis and treatment and a potentially better prognosis.


Telomere shortening during aging: Attenuation by antioxidants and anti-inflammatory agents.
Telomeres are a repeated sequence -of bases found at the ends of chromosomes. In humans, this sequence is TTAGGG, which is repeated over 2000 times. Telomeres protect the ends chromosomes from fusion with nearby chromosomes, and allow effective replication of DNA. Each time a cell divides, 25-200 base pairs are lost from the terminal sequence of chromosomes. By becoming truncated during cell division, telomeres protect essential genes from being shortened and thus inactivated. In addition, telomeres are sensitive to inflammation and oxidative stress, which can further promote telomere shortening. Reduction in the length of telomeres leads to the cessation of cell division and thus cellular senescence and apoptosis. This review discusses evidence for the role of oxidative stress and inflammation in regulating the length of telomeres in mammalian cells during senescence. Evidence is presented suggesting that antioxidants and anti-inflammatories can reduce the pace of shortening of telomere length during aging. The distinctive properties of transformed cells suggest that treatment with such materials will have a deleterious rather than a protective effect on such abnormal cells.


Clinicopathological characteristics and survival outcomes for patients with mucinous colorectal cancer liver metastases undergoing hepatic resection: A systematic review and meta-analysis.
Mucinous adenocarcinoma represents a distinct histological subtype of colorectal cancer. To date there has been limited data available for patients with colorectal cancer liver metastases (CRCLM) derived from mucinous adenocarcinoma. This systematic review and meta-analysis aims to provide data on the clinicopathological and survival outcomes of this cohort. Databases were searched for studies comparing clinicopathological and survival outcomes between patients with mucinous CRCLM and CRCLM from adenocarcinoma not otherwise specified who underwent liver resection. A random-effects model was used for analysis. Eight studies describing 9157 patients were included. Mucinous CRCLM were positively associated with colon tumors (OR 1⋅64, P = 0⋅01), T3/T4 tumors (OR 1⋅58, P = 0⋅02), node positive tumors (OR 1⋅55, P = 0⋅005). The review also identified a trend towards worse overall survival in patients with mucinous CRCLM. Despite the distinct clinicopathological characteristics and impaired long term outcomes of mucinous CRCLM, resection should remain the gold standard where possible.


NT-Pro BNP Predicts Myocardial Injury Post-vascular Surgery and is Reduced with CoQ10: A Randomized Double-Blind Trial.
NT-Pro BNP levels provide incremental value in perioperative risk assessment prior to major noncardiac surgery. Whether they can be pharmacologically modified in patients prior to an elective vascular operation is uncertain. A double-blind, randomized controlled trial was implemented at a single institution. Patients were screened during their preoperative vascular clinic appointment and randomly assigned to CoQ10 (400 mg per day) versus Placebo for 3 days prior to surgery. Biomarkers, including NT-Pro BNP, troponin I and C-reactive protein were obtained prior to and following surgery for up to 48 hours. The primary endpoint was postoperative NT-Pro BNP levels, and secondary endpoint measures included myocardial injury, defined by an elevated cardiac troponin level and length of stay. One hundred and twenty-three patients were randomized to receive either CoQ10 (N = 62) versus Placebo (N = 61) for 3 days before vascular surgery. Preoperative cardiac risks included ischemic heart disease (N = 52), CHF (N = 12), stroke (N = 23), and diabetes mellitus (N = 48) and the planned vascular procedures were infrainguinal (N = 78), carotid (N = 36), and intraabdominal (N = 9). There were no intergroup differences in these clinical variables. NT-Pro BNP levels (median; IQs) in the CoQ10 and Placebo groups were 179 (75-347) and 217 (109-585) pg/ml, respectively, (P = 0.08) preoperatively, and 397 (211-686) and 591 (288-1,433) pg/ml respectively, (P = 0.01) at 24 hours following surgery. Patients with an elevated NT-Pro BNP had a higher incidence of myocardial injury, (58% vs. 20%; P < 0.01) and a longer hospital stay (4.4 ± 3.8 vs. 2.8 ± 3.2 days; P < 0.02) compared with individuals without an elevated NT-Pro BNP level. NT-Pro BNP levels predict adverse events post-vascular surgery and are lowered in those patients assigned to preoperative administration of CoQ10. clinicaltrials.gov Identifier: NCT03956017. Among patients undergoing elective vascular surgery, 123 patients were randomized to either CoQ10 (400 mg/day) versus placebo for three days preoperatively. NT-Pro BNP levels (median; IQs) in the CoQ10 and Placebo groups were 179 (75-347) and 217 (109-585) pg/ml, respectively, (P = 0.08) preoperatively, and 397 (211-686) and 591 (288-1,433) pg/ml, respectively, (P = 0.01) post-surgery. Patients with an elevated NT-Pro BNP had a higher incidence of myocardial injury (58% vs. 20%; P < 0.01) and a longer hospital stay (4.4 ± 3.8 vs. 2.8 ± 3.2 days; P < 0.02) compared with individuals without an NT-Pro BNP elevation. In conclusion, BNP predicts adverse outcomes and can be reduced with preoperative CoQ10.


Automatic detection of fragile X chromosomes using an X centromere probe.
In order to score for the fragile X syndrome, blood samples are prepared with absorption stain labeling by in situ hybridisation of the X chromosome centromeres. Metaphases are located, digitised at high resolution, and segmented fully automatically. A three stage adaptive classification scheme for labeled X chromosomes is then applied. This consists of a simple box classifier to identify plausible X and false positive X chromosomes, followed by a quadratic discriminant classifier that is re-trained for each sample. The modal number of X chromosomes is then determined for each sample and used to refine the classification. A simple fragile site detector is applied to the distal portion of the detected X chromosome long arms. From the results we estimate computer and operator time requirements for a screening system in which the operator reviews only the apparently fragile X chromosomes detected by the computer.


An assessment of the current epidemiological and laboratory capacities for influenza-like illnesses and severe acute respiratory infection surveillance, Yemen 2022.
We aim to re-activate influenza sentinel surveillance system in Yemen after disruption related to repurposing for COVID-19 pandemic. WHO Country Office (CO) in collaboration with Yemen's Ministry of Public Health and Population (MOPH&P) jointly conducted an assessment mission to assess the current situation of the influenza sentinel surveillance system and assess its capacity to detect influenza epidemics and monitor trends in circulating influenza and other respiratory viruses of epidemic and pandemic potential. This study presents the results of the assessment for three sentinel sites located in Aden, Taiz, and Hadramout/Mukalla. A mixed methods approach was used to guide the assessment process and to help achieve the objectives. Data were collected as follows: desk review of the sentinel sites records and data; interviews with stakeholders, including key informants and partners; and direct observation through field visits to the sentinel sites, MOPH&P and the Central Public Health Laboratory (CPHL). Two assessment checklists were used: assessment of sentinel sites for SARI surveillance, and checklist for assessment of availability of SARI sentinel surveillance. COVID-19 has affected health systems and services, and this was demonstrated in this assessment. The influenza sentinel surveillance system in Yemen is not effectively functional; however, there is plenty of room for improvement if investment in the system's restructuring, training, building technical and laboratory capacities, and conducting continuous and regular supervision visits.


Comparison between single anterior and single posterior approaches of debridement interbody fusion and fixation for the treatment of mono-segment lumbar spine tuberculosis.
To compare the efficacy of single anterior and single posterior approach of debridement, interbody fusion, and fixation for the treatment of mono-segment lumbar spine tuberculosis (TB) patients. Eighty-seven patients with mono-segment lumbar TB who underwent debridement, interbody fusion, and fixation through either single anterior (Group A) or single posterior approach (Group B) from January 2007 to January 2017 were enrolled in this study. The duration of the operation, blood loss, complication rate, visual analog scale (VAS), Oswestry disability index (ODI), Frankel scale, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), kyphosis angle, correction rate, correction loss, and time taken for bone graft fusion were compared between the groups. The average period of follow-up was 34.3 ± 9.5 months (24-56 months). No significant differences were observed between patients in Group A and patients in Group B in terms of gender, age, body mass index (BMI), duration of illness and preoperative evaluative indices (P > 0.05). The mean operation time and blood loss was significantly higher in Group A (P = 0.000), along with a slightly higher rate of complications compared with Group B (P = 0.848). The VAS, ODI and Frankel scale scores showed significant improvement in both groups (P = 0.000), along with the ESR, CRP and kyphosis indices (P = 0.000), which were similar in both groups at the final follow-up. Both single anterior and single posterior approaches of debridement, interbody fusion and fixation are effective for mono-segment lumbar TB patients, although the single posterior approach is of a shorter duration and results in less blood loss.