The effect of bureaucratic corruption on household food insecurity: evidence from Sub-Saharan Africa.
Corruption is a worldwide phenomenon, but the crisis seems to have no bounds in Sub-Saharan Africa, where the absurdity has penetrated and continues to impair the public service sector. As long as the anomaly continues, two outcomes are inevitable. First, an average member of the public runs the risk of paying more for any government service. Second, some or all resources earmarked for other essential needs might get sacrificed to pay for a needed public service. Such unforeseen adverse shocks could potentially increase the chances of wicked problems such as food insecurity. Consequently, this paper examined the welfare effect of bureaucratic corruption on households' ability to procure food in a safe and socially acceptable manner in sub-Saharan Africa using pooled Afrobarometer micro-level data from Rounds 5, 6, and 7 spanning 2011 to 2018. Estimates from logistic regression and the endogenous dummy variable regression that addressed the endogeneity of bureaucratic corruption in the food insecurity model revealed that bureaucratic corruption induced the experience of household food insecurity. Further analyses showed that some public entities have a more significant debilitating effect than others on household food security conditions. More importantly, any contact with government institutions causes household food security status to spiral downward. These results suggest that public institutions in Sub-Saharan Africa are weak and undoubtedly contribute to household food insecurity. Therefore, there is a need for a paradigm shift in how these entities serve the public or else a lasting solution to food insecurity might remain elusive in the region.


Immunological profile of breast cancer patients in early or advanced disease.
Immune reactivity of patients with early or advanced breast cancer, compared with healthy controls, has been measured using in vivo and in vitro tests. The results of our study show that impairment of cellular responsiveness occurred in women with advanced disease.


DEAE-silica gel and DEAE-controlled porous glass as ion exchangers for isolation of glycolipids.
DEAE-silica gel and DEAE-controlled porous glass have been used for the quantitative isolation of gangliosides and neutral glycosphingolipids from animal tissues and cells. A direct comparative study between DEAE-silica gel, DEAE-controlled porous glass and DEAE-Sephadex was made; the results indicated that DEAE-silica gel is preferable to the other two ion exchangers. DEAE-silica gel has also been found to be suitable for the fractionation of ganglioside mixtures.


The immunosuppressive effect of Buchang-tang through inhibition of mitogen-activated protein kinase and nuclear factor activation in MOLT-4 cells.
Buchang-tang (BCT) has been known to suppress inflammatory and autoimmune responses. Accordingly, BCT has been clinically used in Korea as an immunomodulatory oriental medicine. Here, we report on the mechanism of action of BCT in activated MOLT-4 cells by determining the affected signaling pathways. BCT inhibits extracellular signal-regulated kinases (ERK)l/2 and p38 activation but does not interfere with phosphorylation of other mitogen-activated protein kinases, c-Jun NH2-terminal kinases 1/2 in MOLT-4 cells. The nuclear localization of nuclear factor of activated T cells 2 (NFATc) was blocked by BCT. Also, degradation of inhibitor kappaB-alpha and transactivation by nuclear factor-kappa B (NF-kappaB)/Rel A were impaired. Furthermore, interlukin (IL)-2 mRNA and protein levels were significantly diminished by BCT treatment. Our data indicate that BCT inhibits ERK1/2, p38 activation, nuclear translocation of NFATc, and NF-kappaB, resulting in diminished secretion of IL-2.


Combined segmental and focal adenomyomatosis involving the body of the gallbladder.
Adenomyomatosis (adenomyomatous hyperplasia) of the gallbladder is a benign process of unknown origin that has been classified into three morphologic types: diffuse, segmental, and focal (fundal). Cases of combined (segmental and focal) forms involving the gallbladder body are very rare. We present the sonographic findings of a case having adenomyomatosis of the gallbladder body with focal as well as segmental forms of the disease.


Female alternative mating tactics, reproductive success and nonapeptide receptor expression in the social decision-making network.
The decision to mate may be one of the most important decisions that animals make. For monogamous species, this decision can carry the added weight of limiting future mating opportunities. The mechanisms that govern these decisions have presumably been shaped by evolution in ways that optimize decision-making processes. In particular, a so-called social decision-making network (SDM) has been proposed, which integrates brain structures comprising the 'social behavior network' with a neural system associated with reward. Here, we investigate the neural phenotypic differences in the SDM for oxytocin and vasopressin receptors (OTR, V1aR) of female socially monogamous prairie voles living in naturalistic conditions. We focus on these receptors because they are profoundly involved in mammalian social behavior. We found that V1aR in the bed nucleus of the stria terminalis, medial amygdala and ventral pallidum, and OTR in the nucleus accumbens and hippocampus significantly differed between pregnant and non-pregnant females. Most of these areas are more closely related to the reward component of the SDM. V1aR in the ventral pallidum was also greater in paired than in single females. Finally, reproductive success within mating tactics was related to receptor density in brain structures across the SDM, particularly those serving as the interface between the social behavior network and the reward system. Our data support the hypothesis that neural phenotype for neuromodulatory nonapeptide receptors within the SDM relates to natural behavior associated with reproductive decisions.


Thiols and polyamines in the cytoprotective effect of taurine on carbon tetrachloride-induced hepatotoxicity.
The mechanism by which taurine (2-aminoethanesulfonic acid) protects hepatocytes injury induced by carbon tetrachloride (CCl4) is not fully understood. In a previous study, we reported that cellular polyamines play an important role in this mechanism. The relationship between cellular glutathione (GSH), protein-SH levels, and lactate dehydrogenase (LDH), with respect to the effect of polyamine on the cytoprotective ability of taurine in CCl4-induced toxicity in isolated rat hepatocytes, was examined. CCl4 induced a LDH release and decreased cellular thiols and polyamine levels. Treating with taurine reversed these depletions. The effect of CCl4 was also reversed by the addition of exogenous polyamines. Pretreating with alpha-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylase, which is a key enzyme in polyamine biosynthesis and therefore used to deplete cellular polyamine, prevented the protective effect of taurine. Adding diethyl maleate, a cellular glutathione-depleting agent, reduced the effect of exogenous polyamines. The role of polyamine in the cytoprotective effect of taurine in CCl4-induced toxicity may therefore be by preventing, among others, GSH and protein-SH depletions.


Plant-Derived Extracts Feed-Addition and Packaging Type Influence Consumer Sensory Perception of Pork.
This paper investigates whether the combination of the addition of extracts derived from plants (plants derived extracts, PDE) to pork feedstuff and the meat conservation conditions (packaging and time exposure) affect consumers' perception of pork quality, studied by means of visual appraisal, purchase intention and a home test. The three PDE groups were control, garlic extract and blended oil composed by carvacrol, timol, cynamic aldehide and eugenol extracts. Meat was packed in film, vacuum or modified atmosphere (MAP) packaging. A visual test was designed comprising a four-day storage step followed by a four-day exposure step in a refrigerated island display case. All studied effects influenced visual appraisal scores, being time exposure and packaging effects more noticeable than PDE or pig-sex effects. Meat from MAP scored higher than the rest. Scores decreased as exposure time increased, but this evolution was less perceptible in vacuum packaging and was faster for meat from the garlic group. Only gender affected the visual appraisal scores, with women scoring higher than men. Neither PDE addition nor pig sex affected to purchase intention whereas both exposure time and packaging type did. A maximum of 2 days of exposure would be recommended. In the home-test, meat from male pigs obtained higher scores than meat from female pigs, and none of the consumer-related effects influenced the given scores.


Characterization of an efficient dengue virus replicon for development of assays of discovery of small molecules against dengue virus.
Dengue virus (DENV) is a public health threat to approximately 40% of the global population. At present, neither licensed vaccines nor effective therapies exist, and the mechanism of viral RNA replication is not well understood. Here, we report the development of efficient Renilla luciferase reporter-based DENV replicons that contain the full-length capsid sequence for transient and stable DENV RNA replication. A comparison of the transient and stable expression of this RNA-launched replicon to replicons containing various deletions revealed dengue replicon containing entire mature capsid RNA element has higher replicon activity. An efficient DNA-launched DENV replicon, pCMV-DV2Rep, containing a full-length capsid sequence, was created and successfully applied to evaluate the potency of known DENV inhibitors. Stable cell lines harboring the DENV replicon were easily established by transfecting pCMV-DV2Rep into BHK21 cells. Steady and high replicon reporter signals were observed in the stable DENV replicon cells, even after 30 passages. The stable DENV replicon cells were successfully used to determine the potency of known DENV inhibitors. A high-throughput screening assay based on stable DENV replicon cells was evaluated and shown to have an excellent Z' factor of 0.74. Altogether, the development of our efficient DENV replicon system will facilitate the study of virus replication and the discovery of antiviral compounds.


Cardiovascular Magnetic Resonance in Heritable Cardiomyopathies.
Cardiovascular magnetic resonance represents the imaging modality of choice for the investigation of patients with heritable cardiomyopathies. The combination of gold-standard volumetric analysis with tissue characterization can deliver precise phenotypic evaluation of both cardiac morphology and the underlying myocardial substrate. Cardiovascular magnetic resonance additionally has an established role in risk-stratifying patients with heritable cardiomyopathy and an emerging role in guiding therapies. This article explores the application and utility of cardiovascular magnetic resonance techniques with specific focus on the major heritable cardiomyopathies.


Differential expression of cytokine genes in THP-1-derived macrophages infected with mild and virulence strains of Shigella flexneri 2a.
Shigella is an intracellular bacterial pathogen that causes bacterial dysentery called shigellosis. The assessment of pro- and anti-inflammatory mediators produced by immune cells against this bacteria are vital in identifying the effectiveness of the immune reaction in protecting the host. In Malaysia, Shigella is ranked as the third most common bacteria causing diarrheal disease among children below 5 years old. In the present study, we aim to examine the differential cytokine gene expressions of macrophages in response to two types of clinical strains of Shigella flexneri 2a (S. flexneri 2a) isolated from patients admitted in Hospital Universiti Sains Malaysia, Kelantan, Malaysia. THP-1-derived macrophages, as the model of human macrophages, were infected separately with S. flexneri 2a mild (SH062) and virulence (SH057) strains for 6, 12, and 24 h, respectively. The gene expression level of inflammatory mediators was identified using real-time quantitative polymerase chain reaction (RT-qPCR). The production of nitric oxide (NO) by the macrophages was measured by using a commercialized NO assay kit. The ability of macrophages to kill the intracellular bacteria was assessed by intracellular killing assay. Induction of tumor necrosis factor-alpha (TNFα), interleukin (IL)-1β, IL-6, IL-12, inducible NO synthase (iNOS), and NO, confirmed the pro-inflammatory reaction of the THP-1-derived macrophages in response to S. flexneri 2a, especially against the SH507 strain. The SH057 also induced a marked increase in the expression levels of the anti-inflammatory cytokine mRNAs at 12 h and 24 h post-infection. In the intracellular killing assay, both strains showed less viable, indicating the generation of pro-inflammatory cytokines in the presence of iNOS and NO was crucial in the stimulation of macrophages for the host defense against shigellosis. Transcription analysis of THP-1-derived macrophages in this study identifies differentially expressed cytokine genes that correlated with the virulence factor of S. flexneri 2a.


Brain abscess mimicking brain metastasis in breast cancer.
61 year old female presented with chief complaints of headache for 30 days, fever for 10 days, altered behavior for 10 days and convulsion for 2 days. She was diagnosed and treated as a case of carcinoma of left breast 5 years ago. MRI brain showed a lobulated lesion in the left frontal lobe. She came to our hospital for whole brain radiation as a diagnosed case of carcinoma of breast with brain metastasis. Review of MRI brain scan, revealed metastasis or query infective pathology. MR spectroscopy of the lesion revealed choline: creatinine and choline: NAA (N-Acetylaspartate) ratios of ∼1.6 and 1.5 respectively with the presence of lactate within the lesion suggestive of infective pathology. She underwent left fronto temporal craniotomy and evacuation of abscess and subdural empyema. Gram stain showed gram positive cocci. After 1 month of evacuation and treatment she was fine. This case suggested a note of caution in every case of a rapidly evolving space-occupying lesion independent of the patient's previous history.


Safety, tolerability, and pharmacokinetics of adamgammadex sodium, a novel agent to reverse the action of rocuronium and vecuronium, in healthy volunteers.
Neuromuscular blockers (NMBs) selectively block neuromuscular transmission at the N2-nicotinic receptor on motor neurons to paralyze skeletal muscles, and are mainly used to facilitate tracheal intubation and surgical procedures. Rapid reversal is necessary in clinical practice to avoid profound block and reduce recovery time. Adamgammadex sodium is a modified γ-cyclodextrin derivative consisting of a lipophilic core and a hydrophilic outer end that forms an inactive tight inclusion complex with free molecules of rocuronium and vecuronium. In preclinical study, adamgammadex produced a concentration-dependent reversion effect of neuromuscular blockade induced by rocuronium in beagle dogs. Furthermore, adamgammadex had a less potential side effects than sugammadex and other clinical used neuromuscular block antagonists. In this study, the objective was to assess the safety, tolerability, and pharmacokinetics of single intravenous injection of adamgammadex in healthy volunteers. Approved by the China Food and Drug Administration, 52 healthy volunteers (half male and half female) were enrolled in this single-center, randomized, double-blind placebo-controlled study. No serious adverse effects were happened in this study. The overall frequency of adverse effects in adamgammadex was similar for that in placebo, and there was no specific adverse effect in adamgammadex. All of the volunteers bearing the adverse effects were recovered to normal without any treatment or intervention. In pharmacokinetic study, the value of half-time, Tmax, and clearance were not changed significantly, and the Cmax and AUC0-∞ increased with a similar ratio of the escalating doses. For dose proportionality analysis of adamgammadex, the estimate of slope was close to 1, and it was not significantly different from 1 after doses (AUC0-∞, 0.9965 [90%CI, 0.9468, 1.046]; Cmax, 0.9462 [90%CI, 0.8800, 1.012]). Therefore, adamgammadex exposure in plasma increased in a dose- proportional manner. The urinary route is a significant excretory pathway for adamgammadex, and it is mostly completed at 8 h. All the results in this study showed that adamgammadex may be a novel safe neuromuscular blockade reversal agent .


Confident memory errors and disrupted reality testing in early psychosis.
Schizophrenia is a psychiatric disorder characterized by a disruption in reality testing most often manifest in the form of delusions and hallucinations. Because determining the reality-basis of prior experiences is dependent on episodic and associative memory, deficits in mnemonic processes could be involved in the genesis of impaired reality testing. In the present study, we used an associative memory paradigm incorporating confidence ratings to examine whether patients with a recent onset of schizophrenia (n = 48) show a greater propensity for confident, yet incorrect responses during retrieval testing than healthy controls (n = 26) and whether such confident incorrect responses, specifically, are more strongly associated with positive symptoms than with negative symptoms. Using an analysis of variance design, we found that first-episode schizophrenia patients made a significantly greater number of confident errors than controls (i.e. they expressed high confidence in having seen pairs of items that were not paired at encoding and high confidence in having not seen pairs of items that were paired at encoding). We also found that the number of confident errors was specifically and differentially associated with positive symptom severity, to a significantly greater degree than with negative symptom severity and psychosocial functioning, and this association was not found between positive symptoms and uncertain responses, nor positive symptoms and overall task performance. These findings suggest that the propensity for incorrect memory judgements with high confidence, specifically, may be uniquely associated with disrupted reality testing and that this type of cognitive impairment is distinct from general deficits in memory and cognition in this respect.


Analgesic Effects and Adverse Reactions of Lidocaine for Patient-Controlled Intravenous Analgesia on Patients Undergoing Open Hepatectomy: A Retrospective Analysis.
The aim of this study was to investigate the effect of lidocaine for patient controlled intravenous analgesia (PCIA) in patients who underwent open hepatectomy. A retrospective analysis. A total of 281 patients who underwent open hepatectomy from July 2018 to December 2018 were included. All patients were assigned into two groups: the lidocaine group (PCIA consisted of lidocaine, sufentanil, tramadol and granisetron) and the control group (PCIA consisted of sufentanil, tramadol and granisetron). The postoperative visual analogue scale (VAS) and complications (including respiratory depression, hypotension, nausea and vomiting, pruritus, numbness of the corners of the mouth, dizziness) between the groups were compared. There were no significant differences between the characteristics, duration of surgery and anesthesia, and recovery of postoperative activity between the two groups. In the first 3 days after the operation, the postoperative VAS score of the lidocaine group was lower than that of the control group at resting state, while after activity, the postoperative VAS contrast results were completely opposite. In particularly, the resting state at 48 hours (h) (1.05 ± 1.25 vs 1.57 ± 1.54) after surgery and the activity state at 72 h (3.02 ± 1.51 vs 2.2 ± 1.66) after surgery (P < 0.05). The incidence of mouth numbness and dizziness were significantly increased in the lidocaine group (P < 0.05). The addition of lidocaine in PCIA was not beneficial to improve the pain during activities and increased the incidence of perioral numbness and dizziness.


CYP2C19 slow metabolizer phenotype is associated with lower antidepressant efficacy and tolerability.
The inter-individual variability in CYP2C19-mediated metabolism may affect the antidepressant treatment. The aim of this study is to evaluate differences in antidepressant efficacy and tolerability between different CYP2C19 metabolizer categories in inpatients suffering from major depressive disorder. The cohort was divided into experimental groups based on CYP2C19 genotype and it contained 24 slow (SMs), 41 normal (NMs), and 37 fast metabolizers (FMs). Efficacy and tolerability were assessed at baseline, and after two and four weeks as a follow-up. The primary efficacy measurement was the change from baseline in Hamilton's Depression Rating Scale (HAMD), while the primary tolerability measurement was the Toronto Side-Effects Scale (TSES) intensity scores at the last visit. The reduction in HAMD score was 36% less pronounced and response rate was exceedingly less prevalent (75% lower) in SMs, compared with NMs. The TSES intensity score was increased in SMs, compared with NMs, by 43% for central nervous system and by 22% for gastrointestinal adverse drug reactions. No significant differences in measured parameters were observed between NMs and FMs. Compared with NM and RM, lower antidepressant efficacy and tolerability was observed in SMs; this association is likely connected with the lower SM capacity to metabolize antidepressant drugs.


In vitro synergy testing of levofloxacin, ofloxacin, and ciprofloxacin in combination with aztreonam, ceftazidime, or piperacillin against Pseudomonas aeruginosa.
The synergistic potential of levofloxacin, ofloxacin and ciprofloxacin combined with aztreonam, ceftazidime, or piperacillin was compared using 24 strains of Pseudomonas aeruginosa with varying susceptibility profiles. Levofloxacin and ciprofloxacin demonstrated similar in vitro activity, with ofloxacin demonstrating less activity compared to the other agents. Predominantly additive effects were seen with all combinations, with no significant differences detected between the fluoroquinolone agents.


Molecular structure, interactions, and antimicrobial properties of curcumin-PLGA Complexes-a DFT study.
Density functional calculations are performed to study the molecular structure, interactions, and antimicrobial activity of curcumin-poly lacto glycolic acid (Cur-PLGA) complexes. The calculations are performed on curcumin (Cur), glycolic acid (SSC and AAT conformers), lactic acid (LA), Cur-SSC, Cur-AAT, Cur-LA, and Cur-PLGA complexes using dispersion corrected M06-2X functional with 6-31 + G* basis set. The condensed Fukui functions of Cur are calculated to identify the favorable reactive sites. Inter- and intramolecular H-bond interactions are analyzed in detail through natural bond orbital, Atoms in Molecule, and Reduced density gradient analyses. The interaction energy values indicate that the interaction between Cur and AAT is stronger than the other studied complexes. Further, our calculations show that the PLGA interacted with Cur is having lower LUMO energy and density values. This indicates that the antimicrobial activity is high in this complex.


Impact of chronic psychosocial stress on autonomic cardiovascular regulation in otherwise healthy subjects.
Elevated psychosocial stress might favor the occurrence of cardiovascular disease; however, mechanisms are incompletely understood. We hypothesized that patients (n=126; 44+/-1 years of age) referred to an internal medicine clinic because of symptoms related to chronic psychosocial stress would demonstrate signs of autonomic dysregulation compared with controls (n=132; 42+/-1 years of age). We used autoregressive spectral analysis of RR interval variability to obtain indirect markers of sympathetic and of vagal (respectively, low-frequency and high-frequency components, both expressed in normalized units) oscillatory modulation of sinoatrial node, as well as of sympathetic vasomotor regulation (low-frequency component of systolic arterial pressure variability) and of cardiac baroreflex sensitivity (alpha-index). Higher values of systolic and diastolic arterial pressure (respectively, 124+/-1 versus 117+/-1 mm Hg and 80+/-1 versus 75+/-1 mm Hg; both P<0.001), altered markers of autonomic regulation (increased normalized low-frequency and reduced high-frequency component of RR variability, P<0.005; increased-low frequency component of systolic arterial pressure variability, P<0.002), and reduced baroreflex sensitivity (19.3+/-1.4 versus 23.0+/-2.0 ms/mm Hg; P<0.05) were observed in patients compared with controls. Autonomic responses to active standing were also blunted in stressed patients. Autonomic markers were significantly correlated to stress perception score and were capable of discriminating between controls and patients with a high degree of accuracy. Chronic real-life stress in humans appears associated to increased arterial pressure and to impaired autonomic regulation of cardiovascular functions. The combination of sympathetic predominance, vagal withdrawal, and blunted baroreflex sensitivity might represent a treatable mechanistic link between psychosocial factors and future incidence of hypertension.


Microarray detection of gene expression changes induced by 1,25(OH)(2)D(3) and a Ca(2+) influx-activating analog in osteoblastic ROS 17/2.8 cells.
1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) treatment of osteoblastic ROS 17/2.8 cells initiates membrane-initiated rapid responses through activation of Ca(2+) influx and longer-term nuclear receptor-mediated changes in gene expression. Ca(2+) influx triggers a change in the phosphorylation state of the bone matrix protein, osteopontin (OPN), detectable at 3 h and prior to nuclear receptor-mediated events. This study aimed to determine if Ca(2+) influx induced by 1,25(OH)(2)D(3) would produce nuclear receptor-independent changes in gene expression. We employed a rat cDNA microarray strategy to screen the transcriptional changes at 3 h of treatment with 1,25(OH)(2)D(3) and with an analog of 1,25(OH)(2)D(3) (25(OH)-16ene-23yne-D(3) [AT]) that we previously showed to activate Ca(2+) influx without binding to the nuclear receptor. Arrays also were screened with cDNA from ROS 17/2.8 cells treated for 24 h, when nuclear receptor-mediated transcriptional events would occur. Rat gene filters (GeneFilter, Research Genetics) were hybridized with labeled cDNA probes from treatment groups. Among 5000 different clones on the array filters, we identified a family of genes which were altered 2-fold or greater following treatment with 1,25(OH)(2)D(3) or analog AT for 3 h. Cluster analysis also revealed genes whose expression was significantly up-regulated at 24 h, including OPN. Analysis of rapid changes in gene expression revealed changes affecting a diverse range of cellular pathways and functions, including protein kinases and phosphatases, Ca(2+) signaling, cell adhesion and secretion. These findings provide clear evidence of rapid changes in gene expression associated with Ca(2+) influx mediated by 1,25(OH)(2)D(3), and shed light on the nuclear-receptor independent signaling pathway affecting OPN phosphorylation.


Modulation of pro-inflammatory and pro-resolution mediators by γ-linolenic acid: an important element in radioprotection against ionizing radiation.
The current study explored the radio-protective property of γ-linolenic acid (GLA) in C57BL/6J mice against low linear energy transfer ionizing radiation (IR; X-rays) and its modulatory effect on the production of lipid mediators such as prostaglandin E2 (PGE2), leukotriene E4 and lipoxin A4 (LXA4) in mice plasma. The effect of GLA pre-treatment on radiation induced inflammation was assessed by estimating plasma levels of high mobility group box 1 protein (HMGB1), TMOP/NO and various anti-oxidant enzymes. γ-linolenic acid pre-treated mice exposed to lethal IR dose (7.5 Gy) showed a decrease in plasma levels of HMGB1, PGE2 and LXA4 and a fall in TMOP/NO ratio and improvement in anti-oxidant enzymes: catalase, glutathione transferase and glutathione peroxidase compared to IR mice, suggesting that GLA suppresses IR-induced inflammation and restores the pro- vs. anti-oxidant ratio to near normal, which could explain its radioprotective action. GLA showed radioprotective action.


Ischnura elegans malikovae subspecies nova (Odonata, Coenagrionidae) from the Far East of Eurasia, with discussion of other possible subspecies.
Ischnura elegans malikovae ssp. n. is described from the southern Far East of Russia (type locality: Russia, Primorskiy Kray, Pozharskiy District, Luchegorsk Town, the Luchegorsk Reservoir). Reconsideration of literature suggested it to broadly range in East Asia including Korea, Japan (Hokkaido and northernmost Honshu), north and north-east China and to be hitherto mistaken for Ischnura elegans elegans (Vander Linden, 1820) in Japan. The main difference of the new subspecies from I. e. elegans is the male paraprocts that are about 1.5 times shorter and scarcely divaricating in dorsal view and directed obliquely upward in lateral view. Ischnura elegans ebneri Schmidt, 1938 is reconsidered as the presumably Anterior Asian subspecies characterised by scarcely or not diverging male paraprocts in dorsal view, versus strongly diverging in I. e. elegans. Based on scarce information in the literature, I. elegans marquardti Schmidt, 1938 is supposed to be a junior synonym of I. elegans ordosi Bartenev, 1912 stat. rev., which is suggested to be an eastern Central Asian subspecies characterised by an incised prothoracic process in males.


Cerebrospinal fluid levels of nitric oxide metabolites predict response to methylprednisolone treatment in multiple sclerosis and optic neuritis.
The role of nitric oxide (NO) in multiple sclerosis (MS) is not clear. We found increased cerebrospinal fluid concentrations of the NO degradation products nitrate (NO(x)) in clinically definite MS but not in clinically isolated syndromes. High CSF concentrations of NO(x) correlated with long attack duration. Patients carrying the truncated CC chemokine receptor allele CCR5 Delta32 had lower serum concentration of NO(x) at later attack stages. NO(x) concentrations did not change after methylprednisolone treatment but high concentrations were associated with more pronounced treatment responses. These findings suggest an association of high CSF levels of NO(x) with more severe disease activity in relapsing-remitting MS.


Werner syndrome diploid fibroblasts are sensitive to 4-nitroquinoline-N-oxide and 8-methoxypsoralen: implications for the disease phenotype.
The clinical phenotype of Werner Syndrome (WRN) includes features reminiscent of accelerated aging and an increased incidence of sarcomas and other tumors of mesenchymal origin. This syndrome results from mutations in the WRN DNA helicase/exonuclease gene. We found that WRN deficient primary fibroblasts, as well as lymphoblastoid cell lines (LCLs), show reduced proliferative survival in response to 4-nitroquinoline-N-oxide (4NQO) and 8-methoxypsoralen (8MOP), compared with WRN-proficient cells. This is the first demonstration of drug hypersensitivity in primary cells of mesenchymal origin from WRN patients. Notably, 8MOP-induced DNA interstrand crosslinks, but not 8MOP mono-adducts, produced S-phase apoptosis in WRN-deficient LCLs. In contrast, 8MOP did not induce S-phase apoptosis in WRN-deficient diploid fibroblasts, in which drug hypersensitivity was entirely due to reduced cell proliferation. Such reduced proliferation of damaged mesenchymal cells in WRN patients may lead to earlier proliferative senescence. In addition, failure of WRN-deficient mesenchymal cells to undergo apoptosis in response to DNA damage in S-phase may promote genomic instability and could help clarify the increased risk of sarcoma in WRN patients. Because interstrand crosslinks are believed to be repaired through homologous recombination, these results suggest an important role for WRN in recombinational resolution of stalled replication forks.


Effect of chemical drying agents on alfalfa hay and milk production response when fed to dairy cows in early lactation.
Third-cutting alfalfa hay cut at bud stage was treated with a drying agent consisting of potassium carbonate, sodium carbonate, and citric acid at the rate of 280.6 L/ha (1 kg/37.47 L water) to alternate swaths 4.27-m wide. Hay samples were taken at cutting and at 4-h intervals during daylight until baling was initiated. Twenty lactating Holstein cows were randomly assigned to untreated and treated alfalfa hay treatments in a switch-back design. Individual feed intakes and milk yields were recorded daily. Milk composition was analyzed once weekly. Drying rates were: .40 and .48% moisture/h for control and Na2-K2CO3-citrate treatments, respectively. There was no significant difference between treatments in feed composition parameters nor in vitro DM digestibility parameters. Cows fed the hay treated with Na2-K2CO3-citrate had a higher mean daily milk yield, adjusted for feed intake, compared with cows fed untreated hay (33.0 versus 32.5 kg/d). There were no significant differences in milk composition between treatments.


It is possible to classify non-erosive reflux disease (NERD) patients into endoscopically normal groups and minimal change groups by subjective symptoms and responsiveness to rabeprazole -- a report from a study with Japanese patients.
The hypothesis that non-erosive reflux disease (NERD) patients comprise various subgroups is gaining popularity. This study was conducted to investigate the possibility of categorizing NERD patients according to symptom types and response to acid-suppressive drug rabeprazole (RPZ) 10 mg/day. NERD patients were classified as grade N (endoscopically normal), M (minimal change), or erosive GERD, and answered a 51-item, yes-or-no questionnaire pre and post-treatment. Compared to erosive GERD, clear differences existed in pretreatment prevalence of symptoms and responsiveness to RPZ in grades N and M; the results suggested stomachaches (especially at night) were significant symptoms in grade N and dysmotility-like symptoms like bloated stomach were significant in grade M while gastroesophageal reflux symptoms were significant in erosive GERD. Clinical significance of classifying NERD was indicated from different symptoms and responsiveness to PPI.


MR imaging of spinal cord in Devic disease.
A 20-year-old man with typical features of Devic disease was studied with magnetic resonance (MR) demonstrating sequential changes of the spinal cord from swelling to atrophy. A good correlation between neurological findings and MR imaging was documented.


Atypical Neural Responses of Cognitive Flexibility in Parents of Children With Autism Spectrum Disorder.
Impaired cognitive flexibility has been repeatedly demonstrated in autism spectrum disorder (ASD). There is strong evidence for genetic involvement in ASD. First-degree relatives of individuals with ASD may show mild deficits in cognitive inflexibility. The present study investigated cognitive flexibility and its neuroelectrophysiological mechanisms in first-degree relatives of individuals with ASD to assess its potential familiality. Forty-five biological parents of individuals/children with ASD (pASD) and thirty-one biological parents of typically developing individuals/children (pTD), matched by gender, age, and IQ, were enrolled. The broad autism phenotype questionnaire (BAPQ) and cognitive flexibility inventory (CFI) were used to quantitatively assess autistic traits and cognitive flexibility in daily life, respectively. The task-switching paradigm was used to evaluate the behavioral flexibility in a structured assessment situation. Event-related potentials (ERPs) induced by this paradigm were also collected. Results showed that compared with the pTD group, the pASD group had lower CFI scores (t = -2.756, p < 0.01), while both groups showed an equivalent "switch cost" in the task-switching task (p > 0.05). Compared with the pTD group, the pASD group induced greater N2 amplitude at F3, F4, Fz, and C4 (F = 3.223, p < 0.05), while P3 amplitude and latency did not differ between the two groups. In addition, there was a significant negative correlation between the CFI total scores and BAPQ total scores in the pASD group (r = -0.734, p < 0.01). After controlling for age and IQ, the N2 amplitude in the frontal lobe of pASD was negatively correlated with the CFI total scores under the repetition sequence (r = -0.304, p = 0.053). These results indicated that pASD had deficit in cognitive flexibility at the self-reported and neurological levels. The cognitive flexibility difficulties of parents of children with ASD were related to autistic traits. These findings support that cognitive flexibility is most likely a neurocognitive endophenotype of ASD, which is worthy of further investigation.


Homecare Robots to Improve Health and Well-Being in Mild Cognitive Impairment and Early Stage Dementia: Results From a Scoping Study.
This scoping study is the first step of a multiphase, international project aimed at designing a homecare robot that can provide functional support, track physical and psychological well-being, and deliver therapeutic intervention specifically for individuals with mild cognitive impairment. Observational requirements gathering study. Semistructured interviews were conducted with 3 participant groups: (1) individuals with memory challenges, mild cognitive impairment (MCI), or mild dementia (patients; n = 9); (2) carers of those with MCI or dementia (carers; n = 8); and (3) those with expertise in MCI or dementia research, clinical care, or management (experts; n = 16). Interviews took place at the university, at dementia care facilities or other workplaces, at participant's homes, or via skype (experts only). Semistructured interviews were conducted, transcribed, and reviewed. Several key themes were identified within the 4 topics of: (1) daily challenges, (2) safety and security, (3) monitoring health and well-being, and (4) therapeutic intervention. A homecare robot could provide both practical and therapeutic benefit for the mildly cognitively impaired with 2 broad programs providing routine and reassurance; and tracking health and well-being. The next phase of the project aims to program homecare robots with scenarios developed from these results, integrate components from project partners, and then test the feasibility, utility, and acceptability of the homecare robot.


Associations Between Lifestyle Factors and Constipation Among Survivors After the Great East Japan Earthquake: A 9-year Follow-up Study.
Disaster survivors experience deterioration in lifestyles and an increase in constipation. After the Great East Japan Earthquake in 2011, some survivors were evacuated for a long term, even after moving to temporary housing and public reconstruction housing. However, annual changes in constipation and the association between lifestyles and constipation among the survivors are still unknown. Overall, 9,234 survivors aged 18 years or older participated in this 9-year follow-up survey after the disaster. Information about the prevalence of constipation and lifestyle factors (diet, physical activity, and mental health) was collected using a self-reported questionnaire. Their dietary intake was categorized into the following two dietary patterns: prudent (fish and shellfish, soybean products, vegetables, fruits, and dairy products) and meat (meat and eggs). Odds ratios for constipation according to lifestyle factors were calculated using a generalized linear mixed model. In women, the prevalence of constipation was the highest at baseline (8.7%) and remained around 5% afterward. In both men and women, older age, poor mental health, and poor physical activity were significantly associated with higher odds ratios of constipation. Moreover, a lower frequency of meals and a lower prudent dietary score were significantly associated with women's constipation. The prevalence of constipation was the highest at baseline and remained around 5% in women. Lifestyle factors, such as poor mental health, physical inactivity, and low frequency of meals were associated with constipation. Our findings suggest continuous support for the survivors with constipation for medium- to long-term after disasters.


Network Analysis of Anxiety Symptoms in Front-Line Medical Staff during the COVID-19 Pandemic.
This research analyses the relations between anxiety symptoms from the network perspective to deepen the understanding of anxiety in front-line medical staff during the COVID-19 pandemic and can also provide a reference for determining potential goals of clinical interventions. A convenience sampling was adopted, and the Generalized Anxiety Disorder 7-item scale (GAD-7) was administered to front-line medical staff through online platforms. A regularized partial correlation network of anxiety was constructed and then we evaluated its accuracy and stability. The expected influence and predictability were used to describe the relative importance and the controllability, using community detection to explore community structure. The gender-based differences and the directed acyclic graph were implemented. The connections between A1 "Feeling nervous, anxious or on edge" and A2 "Not being able to stop or control worrying", A6 "Becoming easily annoyed or irritable" and A7 "Feeling afraid as if something awful might happen", etc., were relatively strong; A2 "Not being able to stop or control worrying" and A3 "Worrying too much about different things" had the highest expected influence, and A2 "Not being able to stop or control worrying" had the highest predictability. The community detection identified two communities. The results of the gender network comparison showed the overall intensity of the anxiety network in women was higher than that in men; DAG indicated that A2 "Not being able to stop or control worrying" had the highest probabilistic priority; the lines from A2 "Not being able to stop or control worrying" to A1 "Feeling nervous, anxious or on edge" and A2 "Not being able to stop or control worrying" to A7 "Feeling afraid as if something awful might happen" represented the most important arrows. There exist broad interconnections among anxiety symptoms of front-line medical staff on the GAD-7. A2 "Not being able to stop or control worrying" might be the core symptom and a potential effective intervention target. It was possible to bring an optimal result for the entire GAD symptom network by interfering with A2 "Not being able to stop or control worrying". GAD may have two "subsystems". The modes of interconnection among anxiety may be consistent between genders.


Lethal and mutagenic effects photoinduced in haploid yeast (Saccharomyces cerevisiae) by two new monofunctional pyridopsoralens compared to 3-carbethoxypsoralen and 8-methoxypsoralen.
The photobiological effects of two monofunctional pyridopsoralens (PPs), pyrido[3,4-c]psoralen and pyrido[3,4-c]-7-methylpsoralen were studied and compared to those of 3-carbethoxypsoralen (3-CPs) and 8-methoxypsoralen (8-MOP) in a haploid wild-type strain of yeast (Saccharomyces cerevisiae). The capacity of PPs to photoinduce lethal effects in the presence of 365-nm radiation was not only higher than that of the monofunctional compound 3-CPs, but also higher than that of the bifunctional compound 8-MOP. This activity was apparently independent of oxygen, and it was found that it was probably due to the induction of monoadducts in DNA. A high effectiveness of PPs on the induction of cytoplasmic 'petite' mutations was observed suggesting a high photoaffinity towards mitochondrial DNA. In contrast to 8-MOP, the strong cell killing activity of PPs was not accompanied by a strong inducing effect on nuclear mutations (HIS+ reversions or canR forward mutations). For these endpoints, PPs were less effective per unit dose of 365-nm radiation and also less efficient per viable cell than 8-MOP. From this, it appears that the lesions photoinduced by the former compounds show a more lethal than (nuclear) mutagenic potential. Furthermore, the fact that PPs were even less mutagenic (nuclear) per viable cell than the monofunctional compound 3-CPs suggests that the activity of these agents may differ in frequency and nature of lesions induced. The photobiological activity of PPs in haploid yeast appears to be in line with the recent proposition for their use in photochemotherapy.


Fertility-enhancing hysteroscopic surgery; multi-center retrospective cohort study of reproductive outcome.
Hysteroscopic surgery and assisted reproduction technology are feasible ways to improve the reproductive outcome. Our aim was to study hysteroscopic septoplasty and myomectomy's effect on infertility and reproductive performance. Retrospective cohort of patients who had unexplained infertility and/or recurrent miscarriages and had myomectomy or septoplasty in the period September 2016-october 2021 with a total of 18 months' follow up. The main outcome measures were spontaneous pregnancy, term pregnancy and miscarriage. For analysis, we used Statistical Package for Social Sciences (SPSS) version 20. One hundred and sixty-five patients were included. The mean age of patients was 39 years. 40 patients had septum resection and 125 patients had hysteroscopic myomectomy. A spontaneous pregnancy rate after surgery was achieved in 46 patients (27.9%). Out of the 64 patients who had failed IVF preoperatively, 32 patients (50%) had a successful IVF post-hysteroscopic surgery and there were more successful cases in the patients who had fibroid resection but this difference did not reach a statistical significance (P value 0.055). In the 79 pregnancies after surgery, preterm birth and miscarriage were seen in 10 patients (12.7%), similarly, respectively after septal or fibroid resection. Miscarriages were less post-operatively. Hysteroscopic myomectomy, compared with hysteroscopic metroplasty, was significantly associated with higher spontaneous pregnancy rate (63.0% Vs 37.0%, P value 0.018), more term pregnancies (87.5% vs. 12.5%, P value 0.001) and less miscarriage rate (40%vs 60%, P value 0.003). Pregnancy post-operatively in patients with primary infertility was more statistically significantly associated with hysteroscopic myomectomy than with hysteroscopic septoplasty (95.8% vs. 4.2%, p value 0.030). In patients who got pregnant postoperatively there was no statistically significant difference in the mode of delivery. In carefully selected patients with unexplained infertility and recurrent miscarriage, hysteroscopic myomectomy, compared with hysteroscopic metroplasty, was significantly associated with higher spontaneous pregnancy, more term pregnancies and less miscarriage rates. More than metroplasty, hysteroscopic myomectomy led to higher spontaneous pregnancies in patients with primary infertility. NCT05560295.


Early morning awakening in unipolar depressives with higher levels of platelet MAO activity.
Platelet monoamine oxidase (MAO) activity was analyzed in 51 patients with Major Depressive Disorder. The enzyme activity was correlated univariately and multivariately using split-half techniques with affective subdiagnosis, sex, body measures, and a great many depressive symptoms. The results indicate that unipolarly depressed patients with higher levels of platelet MAO activity woke up earlier in the morning than they had before becoming depressed. Waking up early appeared to be one least common denominator behind higher MAO activities and a unipolar subdiagnosis. Earlier reports on univariately significant differences in MAO activity between affective subdiagnoses or between the sexes were not replicated. Positive trend correlations were found between homovanillic acid and 5-hydroxyindoleacetic acid in cerebrospinal fluid and platelet MAO activity. Urinary free cortisol correlated significantly with platelet MAO activity, but only in unipolars.


A resting-state study of volumetric and functional connectivity of the habenular nucleus in treatment-resistant depression patients.
To investigate the volumetric and functional connectivity of the habenular nucleus in treatment-resistant depression (TRD) patients using the resting-state functional magnetic resonance imaging (rs-fMRI) approach. A total of 15 TRD patients, who visited the Mental Health Institute of the First Hospital Affiliated with Jilin University between August 2014 and March 2015, along with 15 normal subjects, were enrolled into this study for structural and functional imaging. Functional connectivity analysis was performed using bilateral habenular nuclei as the region of interest in contrast to whole-brain voxels. No significant difference of absolute volume was found in bilateral habenular nuclei between TRD patients and healthy controls, or after controlling for individual total intracranial volume. However, functional connectivity analysis showed increased connectivity between the right habenular nucleus with the medial superior frontal gyrus, anterior cingulate cortex and medial orbitofrontal gyrus, and decreased connectivity with the corpus callosum in the TRD group. For the left habenular nucleus seed, the brain region with increased functional connectivity in the inferior temporal gyrus and decreased functional connectivity in the insular was found in the TRD patients. Abnormal functional connectivity was present between the habenular nucleus and the default mode network in TRD patients. Dysfunction in habenular nucleus-related circuitry for processing negative emotion might form the pathological basis for TRD. Significant asymmetric functional connectivity was also found between bilateral habenular nuclei in TRD patients. Such asymmetry suggests potentially divergent strategy for intervention on bilateral habenular nucleus regions in the future management of depression.


M-30 and 4HNE are sequestered in different aggresomes in the same hepatocytes.
M-30 and 4HNE adducts are two markers of active liver disease. M-30 is a serologic marker and 4HNE adducts are histologic markers. M-30 is a marker for apoptosis because it is a fragment of cytokeratin-18 left over from proteolysis by caspase 3. 4HNE is a marker of oxidative stress because it results from lipid peroxidation. Both markers are commonly found in nonalcoholic steatohepatitis and in alcoholic hepatitis. Liver biopsies from patients with steatohepatitis, 11 alcoholic and 11 non-alcoholics were stained for 4HNE and M-30. Almost all of the biopsies in both groups showed 4HNE- and M-30-positive aggresomes in hepatocytes. Mallory Denk bodies (MDB) stained variably positive for M-30, whereas 4HNE was present in aggresomes independent of MDBs. However, they were sometimes located in hepatocytes which also contained MDBs as shown by confocal microscopy of double stained biopsies. The results indicate that the formation of M-30 and 4HNE aggresomes occurs through different pathways of liver cell injury in both types of steatohepatitis.


Hypertension management in diabetic patients: prescribing trends from 1999 to 2005 in three Japanese university hospitals.
In hypertensive patients with diabetes, antihypertensive therapy is important in reducing the risk of macro- and microvascular complications. In contrast to the guidelines issued by the American Diabetes Association (ADA) in and after 2002, the guidelines issued by the Japanese Society of Hypertension (JSH) in 2000 and 2004 maintained the traditional view that beta-blockers and thiazides should be rated as second-line drugs. However, both sets of guidelines recommended angiotensin converting enzyme inhibitors and angiotensin II receptor blockers (ARBs) as first-line agents for such patients. We examined the use of antihypertensives in hypertensive patients with and without diabetes using the prescription data for 1999, 2002 and 2005 from three Japanese university hospitals. When compared with 1999, the proportion of patients with and without diabetes using ARBs was dramatically increased in 2005 from 1.5 to 55% and from 1.5 to 40%, while that of angiotensin converting enzyme inhibitors decreased from 52 to 32% and 35 to 23%, respectively. A relatively stable proportion of patients (around 10% with and without diabetes) used beta-blockers and around 60% of patients with and without diabetes used calcium channel blockers (CCBs) and very few (<5%) used thiazides. The rapid increase in use of ARBs and under-use of thiazides may be explained by the fee schedule in the Japanese health insurance system. The paucity of large-scale clinical trials may also hinder evaluation of the traditional view of the role of beta-blockers and thiazides in treatment of Japanese patients with diabetes.


Impact assessment of particulate pollution on maternal mortality in Nigeria.
Recently, the World Health Organization reported that 20% of all global maternal deaths happened in Nigeria between 2005 and 2015. In developing countries, these maternal deaths are mainly from air pollution. Due to poor facilities and documentation, the extent of danger is not known. This research seeks to estimate the available pollutants and its direct and indirect impact on maternal mortality. Ten (10) years (2010-2019) datasets of black carbon, sulfur dioxide, dust, carbon monoxide, organic carbon particulates, sea-salts, and sulphate particulates were obtained from the second modern-era retrospective analysis for research and applications (MERRA-2). The dataset was obtained for the six geopolitical zones of Nigeria and analyzed using statistical tool, models, spatial interpolation, and risk analysis. The volumetric and radioecological risk was also analyzed. It was observed the dust content had minute volume of heavy metal and/or radionuclide particles that may be unharmful in the short term but lethal in the long term. The risk quotient and total dose rate per organism are given as 0.00000396 and 0.0000396 µGy h-1. The result in this manuscript corroborates existing data on maternal mortality in Nigeria. It is recommended that the safety of pregnant woman depends on significant efforts of authorities to enact and enforce environmental laws to mitigate air pollution.


Radiomic-Based MRI for Classification of Solitary Brain Metastases Subtypes From Primary Lymphoma of the Central Nervous System.
Differential diagnosis of brain metastases subtype and primary central nervous system lymphoma (PCNSL) is necessary for treatment decisions. The application of machine learning facilitates the classification of brain tumors, but prior investigations into primary lymphoma and brain metastases subtype classification have been limited. To develop a machine-learning model to classify PCNSL, brain metastases with primary lung and non-lung origin. Retrospective. A total of 211 subjects with pathologically confirmed PCNSL or brain metastases (training cohort 168 and testing cohort 43). A 3.0 T axial contrast-enhanced T1-weighted spin-echo inversion recovery sequence (T1WI-CE), axial T2-weighted fluid-attenuation inversion recovery sequence (T2FLAIR) ASSESSMENT: Several machine-learning models (support vector machine, random forest, and K-nearest neighbors) were built with least absolute shrinkage and selection operator (LASSO) using features from T1WI-CE, T2FLAIR, and clinical. The model with the highest performance in the training cohort was selected to differentiate lesions in the testing cohort. Then, three radiologists conducted a two-round classification (with and without model reference) using images and clinical information from testing cohorts. Five-fold cross-validation was used for model evaluation and calibration. Model performance was assessed based on sensitivity, specificity, accuracy, and area under the receiver operating characteristic curve (AUC). Twenty-five image features were selected by LASSO analysis. Random forest classifier was selected for its highest performance on the training set with an AUC of 0.73. After calibration, this model achieved an accuracy of 0.70 on the testing set. Accuracies of all three radiologists improved under model reference (0.49 vs. 0.70, 0.60 vs. 0.77, 0.58 vs. 0.72, respectively). The random forest model based on conventional MRI and clinical data can diagnose PCNSL and brain metastases subtypes (lung and non-lung origin). Model classification can help foster the diagnostic accuracy of specialists and streamline prognostication workflow. 4 TECHNICAL EFFICACY: Stage 2.


In silico and in vitro Estimation of Structure and Biological Affinity of 1,3- Oxazoles: Fragment-to-fragment Approach.
The fragment-to-fragment approach for the estimation of the biological affinity of the pharmacophores with biologically active molecules has been proposed. It is the next step in the elaboration of molecular docking and using the quantum-chemical methods for the complex modeling of pharmacophores with biomolecule fragments. The parameter φ 0 was used to estimate the contribution of π-electron interactions in biological affinity. It is directly related to the position of the frontier levels and reflects the donor-acceptor properties of the pharmacophores and stabilization energy of the [Pharm꞉BioM] complex Results: By using quantum-chemical calculations, it was found that the stacking interaction of oxazoles with phenylalanine is 7-11 kcal/mol, while the energy of hydrogen bonding of oxazoles with the amino group of lysine is 5-9 kcal/mol. The fragment-to-fragment approach can be applied for the investigation of the dependence of biological affinity on the electronic structure of pharmacophores.c Conclusion: The founded quantum-chemical regularities are confirmed with the structure-activity relationships of substituted oxazoles.


Redo carotid surgery: An analysis of materials and configurations used in carotid reoperations and their influence on perioperative stroke and subsequent recurrent stenosis.
The ideal method of arterial reconstruction in operations for recurrent carotid disease after prior endarterectomy is unknown. The goal of this study was to review a series of carotid reoperations and to determine whether the surgical technique influenced the rate of perioperative stroke, late stroke, or secondary restenosis. A retrospective review was conducted of 82 carotid reoperations performed on 74 patients at our institution. The patient population included 39 men (52.7%) and 35 women (47.3%), with a mean age of 67.5 years. The indications for redo surgery included transient ischemic attack or amaurosis fugax in 35.3% of the patients, stroke in 6.1%, and asymptomatic restenosis (>80%) in 58.5%. Patch angioplasty with or without redo endarterectomy was used in 47 cases (57.3%), with saphenous vein in 26 (31.7%), Dacron in 15 (18.3%), and polytetrafluoroethylene in 6 (7.3%). Interposition grafting was used in 35 cases (42.7%), with saphenous vein in 9 (11.0%), Dacron in 10 (12.2%), and polytetrafluoroethylene in 16 (19.5%). The perioperative complications included three strokes (3.7%). There was a trend toward increased perioperative neurologic complications with interposition grafting when compared with patch angioplasty (8.6% vs 2.1%), although this did not reach statistical significance. Long-term clinical follow-up was obtained in all cases with a mean duration of 35 months, with follow-up duplex scanning performed in 89.2%. The late failures of redo surgery included four significant secondary restenoses and five total occlusions. There was a trend towards improved long-term results with interposition grafting as opposed to patch angioplasty. However, the cases in which reconstruction was performed with a vein had a significantly higher rate of late failures (stroke, secondary recurrent stenosis, or occlusion) than those in which reconstruction was performed with any prosthetic material (26.7% vs 2.3%; P =.002 by Fisher exact test). The use of autologous material for redo carotid surgery in any configuration appears to significantly increase the rate of subsequent recurrent stenosis or total occlusion of the operated artery. The reason for this finding is unclear but may be related to both host and technical factors. Prosthetic material may be more durable in the long-term for redo carotid surgery. Interposition grafting for redo carotid surgery may increase the perioperative neurologic complication rate to some degree; however, this was not statistically significant in this series. Interposition grafting may be a more durable solution in long-term follow-up than redo endarterectomy and patch angioplasty. A longer follow-up period will be needed to confirm this conclusion.


Pro/Con debate: is procalcitonin useful for guiding antibiotic decision making in critically ill patients?
You are concerned about the escalating use of antibiotics in your intensive care unit (ICU). This has put a strain on the ICU budget and is possibly resulting in the emergence of resistant bacteria. You review the situation with your team and one suggestion is to consider using biomarkers such as procalcitonin to better guide appropriate antibiotic decision making.


Beam characterisation studies of the 62 MeV proton therapy beamline at the Clatterbridge Cancer Centre.
The Clatterbridge Cancer Centre (CCC) in the United Kingdom is the world's first hospital proton beam therapy facility, providing treatment for ocular cancers since 1989. A 62 MeV beam of protons is produced by a Scanditronix cyclotron and transported through a passive delivery system. In addition to the long history of clinical use, the facility supports a wide programme of experimental work and as such, an accurate and reliable simulation model of the treatment beamline is highly valuable. However, as the facility has seen several changes to the accelerator and beamline over the years, a comprehensive study of the CCC beam dynamics is needed to firstly examine the beam optics. An extensive analysis was required to overcome facility related constraints to determine fundamental beamline parameters and define an optical lattice written with the Methodical Accelerator Design (MAD-X) and the particle tracking Beam Delivery Simulation (BDSIM) code. An optimised case is presented and simulated results of the optical functions, beam distribution, losses and the transverse rms beam sizes along the beamline are discussed. Corresponding optical and beam information was used in TOPAS to simulate transverse beam profiles and compared to EBT3 film measurements. We provide an overview of the magnetic components, beam transport, cyclotron, beam and treatment related parameters necessary for the development of a present day optical model of the facility. This work represents the first comprehensive study of the CCC facility to date, as a basis to determine input beam parameters to accurately simulate and completely characterise the beamline.


Nardostachys jatamansi and levodopa combination alleviates Parkinson's disease symptoms in rats through activation of Nrf2 and inhibition of NLRP3 signaling pathways.
Levodopa combined with traditional Chinese medicine has a synergistic effect on Parkinson's disease (PD). Recently, we demonstrated that Nardostachys jatamansi (D. Don) DC. [syn. Patrinia jatamansi D.Don, N. grandiflora DC.] (Valerianaceae) (NJ) can alleviate PD. To explore the synergistic effect of NJ combined with levodopa against PD. The PD model was established by injecting rotenone. Eighty-four Sprague-Dawley rats were randomly divided into seven groups: sham, model, different doses of NJ (0.31, 0.62, or 1.24 g/kg) combined with levodopa (25 mg/kg), and levodopa alone (25 and 50 mg/kg) groups. The synergistic effect of the combination was investigated by pharmacodynamic investigation and detection of expression of nuclear factor erythro2-related factor 2 (Nrf2) and NLR family proteins containing Pyrin-related domain 3 (NLRP3) pathways. Compared with the model group, NJ + levodopa (1.24 g/kg + 25 mg/kg) increased the moving distance of PD rats in the open field (2395.34 ± 668.73 vs. 1501.41 ± 870.23, p < 0.01), enhanced the stay time on the rotating rod (84.86 ± 18.15 vs. 71.36 ± 17.53, p < 0.01) and the combination was superior to other treatments. The synergistic effects were related to NJ + levodopa (1.24 g/kg + 25 mg/kg) increasing the neurotransmitter levels by 38.80%-88.67% in PD rats, and inhibiting oxidative stress and NLRP3 pathway by activating Nrf2 pathway. NJ combined with levodopa is a promising therapeutic candidate for PD, which provides a scientific basis for the subsequent clinical combination therapy of levodopa to enhance the anti-PD effect.


Immunohistochemical localization of somatostatin-like immunoreactivity in skin lesions from patients with urticaria pigmentosa.
Using the indirect immunofluorescence technique of Coons and collaborates, somatostatin-like immunoreactivity was found in skin lesions of patients presented with urticaria pigmentosa. The cytoplasmic immunoreactivity was sometimes of a granular type. In addition, immunofluorescence was also observed in certain surrounding connective tissue elements. No specific staining was seen when supplementing the first antiserum with control serum, nor could any unique specific immunofluorescence by found in the pathological areas (compared with skin of normal healthy volunteers) after incubation with antibodies to substance P, vasoactive intestinal polypeptide or avian pancreatic polypeptide. No thyrotropin releasing hormone or enkephalin immunoreactivity was seen in skin from either the patients or the controls.


The Multidisciplinary Issue of Obesity: Epidemiological Studies, Company Strategies and Policy Actions: A Systematic and Methodological Review of the Research Approaches.
The work is a review of studies carried out in recent years on the epidemic of obesity. The issue of obesity includes several disciplines: medical-health, socio-economic impacts and policy actions. This review focuses on the three main areas of study: the first area is about patent epidemiological researches, the second one analyzes the companies that focus on research and development towards less obesogenic foods and the third one investigates on the policies actions adopted by European governments to address the problem of obesity. This study underlined a more strong scientific production relative to US and UK countries compared with the southern countries of the world where the attention of scientists and politicians to the obesity is lower due to the problems of food security rather than to those of inappropriate lifestyle. The study of the cause and effects of this phenomenon through epidemiological researches is a good tool to counteract obesity. However, the development of policies controlling and contrasting obesogenic food production is fundamental like greater communication to consumers on the risks of obesity and foods processing.


Brainstem gangliogliomas.
Gangliogliomas are rare neurogliogenic tumors of the central nervous system. Primary involvement of the brainstem is characterized by variable presentations and a long clinical course before diagnosis. Identification of this group of tumors is essential because clinical improvement and prolonged survival have been documented following partial surgical resection.


Sudden infant death syndrome in Cardiff, association with epidemic influenza and with temperature - 1955-1974.
The effects of social class, season, low temperature and sudden falls in temperature are investigated in 286 cases of Sudden Infant Death Syndrome in Cardiff in the years 1955--1974. The association with low temperature was striking: unsuspected hypothermia may be an important feature of these deaths. Sudden infant death incidence was associated with influenza A but not influenza B epidemics.


Systematic review and meta-analysis of internet-delivered interventions providing personalized feedback for weight loss in overweight and obese adults.
Obesity levels continue to rise annually. Face-to-face weight loss consultations have previously identified mixed effectiveness and face high demand with limited resources. Therefore, alternative interventions, such as internet-delivered interventions, warrant further investigation. The aim was to assess whether internet-delivered weight loss interventions providing personalized feedback were more effective for weight loss in overweight and obese adults in comparison with control groups receiving no personalized feedback. Nine databases were searched, and 12 studies were identified that met all inclusion criteria. Meta-analysis, identified participants receiving personalized feedback via internet-delivered interventions, had 2.13 kg mean difference (SMD) greater weight loss (and BMI change, waist circumference change and 5% weight loss) in comparison with control groups providing no personalized feedback. This was also true for results at 3 and 6-month time points but not for studies where interventions lasted ≥12 months. This suggests that personalized feedback may be an important behaviour change technique (BCT) to incorporate within internet-delivered weight loss interventions. However, meta-analysis results revealed no differences between internet-delivered weight loss interventions with personalized feedback and control interventions ≥12 months. Further investigation into longer term internet-delivered interventions is required to examine how weight loss could be maintained. Future research examining which BCTs are most effective for internet-delivered weight loss interventions is suggested.


Stronger Impact of COVID-19 in Nursing Homes of a French Region During the Second Pandemic Wave.
Quantify the effects of characteristics of nursing homes and their surroundings on the spread of COVID-19 outbreaks and assess the changes in resident protection between the first 2 waves (March 1 to July 31 and August 1 to December 31, 2020). An observational study was carried out on data on COVID-19 outbreaks extracted from a database that monitored the spread of the virus in nursing homes. The study concerned all 937 nursing homes with >10 beds in Auvergne-Rhône-Alpes region, France. The rate of nursing homes with at least 1 outbreak and the cumulative number of deaths were modeled for each wave. During the second (vs the first wave), the proportion of nursing homes that reported at least 1 outbreak was higher (70% vs 56%) and the cumulative number of deaths more than twofold (3348 vs 1590). The outbreak rate was significantly lower in public hospital-associated nursing homes than in private for-profit ones. During the second wave, it was lower in public and private not-for-profit nursing homes than in private for-profit ones. During the first wave, the probability of outbreak and the mean number of deaths increased with the number of beds (P < .001). During the second wave, the probability of outbreak remained stable in >80-bed institutions and, under proportionality assumption, the mean number of deaths was less than expected in >100-bed institutions. The outbreak rate and the cumulative number of deaths increased significantly with the increase in the incidence of hospitalization for COVID-19 in the surrounding populations. The outbreak in the nursing homes was stronger during the second than the first wave despite better preparedness and higher availabilities of tests and protective equipment. Solutions for insufficient staffing, inadequate rooming, and suboptimal functioning should be found before future epidemics.


Lower extremity edema due to deep vein thrombosis in patients with recurrent cervix cancer.
Seven patients with recurrent cervix cancer and concurrent lower extremity edema and pain were studied with contrast venography. Five patients (83%) were proven to have deep venous thrombosis. Significant objective and subjective response to therapeutic intravenous heparinization was obtained in all patients with DVT. The low morbidity and high rate of efficacy of treating this problem should encourage the physician to investigate this problem, in order to offer palliation.


Role of Anti-Carbamylated Protein Antibodies Compared to Anti-Citrullinated Protein Antibodies in Indigenous North Americans With Rheumatoid Arthritis, Their First-Degree Relatives, and Healthy Controls.
Rheumatoid arthritis (RA) is characterized by the presence of autoantibodies, including seropositivity for rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPAs). In addition, antibodies to carbamylated proteins (anti-CarP) are present in patients with RA and are associated with joint damage. This study was undertaken to assess the presence of anti-CarP antibodies in indigenous North Americans (First Nations [FN] populations) with RA compared to their at-risk first-degree relatives (FDRs) and healthy controls. Anti-CarP IgG and ACPAs (specifically, anti-cyclic citrullinated peptide [anti-CCP] antibodies) were measured by enzyme-linked immunosorbent assay in the sera of FN patients with RA (n = 95), their unaffected FDRs (n = 109), and healthy FN controls (n = 85). Antibodies to additional citrullinated peptides were measured using a multiplex ACPA array, and the number of peptides recognized was reported as an ACPA score. Groups were compared using the chi-square test and Mann-Whitney U test. Associations between RA and seropositivity for RF, ACPAs, and anti-CarP antibodies were determined by logistic regression. Anti-CarP antibodies were more frequent in FN patients with RA (44.3%) compared to FDRs (18.3%) and FN controls (4.7%) (both P < 0.0001 versus RA). Moreover, anti-CarP antibodies were more frequent in FDRs than in FN controls (P = 0.008). The ACPA score was higher in anti-CCP-positive FN patients with RA than in anti-CCP-positive FN FDRs (median score 7 [interquartile range (IQR) 7] versus median score 1 [IQR 4]; P = 0.04). The association with RA was strongest when all 3 autoantibodies (RF, anti-CCP, and anti-CarP) were present in the patients' serum (odds ratio 194, 95% confidence interval 23-1,609, P < 0.0001). Anti-CarP antibodies are prevalent in FN patients with RA and also more common in their at-risk FDRs compared to healthy controls. The results indicate an association of RF, ACPAs, and anti-CarP with RA that is strongest when all 3 autoantibodies are present. These findings may provide new insights into the evolution of autoimmunity in preclinical RA.


Rapid determination of total phenolic content of whole wheat flour using near-infrared spectroscopy and chemometrics.
Phenolics in whole wheat products provide many health benefits. Wheat breeders, producers, and end-users are becoming increasingly interested in wheats with higher total phenolic content (TPC). Whole wheat flour with higher phenolics may have greater marketing value in the future. However, conventional methods determining TPC are costly and labor-intensive, which are not practical for wheat breeders to analyze several thousands of lines within a limited timeframe. We presented a novel application of near-infrared spectroscopy for TPC prediction in whole wheat flour. The optimal regression model demonstrated R2 values of 0.92 and 0.90 for the calibration and validation sets, and a residual prediction deviation value of 3.4. The NIR method avoids the tedious extraction and TPC assay procedures, making it more convenient and cost-effective. Our result also demonstrated that NIR can accurately quantify phenolics even at low concentration (less than 0.2%) in the food matrix such as whole wheat flour.


Occurrence, bio-concentration and distribution of rare earth elements in wild mushrooms.
Using validated methodology, this study explores the bioconcentration potential and status of rare earth elements (REE) and yttrium (Y) in wild mushrooms collected from Belarus, China and Poland and in the associated forest topsoil. Baseline data for REE and Y distributions in the morphological parts of the fruiting bodies of Caloboletus calopus, Cantharellus cibarius, Craterellus cornucopioides, Imleria badia, Laccaria amethystina, Lactifluus piperatus, Leccinum scabrum and Suillus grevillei are presented. REE were in the range of 14 to 42 mg kg-1 dw in forest topsoil and from 35 to 48 mg kg-1 dw in profiled soil layers from the Sobowidz site in Poland. Forest topsoil sampled in Belarus contained 67 mg kg-1 dw. Yttrium concentrations in soil ranged from 2.9 to 10 mg kg-1 dw. The median REE concentration in wild mushrooms was around 200 μg kg-1 dw (20 μg kg-1 fresh weight). This implies negligible dietary intake even for high level consumers. The bioconcentration factors (BCF) of individual REE and Y ranged from 0.0002 to 0.0229, showing bio-exclusion. The BCF tended to be similar for groups of REE (La to Tb and Dy to Lu) depending on the mushroom species and site. REE from Dy to Lu were better bioconcentrated than those from La to Tb. The similarity of the BCFs of individual REE by species at a given site implies the same absorption pathway, although a lower concentration in the topsoil favoured bioconcentration. REE and Y concentrations varied between species as well as within the same species between sites. Their accumulation in mushrooms appears to reflect condition at the site of collection, and may also be species-specific but confirming this would require further investigation of different species, topsoils and sites.


Successful autologous peripheral blood stem cell transplantation in transformed follicular lymphoma previously treated with radioimmunotherapy (iodine (131)I tositumomab).
While the use of radioimmunotherapy for lymphoma increases, the feasibility and efficacy of autologous stem cell transplant for subsequent relapse remains unknown. We report a 48-year-old male with transformed follicular mixed non-Hodgkin's lymphoma. After treatment with three different combination chemotherapy regimens, at relapse he received radioimmunotherapy with iodine (131)I tositumomab (anti-CD20), with very good response. At later relapse, a second course of (131)I tositumomab was given unsuccessfully. He underwent peripheral blood stem cell harvest, chemoradiotherapy conditioning and autologous transplantation with prompt engraftment and without significant complications. He remains in complete remission with normal blood counts 25 months post autograft.


Gene cloning, expression, and crystallization of a thermostable exo-inulinase from Geobacillus stearothermophilus KP1289.
The gene ( inuA) encoding exo-inulinase (EC 22.214.171.124) was cloned from the thermophilic Geobacillus stearothermophilus ( Bacillus stearothermophilus) KP 1289 growing at between 41 degrees C and 69 degrees C. The inuA gene consisted of 1,482 bp encoding a protein of 493 amino acids. The deduced polypeptide of molecular mass ( M) 56,744 Da showed strong sequence similarity to Pseudomonas mucidolens exo-inulinase, Bacillus subtilis levanase, Paenibacillus polymyxa ( Bacillus polymyxa) fructosyltransferase, and so on, indicating that the enzyme belonged to glycosyl hydrolase family 32. The M of the purified exo-inulinase, expressed in Escherichia coli HB101, was estimated as approximately 54,000 Da by both SDS-PAGE and gel filtration. These results suggested that the active form of the enzyme is a monomer. The enzyme was active between 30 and 75 degrees C with an optimum at 60 degrees C. The properties were identical to those of the native enzyme. Additionally, for the first time for a prokaryotic GH32 protein, crystals of the recombinant enzyme were obtained.


A protocol for a multicenter randomized and personalized controlled trial using rTMS in patients with disorders of consciousness.
Improving the functional recovery of patients with DoC remains one of the greatest challenges of the field. Different theories exist about the role of the anterior (prefrontal areas) versus posterior (parietal areas) parts of the brain as hotspots for the recovery of consciousness. Repetitive transcranial magnetic stimulation (rTMS) is a powerful non-invasive brain stimulation technique for the treatment of DoC. However, a direct comparison of the effect of TMS treatment on the front versus the back of the brain has yet to be performed. In this study, we aim to assess the short- and long-term effects of frontal and parietal rTMS on DoC recovery and characterize responders phenotypically. Ninety patients with subacute and prolonged DoC will be included in a two-part multicenter prospective study. In the first phase (randomized controlled trial, RCT), patients will undergo four rTMS sessions in a crossover design over 10 days, targeting (i) the left dorsolateral prefrontal cortex (DLPFC) and (ii) the left angular gyrus (AG), as well as (iii & iv) their sham alternatives. In the second phase (longitudinal personalized trial), patients will receive personalized stimulations for 20 working days targeting the brain area that showed the best results in the RCT and will be randomly assigned to either active or sham intervention. The effects of rTMS on neurobehavioral and neurophysiological functioning in patients with DoC will be evaluated using clinical biomarkers of responsiveness (i.e., the Coma Recovery Scale-Revised; CRS-R), and electrophysiological biomarkers (e.g., power spectra, functional and effective connectivity, perturbational complexity index before and after intervention). Functional long-term outcomes will be assessed at 3 and 6 months post-intervention. Adverse events will be recorded during the treatment phase. This study seeks to identify which brain region (front or back) is best to stimulate for the treatment of patients with DoC using rTMS, and to characterize the neural correlates of its action regarding recovery of consciousness and functional outcome. In addition, we will define the responders' profile based on patients' characteristics and functional impairments; and develop biomarkers of responsiveness using EEG analysis according to the clinical responsiveness to the treatment. https://clinicaltrials.gov/ct2/show/NCT04401319, Clinicaltrials.gov, n° NCT04401319.


Differences in Obesity Among Black and White Children, Adolescents, and Adults With Congenital Heart Disease.
Congenital heart disease (CHD) survivors have an elevated risk for obesity-related comorbidities, but little is known about racial differences in obesity rates for this population. The authors aimed to compare rates of obesity in CHD survivors to national estimates using National Health and Nutrition Examination Assessment Survey (NHANES) and to characterize racial disparities in obesity among CHD survivors across age ranges. Retrospective chart review included 4496 CHD survivors (4050 white and 446 black) with a range of lesion severities from a pediatric and an adult medical center. White children with CHD had a higher prevalence of obesity compared with NHANES estimates. In contrast, white young adults with CHD had a lower prevalence of obesity compared with NHANES. Blacks with CHD had a 58% increased risk of obesity in young adulthood and a 33% increased risk in late adulthood compared with whites with CHD. Obesity interventions are needed among CHD survivors across the lifespan, particularly among adult non-Hispanic blacks.


A complex case of megalourethra and its repair.
Megalourethra is a rare malformation of the urethra caused by a lack of corpus sponigosum and in some cases corpora cavernosa in the region of the distal urethra. The absence of these structures causes a ballooning of the urethra despite there being no mechanical obstruction. A male child presented with so-called fusiform megalourethra, with absence of the corpora cavernosa and urethral duplication. A voiding cystourethrogram was used to diagnose a fusiform megalourethra with pronounced meatal stenosis and extreme stenosis of pendulous urethra. In addition, there was urethral duplication in the form of an accessory urethra stretching from the urethral colliculus to the perineum. Absence of the corpora cavernosa was also suspected in the distal urethra. The surgical procedure involved pendulous urethroplasty with an onlay technique using urethral duplication and penile reduction. This method of treating megalourethra has not been previously reported. The operative technique for fusiform megalourethra with genital malformation has to be tailored to each individual case, depending on the intraoperative and endoscopic findings.


Gas-gangrene following arthroscopic surgery.
An arthroscopic anterior cruciate ligament repair was followed by gas-gangrene and the development of a compartment syndrome. Treatment consisted of extensive fasciotomy, debridement, and antibiotic therapy with penicillin G, cefotiam, and metronidazole. The patient was also treated with five sessions of hyperbaric oxygen in a pressure chamber for a duration of 2 h per session. This therapeutic regimen resulted in the preservation of a functionally intact extremity despite severe complication.


Management of late-detected DDH in children under three years of age: 49 children with follow-up to skeletal maturity.
When the present study was initiated, we changed the treatment for late-detected developmental dislocation of the hip (DDH) from several weeks of skin traction to markedly shorter traction time. The aim of this prospective study was to evaluate this change, with special emphasis on the rate of stable closed reduction according to patient age, the development of the acetabulum, and the outcome at skeletal maturity. From 1996 to 2005, 49 children (52 hips) were treated for late-detected DDH. Their mean age was 13.3 months (3 to 33) at reduction. Prereduction skin traction was used for a mean of 11 days (0 to 27). Gentle closed reduction under general anaesthesia was attempted in all the hips. Concurrent pelvic osteotomy was not performed. The hips were evaluated at one, three and five years after reduction, at age eight to ten years, and at skeletal maturity. Mean age at the last follow-up was 15.7 years (13 to 21). Stable closed reduction was obtained in 36 hips (69%). Open reduction was more often necessary in patients ≥ 18 months of age at reduction (50%) compared with those under 18 months (24%). Residual hip dysplasia/subluxation occurred in 12 hips and was significantly associated with avascular necrosis (AVN) and with high acetabular index and low femoral head coverage the first years after reduction. Further surgery, mostly pelvic and femoral osteotomies to correct subluxation, was performed in eight hips (15%). The radiological outcome at skeletal maturity was satisfactory (Severin grades 1 or 2) in 43 hips (83%). Gentle closed reduction can be attempted in children up to three years of age, but is likely to be less successful in children aged over 18 months. There is a marked trend to spontaneous improvement of the acetabulum after reduction, even in patients aged over 18 months and therefore simultaneous pelvic osteotomy is not always necessary.


Identification of Two Genetic Loci Associated with Leukopenia after Chemotherapy in Patients with Breast Cancer.
To identify molecular predictors of grade 3/4 neutropenic or leukopenic events (NLE) after chemotherapy using a genome-wide association study (GWAS). A GWAS was performed on patients in the phase III chemotherapy study SUCCESS-A (n = 3,322). Genotyping was done using the Illumina HumanOmniExpress-12v1 array. Findings were functionally validated with cell culture models and the genotypes and gene expression of possible causative genes were correlated with clinical treatment response and prognostic outcomes. One locus on chromosome 16 (rs4784750; NLRC5; P = 1.56E-8) and another locus on chromosome 13 (rs16972207; TNFSF13B; P = 3.42E-8) were identified at a genome-wide significance level. Functional validation revealed that expression of these two genes is altered by genotype-dependent and chemotherapy-dependent activity of two transcription factors. Genotypes also showed an association with disease-free survival in patients with an NLE. Two loci in NLRC5 and TNFSF13B are associated with NLEs. The involvement of the MHC I regulator NLRC5 implies the possible involvement of immuno-oncological pathways.


Localization of the marginal zone of the tectorial membrane in situ, unfixed, and with in vivo-like ionic milieu.
In order to determine the normal positional relationship between the tectorial membrane and the organ of Corti, a preparation method was developed which made it possible to study the unfixed tectorial membrane in its normal position in relation to the cochlea and with in vivo-like ionic conditions. With this method, post-mortem changes visible with the light microscope were detectable after 60 to 90 min instead of the normal 30 min. When endolymph of artifical endolymph are present in the scala media, the marginal zone lies in close contact with the surface of the organ of Corti. If the endolymph is replaced by artificial perilymph, first the marginal zone of the tectorial membrane, and later the whole membrane shrinks. At this stage, latex particles suspended in the perilymph are free to enter the subtectorial space.


[The coronary flow reserve during reperfusion in myocardial infarction].
The study of coronary flow reserve on the reperfused myocardium damaged by 90 minutes of severe ischemia. Nine mongrel dogs of either sex, weighing 12 to 17 kg were studied. Each dog was anesthesiated with 30 mg of pentobarbital and ventilated with room air. A thoracotomy was done and the left descendent coronary artery was isolated. Aorta and right atria pressures was measured using a Siemmens-Elema transducers and mingograf recording-804 (Siemmens Instruments). Coronary blood flow was measures with a Caroline Medical Electromagnetic flowmeter, 501D. The index studied was the coronary resistance, calculated as the quotient of the diastolic aortic pressure and the diastolic blood flow. The coronary reserve was studied during reactive hyperemia produced by 10 seconds of coronary occlusion in the 5, 10, 15 and 20 minutes of reperfusion. The infarcted area was detected by TTC (triphenyltetrazolium) method. All the hearts examined showed infarcted area. The diastolic coronary resistance during the reactive hyperemia in the 20 minutes of reperfusion was higher than the control value. The coronary vascular reserve was decreased during reperfusion, in the myocardial infarction.


Therapeutic effects of sub-mucous diathermy of inferior turbinates: Sub-mucous high frequency dessication with special reference to ethnic groups in Malaya.
No abstract available.


GLP-1 and nicotine combination therapy engages hypothalamic and mesolimbic pathways to reverse obesity.
Glucagon-like peptide-1 receptor (GLP-1R) agonists promote nicotine avoidance. Here, we show that the crosstalk between GLP-1 and nicotine extends beyond effects on nicotine self-administration and can be exploited pharmacologically to amplify the anti-obesity effects of both signals. Accordingly, combined treatment with nicotine and the GLP-1R agonist, liraglutide, inhibits food intake and increases energy expenditure to lower body weight in obese mice. Co-treatment with nicotine and liraglutide gives rise to neuronal activity in multiple brain regions, and we demonstrate that GLP-1R agonism increases excitability of hypothalamic proopiomelanocortin (POMC) neurons and dopaminergic neurons in the ventral tegmental area (VTA). Further, using a genetically encoded dopamine sensor, we reveal that liraglutide suppresses nicotine-induced dopamine release in the nucleus accumbens in freely behaving mice. These data support the pursuit of GLP-1R-based therapies for nicotine dependence and encourage further evaluation of combined treatment with GLP-1R agonists and nicotinic receptor agonists for weight loss.


The acyl-CoA-binding protein Acb1 regulates mitochondria, lipid droplets, and cell proliferation.
Mitochondria are involved in many cellular activities, including energy metabolism and biosynthesis of nucleotides, fatty acids and amino acids. Mitochondrial morphology is a key factor in dictating mitochondrial functions. Here, we report that the acyl-CoA-binding protein (ACBP) Acb1 in the fission yeast Schizosaccharomyces pombe is required for the maintenance of tubular mitochondrial morphology and proper mitochondrial respiration. The absence of Acb1 causes severe mitochondrial fragmentation in a dynamin-related protein Dnm1-dependent manner and impairs mitochondrial respiration. Moreover, Acb1 regulates the remodelling of lipid droplets in nutrient-rich conditions. Importantly, Acb1 promotes cell survival when cells are cultured in nutrient-rich medium. Hence, our findings establish roles of ACBP in regulating mitochondria, lipid droplets and cell viability.


The rise of Xanax in South African schools: Toward a framework for connecting drugs and education.
This article addresses the dramatic rise in the illicit use of Xanax, an anti-anxiety medication, among South African school learners from roughly the mid 2010s. Based on interviews conducted in secondary schools in Durban, I argue for the importance of locating the benzodiazepine in relation to other known drugs that include cannabis, heroin, alcohol, ecstasy, mandrax, and cocaine. Xanax is typically seen as a stronger version of cannabis/weed but not as potent as drugs such as heroin, which drive students away from school. Xanax pills are also easy to conceal and, for women in particular, do not involve the stigma of smoking. A second argument rests on taking seriously learners' statements that they use drugs to distract themselves from everyday problems and stresses. Locating schools in the context of a youth unemployment rate of more than 50 percent, I argue that Xanax fits with the ambiguous position of learners who are aware of the illusive connections between schooling and desirable work but are reluctant to turn their back on institutions that, in the absence of alternatives, offer some hope for social mobility.


Effect of home-based online training and activity feedback on oxygen uptake in patients after surgical cancer therapy: a randomized controlled trial.
Exercise training is beneficial in enhancing physical function and quality of life in cancer patients. Its comprehensive implementation remains challenging, and underlying cardiopulmonary adaptations are poorly investigated. This randomized controlled trial examines the implementation and effects of home-based online training on cardiopulmonary variables and physical activity. Of screened post-surgical patients with breast, prostate, or colorectal cancer, 148 were randomly assigned (1:1) to an intervention (2 × 30 min/week of strength-endurance training using video presentations) and a control group. All patients received activity feedback during the 6-month intervention period. Primary endpoint was change in oxygen uptake after 6 months. Secondary endpoints included changes in cardiac output, rate pressure product, quality of life (EORTC QoL-C30), C-reactive protein, and activity behavior. One hundred twenty-two patients (62 intervention and 60 control group) completed the study period. Change in oxygen uptake between intervention and control patients was 1.8 vs. 0.66 ml/kg/min (estimated difference after 6 months: 1.24; 95% CI 0.23 to 2.55; p = 0.017). Rate pressure product was reduced in IG (estimated difference after 6 months: - 1079; 95% CI - 2157 to - 1; p = 0.05). Physical activity per week was not different in IG and CG. There were no significant interaction effects in body composition, cardiac output, C-reactive protein, or quality of life. Home-based online training among post-surgery cancer patients revealed an increase of oxygen uptake and a decrease of myocardial workload during exercise. The implementation of area-wide home-based training and activity feedback as an integral component in cancer care and studies investigating long-term effects are needed. DRKS-ID: DRKS00020499 ; Registered 17 March 2020.


The use of gold bands for flow immunoelectrochemical devices.
Gold bands sputtered over a polymeric material, Kapton, have been employed not only for electrochemical detection but also for the development of enzyme immunoassays in a flow system. The immunological interactions on bands acting as reactors are considered for a model analyte, IgM. Different formats of flow immunoassays, competitive and non-competitive, have been checked. Compared with previous results, automation gives rise to in a reduction in analysis time and in reagent consumption. Lower limits of detection are also obtained. Detection, which is also carried out in the flow system, is based on the oxidation of naphthol, the product of the enzymatic hydrolysis of naphthyl-phosphate.


Quantification of transmembrane currents during action potential propagation in the heart.
The measurement, quantitative analysis, theory, and mathematical modeling of transmembrane potential and currents have been an integral part of the field of electrophysiology since its inception. Biophysical modeling of action potential propagation begins with detailed ionic current models for a patch of membrane within a distributed cable model. Voltage-clamp techniques have revolutionized clinical electrophysiology via the characterization of the transmembrane current gating variables; however, this kinetic information alone is insufficient to accurately represent propagation. Other factors, including channel density, membrane area, surface/volume ratio, axial conductivities, etc., are also crucial determinants of transmembrane currents in multicellular tissue but are extremely difficult to measure. Here, we provide, to our knowledge, a novel analytical approach to compute transmembrane currents directly from experimental data, which involves high-temporal (200 kHz) recordings of intra- and extracellular potential with glass microelectrodes from the epicardial surface of isolated rabbit hearts during propagation. We show for the first time, to our knowledge, that during stable planar propagation the biphasic total transmembrane current (I(m)) dipole density during depolarization was ∼0.25 ms in duration and asymmetric in amplitude (peak outward current was ∼95 μA/cm(2) and peak inward current was ∼140 μA/cm(2)), and the peak inward ionic current (I(ion)) during depolarization was ∼260 μA/cm(2) with duration of ∼1.0 ms. Simulations of stable propagation using the ionic current versus transmembrane potential relationship fit from the experimental data reproduced these values better than traditional ionic models. During ventricular fibrillation, peak I(m) was decreased by 50% and peak I(ion) was decreased by 70%. Our results provide, to our knowledge, novel quantitative information that complements voltage- and patch-clamp data.