Harnessing physicochemical properties of virus capsids for designing enzyme confined nanocompartments.
Viruses have drawn significant scientific interest from a wide variety of disciplines beyond virology because of their elegant architectures and delicately balanced activities. A virus-like particle (VLP), a noninfectious protein cage derived from viruses or other cage-forming proteins, has been exploited as a nano-scale platform for bioinspired engineering and synthetic manipulation with a range of applications. Encapsulation of functional proteins, especially enzymes, is an emerging use of VLPs that is promising not only for developing efficient and robust catalytic materials, but also for providing fundamental insights into the effects of enzyme compartmentalization commonly observed in cells. This review highlights recent advances in employing VLPs as a container for confining enzymes. To accomplish larger and more controlled enzyme loading, various different enzyme encapsulation strategies have been developed; many of these strategies are inspired from assembly and genome loading mechanisms of viral capsids. Characterization of VLPs' physicochemical properties, such as porosity, could lead to rational manipulation and a better understanding of the catalytic behavior of the materials.


Using the Alberta Infant Motor Scale to early identify very low-birth-weight infants with cystic periventricular leukomalacia.
We examined whether the Alberta Infant Motor Scale (AIMS) is able to identify very low-birth-weight (VLBW) preterm infants with cystic periventricular leukomalacia (PVL) as early as 6 months of corrected age. Longitudinal follow-up AIMS assessments were done at 6, 12, and 18 months old for 35 VLBW infants with cystic PVL (cPVL(+)), 70 VLBW infants without cystic PVL (cPVL(-)), and 76 term infants (healthy controls: HC). Corrected age was used for the preterm infants. The cPVL(+) group had significantly lower prone, supine and sitting subscales at age 6, 12, and 18 months than the cPVL(-) group (all p<0.05). The cPVL(-) group showed significantly lower supine, prone, sitting, and standing subscales than the HC group only at age 6 months. At age 6 months, the areas under the receiver operator curve used to discriminate the cPVL(+) infants from cPVL(-) infants were 0.82±0.04 for prone, 0.93±0.02 for supine, 0.83±0.05 for sitting, and 0.62±0.07 for standing. The AIMS may help early identify VLBW infants with cystic PVL at age 6 months old.


Evolution: A Mosaic-type Centromere in an Early-Diverging Fungus.
Centromeres in eukaryotes can be classified into three categories: point centromeres, regional centromeres, or holocentric. Now, a hybrid-type centromere is found in a pathogenic fungus that lacks the key kinetochore component CENP-A.


Viral envelope glycoprotein processing by proprotein convertases.
The proprotein convertases (PCs) are a family of nine mammalian enzymes that play key roles in the maintenance of cell homeostasis by activating or inactivating proteins via limited proteolysis under temporal and spatial control. A wide range of pathogens, including major human pathogenic viruses can hijack cellular PCs for their own purposes. In particular, productive infection with many enveloped viruses critically depends on the processing of their fusion-active viral envelope glycoproteins by cellular PCs. Based on their crucial role in virus-host interaction, PCs can be important determinants for viral pathogenesis and represent promising targets of therapeutic antiviral intervention. In the present review we will cover basic aspects and recent developments of PC-mediated maturation of viral envelope glycoproteins of selected medically important viruses. The molecular mechanisms underlying the recognition of PCs by viral glycoproteins will be described, including recent findings demonstrating differential PC-recognition of viral and cellular substrates. We will further discuss a possible scenario how viruses during co-evolution with their hosts adapted their glycoproteins to modulate the activity of cellular PCs for their own benefit and discuss the consequences for virus-host interaction and pathogenesis. Particular attention will be given to past and current efforts to evaluate cellular PCs as targets for antiviral therapeutic intervention, with emphasis on emerging highly pathogenic viruses for which no efficacious drugs or vaccines are currently available.


Neonatal Cardiovascular Function after Antenatal Sildenafil for Severe, Early-Onset Intrauterine Growth Restriction: A Substudy of the STRIDER-NZAus Randomized Placebo-Controlled Trial.
We evaluated the effect of antenatal sildenafil on neonatal cardiovascular function in a subgroup of 27 infants of mothers participating in the STRIDER-NZAus randomized controlled trial. In this small study, we found no association between antenatal sildenafil and neonatal cardiac dysfunction including no pulmonary hypertension in exposed or unexposed infants.


Toxic effects of nickel oxide (NiO) nanoparticles on the freshwater alga Pseudokirchneriella subcapitata.
Over the last decade, concerns have been raised regarding the potential health and environmental effects associated with the release of metal oxide nanoparticles (NPs) into ecosystems. In the present work, the potential hazards of nickel oxide (NiO) NPs were investigated using the ecologically relevant freshwater alga Pseudokirchneriella subcapitata. NiO NP suspensions in algal OECD medium were characterized with regard to their physicochemical properties: agglomeration, surface charge, stability (dissolution of the NPs) and abiotic reactive oxygen species (ROS) production. NiO NPs formed loose agglomerates and released Ni2+. NiO NPs presented a 72 h-EC50 of 1.6 mg L-1, which was evaluated using the algal growth inhibition assay and allowed this NP to be classified as toxic. NiO NPs caused the loss of esterase activity (metabolic activity), the bleaching of photosynthetic pigments and the intracellular accumulation of reactive oxygen species (ROS) in the absence of the disruption of plasma membrane integrity. NiO NPs also disturbed the photosynthetic process. A reduction in the photosynthetic efficiency (ΦPSII) accompanied by a decrease in the flow rate of electrons through the photosynthetic chain was also observed. The leakage of electrons from the photosynthetic chain may be the origin of the ROS found in the algal cells. The exposure to NiO NPs led to the arrest of the cell cycle prior to the first cell division (primary mitosis), an increase in cell volume and the presence of aberrant morphology in the algal cells. In this work, the use of different approaches allowed new clues related to the toxicity mechanisms of NiO NPs to be obtained. This work also contributes to the characterization of the environmental and toxicological hazards of NiO NPs and provides information on the possible adverse effects of these NPs on aquatic systems.


Drag reduction and shear-induced cells migration behavior of microalgae slurry in tube flow.
To optimize the designing of microalgae slurry pumping system and enhance the efficiency of microalgae products production, the flow characteristics of microalgae slurries (Chlorella pyrenoidosa) in tube flow were for the first time investigated combining experiments and numerical simulation. The drag reduction behavior of microalgae slurry in the fully developed laminar flow regime was studied. In addition, the transition Reynolds number of microalgae slurries from laminar flow to turbulent flow was about 1000-1300, which was similar to the expression of two-phase flow. To provide a further understanding of flow feature of microalgae slurries in tube, a two-phase mixture model was proposed by considering the heterogeneity of concentration due to the shear-induced microalgae cells migration behavior. Simulation results revealed that the heterogeneous distribution of concentration was affected by average velocity and volume fraction of microalgae slurries, significantly affecting the flow resistance and flow stability of microalgae slurry in the tube flow.


Human seminal plasma cadmium: comparison with fertility and smoking habits.
Cadmium, selenium and zinc were determined in seminal plasma and serum of 64 men by atomic absorption spectrometry (AAS). The mean (+/- SD) cadmium concentrations in seminal plasma and serum were 0.22 +/- 0.22 micrograms and 0.28 +/- 0.10 micrograms, respectively, but they did not correlate with each other. Smokers (n = 31) had significantly (p less than 0.01) higher serum cadmium concentrations than non-smokers (n = 31). Also seminal plasma cadmium in smokers was elevated, but a significant difference to non-smokers was only found if more than 20 cigarettes were consumed daily. No differences were found in semen quality and fertility between smokers and non-smokers. The seminal plasma cadmium had no correlation to selenium or zinc which, however, displayed a positive correlation (r = 0.852, p less than 0.001) to each other. It is concluded that smoking increases the exposure to cadmium. Although no obvious reproductive suppression was observed, heavy smoking may possibly enhance toxic effects in men under other detrimental exposures.


Positive inductive effect of IL-2 on virus-specific cellular responses elicited by a PRRSV-ORF7 DNA vaccine in swine.
This study investigated the effect of swine interleukin 2 (IL-2) and swine interleukin 4 (IL-4) on the development of immune responses induced by a PRRSV-ORF7 DNA vaccine (phCMV-ORF7). The two cytokines were cloned separately in the eukaryotic expression vector phCMV, and delivered via gene gun as adjuvants for the DNA vaccine. Groups of 3-week-old certified PRRSV-free, castrated male, Yorkshire crossbred pigs, were vaccinated with or without the IL-2 or IL-4. The ensuing humoral and cellular immune responses were analyzed by a PRRSV-specific ELISA, and by an in vitro blastogenic response of peripheral blood mononuclear cells (PBMC) stimulated by viral antigen, respectively. The animals were boosted 21 days post-vaccination and challenged 28 days afterward. The virus loads post-challenge were measured by real time PCR. The group of swine receiving the vaccine plus IL-2 had significant virus-specific blastogenic responses 3 weeks after the vaccine-cytokine boost, when compared to those of the experimental pigs that received the vaccine plus IL-4, vaccine alone, unvaccinated controls or the pigs vaccinated with the DNA vaccine cloned in the reverse orientation (phCMV-ORF7(Rev)). None of the experimental swine had detectable specific antibodies against the virus during the vaccination phase. The virus load peak in vaccinated animals was delayed by about 72h as compared to that of the control pigs (unvaccinated and vaccinated with the phCMV-ORF7(Rev) construct). Interestingly, animals that received the phCMV-ORF7 vaccine alone consistently had low virus loads throughout the study. These results demonstrate that IL-2 has a positive inductive effect on the activation of vaccine-induced virus-specific cellular immunity, while IL-4 appeared to have a suppressive effect. Our data also suggest that ORF7 may play a role in reducing the virus load in PRRSV infected animals.


Functional outcomes and safety of GreenLight photovaporization of the prostate in the high-risk patient with lower urinary tract symptoms due to benign prostatic enlargement.
Photovaporization of the prostate (PVP) with GreenLight Laser is a surgical treatment for lower urinary tract symptoms. It is considered safe in elderly patients with comorbidities, however, the evidence is inconclusive. The objective of this study is to evaluate the efficacy and safety outcomes of PVP according to the American Society of Anesthesiologists Physical Status (ASAPS). A cohort of 675 patients who underwent PVP between 2012 and 2018 was evaluated. Patients were classified according to their ASAPS as low (I and II) and high risk (III and IV). Surgical characteristics and improvement of symptoms and Quality of Life (QoL) were evaluated. The median age of high-risk group was higher than low-risk group. The high-risk group had more history of anticoagulation, antiaggregation, urinary catheterization, urinary retention and urethral stricture. Longer times of hospitalization (23.7 [interquartile range {IQR} = 18.9-41.35] vs 21.8 hours [IQR = 18.7-26.6], P = .008) and catheterization (19.55 [IQR = 15.6-35.57] vs 17.67 hours [IQR = 14.76-22.5], P = .004) were found in the high-risk group. Conversion and bleeding control were not different between groups. In the follow-up, improvement of International Prostate Symptoms Score (IPSS) and QoL was significant in all patients when compared before and after surgery scores (P < .001). There were no difference between groups for QoL, however, IPSS was lower for the low-risk group (8 [IQR = 4-14.5] vs 5 [2-12], P = .001). PVP with GreenLight Laser is a safe and efficient procedure for all patients despite their comorbidities, with comparable middle-term outcomes which makes it a standard treatment for the entire aging population, improving their QoL.


Dynamic and causality linkages from transportation services and tourism development to economic growth and carbon emissions: New insights from Quantile ARDL approach.
The present study investigates the pathway toward sustainability in Malaysia while observing the effects of tourism and transportation services on economic growth and carbon emissions. The study applied the quantile autoregressive distributed lag approach during the period 1970-2018, along with Granger causality to explore dynamic and asymmetric causal associations between the proposed variables. The empirical outcomes indicate that the error correction parameters are significant across major quantiles, confirming the presence of steady-state equilibrium in the long run. The results demonstrate that tourism and transportation services contribute significantly to economic growth in the long run; however, their contribution varies at different quantiles. On the other hand, tourism and transportation services were found to mitigate carbon dioxide emissions mainly across higher emission quantiles, confirming the sustainability of the transportation and tourism sector in Malaysia. We also observe a bidirectional causality between model variables. These results suggest important policy implications. Integr Environ Assess Manag 2022;18:1272-1287. © 2021 SETAC.


Mortality rate of end-stage kidney disease patients in Taiwan.
End-stage kidney disease (ESKD) is a global burden that reflects each country's unique condition. We used the National Health Insurance Research Database (NHIRD) of Taiwan to decipher changes in the mortality and international survival rates and to determine the effectiveness of the pre-end-stage renal disease care program (pre-ESRD care program) to guide future health policies for ESKD. We conducted a retrospective cohort analysis of the NHIRD data along with records from the catastrophic illness certificate program of ESKD patients from 2010 to 2018. From 2010 to 2018, the annual dialysis-related mortality rate in Taiwan increased from 10.6 to 11.8 deaths per hundred patient-years. The mortality rate for patients below 40 years appears to be decreasing, reflecting the improved quality of care for ESKD patients. Patients above 75 years showed increasing mortality, indicating the prolonged survival and aging of the ESKD population. Patients undergoing dialysis who participated in the pre-ESRD care program had a higher post-dialysis initiation life expectancy than those who did not participate. Among the program enrollees, the post-dialysis initiation life expectancy was higher in patients who had participated for more than one year. Taiwan has one of the highest ESKD patient survival rates globally. From 2010 to 2018, the reduced mortality in young patients and aging of the ESKD population might indicate that the quality of care in Taiwan for ESKD has improved. Furthermore, a better survival rate after dialysis initiation was observed in the pre-ESRD care program participants.


The C175R mutation alters nuclear localization and transcriptional activity of the nephronophthisis NPHP7 gene product.
Nephronophthisis (NPH) is a rare autosomal ciliopathy, but the leading cause for hereditary end-stage renal disease in children. Most NPH family members form large protein networks, which appear to participate in structural elements of the cilium and/or function to restrict access of molecules to the ciliary compartment. The zinc-finger protein GLIS2/NPHP7 represents an exception as it has been implicated in transcriptional regulation; only two families with GLIS2/NPHP7 mutations and typical NPH manifestations have been identified so far. We describe here that the recently identified GLIS2/NPHP7(C175R) point mutation abolished the nuclear localization of GLIS2/NPHP7. Forced nuclear import did not rescue the transcriptional defects of GLIS2/NPHP7(C175R), indicating additional defects as DNA-binding protein. We further observed that wild type, but not GLIS2/NPHP7(C175R), prevented the cyst formation caused by depletion of nphp7 in zebrafish embryos. Taken together, our findings indicate that the C175R mutation affects both localization and function of GLIS2/NPHP7, supporting a role of this mutation in NPH, but questioning the direct involvement of GLIS2/NPHP7 in ciliary functions.


Brainstem correlates of gustatory similarity in the hamster.
Responses of neurons in the nucleus tractus solitarius (NTS) and parabrachial pons (Pb pons) of the hamster to 10 gustatory stimuli were compared to behavioral similarities among these compounds. Animals were given a conditioned taste aversion to one of the 10 stimuli by pairing it with an induced gastrointestinal illness. Following this procedure, the degree of generalization of the learned taste aversion to each of the other compounds was measured. Behavioral similarity profiles were derived for each stimulus from the similarities in the generalization profiles of each pair of compounds. The across-neuron correlations in the firing rates evoked by these stimuli in the NTS cells corresponded quite well to these behavioral profiles, as did these neural correlations among Pb pontine cells, except for those correlations involving quinine. Sucrose-best cells in the Pb pons are too broadly responsive to account for the behavioral similarity functions for sweet-tasting stimuli, although other best-stimulus categories of cells (NaCl- and HCl-best) showed response profiles quite similar to the behavioral profiles, as did all best-stimulus classes of cells in the NTS.


Equality and progress for BME staff will require 'change from the top'.
Senior nurses must help drive the organisational change needed to improve the experience of black and minority ethnic staff in the NHS, says a diversity expert.


Cross-species replication of a resistin mRNA QTL, but not QTLs for circulating levels of resistin, in human and baboon.
Resistin has been associated with inflammation and risk for cardiovascular disease. We previously reported evidence of a QTL on chromosome 19p13 affecting the abundance of resistin (RETN) mRNA in the omental adipose tissue of baboons (L0D score 3.8). In this study, whole genome transcription levels were assessed in human lymphocyte samples from 1240 adults participating in the San Antonio Family Heart Study, using the Sentrix Human-6 Expression Beadchip. Lymphocytes were surveyed, as it has been proposed that their expression levels may reflect those in harder to ascertain tissues, such as adipose tissue, that are thought to be more directly relevant to disease procesn was conducted to detect loci affecting RETN mRNA levels. We obtained significant evidence for a QTL influencing the RETN expression (LOD score 10.7) on chromosome 19p. This region is orthologous/homologous to the region previously localized on baboon chromosome 19. The strongest positional candidate gene in this region is the structural gene for resistin, itself. We also found evidence for a QTL influencing resistin protein levels (LOD score 5.3) on chromosome 14q. This differs from our previously reported QTL on chromosome 18 in baboons. The different QTLs for circulating protein suggests that post-translational processing and turnover may be influenced by different or multiple genes in baboons and humans. The parallel findings of a cis-eQTL for RETN mRNA in baboon omental tissue and human lymphocytes lends support to the strategy of using lymphocyte gene expression levels as a surrogate for gene expression levels in other tissues.


Synthesis of Analogues of BCTC Incorporating a Pyrrolidinyl Linker and Biological Evaluation as Transient Receptor Potential Vanilloid 1 Antagonists.
A series of novel pyrrolidinyl linker TRPV1 antagonists were prepared in an effort to lower the hyperthermic side-effects of first-generation antagonist BCTC. These compounds were investigated for antagonism of hTRPV1 activation by capsaicin and acid in vitro. Preliminary results suggested the compounds 10a, 10b, 10c and 10j had favorable TRPV1 antagonism activity. In further studies in vivo, 10b, comparable to BCTC, showed potent analgesic activity in capsaicin-induced and heat-induced pain models. In addition, 10b indicated a reduced risk of body temperature elevation. All of these demonstrated that 10b can be considered as a safe candidate for the further development of analgesic drugs.


Female urethral diverticula.
Urethral diverticula are frequently under-diagnosed. The pathogenesis of this condition is poorly understood, and these lesions represent a spectrum of disorders ranging from isolated suburethral cysts to herniation of the urethral lining into the vaginal mucosa. Women with this disorder frequently complain of a host of symptoms referable to the lower urinary and genital tracts. Accurate diagnosis is based on history and clinical evaluation. Perineal ultrasound and MRI are often helpful. Repeated courses of antibiotics and urethral dilatation often fail to resolve the problem, and definitive intervention usually requires surgical excision to provide relief. This chapter describes the current management of this condition, and it heralds a re-look at the patho-aetiology in view of recent MRI findings of symptomatic non-communicating microcystic lesions.


Histone H3 lysine 4 mono-methylation does not require ubiquitination of histone H2B.
The yeast Set1-complex catalyzes histone H3 lysine 4 (H3K4) methylation. Using N-terminal Edman sequencing, we determined that 50% of H3K4 is methylated and consists of roughly equal amounts of mono, di and tri-methylated H3K4. We further show that loss of either Paf1 of the Paf1 elongation complex, or ubiquitination of histone H2B, has only a modest effect on bulk histone mono-methylation at H3K4. Despite the fact that Set1 recruitment decreases in paf1delta cells, loss of Paf1 results in an increase of H3K4 mono-methylation at the 5' coding region of active genes, suggesting a Paf1-independent targeting of Set1. In contrast to Paf1 inactivation, deleting RTF1 affects H3K4 mono-methylation at the 3' coding region of active genes and results in a decrease of global H3K4 mono-methylation. Our results indicate that the requirements for mono-methylation are distinct from those for H3K4 di and tri-methylation, and point to differences among members of the Paf1 complex in the regulation of H3K4 methylation.


Prevalence of antibodies against oxidised LDL in a cohort of 163 patients with positive anti-phospholipid antibodies and recent thrombosis.
We evaluated the prevalence of anti-beta2-glycoprotein I (a-beta2-GPI), anti-phosphatidylserine/prothrombin (a-PP), anti-prothrombin (a-PT), and anti-oxidised low-density lipoprotein (a-oxLDL) antibodies in a cohort of patients with a recent thrombotic event. Among consecutive sera sent to an autoimmune laboratory for routine testing for anti-cardiolipin antibodies (aCL) 473 were found positive for IgG and/or IgM aCL. The referring physicians were requested for clinical information about thrombo-embolic events occurring within 6 months prior to testing. One hundred and sixty-three individuals of which 82 had suffered from cerebro-vascular infarction and 49 from deep venous thromboses or pulmonary emboli were included in the study. Ninety-four sera were positive for IgG aCL and 69 were negative. There was a strong correlation between the presence of IgG aCL and the three other phospholipid-related antibodies: a-beta2-GPI, a-PP, and a-PT. However, IgG a-oxLDL antibodies were almost equally distributed among sera positive and negative for IgG aCL. The presence of antibodies of all subgroups was most pronounced among patients with venous thrombo-embolic disease. In this cohort antibodies to beta2-GPI, PP, PT seem to coexist with aCL. However, a-oxLDL antibodies appear to define a subset of patients, who were older, had more arterial vascular disease, and with no apparent association to the presence of IgG aCL.


Designable synthesis of nanocomposite hydrogels with excellent mechanical properties based on chemical cross-linked interactions.
A new type of nanocomposite hydrogels based on covalent cross-linked interactions with excellent mechanical properties and good stability has been prepared by using in situ free-radical polymerization; polystyrene nanoparticles with photo-activity are used as the cross-linking agent.


Assessment of flow mechanics in the lower extremity venous system.
The Reynolds number (Re) is a dimensionless parameter that describes fluid flow mechanics. Veins are compliant and collapsible vascular conduits that can accommodate large volume changes in response to small pressure changes. However, only sparse information is available about flow parameters such as the Re in the venous system. Bilateral duplex ultrasound examination of 15 healthy volunteers (30 limbs) was performed before and after exercise (four flights of stairs) of the veins of the lower extremity (left and right sides) and inferior vena cava. These volunteers had been confirmed to not have any signs or symptoms of lower extremity venous disease via focused history and physical examination findings. Most of the volunteers were women (73%). Their mean age was 37 ± 12.8 years. The Re was highest in the inferior vena cava among all the veins examined (470 ± 144 before exercise and 589 ± 205 after exercise; P = .04). The association between the change in Re before and after exercise and the specific vein examined was also significant for the right and left external iliac veins, right and left common femoral veins, right and left profunda femoris veins, right and left femoral veins, and right common iliac vein. Resistance and velocity maps for the lower extremity venous system were also created. The velocity increased and the resistance decreased as one moved up the venous tree toward the right atrium. The Re increased for most of the lower extremity veins after exercise in our healthy volunteers. However, the critical value for turbulent flow was not reached despite the exercise.


[Pregnancy and delivery in a patient with non-Hodgkin lymphoma--a case report].
Neoplasmatic diseases during pregnancy are relatively rare, with the incidence of approximately 1/1000 pregnancies. The symptoms of neoplasmatic processes are unspecific and often mirror physiological changes during pregnancy Chemotherapy is the main therapeutic management of non-Hodgkin lymphomas. The strategy of the treatment and its influence on the course of pregnancy remain controversial. The aim of this study was to present the case of a pregnant woman with non-Hodgkin lymphoma. We described the case of a 27-year-old pregnant nullipara with anemia, breathlessness, cough and general weakness with diagnosed diffused large B-cell lymphoma. During pregnancy the patient received six cycles of CHOP chemotherapy without any serious complications. On 37 week of gestation the caesarean section was performed. Coexisting non-Hodgkin lymphomas and pregnancy are seldom the case and the treatment requires complex chemotherapy.


In vitro antiseptic susceptibilities for Staphylococcus pseudintermedius isolated from canine superficial pyoderma in Japan.
Topical therapy, particularly with chlorhexidine, is becoming increasingly common as a treatment option for canine pyoderma; however, there are limited studies on the susceptibility of Staphylococcus pseudintermedius to chlorhexidine compounds. To determine the in vitro susceptibility of both meticillin-resistant and meticillin-susceptible S. pseudintermedius isolates to chlorhexidine and other antiseptic agents and the presence of multidrug efflux pump genes. One hundred S. pseudintermedius isolates from 23 initial and 77 recurrent cases of canine pyoderma. After bacterial identification and mecA testing, minimal inhibitory concentrations (MICs) of antiseptic agents were determined. Multidrug efflux pump genes, including qacA, qacB and smr, were identified. Of the 100 isolates, 57 were identified as meticillin-resistant S. pseudintermedius. The MIC(90) of chlorhexidine acetate, chlorhexidine gluconate, acriflavine, ethidium bromide and benzalkonium chloride were 1, 1, 2, 0.5 and 2 μg/mL, respectively. Multidrug efflux pump genes qacA, qacB and smr were not detected in any of the isolates. The MICs for chlorhexidine and other antiseptics remain low, and multidrug efflux pump genes were not found in the tested isolates.


Potentially toxic metals contamination, health risk, and source apportionment in the agricultural soils around industrial areas, Firozabad, Uttar Pradesh, India: a multivariate statistical approach.
Potentially toxic metals (PTMs) contamination in the soil poses a serious danger to people's health by direct or indirect exposure, and generally it occurs by consuming food grown in these soils. The present study assessed the pollution levels and risk to human health upon sustained exposure to PTM concentrations in the area's centuries-old glass industry clusters of the city of Firozabad, Uttar Pradesh, India. Soil sampling (0-15 cm) was done in farmers' fields within a 1 km radius of six industrial clusters. Various environmental (geo-accumulation index, contamination factor, pollution load index, enrichment factor, and ecological risk index) and health risk indices (hazard quotient, carcinogenic risk) were computed to assess the extent of damage caused to the environment and the threat to human health. Results show that the mean concentrations of Cu (33 mg kg-1), Zn (82.5 mg kg-1), and Cr (15.3 mg kg-1) were at safe levels, whereas the levels of Pb, Ni, and Cd exceeded their respective threshold limits. A majority of samples (88%) showed considerable ecological risk due to the co-contamination of these six PTMs. Health risk assessment indicated tolerable cancer and non-cancer risk in both adults and children for all PTMs, except Ni, where adults were exposed to potential threat of cancer. Pearson's correlation study revealed a significant positive correlation between all six metal pairs and conducting principal component analysis (PCA) confirmed the common source of metal pollution. The PC score ranked different sites from highest to lowest according to PTM loads that help to establish the location of the source. Hierarchical cluster analysis grouped different sites into the same cluster based on similarity in PTMs load, i.e., low, medium, and high.


Learning, memory, and glial cell changes following recovery from chronic unpredictable stress.
Previous research has indicated that chronic stress induces inflammatory responses, cognitive impairments, and changes in microglia and astrocytes. However, whether stress-induced changes following recovery are reversible is unclear. The present study examined the effects of chronic unpredictable stress (CUS) following recovery on spatial learning and memory impairments, changes in microglia and astrocytes, and interleukine-1β (IL-1β) and glial-derived neurotrophic factor (GDNF) levels. Mice were randomly divided into control, stress, and recovery groups, and CUS was applied to mice in the stress and recovery groups for 40 days. Following the application of CUS, the recovery group was allowed 40 days without stress. The results of the Morris water maze illustrated that CUS-induced spatial learning and memory impairments could be reversed or even improved by a period of recovery. Immunohistochemical tests revealed that CUS-induced alterations in microglia could dissipate with time in the CA3 region of the hippocampus and prelimbic areas. However, CUS-induced activation of astrocytes was sustained in the CA3 area following recovery. Western blot analyses revealed that CUS induced a significant increase of GDNF and a significant decrease in IL-1β. Additionally, increased GDNF levels were sustained in the hippocampus during recovery. In conclusion, this study provides evidence that CUS-induced learning and memory impairments could be reversible following recovery. However, activated astrocytes and increased GDNF levels in the hippocampus remained elevated after recovery, suggesting that activated astrocytes and increased GDNF play important roles in the adaptation of the brain to CUS and in repairing CUS-induced impairments during recovery.


Comparing strategies to assess multiple behavior change in behavioral intervention studies.
Alternatives to individual behavior change methods have been proposed, however, little has been done to investigate how these methods compare. To explore four methods that quantify change in multiple risk behaviors targeting four common behaviors. We utilized data from two cluster-randomized, multiple behavior change trials conducted in two settings: small businesses and health centers. Methods used were: (1) summative; (2) z-score; (3) optimal linear combination; and (4) impact score. In the Small Business study, methods 2 and 3 revealed similar outcomes. However, physical activity did not contribute to method 3. In the Health Centers study, similar results were found with each of the methods. Multivitamin intake contributed significantly more to each of the summary measures than other behaviors. Selection of methods to assess multiple behavior change in intervention trials must consider study design, and the targeted population when determining the appropriate method/s to use.


Involvement of FGF-2 modulation in the antidepressant-like effects of liquiritin in mice.
It has been reported that liquiritin produced an antidepressant-like effect in rodents. However, little information is known regarding its antidepressant activity with the regulation of fibroblast growth factor 2 (FGF-2), a protein maintaining development and maturation of the nervous central system. Therefore, the aim of the present study was to investigate the underlying FGF-2 modulation involved in the antidepressant-like effects of liquiritin. In the present study, mice were orally administrated with liquiritin for 7 days prior to LPS injection. The depressive-like behaviors, levels of FGF-2, number of Iba1 positive cells, expression of proinflammatory cytokines and density of dendritic spines were evaluated. The results showed that liquiritin significantly ameliorated the depressive-like behaviors in mice response to LPS injection. Liquiritin reversed the reduction of FGF-2 levels in the hippocampus of LPS induced mice. In addition, the microglial activation caused by LPS was attenuated by liquiritin, in accordance with downregulation in mRNA levels of proinflammatory cytokines. Moreover, liquiritin also increased the density of dendritic spines in the hippocampus, which was suppressed by LPS. In conclusion, our findings demonstrated that liquiritin exerted the antidepressant-like effects in LPS-induced depression through FGF-2 enhancement by inhibiting neuroinflammation and maintaining synaptogenesis.


Extracellular protease trypsin activates amiloride-insensitive sodium channels in human leukemia cells.
Sodium influx is tightly regulated in the cells of blood origin. Amiloride-insensitive sodium channels were identified as one of the main sodium-transporting pathways in leukemia cells. To date, all known regulatory pathways of these channels are coupled with intracellular actin cytoskeleton dynamics. Here, to search for physiological mechanisms controlling epithelial Na+ channel (ENaC)-like channels, we utilized leukemia K562 cells as a unique model to examine single channel behavior in a whole-cell patch-clamp experiments. We have shown for the first time that extracellular serine protease trypsin directly activates sodium channels in plasma membrane of K562 cells. The whole-cell single current recordings clearly demonstrate no inhibition of trypsin-activated channels by amiloride or benzamil. Involvement of proteolytic cleavage in channel opening was confirmed in experiments with soybean trypsin inhibitor. More importantly, stabilization of F-actin with intracellular phalloidin did not prevent trypsin-induced channel activation indicating no implication of cytoskeleton rearrangements in stimulatory effect of extracellular protease. Our data reveals a novel mechanism modulating amiloride-insensitive ENaC-like channel activity and integral sodium permeability in leukemia cells.


Use of native species to improve carbon sequestration and contribute towards solving the environmental problems of the timberlands in Biscay, northern Spain.
The rapid transformation of natural forest areas into fast-growing exotic species plantations, where the main objective is timber and pulp production, has led to a neglect of other services forests provide in many parts of the world. One example of such a problem is the county of Biscay, where the management of these plantations has negative impacts on the environment, creating the necessity to evaluate alternative tree species for use in forestry. The actual crisis in the forest sector of the region could be an opportunity to change to native species plantations that could help restore ecosystem structure and function. However, forest managers of the region are using the current interest on carbon sequestration by forest to persist with the "pine and eucalyptus culture", arguing that these species provide a big C sequestration service. Moreover, they are promoting the expansion of eucalyptus plantations to obtain biomass for the pulp and paper industry and for bioenergy. The aim of this paper is to answer the following questions: Is this argument used by the foresters well-founded? or, could the use of native species in plantations improve the C sequestration service in Biscay while avoiding the environmental problems the actual plantations cause? To answer these questions we created three alternative future scenarios: a) the Services scenario, where there is a substitution of fast-growing exotic plantations by native broadleaf species plantations; b) the Biomass scenario, where there is a bet on eucalyptus plantations; and c) the Business as usual scenario. The changes in the C stock in living biomass in these scenarios have been simulated by a hybrid approach utilising inventories and models, and the period considered was 150 years. Our results show that the substitution of existing exotic plantations by plantations of native species has the greatest potential for increasing C sequestration. Although short- and mid-term outcomes may differ, when the long-term (more than 50 years) is considered, the C stock in the living biomass in the Services scenario is the greatest, accumulating 38% more C than the Business as usual scenario and 70% more C than the Biomass scenario at the end of the study period. Thus, changing pine and eucalyptus by native species in plantations, while solving some of the environmental problems of the actual plantations, sequesters more C in the long-term. As C sequestration initiatives only make sense if there is a good chance of long-term persistence of the C stocks created, there is no C sequestration argument for the foresters to continue with the actual policy of the use of fast-growing exotic species.


Electrophysiologic effects of intravenous dipyridamole.
We evaluated the electrophysiologic effects of dipyridamole given intravenously to 24 patients during intracardiac electrophysiologic study. Electrophysiologic parameters were measured before and 5 minutes following infusion of 0.5 mg/kg of dipyridamole. The drug significantly shortened the sinus cycle length by 26 per cent (P less than 0.001), sinuatrial conduction time by 15 per cent (P less than 0.01), maximal sinus node recovery time by 21 per cent (P less than 0.001), atrial and atrioventricular nodal effective refractory period by 8 and by 11 per cent, respectively (both P less than 0.01), ventricular effective refractory period by 4 per cent (P less than 0.001), paced cycle length to atrioventricular nodal Mobitz type II block by 5 per cent (P = 0.046), and QT interval during sinus rhythm by 10 per cent (P less than 0.01). After dipyridamole, the PA interval increased by 16 per cent (P less than 0.001), the AH interval by 11 per cent (P less than 0.01), and the corrected QT interval by 5 per cent (P less than 0.01). During retrograde conduction we observed a shortening of the ventriculoatrial interval by 6 per cent (P = 0.036), retrograde atrioventricular nodal effective refractory period by 5 per cent (P less than 0.001), paced cycle length to atrioventricular nodal Wenckebach and atrioventricular nodal Mobitz type II block both by 8 per cent (P less than 0.01). We conclude that intravenous dipyridamole increases sinus node automaticity and reduces atrial, atrioventricular nodal and ventricular refractory periods, prolongs intra-atrial and atrioventricular nodal conduction, but does not produce any changes in His-Purkinje system conduction times.(ABSTRACT TRUNCATED AT 250 WORDS)


Evaluation of a novel chemiluminescent microplate enzyme immunoassay for hepatitis B surface antigen detection.
Hepatitis B virus surface antigen (HBsAg) is an important biomarker used in the diagnosis of hepatitis B virus (HBV) infection, but false-negative results are still reported in the detection of HBsAg using commercial assays. In this study, we evaluated the qualitative properties of a novel HBsAg chemiluminescence enzyme immunoassay (CLEIA) assay--WTultra. WHO standard sample dilution series and samples from low-level HBsAg carriers (<1 ng/mL) were used to evaluate the sensitivity of the WTultra assay. Boston Biomedica, Inc. (BBI) hepatitis B seroconversion panels were used to assess the ability of the WTultra assay to detect the window period. In addition, dilution series of 22 serum samples with different genotypes, serotypes and HBsAg mutations were used to assess the WTultra assay, and these were compared with other commercial assays. The lower detection limit of the WTultra assay was 0.012 IU/mL, and it showed a high sensitivity (97.52%, 95% CI, 94.95-99.00) in the detection of 282 low-level HBsAg carriers (<1 ng/mL). In samples with various HBV genotypes, serotypes and HBsAg mutations, the WTultra assay yielded 117 positive results in 132 samples, which was significantly higher than the results with the other four commercial assays (89, 83, 65 and 45, respectively, p<0.01). In the assays of mutant strains, the WTultra assay detected 82 positive results in 90 samples, which was significantly better than the results for the Hepanostika HBsAg Ultra (58 positive) and Architect (55 positive) (p<0.01) assays, which in turn were significantly better than the Murex V.3 (41 positive, p=0.026) and AxSYM V2 (29 positive, p<0.01) assays. However, in the detection of 42 samples of wild-type strains with various genotypes and serotypes, no significant differences were observed among the WTultra (35 positive), Architect (28 positive) and Hepanostika HBsAg Ultra (31 positive) assays. However, the WTultra assay detected significantly more samples than the Murex V.3 (24 positive, p<0.01) and AxSYM V2 (16 positive, p<0.01) assays. In conclusion, the WTultra HBsAg assay has a high detection sensitivity and presents excellent results for the detection of mutants.


Specific fluorometric assay for direct determination of amikacin by molecularly imprinting polymer on high fluorescent g-C3N4 quantum dots.
Here, a specific and reliable fluorometric method for the rapid determination of amikacin was developed based on the molecularly imprinting polymer (MIP) capped g-C3N4 quantum dots (QDs). g-C3N4 QDs were obtained by facile and one-spot ethanol-thermal treatment of bulk g-C3N4 powder and showed a high yield fluorescence emission under UV irradiation. The MIP layer was also created on the surface on QDs, via usual self-assembly process of 3-aminopropyl triethoxysilane (APTES) functional monomers and tetraethyl ortho-silicate (TEOS) cross linker in the presence of amikacin as template molecules. The synthesized MIP-QDs composite showed an improved tendency toward the amikacin molecules. In this state, amikacin molecules located adjacent to the g-C3N4 QDs caused a remarkable quenching effect on the fluorescence emission intensity of QDs. This effect has a linear relationship with amikacin concentration and so, formed the basis of a selective assay to recognize amikacin. Under optimized experimental conditions, a linear calibration graph was obtained as the quenched emission and amikacin concentration, in the range of 3-400 ng mL-1 (4.4-585.1 nM) with a detection limit of 1.2 ng mL-1 (1.8 nM). The high selectivity of MIP sites as well as individual fluorescence properties of g-C3N4 QDs offers a high specific and sensitive monitoring method for drug detection. The method was acceptably applied for the measurement of amikacin in biological samples.


Pretracheal cervical granular cell myoblastoma.
This case report deals with a solitary granular cell myoblastoma extrinsic to the proximal trachea. This lesion can be encountered frequently by the plastic surgeon; its histology, incidence and treatment are reviewed here. It is important to reemphasize that local extirpation is appropriate treatment of what is almost always a benign neoplasm, and intraoperative pathological diagnosis guides the surgeon in providing curative therapy.


Arsenic induces human chondrocyte senescence and accelerates rat articular cartilage aging.
Arsenic-contaminated drinking water is known to be a serious human health problem. A previous epidemiological study has indicated that arsenic levels in blood were higher in arthritis patients compared to age-matched control subjects. Bone is known as an important arsenic store compartment in the body. Arsenic exposure has been suggested to promote senescence in human mesenchymal stem cells that may affect the balance of adipogenic and osteogenic differentiation. The toxicological effect and mechanism of arsenic exposure on articular chondrocytes still remain unclear. Here, we investigated the arsenic-induced senescence in cultured human articular chondrocytes and long-term arsenic-exposed rat articular cartilage. Arsenic trioxide (As2O3; 1-5 μM) significantly induced senescence in human articular chondrocytes by increasing senescence-associated β-galactosidase (SA-β-Gal) activity and protein expression of p16, p53, and p21. Arsenic induced the phosphorylation of p38 and c-Jun N-terminal kinase (JNK) proteins. The inhibitors of p38 and JNK significantly reversed the arsenic-induced chondrocyte senescence. Arsenic could also trigger the induction of GATA4-NF-κB signaling and senescence-associated secretory phenotype (SASP) by increasing IL-1α, IL-1β, TGF-β, TNF-α, CCL2, PAI-1, and MMP13 mRNA expression. The increased cartilage senescence and abrasion were also observed in a rat model long-term treatment with arsenic (0.05 and 0.5 ppm) in drinking water for 36 weeks as compared to age-matched control rats. The phosphorylation of p38 and JNK and the induction of GATA4-NF-κB signaling and SASP were enhanced in the rat cartilages. Taken together, these findings suggest that arsenic exposure is capable of inducing chondrocyte senescence and accelerating rat articular cartilage aging and abrasion.


Association between knee inflammation and knee pain in patients with knee osteoarthritis: a systematic review.
To systematically review the literature on the relationship between markers of inflammation and pain in patients with knee osteoarthritis (OA). We searched MEDLINE, Web of Science and EMBASE databases from inception until June 2021. Eligible articles had to report on the association between inflammation (as measured by effusion, synovitis, baker's cysts, cytokines and C-reactive protein) and pain in patients with radiographic knee OA. Two reviewers independently performed a screening on title and abstracts, data extraction and risk of bias assessment using the Newcastle-Ottawa Scale (NOS). A best evidence synthesis was conducted for each inflammatory sign included in this review. 37 studies were included. Articles reported on the following measures: effusion or synovitis assessed via ultrasound (n = 9) or magnetic resonance imaging (MRI) (n = 17); baker's cyst (n = 3); cytokine concentrations (n = 11); and C-reactive protein levels (n = 4). The strength of the association between inflammation and pain does not exceed the moderate level (i.e., correlation coefficient values ranging from 0.19 to 0.61). Moderate levels of evidence were found for the association between synovitis (measured with ultrasound or contrast enhanced MRI) and pain. The levels of evidence between effusion (assessed via ultrasound), effusion/synovitis (assessed via non-contrast enhanced MRI), Baker's cyst, cytokines, C-reactive protein and pain were conflicting. Different inflammatory markers are associated with pain but the correlation ranges from weak to moderate, and the quality of evidence from conflicting to moderate. Further research is needed to strengthen the level of evidence and to establish mechanisms.


Influence of immunization with allogeneic spleen cells on the number of viable neonates in mice.
Female CBA/J (H-2k) mice mated with male DBA/2J (H-2d) mice show a high level of fetal resorption, which can be reduced by immunization with BALB/c (H-2d) spleen cells. The morphologically defined fetal resorption rate upon which evaluation of the outcome of pregnancy has previously been based in this strain combination is not equivalent to the rate of production of viable neonates.


Successful resection of a cervical pregnancy with original diagnosis of bladder wall invasion and rupture potential.
Cervical pregnancy is a rare life-threatening form of ectopic pregnancy. In the past, hysterectomy was often the only choice available because of profuse hemorrhage that accompanied the attempts of removal of the cervical pregnancy. We present a case of a successful surgical resection of a cervical pregnancy. Diagnosis of a viable cervical pregnancy was made at 9 weeks by ultrasound. Acute abdominal pain, massive vaginal bleeding, and impending shock occurred suddenly in this patient. In order to preserve her future fertility, we used a series of modified procedures, step-by-step, to minimize and control acute hemorrhaging, including transient ligation of the cervicovaginal branches of the uterine vessels with an 18-Fr Foley catheter, vasopressin use, resection of the ectopic pregnancy mass, compression using a 24-Fr Foley catheter, and finally, wound closure. Intraoperative blood loss was less than 400 mL. This treatment was successful, with resumption of normal menstrual cycles and a normal transvaginal ultrasonographic appearance of the cervical canal documented 3 months after the initial diagnosis. The use of modified surgical procedures, step-by-step, is a good alternative to total hysterectomy for managing cervical pregnancies that require urgent attention.


Lenalidomide and the Expanding Toolkit to Manage Kaposi Sarcoma.
Lenalidomide recently was shown to have clinical activity in patients with human immunodeficiency virus-associated Kaposi sarcoma. Immunomodulatory imine drugs thus provide another tool in the treatment of this challenging neoplasm. See related article by Reid et al., p. 2646.


Serotypes of CNF1-producing Escherichia coli strains that cause extraintestinal infections in humans.
The O:K:H serotypes of 137 necrotoxigenic Escherichia coli (NTEC) producing the cytotoxic necrotizing factor type 1 (CNF1) isolated from human extraintestinal infection were determined. Although NTEC producing CNF1 belonged to 58 different serotypes, only 10 of them accounted for 54% of strains. The most common serotypes, in order of frequency, were: O4:K?:H5, O6:K13:H1, O83:K1:H31, O75:K95:H5, O2:K1:H6, O2:K7:H-, O75:K1:H7, O2:K?:H1, O4:K12:H1 and O22:K13:H1. CNF1 strains of serotypes O2:K7:H- and O4:K12:H1 express P-fimbriae, whereas CNF1 strains of serotypes O2:K?:H1, O2:K1:H6 and O75:K95:H5 possess the adhesin responsible for MRHA type III. Among CNF1 strains of serotype O4:K?:H5 there exist some that express P-fimbriae and others that possess MRHA type III. Lastly, the majority of CNF1 strains of serotypes O6:K13:H1, O22:K13:H1, O75:K1:H7 and O83:K1:H31 do not express P-fimbriae nor the adhesin responsible to MRHA type III. Our results show that extraintestinal infections are caused by a limited number of virulent clones, as suggested by the theory of special pathogenicity.


Genomic characterization and linkage mapping of the apple allergen genes Mal d 2 (thaumatin-like protein) and Mal d 4 (profilin).
Four classes of apple allergens (Mal d 1, -2, -3 and -4) have been reported. By using PCR cloning and sequencing approaches, we obtained genomic sequences of Mal d 2 (thaumatin-like protein) and Mal d 4 (profilin) from the cvs Prima and Fiesta, the two parents of a European reference mapping population. Two copies of the Mal d 2 gene (Mal d 2.01 A and Mal d 2.01 B) were identified, which primarily differed in the length of a single intron (378 or 380 nt) and in one amino acid in the signal peptide. Both Mal d 2.01 A and Mal d 2.01 B were mapped at identical position on linkage group 9. Genomic characterization of four Mal d 4 genes (Mal d 4.01 A and B, Mal d 4.02 A and Mal d 4.03 A) revealed their complete gDNA sequences which varied among genes in length from 862 to 2,017 nt. They all contained three exons of conserved length: 123, 138, and 135 nt. Mal d 4.01 appeared to be duplicated in two copies and located on linkage group 9. Mal d 4.02 A and Mal d 4.03 A were single copy genes located on linkage group 2 and 8, respectively.


Divisibility patterns of natural numbers on a complex network.
Investigation of divisibility properties of natural numbers is one of the most important themes in the theory of numbers. Various tools have been developed over the centuries to discover and study the various patterns in the sequence of natural numbers in the context of divisibility. In the present paper, we study the divisibility of natural numbers using the framework of a growing complex network. In particular, using tools from the field of statistical inference, we show that the network is scale-free but has a non-stationary degree distribution. Along with this, we report a new kind of similarity pattern for the local clustering, which we call "stretching similarity", in this network. We also show that the various characteristics like average degree, global clustering coefficient and assortativity coefficient of the network vary smoothly with the size of the network. Using analytical arguments we estimate the asymptotic behavior of global clustering and average degree which is validated using numerical analysis.


Acquired cystic kidney disease: occurrence in patients on chronic peritoneal dialysis.
Acquired cystic kidney disease (ACKD) is a well-known complication of long-term hemodialysis. To the best of our knowledge, only six patients on continuous ambulatory peritoneal dialysis have been reported to develop this disease. We herein report two such cases, and concluded that the morphology of ACKD seems to be independent of the type of dialysis and that hemodialysis is not necessary for the development of ACKD.


Succession of failures in surgical management of fragility fracture of the pelvis.
We report a case of a 79-years old man who sustained a Fragility Fracture of the Pelvis (FFP) classified type IVb according to Rommens and Hofmann. After a delayed diagnosis with persistence of pain and loss of mobility, a bilateral sacroplasty was performed. Although pain relief was achieved, a fracture progression (FP) occurred with bilateral neurologic compression of L5 and S1 nerve roots with pain recurrence. A percutaneous ilio-lumbar reduction was attempted with cemented augmentation and bilateral ilio-sacral screwing. Reduction was not achieved and screws finally pulled-out. The patient died one year after institutionalization with a significant loss of mobility and autonomy. Misunderstanding in management of FFP according to Rommens and Hofmann recommendations can lead to bad results with fracture progression, implants failure, pain recurrence, loss of function, loss of autonomy and finally death of the patient.


A Quintuple-Layered Binary Chalcogenide Sb2Te3 Single Crystal and Its Transport Properties for Thermoelectric Applications.
The binary chalcogenide material Sb2Te3 was synthesized via the melting technique. The synthesized materials were converted to a single crystal through the Bridgman-Stockbarger technique. The phase purity and structural properties of the grown crystal were analyzed using powder X-ray diffraction and single-crystal X-ray diffraction measurements. X-ray photoemission spectroscopy reveals the local intermolecular bonding, changes in the stoichiometry, and the oxidation states of the elements present in the crystal. Transport properties like electrical resistivity, Seebeck coefficient, and thermal conductivity were measured. The power factor and figure of merit (ZT) of the grown crystal were calculated.


Interactions between mitochondrial bioenergetics and cytoplasmic calcium in cultured cerebellar granule cells.
The mitochondrion has moved to the center stage in the drama of the life and death of the neuron. The mitochondrial membrane potential controls the ability of the organelle to generate ATP, generate reactive oxygen species and sequester Ca(2+) entering the cell. Each of these processes interact, and their deconvolution is far from trivial. The cultured cerebellar granule cell provides a model in which knowledge gained from studies on isolated mitochondria can be applied to study the role played by the organelles in the maintenance of Ca(2+) homeostasis in the cell under resting, stimulated and pathophysiological conditions. In particular, mitochondria play a complex role in the response of the neuron to excitotoxic stimulation of NMDA and AMPA-kainate selective glutamate receptors. One goal of research in this area is to provide clues as to possible ways in which modulators of mitochondrial function may be used as neuroprotective agents, since mitochondrial Ca(2+) accumulation seems to play a key role in glutamate excitotoxicity.


Integrated pharmacokinetics of major bioactive components in MCAO rats after oral administration of Huang-Lian-Jie-Du-Tang.
Huang-Lian-Jie-Du-Tang (HLJDT, or Oren-gedoku-to in Japanese), an important multi-herb remedy in China and other Asia countries, has been used clinically to treat cerebral ischemia for decades. According to the previous studies we have reported, an HPLC method was developed and validated for determination of berberine, palmatine, baicalin, baicalein and geniposide simultaneously in MCAO rat plasma after administration of HLJDT aqueous extract. A classified integral pharmacokinetic method was put forward after having compared the integrated concentration-time profile with that of single component. An AUC based weighting approach was used for integrated principle. The results indicated the classified integral pharmacokinetic profile of index components from HLJDT could reveal the pharmacokinetic behavior of original components, and was corresponding to the holistic pharmacological effects of anti-ischemia with HLJDT. This study was aimed to explore an approach that could be applied to integrate the pharmacokinetic behavior of different components derived from HLJDT. The integrated pharmacokinetic results also provided more information for further understanding of the clinical cerebrovascular disease in use of HLJDT.


Inhibition of nigral and neocortical cells by gamma-hydroxybutyrate: a microiontophoretic investigation.
gamma-Hydroxybutyrate (GHB) and gamma-aminobutyrate (GABA) were applied microiontophoretically near spontaneously active cells in the substantia nigra and the neocortex of chloral hydrate-anaesthetized rats. Whereas GABA in "low doses" (i.e. 20 nA ejection currents) depressed the activity of cells in both areas, GBH reduced the firing rate only when the compound was expelled with two to three times higher ejection currents. Under these conditions GHB depressed about half of the nigral but the majority of the neocortical cells tested. The depressant action of GABA was readily antagonized by microiontophoretic bicuculline methiodide whereas the effects of GHB were resistant to this alkaloid. Intraperitoneally administered GHB in doses of 300 and 600 mg/kg reduced the firing rate of the majority of spontaneously active neocortical cells. In conclusion, GHB inhibits the firing of nigral and neocortical neurons. However its effects are not mediated through the activation of bicuculline-sensitive GABA receptors.


Intestinal sensing of nutrients.
Ingestion of a meal triggers a range of physiological responses both within and outside the gut, and results in the remote modulation of appetite and glucose homeostasis. Luminal contents are sensed by specialised chemosensitive cells scattered throughout the intestinal epithelium. These enteroendocrine and tuft cells make direct contact with the gut lumen and release a range of chemical mediators, which can either act in a paracrine fashion interacting with neighbouring cells and nerve endings or as classical circulating hormones. At the molecular level, the chemosensory machinery involves multiple and complex signalling pathways including activation of G-protein-coupled receptors and solute carrier transporters. This chapter will discuss our current knowledge of the molecular mechanisms underlying intestinal chemosensation with a particular focus on the relatively well-characterised nutrient-triggered secretion from the enteroendocrine system.


Assessing the impact of replacing foods high in saturated fats with foods high in unsaturated fats on dietary fat intake among Canadians.
The 2019 Canada's Food Guide (CFG) recommends that foods containing mostly unsaturated fatty acid (UFA) should replace foods that contain mostly SFA to reduce SFA intakes. The objective of this study was to model the theoretical changes in intake of SFA at the population level if all Canadians adhered to that recommendation. Dietary intakes from 24-h recalls in the nationally representative 2015 Canadian Community Health Survey-Nutrition were used for these analyses. Foods identified as high in SFA based on Health Canada's criteria [≥2 g SFA per reference amount and/or ≥15% of energy (%E) of the food's content as SFA] were replaced by an equal amount (gram per gram) of substitution foods that were lower in SFA and had a higher UFA to SFA ratio. Distributions of SFA and other nutrients before and after substitutions were estimated using the National Cancer Institute (NCI) method based on dietary intakes data from a 24-h recall repeated in 37% of the population. The mean (95% CI) dietary SFA intake among Canadians 2 y or older would be theoretically reduced from 10.8%E (10.7, 11.0%E) to 5.8%E (5.7, 5.9%E) if all high-SFA foods consumed were replaced by the corresponding low-SFA/high-UFA foods. Modeled usual intake of SFA after substitution was <10%E in 100% of Canadians, irrespective of sex and age. Almost half (44%) of the modeled reduction in SFA intake was attributed to replacement of SFA-rich foods not recommended in the 2019 CFG. This food-based substitution modeling analysis suggests that consumption of SFA would be below 10%E in Canada if all Canadians adhered to the 2019 CFG recommendation that foods containing mostly UFA should replace foods that contain mostly SFA.


Relationship between initial management strategy and survival in patients with gastric outlet obstruction due to gastric cancer.
The optimal management of gastric outlet obstruction (GOO) due to gastric cancer (GC) is unclear. We examined the relationships between clinical and management variables and outcomes in patients with GC having GOO. The GOO management and clinical course were reviewed in patients with GC and GOO. Cox regression and Kaplan-Meier analyses were used to identify variables predictive of overall survival (OS). The study included 59 patients. Eleven had imaging evidence of metastasis and 35 had pathologically confirmed peritoneal disease. Initial management included resection in 23 patients, feeding jejunostomy ± decompressive gastrostomy (JT/GT) in 25, surgical gastrojejunostomy in five, and endoscopic intervention in six. Seven patients with initial JT/GT underwent resection after neoadjuvant therapy. Median OS (95% confidence interval [CI]) was 21.4 (0.0-45.1) months in the upfront resection group (median follow-up, 14.7 months) and not reached in those with initial JT/GT, neoadjuvant therapy, and later resection (median follow-up, 26.5 months) (P = .18). On multivariable analysis, clinically positive nodes (hazard ratio [HR]: 3.76; 95% CI, 1.17-12.12; P = .03), metastasis on CT (HR: 3.97; 95% CI: 1.53-10.26;P = .01), and resection (HR: 0.37; 95% CI: 0.17-0.79;P = .01) independently predicted OS. In GOO due to GC, OS is similar after treatment with upfront resection compared with JT/GT, neoadjuvant therapy, and later resection. Upfront JT/GT may allow patients to tolerate chemotherapy and improve selection for gastrectomy.


Nutritional rickets and z scores for height in the United Arab Emirates: to D or not to D?
Vitamin D deficiency is still prevalent worldwide, including the Middle East. A cohort of patients with nutritional rickets was treated with vitamin D(2) (ergocalciferol) alone. After this intervention, patients were followed to document changes in z scores for height after treatment. The secondary aim was to determine the proportion of affected children who had vitamin D deficiency or calcium deficiency. Z score for height was calculated as the difference between the observed value and the median value, divided by the SD of the population. Z scores were compared in patients before and after treatment. The improvement in z score after treatment was 0.86 +/- 0.95. The 95% confidence interval for the mean difference was 1.32-0.40 (t = 3.95, P < 0.001). With a diagnostic cut-off for 25 hydroxyvitamin D(3) (25D) deficiency of <25 nmol/L, only half were diagnosed with severe vitamin D deficiency. The remaining patients had presumable calcium deficiency. The alkaline phosphatase (ALP) was negatively correlated to z scores, implying that higher ALP concentrations predicted severe bone disease (lower z scores). The variables 25D and age were moderately and positively correlated (Pearson's r = 0.59, 95%CI: 0.15-0.84; P = 0.01), indicating that younger infants had the lowest 25D levels. Vitamin D alone was efficient in resolving radiological and biochemical disturbances as well as improving z scores for height in a cohort of children with nutritional rickets, which included patients with 25D deficiency as well as calcium deficiency. The results support the hypothesis of the interplay and continuum of 25D deficiency and calcium deficiency in the pathogenesis of rickets.


Setting optimal parameters for in vitro electrotransfection of B16F1, SA1, LPB, SCK, L929 and CHO cells using predefined exponentially decaying electric pulses.
To achieve the maximal introduction of plasmid DNA into cells and, at the same time, to prevent undesirable cell deaths, electrotransfection conditions should be determined for every single cell type individually. In the present study, we determined the optimal electrotransfection parameters for in vitro transfection of B16F1, SA1, LPB, SCK, L929 and CHO cells. Some of these varying parameters were electric field strength, number of applied pulses and their duration, osmolarity of electroporation buffer, plasmid DNA concentration and temperature at which the electroporation was carried out. The maximal transfection rates at optimal electrotransfection parameters in B16F1, SA1, LPB, SCK, L929 and CHO were 85%, 40%, 60%, 1%, 40% and 65%, respectively. The obtained results confirmed that the electroporation is a useful procedure for an in vitro transfection of the majority of mammalian cells. The method, if optimized, may generate reproducibly high proportion of transfected cells among the cell types that are sensitive to electric field action. Thus, the determined parameters could serve for the subsequent implementations of this method.


Targeting the Apo2L/TRAIL system for the therapy of autoimmune diseases and cancer.
Apo 2 ligand/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL), is a member of the TNF family of cytokines, which can induce apoptotic cell death in cells expressing at least one of their specific death receptors, DR4 (TRAIL-R1) or DR5 (TRAIL-R2). In the last decade, the Apo2L/TRAIL system of apoptosis has attracted significant interest as a potential drug-targeting pathway for human therapy, due to the ability of that cytokine to trigger apoptosis in various types of cancer cells while displaying low or no toxicity to normal cells. Recent results suggest that manipulating the Apo2L/TRAIL system may be also useful for the treatment of inflammatory disorders such as rheumatoid arthritis. For its possible therapeutic use, a number of receptor-specific Apo2L/TRAIL molecular variants and agonistic monoclonal antibodies have been developed, and some of them are in clinical trials. In addition, Apo2L/TRAIL-resistant tumors can be sensitized to Apo2L/TRAIL by selected novel or classical chemotherapeutic agents, opening new possibilities for combined therapies. We will briefly review the current status of Apo2L/TRAIL-based therapies for human disease, their promises and limitations.


Robot-assisted removal of inferior vena cava filter.
This case describes a 57-year-old morbidly obese woman with complications of a permanent Bard inferior vena cava (IVC) filter (BD Bard, Covington, Ga) placed in 2005. She complained of recurrent abdominal pain for 6 years associated with constipation, nausea, and bloating. Computed tomography venography showed an IVC filter with malposition, strut fracture, and extrusion, and a fractured strut protruded outside of the vena cava, adjacent to the distal right common iliac artery. The da Vinci Xi Surgical System (Intuitive Surgical, Sunnyvale, Calif) was used to remove the IVC filter and its displaced fractured strut. The operation time was 189 minutes, with an estimated blood loss of 200 mL. She was discharged home on postoperative day 2 with no complications. She had complete resolution of abdominal pain at her follow-up appointment.


Development of a sensitive and specific time resolved fluorimetric immunoassay for the bovine acute phase protein haptoglobin (Hp).
Haptoglobin (Hp) is recognised as a major acute phase protein in the bovidae and its presence in serum is used as an indicator of inflammation. A mouse monoclonal antibody (1D9) specific for bovine Hp was labelled with a lanthanide (Eu) chelate and used to develop a competitive immunoassay. This competitive immunoassay allowed direct measurement of Hp in serum and was validated for intra- and interassay coefficients of variation (below 8%). Cross-reactivity with other serum proteins was measured (less than 0.1%) and limits of detection for Hp in serum were established for adult male (0.344 microgram/ml) and adult female cattle (1.589 micrograms/ml). The immunoassay was compared with an established haptoglobin-haemoglobin binding assay.


An educate, test and treat model towards elimination of hepatitis C infection in Egypt: Feasibility and effectiveness in 73 villages.
Egypt has one of the highest burdens of HCV infection worldwide. It has a large treatment programme, but reaching rural communities represents a major challenge. We report on the feasibility and effectiveness of a comprehensive community-based HCV prevention, testing and treatment model whose goal was to eliminate infection from all adult villagers. An HCV "educate, test and treat" programme was implemented in 73 villages across 7 governorates in Egypt between 06/2015 and 06/2018. The programme model comprised community mobilisation facilitated by a network of village promoters to support the education, testing and treatment of patients, as well as fundraising in the local community. Comprehensive testing, linkage to care and treatment were provided for all eligible villagers aged 12 to 80 years. Of 221,855 eligible villagers, 204,749 (92.3%, 95% CI 91.6-93.5) were screened for HCV antibody and HBsAg, of whom 33,839 (16.5%, 95% CI 12.2-16.1) and 763 (0.4%, 95% CI 0.3-0.5) were positive, respectively. Nearly all 33,839 HCV antibody positive individuals had a sample immediately collected for HCV RNA testing, and 15,892 were HCV RNA positive. The overall prevalence of HCV viraemia was 7.8%. A total of 14,495 (91.2%, 95% CI 89.9-96.4) patients received treatment within a median of 2.1 weeks from serological diagnosis (IQR 0.6-3.3 weeks) and a sustained virological response was achieved among 14,238 of the treated cases (98.3%, 95% CI 96.7-98.6). Cirrhosis was present in 3,192 patients (20.1%), of whom 166 (5.2%) were diagnosed with hepatocellular carcinoma. There was treatment coverage and cure of 84.6% of the estimated 17,137 infected persons aged 12-80 years across the 73 villages. In this study of more than 200,000 villagers, we demonstrated the feasibility and effectiveness of a community-based "educate, test and treat" programme as a model for the elimination of HCV infection in rural communities. A large community-based educate, test and treat hepatitis C programme was conducted in more than 200,000 villagers across 73 villages in Egypt. This study demonstrates that a simplified care model can achieve high uptake of testing, linkage to care and treatment, with high cure rates. We consider this a model for the elimination of hepatitis C virus infection in rural communities, which can be applied to other countries highly affected by hepatitis C.


Defective lateralized attention for non-verbal sounds in developmental dyslexia.
The performance of dyslexic and control children--matched for age, sex, handedness and performance IQ--was compared on a dichotic listening task in which the stimuli were environmental sounds. Two findings emerged. First, the dyslexic group showed a normal, left ear perceptual advantage for these non-verbal materials. Second, the dyslexics were incapable of occluding dichotically presented sounds to the left ear when required to deploy attention only to sounds entering the right ear. This failure of unilateral selective attention was not found in the controls, nor in either group under a condition of left ear only attention. The data were interpreted as undermining the bihemispheric non-verbal processing hypothesis of developmental dyslexia. It was argued that the dyslexics' apparent inability to override voluntarily the reflexive lateral orienting mechanism was most consistent with explanatory models emphasizing defective functioning, or even malformation, of the left cerebral hemisphere alone.


Leisure-time exercise, physical activity during work and commuting, and risk of metabolic syndrome.
Data are limited regarding effect of intensity of leisure-time physical activity on metabolic syndrome. Furthermore, no prospective data are available regarding effect of occupational and commuting physical activity on metabolic syndrome. We compared metabolic syndrome risk by intensity level of leisure-time exercise and by occupational and commuting physical activity in Japanese workers. We followed 22,383 participants, aged 30-64 years, without metabolic syndrome until 2014 March (maximum, 5 years of follow-up). Physical activity was self-reported. Metabolic syndrome was defined by the Joint Statement criteria. We used Cox regression models to estimate the hazard ratios (HRs) and 95 % confidence intervals (CIs) of metabolic syndrome. During a mean follow-up of 4.1 years, 5361 workers developed metabolic syndrome. After adjustment for covariates, compared with engaging in no exercise, the HRs (95 % CIs) for <7.5, 7.5 to <16.5, and ≥16.5 metabolic equivalent hours of exercise per week were 0.99 (0.90, 1.08), 0.99 (0.90, 1.10), and 0.95 (0.83, 1.08), respectively, among individuals engaging in moderate-intensity exercise alone; 0.93 (0.75, 1.14), 0.81 (0.64, 1.02), and 0.84 (0.66, 1.06), among individuals engaging in vigorous-intensity exercise alone; and 0.90 (0.70, 1.17), 0.74 (0.62, 0.89), and 0.81 (0.69, 0.96) among individuals engaging in the two intensities. Higher occupational physical activity was weakly but significantly associated with lower risk of metabolic syndrome. Walking to and from work was not associated with metabolic syndrome. Vigorous-intensity exercise alone or vigorous-intensity combined with moderate-intensity exercise and worksite intervention for physical activity may help prevent metabolic syndrome for Japanese workers.


Lentivirus vector driven by polybiquitin C promoter without woodchuck posttranscriptional regulatory element and central polypurine tract generates low level and short-lived reporter gene expression.
Lentivirus (LV) encoding woodchuck posttranscriptional regulatory element (WPRE) and central polypurine tract (cPPT) driven by CMV promoter have been proven to act synergistically to increase both transduction efficiency and gene expression. However, the inclusion of WPRE and cPPT in a lentiviral construct may pose safety risks when administered to human. A simple lentiviral construct driven by an alternative promoter with proven extended duration of gene expression without the two regulatory elements would be free from the risks. In a non-viral gene delivery context, gene expression driven by human polybiquitin C (UbC) promoter resulted in higher and more persistent expression in mouse as compared to cytomegalovirus (CMV) promoter. In this study, we measured the efficiency and persistency of green fluorescent protein (GFP) reporter gene expression in cells transduced with LV driven by UbC (LV/UbC/GFP) devoid of the WPRE and cPPT in comparison to the established LV construct encoding WPRE and cPPT, driven by CMV promoter (LV/CMV/GFP). However, we found that LV/UbC/GFP was inferior to LV/CMV/GFP in many aspects: (i) the titer of virus produced; (ii) the levels of reporter gene expression when MOI value was standardized; and (iii) the transduction efficiency in different cell types. The duration of reporter gene expression in selected cell lines was also determined. While the GFP expression in cells transduced with LV/CMV/GFP persisted throughout the experimental period of 14 days, expression in cells transduced with LV/UbC/GFP declined by day 2 post-transduction. In summary, the LV driven by the UbC promoter without the WPRE and cPPT does not exhibit enhanced or durable transgene expression.


Airmen and health-care providers' attitudes toward the use of genomic sequencing in the US Air Force: findings from the MilSeq Project.
The use of genomic sequencing (GS) in military settings poses unique considerations, including the potential for GS to impact service members' careers. The MilSeq Project investigated the use of GS in clinical care of active duty Airmen in the United States Air Force (USAF). We assessed perceived risks, benefits, and attitudes toward use of GS in the USAF among patient participants (n = 93) and health-care provider participants (HCPs) (n = 12) prior to receiving or disclosing GS results. Participants agreed that there are health benefits associated with GS (90% patients, 75% HCPs), though more HCPs (75%) than patients (40%) agreed that there are risks (p = 0.048). The majority of both groups (67% HCPs, 77% patients) agreed that they trust the USAF with genetic information, but far fewer agreed that genetic information should be used to make decisions about deployment (5% patients, 17% HCPs) or duty assignments (3% patients, 17% HCPs). Despite their hesitancy, patients were supportive of the USAF testing for nondisease traits that could impact their duty performance. Eighty-seven percent of patients did not think their GS results would influence their career. Results suggest favorable attitudes toward the use of GS in the USAF when not used for deployment or assignment decisions.


Lack of evidence of association between MTHFR C677T polymorphism and congenital heart disease in a TDT study design.
Hyperhomocysteinemia is frequently associated with congenital defects of the heart and neural tube. A common missense mutation in the MTHFR gene (C to T substitution at position 677 changing valine to alanine) produces a variant with reduced enzymatic action, resulting in higher plasma levels of homocysteine. The aim of this study is to investigate whether MTHFR C677T functional genetic variant is associated with an increased risk of congenital heart disease (CHD) development using a family-based case-control design and the Transmission Disequilibrium Test (TDT) approach. We selected 91 consecutive patients with congenital heart disease for the study. From these patients we were able to obtain samples on 147 parents. The C677T polymorphism at the MTHFR gene was determined from each participant. A statistically significant association was disclosed in univariate analysis using a family-based case-control design (p<0.0001 assuming an additive genetic model, p<0.0001 assuming a dominant genetic model, and p=0.01 assuming a recessive genetic model). This association was explained by an increased frequency of the T allele in patients as compared to their fathers. However, by using a TDT approach a highly non-significant result was obtained and no association could be defined between this locus and congenital heart disease. We did not find sufficient evidence for an association between MTHFR C677T genotype and congenital heart disease in our study group. Previous reports on such association may be due to population genetic structure.


Fixed nitrogen removal mechanisms associated with sulfur cycling in tropical wetlands.
Wetland ecosystems play an important role in nitrogen cycling, yet the role of anaerobic ammonium oxidation (anammox) in tropical wetlands remains unclear. In the current study the anammox process accounted for 29.8 ~ 57.3% of nitrogen loss in ex situ activity batch tests of microcosms established from anoxic sediments of different tropical wetlands, with the highest activity being 17.95±0.51 nmol-N/g dry sediment/h. This activity was most likely driven by sulfide oxidation with dissimilatory nitrate reduction to ammonium (sulfide-driven DNRA). Microbial community analyses revealed a variety of anammox bacteria related to several known lineages, including Candidatus Anammoximicrobium, Candidatus Brocadia and Candidatus Kuenenia, at different wetlands. Metagenome predictions, batch tests, and isotope-tracing suggested that the high level of anammox activity was due to sulfide-driven DNRA. This was corroborated by a strong correlation (through Pearson's analysis) between the abundance of anammox bacteria and the nrfA (a dissimilatory nitrate reduction to ammonium gene) and dsrA (a sulfate reductase gene) genes, as well as sulfate, ammonium and nitrate concentrations. These correlations suggest syntrophic interactions among sulfate-reducing, sulfide-driven DNRA, and anammox bacterial populations. A better understanding of the role of sulfur in nitrogen loss via the anammox reaction in natural systems could inform development of a viable wastewater treatment strategy that utilizes sulfate to minimize the activity of denitrifying bacteria and thus to reduce nitrous oxide emissions from wastewater treatment plants.


Serological studies on the antigenic relationship between herpes simplex virus and varicella-zoster virus.
If crossreacting antibodies between varicella-zoster virus (VZV) and herpes simplex virus (HSV) exist, one would expect more positive reactions with VZV in a group of HSV positive patients than in a group of HSV negative patients. This statement can only apply to a group of individuals where positive and negative reactions with respect to HSV and VZV are evenly distributed. Such a distribution can only be found among children. Therefore, the relationship between HSV-1 and VZV was the only one which was considered in this investigation, since the incidence of HSV-2 antibodies in children is very rare. The sera from 197 children were examined using the neutralization test (NT), the complement fixation test (CFT) and the indirect immunofluorescent assay (IFT) and could be classified as either HSV positive (80) or HSV negative (117). The children's ages were similar in both groups. Approximately the same proportion of VZV positive sera was found in both groups when examined using IFT (53% in the HSV positive and 47% in the HSV negative group). However, when the CFT was applied the proportion of VZV positive sera in the two groups differed markedly (22% of the HSV positive sera and 38% of the HSV negative sera). These findings suggest that crossreactivity observed between HSV and VZV in acute HSV and VZV infections is evidently not dependent on crossreacting antibodies but is apparently confined to the cellular level of the immune response.


Effect of resveratrol and combination of resveratrol and donepezil on the expression of microglial cells and astrocytes in Wistar albino rats of colchicine-induced Alzheimer's disease.
The goal was to evaluate the effect of resveratrol (RS) and combination therapy of RS and donepezil (DPZ), on the numerical expression of microglial cells and astrocytes, in the frontal cortex, regions of the hippocampus in colchicine-induced Alzheimer's disease (AD) model. The study involved male albino Wistar rats of three months, age and consisted of 6 groups, with six animals each. The immunohistochemical staining with mouse monoclonal anti-human CD 68 and mouse monoclonal anti-GFAP was performed to assess the number of microglial cells and astrocytes, respectively. AD group showed an increase in the number of microglia, and the numbers declined in the treatment groups, RS 10, RS 20, RS10/10 and DPZ + RS (p < 0.001). Astrocyte count was increased in the treatment groups in contrast to the AD group (p < 0.05). The DPZ + RS combination group revealed substantial elevation in the number of astrocytes and decreased microglial number among all the groups (p < 0.001). RS administration has diminished the microglial number and elevated the number of astrocytes. The elevated reactive astrocytes have decreased the microglial population. However, the limitation of our study is utilizing the colchicine for the induction of neurodegeneration. Using the transgenic models of AD may give a better insight into the pathogenesis and effect of RS. Another limitation of this study is the administration of RS and DPZ through different routes. The prospects of this research include studying the probiotic nature of RS and the effect of RS in other neurodegenerative disorders.


Antigenic/allergenic characterization of American and German cockroach extracts.
Cockroach allergens have been implicated as clinically significant sensitizing agents in the induction/exacerbation of "urban asthma." In the present study, approximately 50% of atopic, predominantly inner-city residents had immediate wheal-and-flare cutaneous reactivity to a commercial American cockroach whole body extract. Crude whole body extracts were prepared in our laboratory from both American (Periplaneta americana) and German (Blatella germanica) cockroach species. Crossed immunoelectrophoresis of American cockroach whole body extract (AWBE) and German cockroach whole body extract (GWBE) detected a total of 50 and 56 precipitin peaks, respectively, when extracts were reacted with hyperimmunized rabbit antisera. Crossed radioimmunoelectrophoresis identified at least five electrophoretically distinct allergens each in AWBE and GWBE. Cockroach whole body extracts produced two major protein peaks when extracts were fractionated on Sephadex G-75. RAST-inhibition studies demonstrated allergens in both peak 1 and the immediate trailing fractions of the column. Direct RAST and end point prick skin testing confirmed the presence of significant/important allergens in column "fraction 2" of AWBE. Skin testing and RAST analysis suggested the occurrence of shared and species-specific allergens between AWBE and GWBE. Collectively, these studies confirm the important sensitizing potential of cockroach allergens, characterize their number and size distribution by crossed radioimmunoelectrophoresis and column chromatography, support the occurrence of significant allergens in column "fraction 2," and suggest the occurrence of both species-specific and shared interspecies allergens.


Quality of life in patients with cervical cancer between the Han nationality and ethnic minorities in the Yunnan Province of China.
Cervical cancer is the fourth most diagnosed cancer and the leading cause of cancer death, and it still poses a crippling threat to women's health. China launched the National Cervical Cancer Screening Program for Rural Women in 2009, and an increasing number of cervical cancer patients have been detected. Health-related quality of life is not only the end point of cancer research but is also related to socioeconomic and clinical factors and has received an increasing amount of attention. In light of the characteristics of the Yunnan nationality, we conducted cross-sectional research to assess and explore the health-related quality of life in both Han and ethnic minority patients. A cross-sectional study was conducted from January 2020 to May 2021 at the Third Affiliated Hospital of Kunming University/Yunnan Cancer Hospital. Patients, including 100 Han patients and 100 ethnic minorities, were interviewed using the FACT-Cx questionnaire within 3 months of receiving treatment. Patients of Han ethnicity and ethnic minorities were comparable in both sociodemographic and clinical features. The total FACT-Cx scores were 139.38 ± 9.83 and 134.39 ± 13.63 in Han and ethnic minority patients, respectively (P < 0.05). Significant differences were shown in physical well-being, emotional well-being and the FACT-Cx subscale between the Han and ethnic minority groups. Independent predictors of the FACT-Cx scale were ethnicity, educational level, participation in the National Cervical Cancer Screening Program for Rural Areas (NCCSPRA) and clinical stage. The results of our study imply that the HRQOL of Han patients is better than that of ethnic minority patients. Thus, clinicians and related health workers should pay more attention to the HRQOL of cervical cancer patients, especially for ethnic minority patients, and provide psychosocial interventions as much as possible to improve their HRQOL. Policies should also aim to strengthen health education regarding cervical cancer and expand the coverage of the NCCSPRA among those who are ethnic minorities, are older and have low educational levels.


Biochemical characterization of Serpula lacrymans iron-reductase enzymes in lignocellulose breakdown.
Putative iron-reductase (IR) genes from Serpula lacrymans with similarity to the conserved iron-binding domains of cellobiose dehydrogenase (CDH) enzymes have been identified. These genes were cloned and expressed to functionally characterize their activity and role in the decomposition of lignocellulose. The results show that IR1 and IR2 recombinant enzymes have the ability to depolymerize both lignin and cellulose, are capable of the reduction of ferric iron to the ferrous form, and are capable of the degradation of nitrated lignin. Expression of these genes during wheat straw solid-state fermentation was shown to correlate with the release of compounds associated with lignin decomposition. The results suggest that both IR enzymes mediate a non-enzymatic depolymerisation of lignocellulose and highlight the potential of chelator-mediated Fenton systems in the industrial pre-treatment of biomass.


Production of non-activated biochar based on Biden pilosa and its application in removing methylene blue from aqueous solutions.
Biden pilosa (BP) is a type of weed commonly found in Thailand that needs to be removed from agricultural areas for protecting main crops. This research proposed a method to reduce BP by using BP as a feedstock for biochar production. Non-activated BP biochar from fresh BP was produced in pilot scale using a drum kiln with a heat-transferring duct at a pyrolysis temperature of 550 °C at a slow heating rate. The physical properties of the non-activated BP biochar were investigated using scanning electron microscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction, and a surface area analyzer. A batch experiment was used to study the adsorption behavior of methylene blue (MB) on BP biochar. The microstructure study of the BP biochar indicated that it has a cell structure similar to that of BP, which shows the non-destructive nature of the proposed technique for BP production. Six dominant peaks at 3283, 2915, 1559, 1403, 1116, and 863/839 cm⁻1 were observed in the FTIR spectrum. The BP biochar exhibited a surface area of 5.21 m2/g and a pore size of 8 nm. The adsorption of MB on the BP biochar followed the Langmuir adsorption isotherm and pseudo-second-order kinetics. The Langmuir-based maximum adsorption capacity of MB on the BP biochar was 200 mg/g at 303 K.


Assessment of safety and efficacy of perinatal or peripubertal exposure to daidzein on bone development in rats.
Neonatal exposure to isoflavones improved bone health in thereafter in previous animal studies. However, since isoflavones possess hormonal activity, it may interfere with reproductive development. In the present study, we assessed the safety and efficiency of perinatal or peripubertal exposure to daidzein on bone and reproductive organ development at early adulthood in rats. Sprague-Dawley pregnant rats (n = 18) were divided into 3 groups: (1) dams and their offspring were fed the control diet. (2) Dams were fed the daidzein diet (0.5 g daidzein/kg diet) during pregnancy and then the control diet at postnatal day 13 and their offspring were fed the control diet. (3) Dams and their offspring were fed the daidzein diet through the experiment. While perinatal exposure to daidzein did not confer a positive effect on bone mineral density on postnatal day 35, peripubertal exposure to daidzein protected against a decline in bone mineral density. Meanwhile, exposure to daidzein during the perinatal or peripubertal period did not affect reproductive organ weights at early adulthood in rats. Further investigations should assess the mechanisms underlying these responses of bone metabolism to daidzein, as well as the safety of daidzein exposure during the perinatal period and throughout life.


Development and initial validation of a 15-item informant version of the Geriatric Depression Scale.
To develop a brief informant version of the Geriatric Depression Scale for use in screening for depression in older adults. A scale development and validation study. Internal medicine and geriatric outpatient clinics located at the James A. Haley Veterans' Medical Center and the University of South Florida Medical Center, Tampa, Florida. A total of 147 patients (81 females and 66 males) and their adult informants. Self and informant versions of the 30-item Geriatric Depression Scale, NEO-FFI, and a health behaviors questionnaire. The 15-item informant version of the GDS was found to have sufficient internal consistency reliability (alpha = 0.86) and retest reliability (r = 0.81) to support its use as a clinical instrument. Construct validity was demonstrated by a pattern of correlations with external demographic and personality variables consistent with those of other versions of the GDS, as well as substantive correlations with these other versions. Efficacy of the GDSI-15 was found to be as good as that for the full 30-item informant version of the GDS. The GDSI-15 may be a useful adjunct or alternative to standard screening methods in assessing patients in outpatient settings.


Adherence to quality measures in a pediatric epilepsy center: a pilot study.
A retrospective study was conducted to determine compliance with the American Academy of Neurology quality measures for epilepsy care in a single tertiary care pediatric epilepsy clinic. Paper and electronic charts of children 0 to 20 years of age, with an established diagnosis of epilepsy, who receive their medical care at the Children's Hospital of Michigan in Detroit, were reviewed. Of the eight quality measures suggested for surveillance, the least compliant measures were counseling for young adults of childbearing age and recommendations regarding epilepsy specific safety issues. The quality measures where greatest adherence was demonstrated were ordering and review of electroencephalogram results at clinic visits and documentation of frequency of seizures. Practitioner education, use of electronic checklists, and an automated tracking system may enhance compliance and ultimately lead to superior patient care.


Corticosteroid inhibition of biosynthesis of lung surfactant phospholipids in early human pregnancy.
Lung slices from human mid-trimester fetuses were incubated for 3 days. Hydrocortisone tended to decrease the biosynthesis of pulmonary phospholipids. It is suggested that cell proliferation is inhibited without inducing functional maturity.