Capsule polysaccharide is a bacterial decoy for antimicrobial peptides.
Antimicrobial peptides (APs) are important host weapons against infections. Nearly all APs are cationic and their microbicidal action is initiated through interactions with the anionic bacterial surface. It is known that pathogens have developed countermeasures to resist these agents by reducing the negative charge of membranes, by active efflux and by proteolytic degradation. Here we uncover a new strategy of resistance based on the neutralization of the bactericidal activity of APs by anionic bacterial capsule polysaccharide (CPS). Purified CPSs from Klebsiella pneumoniae K2, Streptococcus pneumoniae serotype 3 and Pseudomonas aeruginosa increased the resistance to polymyxin B of an unencapsulated K. pneumoniae mutant. Furthermore, these CPSs increased the MICs of polymyxin B and human neutrophil alpha-defensin 1 (HNP-1) for unencapsulated K. pneumoniae, Escherichia coli and P. aeruginosa PAO1. Polymyxin B or HNP-1 released CPS from capsulated K. pneumoniae, S. pneumoniae serotype 3 and P. aeruginosa overexpressing CPS. Moreover, this material also reduced the bactericidal activity of APs. We postulate that APs may trigger in vivo the release of CPS, which in turn will protect bacteria against APs. We found that anionic CPSs, but not cationic or uncharged ones, blocked the bactericidal activity of APs by binding them, thereby reducing the amount of peptides reaching the bacterial surface. Supporting this, polycations inhibited such interaction and the bactericidal activity was restored. We postulate that trapping of APs by anionic CPSs is an additional selective virulence trait of these molecules, which could be considered as bacterial decoys for APs.


Spontaneous cervicothoracic epidural misinterpreted as transient ischemic attack (TIA).
The acute onset of a spontaneous spinal epidural hematoma (SSEH) is an uncommon cause of spinal cord compression. Early diagnosis and treatment are critical to avoid significant residual postoperative neurological deficits. A 15-year-old male presented with the sudden onset of a hemiparesis which recovered (4/5 weakness). The brain MR was negative, but spinal MRI revealed a dorsolateral extradural lesion extending from C7 to D1. At surgery, this proved to be a hematoma that we readily removed. Spontaneous epidural hematomas are rare. They should be diagnosed promptly with MR, and typically warrant urgent/emergent surgical excision. Further, cases of SSEH resulting in hemiparesis may occasionally be misdiagnosed as attributed to a stroke or transient ischemic attack.


Effect of spasticity of the ankle plantar flexors on the walking speed of hemiplegic stroke patients after maximum walking speed exercises.
Yamada T, Ohta M, Tamari M. Effect of spasticity of the ankle plantar flexors on the walking speed of hemiplegic stroke patients after maximum walking speed exercises. Jpn J Compr Rehabil Sci 2021; 12: 64-69. This study examined the effect of ankle plantar flexor spasticity on the walking speed of hemiplegic stroke patients immediately following maximum walking speed exercises. A total of 23 hemiplegic stroke patients were divided into two groups based on the presence (n = 13) or absence (n = 10) of ankle plantar flexor spasticity on the paralyzed side. Gait speed, propulsive force during pre-swing, paretic side ankle plantar flexion movement during pre-swing, paretic side ankle dorsiflexion angle during the stance phase, angular velocity of paretic side dorsiflexion during the stance phase, paretic side trailing limb angle in the terminal stance, paretic side plantar flexion angle in the terminal stance, and the timing of maximum dorsiflexion of the ankle joint on the paretic side were measured before and after the maximum walking speed exercises, using a three-dimensional motion analyzer. In the spasticity group, no significant improvement was observed in any of the categories. In contrast, in the non-spasticity group, significant improvement was observed in all categories, except for the paretic side ankle dorsiflexion angle. This study showed that maximum walking speed exercises immediately improved walking speed in hemiplegic stroke patients without ankle plantar flexor spasticity.


Adhesion molecules in skeletogenesis: II. Neural cell adhesion molecules mediate precartilaginous mesenchymal condensations and enhance chondrogenesis.
Neural cell adhesion molecules (NCAM) was expressed transiently by mesenchymal cells in precartilaginous condensations of the embryonic chicken limb but was lost upon differentiation into cartilage. Consequently, NCAM was present in the periphery of the limb anlagen but was absent in the cartilaginous center of the growing limb. To determine NCAM function in limb bud chondrogenesis we incubated dissociated stage 22/23 distal mesenchymal limb bud cells with Fab' fragments of antibodies to NCAM. Cell aggregation was inhibited by incubating the cells with anti-NCAM Fab'. These results suggest that NCAM may mediate the formation of precartilaginous condensations. This hypothesis was further tested using micromass cultures. NCAM expression in micromass cultures in vitro recapitulated that in vivo. NCAM was enriched in condensations of 2 day cultures, but was diminished and concentrically distributed around cartilage nodules in 4 day cultures. Anti-NCAM Fab' fragments reduced the area occupied by precartilaginous condensations and the degree of chondrogenic differentiation. Control antibody against chicken embryo fibroblasts had no effect. The effect of overexpressing NCAM was analyzed by electroporating expression vectors directing the synthesis of chicken NCAM. Limb bud cells cultured after electroporation with an NCAM expression vector displayed larger cartilage nodules and greater chondrogenic differentiation than cells electroporated with vector alone. The expression of NCAM in electroporated cells also increased. Control experiments using plasmids encoding beta-galactosidase indicated that approximately 10% of the limb bud cells were transfected under these conditions. The results suggest that NCAM is involved in the chondrogenesis pathway by mediating the formation of precartilaginous condensations.


Shift of large-scale atmospheric systems over Europe during late MIS 3 and implications for Modern Human dispersal.
Understanding the past dynamics of large-scale atmospheric systems is crucial for our knowledge of the palaeoclimate conditions in Europe. Southeastern Europe currently lies at the border between Atlantic, Mediterranean, and continental climate zones. Past changes in the relative influence of associated atmospheric systems must have been recorded in the region's palaeoarchives. By comparing high-resolution grain-size, environmental magnetic and geochemical data from two loess-palaeosol sequences in the Lower Danube Basin with other Eurasian palaeorecords, we reconstructed past climatic patterns over Southeastern Europe and the related interaction of the prevailing large-scale circulation modes over Europe, especially during late Marine Isotope Stage 3 (40,000-27,000 years ago). We demonstrate that during this time interval, the intensification of the Siberian High had a crucial influence on European climate causing the more continental conditions over major parts of Europe, and a southwards shift of the Westerlies. Such a climatic and environmental change, combined with the Campanian Ignimbrite/Y-5 volcanic eruption, may have driven the Anatomically Modern Human dispersal towards Central and Western Europe, pointing to a corridor over the Eastern European Plain as an important pathway in their dispersal.


Regulation of SV40 DNA replication by phosphorylation of T antigen.
The role of phosphorylation in regulating the biochemical properties of SV40 large T antigen has been examined. Treatment of purified T antigen with calf intestinal alkaline phosphatase resulted in the removal of 80% of the 32P label. This partially dephosphorylated T antigen displayed an increase in its ability to support DNA replication in vitro. This increase in replication activity was paralleled by an activation of specific DNA binding to site II, a necessary element within the origin of SV40 DNA replication. In contrast, the ATPase activity of dephosphorylated T antigen remained unchanged. These results demonstrate that DNA replication is regulated by phosphorylation of an origin specific DNA binding protein.


[Self-reported physical activity in comparison with anthropometric body fat indicators in school children].
Obesity is a public health problem associated with physical inactivity. Autoreported physical activity was related with anthropometric indicators of body fat in a group of school children. The descriptive, cross-sectional study that included 1,593 children aged 10 to 14 years from Bogotá and five provinces of central and eastern Colombia. Body weight, height, arm circumference and triceps skinfold were measured. Data on leisure time physical activity and type of activity were obtained by interview of each participant. The proportion of children reporting no leisure time physical activity was high (19% in Bogotá, 28% in the central-eastern areas). Low physical activity was characteristically higher in girls and associated with public schools (in contrast with private schools). Physical activity was not associated with anthropometric indicators. The lack of association between physical activity and body adiposity may be due to the method of inquiry where the physical activity being reported was insufficient to induce changes in body composition. Additional studies are necessary that evaluate in greater detail the frequency, intensity and duration of physical activity to provide more definitive conclusions. However, the higher prevalence of inactivity in girls and the differences by type school constitute causes for concern.


[Morpho-functional analysis of the steroid-producing cells in pink salmon fry gonads Oncorhynhus gorbuscha (Walbaum) in normal condition and after estradiol treatment].
Localization and peculiarities of steroid-producing cells of gorbuscha fry gonads were studied in normal conditions and after experimental conditions. In females steroid-producing cells are found also in the follicle tunica and between interstitial cells, greatly differing in ultrastructure in these two localities. In males, these cells are located only in the testicular tunica, being homogeneous in ultrastructure. Chronical hormonal treatment of the fry with oestradiol-dipropionate induced in males, contrary to females, a considerable increase in the number and functional activity of steroid-producing cells and the appearance of these cells in the stroma of testis also. In females only a mass appearance of lipid-like droplets in the cytoplasm of steroid-producing cells is observed, which is also characteristic of males. The revealed morpho-functional peculiarities of steroid-producing cells are discussed in terms of their presumed important role in regulation of sex differentiation in fishes.


Chemistry and Pharmacological Actions of Delphinidin, a Dietary Purple Pigment in Anthocyanidin and Anthocyanin Forms.
Anthocyanins are naturally occurring water-soluble flavonoids abundantly present in fruits and vegetables. They are polymethoxyderivatives of 2-phenyl-benzopyrylium or flavylium salts. Delphinidin (Dp) is a purple-colored plant pigment, which occurs in a variety of berries, eggplant, roselle, and wine. It is found in a variety of glycosidic forms ranging from glucoside to arabinoside. Dp is highly active in its aglycone form, but the presence of a sugar moiety is vital for its bioavailability. Several animal and human clinical studies have shown that it exerts beneficial effects on gut microbiota. Dp exhibits a variety of useful biological activities by distinct and complex mechanisms. This manuscript highlights the basic characteristics, chemistry, biosynthesis, stability profiling, chemical synthesis, physicochemical parameters along with various analytical methods developed for extraction, isolation and characterization, diverse biological activities and granted patents to this lead anthocyanin molecule, Dp. This review aims to open pathways for further exploration and research investigation on the true potential of the naturally occurring purple pigment (Dp) in its anthocyanidin and anthocyanin forms beyond nutrition.


Effect of Divalent Cations and Other Ions on the Tetrahydrofuran Crystal Inhibition of Quaternary Ammonium Salts-Relevance to the Efficiency of Gas Hydrate Quaternary Anti-agglomerants.
Gas hydrate anti-agglomerants (AAs) are a class of low-dosage hydrate inhibitor that are used to prevent plugging of gas hydrates in oil and condensate upstream flow lines. Industrial AAs are mostly cationic surfactants which are "hydrate-philic", i.e., they are designed to interact with and modify gas hydrate crystal growth. Tetrahydrofuran (THF) hydrate crystal growth studies have been used for many years to determine useful functional groups to incorporate into AA surfactants. In particular, quaternary ammonium and phosphonium salts with optimized alkyl groups show good THF crystal growth inhibition, which is a key property for AAs. AAs are often screened and tested in model brines containing sodium chloride despite the produced water containing various divalent cations. Recent studies have shown that AAs performed better when tested in brines containing both sodium and calcium ions rather than just sodium ions. Here, we present THF hydrate crystal growth studies on quaternary ammonium and phosphonium salts and other related molecules including guanidinium salts and amine oxides. Tests were carried out with a variety of cations including sodium, calcium, magnesium, and lithium at identical pre-determined subcooling, in order to investigate the effect of the ion size and charge density on the crystal growth inhibition. We also investigate the effect of using the more polarizable iodide ions compared to chloride ions. Our results show that crystal growth inhibition in solutions with calcium ions is somewhat greater than that with sodium ions, in agreement with past studies on the effect of AA performance with mono- and divalent cations. However, the variation does not seem to be primarily related to the charge density and polarizing ability of the cations. This study therefore provides evidence that AAs should be tested in brines containing all the ions present in the produced water and not just sodium chloride brine.


Influence of serum concentrations of catecholamines and i.v. or volatile anaesthesia on evoked electromyography in the hand.
We have examined the correlation between serum concentrations of catecholamines and the evoked electromyographic (EEMG) response from the first dorsal interosseous muscle of the hand in 20 patients during minor surgery under propofol or enflurane anaesthesia without neuromuscular blocking drugs. The supinated forearm, with the wrist fully extended, was strapped firmly to an armboard and immobilized with adhesive tape. In the propofol group, the mean EEMG response to the first stimulus in the train-of-four (T1) decreased to 83.0% (95% confidence intervals (CI) 78.7-87.3%) of baseline, while in the enflurane group the mean EEMG T1 response decreased to 84.0% (95% CI 81.6-86.4%) of baseline. The decrease in the EEMG response occurred over 20 min and did not correlate with plasma concentrations of adrenaline or noradrenaline (correlation coefficients all < 0.26). We conclude that the decrease in EEMG response during the first 30 min of anaesthesia occurred during both i.v. and inhalation anaesthesia, and that changes in plasma concentrations of catecholamines did not cause the decrease in the EEMG response.


The Determination of Rod and Cone Photoreceptor Fate.
Photoreceptors have been the most intensively studied retinal cell type. Early lineage studies showed that photoreceptors are produced by retinal progenitor cells (RPCs) that produce only photoreceptor cells and by RPCs that produce both photoreceptor cells and other retinal cell types. More recent lineage studies have shown that there are intrinsic, molecular differences among these RPCs and that these molecular differences operate in gene regulatory networks (GRNs) that lead to the choice of the rod versus the cone fate. In addition, there are GRNs that lead to the choice of a photoreceptor fate and that of another retinal cell type. An example of such a GRN is one that drives the binary fate choice between a rod photoreceptor and bipolar cell. This GRN has many elements, including both feedforward and feedback regulatory loops, highlighting the complexity of such networks. This and other examples of retinal cell fate determination are reviewed here, focusing on the events that direct the choice of rod and cone photoreceptor fate.


Role of Exosomal MicroRNAs and myomiRs in the Development of Cancer Cachexia-Associated Muscle Wasting.
Cachexia is a complex metabolic syndrome that promotes great weight loss, with marked muscle mass wasting. In the last years, many efforts have been directed to improve the understanding of the mechanisms involved in the disease. This syndrome is present in up to 80% of cancer patients and, despite its clinical relevance, is underdiagnosed. The orchestration of the molecular and biochemical disruptions observed in cachexia is paralleled by inflammation and the communication among the different body compartments, including the tumor and the skeletal muscle, is still not completely described. One of the mechanisms that may be involved in the transduction of the inflammatory signals and the activation of catabolic status in muscle is the participation of exosomes containing microRNAs (miRNAs) and muscle-specific miRNAs (myomiRs). Exosomes are nanovesicles, measuring from 30 to 100 µm, and able to carry miRNAs in the circulation, promoting cell-cell and tissue-tissue communication in an autocrine, paracrine, and endocrine manner. miRNAs transported in exosomes are preserved from degradation, while these nanoparticles deliver the cargo to specific cell targets, making communication more efficient. Several miRNAs are known to modulate inflammatory pathways, to induce metastasis, to mediate cancer aggressiveness and even to participate in the regulation of protein synthesis and degradation pathways in the skeletal muscle. The aim of this mini-review is to describe the present knowledge about the role of exosomal miRNAs and myomiRs in the induction of muscle mass wasting in cancer cachexia state and to explain which transcription factors, proteins, and pathways are regulated by these molecules.


Anaesthesia for robotic gynaecological surgery.
Robotic surgery is gaining widespread popularity due to advantages such as reduced blood loss, reduced postoperative pain, shorter hospital stay and better visualisation of fine structures. Robots are being used in urological, cardiac, thoracic, orthopaedic, gynaecological and general surgery. Robotic surgery received US Food and Drug Administration approval for use in gynaecological surgery in 2005. The various gynaecological robotic operations being performed are myomectomy, total and supracervical hysterectomy, ovarian cystectomy, sacral colpopexy, tubal reanastomosis, lymph node dissection, surgery of retroperitoneal ectopic pregnancy, Moskowitz procedure and endometriosis surgery. The anaesthetic considerations include difficult access to the patient intraoperatively, steep Trendelenburg position, long surgical duration and the impact of pneumoperitoneum. We highlight the complications encountered in these surgeries and methods to prevent these complications. Robotic gynaecological surgery can be safely performed after considering the physiological effects of the steep Trendelenburg position and of pneumoperitoneum. The benefits of the surgical procedure should be weighed against the risks in patients with underlying cardiorespiratory problems.


The Effect of Preventive Agents (Mouthwashes/Gels) on the Color Stability of Dental Resin-Based Composite Materials.
The color of dental restorative material should be maintained throughout its functional lifetime in an oral environment. However, the frequent use of mouthwash may affect the color stability of these composite restorations. The aim of this study is to assess the effects of using various mouthwashes on the color stability of various dental restorative composite materials. For this purpose, four mouthwashes/gels (Flocare gel (0.4% stannous fluoride), Pascal gel (topical APF fluoride), Pro-Relief mouthwash (sodium fluoride), and Plax Soin mouthwash (sodium fluoride)), and distilled water as a control, were selected. These were divided into five groups: Group 1: Flocare gel; Group 2: Pascal gel; Group 3: Pro-Relief mouthwash; Group 4: Plax Soin mouthwash; and Group 5: distilled water (control). Prepared restorative materials samples were immersed in the groups of mouthwashes/gels and the distilled water (control) for 24, 48, and 72 h. The discoloration that all materials exhibited with all immersion groups was significantly different at each of the three time periods for all groups (p < 0.05). Results from immersion in Flocare gel, Pascal gel, Pro-Relief mouthwash, and Plax Soin mouthwash were statistically significant (p < 0.05). The color change chroma was not significant for Pro-Relief and Plax Soin mouthwash (p > 0.05). Mouthwashes/gels affect color shifting for all composite resin materials, and changes are exaggerated over time. However, discoloration effects are not perceptible to the human eye.


Kynurenines and vitamin B6: link between diabetes and depression.
The increased association between depression and diabetes mellitus is generally acknowledged. Recent studies suggest that depression leads to diabetes. However, the underlying molecular mechanisms for this association remain unclear. Literature and our data indicate that inflammatory and/or stress factors in depression up-regulate tryptophan (TRP) conversion into kynurenine (KYN), a substrate for nicotinamide adenine dinucleotide (NAD) biosynthesis. Deficiency of vitamin B6, a cofactor of the key enzymes of KYN - NAD pathway, shunts KYN metabolism from formation of NAD towards production of xanthurenic (XA) and kynurenic (KYNA) acids. Human and experimental studies reveal that XA, KYNA and their metabolites interfere with production, release and biological activity of insulin. We propose that inflammation- and/or stress-induced up-regulation of TRP - KYN metabolism in combination with vitamin B6 deficiency is one of the mechanisms mediating increased risk of diabetes in depression. Consequently, monitoring formation of diabetogenic KYN derivatives might help to identify subjects-at-risk for the development of diabetes. Pharmacological down-regulation of the TRP - KYN - NAD pathway and maintenance of adequate vitamin B6 status might help to prevent the development of diabetes in depression and other conditions associated with inflammation/stress- induced excessive production of KYN and vitamin B6 deficiency, e.g., obesity, cardiovascular diseases, aging, menopause, pregnancy, and hepatitis C virus infection.


Post-operative delirium is an independent predictor of 30-day hospital readmission after spine surgery in the elderly (≥65years old): A study of 453 consecutive elderly spine surgery patients.
In the last decade, costs of U.S. healthcare expenditures have been soaring, with billions of dollars spent on hospital readmissions. Identifying causes and risk factors can reduce soaring readmission rates and help lower healthcare costs. The aim of this is to determine if post-operative delirium in the elderly is an independent risk factor for 30-day hospital readmission after spine surgery. The medical records of 453 consecutive elderly (≥65years old) patients undergoing spine surgery at Duke University Medical Center from 2008 to 2010 were reviewed. We identified 17 (3.75%) patients who experienced post-operative delirium according to DSM-V criteria. Patient demographics, comorbidities, and post-operative complication rates were collected for each patient. Elderly patients experiencing post-operative delirium had an increased length of hospital stay (10.47days vs. 5.70days, p=0.009). Complication rates were similar between the cohorts with the post-operative delirium patients having increased UTI and superficial surgical site infections. In total, 12.14% of patients were re-admitted within 30-days of discharge, with post-operative delirium patients experiencing approximately a 4-fold increase in 30-day readmission rates (Delirium: 41.18% vs. No Delirium: 11.01%, p=0.002). In a multivariate logistic regression analysis, post-operative delirium is an independent predictor of 30-day readmission after spine surgery in the elderly (p=0.03). Elderly patients experiencing post-operative delirium after spine surgery is an independent risk factor for unplanned readmission within 30-days of discharge. Preventable measures and early awareness of post-operative delirium in the elderly may help reduce readmission rates.


The novel dehydroepiandrosterone (DHEA) derivative BNN27 counteracts delay-dependent and scopolamine-induced recognition memory deficits in rats.
Experimental evidence indicates that the neurosteroids dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) are involved in cognition. BNN27 is a novel 17C spiroepoxy-DHEA derivative, which devoid of steroidogenic activity. The neuroprotective effects of BNN27 have been recently reported. The present study was designed to investigate the effects of BNN27 on recognition memory in rats. For this purpose, the novel object task (NOT), a procedure assessing non-spatial recognition memory and the novel location task (NLT), a procedure evaluating spatial recognition memory were used. Intraperitoneal (i.p.) administration of BNN27 (3 and 10mg/kg) antagonized delay-dependent deficits in the NOT in the normal rat, suggesting that this DHEA derivative affected acquisition, storage and retrieval of information. In addition, BNN27 (3 and 10mg/kg, i.p.) counteracted the scopolamine [0.2mg/kg, subcutaneously (s.c.)]-induced non-spatial and spatial recognition memory deficits. These findings suggest that BNN27 may modulate different aspects of recognition memory, potentially interacting with the cholinergic system, relevant to cognition.


Early mobilisation practice in intensive care units: A large-scale cross-sectional survey in China.
The field of early rehabilitation has developed slowly in mainland China and there are limited data on the implementation of early mobilisation (EM) practice in intensive care unit (ICUs) in China. To investigate the implementation of EM in ICUs in mainland China and to analyse its influencing factors. A cross-sectional electronic survey was conducted in 444 ICUs across 11 provinces in China. Head nurses provided data on institutional characteristics and EM practice in ICUs. Logistic regression models were used to identify factors associated with the implementation of EM. In all, 56.98% (253/444) of ICUs implemented EM with comprehensive or complete implementation in 86 ICUs. Of the 191 ICUs that did not use EM, 136 planned to implement EM in the near future. Of the 253 ICUs that used EM, 21.34% of ICUs implemented EM for all eligible patients, while 24.90% would evaluate and carry out EM within 48 h after ICU admission, 39.13% had collaborative EM teams, 34.39% reported the use of EM protocols, 14.63% reported multidisciplinary rounds and 17.39% had medical orders and charging standards for all EM activities. Only 18.18% of ICUs conducted frequent professional training for EM, and abnormal events occurred in 15.41% of ICUs during EM practice. Multivariate logistic regression analysis revealed that an economically strong province, the presence of a dedicated therapist team, more ICU beds and a higher staff-to-bed ratio favoured the implementation of EM. Furthermore, multidisciplinary rounds, well-established medical orders and charging standards, and a high frequency of professional training can lead to the comprehensive promotion and development of EM practice in ICUs. Both the implementation rate and quality of EM practice for critically ill patients require improvement. EM practice in Chinese ICUs is still nascent and requires development in a variety of domains. To facilitate the implementation of EM in ICUs, more human resources, especially the involvement of a professional therapist team, should be deployed. In addition, health providers should actively organize multidisciplinary rounds and professional training and formulate appropriate EM medical orders and charging standards.


The cellular and molecular basis of direction selectivity of Aδ-LTMRs.
The perception of touch, including the direction of stimulus movement across the skin, begins with activation of low-threshold mechanosensory neurons (LTMRs) that innervate the skin. Here, we show that murine Aδ-LTMRs are preferentially tuned to deflection of body hairs in the caudal-to-rostral direction. This tuning property is explained by the finding that Aδ-LTMR lanceolate endings around hair follicles are polarized; they are concentrated on the caudal (downward) side of each hair follicle. The neurotrophic factor BDNF is synthesized in epithelial cells on the caudal, but not rostral, side of hair follicles, in close proximity to Aδ-LTMR lanceolate endings, which express TrkB. Moreover, ablation of BDNF in hair follicle epithelial cells disrupts polarization of Aδ-LTMR lanceolate endings and results in randomization of Aδ-LTMR responses to hair deflection. Thus, BDNF-TrkB signaling directs polarization of Aδ-LTMR lanceolate endings, which underlies direction-selective responsiveness of Aδ-LTMRs to hair deflection.


FeOF/TiO2 Hetero-Nanostructures for High-Areal-Capacity Fluoride Cathodes.
Iron fluoride compounds offer an exciting pathway toward low-cost and high-capacity conversion-type lithium-ion battery (LIB) cathodes. However, due to the sluggishness of the electronic and ionic transport in iron fluorides, mass loadings of active materials in previous studies are typically less than 2.5 mg cm-2, which is too low for practical applications. Herein, we improve the charge transport in fluoride electrodes at both nano- and mesoscales to enable high-mass-loading fluoride electrodes. At the nanoscale, we prepare electronically conducting LixTiO2 composites with FeOF nanoparticles to reduce electron transport distance to 5-10 nm, which is one of the shortest among reports. At the mesoscale, we design a percolating three-dimensional porous carbon nanotube (CNT) network to enable fast pathways for both electrons and ions. The resulting spongelike material, FeOF/TiO2@CNT, substantially enhances the kinetics of the conversion reaction in FeOF, boosts extra lithium storage capacity, and reduces the voltage hysteresis. Steady cycling over 300 cycles is achieved at a high mass loading of 8.7 mg cm-2 (FeOF/TiO2) (1.74 mAh cm-2). Such areal capacity of lithium storage is significantly higher than previously reported iron fluorides-based structures, a significant step forward toward the development of low-cost metal fluoride electrodes.


Is it cost-effective to treat recurrent hepatitis C infection in orthotopic liver transplantation patients?
Hepatitis C virus (HCV) recurs in the allograft almost universally after orthotopic liver transplantation (OLT), with a variable course ranging from mild hepatitis to frank cirrhosis. The uncertain prognosis after OLT has lead to widely increased use of antiviral therapy in the post-OLT setting. We compared two scenarios (antiviral therapy versus no antiviral therapy) using a Markov-based decision analytic model to simulate costs and health outcomes for recurrent HCV in three age and sex cohorts of post-OLT patients. Efficacy outcomes included total costs, cases of cirrhosis prevented, cases of death prevented, life-years gained, and cost per life-year saved. One-way sensitivity analyses were performed for sustained viral response; annual drug cost, discount rate, compliance, cirrhosis rate, decompensation rate, and cost of dying. Two-way sensitivity analyses were performed to compare effects of (1) changing sustained viral response and antiviral therapy costs, and (2) changing the sustained viral response and cirrhosis rate. The incremental cost-effectiveness ratio for the reference patient cohort of 1,000 men aged 55 years was $29,100 per life-year saved. The model was sensitive to drug costs, cirrhosis rate, and sustained viral response. The two-way sensitivity analysis showed that antiviral therapy remained cost-effective even if drug costs increased, as long as these increases were associated with higher sustained viral responses. The cost-effectiveness ratio also was sensitive to age and sex of cohort. The decision to treat HCV after OLT with antiviral therapy usually is based on many considerations. Such treatment can be cost-effective if baseline assumptions are met. Our model was sensitive to antiviral drug costs, cirrhosis rate, and sustained viral response. Patients with a progressive course of recurrent HCV are likely to have the greatest gain from antiviral therapy.


Usefulness of point-of-care multiplex PCR to rapidly identify pathogens responsible for ventilator-associated pneumonia and their resistance to antibiotics: an observational study.
The use of multiplex PCR to shorten time to identification of pathogens and their resistance mechanisms for patients with ventilator-associated pneumonia (VAP) is attractive, but poorly studied. The multiplex PCR-based Unyvero pneumonia cartridge assay can directly identify 20 bacteria and one fungus, amongst the most frequently causing VAP, and 19 of their resistance markers in clinical specimens (bronchoalveolar lavage or tracheal aspirate), with a turnaround time of 4-5 h. We performed this study to evaluate the concordance between the multiplex PCR-based Unyvero pneumonia cartridge assay and conventional microbiological techniques to identify pathogens and their resistance mechanisms in patients with VAP. All patients suspected of having VAP (January 2016 to January 2019), who underwent fiberoptic bronchoscopy with bronchoalveolar lavage fluid (BALF) and whose BALF microscopy examination revealed intracellular bacteria, were included. BALF conventional cultures (gold standard), antimicrobial susceptibility testing and processing for the Unyvero pneumonia cartridge were done. Culture and Unyvero results were compared. Compared to cultures of the 93 samples processed for both techniques, Unyvero correctly identified pathogens in 68 (73%) proven VAP episodes, was discordant for 25 (27%), detected no pathogen in 11 and overdetected a not otherwise found pathogen in six. For the eight remaining discordant results, the pathogen responsible for VAP was not included in the Unyvero cartridge panel or it grew at a non-significant level in culture. Amongst the 31 (33%) resistance mechanism discordances observed, 22 were resistance detection failures and 24 concerned Pseudomonas aeruginosa. Compared to conventional microbiological cultures, the Unyvero pneumonia cartridge had poor diagnostic performance: it correctly identified pathogens and their resistance mechanisms in 73% and 67% of VAP cases, respectively. The lack of performance on the resistance mechanism was more pronounced when the pathogen detected was a Pseudomonas aeruginosa.


CB1 receptor mediates the effects of glucocorticoids on AMPK activity in the hypothalamus.
AMP-activated protein kinase (AMPK), a regulator of cellular and systemic energy homeostasis, can be influenced by several hormones. Tissue-specific alteration of AMPK activity by glucocorticoids may explain the increase in appetite, the accumulation of lipids in adipose tissues, and the detrimental cardiac effects of Cushing's syndrome. Endocannabinoids are known to mediate the effects of various hormones and to influence AMPK activity. Cannabinoids have central orexigenic and direct peripheral metabolic effects via the cannabinoid receptor type 1 (CB1). In our preliminary experiments, WT mice received implants of a corticosterone-containing pellet to establish a mouse model of Cushing's syndrome. Subsequently, WT and Cb1 (Cnr1)-knockout (CB1-KO) littermates were treated with corticosterone and AMPK activity in the hypothalamus, various adipose tissues, liver and cardiac tissue was measured. Corticosterone-treated CB1-KO mice showed a lack of weight gain and of increase in hypothalamic and hepatic AMPK activity. In adipose tissues, baseline AMPK activity was higher in CB1-KO mice, but a glucocorticoid-induced drop was observed, similar to that observed in WT mice. Cardiac AMPK levels were reduced in CB1-KO mice, but while WT mice showed significantly reduced AMPK activity following glucocorticoid treatment, CB1-KO mice showed a paradoxical increase. Our findings indicate the importance of the CB1 receptor in the central orexigenic effect of glucocorticoid-induced activation of hypothalamic AMPK activity. In the periphery adipose tissues, changes may occur independently of the CB1 receptor, but the receptor appears to alter the responsiveness of the liver and myocardial tissues to glucocorticoids. In conclusion, our data suggest that an intact cannabinoid pathway is required for the full metabolic effects of chronic glucocorticoid excess.


Modulation of [3H]serotonin release by dihydropyridines in spinal cord synaptosomes.
The release of [3H]monoamines from preloaded synaptosomes from spinal cord is K(+)-dependent and can be modulated by L-type Ca2+ channel agonists such as the 1,4-dihydropyridine (1,4-DHP), Bay K 8644. Whereas the basal release of [3H]monoamines was not altered by Bay K 8644, K(+)-stimulated release of [3H]norepinephrine was enhanced 35% and [3H]serotonin 50%. Modulation of release by Bay K 8644 was dependent on the K+ concentration in the medium, being present only at submaximal depolarization with 15 mM K+. Enhanced release in the presence of Bay K 8644 was concentration-dependent and Ca2(+)-dependent. Ca2(+)-independent release induced by fenfluramine was not enhanced by Bay K 8644. Both nimodipine and nitrendipine, 1,4-DHP antagonists, produced a concentration-dependent block of the Bay K 8644-induced monoamine release and had no independent effect on basal or K(+)-stimulated release. omega-Conotoxin GVIA (omega-CgTx) produced a concentration dependent decrease of K(+)-stimulated serotonin release, which antagonized the stimulatory effect of low concentrations of Bay K 8644. However, omega-CgTx did not alter the enhancement of K(+)-stimulated release at higher concentrations of Bay K 8644. The data from the present work establish the conditions for modulation of K(+)-evoked monoamine release in spinal cord by 1,4-DHP agonists and suggest a role for the L-type voltage dependent Ca2+ channel in this process.


Why nurses choose not to undertake clinical supervision--the findings from one ICU.
A two-year action research study explored the implementation of clinical supervision in an intensive care unit (ICU). This paper focuses on one aspect of that study--the lack of uptake of clinical supervision. The themes that emerged from interview data focused on: resources, the purpose of clinical supervision, having good enough support elsewhere and personal issues. Some similarities were found to the blocks to clinical supervision which Hawkins and Shohet previously reported (1989).


Prokinetic effects of LD02GIFRO on functional gastrointestinal disorder in rats.
LD02GIFRO is a novel prokinetic agent formulated with Poncirus fructus and Zanthoxylum sp. fruits. The aim of the present study was to evaluate the effect of LD02GIFRO on delayed gastrointestinal transit (GIT) and colorectal hypersensitivity. To investigate the effect of LD02GIFRO, a rat model of delayed GIT was induced via three mechanisms; postoperative ileus (POI), morphine, and POI plus morphine. Visceromotor responses (VMR) to colorectal distension (CRD) were also evaluated. POI was induced by laparotomy surgery and manipulation of the small intestine under anesthesia, and GIT was calculated by measuring the length that Evans Blue travelled through the gastrointestinal tract in a given time. Oral administration of 260 mg/kg LD02GIFRO caused Evans Blue to migrate significantly further in the delayed GIT models induced by POI, morphine and POI plus morphine compared with the control (P<0.05). This effect was inhibited by atropine, a muscarinic receptor antagonist, and completely abolished by GR125487, a 5-HT4-receptor antagonist. Furthermore, intraperitoneal administration of 600 and 900 mg/kg LD02GIFRO significantly reduced VMR to CRD in acute and chronic colorectal hypersensitive rat models, induced by acetic acid and trinitrobenzenesulfonic acid, to almost normal levels (P<0.01). In the present study, LD02GIFRO successfully ameliorated delayed GIT models and colorectal hypersensitivity models, suggesting that LD02GIFRO may be an effective therapeutic treatment for patients with functional gastrointestinal disorders and abnormalities in GIT.


Higher contribution of globally rare bacterial taxa reflects environmental transitions across the surface ocean.
Microbial taxa range from being ubiquitous and abundant across space to extremely rare and endemic, depending on their ecophysiology and on different processes acting locally or regionally. However, little is known about how cosmopolitan or rare taxa combine to constitute communities and whether environmental variations promote changes in their relative abundances. Here we identified the Spatial Abundance Distribution (SpAD) of individual prokaryotic taxa (16S rDNA-defined Operational Taxonomic Units, OTUs) across 108 globally-distributed surface ocean stations. We grouped taxa based on their SpAD shape ("normal-like"- abundant and ubiquitous; "logistic"- globally rare, present in few sites; and "bimodal"- abundant only in certain oceanic regions), and investigated how the abundance of these three categories relates to environmental gradients. Most surface assemblages were numerically dominated by a few cosmopolitan "normal-like" OTUs, yet there was a gradual shift towards assemblages dominated by "logistic" taxa in specific areas with productivity and temperature differing the most from the average conditions in the sampled stations. When we performed the SpAD categorization including additional habitats (deeper layers and particles of varying sizes), the SpAD of many OTUs changed towards fewer "normal-like" shapes, and OTUs categorized as globally rare in the surface ocean became abundant. This suggests that understanding the mechanisms behind microbial rarity and dominance requires expanding the context of study beyond local communities and single habitats. We show that marine bacterial communities comprise taxa displaying a continuum of SpADs, and that variations in their abundances can be linked to habitat transitions or barriers that delimit the distribution of community members.


[Sonography in the diagnosis of appendicitis--a prospective study].
In a prospective study the significance of ultrasonography in the diagnosis of appendicitis was evaluated. On 104 patients--57 women and 47 men between the ages of 5 and 88 years--with a preliminary diagnosis of acute appendicitis, ultrasonography was performed using a graded compression technique with small curved-array transducers following physical examination. In 32 of 36 patients with operatively confirmed appendicitis the inflamed appendix could be visualized clearly. All 6 perityphlitic abscesses and 4 of 5 perforations were detected correctly by ultrasonography. In 18 patients the use of sonography led to important differential diagnoses other than appendicitis, which in 4 cases required surgery. By direct visualization of the inflamed appendix and its periappendicidal complications the clinical diagnosis of acute appendicitis can be improved. As a result of sonographic detection or exclusion of other diseases, ultrasonography facilitates the--often difficult--clinical differential diagnosis of right lower abdominal pain.


Malnutrition in patients who underwent surgery for spinal metastases.
Malnutrition is common among cancer patients and has been associated with increased morbidity and mortality. The primary objective of this study was to evaluate the nutritional status of patients who underwent surgical treatment for spinal metastases. In addition, the association between nutritional status and length of stay, health related quality of life (HRQOL), the occurrence of adverse events and survival was investigated. A single center prospective observational cohort study including patients with spinal metastases who underwent surgical treatment was performed. Demographic, diagnostic, treatment, and HRQOL (SOSGOQ2.0 and EQ-5D-3L) data were prospectively collected at baseline and 12 weeks post-treatment. Nutritional status was evaluated with the Patient-Generated Subjective Global Assessment (PG-SGA). A total of 39 patients were included. Malnutrition as determined by the PG-SGA was present in 36 (92%) of the patients, of whom 32 (82%) were moderately malnourished and 4 (10%) were severely malnourished. Malnourishment was associated with lower baseline SOSGOQ2.0 total scores, SOSGOQ2.0 physical function, mental health and social functioning scores, EQ-5D total scores and EQ-5D mobility scores. No association between malnutrition and survival could be determined. The prevalence of malnutrition among surgically treated patients with spinal metastases is high. Malnutrition demonstrated to be associated with lower baseline HRQOL scores. Future larger studies are needed to further investigate the prognostic significance of malnutrition.


Urinary catecholamine levels and dentofacial injuries in children.
This study investigated the relationship between urinary catecholamine levels and dentofacial injuries in 221 children, boys and girls, aged 8 to 10 years. Dentofacial injuries were recorded by a questionnaire and a clinical examination. Three 24-h urine samples, taken with an interval of 1 year between each, were available for each subject. A representative urine sample from each examination was analyzed by the high-performance liquid chromatography technique to assay the catecholamine content. Socioeconomic factors were recorded by a questionnaire. Of the examined children 58 (24 boys and 34 girls) with complete 24-h urine samples showed neither historical nor clinical evidence of dentofacial injuries and constituted the control group. Two case groups, A and B, with historical and/or clinical evidence of dentofacial injuries were matched by age and gender. Differences in the quantitative and qualitative data were tested by the paired t-test and the chi 2 test, respectively, while a regression analysis was applied to measure the effects of norepinephrine on epinephrine and dopamine. The 95% probability level was used. The results showed significant differences between control and case group A in the epinephrine and norepinephrine levels of the second urine sample. Significant differences were also found between control and case group B at the first urine sample in epinephrine and dopamine and at the second in epinephrine. Injured boys had significantly higher values of all catecholamines except for epinephrine in the second urine sample than injured girls. The only significant difference found between boys and girls without dentofacial injuries was in norepinephrine in the second urine sample. The data suggested that children with dentofacial injuries are more frequently under emotional stress and consequently emotionally stressful children run a greater risk of sustaining such injuries.


[Cellular compatibility of small intestinal submucosa in vitro].
This study was aimed to evaluate the cellular compatibility of the small intestinal submucosal(e) (SIS). Prepared by use of pig jejunum. SIS were cocultured with human embryonic periosteal osteoblasts (HEPOB), human embryonic skin fibroblasts (HESFB) and rabbit renal vascular endothelial cells (RRVEC) respectively. The cell growth, attachment, cell cycle, cell apoptosis rate were detected to evaluate the cellular compatibility of SIS. The three kinds of cells attached onto SIS and grew well. SIS accelerated the growth of RRVEC. No effects of SIS were detected on cell cycle and cell apoptosis rate in the three kinds of cells. SIS has good cellular compatibility without cytotoxicity. The porous structure of SIS is suited for the growth of HEPOB, HESFB and RRVEC in three dimensions in the scaffold. SIS is a good bio-derived material of tissue engineering.


The genetic locus controlling supernodulation in soybean (Glycine max L.) co-segregates tightly with a cloned molecular marker.
The genetic locus (nts) controlling nitrate-tolerant nodulation, supernodulation, and diminished autoregulation of nodulation of soybean (Glycine max (L.) Merill) was mapped tightly to the pA-132 molecular marker using a restriction fragment length polymorphism (RFLP) detected by subclone pUTG-132a. The nts (nitrate-tolerant symbiotic) locus of soybean was previously detected after its inactivation by chemical mutagenesis. Mutant plant lines were characterized by abundant nodulation (supernodulation) and tolerance to the inhibitory effects of nitrate on nodule cell proliferation and nitrogen fixation. The large number of RFLPs between G. max line nts382 (homozygous for the recessive nts allele) and the more primitive soybean G. soja (PI468.397) allowed the detection of co-segregation of several diagnostic markers with the supernodulation locus in F2 families. We located the nts locus on the tentative RFLP linkage group E about 10 cM distal to pA-36 and directly next to marker pA-132. This very close linkage of the molecular marker and the nts locus may allow the application of this clone as a diagnostic probe in breeding programs as well as an entry point for the isolation of the nts gene.


Thrombocytopenia in pediatric patients on concurrent cannabidiol and valproic acid.
In January 2019, a new plant-derived purified cannabidiol preparation, approved by the US Food and Drug Administration, became commercially available for patients ≥2 years old with Lennox-Gastaut syndrome or Dravet syndrome. Among our patients who were prescribed the new cannabidiol formulation, we observed several cases of thrombocytopenia and therefore embarked on this study. We conducted a single-center systematic chart review of all pediatric patients (<21 years old) who were prescribed cannabidiol from January to August 2019. We evaluated salient features of the patients' epilepsy syndrome, age, concurrent medications, and surveillance laboratory results before and after cannabidiol initiation. Among 87 patients, nine (10%) developed thrombocytopenia (platelet nadir range = 17 000-108 000) following initiation of cannabidiol. Each of these nine children was on combination therapy of cannabidiol with valproic acid. Whereas no children on cannabidiol without valproic acid (0/57) developed thrombocytopenia, nine of 23 treated with combination valproic acid and cannabidiol developed platelets < 110 000/µL (P < .0001). We report a novel and clinically important side effect of thrombocytopenia in one-third of patients treated concurrently with cannabidiol and valproic acid. If this finding is confirmed, clinicians should perform close monitoring for thrombocytopenia when adding cannabidiol to a regimen that includes valproic acid.


Carbon-13 NMR shielding in the twenty common amino acids: comparisons with experimental results in proteins.
We have used ab initio quantum chemical techniques to compute the (13)C(alpha) and (13)C(beta) shielding surfaces for the 14 amino acids not previously investigated (R. H. Havlin et al., J. Am. Chem. Soc. 1997, 119, 11951-11958) in their most popular conformations. The spans (Omega = sigma(33) - sigma(11)) of all the tensors reported here are large ( approximately 34 ppm) and there are only very minor differences between helical and sheet residues. This is in contrast to the previous report in which Val, Ile and Thr were reported to have large ( approximately 12 ppm) differences in Omega between helical and sheet geometries. Apparently, only the beta-branched (beta-disubstituted) amino acids have such large CSA span (Omega) differences; however, there are uniformly large differences in the solution-NMR-determined CSA (Deltasigma = sigma(orth) - sigma(par)) between helices and sheets in all amino acids considered. This effect is overwhelmingly due to a change in shielding tensor orientation. With the aid of such shielding tensor orientation information, we computed Deltasigma values for all of the amino acids in calmodulin/M13 and ubiquitin. For ubiquitin, we find only a 2.7 ppm rmsd between theory and experiment for Deltasigma over an approximately 45 ppm range, a 0.96 slope, and an R(2) = 0.94 value when using an average solution NMR structure. We also report C(beta) shielding tensor results for these same amino acids, which reflect the small isotropic chemical shift differences seen experimentally, together with similar C(beta) shielding tensor magnitudes and orientations. In addition, we describe the results of calculations of C(alpha), C(beta), C(gamma)1, C(gamma)2, and C(delta) shifts in the two isoleucine residues in bovine pancreatic trypsin inhibitor and the four isoleucines in a cytochrome c and demonstrate that the side chain chemical shifts are strongly influenced by chi(2) torsion angle effects. There is very good agreement between theory and experiment using either X-ray or average solution NMR structures. Overall, these results show that both C(alpha) backbone chemical shift anisotropy results as well as backbone and side chain (13)C isotropic shifts can now be predicted with good accuracy by using quantum chemical methods, which should facilitate solution structure determination/refinement using such shielding tensor surface information.


Sex before the State: Civic Sex, Reproductive Innovations, and Gendered Parental Identity.
Certain changes in the way that states classify people by sex as well as certain reproductive innovations undercut the rationale for state identification of people as male or female in signifying gendered parental relationships to children. At present, people known to the state as men may be genetic mothers to their children; people known to the state as women may be genetic fathers to their children. Synthetic gametes would make it possible for transgender men to be genetically related to children as fathers and transgender women to be genetically related to children as mothers, even if they have otherwise relied on naturally-occurring gametes to be genetic mothers and genetic fathers of children respectively. Synthetic gametes would presumably make it possible for any person to be the genetic father or genetic mother of children, even in a mix-and-match way. Other reproductive innovations will also undercut existing expectations of gendered parental identity. Uterus transplants would uncouple the maternal function of gestation from women, allowing men to share in maternity that way. Extracorporeal gestation ((ExCG)-gestation outside anyone's body-would also undercut the until-now absolute connection between female sex and maternity. In kind, effects such as these-undoing conventionally gendered parenthood-undercut the state's interest in knowing whether parents are male or female in relation to a given child, as against knowing simply whether someone stands in a parental relationship to that child, as a matter of rights and duties.


Involvement of cannabinoid receptor CB2 in dectin-1-mediated macrophage phagocytosis.
Cannabinoid receptors are expressed in macrophages, but little is known of their roles. We here examined their involvement in phagocytosis. The presence of 2-arachidonylglycerol, an endocannabinoid, augmented the phagocytosis of zymosan by mouse macrophages, while the phagocytosis of Escherichia coli, Staphylococcus aureus, apoptotic cells or latex beads remained unaffected. An agonist of the cannabinoid receptors CB1 and CB2 also stimulated the phagocytosis of zymosan. The stimulatory effect of 2-arachidonylglycerol was abolished when phagocytosis reactions were carried out in the presence of an antagonist of CB2 but not of CB1. Furthermore, the phagocytosis of zymosan in the presence of 2-arachidonylglycerol was severely inhibited by the addition of a beta-glucan-containing carbohydrate or antibody neutralizing dectin-1, a beta-glucan-recognizing phagocytosis receptor. These results suggested that the activation of CB2 in macrophages leads to the stimulation of dectin-1-mediated phagocytosis.


Immunology and functional genomics of Behçet's disease.
Behçet's disease (BD) is a multisystemic inflammatory disorder. Although the cause and pathogenesis of BD are still unclear, there is evidence for genetic, immunologic and infectious factors at the onset or in the course of BD. This review focuses on the functional genomics and immunology of BD. HLA-B51 is the major disease susceptibility gene locus in BD. An increased number of gammadelta T cells in the peripheral blood and in the involved tissues have been reported. However, the T cells at the sites of inflammation appear to be a phenotypically distinct subset. There is also a significant gammadelta T cell proliferative response to mycobacterial 65-kDa heat shock protein peptides. Homologous peptides derived from the human 60-kDa heat shock protein were observed in BD patients. There is evidence that natural killer T cells may also play a role in BD.


Predictors of Papanicolaou testing in working women in Bangkok, Thailand.
Cervical cancer is the leading cause of death among women in Thailand. A significant number of Thai women have never received cervical cancer screening. This study examined the perceived susceptibility, benefits, and barriers that influence Papanicolaou testing and examined the relationships between socioeconomic factors and obtaining a Papanicolaou test among women working in 1 government agency and 3 private sector companies in Bangkok, Thailand. The Health Belief Model was used to guide the cross-sectional design of the study. The Susceptibility, Benefits, and Barriers Scale was mailed to 300 working women. The response rate to the survey was 63% (N = 189). Logistic regression analysis showed that perceived barriers were significant predictors of Papanicolaou testing (beta = -.13, P < .001). Women who reported barriers were significantly less likely to obtain a Papanicolaou test (odds ratio, 0.88; P < .001). The specific barriers to engaging in Papanicolaou testing were embarrassment, fear, time constraints, knowledge deficits, and cost. Marital status, age, education, and family income were other factors related to Papanicolaou testing. Findings suggest that screening rates may be improved by addressing a combination of research, health policy, and cultural factors in these women through a nationwide campaign.


Concentration of electrolytes in the sweat of malnourished children.
The sweat test was performed by the method of Gibson and Cooke on 36 children with second and third degree malnutrition, aged from 2 months to 4 years. The results were compared with those from 32 healthy, well nourished controls in the same age range. Determinations were made of sodium and chloride concentrations, chloride/sodium ratio, and the sum of the concentrations of the two electrolytes in each sample. The malnourished children were found to have higher sodium and chloride concentrations than the well nourished ones. None of the normal or malnourished children had a sweat chloride value greater than 60 mmol/l; chloride values within a suspicious range (between 40 and 60 mmol/l) were found in two malnourished children. Two well nourished controls and six malnourished children showed suspicious sweat sodium concentrations; in one child with third degree malnutrition the sodium content was greater than 60 mmol/l. In all results in the suspicious range, or greater than 60 mmol/l, the chloride/sodium ratio was less than 1, and the sum of the two electrolytes was below 140 mmol/l. Based on these results, we conclude that malnourished children have raised sweat sodium and chloride concentrations when compared with well nourished children. The electrolyte values for most of them are not in a suspicious range or consistent with a diagnosis of cystic fibrosis. Unlike that found in cystic fibrosis, the sodium/chloride ratio in our subjects was less than 1 and the sum of both electrolytes never exceeded 140 mmol/l.


Trunk muscles strength and endurance in chronic low back pain patients with and without clinical instability.
Previous research has shown inconsistent findings regarding muscle endurance in chronic low back pain (CLBP). Questions also remain about muscle endurance in patients with clinical instability. The aim of this study was to investigate trunk muscles strength and endurance in CLBP patients with and without clinical instability. 32 CLBP patients (15 with and 17 without clinical instability) and 39 matched healthy subjects participated in this study. The standing extension test was performed to assess the strength and endurance of the lumbar extensors while recording their electromyographic activity. The patients' disability was evaluated using the Oswestry and Roland-Morris Disability Questionnaires. Patients with clinical instability showed lower maximal voluntary exertion (MVE) and higher time to fatigue (TTF) compared to healthy subjects (P=0.000 and P=0.008, respectively) and patients without instability (P=0.002 and P=0.02, respectively). There was no difference in these variables between patients without instability and healthy controls. A negative relationship between MVE and TTF and a positive correlation between disability and pain intensity were seen. Strength training of trunk extensor muscles can be considered as part of the treatment protocol for CLBP patients with clinical instability. Although patients without instability suffered from pain or disability, they showed more similarity to healthy subjects in terms of trunk muscles strength and endurance.


Morphological and molecular characterization of the new aethaloid species Didymium yulii.
Five specimens, initially presumed to be Fuligo septica or Mucilago crustacea, were collected from Jilin Province and the Inner Mongolia Autonomous Region in China, but all five turned out to represent a new aethaloid species, Didymium yulii. This new species is characterized by pseudocapillitia without capillitia and an aethalioid fruiting body, features that are morphologically distinct from those of any other species of Didymium. To assess the phylogenetic relationships between D. yulii and other members of Didymium and in the Didymiaceae, sequences from two nonoverlapping targeted portions of nuc 18S rDNA (~450 bp and ~1050 bp) and translation elongation factor 1-alpha (tef1) were obtained and analyzed. The results indicate that D. yulii forms a single clade separate from other species of Didymium and the clade that contains M. crustacea, which strongly supports the identification of the five specimens as a new species.


Evidence for the involvement of cAMP-dependent protein kinase in the exocytosis of amylase from parotid acinar cells.
To determine the role of cAMP-dependent protein kinase in the exocytosis of amylase from rat parotid acini, I studied the effects of various cAMP analogues on amylase release and protein phosphorylation in saponin-permeabilized parotid cells. The dose-dependent responses of amylase release and protein phosphorylation evoked by cAMP, dibutyryl-cAMP, and 8-chlorophenylthio-cAMP were closely correlated. Furthermore, when the permeabilized cells were incubated with a combination of site-selective cAMP analogues, such as N6-benzoyl-cAMP plus 8-thiomethyl-cAMP (RII-directed) or N6-benzoyl-cAMP plus 8-aminohexylamino-cAMP (RI-directed), synergistic stimulation of amylase release was clearly observed. As reported previously [T. Takuma (1988) Biochem. J. 256, 867-871], however, the protein phosphorylation evoked by 8-chlorophenylthio-cAMP was markedly inhibited by H-8 without a significant decrease in amylase release. These results suggest that cAMP-dependent protein kinase is involved in the regulation of amylase exocytosis, although the role of its catalytic subunit is still uncertain.


Nano- and microdelivery systems for marine bioactive lipids.
There is an increasing body of evidence of the positive impact of several marine lipids on human health. These compounds, which include ω-3 polyunsaturated fatty acids, have been shown to improve blood lipid profiles and exert anti-inflammatory and cardioprotective effects. The high instability of these compounds to oxidative deterioration and their hydrophobicity have a drastic impact in their pharmacokinetics. Thus, the bioavailability of these compounds may be affected, resulting in their inability to reach the target sites at effective concentrations. In this regard, micro/nanoparticles can offer a wide range of solutions that can prevent the degradation of targeted molecules, increase their absorption, uptake and bioavailability. In this work we will present the options currently available concerning micro- and nanodelivery systems for marine lipids; with emphasis on micro/nanoparticles; such as micro/nanocapsules and emulsions. A wide range of bottom-up approaches using casein, chitosan, cyclodextrins, among others; will be discussed.


Recent advances in epidemiology and prevention of atopic eczema.
Atopic dermatitis (AD), named also atopic eczema, is a chronic relapsing inflammatory skin disease with a considerable social and economic burden. The primum movens of AD is in most cases a genetic and/or immune-supported defect of the skin barrier, facilitating penetration and sensitization to food or airborne allergens, as well as infections by Staphylococcus aureus, herpes simplex virus, or other microbes. New pathogenetic concepts have generated new approaches to prevention and therapy of AD. In particular, the daily use of emollients in newborns at high risk of AD has shown interesting results, with a reduction in the cumulative incidence of AD ranging from 32% to 50% of the treated infants. On the other hand, the AD preventive efficacy of food and/or inhalant allergen avoidance has been questioned, and supplementation strategies (vitamin D, probiotics, or other compounds) need to be further investigated.


Characteristics of tinnitus induced by acute acoustic trauma: a long-term follow-up.
We investigated the prevalence, characteristics and subjective perceived handicap caused by long-term tinnitus induced by acute acoustic trauma (AAT) in 418 former military conscripts. They had been treated between 1984 and 1989 because of AAT from exposure to impulse noise caused by firearm shooting. All 418 patients reported tinnitus after the AAT. At discharge from the military service, 122 (29%) still reported tinnitus. In 1999, of these 122 patients, 101 were reached and 66 still had tinnitus. The Tinnitus Handicap Questionnaire demonstrated various difficulties in life because of tinnitus, not attributable only to tinnitus loudness. Psychological factors also seem to play an important role. The effects of AAT and possible compensation have been evaluated so far mostly by audiometric findings, but in some cases tinnitus may be an even more serious threat to life satisfaction than mild hearing impairment.


Targeted nanodelivery of siRNA against KRAS G12D inhibits pancreatic cancer.
Pancreatic cancer (PC) stands as a most deadly malignancy due to few effective treatments in the clinics. KRAS G12D mutation is a major driver for most PC cases, and silencing of KRAS G12D is considered as a potential therapeutic strategy for PC, which is nevertheless crippled by lacking a pragmatic delivery system for siRNA against KRAS G12D (siKRAS). Here, we report that cRGD peptide-modified bioresponsive chimaeric polymersomes (cRGD-BCP) mediate highly efficient siKRAS delivery to PANC-1 tumor, potently silencing KRAS G12D mRNA in tumor cells and effectively suppressing PC tumor growth in mice. cRGD-BCP exhibited remarkable encapsulation of siKRAS (loading content > 14 wt.%, loading efficiency > 90%) to form stable and uniform (ca. 68 nm) nanovesicles (cRGD-BCP-siKRAS). Of note, cRGD density greatly impacted the cellular uptake and silencing efficiency of cRGD-BCP-siKRAS in PANC-1 cells, in which an optimal cRGD density of 15.7 mol.% achieved 3.7- and 3.6-fold enhancement of internalization and gene silencing, respectively, compared with non-targeted BCP-siKRAS. cRGD-BCP-siKRAS was practically intact after 3-week storage at 4°C. Intriguingly, cRGD-BCP-siKRAS markedly enhanced the uptake of siKRAS in PANC-1 tumor, and at a siKRAS dose of 3 mg/kg knocked down 90% KRAS G12D gene, resulting in potent tumor inhibition and extraordinary survival benefits (median survival time: 101 days versus 38 (PBS group) and 59 days (BCP-siKRAS)) with 40% mice achieved complete regression. It appears that cRGD-mediated nanodelivery of siKRAS provides a potential cure for pancreatic cancer. STATEMENT OF SIGNIFICANCE: Small interfering RNA (siRNA) emerges as a specific and powerful biopharmaceuticals against cancers; however, inefficient in vivo delivery impedes its clinical translation. In spite of the fact that KRAS G12D mutation has been identified as a major driver for most pancreatic cancer, its notorious non-druggability renders little success on development of molecular targeted drugs. Pancreatic cancer is deemed as current king-of-cancer. Here, we show that cyclic RGD peptide installed bioresponsive polymersomes are able to efficiently deliver siRNA against KRAS G12D to pancreatic tumor, resulting in 90% gene knock-down and effective tumor inhibition. Strikingly, two out of five mice have been cured. This targeted nanodelivery of siRNA provides a high-efficacy treatment strategy for pancreatic cancer.


Contemporary Management of Complex and Non-Complex Rhegmatogenous Retinal Detachment Due to Giant Retinal Tears.
To investigate the clinical features and surgical outcomes of rhegmatogenous retinal detachment (RRD) associated with giant retinal tears (GRTs) at a tertiary referral center. A retrospective, non-consecutive interventional case series of GRT-associated RRDs that underwent primary surgical repair at the University of Michigan W.K. Kellogg Eye Center between January 1, 2011 and July 1, 2020. Clinical characteristics and preoperative, perioperative, and postoperative data were collected. Forty-eight eyes of 47 patients with GRT-associated RRDs met inclusion criteria, including those that were children (under 12 years, N=4, 8.3%), associated with a history of trauma (N=20, 41.7%) or with grade C proliferative vitreoretinopathy (PVR-C) (N=7, 14.6%) at baseline. Median age was 46 years (interquartile range (IQR): 29 years, range: 4 to 72 years), median follow-up was 28 months (IQR: 43 months, range: 3-124 months), and 83.3% (N=40) of subjects were male. Primary surgical repair for GRT-associated RRDs included pars plana vitrectomy (PPV) (N=40, 83.3%), scleral buckle (SB) (N=1, 2.1%), or combined PPV/SB (N=7, 14.6%). Surgical approach commonly involved the use of perfluorocarbon liquid (N=43, 90%) and gas tamponade (N=39, 81%). Single surgery anatomic success (SSAS) was 75% (95% CI: 60%, 85%) at 3 months and 65% (95 CI: 47%, 78%) at 2 years. Final anatomic success was achieved in all 48 eyes (100%). Median visual acuity improved from 20/250 preoperatively to 20/60 at final follow-up, with 44% (N=20) of eyes achieving postoperative visual acuity of 20/40 or better. In this series from a tertiary referral center, both complex and non-complex GRT-associated RRDs were most commonly managed with PPV alone, perfluorocarbon liquid, and gas tamponade with favorable final anatomic and visual outcomes comparable to other modern GRT series.


Influence of gum-chewing on postoperative bowel activity after laparoscopic surgery for gastric cancer: A randomized controlled trial.
In some studies, gum-chewing was demonstrated to have a beneficial effect on resumption of bowel function; however, other contradictory findings in other studies refute the effects of gum-chewing on peristaltic movements and digestive system stimulation. In addition, most previous studies were after colorectal or gynecology surgery, whereas few reports focused on the effect of gum-chewing after gastrectomy. The aim of this randomized controlled trial was to assess the effectiveness of gum-chewing on postoperative bowel function in patients who had undergone laparoscopic gastrectomy. From March 2014 to March 2016, 75 patients with gastric cancer received elective laparoscopic surgery in Shanghai Tongji hospital and were postoperatively randomly divided into 2 groups: 38 in a gum-chewing (Gum) group and 37 in a control (No gum) group. The patients in the Gum group chewed sugarless gum 3 times daily, each time for at least 15 minutes, until the day of postoperative exhaust defecation. The mean time to first flatus (83.4 ± 35.6 vs. 79.2 ± 24.2 hours; P = 0.554) and the mean time to first defecation (125.7 ± 41.2 vs. 115.4 ± 34.2 hours; P = 0.192) were no different between the no gum and Gum groups. There was also no significant difference in the incidence of postoperative ileus (P = 0.896) and postoperative hospital stay (P = 0.109) between the 2 groups. The postoperative pain score at 48 hours (P = 0.032) in the Gum group was significantly higher than in the no gum group. There was no significant difference between the 2 groups in regards to patient demographics, comorbidities, duration of surgery, complications, and nausea/vomiting score. Gum-chewing after laparoscopic gastrectomy did not hasten the return of gastrointestinal function. In addition, gum-chewing may increase patient pain on the second postoperative day.


Missed opportunities in primary care: the importance of identifying depression through screening, family history, and chronic disease management.
This study explored the adequacy of depression screening in a community health center. The medical charts of individuals (N = 90) enrolled at a community health center were randomly selected, reviewed, and compared to current standard-of-care guidelines for four elements: family history, screening for depression, control of chronic illnesses, and missed opportunities for preventive care. Family history documentation collected by the providers was limited and 44.4% had no family history. There was no routine depression screening process, although 48.9% of the clients had red flags (warning signals) for depression. Laboratory values used for screening control of chronic disease in the medical records were: fasting glucose levels ⩽100 mg/dL (46%), total cholesterol levels ⩽200 mg/dL (38%), and blood pressure ⩽120/80 mmHg (23%). The results highlight the need to focus on depression screening as part of preventive care and the management of chronic disease in the primary care setting.


Non-endoscopic tests in the diagnosis of Helicobacter pylori infection.
The urea breath test (UBT) and serological antibody detection are simpler and less expensive than endoscopic tests for the diagnosis of Helicobacter pylori. For the UBT, either non-radioactive 13C or radioactive 14C is used as an isotopic marker. 14C-UBTs are cheaper and are safe, but licensing regulations may make them inconvenient. Some UBTs have been simplified by omitting the normal test meal and encapsulating the urea to avoid metabolism by oral bacteria. These modified test need further validation, especially when used for assessing H. pylori status after treatment. Serological tests detect circulating IgG or IgA. They are of variable accuracy, the best performing as well as UBTs. Paired serum samples pre-treatment and 6 months post-treatment accurately assess treatment success. Rapid in-office tests appear less accurate and cannot be used for post-treatment assessment. In practice, for primary diagnosis of H. pylori infection, endoscopic tests are best because endoscopy allows assessment of treatment indications. Where indications already exist or taking biopsies is dangerous. UBTs or serology are suitable, but serology is cheaper and more convenient. After treatment, endoscopy is usually unnecessary and UBTs accurately assess H. pylori status at 4 weeks. Serology is an alternative only if results are not required before 6 months.


Assessment of disability in multiple sclerosis a new approach to epidemiological study.
The Kurtzke system and overall disability scales (KS) for multiple sclerosis were adapted to questionnaire form (QKS). A qualified nurse recorded Kurtzke ratings, by QKS, from 36 multiple sclerosis patients and 11 healthy controls. These scores were compared with ratings obtained by a doctor with neurological training using the conventional history/examination technique. The results obtained by these 2 methods were closely comparable. The use of a questionnaire appears to be a valid and accurate approach to the determination of disability in multiple sclerosis and may be of particular value in epidemiology and therapeutic trials in this condition.


Mechanisms of Sb(III) Photooxidation by the Excitation of Organic Fe(III) Complexes.
Organic Fe(III) complexes are widely distributed in the aqueous environment, which can efficiently generate free radicals under light illumination, playing a significant role in heavy metal speciation. However, the potential importance of the photooxidation of Sb(III) by organic Fe(III) complexes remains unclear. Therefore, the photooxidation mechanisms of Sb(III) were comprehensively investigated in Fe(III)-oxalate, Fe(III)-citrate and Fe(III)-fulvic acid (FA) solutions by kinetic measurements and modeling. Rapid photooxidation of Sb(III) was observed in an Fe(III)-oxalate solution over the pH range of 3 to 7. The addition of tert-butyl alcohol (TBA) as an ·OH scavenger quenched the Sb(III) oxidation, suggesting that ·OH is an important oxidant for Sb(III). However, the incomplete quenching of Sb(III) oxidation indicated the existence of other oxidants, presumably an Fe(IV) species in irradiated Fe(III)-oxalate solution. In acidic solutions, ·OH may be formed by the reaction of Fe(II)(C2O4) with H2O2, but a hypothetical Fe(IV) species may be generated by the reaction of Fe(II)(C2O4)2(2-) with H2O2 at higher pH. Kinetic modeling provides a quantitative explanation of the results. Evidence for the existence of ·OH and hypothetical Fe(IV) was also observed in an irradiated Fe(III)-citrate and Fe(III)-FA system. This study demonstrated an important pathway of Sb(III) oxidation in surface waters.


Decreased lysophospholipase and increased phospholipase A2 activity in ileal mucosa from patients with Crohn's disease.
Lysophospholipase (EC 188.8.131.52) and phospholipase A2 (EC 184.108.40.206) were determined in ileal mucosa from patients with Crohn's disease (CD) and non-inflammatory bowel diseases ( NIBD ). In addition, the activities of alkaline phosphatase, sucrase, maltase, and lactase were determined. The lysophospholipase activity, like that of alkaline phosphatase, sucrase and maltase, was decreased in affected areas of CD, whereas the phospholipase A2 activity was rather increased. Lysophospholipase and phospholipase A2 activities in apparently unaffected mucosa from CD patients were in between those in healthy mucosa from NIBD patients and those in affected mucosa from CD patients. These findings point to the possibility that the mucosal activity of lysophospholipase, like that of other brush border enzymes, is decreased in CD. This may render the mucosa less capable to handle lysolecithin, a potentially harmful agent formed in the intestine and known to induce inflammation in a number of experimental systems.


Macrocyclic lanthanide complexes as artificial nucleases and ribonucleases: effects of pH, metal ionic radii, number of coordinated water molecules, charge, and concentrations of the metal complexes.
We have been interested in the design, synthesis, and characterization of artificial nucleases and ribonucleases by employing macrocyclic lanthanide complexes because their high thermodynamic stability, low kinetic lability, high coordination number, and charge density (Lewis acidity) allow more design flexibility and stability. In this paper, we report the study of the use of the europium(III) complex, EuDO2A+ (DO2A is 1,7-dicarboxymethyl-1,4,7,10-tetraazacyclododecane) and other lanthanide complexes (i.e., LaDO2A+, YbDO2A+, EuK21DA+, EuEDDA+, and EuHEDTA where K21DA is 1,7-diaza-4,10,13-trioxacyclopentadecane-N,N'-diacetic acid, EDDA is ethylenediamine-N,N'-diacetic acid, and HEDTA is N-hydroxyethyl-ethylenediamine-N,N',N'-triacetic acid), as potential catalysts for the hydrolysis of the phosphodiester bond of BNPP (sodium bis(4-nitrophenyl)-phosphate). For the pH range 7.0-11.0 studied, EuDO2A+ promotes BNPP hydrolysis with the quickest rates among LaDO2A+, EuDO2A+, and YbDO2A+. This indicates that charge density is not the only factor affecting the reaction rates. Among the four complexes, EuDO2A+, EuK21DA+, EuEDDA+, and EuHEDTA, with their respective number of inner-sphere coordinated water molecules three, two, five, and three, EuEDDA+, with the greatest number of inner-sphere coordinated water molecules and a positive charge, promotes BNPP hydrolysis more efficiently at pH below 8.4, and the observed rate trend is EuEDDA+ > EuDO2A+ > EuK21DA+ > EuHEDTA. At pH > 8.4, the EuEDDA+ solution becomes misty and precipitates form. At pH 11.0, the hydrolysis rate of BNPP in the presence of EuDO2A+ is 100 times faster than that of EuHEDTA, presumably because the positively charged EuDO2A+ is more favorable for binding with the negatively charged phosphodiester compounds. The logarithmic hydrolysis constants (pKh) were determined, and are reported in the parentheses, by fitting the kinetic k(obs) data vs pH for EuDO2A+ (8.4), LaDO2A+ (8.4), YbDO2A+ (9.4), EuK21DA+ (7.8), EuEDDA+ (9.0), and EuHEDTA (10.1). The preliminary rate constant-[EuDO2A+] data at pH 9.35 were fitted to a monomer-dimer reaction model, and the dimer rate constant is 400 times greater than that of the monomer. The fact that YbDO2A+ catalyzes BNPP less effectively than EuDO2A+ is tentatively explained by the formation of an inactive dimer, [Yb(DO2A)(OH)]2, with no coordination unsaturation for BNPP substrate binding.


Gambogic acid induces apoptosis and regulates expressions of Bax and Bcl-2 protein in human gastric carcinoma MGC-803 cells.
The selective induction of apoptosis of gambogic acid (GA) on MGC-803 cells and its probable molecular mechanism were studied. GA greatly inhibited (24, 48, 72 h) the growth of MGC-803 cells (by MTT); the IC(50) value was 0.96 microg/ml at 48 h. Meanwhile, no influence was observed on body weight, number of WBC (white blood cells) in blood or karyote in marrow of rats after GA was injected intravenously. We conclude that GA does not affect normal cells, but that it can induce apoptosis in tumor cells selectively and there were marked morphological changes. A great quantity of apoptotic cells and increasing G(2)/M phase cells were observed by flow cytometry, and a significant percentage of early apoptotic cells were observed by Annexin-V/PI double staining assay. The increase of bax gene and the decrease of bc1-2 gene expressions were detected by immunohistochemistry. Activation of bax and suppression of bc1-2 may contribute to the apoptosis mechanism.


Current trends in plague research: from genomics to virulence.
Yersinia pestis is the causative agent of plague, which diverged from Yersinia pseudotuberculosis within the past 20,000 years. Although these two species share a high degree of homology at the DNA level (>90%), they differ radically in their pathogenicity and transmission. In this review, we briefly outline the known virulence factors that differentiate these two species and emphasize genetic studies that have been conducted comparing Y. pestis and Y. pseudotuberculosis. These comparisons have led to a better understanding of the genetic contributions to the differences in the virulence and pathogenicity between these two organisms and have generated information that can be applied in future diagnostic and vaccine development. Comparison of the genetic differences between Y. pestis and Y. pseudotuberculosis has also lent insight into the emergence of acute pathogens from organisms causing milder diseases.


Object exploration facilitates 4-month-olds' mental rotation performance.
How do infants learn to mentally rotate objects, to imagine them rotating through different viewpoints? One possibility is that development of infants' mental rotation (MR) is facilitated by visual and manual experience with complex objects. To evaluate this possibility, eighty 4-month-olds (40 females, 40 males) participated in an object exploration task with Velcro "sticky mittens" that allow infants too young to grasp objects themselves to nonetheless explore those objects manually as well as visually. These eighty infants also participated in a visual habituation task designed to test MR. Half the infants (Mittens First group) explored the object prior to the MR task, and the other half afterwards (Mittens Second group), to examine the role of immediate prior object experience on MR performance. We compared performance of male and female infants, but found little evidence for sex differences. However, we found an important effect of object exploration: The infants in the Mittens First group who exhibited the highest levels of spontaneous object engagement showed the strongest evidence of MR, but there were no consistent correlations between these measures for infants in the Mittens Second group. These findings suggest an important contribution from object experience to development of MR.


Caveolins as Regulators of Stress Adaptation.
Caveolins have been recognized over the past few decades as key regulators of cell physiology. They are ubiquitously expressed and regulate a number of processes that ultimately impact efficiency of cellular processes. Though not critical to life, they are central to stress adaptation in a number of organs. The following review will focus specifically on the role of caveolin in stress adaptation in the heart, brain, and eye, three organs that are susceptible to acute and chronic stress and that show as well declining function with age. In addition, we consider some novel molecular mechanisms that may account for this stress adaptation and also offer potential to drive the future of caveolin research.


Harvesting Chlorella vulgaris via rapid sedimentation induced by combined coagulants and tapered shear.
In this study, a rapid sedimentation induced by combined coagulants and gradual shear was developed to harvest Chlorella vulgaris. The microalgal harvesting efficiency was observably promoted by the synergistic effect between FeCl3 and PAM, especially in the first 10 min. A higher harvesting efficiency, 95.61%, could be achieved within approximately 3 min due to the large and dense flocs generated by the combined coagulants. In contrast, the efficiencies were only 54.25 and 60.20% with FeCl3 and PAM, independently. When coagulation was performed under gradually reduced shear (from 50 to 30 rpm), smaller clusters or cells filled the pores of the aggregates via interception, which caused the flocs to become larger and more compact. The sedimentation time was shortened to 30 s for microalgal coagulation induced by the simultaneous use of combined coagulants and tapered shear, providing an effective approach to harvesting microalgae.


Inheritance and recombination of mitochondrial genomes in plants, fungi and animals.
It is generally assumed that mitochondrial genomes are uniparentally transmitted, homoplasmic and nonrecombining. However, these assumptions draw largely from early studies on animal mitochondrial DNA (mtDNA). In this review, we show that plants, animals and fungi are all characterized by episodes of biparental inheritance, recombination among genetically distinct partners, and selfish elements within the mitochondrial genome, but that the extent of these phenomena may vary substantially across taxa. We argue that occasional biparental mitochondrial transmission may allow organisms to achieve the best of both worlds by facilitating mutational clearance but continuing to restrict the spread of selfish genetic elements. We also show that methodological biases and disproportionately allocated study effort are likely to have influenced current estimates of the extent of biparental inheritance, heteroplasmy and recombination in mitochondrial genomes from different taxa. Despite these complications, there do seem to be discernible similarities and differences in transmission dynamics and likelihood of recombination of mtDNA in plant, animal and fungal taxa that should provide an excellent opportunity for comparative investigation of the evolution of mitochondrial genome dynamics.


Human Papillomavirus Genome-Wide Identification of T-Cell Epitopes for Peptide Vaccine Development Against Cervical Cancer: An Integration of Computational Analysis and Experimental Assay.
Human papillomavirus (HPV) has long been documented as the primary factor causing cervical cancer and other complications, and development of immunotherapeutic vaccines against HPV is thought to be an important approach in preventing women from HPV infections. It is known that the first step in vaccine development is to find potent T-cell epitopes in HPV proteins that can be effectively recognized and presented by the human leukocyte antigen (HLA) system. In the current study, we proposed a synthetic pipeline that integrates computational analysis and experimental assay to discover new peptide epitopes from HPV genome with high affinity to the HLA-A*0201, one of the most frequent HLA allele in Caucasian and Asian populations. In the procedure, a structure-based three-dimensional quantitative structure-activity relationship (3D-QSAR) methodology was described and several 3D-QSAR predictors were established using a set of activity-known HLA binders. The best predictor was then employed to perform extrapolation over the HPV genome to screen potential protein fragments with high HLA binding potency. Consequently, 10 peptides were suggested as promising candidates and their affinities toward HLA-A*0201 were assayed using a standard T2 cell surface stabilization test. Four peptides--LLITSNINA from protein E1 (BL50 = 7244 nM), VLLCVCLLI from protein E5 (BL50 = 9118 nM), VLLLWITAA from protein E5 (BL50 = 3388 nM), and LLMGTLGIV from protein E7 (BL50 = 5500 nM)--were identified as high-affinity binders. Further, the structural basis and binding mode of HLA-A*0201-LLITSNINA complex was examined in detail, revealing a complicated network of nonbonded interactions across the complex interface that should render high stability and specificity for the interaction system.


Is the Lung Built for Exercise? Advances and Unresolved Questions.
Nearly 40 yr ago, Professor Dempsey delivered the 1985 ACSM Joseph B. Wolffe Memorial Lecture titled: "Is the lung built for exercise?" Since then, much experimental work has been directed at enhancing our understanding of the functional capacity of the respiratory system by applying complex methodologies to the study of exercise. This review summarizes a symposium entitled: "Revisiting 'Is the lung built for exercise?'" presented at the 2022 American College of Sports Medicine annual meeting, highlighting the progress made in the last three-plus decades and acknowledging new research questions that have arisen. We have chosen to subdivide our topic into four areas of active study: (i) the adaptability of lung structure to exercise training, (ii) the utilization of airway imaging to better understand how airway anatomy relates to exercising lung mechanics, (iii) measurement techniques of pulmonary gas exchange and their importance, and (iv) the interactions of the respiratory and cardiovascular system during exercise. Each of the four sections highlights gaps in our knowledge of the exercising lung. Addressing these areas that would benefit from further study will help us comprehend the intricacies of the lung that allow it to meet and adapt to the acute and chronic demands of exercise in health, aging, and disease.


Environmental monitoring through use of silica-based TLD.
The sensitivity of a novel silica-based fibre-form thermoluminescence dosimeter was tested off-site of a rare-earths processing plant, investigating the potential for obtaining baseline measurements of naturally occurring radioactive materials. The dosimeter, a Ge-doped collapsed photonic crystal fibre (PCFc) co-doped with B, was calibrated against commercially available thermoluminescent dosimetry (TLD) (TLD-200 and TLD-100) using a bremsstrahlung (tube-based) x-ray source. Eight sampling sites within 1 to 20 km of the perimeter of the rare-earth facility were identified, the TLDs (silica- as well as TLD-200 and TLD-100) in each case being buried within the soil at fixed depth, allowing measurements to be obtained, in this case for protracted periods of exposure of between two to eight months. The values of the dose were then compared against values projected on the basis of radioactivity measurements of the associated soils, obtained via high-purity germanium gamma-ray spectrometry. Accord was found in relative terms between the TL evaluations at each site and the associated spectroscopic results. Thus said, in absolute terms, the TL evaluated doses were typically less than those derived from gamma-ray spectroscopy, by ∼50% in the case of PCFc-Ge. Gamma spectrometry analysis typically provided an upper limit to the projected dose, and the Marinelli beaker contents were formed from sieving to provide a homogenous well-packed medium. However, with the radioactivity per unit mass typically greater for smaller particles, with preferential adsorption on the surface and the surface area per unit volume increasing with decrease in radius, this made for an elevated dose estimate. Prevailing concentrations of key naturally occurring radionuclides in soil, 226Ra, 232Th and 40K, were also determined, together with radiological dose evaluation. To date, the area under investigation, although including a rare-earth processing facility, gives no cause for concern from radiological impact. The current study reveals the suitability of the optical fibre based micro-dosimeter for all-weather monitoring of low-level environmental radioactivity.


Beta-carotene chemical stability in Nanoemulsions was improved by stabilized with beta-lactoglobulin-catechin conjugates through free radical method.
Beta-lactoglobulin (BLG)–catechin conjugates were prepared by a free radical method and investigated with sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE), electrospray ionization–mass spectrometry (ESI-MS), and far-UV circular dichroism (CD). Covalent binding between BLG and catechin were confirmed with SDS-PAGE and ESI-MS. About 93% of beta-lactoglobulin was conjugated with catechin or catecin fragments according to the gel intensity analysis software. Far-UV CD results showed that the content of β-sheet decreased with a corresponding increase in unordered structures after grafting. Both nanoemulsions with mean particle size between 160 and 170 nm were prepared. Both the rate of particle growth and the total beta-carotene (BC) loss at 50 °C were significantly greater than at 4 and 25 °C. The retention rates of BC in nanoemulsions were 27.8% and 48.6% for BLG and BLG–catechin conjugates, respectively, after 30 days of storage at 50 °C. The BC retention encapsulated in nanoemulsion was significantly improved using BLG–catechin conjugates, compared with BLG alone. The increase of BC retention in nanoemulsions encapsulated with BLG–catechin conjugates was due to the significant improvement of antioxidative properties (reducing power, free radical scavenging activity, and hydroxyl radical scavenging activity) of BLG after covalent binding with catechin. The results indicated that the proteins modified with polyphenols can be widely used in a labile bioactive compounds encapsulation delivery system.


Role of hepatic resident and infiltrating macrophages in liver repair after acute injury.
Treatment of liver disease, caused by hepatotoxins, viral infections, alcohol ingestion, or autoimmune conditions, remains challenging and costly. The liver has a powerful capacity to repair and regenerate, thus a thorough understanding of this tightly orchestrated process will undoubtedly improve clinical means of restoring liver function after injury. Using a murine model of acute liver injury caused by overdose of acetaminophen (APAP), our studies demonstrated that the combined absence of liver resident macrophages (Kupffer cells, KCs), and infiltrating macrophages (IMs) resulted in a marked delay in liver repair, even though the initiation and extent of peak liver injury was not impacted. This delay was not due to impaired hepatocyte proliferation but rather prolonged vascular leakage, which is caused by APAP-induced liver sinusoidal endothelial cell (LSEC) injury. We also found that KCs and IMs express an array of angiogenic factors and induce LSEC proliferation and migration. Our mechanistic studies suggest that hypoxia-inducible factor (HIF) may be involved in regulating the angiogenic effect of hepatic macrophages (Macs), as we found that APAP challenge resulted in hypoxia and stabilization of HIF in the liver and hepatic Macs. Together, these data indicate an important role for hepatic Macs in liver blood vessel repair, thereby contributing to tissue recovery from acute injury.