A Routine Method for the Extraction and HPLC-DAD Profiling of Major Plant and Food Carotenoids.
Carotenoids are ubiquitously present in Nature, and especially in plants and derived foods. The carotenoid profiling is necessary to understand relevant aspects in relation to their biochemistry and genetics, as well as their important roles on human health and animal ecophysiology. Here we propose a simple methodology for the routine extraction and efficient HPLC separation of the most common plant and food carotenoids from plant and animal origins.


Classification of acute respiratory disorders of all newborns in a tertiary care center.
To assess the usefulness of current diagnostic criteria in the understanding of neonatal respiratory distress in a tertiary care hospital. We prospectively studied 2824 consecutive deliveries to determine the frequency of respiratory disorders of all types. We used definitions based on standard texts, with borderline cases being classified as having the disease in question. Somewhat less than half of all symptomatic infants met textbook criteria for a respiratory diagnosis. Of this subset, the most common diagnosis was respiratory distress syndrome (RDS), followed by transient tachypnea of newborn (TTN), meconium aspiration syndrome (MAS), pneumonia and others. The 323 infants who fit no standard diagnosis all had self-limited conditions similar to TTN. Most (52%) were well in less than 12 hours. Those still symptomatic after 12 hours differed from the definition of TTN by having a clear chest film (38%) and/or by requiring mechanical ventilation (10%). A slight revision of the traditional diagnostic criteria allowed classification of all these cases. More than 50% of newborns with acute respiratory symptoms do not fit textbook definitions, even broad definitions which include borderline cases. The concept of TTN should be expanded to include cases with a normal chest film. In addition, we suggest adding the category "transient respiratory insufficiency of the newbom" (TRIN) for babies ventilated briefly but not demonstrably surfactant deficient or infected. This category probably includes infants with many contributing etiologies.


Cholesterol metabolism in non-obese women--Failure of physical conditioning to alter levels of high density lipoprotein cholesterol.
The effects of a 6-week program of vigorous exercise were studied in 14 non-obese females aged 22--26. Preceding and following a regimen consisting of 30--45 min of jogging 5 days per week, treadmill performance, body weight, total plasma cholesterol, and plasma high density lipoprotein (HDL) cholesterol were assessed. Aerobic performance improved markedly after training as demonstrated by a reduced heart rate at each submaximal treadmill workload, and by an increase in maximal attainable workload. In the absence of a significant change in body weight, total cholesterol fell significantly after training (171 +/- 6 vs 161 +/- 5 mg/dl, P less than 0.05) whereas HDL cholesterol was not significantly altered (63 +/- 5 vs 58 +/- 3 mg/dl). The ratio of total cholesterol to HDL cholesterol fell insignificantly (2.92 +/- 0.19 vs 2.86 +/- 0.14). Our findings differ from prior reports of elevations of high density lipoprotein levels following physical conditioning in men. We suggest that hormonal or other factors leading to higher baseline levels of HDL in women counteract the expected alterations in lipoprotein metabolism induced by physical training.


Increased brain serotonin metabolism during rebound sleep in sleep-deprived rats.
Adult male Wistar rats were almost totally deprived of sleep by handling for 24 hr. 5-Hydroxyindolacetic acid concentrations in the dorsal raphe nucleus area and thalamus increased by 140-180%, immediately after sleep deprivation and when the rats had a 3- or 30-min rebound sleep. The higher levels of 5-hydroxyindolacetic acid were still observed after the rats were awakening from a 4-hr sleep. The concentrations of 5-hydroxytryptamine (serotonin) decreased after sleep deprivation and increased during and after sleep, but the differences were not significant. Tryptophan accumulated in the dorsal raphe area and thalamus after sleep deprivation, and an elevated level did not return to baseline concentrations until the rats were awakening. Tryptophan hydroxylase activity did not change in the dorsal raphe area during and after sleep deprivation. These results suggest that the release and synthesis of 5-hydroxytryptamine in the dorsal raphe area and thalamus increased when the rats had a sleep pressure or a rebound sleep after total sleep deprivation. An increased transport of tryptophan into the brain may be closely involved in sleep-inducing mechanisms.


Camphor-based Schiff base ligand SBAIB: an enantioselective catalyst for addition of phenylacetylene to aldehydes.
A series of Schiff base ligands were synthesized from (1R)-camphor. Under the optimal conditions, (+)-SBAIB-a, 10 was found to be an excellent catalyst for the enantioselective addition of phenylacetylene to various aldehydes without utilizing either achiral additives or Ti(O(i)Pr)(4). This approach yielded (R)-propargylic alcohols in extremely high yields (up to 99%) and excellent enantioselectivities (up to 92%). The corresponding (S)-propargylic alcohols were synthesized in good to high enantioselectivities (up to 91%) and excellent yields (up to 99%) using (-)-SBAIB-a, 41.


Assessing the risks on human health associated with inorganic arsenic intake from groundwater-cultured milkfish in southwestern Taiwan.
The risk of consuming groundwater-cultured milkfish (Chanos chanos) was assessed. Samples of water and milkfish from groundwater-cultured ponds in southwestern Taiwan were analyzed. One third of the 12 sampled ponds had arsenic concentrations in the water higher than 50 microg/L, which is the maximum allowed concentration for arsenic in aquacultural water in Taiwan. Of the total amount of arsenic in water, the percentage of inorganic arsenic was 67.5+/-8.8%. The inorganic arsenic level in milkfish was 44.1+/-10.2%. The bioconcentration factors (BCFs) of milkfish for total arsenic and inorganic arsenic were 11.55+/-4.42 and 6.8+/-2.64, respectively. The target cancer risk (TR) for intake of the milkfish from those ponds was higher than the safe standard 1 x 10(-6), while in 8 of the ponds the TR values were higher than 1 x 10(-4). Among the 12 ponds, 7 of those had the target hazard quotient (THQ) for intake of the milkfish higher than the safe standard 1. The actual consumption (IRF) of milkfish from most of those ponds were higher than the calculated acceptable consumption (RBIRF), based on TR = 1 x 10(-6)-1 x 10(-4). Only three sampled ponds (Putai 2, Peimen 2 and Peimen 3) did not show differences between the IRF and the RBIRF. Based on the standard TR = 1 x 10(-6), both the risk-based concentration for inorganic arsenic in milkfish (RBC(f)) and the risk-based concentration for inorganic arsenic in pond water (RBC(w)) were lower than the levels of inorganic arsenic in reared milkfish (C(b)) and the concentration of inorganic arsenic in pond water (C(w)), respectively. When the calculation was based on TR = 1 x 10(-4), only one sampled pond (Putai 3) had a RBC(f) value higher than C(b). The inhabitants might be exposed to arsenic pollution with carcinogenic and non-carcinogenic risks.


Critique of the toxicology and carcinogenesis studies of iodinated glycerol in F344/N rats and B6C3F1 mice.
Carter-Wallace conducted a detailed audit and evaluation of the data available from the carcinogenicity studies with iodinated glycerol conducted in the B6C3F1 mouse and the F344/N rat by the National Toxicology Program (NTP). We conclude that there is no evidence of carcinogenicity of the compound in either the B6C3F1 mouse or the F344/N rat.


Isobutanol production by combined in vivo and in vitro metabolic engineering.
The production of the biofuel, isobutanol, in E. coli faces limitations due to alcohol toxicity, product inhibition, product recovery, and long-term industrial feasibility. Here we demonstrate an approach of combining both in vivo with in vitro metabolic engineering to produce isobutanol. The in vivo production of α-ketoisovalerate (KIV) was conducted through CRISPR mediated integration of the KIV pathway in bicistronic design (BCD) in E. coli and inhibition of competitive valine pathway using CRISPRi technology. The subsequent in vitro conversion to isobutanol was carried out with engineered enzymes for 2-ketoacid decarboxylase (KIVD) and alcohol dehydrogenase (ADH). For the in vivo production of KIV and subsequent in vitro production of isobutanol, this two-step serial approach resulted in yields of 56% and 93%, productivities of 0.62 and 0.074 g L-1 h-1, and titers of 5.6 and 1.78 g L-1, respectively. Thus, this combined biosynthetic system can be used as a modular approach for producing important metabolites, like isobutanol, without the limitations associated with in vivo production using a consolidated bioprocess.


[Leg re-contouring by using a new technique of partially removing gastrocnemius].
To evaluate a method to partially remove gastrocnemius for improvement of the contour of the leg. Thirteen patients with bulked calf were undergoing the treatment. With a self-designed apparatus, the gastrocnemius was partially removed by placing the device in the muscle through an incision in the popliteal fossa. The follow-ups were carried out for 1-6 months. Thirteen patients were successfully treated by above mentioned technique. The removed amount of muscle was weighted between 11 g and 201 g, averaged 77 g. All of the patients could be able to walk three days after the operation. But, the normal walk had to take 1 month after of the surgery for recovering. The function of the ankle joint was not obviously influenced. The above mentioned technique is a safe and effective method for re-contouring the leg.


Simultaneous reversal of risk factors for cardiac death and intensified therapy in long-term survivors of paediatric end-stage renal disease over the last 10 years.
In an extended long-term follow-up of patients on chronic renal replacement therapy (RRT) since childhood (LERIC study), we observed a substantial reduction in cardiovascular (CV) death over the last decade. In this study, we investigated the contemporaneous changes in risk factors for CV death and cardioprotective therapy. The cohort consisted of 140 Dutch patients, who were born before 1979 and started RRT before 15 years of age between 1972 and 1992. We compared the prevalence of various factors in 2000 and 2010 by calculating matched odds ratios (OR(matched)). Median age of patients was 38.5 years (range 23.2-50.8) in 2010, after a median time on RRT of 28 years. The prevalence of CV risk factors decreased from 41.3% in 2000 to 18.8% in 2010. The OR(matched) in 2010 compared with 2000 for left ventricular hypertrophy, hypertension and hypercholesterolaemia were 0.26 (95% CI 0.09-0.66), 0.22 (95% CI 0.01-0.59) and 0.04 (95% CI 0.01-0.25), respectively. The rate of nonfatal CV events dropped, although not significantly, from 1.75/100 (95% CI 1.3-2.4) per patient year (py) in 1972-2000 to 0.95/100 (95% CI 0.5-1.7) py in 2000-2010. ACE inhibitors/angiotensin receptor blockers and cholesterol lowering medication were prescribed significantly more often in the period 2000-10 [OR(matched) = 7.40 (95% CI 2.90-24.10) and 11.5 (95% CI 4.20-43.90)]. Trends were similar among those who survived and those who did not survive the last decade. We observed a decrease in clinical CV disease synchronous to intensified antihypertensive and antidyslipidaemic therapy in long-term survivors of paediatric renal failure. This advocates a vigorous cardioprotective management in these patients.


Soft and Hard Tissue Remodeling after Endodontic Microsurgery: A Cohort Study.
The aim of this study was to investigate the impact of the incision type, with or without a coronally repositioning flap (CRF), on soft tissue healing and crestal bone remodeling after endodontic microsurgery (EMS). Clinical pictures and cone-beam computed tomography images from 47 patients (120 teeth) taken before surgery and at the follow-up appointment were included in this study. Clinical pictures were qualitatively evaluated by 2 endodontists for the gingival marginal level (GML) (recession, same position, or coronal root coverage), papillary height (same position/receded), and for presence/absence of scars for each tooth. Cone-beam computed tomography images were used to calculate the changes in the distance between the cementoenamel junction and the crestal bone level (CBL) between the preoperative and follow-up scans. Statistical analyses were performed to determine a correlation between patient-related factors (age, sex, tooth type, position, and presence/absence of a crown), incision techniques, and changes within the CBL. Gingival recession was more prevalent in mandibular teeth, molar teeth, and teeth that received intrasulcular or papilla-based incisions (P < .05). Scar formation was affected by the flap design (P < .05). CRF was the only technique resulting in coronal root coverage (P < .05). There were no changes observed in the papillary height between the various flap designs. There was also no statistically significant difference in the crestal bone height between the preoperative and follow-up scan measurements (P > .05). Soft tissue changes are evident after EMS and can be affected by the flap design selected, as well as the site being treated. Application of CRF can improve the position of GML after EMS. There are insignificant changes within the CBL at the facial aspect of the root after EMS.


Cervicovaginal microbiota dysbiosis correlates with HPV persistent infection.
HPV persistent infection is a main event leading to the development of cervical intraepithelial neoplasia and cervical cancer. Earlier to distinguish HPV persistent and transient infection is meaningful but the methods are limited. This study used 16S rDNA sequencing to determine the cervicovaginal microbiota of HPV persistent infection, transient infection and health women. Sequences analysis was performed and according to subsequent statistical analysis, the structure of cervicovaginal microbiota of healthy and transient infection individuals is relatively single, Firmicutes occupy the main composition. However, that of the HPV persistent infection presented a complicated trend and the abundance of Proteobacteria, Actinobacteria, Bacteroidetes and Fusobacteria was higher. The significance p-values of the average species abundance of Firmicutes, Proteobacteria and Bacteroides between HPV persistent and transient infection groups were 0.003, 0.018 and 0.005, respectively. The study also found 36 biomarkers of cervicovaginal microbiota dysbiosis for LDA score>4 among different groups. At genus level, Prevotella, Sphingomonas and Anaerococcus correlated with HPV persistent infection. At species level, Lactobacillus iners correlated with HPV transient infection. Besides, local immune microenvironment was changed with cervicovaginal microbiota dysbiosis. Interleukin-6 and TNF-α were significantly upregulated in cervical secretions from HPV persistent infection compared with those from transient infection and healthy women. Peripheral blood Regulatory T cells and myeloid-derived suppressor cells in patients with HPV persistent infection were also significantly increased. In conclusion, this study identified cervicovaginal microbiota dysbiosis closely related to HPV persistent infection, which provided a new idea and method for the prevention of cervical cancer.


Omicron BA.2.75 variant is efficiently neutralised following BA.1 and BA.5 breakthrough infection in vaccinated individuals, Israel, June to September 2022.
We evaluated neutralising antibody titres against wild type (WT) SARS-CoV-2 and four Omicron variants (BA.1, BA.2, BA.5 and BA.2.75) in fully vaccinated (three doses of Comirnaty vaccine) healthcare workers (HCW) in Israel who had breakthrough BA.1/BA5 infections. Omicron breakthrough infections in vaccinated individuals resulted in increased neutralising antibodies against the WT and Omicron variants compared with vaccinated uninfected HCW. HCW who recovered from BA.1 or BA.5 infections showed similar neutralising antibodies levels against BA.2.75.


Use of Micro Botulinum Toxin for a Face-lifting Effect: A Systematic Review.
Micro-Botox (Micro-btx) was described in 2000 for the paralysis of superficial muscle fibers to address facial rhytides. Increasingly, there are reports of its off-label use for a face-lifting effect. To evaluate the literature for such results. A systematic review was performed according to PRISMA; only Level ≥ III evidence from 2000 to 2020 were included. Data extracted include patient demographics, type of botulinum toxin, dilution, dosage, injection sites and spacing, needle size and syringe, follow-up, patient and physician assessment, and complications. Three hundred seventy-two patients (average 35.2 years) underwent different botulinum toxin injections (average 39 units/hemiface) of varying dilutions with 30- to 32-G needles, typically with 1-mL syringes, by forming 0.2- to 0.5-cm wheals 1 cm apart. Follow-up averaged 10.5 weeks with both subjective and objective assessments. Facial asymmetry and minor bruising were common. Subjective assessment of face-lifting effects between patients and physicians was highly discordant and injection sites reported were highly variable. Much heterogeneity in dosage, injection sites, definition of "face-lifting," and assessment methods remain, all of which preclude accurate and objective evaluation of the current evidence for micro-btx. Future studies should address these variables, given the growing interest in such nonsurgical options for a face-lifting effect.


Increased susceptibility to lipid peroxidation in skeletal muscles of dystrophic hamsters.
The results showed that the total content of lipids, which could be peroxidized with Fe(2 +)/ascorbate stimulation in vitro, was 45.4% and 53.7% higher than normal in the dystrophic hamster muscle at the age of 1 and 3 months, respectively. Correspondingly, the susceptibility to lipid peroxidation (stimulated by ADP-chelated iron at 37 degrees C) was 38.6-74.3% higher in dystrophic muscles. The increases were not related to necrotic lesions and inflammation observed. The activities of glucose-6-phosphate dehydrogenase, glutathione reductase, thioredoxin reductase and catalase were increased in dystrophic muscles but those of superoxide dismutases and glutathione peroxidase were unaffected.


Key to Treating COVID-19: Removing Phlegm from Small Airways.
According to autopsy reports, patients who died from COVID-19 had a lot of mucus in the lung that obstructed the airways, reduced the effect of mechanical ventilation, and even led to pulmonary failure. Traditional Chinese medicine literature mentions that "Inability to remove phlegm impairs the lung, which leads to death." Hence one of the most urgent problems to be solved is to remove phlegm from the small airways. This article elaborates ten methods to remove phlegm for clinical reference.


Understanding Surprise Out-of-Network Billing in Hand and Upper Extremity Care.
Surprise billing occurs when insured patients receive unexpected out-of-network charges and fees even when the emergency department, facility, or primary physician who provided care is in their insurance network. This issue is particularly relevant for hand surgery. The multidisciplinary nature of hand care and the number of ancillary services involved result in various levels at which out-of-network billing can be introduced, even when the hand surgeon is in-network for the patient. In addition, surprise billing is often associated with emergency department encounters, elective surgeries, and ambulance and helicopter transfers. In this article, we review surprise billing as it pertains to hand surgery. Little is known about surprise billing in hand care; however, we believe that these practices may substantially affect the patient population. We define key elements of surprise billing, review the literature, discuss the relevance and potential of surprise billing in hand surgery in various settings, and provide an overview of the status of health policy surrounding this practice. It is imperative for hand surgery as a field to understand the prevalence, operationalization, and policies of surprise billing better to prevent the exploitation of patients.


A head swivel technique for breast tangents.
Two of the major problems with treating breast tangents are the difficulties in simulating the treatment and the reproducibility of the setup on a day to day basis. This paper describes a simple technique which takes advantage of the head swivel capability of certain cobalt-60 units to allow simulation and treatment of the breast and chest wall based upon a setup at the field edges which are normally not on mobile breast tissue. The technique offers some of the advantages of half block techniques but does not require the use of half blocks or bridges.


[Special sound probe for foreign body localisation (author's transl)].
A recently developed sound probe (10 MHz and 3 mm diameter) is suitable for sparing preoperative localisation of foreign bodies in perforated eyes; especially mural foreign bodies can be exactly located intraoperatively. Followed scleral incision foreign bodies can be extracted on the optimal route.


Oviposition specificity in single vs. cluster egg-laying butterflies: a discrimination phase in Colias eurytheme?
Oviposition preferences and rates of the pierid butterfly Colias eurytheme were examined in laboratory tests. Oviposition rates with only a non-preferred host plant present were not lower than rates observed when both preferred and non-preferred hosts were present. There was no correlation between strength of preference in simultaneous choice tests and the extent to which oviposition rate declined when the preferred host was absent. The results are consistent with the hypothesis that butterflies which lay their eggs singly will accept non-preferred hosts for oviposition more readily than cluster egg-layers.


Catalytic competence, a new criterion for affinity labeling. Demonstration of the reversible enzymatic interconversion of estrone and estradiol-17 beta covalently bound to human placental estradiol-17 beta dehydrogenase.
Human placental estradiol-17beta dehydrogenase is rapidly inactivated upon treatment with 3-bromoacetoxyestrone. Pseudo-first order kinetic data are obtained and inactivation is accompanied by incorporation of 1 mol of 3-acetoxyestrone/mol of subunit (Mr =34,000). Treatment of the inactivated enzyme with (4S)-[4-2H]DPNH results in the formation of covalently bound [17alpha-2H]estradiol-17beta, which can be released by hydrolysis and identified by gas chromatography-mass sepctrometry. When (4R)-[4-2H]DPNH was used, deuterium was not transferred. Thus, the normal stereochemistry of hydridetransfer is preserved for both partners. After treatment with p-mercuribenzoate, affinity-labeled estradiol-17beta dehyrogenase is no longer able to caralyze reduction its covalently bound estrone; in the presence of DPNH and native enzyme, however, reduction occurs, demonstrating that affinity-labeled enzyme can itself serve as subtrate for native estradiol-17beta dehydrogenase. The reversible enzymatic interconversion of covalently bound estrone was demonstrated using a transhydrogenase assay. The ability of an enzyme to catalyze its normal reaction with a covalently bound substrate is termed catalytic competence, and is considered to be a new criterion for affinity labeling.


An amplified fluorescence polarization assay for sensitive sensing of organophosphorus pesticides via MnO2 nanosheets.
It is highly desirable to develop a simple, efficient and sensitive strategy for organophosphorus pesticides (OPs) in both environment pollution and human health. Herein, a novel amplified fluorescence polarization (FP) biosensor was established for highly sensitive detection of OPs using MnO2 nanosheets as the signal enhancer. In this system, OPs can suppress the activity of acetylcholinesterase (AChE) efficiently, blocking the hydrolysis reaction of acetylthiocholine (ATCh) to generate thiocholine (TCh) by AChE. TCh can lead the decomposition of MnO2 nanosheets to manganese ions. So, without the influence of TCh, MnO2 nanosheets can maintain its original shape and form a stable complex with FAM-DNA, which greatly enhanced the FP signal. This method can tremendously improve the sensitivity of FP with a detection limit of 0.01 ng/mL for diazinon. In addition, it was also applicable to determine other four OPs and investigate the level of diazinon in real water samples. Consequently, the proposed approach provides a new promising platform for detection of OPs and is expected to be used in application of environmental monitoring.


Improving distributed PV integration with dynamic thermal rating of power distribution equipment.
The rapid development of distributed photovoltaic (PV) systems poses great challenges to the integration capability of distribution networks. Traditionally, the transfer capacity of power distribution equipment is calculated as the maximum loading that prevents overheating under the assumption of extreme weather conditions. Dynamic thermal rating (DTR), which evaluates equipment capacity based on real-time weather conditions, could enhance the transfer capacity to improve distributed PV integration. Through case studies in Texas, Switzerland, and China, we show that the application of DTR on power distribution equipment could increase installed PV capacities by 15%-27% and improve net revenues by 4%-27%. We also find that the application of DTR would be positively affected by climate change and is more profitable under the PV policies with higher tariffs for the surplus generation fed into the grid. Compared to energy storage systems, DTR provides a more cost-competitive option to enhance the integration capability of distribution networks.


Sudden cardiac death and preparticipation screening: the debate continues-in support of electrocardiogram-inclusive preparticipation screening.
Sudden cardiac death (SCD) is the leading cause of death in young athletes during exercise, and there is international agreement among major medical and sporting bodies that young athletes should undergo preparticipation cardiovascular screening. However, there is currently no universally accepted screening protocol, and substantial debate exists about what constitutes the ideal approach to preparticipation screening. The primary objective of preparticipation screening is the detection of intrinsic structural or electrical cardiovascular disorders that predispose an athlete to SCD. Considerable evidence exists suggesting that screening athletes with only a history and physical examination leaves most athletes with a serious underlying cardiovascular disease undetected and, thus, cannot adequately achieve the primary objective of screening. Preparticipating cardiovascular screening inclusive of an electrocardiogram (ECG) greatly enhances the ability to identify athletes at risk and is the only model shown to be cost-effective and may reduce the rate of SCD. The major obstacle to ECG screening in the United States is the lack of a physician workforce skilled in interpretation of an athlete's ECG. However, recent studies have demonstrated a capacity to distinguish physiologic ECG alterations in athletes from findings suggestive of underlying pathology that is both feasible and has a low false-positive rate. Efforts are underway to increase physician education in ECG interpretation. After 2 decades debating the proper screening strategy to identify athletes at risk, the weight of scientific evidence suggests that a screening program inclusive of ECG is the only strategy that merits promotion.


Do either early warning systems or emergency response teams improve hospital patient survival? A systematic review.
For critical care to be effective it must have a system in place to achieve optimal care for the deteriorating ward patient. To systematically review the available literature to assess whether either early warning systems or emergency response teams improve hospital survival. In the event of there being a lack of evidence regarding hospital survival, secondary outcome measures were considered (unplanned ICU admissions, ICU mortality, length of ICU stay, length of hospital stay, cardiac arrest rates). The Ovid Medline, EMBASE, CINAHL, Web of Science, Cochrane library and NHS databases were searched in September 2012 along with non-catalogued resources for papers examining the effect of early warning systems or emergency response teams on hospital survival. Inclusion criteria were original clinical trials and comparative studies in adult inpatients that assessed either an early warning system or emergency response team against any of the predefined outcome measures. Exclusion criteria were previous systematic reviews, non-English abstracts and studies incorporating paediatric data. Studies were arranged in to sections focusing on the following interventions: Early warning systems - Single parameter systems - Aggregate weighted scoring systems (AWSS) Emergency response teams - Medical emergency teams - Multidisciplinary outreach services . In each section an appraisal of the level of evidence and a recommendation has been made using the SIGN grading system. 43 studies meeting the review criteria were identified and included for analysis. 2 studies assessed single parameter scoring systems and 4 addressed aggregate weighted scoring systems. A total of 20 studies examined medical emergency teams and 22 studies examined multidisciplinary outreach teams. The exclusion of non English studies and those including paediatric patients does limit the applicability of this review. Much of the available evidence is of poor quality. It is clear that a 'whole system' approach should be adopted and that AWSS appear to be more effective than single parameter systems. The response to deterioration appears most effective when a clinician with critical care skills leads it. The need for service improvement differs between health care systems.


Correlation between spontaneous oscillations of cytosolic free Ca2+ and tumor necrosis factor-induced degranulation in adherent human neutrophils.
By using a hemolytic plaque assay to detect release of lactoferrin and myeloperoxidase, tumor necrosis factor (TNF) was shown previously to induce secretion of these granule proteins from single adherent neutrophils. Secretion was inhibited by loading neutrophils with calcium chelators, indicating a crucial role of cytosolic free [Ca2+] in the signal transduction mechanism of TNF. In the present study, using a microfluorometer technique to follow changes in the cytosolic free [Ca2+] in single adherent neutrophils, we were not able to detect any TNF-induced [Ca2+] transients. However, these adherent cells exhibited spontaneous oscillations of their cytosolic free [Ca2+], as previously reported (Jaconi, M.E.E., Rivest, R.W., Schlegel, W., Wollheim, C.B., Pittet, D., and Lew, P.D. (1988) J. Biol. Chem. 263, 10557-10560). A close correlation was found between a reduced oscillatory activity of cytosolic free [Ca2+] and a reduced ability of TNF to induce degranulation, by reducing the extracellular [Ca2+] or loading the cells with a calcium chelator (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid). In addition, when the cells were incubated at 37 degrees C for 3 h there was a parallel decline in the spontaneous oscillatory activity of cytosolic free [Ca2+] and TNF-induced secretion of lactoferrin. Control experiments showed that phorbol 12-myristate 13-acetate-induced secretion was not affected under the same conditions, indicating that the secretory process per se was not disturbed. We conclude that TNF by itself does not give rise to any changes of the cytosolic free [Ca2+] but that the spontaneous oscillatory activity of cytosolic free [Ca2+] in adherent neutrophils is necessary for TNF-induced degranulation.


Río-Hortega's drawings revisited with fluorescent protein defines a cytoplasm-filled channel system of CNS myelin.
A century ago this year, Pío del Río-Hortega (1921) coined the term 'oligodendroglia' for the 'interfascicular glia' with very few processes, launching an extensive discovery effort on his new cell type. One hundred years later, we review his original contributions to our understanding of the system of cytoplasmic channels within myelin in the context of what we observe today using light and electron microscopy of genetically encoded fluorescent reporters and immunostaining. We use the term myelinic channel system to describe the cytoplasm-delimited spaces associated with myelin; being the paranodal loops, inner and outer tongues, cytoplasm-filled spaces through compact myelin and further complex motifs associated to the sheath. Using a central nervous system myelinating cell culture model that contains all major neural cell types and produces compact myelin, we find that td-tomato fluorescent protein delineates the myelinic channel system in a manner reminiscent of the drawings of adult white matter by Río-Hortega, despite that he questioned whether some cytoplasmic figures he observed represented artefact. Together, these data lead us to propose a slightly revised model of the 'unrolled' sheath. Further, we show that the myelinic channel system, while relatively stable, can undergo subtle dynamic shape changes over days. Importantly, we capture an under-appreciated complexity of the myelinic channel system in mature myelin sheaths.


Surgical salvage of human papillomavirus-positive oropharyngeal cancer: Secondary analysis of a randomized controlled trial.
Survival outcomes are generally better for human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) than other forms of head and neck cancer. However, less is known about oncologic outcomes, late adverse events, and gastrostomy tube dependence associated with salvage surgery after the failure of definitive chemoradiation in patients with HPV+ OPSCC. A secondary analysis of the Radiation Therapy Oncology Group 1016 randomized trial, which compared radiotherapy plus cetuximab to radiotherapy plus cisplatin in patients with HPV+ OPSCC, was performed. The oncologic and adverse event outcomes for patients who underwent salvage surgery were examined. Among the 805 patients who were assigned to treatment and were eligible for analysis, 198 developed treatment failure. Salvage surgery was required for 61 patients (7.6%), with 33 patients undergoing salvage surgery after locoregional failure (LRF) and 28 patients undergoing salvage neck dissection within the 20 weeks after treatment. Patients with LRF who underwent salvage surgery experienced improved overall survival in comparison with patients with LRF who did not undergo surgery (45% vs. 17% at 5 years after treatment; hazard ratio, 0.41; 95% confidence interval [CI], 0.23-0.74). Surgical salvage after LRF was associated with similar frequencies of late grade 3/4 dysphagia in comparison with LRF without surgery (24% [95% CI, 13%-41%] vs. 20% [95% CI, 12%-32%]; p = .64) and with similar gastrostomy tube dependence at 2 years (29% [95% CI, 15%-49%] vs. 13% [95% CI, 5%-28%]; p = .12). Salvage surgery in patients with HPV+ OPSCC is associated with favorable survival and adverse event outcomes.


Metamaterial-enabled arbitrary on-chip spatial mode manipulation.
On-chip spatial mode operation, represented as mode-division multiplexing (MDM), can support high-capacity data communications and promise superior performance in various systems and numerous applications from optical sensing to nonlinear and quantum optics. However, the scalability of state-of-the-art mode manipulation techniques is significantly hindered not only by the particular mode-order-oriented design strategy but also by the inherent limitations of possibly achievable mode orders. Recently, metamaterials capable of providing subwavelength-scale control of optical wavefronts have emerged as an attractive alternative to manipulate guided modes with compact footprints and broadband functionalities. Herein, we propose a universal yet efficient design framework based on the topological metamaterial building block (BB), enabling the excitation of arbitrary high-order spatial modes in silicon waveguides. By simply programming the layout of multiple fully etched dielectric metamaterial perturbations with predefined mathematical formulas, arbitrary high-order mode conversion and mode exchange can be simultaneously realized with uniform and competitive performance. The extraordinary scalability of the metamaterial BB frame is experimentally benchmarked by a record high-order mode operator up to the twentieth. As a proof of conceptual application, an 8-mode MDM data transmission of 28-GBaud 16-QAM optical signals is also verified with an aggregate data rate of 813 Gb/s (7% FEC). This user-friendly metamaterial BB concept marks a quintessential breakthrough for comprehensive manipulation of spatial light on-chip by breaking the long-standing shackles on the scalability, which may open up fascinating opportunities for complex photonic functionalities previously inaccessible.


Who should be counselors in methadone maintenance programs: ex-addicts or nonaddicts?
Counselors play a central role in most methadone maintenance programs. Yet the choice of who should be employed as counselors is based on little more than personal whims of decision makers. And in evaluating the effectiveness of this highly controlled rehabilitative therapy, the influence of the counselors as an important factor is often ignored. The total changeover of the counselors from an ex-addict to a nonaddict group in an otherwise stable clinic provided an unusual opportunity to compared the performance of the two groups. Both the objective and subjective data supported the hypothesis that ex-addicts as a group compared unfavorably with a similar group of nonaddicts when employed as counselors in a methadone maintenance clinic.


Cultural interconnectedness and in-group cooperation as sources of innovation.
I argue that the increased rate of innovation in eighteenth-century England cannot be understood without accounting for the unprecedented level of contact between England and other societies as a consequence of sixteenth-century colonialism. I propose cultural interconnectedness and in-group cooperation as two potential alternative explanations for the psychological changes and innovative behavior described by Baumard.


Influx of extracellular calcium participates in rituximab-enhanced ionizing radiation-induced apoptosis in Raji cells.
We have previously shown that rituximab has a significant radiosensitizing effect on Raji cells in vitro. To investigate whether calcium signals participate in rituximab- and radiation-induced cell death in Raji cells, confocal laser scanning microscopy was used to detect kinetic changes in intracellular free calcium concentration ([Ca2+]i). Cell survival, the rates of apoptosis in Raji cells and the kinetics of γ-H2AX foci induction and loss were also evaluated. X-irradiation of Raji cells induced an initial increase of [Ca2+]i in both the presence and absence of extracellular calcium, followed by a decrease in [Ca2+]i over time. Rituximab enhanced both the amplitude and the duration of intracellular calcium signals in the irradiated cells. EGTA significantly inhibited radiation- or radiation/rituximab combination treatment-induced apoptosis. However, the calcium chelators EGTA and BAPTA/AM conferred no survival advantage on the irradiated cells. Furthermore, although no significant difference was seen after 1h, the treatment of cells with a combination of irradiation and rituxiamb caused an increase of γ-H2AX foci when compared with irradiated cells after 8h. Both EGTA and BAPTA/AM suppressed the number of γ-H2AX foci induced by either radiation or radiation combined with rituximab. Our results suggest that rituximab increases the level of [Ca2+]i in irradiated Raji cells. The entry of calcium from the extracellular space plays an essential role in [Ca2+]i-dependent radiation-induced apoptosis in Raji cells. The calcium chelators inhibited the formation of γ-H2AX foci, which are thought to prevent the activation of Ca2+/Mg(2+)-dependent endonucleases and subsequent DNA fragmentation. The calcium chelators most likely modulate only particular features of apoptosis and fail to change the fates of cells that are already committed to die.


Data in support of the detection of genetically modified organisms (GMOs) in food and feed samples.
Food and feed samples were randomly collected from different sources, including local and imported materials from the Syrian local market. These included maize, barley, soybean, fresh food samples and raw material. GMO detection was conducted by PCR and nested PCR-based techniques using specific primers for the most used foreign DNA commonly used in genetic transformation procedures, i.e., 35S promoter, T-nos, epsps, cryIA(b) gene and nptII gene. The results revealed for the first time in Syria the presence of GM foods and feeds with glyphosate-resistant trait of P35S promoter and NOS terminator in the imported soybean samples with high frequency (5 out of the 6 imported soybean samples). While, tests showed negative results for the local samples. Also, tests revealed existence of GMOs in two imported maize samples detecting the presence of 35S promoter and nos terminator. Nested PCR results using two sets of primers confirmed our data. The methods applied in the brief data are based on DNA analysis by Polymerase Chain Reaction (PCR). This technique is specific, practical, reproducible and sensitive enough to detect up to 0.1% GMO in food and/or feedstuffs. Furthermore, all of the techniques mentioned are economic and can be applied in Syria and other developing countries. For all these reasons, the DNA-based analysis methods were chosen and preferred over protein-based analysis.


Hypothenar hammer syndrome: a discrete syndrome to be distinguished from hand-arm vibration syndrome.
Hypothenar hammer syndrome (HHS) is a cause of vascular insufficiency to the hand and may be manifest as Raynaud's phenomenon. The cause is trauma to the vulnerable portion of the ulnar artery as it passes over the hamate bone, which may result in thrombosis, irregularity or aneurysm formation. This review was undertaken in order to clarify the features of HHS that may differentiate it from hand-arm vibration syndrome. A tiered review of world literature was undertaken using Medline and EMBase as the primary search engines. Fifty-two relevant articles were critically reviewed. Colour and temperature changes occur more diffusely in HHS than in classical Raynaud's phenomenon and the absence of the triphasic colour change may alert clinicians to the diagnosis, which may be confirmed by Allen's test. Doppler or arteriographic studies are required for confirmation. It is important to recognize the possibility of HHS in the occupational setting as a potentially curable cause of Raynaud's phenomenon, distinct from hand-arm vibration syndrome. The possibility exists of HHS occurring as a result of repeated hypothenar trauma from vibrating tools, in which case the nature and magnitude of the individual episode of trauma may be more important than the weighted acceleration level of vibration exposure.


Habitat selection in tadpoles of Ranidella signifera and R. riparia (Anura: Leptodactylidae).
Two leptodactylid frog species Ranidella signifera and R. riparia occupy adjacent but different habitat types in the Flinders Ranges of South Australia. R. signifera is found in slow-flowing creeks with mud or sand substrates. R. riparia occupies fast-flowing rocky creeks. The two coexist in a narrow overlap zone with heterogeneous habitats. Laboratory experiments were used to test habitat preferences of tadpoles in a tub with sand and rock substrates. R. riparia was most commonly found on the rock substrate. R. signifera showed no distinct preference for sand, but when mixed with R. riparia increased its use of the habitat in the spaces between and under rocks. This was particularly apparent in flowing water where 81% of all R. signifera tadpoles were observed in this sheltered habitat.The data suggest that R. signifera tadpoles have reduced fitness in flowing water because they cannot exploit exposed feeding sites where most of the algae grow, and that interspecific interactions with R. riparia tadpoles reduce their fitness further. This helps to explain why R. signifera do not extend their distribution into R. riparia occupied creeks. The data do not explain why R. riparia do not colonize the slow muddy creeks occupied by R. signifera.


Gene order of the histidine utilization (hut) operons in Klebsiella aerogenes.
P1-sensitive mutants of Klebsiella aerogenes were isolated and the gene order of the hut region was then determined using P1-mediated transduction. The genes are located in the Klebsiella chromosome between gal and bio as in Salmonella typhimurium. The gene order, gal, hutI, hutG, hutC, huU, hutH, bio is also the same as that observed in S. typhimurium.


Relief of cannabis withdrawal symptoms and cannabis quitting strategies in people with schizophrenia.
This study examined the response to cannabis withdrawal symptoms and use of quitting strategies to maintain abstinence in people with schizophrenia. A convenience sample of 120 participants with schizophrenia who had at least weekly cannabis use and a previous quit attempt without formal treatment were administered the 176-item Marijuana Quit Questionnaire to characterize their "most serious" (self-defined) quit attempt. One hundred thirteen participants had withdrawal symptoms, of whom 104 (92.0%) took some action to relieve a symptom, most commonly nicotine use (75%). 90% of withdrawal symptoms evoked an action for relief in a majority of participants experiencing them, most frequently anxiety (95.2% of participants) and cannabis craving (94.4%). 96% of participants used one or more quitting strategies to maintain abstinence during their quit attempt, most commonly getting rid of cannabis (72%) and cannabis paraphernalia (67%). Religious support or prayer was the quitting strategy most often deemed "most helpful" (15%). Use of a self-identified most helpful quitting strategy was associated with significantly higher one-month (80.8% vs. 73.6%) and one-year (54.9% vs. 41.3%) abstinence rates. Actions to relieve cannabis withdrawal symptoms in people with schizophrenia are common. Promotion of effective quitting strategies may aid relapse prevention.


Atomistic insights into the binding of SARS-CoV-2 spike receptor binding domain with the human ACE2 receptor: The importance of residue 493.
SARS-CoV-2 is a coronavirus that has created a global pandemic. The virus contains a spike protein which has been shown to bind to the ACE2 receptor on the surface of human cells. Vaccines have been developed that recognize elements of the SARS-CoV-2 spike protein and they have been successful in preventing infection. Recently, the Omicron variant of the SARS-CoV-2 virus was reported and quickly became a variant of concern due to its transmissibility. This variant contained an unusually large number (32) of point mutations, of which 15 of those mutations are in the receptor binding domain of the spike protein. While several computational and experimental investigations comparing the binding of the Omicron and wild type RBD to the human ACE2 receptor have been conducted, many of these report contradictory findings. In order to assess the differential binding ability, we conducted 2 μs of classical molecular dynamics (cMD) simulation to estimate the binding affinities and behaviors. Based upon MM-GBSA binding affinity, per-residue energy decomposition analysis, center of mass distance measurements, ensemble clustering, pairwise residue decomposition and hydrogen bonding analysis, our results suggest that a single point mutation is responsible for the enhanced binding of the Omicron mutant relative to the WT. While the 15-point mutations in the receptor binding domain contribute positively and negatively to the affinity of the spike protein for the human ACE2 receptor, it is the point mutation Q493R that confers enhanced binding while the Q493K mutation results in similar binding. The MM-GBSA binding estimations over a 2 μs trajectory, suggest that the wild type binds to ACE2 with a value of -29.69 kcal/mol while the Q493K and Q493R Omicron mutants bind with energy values of -26.67 and -34.56 kcal/mol, respectively. These values are significantly different, given the error estimates associated with the MM-GBSA method. In general, while some mutations increase binding, more mutations diminish binding, leading to an overall similar picture of binding for Q493K and enhanced binding for Q493R.


Echocardiographic abnormalities in patients with transfusion-dependent anemia and secondary myocardial iron deposition.
The heart was evaluated by echocardiography in 56 patients at risk for myocardial iron deposition. Fifty-four had congenital anemia for which they required repeated transfusions, and two had primary hemochromatosis. The data, plotted according to one of three functions of the body surface area, were compared to values obtained in 105 normal subjects whose age spanned a similar range. Left ventricular wall thickness, transverse dimension and mass, as well as left atrial transverse dimension, were increased in the majority of patients with chronic iron overload despite the infrequent occurrence of cardiac enlargement on routine chest films (32 per cent) or electrocardiographic abnormality (16 per cent). Left ventricular ejection fraction was normal in all but four patients. These four patients died within a six month follow-up period suggesting that deterioration in systolic function is an indicator of poor prognosis. Our findings indicate that echocardiography provides a simple noninvasive means for assessing changes in cardiac structure and function that should prove useful in the serial evaluation of patients who are at risk for the development of myocardial iron deposition.


Neuroinflammation in plaque and vascular beta-amyloid disorders: clinical and therapeutic implications.
The cerebral beta-amyloid (Abeta) disorders show a great variability in the distribution of parenchymal and vascular amyloid deposits. To study the relationship between amyloid deposition and inflammatory responses in three distinct subtypes of cerebral Abeta disorders. The distribution of inflammatory proteins and cells in vascular and plaque amyloid deposits was evaluated in postmortem brain tissue using immunohistochemistry. The effects of a mixture of Abeta peptides and inflammation-related Abeta-associated proteins were studied in postmortem obtained human microglia cell cultures. The chronic inflammatory response is associated with amyloid plaques (but not with amyloid in the walls of larger vessels) in Alzheimer's disease (AD), with amyloid in cerebral arteries in hereditary cerebral hemorrhage with amyloidosis-Dutch type and with amyloid microangiopathy in the vascular variant of AD. Abeta(1-42) fibrils complexed with complement factor C1q and serum amyloid P component (the relevant amyloid-associated proteins) stimulate the production of proinflammatory cytokines in human microglia cell cultures and this production is attenuated by minocycline. The pattern of the chronic inflammatory response associated with fibrillar Abeta is strikingly different in the three studied types of Abeta disorders. The site of the fibrillar Abeta-induced chronic inflammatory response is closely related to clinical symptoms. Minocycline is a drug of interest to inhibit microglia-mediated neuroinflammatory response in Abeta brain disorders.


Orthorexia Nervosa in China: An Exploration of Phenomenology and Clinical Correlates Among University Students.
Orthorexia nervosa, characterized by pathological preoccupation with healthy eating and food purity, is conceptualized as being linked to cultural concepts of health pervasive in contemporary Western societies. However, little is known about the phenomenology and clinical correlates of orthorexia nervosa in non-Western cultures. The current study examined symptoms of orthorexia nervosa, obsessive-compulsive disorder, depression, anxiety, and fear of negative evaluation among 418 Chinese university students. A minority of participants endorsed frequent or impairing orthorexia nervosa symptoms, and females reported slightly higher severity of orthorexia nervosa symptoms than males. Orthorexia nervosa symptom severity was moderately associated with obsessive-compulsive and anxiety symptoms, and weakly associated with depressive symptoms and fear of negative evaluation. Although this study generates initial data about orthorexia nervosa among Chinese students, further research is greatly needed to establish the prevalence and clinical characteristics of orthorexia nervosa in Western and Non-Western cultures.


Avian lymphoid leukosis prophylaxis with mibolerone.
Duplicate trials with mibolerone at a dose of 1 microng/g of diet for the first 49 days of age reduced the incidence of lymphoid leukosis (LL) significantly (P less than .005) in chickens inoculated as day-old chicks with Rous-associated virus type 1 (RAV-1). The incidence of LL was not reduced in virus-challenged chickens administered mibolerone at 4 microng per gram of diet during days 29 through 49 of age. The bursal lymphocytic follicles atrophied significantly with both the 1- and 4-microng doses; but, on the basis of histologic examination, atrophy was more complete with the 1-microng dose of mibolerone administered during the first 49 days of age. Mibolerone appears to prevent LL development by producing early bursal atrophy of key target cells. These data suggest that mibolerone orally administered at 1 microng/g of diet during the first 49 days of age appears to be useful for LL prophylaxis. Field trials are under way to assess the effectiveness of mibolerone under natural conditions.


Population-based Screening for BRAF V600E in Metastatic Colorectal Cancer Reveals Increased Prevalence and Poor Prognosis.
BRAF V600E mutations portend poor prognosis in metastatic colorectal cancer (mCRC); however, the true prevalence and prognosis are unknown, as unwell patients may not undergo BRAF sequencing. We reviewed a population-based cohort of 1,898 patients with colorectal cancer that underwent reflexive IHC mismatch repair (MMR) and BRAF V600E testing. Outcomes among IHC-detected BRAF V600E mCRC (BRAF IHC) were compared with patients with next-generation sequencing (NGS)-identified BRAF V600E-mutated mCRC from two institutions (BRAF NGS) with patients spanning from 2004 to 2018. All-stage population prevalence of BRAF V600E was 12.5% (238/1,898) and did not differ between early and metastatic stages (P = 0.094). Prevalence among mCRC was 10.6% (61/575), of whom 51 (83.6%) were referred to oncology and 26 (42.6%) had NGS testing. BRAF IHC had worse median overall survival (mOS) than BRAF NGS [5.5 vs. 20.4 months; HR, 2.90; 95% confidence interval (CI), 1.89-4.45; P < 0.0001], which persisted in multivariate analysis (P < 0.0001). Across a combined NGS and IHC cohort, BRAF V600E tumors with deficient MMR showed worse mOS compared with MMR proficient tumors (8.9 vs. 17.2 months; HR, 1.46; 95% CI, 0.96-2.27; P = 0.043). In this combined cohort, first-line progression-free survival was 5.9 months, with minimal differences between regimens. Within the population-based cohort, attrition between treatment lines was high with only 60.7% receiving first-line chemotherapy and 26.2% receiving second line. Patients with BRAF V600E-mutated mCRC have a worse prognosis than previously suggested, potentially arising from referral bias for testing. High attrition between lines of therapy suggests efficacious therapies need to be prioritized early for patients to benefit.


Desert hedgehog is a mediator of demyelination in compression neuropathies.
The secreted protein desert hedgehog (dhh) controls the formation of the nerve perineurium during development and is a key component of Schwann cells that ensures peripheral nerve survival. We postulated that dhh may play a critical role in maintaining myelination and investigated its role in demyelination-induced compression neuropathies by using a post-natal model of a chronic nerve injury in wildtype and dhh(-/-) mice. We evaluated demyelination using electrophysiological, morphological, and molecular approaches. dhh transcripts and protein are down-regulated early after injury in wild-type mice, suggesting an intimate relationship between the hedgehog pathway and demyelination. In dhh(-/-) mice, nerve injury induced more prominent and severe demyelination relative to their wild-type counterparts, suggesting a protective role of dhh. Alterations in nerve fiber characteristics included significant decreases in nerve conduction velocity, increased myelin debris, and substantial decreases in internodal length. Furthermore, in vitro studies showed that dhh blockade via either adenovirus-mediated (shRNA) or pharmacological inhibition both resulted in severe demyelination, which could be rescued by exogenous Dhh. Exogenous Dhh was protective against this demyelination and maintained myelination at baseline levels in a custom in vitro bioreactor to applied biophysical forces to myelinated DRG/Schwann cell co-cultures. Together, these results demonstrate a pivotal role for dhh in maintaining myelination. Furthermore, dhh signaling reveals a potential target for therapeutic intervention to prevent and treat demyelination of peripheral nerves in compression neuropathies.


Picrotoxin blockade of invertebrate glutamate-gated chloride channels: subunit dependence and evidence for binding within the pore.
Glutamate-gated chloride channels have been described in nematodes, insects, crustaceans, and mollusks. Subunits from the nematode and insect channels have been cloned and are phylogenetically related to the GABA and glycine ligand-gated chloride channels. Ligand-gated chloride channels are blocked with variable potency by the nonselective blocker picrotoxin. The first two subunits of the glutamate-gated chloride channel family, GluClalpha and GluClbeta, were cloned from the free living nematode Caenorhabditis elegans. In this study, we analyze the blockade of these novel channels by picrotoxin. In vitro synthesized GluClalpha and GluClbeta RNAs were injected individually or coinjected into Xenopus oocytes. The EC50 values for picrotoxin block of homomeric GluClalpha and GluClbeta were 59 microM and 77 nM, respectively. Picrotoxin block of homomeric GluClbeta channels was promoted during activation of membrane current with glutamate. In addition, recovery from picrotoxin block was faster during current activation by glutamate. A chimeric channel between the N-terminal extracellular domain of GluClalpha and the C-terminal membrane-spanning domain of GluClbeta localized the higher affinity picrotoxin binding site to the membrane-spanning domains of GluClbeta. A point mutation within the M2 membrane-spanning domain of GluClbeta reduced picrotoxin sensitivity >10,000-fold. We conclude that picrotoxin blocks GluCl channels by binding to a site accessible when the channel is open.


Schwann cells divide in a demyelinating lesion of the central nervous system.
A demyelinating lesion was induced in the rat central nervous system (CNS) by the microinjection of lysophosphatidylcholine into the spinal cord. Animals were given a single dose of tritiated thymidine 6-72 h before perfusion fixation. Correlative light microscope autoradiography and electron microscopy revealed many labeled Schwann cell nuclei that were associated with demyelinated axons in 1-3 week lesions. Myelinating Schwann cells were rarely labeled. The results indicate that Schwann cells proliferate in the CNS. They appear to divide on contact with demyelinated axons and to stop dividing when they form myelin.


Experimental modification of interlimb coordination during locomotion of a Crusacea.
An anlaysis of the phase relationship between the same side legs (homolateral coupling) of Rock Lobster (Crustacea) is performed during sequence of locomtion. On intact animals the phase relationship is similar to the most common insect or mammalian patterns ('alternating model'). After successive autotomy of the walking legs, another coordination pattern occurs progressively; it is an 'in phase model'. From these experiments it can be concluded that there exists a central motor program tightly coordinating each thoracic ganglion and that the alternating pattern could be due to a reorganization of the synchronous system by a peripheral proprioceptive inflow.


Comparison of efficacy of two oximes (HI-6 and obidoxime) in soman poisoning in rats.
The action of HI-6 (1-[[[(4-aminocarbonyl)pyridiniol]methoxy]methyl]-2-[ (hydroxyimino)methyl] pyridinium dichloride monohydrate) and obidoxime on soman-induced anticholinesterase and stressogenic effects was studied in rats. HI-6 significantly affected acetylcholinesterase inhibition in erythrocytes, brain and diaphragm and practically eliminated the stressogenic effects of soman, i.e. an increase in plasma corticosterone level and liver tyrosine amino-transferase activity, while obidoxime, on the other hand, had very little influence on soman-induced inhibition of acetylcholinesterase activity and the stressogenic effects of soman. These findings support a hypothesis that the effects of HI-6 are not solely due to reactivation of the enzyme. They also demonstrate its importance in the treatment of soman poisoning in rats.


Lessons learned in the abuse of pain-relief medication: a focus on healthcare costs.
The increasing prevalence of chronic pain with its major societal impact and the escalating use of opioids in managing it, along with their misuse, abuse, associated fatalities and costs, are epidemics in modern medicine. Over the past two decades, multiple lessons have been learned addressing various issues of abuse. Multiple measures have already been incorporated and more are expected to be incorporated in the future, which in turn may curtail the abuse of drugs and reduce healthcare costs, but these measures may also jeopardize access to appropriate pain treatment. This manuscript describes the lessons learned from the misuse, abuse and diversion of opioids, escalating healthcare costs and the means to control this epidemic.


Hydrogen peroxide - production, fate and role in redox signaling of tumor cells.
Hydrogen peroxide (H2O2) is involved in various signal transduction pathways and cell fate decisions. The mechanism of the so called "redox signaling" includes the H2O2-mediated reversible oxidation of redox sensitive cysteine residues in enzymes and transcription factors thereby altering their activities. Depending on its intracellular concentration and localization, H2O2 exhibits either pro- or anti-apoptotic activities. In comparison to normal cells, cancer cells are characterized by an increased H2O2 production rate and an impaired redox balance thereby affecting the microenvironment as well as the anti-tumoral immune response. This article reviews the current knowledge about the intracellular production of H2O2 along with redox signaling pathways mediating either the growth or apoptosis of tumor cells. In addition it will be discussed how the targeting of H2O2-linked sources and/or signaling components involved in tumor progression and survival might lead to novel therapeutic targets.


Structural studies of the adrenal zona glomerulosa and renal juxtaglomerular apparatus in pregnant sheep.
The ultrastructural changes in the adrenal zona glomerulosa and renal juxtaglomerular apparatus have been examined during normal pregnancy in sheep. As pregnancy progressed, increasing numbers of cells in the adrenal zona glomerulosa displayed mitochondria with straight tubular "rod-like" structures replacing their normal lamelliform cristae; groups of cells showing these mitochondrial changes were predominantly located in the middle and superficial regions of the zona glomerulosa, but at all stages remained interspersed with cells with apparently normal mitochondria. In the same animals, the renal juxtaglomerular index was raised, reflecting an increase in renin storage, and juxtaglomerular myoepithelioid cells showed increased numbers of cytoplasmic granules, but no apparent increase in granular endoplasmic reticulum and Golgi profiles; there were no distinguishing morphological changes in juxtaglomerular peripolar cells. These findings provide morphologic evidence of stimulation of the adrenal zona glomerulosa in association with increased juxtaglomerular renin storage during pregnancy. The mitochondrial changes observed in an increasing proportion of cells in the zona glomerulosa closely resemble those seen in sodium-depleted animals, and may reflect the altered steroidogenic capacity of the adrenal gland in pregnant sheep. The finding of groups of cells displaying altered mitochondria lying next to cells with normal mitochondria suggests the presence of cells with different sensitivities to stimuli for aldosterone production or may indicate the presence of different cell types in the zona glomerulosa responding to different stimuli.


Shark cartilage-containing preparation: protection against reactive oxygen species.
There is overwhelming evidence to indicate that free radicals cause oxidative damage to lipids, proteins and nucleic acids and are involved in the pathogenesis of several degenerative diseases. Therefore, antioxidants, which can neutralize free radicals, may be of central importance in the prevention of these disease states. The protection that fruits and vegetables provide against disease has been attributed to the various antioxidants contained in them. Recently, an anti-inflammatory and analgesic activity of a water-soluble fraction from shark cartilage has been described. Using electrophoretical assays, bacteria survival and transformation and the Salmonella/mammalian-microsome assay, we investigated the putative role of shark cartilage-containing preparation in protecting cells against reactive oxygen species induced DNA damage and mutagenesis. If antimutagens are to have any impact on human disease, it is essential that they are specifically directed against the most common mutagens in daily life. Our data suggest that shark cartilage-containing preparation can play a scavenger role for reactive oxygen species and protects cells against inactivation and mutagenesis.


Endovascular thrombectomy for large vessel occlusion acute ischemic stroke after cardiac surgery.
Acute ischemic stroke (AIS) can be a catastrophic complication of cardiac surgery previously without effective treatment. Endovascular thrombectomy (EVT) is a potentially life-saving intervention. We examined patients at our institution who had EVT to treat AIS post cardiac surgery. We retrospectively reviewed a stroke database from January 1, 2016 to October 31, 2021 to identify patients who had undergone EVT to treat AIS following cardiac surgery. Demographic data, operation type, stroke severity, imaging features, management and outcomes (mortality and modified Rankin Score (mRS)) were assessed. Of 5022 consecutive patients with AIS, 870 underwent EVT. Seven patients (0.8%) had EVT following cardiac surgery. Operations varied: two coronary artery bypass grafting (CABG), two transcatheter AVR, one redo surgical aortic valve replacement (AVR), one mitral valve repair and one patient with combined aortic and mitral valve replacements and CABG. Meantime postsurgery to stroke symptoms onset was 3 days (range 0-9 days). Median NIHSS was 26 (range 10-32). Five patients had middle cerebral artery occlusion and two internal carotid artery (n = 2). Median time between onset of symptoms and recanalization was 157 min (range 97-263). Two patients received Intra-arterial Thrombolysis. All patients survived and were discharged to another hospital (n = 3), home (n = 2), or rehabilitation facility (n = 2). Median 3-month mRS was 3 (range 0-6). We report the largest case series of EVT after cardiac surgery. EVT can be associated with excellent outcomes in these patients. Close neurological monitoring postoperatively to identify patients who may benefit from intervention is key.


Effects of menopause on blood manganese levels in women: analysis of 2008-2009 Korean National Health and Nutrition Examination Survey data.
We present data from the Korean National Health and Nutrition Examination Survey 2008-2009 on the association between blood manganese (Mn) levels and menopausal status in women. The present analysis was restricted to female participants who completed the health examination survey, including blood Mn measurements (n=1826). Menopausal status was categorized into pre- and post-menopausal. Multivariable linear regression analyses were performed to determine whether menopausal status or serum ferritin were significant predictors of blood Mn level and to investigate whether menopausal status modifies the association between blood Mn and serum ferritin after adjusting for covariates. The geometric means (GMs) of blood Mn in the low and low-normal serum ferritin groups were significantly higher than the GM of blood Mn in the normal group. The GM of blood Mn in premenopausal women was significantly higher than in postmenopausal women Multivariable linear regression analyses showed that both serum ferritin and menopausal status were predictors of blood Mn, after adjusting for various covariates, and menopausal status acted as a modifier of the effect of ferritin on blood Mn levels. Blood Mn levels were 11.0% and 22.7% lower in premenopausal women when serum ferritin increased from 10 μg/dL to 60 and 100 μg/dL, respectively, but the decrease in blood Mn based on the increase in serum ferritin was minimal in postmenopausal women. To our knowledge, this is the first report that menopausal status was a predictor of blood Mn level after adjusting for serum ferritin. In conclusion, the present study showed that both serum ferritin and menopausal status were predictors of blood Mn, after adjusting for various covariates, and menopausal status acted as a modifier of the effect of ferritin on blood Mn levels.


Surgical complications and the risk factors of laparoscopy-assisted distal gastrectomy in early gastric cancer.
Information on surgical complications of laparoscopy-assisted distal gastrectomy (LADG) and their risk factors is limited in the literature despite increasing popularity of this procedure. This study was performed to identify the surgical complications and their associated risk factors of LADG in early gastric cancer. LADG was performed in 347 gastric cancer patients from January 2002 to December 2006 at the Korean National Cancer Center by four surgeons with ample experience of open gastric surgery before LADG. LADG indications for cases of gastric cancer at our institution are preoperatively diagnosed cT1N0 or cT1N1, except in cases with an absolute indication for endoscopic resection. Lymph node dissection of more than D1 + beta was performed in all patients. Intraoperative and postoperative complications were reviewed and their risk factors were retrospectively analyzed by prospective database information. Forty complications occurred in 34 patients (9.8%), but there was no mortality. Intraoperative complications occurred in nine patients (2.6%), and open conversion was performed in eight (2.3%) of these patients. Early and late postoperative complications occurred in 21 (6.1%) and 10 (2.9%) patients, respectively. The most serious complication was vascular injury resulting in bleeding or organ ischemia, which occurred in seven patients. Degree of lymph node dissection and surgical inexperience were found to be risk factors of surgical complication (P = .023, odds ratio 2.832, 95% confidence interval 1.155-6.946 vs. P = .028, odds ratio 2.975, 95% confidence interval 1.127-7.854). Lymph node dissection during LADG should be performed cautiously to prevent surgical complications like vascular injuries, especially during the surgeon's early learning period.


Mnk2 alternative splicing modulates the p38-MAPK pathway and impacts Ras-induced transformation.
The kinase Mnk2 is a substrate of the MAPK pathway and phosphorylates the translation initiation factor eIF4E. In humans, MKNK2, the gene encoding for Mnk2, is alternatively spliced yielding two splicing isoforms with differing last exons: Mnk2a, which contains a MAPK-binding domain, and Mnk2b, which lacks it. We found that the Mnk2a isoform is downregulated in breast, lung, and colon tumors and is tumor suppressive. Mnk2a directly interacts with, phosphorylates, activates, and translocates p38α-MAPK into the nucleus, leading to activation of its target genes, increasing cell death and suppression of Ras-induced transformation. Alternatively, Mnk2b is pro-oncogenic and does not activate p38-MAPK, while still enhancing eIF4E phosphorylation. We further show that Mnk2a colocalization with p38α-MAPK in the nucleus is both required and sufficient for its tumor-suppressive activity. Thus, Mnk2a downregulation by alternative splicing is a tumor suppressor mechanism that is lost in some breast, lung, and colon tumors.


Congenital double upper lip: A case report and review of the literature.
Congenital double lip is a rare developmental anomaly which usually involves the upper lip more than the lower lip. It may occur in isolation or as a part of Ascher's syndrome. Sometimes upper and lower double lips occur simultaneously. The occurrence of double lip may result in facial deformity especially when the patient attempts to talk, smile or even show the teeth. It may also interfere with speech or mastication. Although surgery may be undertaken to facilitate speech and mastication, the majority of cases are operated for cosmetic reasons. A case of congenital double upper lip, which was surgically treated after orthodontic treatment, for cosmetic reasons, is reported. The different surgical approaches to the management of double upper lip are reviewed with a note on timing of surgery in patients who have concurrent orthodontic or prosthodontic problems. Although the majority of cases of double lip are treated by Plastic Surgeons and Oral and Maxillofacial Surgeons, it is important to make dentists aware of this condition since they may be the first clinicians to encounter patients with this abnormality.


Novel and recurrent KIF21A mutations in congenital fibrosis of the extraocular muscles type 1 and 3.
To characterize the disease-causing mutations and associated clinical phenotypes in 5 Chinese families with congenital fibrosis of the extraocular muscles (CFEOM). Ophthalmic investigations included visual acuity, levator function, documentation of compensatory head position, ocular motility, and slitlamp and fundus examinations. The kinesin family member 21A gene (KIF21A) was sequenced for mutation detection. Genotyping and linkage analysis were performed for the KIF21A/FEOM1 and FEOM3 loci. Four families were clinically classified as having CFEOM type 1 (CFEOM1) with full expression of severe ptosis and ophthalmoplegia. One family had CFEOM type 3 (CFEOM3) with typically varying expression of phenotypes between individuals. Recurrent heterozygous KIF21A mutations were identified in 2 CFEOM1 families (2860C>T) and the CFEOM3 family (2861G>A). In another CFEOM1 family, a novel missense mutation (84C>G, C28W) was revealed. The novel KIF21A mutation 84C>G demonstrated in a CFEOM1 family affects the kinesin motor domain, supporting that mutations may also occur outside the commonly involved coiled-coil domain. The 2861G>A mutation found in a CFEOM3 family has been previously reported in CFEOM1, further supporting that different phenotypes can arise from identical mutations. Clinical Relevance Clinical and genetic characterization are complementary tools for diagnostic, prognostic, and treatment purposes in CFEOM.


Rapid effector function of memory CD8+ T cells requires an immediate-early glycolytic switch.
Antigen-experienced memory T cells acquire effector function with innate-like kinetics; however, the metabolic requirements of these cells are unknown. Here we show that rapid interferon-γ (IFN-γ) production of effector memory (EM) CD8(+) T cells, activated through stimulation mediated by the T cell antigen receptor (TCR) and the costimulatory receptor CD28 or through cognate interactions, was linked to increased glycolytic flux. EM CD8(+) T cells exhibited more glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity at early time points, before proliferation commenced, than did naive cells activated under similar conditions. CD28 signaling via the serine-threonine kinase Akt and the metabolic-checkpoint kinase mTORC2 was needed to sustain TCR-mediated immediate-early glycolysis. Unlike glycolysis in proliferating cells, immediate-early glycolysis in memory CD8(+) T cells was rapamycin insensitive. Thus, CD8(+) memory T cells have an Akt-dependent 'imprinted' glycolytic potential that is required for efficient immediate-early IFN-γ recall responses.


Dynamic wetting of dilute polymer solutions: the case of impacting droplets.
The moving contact line of a dilute polymer solution that advances over, or recedes from a solid substrate, is a fundamental problem of fluid dynamics with important practical applications. In particular, the case of droplets impacting on hydrophobic surfaces received much attention in the recent past. Experiments show that while the advancing motion proceeds as with Newtonian liquids, recession is severely inhibited. This phenomenon was initially understood as an effect of elongational viscosity, which was believed to cause large energy dissipation in the fluid. Later on, a hydrodynamic mechanism was proposed to suggest that the slowing down of the contact line is due to non-Newtonian normal stresses generated near the moving droplet edge. Recent experiments however ruled out the role of elongational viscosity, showing that the fluid velocity measured inside the droplet during retraction is the same in water drops and polymer solution drops. Direct visualization of fluorescently stained λ-DNA molecules showed that polymer molecules are stretched perpendicularly to the contact line as the drop edge sweeps the substrate, which suggests an effective friction arises locally at the drop edge, causing the contact line to slow down.


Effect of displacement rate on the tensile mechanics of pediatric cervical functional spinal units.
This study examined the effect of loading (displacement) rate on the tensile mechanics of cervical spine functional spinal units. A total of 40 isolated functional spinal units (two vertebrae and the adjoining soft tissues) from juvenile male baboons (10+/-0.6-human equivalent years old) were subjected to tensile loading spanning four orders of magnitude from 0.5 to 5000 mm/s. The stiffness, ultimate failure load, and corresponding displacement at failure were measured for each specimen and normalized by spinal geometry to examine the material properties as well as the structural properties. The tensile stiffness, failure load, normalized stiffness, and normalized failure load significantly increased (ANOVA, p<0.001) with increasing displacement rate. From the slowest to fastest loading rate, a two-fold increase in stiffness and four-fold increase in failure load were observed. The tensile failure strains (1.07+/-0.31 mm/mm strain) were not significantly correlated with loading rate (ANOVA, p=0.146). Both the functional (non-destructive stiffness and normalized stiffness) and failure mechanics of isolated functional spinal units exhibited a power-law relationship with displacement rate. Modeling efforts utilizing these rate-dependent characteristics will enhance our understanding of the tensile viscoelastic response of the spine and enable improved dynamic injury prevention schemes.


Taming of the DIBAL Promoted Debenzylation of α-Cyclodextrin. Kinetics, Substituent Effects and Efficient Synthesis of Lings Tetrol.
The kinetics of the reaction of perbenzyl α-cyclodextrin was studied varying the concentration of DIBAL and substrate, and the temperature. The initial debenzylation was found to be 1st order in substrate and follow the relationship 0.0675+0.179[DIBAL]2 with respect to the concentration of DIBAL. The second and the third debenzylation which led to the 3A ,6A ,6D -triol (Lings triol) were both found to be 1st order in substrate concentration and zero order in DIBAL concentration. Longer reaction times with DIBAL in high concentration gave further debenzylation to comparatively complex mixtures containing the 2B,3A ,6A ,6D -tetrol and the 3A ,6A ,6C ,6D -tetrol. In contrast reaction at 0.1 M DIBAL gave the symmetrical 3A ,6A ,3D,6D-tetrol (Lings tetrol) in 60 % yield. The effect of chlorine or methyl substitution of the phenyl groups of perbenzyl α-cyclodextrin was also investigated. Per 4-chlorobenzyl slowed down the reaction with DIBAL, while 4-methylbenzyl increased the reaction rate, but still gave the corresponding 6 A-monool or 6A ,6D -diol products. A Hammett reaction constant of -4.9 was found for the first debenzylation showing a high degree of positive charge in the transition state. The per(2,4-dichlorobenzyl)-α-cyclodextrin-derivative was completely resistant to DIBAL, however upon addition of trimethyl aluminium this derivative also reacted to give the 6A ,6D -diol product.


External versus endoscopic approach in the surgical treatment of glottic cancer.
Laryngeal carcinomas in the early stages of evolution can be treated by different therapies. In this paper we present our personal experience with T1 and small T2 laryngeal glottic cancer treated by conventional surgery and by endoscopic laser surgery. In the period 1983-1997, we saw 573 patients affected by T1 and limited T2 glottic tumours. In particular, we treated 325 case of T1a tumour, 185 T1b and 63 T2 (ventricle floor). As regards surgical techniques, we employed cordectomy by laryngofissure in 196 patients; laser cordectomy in 129 cases; widened laser cordectomy in 63 cases; fronto-lateral laryngectomies according to Leroux-Robert in 110 patients; laser cordo-commissurectomies in 37 cases; horizontal glottectomies according to Calearo-Teatini in 9 cases, and laser glottectomies in 29 patients. The average oncological results, considered for every stage and every surgical technique were 84.4% (484 cancers definitively controlled by primary surgery). For comparison of oncological and clinical results, we evaluated patients affected by tumours with similar extension that had been treated by different surgical techniques. Oncological results were similar in the two groups. In the group treated by laser surgery we found a shorter clinical course and the best possibility of salvage therapy in the case of local recurrence.


Cell adhesion molecules and cytokines in middle ear effusions in children with or without recent acute otitis media.
We sought to compare the levels of cytokines and cell adhesion molecules in middle ear effusions (MEEs) of children with (group 1) or without (group 2) acute otitis media (AOM) within 3 months of obtaining MEE and to correlate these levels with hearing loss. MEE were collected from children (49 and 51 children composed groups 1 and 2, respectively) with otitis media with effusion (OME) undergoing tube placement who had an audiogram performed preoperatively. MEE was assessed as serous or mucoid. Cytokines and cell adhesion molecules were measured by enzyme-linked immunosorbent assay. Data were analyzed with the Student t test, chi(2) test, and the Pearson correlation test. Concentrations of interleukin (IL)-1, IL-6, and vascular cell adhesion molecules (VCAM) were greater in the MEE of the children in group 1 compared with those of group 2 children. (P < 0.001 for IL-1 and IL-6; P < 0.05 for VCAM). The concentrations of IL-1, IL-6, VCAM, and E-selectin were greater in serous than in mucoid MEE. (P < 0.05). Concentrations of IL-6 correlated with the concentrations of the other 2 cytokines and the 3 cell adhesion molecules. Only concentrations of IL-6 in MEE correlated with the degree of hearing loss (P < 0.002). The inflammatory response leading to OME involves multiple cytokines regardless of an AOM episode in the 3 months before obtaining MEE. IL-6 is an important cytokine in the pathogenesis of OME.


Adenoviral-mediated delivery of early growth response factor-1 gene increases tissue perfusion in a murine model of hindlimb ischemia.
To test the hypothesis that overexpression of early growth response factor-1 (Egr-1) contributes to the revascularization of ischemic limbs, a constitutively active form of Egr-1 (Egr-1*) was made and evaluated in vitro and in vivo. Analyses of the transduced myocytes revealed significant upregulation of bFGF, PDGF-A, PDGF-B, IGF-II, and TGF-beta1. A coculture assay of the paracrine effects indicated that Ad-Egr-1* promoted proliferation and migration of endothelial cells. When Ad-Egr-1* was injected into the tibialis anterior muscle of mice, followed by explant culture in growth factor-reduced Matrigel, many capillary-like structures were observed in the Egr-1* group compared with minimal sprouting from the LacZ group, suggesting an angiogenic potential of Egr-1*. Next we evaluated Ad-Egr-1* in a murine model of hindlimb ischemia. Compared with slow revascularization in the control PBS or LacZ group, a rapid increase in tissue perfusion was observed in the Egr-1* group and the difference in flux ratio was statistically significant at day 7. In the injected muscle, expression of Egr-1*, upregulation of its target genes, and increased number of vessels staining positive for smooth muscle alpha-actin were observed. These results suggest that Egr-1 plays an important role in vascular recovery after occlusion and could be a potential target for therapeutic angiogenesis.


Alpha1-adrenoreceptor in human hippocampus: binding and receptor subtype mRNA expression.
Alpha1-adrenoreceptors (AR), of which three subtypes exist (alpha1A-, alpha1B- and alpha1D-AR) are G-protein-coupled receptors that mediate the actions of norepinephrine and epinephrine both peripherally and centrally. In the CNS, alpha1-ARs are found in the hippocampus where animal studies have shown the ability of alpha1-AR agents to modulate long-term potentiation and memory; however, the precise distribution of alpha1-AR expression and its subtypes in the human brain is unknown making functional comparisons difficult. In the human hippocampus, 3H-prazosin (alpha1-AR antagonist) labels only the dentate gyrus (molecular, granule and polymorphic layers) and the stratum lucidum of the CA3 homogeneously. Human alpha1A-AR mRNA in the hippocampus is observed only in the dentate gyrus granule cell layer, while alpha1D-AR mRNA expression is observed only in the pyramidal cell layers of CA1, CA2 and CA3, regions where 3H-prazosin did not bind. alpha1B-AR mRNA is not expressed at detectable levels in the human hippocampus. These results confirm a difference in hippocampal alpha1-AR localization between rat and humans and further describe a difference in the localization of the alpha1A- and alpha1D-AR mRNA subtype between rats and humans.


The effect of cutting style on the biosynthesis of phenolics and cellular antioxidant capacity in wounded broccoli.
To explore the effect of cutting style on the biosynthesis of phenolic compounds and cellular antioxidant capacity in wounded broccoli subjected to different cutting styles (heads, florets, 1/2 florets and shredded florets), the mechanism of the accumulation of phenolic compounds was investigated at the transcriptional level, and cellular antioxidant capacity was measured using a breast cancer cell MCF-7 culture model. The results indicated that the relative expression of the genes encoding phenylalanine ammonia-lyase, cinnamic acid 4-hydroxylase and 4-coumarin coenzyme A ligase, three enzymes involved in phenylpropanoid metabolism, was upregulated and that contributed to the synthesis of individual phenolic compounds, including catechin, hydroxybenzoic acid, chlorogenic acid, caffeic acid, sinapic acid, catechin gallate, rutin, cinnamic acid and quercetin. This research constructes the phenol synthesis pathway in wounded broccoli. Moreover, the relative expression of critical genes including superoxide dismutase, peroxidase, catalase, glutathione peroxidase and glutathione reductase involved in the metabolism of reactive oxygen species (ROS) increased, resulting in enhanced antioxidant capacity in wounded broccoli. Cell antioxidant capacity (CAA) of heads, florets, 1/2 florets and shredded florets increased by 52.7%, 59.2%, 64.8% and 86.5%, respectively, compared to whole broccoli. The enhancement of CAA was greater as the intensity of wounding increased, indicating that enhancement of antioxidant activity occurred at the cellular level. This research helps provide a reliable and persuasive theoretical basis for nutritional value assessment at the cellular level in wounded broccoli.


Biofilms of Pathogenic Nontuberculous Mycobacteria Targeted by New Therapeutic Approaches.
Microbial infections of the cornea are potentially devastating and can result in permanent visual loss or require vision-rescuing surgery. In recent years, there has been an increasing number of reports on nontuberculous mycobacterial infections of the cornea. Challenges to the management of nontuberculous mycobacterial keratitis include delayed laboratory detection, low index of clinical suspicion, poor drug penetration, slow response to therapy, and prolonged use of antibiotic combinations. The ability of nontuberculous mycobacteria to evade the host immune response and the ability to adhere and to form biofilms on biological and synthetic substrates contribute to the issue. Therefore, there is an urgent need for new antimicrobial compounds that can overcome these problems. In this study, we evaluated the biofilm architectures for Mycobacterium chelonae and Mycobacterium fortuitum in dynamic flow cell chamber and 8-well chamber slide models. Our results showed that mycobacterial biofilms were quite resistant to conventional antibiotics. However, DNase treatment could be used to overcome biofilm resistance. Moreover, we successfully evaluated a new antimicrobial compound (AM-228) that was effective not only for planktonic mycobacterial cells but also for biofilm treatment and was compared favorably with the most successful "fourth-generation" fluoroquinolone, gatifloxacin. Finally, a new treatment strategy emerged: a combination of DNase with an antibiotic was more effective than an antibiotic alone.


[Atraumatic rupture of the spleen. A proposal of new attitudes. Apropos a case in brucellosis].
A case of spontaneous spleen rupture during acute brucellosis, followed by clinical and ultrasound examinations until the natural resolution of the subcapsular hematoma, is presented. The causes of this complication are reviewed and a new classification is proposed, creating 3 groups of nontraumatic ruptures: spontaneous, with basal splenic disease and associated to other pathology. We highlight the several states of spleen ruptures--some with spontaneous resolution--and the utility of the radiological techniques to carry out a follow-up on them, which can in some cases help avoid surgical intervention.


Design, Synthesis, and Evaluation of Biological Activity of Ferrocene-Ispinesib Hybrids: Impact of a Ferrocenyl Group on the Antiproliferative and Kinesin Spindle Protein Inhibitory Activity.
With the aim to combine more than one biologically-active component in a single molecule, derivatives of ispinesib and its (S) analogue were prepared that featured ferrocenyl moieties or bulky organic substituents. Inspired by the strong kinesin spindle protein (KSP) inhibitory activity of ispinesib, the compounds were investigated for their antiproliferative activity. Among these compounds, several derivatives demonstrated significantly higher antiproliferative activity than ispinesib with nanomolar IC50 values against cell lines. Further evaluation indicated that the antiproliferative activity is not directly correlated with their KSP inhibitory activity while docking suggested that several of the derivatives may bind in a manner similar to ispinesib. In order to investigate the mode of action further, cell cycle analysis and reactive oxygen species formation were investigated. The improved antiproliferative activity of the most active compounds may be assigned to synergic effects of various factors such as KSP inhibitory activity due to the ispinesib core and ability to generate ROS and induce mitotic arrest.


The Role of Community Education in Increasing Knowledge of Breast Health and Cancer: Findings from the Asian Breast Cancer Project in Boston, Massachusetts.
In the past decade, cancer rates have significantly decreased in the USA, but breast cancer survival is lower in Asian American women, likely due to lower rates of screening behaviors in Asian Americans compared to other ethnicities, which could lead to later stage cancer diagnosis and increased mortality. This paper reports on the Asian Breast Cancer (ABC) Project, a three-phase peer-led community program designed to promote cancer prevention by improving breast cancer screening rates among Chinese and Vietnamese women in the Greater Boston area. The three phases of planning and coalition building, community health worker training, and the community workshop intervention are described. The workshop intervention was evaluated by comparing pre- and post-workshop questionnaires evaluating knowledge about breast cancer screening and prevention. Two hundred fifty-two women participated in the program across 14 workshops. Each participant completed questionnaires about demographics, access to health care, and a five-item self-administered questionnaire about breast cancer knowledge. Results showed that the majority of the women had received a clinical breast exam or mammogram in the past 12 months (69 and 59 %, respectively), and older women were more likely to get a mammogram (85 %) or clinical breast exams (74 %) compared to younger women. Eighty-one percent of women were interested in reminder systems. Baseline knowledge was high for three survey questions about mammograms and breast cancer risk (88-97 %). For questions with fewer correct answers at baseline, knowledge about the meaning of lumps in the breast significantly increased (69 to 80 % correct, p < 0.0001), as well as knowledge about frequency of clinical breast exam (48 to 67 % correct, p < 0.0001). This pilot project indicated a partial effectiveness of the community workshop in a population with high baseline knowledge. The education workshop increased knowledge about breast lumps and clinical exam frequency. We also identified that reminder systems and appointment assistance are desired by this population. Our findings inform future cancer screening strategies for Asian Americans.


Design of chiral sulfoxide-Schiff base hybrids and their application in Cu-catalyzed asymmetric Henry reactions.
A new class of chiral sulfoxide-Schiff base ligands has been developed by the rational combination of two privileged chiral backbones. These sulfoxide-Schiff base ligands were found to be highly efficient for Cu-catalyzed asymmetric Henry reactions (up to 98% yield and 96% ee).


Ecological paradigms to understand the dynamics of metastasis.
The process by which prostate cancer cells non-randomly disseminate to the bone to form lethal metastases remains unknown. Metastasis is the ultimate consequence of the long-range dispersal of a cancer cell from the primary tumor to a distant secondary site. In order to metastasize, the actively emigrating cell must move. Movement ecology describes an individual's migration between habitats without the requirement of conscious decision-making. Specifically, this paradigm describes four interacting components that influence the dynamic process of metastasis: (1) the microenvironmental pressures exerted on the cancer cell, (2) how the individual cell reacts to these external pressures, (3) the phenotypic switch of a cell to gain the physical traits required for movement, and (4) the ability of the cancer cell to navigate to a specific site. A deeper understanding of each of these components will lead to the development of novel therapeutics targeted to interrupt previously unidentified steps of metastasis.


Surgery Improves Patient-Reported Outcomes in Patients with Intestinal and Pancreatic NETs: A Prospective Analysis.
Incorporation of patient-reported outcomes such as health-related quality of life has become increasingly important in the management of chronic diseases such as cancer. In this prospective study, we examined the effect of surgical resection on quality of life in patients with intestinal and pancreatic neuroendocrine tumors (NETs). Thirty-two patients underwent NET resection at our institution from January 2020 to January 2022. All patients completed the 12-item short-form quality-of-life survey prior to surgery, as well as at the 3-, 6-, and 12-month postoperative time points. The presence and severity of specific carcinoid syndrome symptoms (diarrhea, flushing, and abdominal pain) were also recorded during pre- and postoperative appointments. Patients experienced significant increases in both mental and physical health after surgery. Mental health scores significantly increased at all three time points (baseline: 51.33; 3-month: 53.17, p = 0.02; 6-month: 57.20, p < 0.001; 12-month: 57.34, p = 0.002), and physical health scores increased at 6 and 12 months (baseline: 50.39; 6-month: 53.16, p = 0.04; 12-month: 55.02, p = 0.003). Younger patients benefited more in terms of physical health, while older patients had more significant increases in mental health. Patients with metastatic disease, larger primary tumors, and those receiving medical therapy had lower baseline quality-of-life scores and greater improvements after surgery. The vast majority of patients in this study also experienced alleviation of carcinoid syndrome symptoms. In addition to prolonging survival, resection of intestinal and pancreatic NETs leads to significantly improved patient-reported quality of life.


Rings, ellipses and horseshoes: how purple bacteria harvest solar energy.
This Review summarises the current state of research on the structure and function of light-harvesting apparatus in purple photosynthetic bacteria. Particular emphasis is placed on the major open questions still outstanding in this field in addition to what is already known.