Prodigiosin inhibits the proliferation of glioblastoma by regulating the KIAA1524/PP2A signaling pathway.
Prodigiosin (PG), a member of a family of natural red pigments produced by a variety of bacteria, was first discovered in Serratia marcescens. PG has been reported to have an apoptosis-inducing effect in many cancers, such as lymphoma, colon cancer and nasopharyngeal carcinoma. For this study, we used three glioblastoma (GBM) cell lines (LN229, U251 and A172) to explore the effect of prodigiosin on GBM cells. A CCK8 assay was used to evaluate cell viability. We determinedthe cell cycle distribution by flow cytometry and measured proliferation by an EdU incorporation assay. The expression of different molecules was investigated by western blotting and RT-PCR. We further confirmed our results by plasmid transfection and lentiviral transduction. The LN229 xenograft model was used to study the effect of prodigiosin in vivo. We confirmed that prodigiosin played an anticancer role in several GBM cell lines through the KIAA1524/PP2A/Akt signalling pathway. Prodigiosin inhibited the protein expression of KIAA1524 by suppressing its transcription, which led to activation of PP2A. Afterward, PP2A inhibited the phosphorylation of Akt, thereby inducing increased expression of p53/p21. Furthermore, it was verified that prodigiosin inhibited the KIAA1524/PP2A/Akt axis in vivo in the LN229 xenograft model. These data improve the understanding of the anticancer effects of prodigiosin and further highlight the potential of prodigiosin for the development of anti-glioma drugs.


Structure-activity relationships of adenosines with heterocyclic N6-substituents.
Two series of N(6)-substituted adenosines with monocyclic and bicyclic N(6) substituents containing a heteroatom were synthesized in good yields. These derivatives were assessed for their affinity ([(3)H]CPX), potency, and intrinsic activity (cAMP accumulation) at the A(1) adenosine receptor in DDT(1) MF-2 cells. In the monocyclic series, the N(6)-tetrahydrofuran-3-yl and thiolan-3-yl adenosines (1 and 26, respectively) were found to possess similar activities, whereas the corresponding selenium analogue 27 was found to be more potent. A series of nitrogen containing analogues showed varying properties, N(6)-((3R)-1-benzyloxycarbonylpyrrolidin-3-yl)adenosine (30) was the most potent at the A(1)AR; IC(50)=3.2 nM. In the bicyclic series, the effect of a 7-azabicyclo[2.2.1]heptan-2-yl substituent in the N(6)-position was explored. N(6)-(7-Azabicyclo[2.2.1]heptan-2-yl)adenosine (38) proved to be a reasonably potent A(1) agonist (K(i)=51 nM, IC(50)=35 nM) while further substitution on the 7''-nitrogen with tert-butoxycarbonyl (31, IC(50)=2.5 nM) and 2-bromobenzyloxycarbonyl (34, IC(50)=9.0 nM) gave highly potent A(1)AR agonists.


Piroxicam in acute musculoskeletal disorders and sports injuries.
Approximately 20 percent of athletes have an acute or chronic injury related to their sport. In acute musculoskeletal disorders, inflammation is an important component of the symptomatology. Recent clinical studies are showing that nonsteroidal anti-inflammatory drugs (NSAIDs) can significantly reduce inflammation and help speed return to full function. In an international study, the efficacy and toleration of piroxicam were compared with that of indomethacin, naproxen, and aspirin in three multicenter, double-blind, parallel studies involving a total of 1,290 patients with acute sprains and tendinitis. The centers compared piroxicam 40 mg once daily for the first two days followed by 20 mg once daily for the remainder of the studies. This regimen was compared with either indomethacin, 50 mg three times per day for two days and 25 mg three times per day for the remainder of the treatment period; naproxen 500 mg twice daily for two days followed by 250 mg in the morning and 500 mg in the evening thereafter; or aspirin 4 g per day for the duration of the study. Treatment normally lasted 14 days; the minimal duration was seven days, with a maximum of 28 days. Overall assessment of efficacy was excellent or good in more than 80 percent of patients. Statistical differences were seen favoring piroxicam over aspirin (p less than 0.05) regarding reduction in tenderness and resumption of daily activities within 16 days (p less than 0.02). The study comparing piroxicam and naproxen showed a statistically significant difference in favor of piroxicam (p less than 0.025). There was no difference between piroxicam and indomethacin in the number of patients who were able to accomplish normal daily activity within 16 days. Furthermore, although efficacy was comparable among the NSAIDs, piroxicam was significantly better-tolerated than either naproxen or indomethacin. Piroxicam was also better-tolerated than aspirin, but a statistical difference was not reached.


Generalised cancer, a function of the relative brainsize.
The prevalence of spontaneous, generalised malignant tumours in 10 mammalian species was compared with their relative brain sizes (RBS), and the outcome, supported by the statistical significance, argues for the psyche as a contributing factor in cancer. The variation in life spans and metabolism of the species was subsequently equalised and applied to the statistics. The mediators are deductively suggested to be the sympathetic nervous system (SNS) and its neurotransmitter noradrenaline, which may exert a direct, lethal effect on tumours. The strain on the autonomous nervous system (ANS), dispersed throughout the brain, is assumed to be increasing with the increasing ratio of neurones belonging to 'receiving, processing and conscious areas' (RPCA), where the extension or density of ANS may be adapted to the dimensions of the body it supplies.Interference in neocortex and other parts of the brain, partly stress-induced, might cause dysfunction of ANS, which aggravates with a proportional increase of RBS.


Estimation of theophylline in plasma by thin-layer chromatography.
1. A quantitative thin-layer chromatographic procedure for theophylline has been evaluated. An internal standard, 3-isobutyl-1-methylxanthine, a compound similar in properties to those of theophylline is added to the specimen prior to extraction to eliminate the need for accurate measurements of volume during extraction or analysis. 2. This method does not show interference from other xanthines and from a number of drugs commonly prescribed with thephylline. It has an acceptable correlation with a reference gas-liquid chromatographic procedure. 3. This procedure is capable of handling batches of six or more samples faster than the serial processing of either high performance liquid chromatography or gas-liquid chromatography.


Characterization of a profilin-like protein from Schistosoma japonicum, a potential new vaccine candidate.
The tegumental membrane of platyhelminth parasites is of crucial importance for modulation of the host response and parasite survival. A complementary deoxyribonucleic acid (cDNA) containing an open reading frame of 390 bp, which encodes a profilin-like tegumental protein with a theoretical isoelectric point of 6.02 and a molecular weight of 14.42 kDa, had been identified by bioinformatic analysis. The coding region of the cDNA was cloned into the prokaryotic expression vector pGEX-4T-1 and expressed in Escherichia coli. The purified recombinant protein named rSj15 was immunogenic and could elicit a high titer of antibody in mice. Western blot analysis revealed that the protein was differentially expressed during the different growth stages of Schistosoma japonicum. Immunohistochemical analysis localized the protein to the tegument and underlying tissue of the S. japonicum adult worm. The rSj15 could induce the expressions of IL-12 in the cultured mouse dendritic cell.


ST Elevation in the COVID-19 Era: A Diagnostic Challenge.
Severe acute respiratory syndrome coronavirus 2 induces a marked prothrombotic state with varied clinical presentations, including acute coronary artery occlusions leading to ST-elevation myocardial infarction (STEMI). However, while STEMI on electrocardiogram (ECG) is not always associated with acute coronary occlusion, this diagnostic uncertainty should not delay cardiac catheterization. We present 2 cases of patients with COVID-19 that presented with STEMI on ECG. While both patients underwent cardiac catheterization, a delay in time to intervention in the patient found to have acute coronary artery occlusion may have contributed to a poor outcome. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: These cases highlight the fact that while not all COVID-19 patients with STEMI on ECG will have acute coronary artery occlusions, there is continued need for prompt percutaneous coronary intervention during the severe acute respiratory syndrome coronavirus 2 pandemic.


Triamcinolone-induced mammary activation in virgin mice.
Intact ICR mice receiving Triamcinolone showed extensive proliferation within the mammary gland. Galactophores and ducts were enlarged. In contrast with the non-treated animals, those treated with Triamcinolone had an evident lobuloalveolar system. Triamcinolone failed to activate the glands of oophorectomized animals. It is thus evident that systemic administration of Triamcinolone to young virgin mice causes mammary stimulation and that this effect only occurs in the presence of the ovary.


Occurrence of glucose polymer in undifferentiated PC12 cells.
A large glucose polymer was found, following pronase digestion, in PC12 pheochromocytoma cells metabolically labeled with [1-3H]galactose. The polymer was excluded from a Bio-Gel A-0.5 m column and adsorbed by immobilized concanavalin A-Sepharose from which it was eluted with 10 mM alpha-methylmannoside. Glucose was found to be the sole component monosaccharide. Except for those capable of degrading glycogen, no exo- or endo-glycosidases cleaved the polymer. This is the first report on the occurrence of a glucose polymer in undifferentiated PC12 cells.


Promising strategies of circular bioeconomy using heavy metal phytoremediated plants - A critical review.
Phytoremediation is an excellent method for removing harmful heavy metals from the environment since it is eco-friendly, uses little energy, and is inexpensive. However, as phytoremediated plants can turn into secondary sources for heavy metals, complete heavy metal removal from phytoremediated plants is necessary. Elimination of toxic heavy metals from phytoremediated plants should be considered with foremost care. This review highlights about important sources of heavy metal contamination, health effects caused by heavy metal contamination and technological breakthroughs of phytoremediation. This review critically emphasis about promising strategies to be engaged for absolute reutilization of heavy metals and spectacular approaches of production of commercially imperative products from phytoremediated plants through circular bioeconomy with key barriers. Thus, phytoremediation combined with circular bioeconomy can create a new platform for the eco-friendly life.


Evaluation of Rapid Multiplex Reverse Transcription-Quantitative Polymerase Chain Reaction Assays for SARS-CoV-2 Detection in Individual and Pooled Samples.
Although coronavirus disease 2019 (COVID-19) is no longer a Public Health Emergency of International Concern (PHEIC), severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has had a vast impact to date. Hence, continuous management is required, given the uncertainty caused by the potential evolution of SARS-CoV-2. Reverse transcription-quantitative PCR (RT-qPCR) diagnosis has been fundamental in overcoming this issue. In this study, the performances of two rapid RT-qPCR assays (Real-Q Direct SARS-CoV-2 Detection Kit and Allplex™ SARS-CoV-2 fast PCR Assay) with short PCR times were comparatively evaluated using a STANDARD M nCoV Real-Time Detection Kit (STANDARD M, conventional RT-qPCR assay). All kits showed a limit of detection values (102-103 copies/reaction). The evaluation showed that the two rapid assay tests had ≥97.89% sensitivity and ≥99.51% specificity (κ = 0.98) for individual samples and ≥97.32% sensitivity and ≥97.67% specificity for pooled samples compared to STANDARD M. These results indicate that the two rapid RT-qPCR kits, which showed significant time reduction in performance, are as effective as a conventional RT-qPCR assay. They are likely to increase not only the number of tests that can be performed but also the efficiency of sustainable management of COVID-19 in the long term.


Pulmonary hypertension and pregnancy--a review of 12 pregnancies in nine women.
To report outcomes in a recent series of pregnancies in women with pulmonary hypertension (PH). Retrospective case note review. Tertiary referral unit (Chelsea and Westminster and Royal Brompton Hospitals). Twelve pregnancies in nine women with PH between 1995 and 2010. Multidisciplinary review of case records. Maternal and neonatal mortality and morbidity. There were two maternal deaths (1995 and 1998), one related to pre-eclampsia and one to arrhythmia. Maternal morbidity included postpartum haemorrhage (five cases), and one post-caesarean evacuation of a wound haematoma. There were no perinatal deaths, nine live births and three first-trimester miscarriages. Mean birthweight was 2197 g, mean gestational age was 34 weeks (range 26-39), and mean birthweight centile was 36 (range 5-60). Five babies required admission to the neonatal intensive care unit, but were all eventually discharged home. All women were delivered by caesarean section (seven elective and two emergency deliveries), under general anaesthetic except for one emergency and one elective caesarean performed under regional block. Maternal and fetal outcomes for women with PH may be improving. However, the risk of maternal mortality remains significant, so that early and effective counselling about contraceptive options and pregnancy risks should continue to play a major role in the management of such women when they reach reproductive maturity.


The influence of calorie source on water and sodium balances during intravenous refeeding of malnourished rabbits.
34 New Zealand rabbits were starved until a mean weight loss of 15% to 20% was achieved and then were parenterally re-fed with four different total parenteral nutrition (TPN) formulae for 6 days. Regimens were isocaloric (85 kcal/kg/day) and isonitrogenous (0.52 gN/kg/day) with the following formulae: group S-GLU-70 (water 100 ml/kg/day, Na 7 mEq/day and 70 30 % of calories as glucose/lipids, n = 9), group S-GLU-50 (water 100 ml/kg/day, Na 7 mEq/day and 50 50 % of calories as glucose/lipids, n = 9), group L-GLU-30 (water 70 ml/kg/day, no sodium and 30 70 % of calories as glucose/lipids, n = 8) and group L-GLU-50 (water 70 ml/kg/day, no sodium and 50 50 % of calories as glucose/lipids, n = 8). The group S-GLU-70 showed the highest water and sodium balances (p = 0.001 respectively, ANOVA test). Group S-GLU-70 showed also a greater weight gain (p = 0.0001) and, although not statistically significant, the lowest albumin at the end of the TPN. Glucose load appears to be responsible for the rapid weight gain and positive water and sodium balances during TPN in depleted non-stressed animals.


Recombinant viruses as vectors for mucosal immunity.
The development and characterization of viral based vaccine vectors is extremely active research field. Much of this work has been facilitated by developments in molecular biology that allow work with large plasmid-based vectors, as well as the use of PCR. Several different vector systems are now available using RNA viruses and DNA viruses. Each vector system has its own strengths and weaknesses. Due to the differences and diversity between the viruses used as vectors, it is doubtful that a single system will be useful for all desired vaccines. However, the further development of existing, as well as potentially new systems, will provide a repertoire for vaccinologists to design the recombinant vaccine which will generate an optimal humoral and immune response for protection against infection or disease caused by pathogens that infect via mucosal surfaces.


Complication rates are reduced for revision adult spine deformity surgery among high-volume hospitals and surgeons.
Revision adult spinal deformity surgery (RASDS) is a particularly high-risk intervention. The aim was to assess complication rates in RASDS by surgeon and hospital operative volume. This was a retrospective analysis of prospectively collected data. Based on a Nationwide Inpatient Sample (NIS) database (2001-2010), patients aged older than 21 years (International Classification of Diseases, Ninth Revision, Clinical Modification) with spine arthrodesis for scoliosis were included. For longitudinal analysis, the 2008-2011 New York State Inpatient Database (NY SID) was queried. The outcome measures included complication rate after RASDS. Cases were identified as primary or revision surgery with or without osteotomy performed. Annual surgeon and hospital volumes were stratified into quartiles via identifier codes. Case complexity was determined using a novel operative complexity index, based on available NIS operative parameters: levels fused, approach, osteotomy, and revision status. The primary end point was morbidity during the hospital stay. New York State Inpatient Database analysis allowed for identification of rate of reoperation for infection or pseudarthrosis/implant failure. One-way analysis of variance was used to assess continuous measures, chi-square for categorical measures. Of 139,150 adult spinal deformity surgery (ASDS) cases, 4,888 revision with hospital identifiers and 1,978 with surgeon identifiers were identified. Higher-volume surgeons performed more revision cases and cases requiring osteotomy. With increasing hospital volume, complication rate for RASDS decreased (9.7% vs. 12.9% at highest- vs. lowest-volume centers, p< .001). The highest-volume surgeons showed significant decreases in the rate of major complications for RASDS (8.8% vs. 10.7% for lowest-volume surgeons, p< .001). A similar trend was observed for ASDS cases requiring osteotomy. Multiple logistic regression analysis showed that the highest-volume hospitals and surgeons showed a reduced odds ratio for all complications compared with lowest-volume hospitals. For the NY SID, 528 RASDS cases indicated reoperation rates for infection and pseudarthrosis/implant failure after RASDS were increased for the lowest-volume hospitals and surgeons. Perioperative complication rate associated with RASDS is lower when patients are treated by high-volume surgeons at high-volume centers. As complex cases requiring osteotomy and combined approaches are more frequent at high-volume centers, an operative complexity index helps predict the likelihood of volume-dependent complication rates. Future interhospital and intersurgeon comparisons should account for these case characteristics so that similar case complexity is compared in these analyses.


Anti-adipogenic diarylheptanoids from Alnus hirsuta f. sibirica on 3T3-L1 cells.
A new diarylheptanoid, (5S)-hydroxy-1-(3,4-dihydroxyphenyl)-7-(4-hydroxyphenyl)-hepta-1E-en-3-one (1), was isolated along with seventeen known diarylheptanoids (2-18) from the methanol extract of Alnus hirsuta f. sibirica leaves using bioactivity-guided fractionation. Among the isolated compounds, compounds 1 and 2 and 4-12 reduced lipid accumulation dose-dependently in 3T3-L1 preadipocytes. Of the compounds active in the present assay system, the most potent compound 7, platyphyllonol-5-O-β-d-xylopyranoside, significantly suppressed the induction of peroxisome proliferator activated receptor γ (PPARγ and CCAAT/enhancer binding protein α (C/EBPα) protein expression, and inhibited adipocyte differentiation induced by troglitazone, a PPARγ agonist. It was demonstrated that compound 7 has anti-adipogenic activity mediated by the regulation of PPARγ dependent pathways.


Oligomerization and chaperone-like activity of Drosophila melanogaster small heat shock protein DmHsp27 and three arginine mutants in the alpha-crystallin domain.
The small Hsp DmHsp27 from Drosophila melanogaster is one of the few small heat shock proteins (sHsps) found within the nucleus. We report that its dimerization is independent of disulfide bond formation and seems to rely on salt bridges. Unlike metazoan sHsps, DmHsp27 forms two populations of oligomers not in equilibrium. Mutations at highly conserved arginine residues in mammalian sHsps have been reported to be associated with protein conformational defects and intracellular aggregation. Independent mutation of three highly conserved arginines (R122, R131, and R135) to glycine in DmHsp27 results in only one population of higher molecular weight form. In vitro, the chaperone-like activity of wild-type DmHsp27 was comparable with that of its two isolated populations and to the single population of the R122G, R131G, and R135G using luciferase as substrate. However, using insulin, the chaperone-like activity of wild-type DmHsp27 was lower than that of R122G and R131G mutants. Altogether, the results characterize wild-type DmHsp27 and its alpha-crystallin domain (ACD) arginine mutants and may give insight into protection mechanism of sHsps.


Resuscitation Compression for Newborn Sheep.
Neonatal maladjustment syndrome is characterized by depressed consciousness, neurologic signs, and reduced or nonexistent suckle reflex. Resuscitation compression (squeezing) has been used in newborn foals and calves to reduce the behavioral symptoms of neonatal maladjustment syndrome. In this review, the authors describe how resuscitation compression can be used in newborn sheep. This technique can improve abnormal neonatal lamb behavior and encourage suckling in resistant lambs.


Pneumolysin-mediated expression of β-defensin 2 is coordinated by p38 MAP kinase-MKP1 in human airway cells.
Antimicrobial peptides act as important innate immune defense mediators against invading microbes such as Streptococcus pneumoniae. Among a number of antimicrobial peptides, β-defensin 2 (BD2) has strong antimicrobial activity against S. pneumoniae. However, little is known about the molecular signaling mechanisms leading to the BD2 expression. Here, we report that BD2 is strongly induced by S. pneumoniae in human airway cells including human middle-ear cells. Among diverse pneumococcal virulence factors, pneumolysin is required for inducing BD2 whose expression is under the control of p38 mitogen-activated protein kinase (MAPK). Pneumolysin also selectively regulates the expression of MAPK phosphatase 1 (MKP1), which inhibits the p38 signaling pathway, thereby leading to upregulation of BD2 to mount an effective defense against S. pneumoniae infection. These results provide novel insights into the molecular mechanisms underlying the coordinative regulation of BD2 expression via p38-MKP1 in the pathogenesis of airway infectious diseases.


Neuropathic pain in Charcot-Marie-Tooth disease.
To determine the frequency and extent to which subjects with Charcot-Marie-Tooth (CMT) disease report pain and to compare qualities of pain in CMT to other painful neuropathic conditions. Descriptive, nonexperimental survey, using a previously validated measurement tool, the Neuropathic Pain Scale (NPS). Participants were recruited from the membership roster of a worldwide CMT support organization. NPS pain descriptors reported in CMT were compared with those reported by subjects with postherpetic neuralgia (PHN), complex regional pain syndrome, type 1 (CRPS-1), also known as reflex sympathetic dystrophy, diabetic neuropathy (DN), and peripheral nerve injury (PNI). Of 617 CMT subjects (40% response rate), 440 (71%) reported pain. with the most severe pain sites noted as low back (70%), knees (53%), ankles (50%), toes (46%), and feet (44%). Of this group, 171 (39%) reported interruption of activities of daily living by pain; 168 (38%) used non-narcotic pain medication and 113 (23%) used narcotics and/or benzodiazepines for pain. The use of pain description was similar for CMT, PHN, CRPS-1, DN, and PNI in terms of intensity and the descriptors hot, dull, and deep. Neuropathic pain is a significant problem for many people with CMT. The frequency and intensity of pain reported in CMT is comparable in many ways to PHN, CRPS-1, DN. and PNI. Further studies are needed to examine possible pain generators and pharmacologic and rehabilitative modalities to treat pain in CMT.


The nucleotide and deduced amino acid sequences of EcoRI fragment containing the 5'-terminal region of Clostridium botulinum type E toxin gene cloned from Mashike, Iwanai and Otaru strains.
Chromosomal DNAs were extracted from toxigenic three Clostridium botulinum type E strains isolated from food-borne botulism. After digestion by EcoRI, the fragments were cloned into Escherichia coli by using bacteriophage lambda gt11 and screened with monoclonal antibody recognizing the light chain component of botulinum type E toxin. The fragments (about 1 kbp size) cloned from each strain were recloned into a plasmid vector pUC118. The E. coli cells transformed with the recombinant plasmids produced 33 kDa protein with or without IPTG (isopropyl-beta-D-thiogalactopyranoside) which reacted with the monoclonal antibody. The nucleotide sequences of the cloned EcoRI fragments from the three type E strains were identical and contain the 5'-terminal region of the type E toxin gene. It was also found that there exist several highly homologous nucleotide sequences among the botulinum types A, C and E, and tetanus toxin genes in both translated and untranslated regions.


Recent medicinal approaches of novel pyrimidine analogs: A review.
Pyrimidine derivatives attract researchers due to their versatile scaffold & their medicinal significance. Pyrimidine associated analogs are majorly contributed to the field of medicinal chemistry. In this review article, the recent new structural design and development of active agent studies and biological approaches are highlighted. In addition, the biological potency and the structure-activity relationship of pyrimidines such as antimicrobial, anticancer, anti-inflammatory, analgesic, anti-diabetic, anti-HIV, anthelmintic, CNS depressants, and cardiac agents are discussed. Finally, this review article may attract the researchers for new structural design and development of novel active pyrimidine scaffolds with more active and less harmful.


Is proprioception calibrated during visually guided movements?
In the present study, a visuomotor adaptation paradigm was used to determine whether proprioception is calibrated during visually guided movements. A full vision group (FV) was given vision of a cursor representing hand position and was asked to aim towards visible targets. A no vision group (NV) performed the same task without vision of the cursor and was given knowledge of results (KR) after movement completion. A directional bias was introduced between the location of the cursor and the location of the hand in an adaptation phase, which resulted in a deviation to the right of the intended target. Of interest was whether participants would still show rightward deviations in a post-test series of trials in which vision was removed (aftereffects). The NV group presented strong aftereffects. However, the FV group only showed modest aftereffects early in the post-test, which rapidly decayed over the course of the post-test. Further analyses showed that the presence of those early aftereffects was due to an offline influence of vision on movement planning.


Analgesic opioid use disorders in patients with chronic non-cancer pain: A holistic approach for tailored management.
Chronic pain is a major public health issue that frequently leads to analgesic opioid prescriptions. These prescriptions could cause addiction issues in high-risk patients with associated comorbidities, especially those of a psychiatric, addictive, and social nature. Pain management in dependent patients is complex and is yet to be established. By combining the views of professionals from various specialties, we conducted an integrative review on this scope. This methodology synthesizes knowledge and results of significant practical studies to provide a narrative overview of the literature. The main results consisted in first proposing definitions that could allow shared vocabulary among health professionals regardless of their specialties. Next, a discussion was conducted around the main strategies for managing prescription opioid dependence, as well as pain in the context of opioid dependence and associated comorbidities. As a conclusion, we proposed to define the contours of holistic management by outlining the main guidelines for creating a multidisciplinary care framework for multi-comorbid patients with chronic pathologies.


Thyrotropin-releasing hormone-immunoreactive nerve terminals synapse on the dendrites of gastric vagal motoneurons in the rat.
Thyrotropin-releasing hormone stimulates vagally mediated gastric acid secretion and motility by an undefined central mechanism in the rat. The present study sought to determine the anatomical basis for this stimulatory effect by examining the ultrastructural relationship of nerve terminals immunoreactive for thyrotropin-releasing hormone with the dendrites of gastric vagal motoneurons. A light and electron microscopic double immunostaining technique was employed using the beta subunit of unconjugated cholera toxin as a neural tracer. Cholera toxin (50 microliters, 0.25%) was injected into the ventral stomach musculature in five rats. After 72 hours' survival, animals were sacrificed by transcardiac perfusion fixation. Retrogradely transported cholera toxin was immunocytochemically localized in vagal gastric motoneurons and their dendrites in the dorsal motor nucleus of the vagus and nucleus of the solitary tract, alone or in combination with the immunocytochemical localization of thyrotropin-releasing hormone. Ultrastructural analysis of double-labeled material revealed thyrotropin-releasing hormone-immunoreactive nerve terminals making asymmetric synaptic contacts on the retrogradely labeled dendrites of vagal gastric motoneurons. Nerve terminals immunoreactive for thyrotropin-releasing hormone also made asymmetric and symmetric synaptic contacts with unlabeled dendrites of undetermined perikaryal origin. In addition, nonsynaptic varicosities immunoreactive for thyrotropin-releasing hormone were frequently observed in the vagal nuclei. The synaptic contacts between thyrotropin-releasing hormone-immunoreactive nerve terminals and vagal gastric motoneuronal dendrites provide one possible basis for the profound stimulatory effect of central thyrotropin-releasing hormone on gastric vagal motor activity.


Disruptive behaviors among nurses in Israel - association with listening, wellbeing and feeling as a victim: a cross-sectional study.
To examine the association between listening and disruptive behaviors and the association between disruptive behavior and the wellbeing of the nurse. To test whether constructive and destructive listening has an incremental validity. A structured questionnaire survey that measured the (constructive & destructive) listening climate at work, exposure to disruptive behaviors, well-being and feeling as a victim. We presented this survey using the Qualtrics software. Of the final sample of 567 respondents who reported that they were nurses, MAge = 38.41, 67% indicated that they were exposed to some form of disruptive behavior. Experiencing listening in the ward was associated with low levels of exposure to disruptive behaviors; exposure to disruptive behaviors, in turn, predicted reduction in the nurses' wellbeing; the reduction in wellbeing was especially pronounced among nurses who felt like a victim. Each of the facets of the listening measure-constructive listening and destructive listening-had incremental validity in predicting exposure to disruptive behaviors. Finally, the effect of exposure to disruptive behavior on wellbeing was curvilinear. Disruptive behavior is a major challenge to the workplace well-being for nurses. The victim mentality has an adverse impact on nurses. Preventive efforts aimed at reducing disruptive behaviors among nurses and decreasing their sense of victimization are crucial for the well-being of nurses.


Haemangiomas and venous malformations of the head and neck: A retrospective analysis of endovascular management in 358 patients.
Haemangioma (HM) and venous malformations of the head and neck are formidable lesions as they cause cosmetic deformity and psychological problems. Their surgical excision is difficult and fraught with problems like operative blood loss, incomplete excision, disfigurement and recurrence. Endovascular techniques like sclerotherapy and embolization are increasingly being used in the treatment of these difficult lesions. This study was undertaken to analyse the efficacy and safety of endovascular techniques in the treatment of HM and slow flow vascular malformations. We retrospectively reviewed the records and clinical photographs of 358 patients of HM and slow flow vascular malformations treated in our institute by endovascular approach over a 15 year period. Pre- and post-treatment photographs were compared and outcomes categorized as complete resolution (>90% reduction), considerable reduction (60-90% reduction), partial reduction (20-60% reduction) and no change (<20% reduction). Complete resolution of the lesion was seen in 30% of the patients while 50% patients showed considerable reduction of the swelling. Complications occurred in 6.4% of patients. We conclude that sclerotherapy is an effective and safe treatment modality for these lesions and may be considered as the primary modality in the treatment of these challenging lesions.


Left ventricular-right atrial communication by perforation of the atrioventricular portion of the membranous septum and severe aortic valve regurgitation caused by infective endocarditis.
We report the case of acquired left ventricle (LV) to right atrial (RA) communication through an aneurysm of the atrioventricular septum caused by infectious endocarditis. A severe aortic valve regurgitation and destruction of the aortic valve was detected by echocardiography. Transesophageal echocardiography revealed a flail aortic valve with vegetation and abnormal shunt flow from the LV to RA with ruptured aneurysm of the membranous septum. An abscess cavity of the aortic ring was introduced. Because of worsening congestive heart failure, the patient underwent emergency aortic valve replacement and patch closure of the communication of the membranous septum. The patient's postoperative course was uneventful.


Differential expression of cell adhesion molecules in variants of K1735 melanoma cells differing in metastatic capacity.
We have investigated the expression of 2 neural-cell adhesion molecules, NCAM and LI, in K1735-C116 and -MI melanoma cells which differ qualitatively in their metastatic potential, i.e., MI cells are metastatic whereas C116 cells are not. We have found that NCAM in C116 cells are expressed as 2 quantitatively major glycosylated polypeptides with Mr of 145,000 and 120,000 and a minor 190,000 Mr polypeptide, whereas MI cells expressed NCAM as 3 glycosylated polypeptides with MR of 200,000, 140,000 and 120,000. The amount of NCAM in MI cells constituted only 60% of the amount observed in C116 cells. In C116 cells, the 145,000 and 120,000 Mr NCAM polypeptides were sulphated whereas NCAM did not appear to be sulphated in MI cells. No phosphorylation of NCAM in the 2 cell lines was observed. LI was expressed as a phosphorylated glycoprotein with Mr of 210,000 in MI cells whereas no LI expression was observed in C116 cells. LI was not sulphated in MI cells.


Effect of dexamethasone on voltage-gated K+ channels in Jurkat T-lymphocytes.
The voltage-gated K+ channel Kv1.3 is an important regulator of lymphocyte function. Activation of lymphocytes is accompanied by stimulation, whereas CD95-induced apoptosis by inhibition, of Kv1.3. The channel serves to maintain cell membrane potential, a prerequisite for signalling through the Ca2+ release-activated Ca2+ channel I(CRAC). As glucocorticoids are known to regulate lymphocyte function, the present study addressed the effect of dexamethasone on voltage-gated K+ channels in Jurkat T-lymphocytes. In whole-cell patch-clamp experiments current families evoked by 200-ms potential steps every 15 s from -70 mV to values from -120 to +100 mV revealed the functional expression of voltage-gated K+ channels. Pre-treatment of Jurkat T-lymphocytes for 2-3 h with 1 microM dexamethasone led to a significant decrease of voltage-gated K+ currents. Fura-2-fluorescence measurements showed that the readdition of Ca2+ to Ca(2+)-depleted cells led to a rapid increase of cytosolic Ca2+ activity. This increase of Ca2+ activity was blunted by both the K+ channel blocker margatoxin (10 nM) and 24 h pre-treatment with dexamethasone (1 microM). In conclusion, dexamethasone inhibits voltage-gated K+ channels in Jurkat T-lymphocytes, an effect impeding Ca2+ entry through I(CRAC).


On the exact measure of disease spread in stochastic epidemic models.
The basic reproduction number, R₀, is probably the most important quantity in epidemiology. It is used to measure the transmission potential during the initial phase of an epidemic. In this paper, we are specifically concerned with the quantification of the spread of a disease modeled by a Markov chain. Due to the occurrence of repeated contacts taking place between a typical infective individual and other individuals already infected before, R₀ overestimates the average number of secondary infections. We present two alternative measures, namely, the exact reproduction number, Re0, and the population transmission number, Rp, that overcome this difficulty and provide valuable insight. The applicability of Re0 and Rp to control of disease spread is also examined.


Further Description of Helicoverpa zea (Lepidoptera: Noctuidae) Male Genitalia and New Genetic Evidence of Synonymy With Respect to the Anomalous Form, "Heliothis stombleri".
The Helicoverpa/Heliothis complex can cause serious damage to agricultural crops. Phenotypic similarity makes it difficult to discriminate between closely related Helicoverpa species. Currently, morphology of the male genitalia complemented with molecular techniques constitutes the best approach for species identification. In this work, a broad microscopic examination of adult Helicoverpa zea (Boddie) males (n = 200) captured in central Argentina was carried out in order to provide a detailed description of the valvae and the phallus. A considerable degree of variability was recorded. Both rounded and sharp valve apices were observed and valvae were not always parallel-sided. Most evident differences were detected concerning the number of cornuti on the phallus. A range of 15-21 cornuti per phallus was recorded, the mode being 18. A significant minority of the samples (3.5%) displayed an abnormal genital condition showing a constricted phallus lacking cornuti, and pointed valvae. This form was initially attributed to a distinct species, Heliothis stombleri, and later proposed as a synonym of H. zea based on additional morphological observations and molecular studies. Here, a phylogenetic analysis combining mitochondrial (cytochrome oxidase subunit I) and nuclear (elongation factor -1 alpha) genes was performed on these and other Helicoverpa specimens collected in the same geographical region, in order to further verify the taxonomic status of H. stombleri. The tree topology clearly grouped H. stombleri with H. zea, supporting the assumption that the former represents, in fact, an anomalous form of the latter. Further experiments are needed to clarify the etiology of this anomaly and its persistence over time.


Gustatory function and taste perception in patients with oral lichen planus and tongue involvement.
The aim of the study was to evaluate if patients with oral lichen planus (OLP) and tongue involvement have impaired taste function and if there is an association to the perception of pain. The test group included patients with OLP and involvement of the tongue without treatment (n = 20). Control subjects had no mucosal or systemic disease affecting taste function and were matched for age and gender (n = 20). Patients' intraoral pain and subjective perception of taste were recorded on a visual analog scale. Taste function was assessed by means of the "taste strips." Measured taste function was slightly but significantly decreased in OLP patients compared to control subjects (p = 0.01). Self-rated taste perception did not differ in both groups (p = 0.8). Post hoc analysis showed that particularly the taste quality "sour" was most affected by the OLP status (p = 0.01). There were no correlations between pain and subjective/objective taste perception. Untreated OLP subjects have lower gustatory function, which they are not aware of. Impaired gustatory function in patients with OLP may affect patient's quality of life. Further studies on larger samples sizes are requested.


Initial Brazilian experience with short-duration in-center daily hemodialysis.
The whole initial Brazilian experience with short-duration in-center daily hemodialysis is summarized here. The study was performed at a time when low-flux membrane and nonproportional dialysis represented the standard dialysis treatment in Brazil. Five patients were treated for 2 years. The subject is developed in a way to narrate the efforts to set the research project and summarize the findings, meeting presentations, and publications that derived from the project. At the end of the study, the main benefits observed consisted of alleviation of the end-stage renal disease anemia; reduction of the frequency of complications during dialysis sessions; a lower degree of azotemia; easier blood pressure control; and improvements in acid-base status, mineral metabolism and bone disease, nutrition, and quality of life.


Consumer acceptance of fermented sausages made from boars is not distracted by respective information.
This study investigated the impact of two information conditions and two androstenone concentrations on the acceptability of fermented sausages made from boar meat. Two batches of salamis were produced by mixing bellies and lean meat resulting in average androstenone levels of 0.408 μg/g vs. 1.585 μg/g melted fat, respectively. Skatole levels were kept below 0.05 μg/g melted fat in the final products. The consumers were provided with either the information that the products consisted of 100% pork or 100% boar meat. In total, 478 visitors of an animal husbandry fair, assumed to be familiar with the consequences of not castrating male piglets, evaluated the salami following a monadic between-subject design. The information did not significantly affect the hedonic scores. The percentage of dislikes was very low, i.e. 3 vs. 6% (p=0.24) for salami LOW and HIGH, respectively. The batch with lower androstenone content was liked slightly but significantly better (p=0.03).


Esophageal Dysphagia in the Elderly.
With a globally aging population, dysphagia is a growing health concern among elderly. Increasing reflux disease has contributed to an increased prevalence of dysphagia from peptic strictures and esophageal cancer. Dysphagia can lead to malnutrition and aspiration pneumonia, causing considerable morbidity and mortality. This review article focuses on recent advances in the approach and management of esophageal dysphagia. Endoscopic functional luminal imaging probe is a novel test that complements upper endoscopy, esophagram, and esophageal manometry for evaluation of esophageal dysphagia. Opioid induced esophageal dysfunction (OIED) is an emerging clinical entity that can mimic achalasia. Strictures refractory to dilation can be treated with intralesional steroid injections, electrosurgical incision, or esophageal stents. Peroral endoscopic myotomy (POEM) is gaining in popularity for treatment of achalasia and other spastic disorders of esophagus. Treatment of esophageal dysphagia may include proton pump inhibitors, endoscopic dilation, or surgery and requires a personalized approach based on risks and benefits. POEM is a valuable therapy for achalasia, but further studies are needed to evaluate its use, and other alternatives, for treatment of OIED and spastic esophageal disorders.


Membrane-delimited cell signaling complexes: direct ion channel regulation by G proteins.
Ion channels are signaling molecules and by themselves perform no work. In this regard they are unlike the usual membrane enzyme effectors for G proteins. The pathways of G protein receptor, G protein and ion channels are, therefore, purely informational in function. Because a single G protein may have several ion channels as effectors, the effects should be coordinated and this seems to be the case. Inhibition of Ca2+ current and stimulation of K+ currents would have a greater impact than either alone. Additional flexibility is provided by spontaneous noise in the complexes of G protein receptor, G protein, and ion channel. By having a non-zero setpoint, the range of control is extended and the responses become bi-directional.


The Donnan-dominated resting state of skeletal muscle fibers contributes to resilience and longevity in dystrophic fibers.
Duchenne muscular dystrophy (DMD) is an X-linked dystrophin-minus muscle-wasting disease. Ion homeostasis in skeletal muscle fibers underperforms as DMD progresses. But though DMD renders these excitable cells intolerant of exertion, sodium overloaded, depolarized, and spontaneously contractile, they can survive for several decades. We show computationally that underpinning this longevity is a strikingly frugal, robust Pump-Leak/Donnan (P-L/D) ion homeostatic process. Unlike neurons, which operate with a costly "Pump-Leak-dominated" ion homeostatic steady state, skeletal muscle fibers operate with a low-cost "Donnan-dominated" ion homeostatic steady state that combines a large chloride permeability with an exceptionally small sodium permeability. Simultaneously, this combination keeps fiber excitability low and minimizes pump expenditures. As mechanically active, long-lived multinucleate cells, skeletal muscle fibers have evolved to handle overexertion, sarcolemmal tears, ischemic bouts, etc.; the frugality of their Donnan dominated steady state lets them maintain the outsized pump reserves that make them resilient during these inevitable transient emergencies. Here, P-L/D model variants challenged with DMD-type insult/injury (low pump-strength, overstimulation, leaky Nav and cation channels) show how chronic "nonosmotic" sodium overload (observed in DMD patients) develops. Profoundly severe DMD ion homeostatic insult/injury causes spontaneous firing (and, consequently, unwanted excitation-contraction coupling) that elicits cytotoxic swelling. Therefore, boosting operational pump-strength and/or diminishing sodium and cation channel leaks should help extend DMD fiber longevity.


Critical appraisal of the orthopaedic literature: therapeutic and economic analysis.
When reading an article of interest in the orthopaedic literature it is necessary to appraise the quality of the evidence therein. First, the reader should determine the design of the study. If the level of the study design in the hierarchy of evidence is lower, the inferences that are drawn from the study are weaker. Second, the article should be assessed for the quality indicators relevant to the design. To the extent that the quality is high, the inferences that are drawn from the study will be strengthened. Making this process explicit, with guidelines to assess the strength of the available evidence, will serve to improve patient care.


A Scoring Algorithm for the Automated Analysis of Glycosaminoglycan MS/MS Data.
The role of glycosaminoglycans (GAGs) in major biological functions is numerous and diverse, yet structural characterization of them by mass spectrometric techniques proves to be challenging. Characterization of GAG structure from tandem mass spectrometry is a tedious and time-consuming process but one that can be automated in a database-independent, high-throughput fashion through the assistance of software implementing a genetic algorithm (J. Am. Soc. Mass Spectrom. 29, 1802-1911, 2018). This work presents the manner in which this data is interpreted by the software, specifically addressing the development of a scoring algorithm. The significance of glycosidic and cross-ring fragment ions and the implications that specific fragments provide for assigning the positions of modifications are discussed. The scoring algorithm is tested for statistical merit using the widely accepted expectation value as the criterion for quality. Using MS/MS data for well-characterized standards, this scoring approach is shown to assign the correct structure, with a low likelihood (1 in 1012 chances) that the assigned structure matches the data due to random chance. The integrated software that automates the structure assignment is called Glycosaminoglycan-Unambiguous Identification Technology (G-UNIT).


A pontine-hypothalamic temperature difference correlated with cutaneous and respiratory heat loss.
The role of cutaneous and respiratory heat loss for selective brain cooling in different species is discussed and new experimental results from a comparative study are summarized. In three species (cat, rabbit and rat) the difference between pontine and hypothalamic temperatures was studied as a function of head heat exchanger vasomotion appraised by the difference between hypothalamic and ear pinna (cats and rabbits) or nasal mucosa (rats) temperatures during the behavioral states of wakefulness and slow wave sleep at an ambient temperature of 24+/-1 degrees C. The results show that: (i) the pontine-hypothalamic temperature difference is an useful indicator of selective brain cooling since it is positive and inversely correlated with the hypothalamic-ear pinna temperature difference in cats and rabbits and with the hypothalamic-nasal mucosa temperature difference in rats; (ii) respiratory heat loss prevails quantitatively over cutaneous heat loss in maintaining this difference.


The benefit of vegetarian diets for reducing blood pressure in Taiwan: a historically prospective cohort study.
Past vegetarians research has often found that they have lower blood pressure (BP). Effects may include their lower BMI and higher intake levels of fruit and vegetables. Besides, the study pursues to extend this evidence in a diverse population containing vegans, lacto-ovo vegetarians and omnivores. The study analyzed data on five hundred vigorous individuals aged 20 years or older from a standard medical screening program and provided validated questionnaire. Criteria were established for vegan, lacto-ovo vegetarian, partial vegetarian and omnivorous dietary patterns. Health screening programs were conducted at a standard medical screening program in Taiwan between 2006 and 2017. Dietary data were gathered by self-administered questionnaire. Five hundred Taiwanese subjects representing the cohort. Multiple regression analyses confirmed that the vegan vegetarians had lower systolic and diastolic BP (mmHg) than omnivorous Taiwanese (β = - 6.8, p < 0.05 and β = - 6.9, p < 0.001). Findings for lacto-ovo vegetarians (β = - 9.1, p < 0.001 and β = - 5.8, p < 0.001) were similar. The vegetarians were also less likely to be using antihypertensive medications. Defining hypertension as systolic BP > 139 mmHg or diastolic BP > 89 mmHg or routine of antihypertensive medications, the odds ratio of hypertension compared with omnivores was 0.37 (95% CI = 0.19-0.74), 0.57 (95% CI = 0.36-0.92) and 0.92 (95% CI = 0.50-1.70), respectively, for vegans, lacto-ovo vegetarians and partial vegetarians. Results were reduced after adjustment for BMI. The study concludes from this relatively large study that vegetarians, especially vegans, with otherwise diverse characteristics but stable diets, do have lower systolic and diastolic BP and less hypertension than omnivores.


A single dose of doxycycline after an ixodes ricinus tick bite to prevent Lyme borreliosis: An open-label randomized controlled trial.
A single dose of doxycycline after a tick bite can prevent the development of Lyme borreliosis in North America, but extrapolation to Europe is hampered by differences in Borrelia burgdorferi sensu lato genospecies and tick species. We assessed the efficacy of prophylaxis after a tick bite in Europe. We conducted an open-label randomized controlled trial, administering a single dose of 200 mg doxycycline within 72 h after removing an attached tick from the skin, compared to no treatment. Potential participants ≥ 8 years of age who reported a recent tick bite online were invited for the study. After informed consent, they were randomly assigned to either the prophylaxis or the no-treatment group. Participants in the prophylaxis group were asked to visit their general practitioner to administer the antibiotics. All participants were followed up by online questionnaires. Our primary outcome was the development of physician-confirmed Lyme borreliosis in a modified-intention-to-treat analysis. This study is registered in the Netherlands Trial Register (NTR3953) and is closed. Between April 11, 2013, and June 10, 2015, 3538 potential participants were randomized, of whom 1689 were included in the modified-intention-to-treat analysis. 10 cases of Lyme borreliosis were reported out of 1041 participants (0.96%) in the prophylaxis group, and 19 cases out of 648 no-treatment participants (2.9%), resulting in a relative risk reduction of 67% (95% CI 31 - 84%), and a number-needed-to-treat of 51 (95% CI 29 - 180). No serious adverse events were reported. This primary care-based trial provides evidence that a single dose of doxycycline can prevent the development of Lyme borreliosis after an Ixodes ricinus tick bite.


Effect of preparative variables on small interfering RNA loaded Poly(D,L-lactide-co-glycolide)-chitosan submicron particles prepared by emulsification diffusion method.
In this study, poly(D,L-lactide-co-glycolide) (PLGA)-chitosan particles were investigated as an effective delivery system for small interfering RNA (siRNA) by emulsification diffusion method. The type, molecular weight and concentration of chitosan, PLGA type as well as centrifugation and freeze-drying process were amongst the investigated variables. PLGA-chitosan particles obtained were positively charged with particle size between approximately 0.4-1 microm depending on type, molecular weight and concentration of chitosan as well as type of PLGA. A better siRNA loading capacity was observed when a higher degree of 'uncapped end groups' were used. The addition of trehalose has also been shown to stabilize these particles from severe aggregation induced by freeze-drying. It was found that physical properties of PLGA-chitosan particles and their siRNA binding capacity were highly influenced by certain preparation parameters. The desired positive charge of submicron size range PLGA-chitosan particles could therefore be obtained by adjusting and optimizing these preparative and formulation parameters.


A PETase enzyme synthesised in the chloroplast of the microalga Chlamydomonas reinhardtii is active against post-consumer plastics.
Polyethylene terephthalate hydrolases (PETases) are a newly discovered and industrially important class of enzymes that catalyze the enzymatic degradation of polyethylene terephatalate (PET), one of the most abundant plastics in the world. The greater enzymatic efficiencies of PETases compared to close relatives from the cutinase and lipase families have resulted in increasing research interest. Despite this, further characterization of PETases is essential, particularly regarding their possible activity against other kinds of plastic. In this study, we exploited for the first time the use of the microalgal chloroplast for more sustainable synthesis of a PETase enzyme. A photosynthetic-restoration strategy was used to generate a marker-free transformant line of the green microalga Chlamydomonas reinhardtii in which the PETase from Ideonella sakaiensis was constitutively expressed in the chloroplast. Subsequently, the activity of the PETase against both PET and post-consumer plastics was investigated via atomic force microscopy, revealing evidence of degradation of the plastics.


Platelet phenotyping in carriers for Glanzmann's thrombasthenia: a simple screening test for assessment of the molecular defect.
Glanzmann's thrombasthenia (GT) is a recessive autosomal bleeding disorder characterized by the abnormality of aggregation due to a platelet glycoprotein (GP) IIb-IIIa deficiency or a dysfunctional complex. Molecular abnormalities have been localized on the gene coding for GP IIb or IIIa. The aim of our work was an attempt to obtain indirectly information on the putative localization of the molecular defect in patients with GT type I or II by the determination of the HPA-1 (GP IIIa) and HPA-3 (GP IIb) alloantigenic systems' expression in GT carriers. If GT results from a defective GP IIb gene, a GT carrier would appear homozygous for HPA-3 by serology, because the normal gene product will be expressed while the abnormal GP IIb gene product will not be present. Conversely, if the abnormality is in the GP IIIa gene, such an individual would appear homozygous for HPA-1. Therefore, the heterozygous status for HPA would result from the normal expression of the two genes for the considered alloantigenic system. Among the four families studied with informative members, our presumptions were strengthened by the preliminary genetic results in one family showing a mutation in the GP IIb gene. Thus, serology could be a simple screening test for the possible defective gene responsible for GT allowing molecular investigation focusing only on GP IIb or IIIa gene.


Use of the laryngeal tube for out-of-hospital resuscitation.
Every physician involved in emergency medicine should be familiar with alternative techniques for managing the difficult airway. We report a case of a patient who was successfully ventilated and oxygenated with a laryngeal tube, when tracheal intubation failed. Ventilation was possible even during continuous chest compressions. Airway equipment, including one supraglottic alternative for patients of all ages and a set for cricothyroidotomy, for those experienced in its use, should be available on every ambulance equipped for advanced life support.


Immunohistochemical evidence of striated muscle cells within midfacial superficial musculoaponeurotic system.
The superficial musculoaponeurotic system (SMAS) is a controversial functional fibro-adipose layer that connects the mimic muscles to the skin and is involved in a variety of facial mimic expressions. The presence of muscle fibers within SMAS fibrous septa is hypothetical. The present study analyzed SMAS fibrous septa composition for the existence of striated muscle cells. Histological serial sections of the sample borders (n=107) of 19 in sano-resected and diagnosed cutaneous tumors of the midfacial region were investigated. Immunohistochemical (actin and myosin) and hematoxylin and eosin staining were performed to detect striated muscle cells in SMAS fibrous septa. A fibro-neuro-musculo-vascular functional unit within SMAS fibrous septa was demonstrated. SMAS striated muscle cells were morphologically independent from preparotideal and periorbital mimic muscles. Intraseptal blood vessels draining the superficial and deep SMAS vascular system were described. Striated muscle cells were demonstrated within SMAS fibrous septa. Nerve cells and vascular tissue together with the SMAS fibro-muscular meshwork demonstrated an autonomous operating functional unit that hypothetical modulated individual mimic expression contributing to the diversity of mimic expression. The SMAS develops with mimic muscle contractions as a synergetic effect during facial crease and fold formation processes.


Social support and functioning in a patient with spinal cord injury: the role of social skills.
This study reports on a patient with spinal cord injury (SCI) in whom the interaction between social skills and social support seems to influence functioning. The International Classification of Functioning, Disability and Health (ICF) was used as a reference framework. Qualitative (i.e. observation, structured, and open interviews with the patient and health professionals) and quantitative data (i.e. spinal cord independence measure, medical records) were collected. Content analysis of the interviews was carried out to identify aspects of social skills and social support. An ICF-based documentation tool (i.e. ICF Assessment Sheet) was used to structure information about the level of functioning of body functions and structures, activity and participation, and environmental and personal factors of a 57-year-old man with incomplete paraplegia during first rehabilitation. The patient presented a variety of effective social skills (i.e. assertiveness, goal direction). However, the adaptation of skills, such as asking for help social problem-solving, sensitivity, and expressivity in social relations, became necessary to acquire. The patient received different types of social support (i.e. emotional, informational, and instrumental) from different sources (e.g. family and friends). The qualitative interviews provided indications for an interaction between social skills and social support. The impact of social skills and social support on functioning is discussed. Social skills can mobilize social support and enhance functioning. However, better understanding of social skills, social support, and their interaction in relation to functioning in SCI is required to develop targeted and effective interventions to strengthen psychosocial resources for the enhancement of functioning in patients with SCI.


Chronic granulocytic leukaemia: a defect in cellular interactions between stromal and haemopoietic stem cells?
Chronic granulocytic leukaemia (CGL) is regarded as a myeloproliferative disorder; in the chronic phase, the disease is characterized by excessive proliferation of myeloid cells apparently in the absence of any physiological demand. The reason(s) why and how this purposeless proliferation of myeloid cells begins remains to be elucidated. Recent studies on cellular interaction between stromal and haemopoietic stem cells (HSC) suggests that the stromal cells exert some form of regulatory influence on the growth and differentiation of HSC. In this communication it is postulated that CGL may be the result of a defect in cellular interactions between the stromal and haemopoietic stem cells.


Designing inorganically functionalized magic-size II-VI clusters and unraveling their surface states.
Surface engineering is a critical step in the functionalization of nanomaterials to improve their optical and electrochemical properties. However, this process remains a challenge in II-VI magic-size clusters (MSCs) due to their high sensitivity to the environment. Herein, we developed a general surface modification strategy to design all-inorganic MSCs by using certain metal salts (cation = Zn2+, In3+; Anion = Cl-, NO3 -, OTf-) and stabilized (CdS)34, (CdSe)34 and (ZnSe)34 MSCs in polar solvents. We further investigated the surface states of II-VI MSCs using electrochemiluminescence (ECL). The mechanism study revealed that the ECL emission was attributed to . Two ECL emissions at 556 nm and 530 nm demonstrated two surface passivation modes on (CdS)34 MSCs, which can be tuned by the surface ligands. The achievement of surface engineering opens a new design space for functional MSC compounds.


Bilateral compartmental syndrome after prolonged surgery in the lithotomy position.
Surgical procedures necessitating patient placement in physiologically abnormal positions can be associated with certain injuries usually arising from compression of nerves or muscles. Bilateral compartmental syndrome of the lower extremities is a grave complication, which, if unrecognized, can lead to either permanent neuromuscular dysfunction or limb loss. We report a case of bilateral four-compartment syndrome occurring after prolonged surgery with the patient in the lithotomy position.


Antimicrobial treatment duration for uncomplicated bloodstream infections in critically ill children: a multicentre observational study.
Bloodstream infections (BSIs) cause significant morbidity and mortality in critically ill children but treatment duration is understudied. We describe the durations of antimicrobial treatment that critically ill children receive and explore factors associated with treatment duration. We conducted a retrospective observational cohort study in six pediatric intensive care units (PICUs) across Canada. Associations between treatment duration and patient-, infection- and pathogen-related characteristics were explored using multivariable regression analyses. Among 187 critically ill children with BSIs, the median duration of antimicrobial treatment was 15 (IQR 11-25) days. Median treatment durations were longer than two weeks for all subjects with known sources of infection: catheter-related 16 (IQR 11-24), respiratory 15 (IQR 11-26), intra-abdominal 20 (IQR 14-26), skin/soft tissue 17 (IQR 15-33), urinary 17 (IQR 15-35), central nervous system 33 (IQR 15-46) and other sources 29.5 (IQR 15-55) days. When sources of infection were unclear, the median duration was 13 (IQR 10-16) days. Treatment durations varied widely within and across PICUs. In multivariable linear regression, longer treatment durations were associated with severity of illness (+ 0.4 days longer [95% confidence interval (CI), 0.1 to 0.7, p = 0.007] per unit increase in PRISM-IV) and central nervous system infection (+ 17 days [95% CI, 6.7 to 27.4], p = 0.001). Age and pathogen type were not associated with treatment duration. Most critically ill children with BSIs received at least two weeks of antimicrobial treatment. Further study is needed to determine whether shorter duration therapy would be effective for selected critically ill children.


House dust mite allergen avoidance: a randomized controlled trial of surface chemical treatment and encasement of bedding.
To test the effectiveness of a house dust mite (HDM) allergen avoidance strategy we conducted a randomized controlled trial in 35 atopic subjects with asthma, aged 13 to 60 living in Sydney - a high HDM allergen environment. After a 3 month run-in period, subjects were randomized to active allergen avoidance treatment (n = 17) or placebo (n = 18) groups and followed for 6 months. The active treatment involved placing impermeable covers over the mattress, pillows and duvet and spraying the remaining bedding, as well as the carpets and furniture, with a tannic acid/acaricidal spray. Subjects kept a daily record of symptoms and peak expiratory flow rates and had 3 monthly assessments of lung function and airway hyperresponsiveness (AHR). Dust samples were collected from the bed, the bedroom floor and the living room floor at 3 monthly intervals and 2 weeks after the treatment. Mean HDM allergen levels at baseline at these sites were, in the active group, 15.5, 9.6 and 10.2 micrograms Der p I/g of fine dust, and, in the placebo group 25.7, 11.8 and 6.3 micrograms/g. Two weeks after the allergen avoidance treatment the HDM allergen level in the beds was reduced to 29% of baseline (95% CI 16-50%, P = 0.038 compared with placebo), but was not significantly different at 3 or 6 months. There was also no significant effect of the allergen avoidance treatment on symptom scores, peak flow variability, lung function or AHR P > 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)


[Measuring patient satisfaction and identifying opportunities for improvement in the preparation of bariatric surgery patients].
To evaluate the satisfaction of patients candidates for bariatric surgery with the performance of a group training program prior to surgery, identifying opportunities for improvement in the program and evaluating participants satisfaction following their implementation. An "ad hoc" designed survey was used, addressed to assess opinions on different aspects of the program, overall satisfaction and identification of areas for improvement. The survey was administered to two groups of patients: the first after one year of implementation of the program to identify suggestions for improvement, and the second after one year of the implementation of the improvement. A total of 112 patients were assessed, 66 in the first pass of the questionnaire and 46 in the second. Both groups were homogeneous in demographic variables The main improvement detected was expert patients in the preparation of the program. After implantation, slight changes in the ratings of the questions were produced, that were not significant. Overall satisfaction rose from 9.5 to 9.74 out of 10. The other proposals for improvement were to improve audiovisuals and to fit the room furniture to the characteristics of the patients. The very high satisfaction levels obtained are usual in studies on hospital satisfaction, our results still being above the studies consulted, as well as in levels of excellence. This prevents statistically significant differences being found. There were no significant differences in the results before and after implementation of improvement. Continuous assessment allows new possibilities for improvement.


A simple, closed-form, mathematical model for gas exchange in microchannel artificial lungs.
Microfabrication techniques are attractive for constructing artificial lungs due to the ability to create features similar in size to those in the natural lung. However, a simple and intuitive mathematical model capable of accurately predicting the gas exchange performance of microchannel artificial lungs does not currently exist. Such a model is critical to understanding and optimizing these devices. Here, we describe a simple, closed-form mathematical model for gas exchange in microchannel artificial lungs and qualify it through application to experimental data from several research groups. We utilize lumped parameters and several assumptions to obtain a closed-form set of equations that describe gas exchange. This work is intended to augment computational models by providing a more intuitive, albeit potentially less accurate, understanding of the operation and trade-offs inherent in microchannel artificial lung devices.


Immunogenicity of an Additional mRNA-1273 SARS-CoV-2 Vaccination in People With HIV With Hyporesponse After Primary Vaccination.
The COVIH study is a prospective coronavirus disease 2019 (COVID-19) vaccination study in 1154 people with HIV (PWH), of whom 14% showed reduced antibody levels after primary vaccination. We evaluated whether an additional vaccination boosts immune responses in these hyporesponders. The primary end point was the increase in antibodies 28 days after additional mRNA-1273 vaccination. Secondary end points included neutralizing antibodies, S-specific T-cell and B-cell responses, and reactogenicity. Of the 66 participants, 40 previously received 2 doses ChAdOx1-S, 22 received 2 doses BNT162b2, and 4 received a single dose Ad26.COV2.S. The median age was 63 years (interquartile range [IQR], 60-66), 86% were male, and median CD4+ T-cell count was 650/μL (IQR, 423-941). The mean S1-specific antibody level increased from 35 binding antibody units (BAU)/mL (95% confidence interval [CI], 24-46) to 4317 BAU/mL (95% CI, 3275-5360) (P < .0001). Of all participants, 97% showed an adequate response and the 45 antibody-negative participants all seroconverted. A significant increase in the proportion of PWH with ancestral S-specific CD4+ T cells (P = .04) and S-specific B cells (P = .02) was observed. An additional mRNA-1273 vaccination induced a robust serological response in 97% of PWH with a hyporesponse after primary vaccination. Clinical Trials Registration. EUCTR2021-001054-57-N.


[Predictive value of global longitudinal strain in patients with cardiomyopathy without hypertrophic change but variants of susceptibility genes].
To explore the predictive value of overall longitudinal strain for the development of cardiomyopathy without hypertrophic changes. Sixty five patients with suspected hypertrophic cardiomyopathy (HCM) but without hypertrophic changes were selected. Genetic variant, overall longitudinal strain, left ventricular ejection fraction, end diastolic volume, end systolic volume, interventricular septal thickness, left ventricular diameter and end diastolic diameter were detected. The risk factors of HCM were analyzed. Forty four variants of 16 genes were identified, among which MYBPC3 13659G>A was the commonest (73.20%) and MYH7 13252C>T was the second (31.25%). MYBPC3 GG genotype, overall longitudinal strain and apical longitudinal strain were correlated with HCM (P<0.05). The increase of longitudinal strain is of great value in predicting the occurrence of HCM.


Exenatide-induced granulomatous panniculitis associated with poly(d,l-lactide-co-glycolide).
The extended-release formulation of exenatide for treatment of Type II diabetes mellitus is encapsulated in microspheres composed of poly(d,l-lactide-co-glycolide) (PLGA) and administered weekly. This medication has been reported to potentially cause injection-site reactions such as pruritus, transient nodules, and foreign body reaction. Here, we report a case of exenatide-induced granulomatous panniculitis. Our patient is a 63-year-old female with Type II diabetes presenting for concerns about painful nodules on her abdomen, developing approximately every week over the past year and migrating. Of note, the lesions appeared following exenatide injections in the same locations. Two deep-seated nodules of 1 cm were identified on examination. There were no overlying skin changes, and the lesions were tender to palpation. Punch biopsies of the two lesions were performed, which revealed a septal panniculitis containing amorphous material, along with a mixed inflammatory infiltrate. Gomori methenamine silver (GMS) and acid-fast bacilli (AFB) stains were negative for organisms. On infrared (IR) spectroscopy examination of the biopsy tissue, the spectral characteristics of (tissue) protein and PLGA were seen. Evaluation of the clinical and histopathologic findings, along with the IR spectroscopy match, determined that exenatide-induced panniculitis was the cause of the patient's nodules. This case highlights the importance of clinicians' awareness regarding injection-site reactions.


Electromagnetic waves along pseudo null curves in Minkowski space.
Considering the importance of Minkowski space in physics, it is an incomplete approach to deal with EM waves only in Euclidean space. For this reason, this paper deals with EM waves along pseudo null curves in Minkowski space. The main purpose of this study is to examine electromagnetic waves by defining an adapted orthogonal frame along the EM wave which contains both electric and magnetic fields. For this purpose, the extended derivative formulas of pseudo null frame are obtained. Depending on the values of Bishop curvatures, the linear transformations between the pseudo null frame and EM wave vector fields are described in two cases. For all these cases, the relations between these frames are stated, respectively. Moreover, the derivative formulas EM wave vectors are stated by means of geometric phase. Furthermore, the necessary and sufficient conditions provided by the geometric phase are expressed for EM wave vectors to be parallel transportation of the pseudo null frame. Finally, an application is given to investigate the obtained results.


Determination of nelfinavir free drug concentrations in plasma by equilibrium dialysis and liquid chromatography/tandem mass spectrometry: important factors for method optimization.
A method was developed and validated for measuring the free fraction of nelfinavir in plasma employing equilibrium dialysis for the separation of free (unbound) drug and liquid chromatography/tandem mass spectrometry for quantitation. Nelfinavir, widely used to treat HIV infection, is a highly bound HIV protease inhibitor with the fraction bound in plasma being greater than 98%. Thus variations in the free fraction may be clinically important when interpreting total drug concentrations. Optimization of the method was carried out considering the influence of sample matrix and physicochemical and absorptive properties of nelfinavir. Nelfinavir free fraction averaged 0.41 +/- 0.094, 0.43 +/- 0.087 and 0.41 +/- 0.063% at nelfinavir plasma concentrations of 1000, 2000 and 3000 ng/ml, respectively. Free nelfinavir concentrations were underestimated with this assay by approximately 25% because of unavoidable losses to adsorption. However, the adsorptive loss was reproducible and consistent across the concentration range of the assay. Within-day and between-day precisions ranged from 6.0 to 9.4% and 15.2 to 27.3%, respectively. The lower limit of quantitation of the unbound concentration of nelfinavir was 1.0 ng/ml, permitting analysis of samples with total concentrations of nelfinavir in plasma that are > or = 400 ng/ml. This developed method proves reproducible and sensitive and its application to patient plasma samples is also reported.


Responses of single units in laminae 2 and 3 of cat spinal cord.
333 units were recorded in laminae 2 and 3 of lumbar cord in decerebrate cats. Recording of small-amplitude spikes was made possible by the use of platinum-surfaced tungsten microelectrodes, continuously variable filters and an analogue delay line display. Stimulation of the lateral Lissauer tract showed that a sample of the units sent axons into this tract. Using iron-plated electrodes, recording sites were marked and shown to be within laminae 2 and 3. Axons of peripheral afferent axons were excluded from the sample, as were long-range descending axons. By using one electrode placed close to a cell body in lamina 4 and a roving electrode in the dendritic region dorsal to the cell body, it was possible to show that the recorded units were not field spread of deeper cells. Of the units 94% had peripheral receptive fields, RF; 30% had small RFs less than 2 sq.cm, intermediate in size between RFs of peripheral axons and RFs of large cells in dorsal horn. These small RF cells occurred in clusters and their RFs constituted a fraction of the larger RF of nearby large cells. Of the units 56% responded to brush and touch, 19% to brush, touch and pressure, while 19% required pressure on skin to excite them. Latency of response to electrical stimulation showed that all cells were excited by myelinated afferents. While no cells were detected exclusively by C afferents, many may have been excited by both A and C afferents. Eighteen per cent of the cells showed a prolonged discharge lasting more than 5 sec after a single stimulus. Some of these long discharge cells continued firing for minutes. Another unusual class, 14% of all cells, habituated very powerfully to intermittant natural or electrical stimuli, and remained unresponsive for many seconds after responding to the first stimulus.


Comparison of circulating lipid profiles, D-dimer and fibrinogen levels between hypertensive patients with and without stroke.
Stroke is one of the leading causes of global mortality and disability, particularly in hypertensive patients. This study aimed to compare lipid profile, fibrinogen, and D-dimer levels between hypertensive patient with and without stroke. This was a facility-based cross-sectional study conducted from November 2022 to January 2023 among 115 hypertensive patients (70 patients without stroke and 45 with stroke) who had follow-up at Yikatit 12 Hospital Medical College, Ethiopia. All data analyses were done using SPSS version 25.0 and comparisons of variables between groups were made using the Chi-square test, independent sample t-test, and Mann-Whitney U test. Multiple logistic regression analysis was done to identify predictors of stroke among hypertensive patients. A p-value <0.05 was assumed to be statistically significant for all statistical tests. Significantly elevated levels of TC, LDL-C, D-DI, and fibrinogen were observed in the stroke group than in the non-stroke group (p-value<0.05). The mean values of TC, D-DI, and fibrinogen were significantly higher in patients with ischemic stroke compared to those with hemorrhagic stroke. Duration of hypertension (AOR: 1.21; CI: 1.10, 2.09), TC (AOR:1.07; CI: 1.01, 1.22), D-DI (AOR: 1.15; CI: 1.05, 1.69) and fibrinogen (AOR:1.19; CI: 1.10, 2.89) were identified to be independent predictors of stroke in hypertensive patients. The circulating levels of TC, LDL-C, D-DI and fibrinogen in hypertensive patients with stroke were significantly higher than in those without stroke. But only TC, D-DI, and fibrinogen were found to be predictors of stroke in hypertensives. Considerably higher TC, D-DI, and fibrinogen levels were also seen in patients with ischemic stroke than in those with hemorrhagic stroke. This confirms the key roles of dyslipidemia (hypercholesterolemia) and aberrant hemostatic activation to stroke development, notably ischemic stroke.


Isolation and Culture of Primary Retinal Ganglion Cells from Rodent Retina.
Primary retinal ganglion cell (RGC) cultures are widely used for evaluating the neuroprotective and neurogenic effects of candidate compounds. The axons of RGCs make up the optic nerve and are responsible for transmitting electrochemical signals to the brain. As the retina is an outgrowth of the brain, both it and the optic nerve are part of the central nervous system (CNS). In the process of culturing RGC, the eye and retina are dissected, meaning the RGC, disconnected from the brain, degenerate without intervention due to the traumatic damage they have endured. Therefore, this in vitro model is invaluable for investigating the CNS therapeutics. Here, we present a protocol for the isolation and culture of primary RGCs from rodent retina.


CRISPR interference to interrogate genes that control biofilm formation in Pseudomonas fluorescens.
Bacterial biofilm formation involves signaling and regulatory pathways that control the transition from motile to sessile lifestyle, production of extracellular polymeric matrix, and maturation of the biofilm 3D structure. Biofilms are extensively studied because of their importance in biomedical, ecological and industrial settings. Gene inactivation is a powerful approach for functional studies but it is often labor intensive, limiting systematic gene surveys to the most tractable bacterial hosts. Here, we adapted the CRISPR interference (CRISPRi) system for use in diverse strain isolates of P. fluorescens, SBW25, WH6 and Pf0-1. We found that CRISPRi is applicable to study complex phenotypes such as cell morphology, motility and biofilm formation over extended periods of time. In SBW25, CRISPRi-mediated silencing of genes encoding the GacA/S two-component system and regulatory proteins associated with the cylic di-GMP signaling messenger produced swarming and biofilm phenotypes similar to those obtained after gene inactivation. Combined with detailed confocal microscopy of biofilms, our study also revealed novel phenotypes associated with extracellular matrix biosynthesis as well as the potent inhibition of SBW25 biofilm formation mediated by the PFLU1114 operon. We conclude that CRISPRi is a reliable and scalable approach to investigate gene networks in the diverse P. fluorescens group.


Clinical issues facing pouch patients: an introduction to a special issue on the ileal pouch.
For over 40 years, restorative proctocolectomy has been used in patients with ulcerative colitis or familial adenomatous polyposis undergoing proctocolectomy. Radiologists are now encountering an increasing number of patients with an ileal pouch and therefore need to understand the clinical issues and concerns in these patients. This review is the introduction of a special issue on the ileal pouch and was written with both surgeon and gastroenterology input. The intent is to assist the radiologist in understanding the clinical questions posed by both the patients and their physicians. Subsequent sessions will address specific imaging modalities and techniques, how the gastroenterologists and surgeons address issues with these patients, and a final session summarizing the sessions and speculating on future investigations and approaches.


[Preliminary results of studies on the incidence, causes and effects of occupational accidents in the Bełchatów Industrial Region. III. Health effects of occupational accidents].
Health effects of accidents at work at the Bełchatów Industrial District have been investigated. Most injuries due to accidents have been bruises, wounds and bone fractures of upper and lower limbs. Much less frequent, as compared to other industrial plants, are injuries of head, chest and abdomen. The causes of those injuries have been discussed. In addition, the activities of occupational health services have been analysed.


Changes in the expression of four heat shock proteins during the aging process in Brachionus calyciflorus (rotifera).
Heat shock proteins (HSPs) are molecular chaperones and have an important role in the refolding and degradation of misfolded proteins, and these functions are related to aging. Rotifer is a useful model organism in aging research, owing to small body size (0.1-1 mm), short lifespan (6-14 days), and senescence phenotypes that can be measured relatively easily. Therefore, we used rotifer as a model to determine the role of four typical hsp genes on the aging process in order to provide a better understanding of rotifer aging. We cloned cDNA encoding hsp genes (hsp40, hsp60, hsp70, and hsp90) from the rotifer Brachionus calyciflorus Pallas, analyzed their molecular characteristics, determined its modulatory response under different temperatures and H2O2 concentrations and investigated the changes in expression of these genes during the aging process. We found that Bchsp70 mRNA expression significantly decreased with aging. In addition, we also studied the effects of dietary restriction (DR) and vitamin E on rotifer lifespan and reproduction and analyzed the changes in expression of these four Bchsp genes in rotifers treated with DR and vitamin E. The results showed that DR extended the lifespan of rotifers and reduced their fecundity, whereas vitamin E had no significant effect on rotifer lifespan or reproduction. Real-time PCR indicated that DR increased the expression of these four Bchsps. However, vitamin E only improved the expression of Bchsp60, and reduced the expression of Bchsp40, Bchsp70, and Bchsp90. DR pretreatment also increased rotifer survival rate under paraquat-induced oxidative stress. These results indicated that hsp genes had an important role in the anti-aging process.


Effects of sazetidine-A, a selective α4β2* nicotinic receptor desensitizing agent, on body temperature regulation in mice and rats.
Nicotine-induced hypothermia is well established, but the nicotinic receptor actions underlying this effect are not clear. Nicotine causes activation and desensitization at a variety of nicotinic receptor subtypes. Sazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] is a novel compound that potently and selectively desensitizes α4β2* nicotinic receptors. The main goal of this study was to investigate the effects of sazetidine-A, on core body temperature (Tc) in mice and rats. Sazetidine-A effects on Tc and the interactions of sazetidine-A with nicotine and selective nicotinic antagonists were investigated to determine the receptor actions underlying nicotine-induced hypothermia. Adult male mice were injected with different dose of nicotine (0.2, 0.4 and 0.8 mg/kg), sazetidine-A (0.3, 1, and 3mg/kg), a mixture of nicotine (0.4 or 0.8 mg/kg) and sazetidine-A (0.3 or 0.6 mg/kg) or saline and Tc was monitored telemetrically. In another set of experiments, the interaction between sazetidine-A and dihydro-β-erythroidine (DHβE), an α4β2* nicotinic receptors antagonist, and methyllycaconitine (MLA), an α7 antagonist, was investigated. Tc of mice was monitored following DHβE (1, 3 and 6 mg/kg), a combination of DHβE (3mg/kg) and sazetidine-A (0.6 mg/kg), MLA (1.5, 3 or 6 mg/kg) or combination of MLA (6 mg/kg) and sazetidine (0.6 mg/kg) or saline. The acute effect of sazetidine-A (1, 3, and 6 mg/kg) on rats Tc was also studied. Acute sazetidine-A caused a pronounced and long-lasting hypothermia in mice; Tc decreased to about 28°C at 100 min and recovered within 230 min. The hypothermic effect of sazetidine in rats was much less in magnitude (about 3°C) and shorter in duration compared with that in mice. Nicotine co-administration with low doses of sazetidine potentiated the magnitude and duration of hypothermia in mice. The α4β2* nicotinic receptors antagonist DHβE significantly prolonged sazetidine-A-induced hypothermia but did not increase its depth. The α7 antagonist MLA caused a modest degree of hypothermia with relatively short duration in mice. MLA failed to counteract the sazetidine-A-induced hypothermia. Overall, our results show that pharmacological modulation of α4β2* nicotinic receptors elicits changes in body temperature that may involve desensitization of these receptors.


Self-learning adaptive traffic signal control for real-time safety optimization.
Adaptive traffic signal control (ATSC) is a promising technique to improve the efficiency of signalized intersections, especially in the era of connected vehicles (CVs) when real-time information on vehicle positions and trajectories is available. Numerous ATSC algorithms have been proposed to accommodate real-time traffic conditions and optimize traffic efficiency. The common objective of these algorithms is to minimize total delay, decrease queue length, or maximize vehicle throughput. Despite their positive impacts on traffic mobility, the existing ATSC algorithms do not consider optimizing traffic safety. This is most likely due to the lack of tools to evaluate safety in real time. However, recent research has developed various real-time safety models for signalized intersections. These models can be used to evaluate safety in real time using dynamic traffic parameters, such as traffic volume, shock wave characteristics, and platoon ratio. Evaluating safety in real time can enable developing ATSC strategies for real-time safety optimization. In this paper, we present a novel self-learning ATSC algorithm to optimize the safety of signalized intersections. The algorithm was developed using the Reinforcement Learning (RL) approach and was trained using the simulation platform VISSIM. The trained algorithm was then validated using real-world traffic data obtained from two signalized intersections in the city of Surrey, British Columbia. Compared to the traditional actuated signal control system, the proposed algorithm reduces traffic conflicts by approximately 40 %. Moreover, the proposed ATSC algorithm was tested under various market penetration rates (MPRs) of CVs. The results showed that 90 % and 50 % of the algorithm's safety benefits can be achieved at MPR values of 50 % and 30 %, respectively. To the best of the authors' knowledge, this is the first self-learning ATSC algorithm that optimizes traffic safety in real time.


Serum electrolytes, osmolality, and cleansing quality after bowel prep for colonoscopy with a PEG solution containing ascorbic acid and electrolytes.
The cleansing procedure with PEG 3350 + ascorbic acid (PEG + Asc; Moviprep®) requires the additional ingestion of clear liquids. We aimed to determine the effects on serum electrolytes, osmolality and cleansing quality, and in a prospective "real world" trial. Patients underwent a standardized split-dose bowel preparation for colonoscopy with PEG + Asc. Serum electrolytes and osmolality were measured before and after the prep procedure. The volume of prep solution (PA) and additional clear liquid (CL) was recorded. Prep quality was assessed using the Ottawa Bowel Prep Grading Scale (OBPS). The primary outcome measures were changes of serum electrolytes and osmolality during the cleansing procedure. A secondary end point was the OPBS. One hundred ninety-one of 219 patients entered the per protocol analysis. Prep quality was considered excellent in 57.6%, moderate in 20.9%, and insufficient in 21.5%. The number of patients with hyponatremia increased from 12 (6.3%) before to 25 (13.2%) after the prep procedure. Mean sodium concentration did not change significantly. The volume of CL correlated inversely with Na+ concentration (r = - 0.409, p < 0.01) and a worse OBPS (r = 0.198, p < 0.01). Bowel preparation with PEG-Asc in clinical routine is generally safe, but patients should be advised not to drink more than 2 l of clear liquid because of imminent electrolyte disturbances. Additionally, the quality of cleansing either remains unchanged or may even worsen.


Neimark-Sacker bifurcation of a two-dimensional discrete-time predator-prey model.
In this paper, we study the dynamics and bifurcation of a two-dimensional discrete-time predator-prey model in the closed first quadrant [Formula: see text]. The existence and local stability of the unique positive equilibrium of the model are analyzed algebraically. It is shown that the model can undergo a Neimark-Sacker bifurcation in a small neighborhood of the unique positive equilibrium and an invariant circle will appear. Some numerical simulations are presented to illustrate our theocratical results and numerically it is shown that the unique positive equilibrium of the system is globally asymptotically stable.


Evaluation of the dry mouth patient.
This paper examines the questions "who is the dry mouth patient and how is the dry mouth patient evaluated"? It reviews the clinical features of dry mouth. It presents current treatment options for dry mouth care.


Definitive hypofractionated radiation therapy for early stage breast cancer: Dosimetric feasibility of stereotactic ablative radiotherapy and proton beam therapy for intact breast tumors.
Few definitive treatment options exist for elderly patients diagnosed with early stage breast cancer who are medically inoperable or refuse surgery. Historical data suggest very poor local control with hormone therapy alone. We examined the dosimetric feasibility of hypofractionated radiation therapy using stereotactic ablative radiotherapy (SABR) and proton beam therapy (PBT) as a means of definitive treatment for early stage breast cancer. Fifteen patients with biopsy-proven early stage breast cancer with a clinically visible tumor on preoperative computed tomography scans were identified. Gross tumor volumes were contoured and correlated with known biopsy-proven malignancy on prior imaging. Treatment margins were created on the basis of set-up uncertainty and image guidance capabilities of the three radiation modalities analyzed (3-dimensional conformal radiation therapy [3D-CRT], SABR, and PBT) to deliver a total dose of 50 Gy in 5 fractions. Dose volume histograms were analyzed and compared between treatment techniques. The median planning target volume (PTV) for SABR, PBT, and 3-dimensional CRT was 11.91, 21.03, and 45.08 cm3, respectively, and were significantly different (P < .0001) between treatment modalities. Overall target coverage of gross tumor and clinical target volumes was excellent with all three modalities. Both SABR and PBT demonstrated significant dosimetric improvements, each in its own unique manner, relative to 3D-CRT. Dose constraints to normal structures including ipsilateral/contralateral breast, bilateral lungs, and heart were all consistently achieved using SABR and PBT. However, skin or chest wall dose constraints were exceeded in some cases for both SABR and PBT plans and was dictated by the anatomic location of the tumor. Definitive hypofractionated radiation therapy using SABR and PBT appears to be dosimetrically feasible for the treatment of early stage breast cancer. The anatomical location of the tumor relative to the skin and chest wall appears to be the primary limiting dosimetric factor.


The transcription factor Egr-1 is a regulator of the human TopBP1 gene.
The human topoisomerase IIbeta binding protein 1 (TopBP1) has been reported to be involved in DNA replication, in DNA damage checkpoints and in apoptosis. Detailed analysis of the TopBP1 promoter revealed that the early growth response protein-1 (Egr-1) induces this promoter. Binding of Egr-1 to the TopBP1 promoter was determined to region -50 to -18 using EMSA and ChIP technology. Furthermore, deletion of the E2F transcription factor binding sites or mutation of the Egr-1 transcription factor binding sites lead to reduced stimulation of the TopBP1 promoter by Egr-1. These data indicate a cooperative regulation of the TopBP1 promoter by Egr-1 and E2F.


A Mobile-Based Surgical Simulation Application: A Comparative Analysis of Efficacy Using a Carpal Tunnel Release Module.
The utilization of surgical simulation continues to grow in medical training. The TouchSurgery application (app) is a new interactive virtual reality smartphone- or tablet-based app that offers a step-by-step tutorial and simulation for the execution of various operations. The purpose of this study was to compare the efficacy of the app versus traditional teaching modalities utilizing the "Carpal Tunnel Surgery" module. We hypothesized that users of the app would score higher than those using the traditional education medium indicating higher understanding of the steps of surgery. A total of 100 medical students were recruited to participate. The control group (n = 50) consisted of students learning about carpal tunnel release surgery using a video lecture utilizing slides. The study group (n = 50) consisted of students learning the procedure through the app. The content covered was identical in both groups but delivered through the different mediums. Outcome measures included comparison of test scores and overall app satisfaction. Test scores in the study group (89.3%) using the app were significantly higher than those in the control group (75.6%). Students in the study group rated the overall content validity, quality of graphics, ease of use, and usefulness to surgery preparation as very high (4.8 of 5). Students utilizing the app performed better on a standardized test examining the steps of a carpal tunnel release than those using a traditional teaching modality. The study findings lend support for the use of the app for medical students to prepare for and learn the steps for various surgical procedures. This study provides useful information on surgical simulation, which can be utilized to educate trainees for new procedures.