Peyer's patch-involved gut microbiota facilitates anti-HBV immunity in mice.
Gut microbiota is crucial for immune homeostasis and is associated with the prognosis of chronic hepatitis B infection. Peyer's patches (PPs), characterized by intestinal mucosa localization, are involved in the gut microbiota-mediated immune response. However, whether and how PPs orchestrate gut microbiota-modulated anti-hepatitis B virus (HBV) response remain elusive. This study aims to elucidate the role of PPs in gut microbiota-mediated anti-HBV adaptive immunity. We investigated the effects of gut microbiota and PPs on adaptive immune responses by transcriptomic, phenotypic, and functional analyzes from an HBV mouse model with gut commensal microbiota and PP-depleting interventions. Depletion of gut microbiota impaired systemic adaptive immune responses, resulting in a delayed HBV antigen clearance. Differentially expressed genes analysis of PPs revealed that pathways related to adaptive immune responses were significantly downregulated in gut microbiota-deficient mice. Notably, the depletion of PPs could abolish gut microbiota-boosted intrahepatic HBV-specific T cell response, leading to a higher serum hepatitis B surface antigen level in mice. PPs orchestrate gut microbiota-mediated intrahepatic anti-HBV cellular immunity, underlining the significance of remote manipulating the "gut microbiota-PPs" axis for achieving optimum anti-HBV response.


Microbiome comparison of Dermanyssus gallinae populations from different farm rearing systems and the presence of common endosymbiotic bacteria at developmental stages.
The hematophagous arthropod, Dermanyssus gallinae (Poultry red mite, PRM) can cause remarkable economic losses in the poultry industry across the globe. Although overall composition of endosymbiotic bacteria has been shown in previous studies, how farm habitats influence the microbiome remains unclear. In the present study, we compared the bacterial communities of D. gallinae populations collected from the cage and free-range farms using next-generation sequences targeting the V3-V4 hypervariable region of the 16S rRNA gene. The QIIME2 pipeline was followed in bioinformatic analyses. Proteobacteria represented a great majority of the total bacterial community of D. gallinae from both farming systems. More specifically, Bartonella-like bacteria (40.8%) and Candidatus Cardinium (21.5%) were found to be predominant genera in free-range and cage rearing systems, respectively. However, the microbiome variation based on farming systems was not statistically significant. In addition, the presence of the five common endosymbiotic bacteria (Wolbachia, Cardinium, Rickettsiella, Spiroplasma, and Schineria) was screened in different developmental stages of D. gallinae. Cardinium was detected in all developmental stages of D. gallinae. On the other hand, Wolbachia and Rickettsiella were only found in adults/nymphs, but neither in the eggs nor larvae. To our knowledge, this study provides the first microbiome comparison at genus-level in D. gallinae populations collected from different farm habitats and will contribute to the knowledge of the biology of D. gallinae.


Dynamic beam shaping.
Computer control of independent collimator jaw positions and dose is combined with multiple-field summation techniques to design optimized radiation field profiles. Clinically relevant examples are shown for dynamic wedges and compensated mantle fields. Calculation, measurement, and verification techniques are discussed.


Effect of ethanol on spontaneous phasic contractions of cat gastric smooth muscle.
Ethanol is generally believed to inhibit extracellular Ca2+ influx, thereby inhibiting gastric muscle contraction. Recently, we observed that verapamil inhibited only the amplitude of spontaneous phasic contractions, whereas ethanol inhibited both amplitude and frequency. In our objective to investigate the mechanism of ethanol's inhibition of gastric motility, the involvement of various protein kinases in ethanol-inhibited spontaneous phasic contractions of the stomach muscle strips was tested. Circular muscle strips (2.0 x 0.2 cm) were prepared from the corpus of cat stomach in order to measure isometric contraction in a chamber filled with Krebs-Ringer solution (pH 7.4, temperature 36 degrees C) bubbled with 5% CO2 in O2. Spontaneous phasic contraction was not affected by various receptor antagonists (I microM atropine, 1 microM hexamethonium, 1 microM phentolamine and 1 microM propranolol) or 1 microM tetrodotoxin. EGTA and verapamil dose-dependently inhibited only the amplitude of spontaneous phasic contractions and not the frequency. Ethanol dose-dependently inhibited both the amplitude and frequency of phasic contractions. The amplitude and frequency of spontaneous phasic contractions were significantly inhibited by protein kinase C and tyrosine kinase inhibitors. However, neither protein kinase C activator nor various phosphatase inhibitors blocked the inhibitory effect of ethanol. Ethanol appears to inhibit spontaneous phasic contractions by a mechanism other than the inhibition of protein kinase C or tyrosine kinase or the inhibition of extracellular Ca2+ influx.


The Effects of Listening to Lullabies and Self-selected Music on Distress and Maternal Attachment in Pregnant Women: A Randomized Controlled Study.
Pregnant women may experience distress as a result of physical and psychosocial changes, and this distress affects the development of maternal attachment negatively. During pregnancy care and follow-up, reducing women's pregnancy-related distress and improving maternal attachment are important. To compare the effects of listening to lullabies and self-selected music in reducing distress and increasing maternal attachment in pregnant women. This study is a randomized controlled trial. It was conducted using power analysis for a type-I error rate of α = 0.05, type-II error rate of β = 0.20, representative power of 0.64, and effect size of 0.81. The study took place at a secondary care hospital in a provincial center in Turkey. The participants were 120 pregnant women who came to the outpatient clinic for pregnancy follow-ups between June 2021 and October 2021. The participants were allocated to one of three groups, with 40 women in each. For 30 minutes every day, for two weeks, the lullaby group (LG) only listened to lullaby records at home, and the multi-music group (MG) listened to self-selected music from different records; the control group (CG) did not listen to any music. The Prenatal Distress Questionnaire and the Maternal Antenatal Attachment Scale were used to collect data. Prenatal distress levels were lower in the intervention groups than in the CG (P < .01), and they were lower in the MG than in the LG (P < .05). Antenatal attachment levels were higher in the intervention groups than in the CG (P < .01), and they were higher in the LG than in the MG (P < .05). For pregnant women, listening to self-selected music was more effective in reducing distress, whereas listening to lullabies selected by the researcher was more effective in increasing attachment. NCT05228392.


Phosphopeptide profiling of receptor kinase mutants.
The family of transmembrane receptor kinase is the largest protein kinase family in Arabidopsis. However many of these kinases have yet uncharacterized functions and little is known about direct substrates of these kinases. Here, we present a large-scale phosphoproteomics method involving label-free quantitation-based comparative phosphopeptide profiling of knockout mutants in receptor-like kinases. This approach, among other physiological and cell biological experiments, is one step in understanding the functional roles of plant kinases in the context of their signaling networks.


Immunosuppressive activity of human chorionic gonadotrophin preparations in vivo: evidence for gonadal dependence.
Human chorionic gonadotrophin preparations (hCG), when injected ip daily for 4 days, suppress the delayed-type hypersensitivity (DTH) response of mice to sheep red blood cells. Preparations of crude hCG, purified hCG subunits, and hCG that was formed by recombining the purified subunits showed immunosuppressive activity in accord with their gonadotrophic activity. The immunosuppressive effects in male and female mice were comparable. However, removal of the gonads completely abrogated the immunosuppressive activity of hCG in both males and females, suggesting that the effect of hCG is mediated by a factor released from the gonads. We conclude that the hCG molecule itself exhibits immunosuppressive activity in vivo in both male and female mice and that the gonads are required for the expression of this activity.


Mutation Characteristics and Phylogenetic Analysis of Five Leishmania Clinical Isolates.
Leishmaniasis is a neglected tropical disease threatening millions of people worldwide. The emergence of antimony-resistant Leishmania strains have brought difficulties to the treatment and elimination of leishmaniasis. This study performed genome sequencing, phylogenetic analysis and mutation analysis of five Leishmania clinical isolates, especially the Leishmania strain L_HCZ isolated in 2016, which shows strong virulence and antimony resistance. By phylogenetic analysis, four isolates (L_DD8, L_801, L_Liu and L_9044) were identified as Leishmania donovani, the isolate L_HCZ was identified as Leishmania infantum and the isolate L_DD8 as a standard strain of L.donovani. Genome-wide mutation analysis was applied to identify mutations related to the drug resistance and virulence of the newly isolated L_HCZ. Compared with the other four Leishmania isolates, L_HCZ had the most mutations in genes associated with antimony resistance, including the ABC transporter, ascorbate-dependent peroxidase, gamma-glutamylcysteine synthetase, glucose-6-phosphate 1-dehydrogenase, ATP-binding cassette protein subfamily A and multi-drug resistance protein-like genes. Among the genes associated with virulence, L_HCZ had the most mutations in cysteine peptidase A, cysteine peptidase B, cysteine peptidase C, heat-shock protein 70, gp63, acid phosphatase, kinesin k39, kinesin, phosphoglycan beta 1, amastin-like surface protein and amastin-like proteins. The mutations in L_HCZ might possibly contribute to its antimony resistance and strong virulence in clinical patients. Whole-genome resequencing has exhibited broad application prospects and may be put into clinical use in the future for parasite identifying and epidemiological investigations.


Synthetic vaccines.
Synthetic vaccines are designed with the help of computer-graphics programs. These displays generated by Arthur J. Olson of the Research Institute of Scripps Clinic show a method whereby parts of a viral protein that are on the surface of a virus, and therefore accessible to antibodies, can be identified. The backbone of the surface domain of the protein on the outer shell of the tomato bushy-stunt virus is displayed (1) on the basis of coordinates determined by Stephen C. Harrison of Harvard University and his colleagues. A single peptide of the protein is picked out in yellow, with the side chains of its component amino acids indicated in atomic detail (2). The peptide is enlarged and a sphere representing a water molecule is displayed (3). The sphere is rolled around the peptide to generate a map of the surface accessible to water (4); it does so, following an algorithm developed by Michael L. Connolly, by placing a dot at each point of its closest contact with the peptide, taking account of the sphere's own van der Waals radius (zone of influence, in effect) and that of each atom of the peptide and the rest of the protein. A similar-dot-surface map is generated to show what parts of the peptide are still accessible to water when three copies of the protein are associated in an array on the surface of the virus (5) and when four such arrays (out of 60) are in position on the outer surface of the virus (6).


Chronic Pain: Prevalence and Management.
Chronic pain is a distinct complication that profoundly affects the lives of individuals with sickle cell disease (SCD). Chronic SCD pain emerges with increasing age and is very prevalent in adults. The pathophysiology of chronic SCD pain is likely distinct from acute SCD pain and therefore needs a different treatment approach. Clinical trials evaluating the treatment of chronic SCD pain are lacking and treatment currently relies on evidence from other chronic pain conditions. Continued investigations into the underlying causes of chronic SCD pain are needed, and clinical trials focused on chronic pain therapy are imperative.


Preduodenal portal vein, malrotation, and high jejunal atresia: a case report.
Preduodenal portal vein (PDPV) is a rare congenital anomaly. In most patients, it is associated with other congenital defects including situs inversus, malrotation, and biliary atresia or occurs as part of the heterotaxia syndrome or polysplenia syndrome. We describe a newborn affected by high jejunal atresia, malrotation, and a complex cardiac anomaly, in whom PDPV was diagnosed at early relaparotomy because of stenosis of the jejunal anastomosis. Occurrence of PDPV with intestinal atresia has not been previously reported in the literature.


Life-cycle preferences over consumption and health: a comment on Bleichrodt and Quiggin.
In a recent issue of the Journal of Health Economics, Bleichrodt and Quiggin (1999) developed a model of life-cycle preferences over consumption and health to analyze QALY-based decision making. This analysis is critically appraised concerning issues of QALY-maximization on an individual and on an aggregate level as well as of the role of death in QALY-models. It is concluded that a more general approach might be useful for the analysis of QALYs and life-cycle preferences over consumption and health.


Insight into the interactions between novel isoquinolin-1,3-dione derivatives and cyclin-dependent kinase 4 combining QSAR and molecular docking.
Several small-molecule CDK inhibitors have been identified, but none have been approved for clinical use in the past few years. A new series of 4-[(3-hydroxybenzylamino)-methylene]-4H-isoquinoline-1,3-diones were reported as highly potent and selective CDK4 inhibitors. In order to find more potent CDK4 inhibitors, the interactions between these novel isoquinoline-1,3-diones and cyclin-dependent kinase 4 was explored via in silico methodologies such as 3D-QSAR and docking on eighty-one compounds displaying potent selective activities against cyclin-dependent kinase 4. Internal and external cross-validation techniques were investigated as well as region focusing, bootstraping and leave-group-out. A training set of 66 compounds gave the satisfactory CoMFA model (q2 = 0.695, r2 = 0.947) and CoMSIA model (q2 = 0.641, r2 = 0.933). The remaining 15 compounds as a test set also gave good external predictive abilities with r2pred values of 0.875 and 0.769 for CoMFA and CoMSIA, respectively. The 3D-QSAR models generated here predicted that all five parameters are important for activity toward CDK4. Surflex-dock results, coincident with CoMFA/CoMSIA contour maps, gave the path for binding mode exploration between the inhibitors and CDK4 protein. Based on the QSAR and docking models, twenty new potent molecules have been designed and predicted better than the most active compound 12 in the literatures. The QSAR, docking and interactions analysis expand the structure-activity relationships of constrained isoquinoline-1,3-diones and contribute towards the development of more active CDK4 subtype-selective inhibitors.


Chlorobisphenol A activated kisspeptin/GPR54-GnRH neuroendocrine signals through ERα and GPER pathway in neuronal GT1-7 cells.
Chlorobisphenol A (ClxBPA) is a kind of novel estrogenic compounds. The present study aims to investigate the effects of three ClxBPA compounds on the kisspeptin/G protein-coupled receptor 54 (GPR54, also named KissR1)-gonadotropin-releasing hormone (GnRH) (KGG) system in neuronal GT1-7 cells with mechanistic insights by estrogen receptor signaling pathways. The study demonstrated that low-concentration ClxBPA induced the cell proliferation, promoted GnRH secretion, upregulated the expression of KGG neuroendocrine signal-related proteins (KissR1, GnRH1 and kisspeptin) and genes including Kiss1, GnRH1, KissR1, luteinizing hormone receptor (Lhr) and follicle-stimulating hormone receptor (Fshr) in GT1-7 cells. Additionally, ClxBPA activated nuclear estrogen receptor alpha (ERα) and member estrogen receptor G protein-coupled estrogen receptor (GPER)-regulated phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) and extracellular signal-regulated kinase (Erk1/2) signaling pathways. Pretreatment of GT1-7 cells with GPER inhibitor G15 and ERα inhibitor ICI reduced the expression of KissR1, GnRH1 and kisspeptin proteins, attenuated mRNA levels of Kiss1, GnRH1, KissR1, Fshr and Lhr genes, and decreased ClxBPA-induced GT1-7 cell proliferation. The results suggested that ClxBPA activated the KGG neuroendocrine signals and induced the proliferation of GT1-7 cells via ERα and GPER signaling pathways. This study provides a new perspective to explore the neuroendocrine toxicity mechanism of ClxBPA. CAPSULE: ClxBPA activated KGG neuroendocrine signaling pathway via ERα and GPER and induced the proliferation of GT1-7 cells.


Real-world Global Outcomes of Retrograde Intrarenal Surgery in Anomalous Kidneys: A High Volume International Multicenter Study.
To analyze the trends and outcomes of retrograde intrarenal surgery for treatment of urolithiasis in anomalous kidneys in a large international multicenter series. We designed a multicentric retrospective study. Nineteen high-volume centers worldwide were included. Pre-, peri- and postoperative data were collected, and a subgroup analysis was performed according to renal anomaly. We analyzed 414 procedures: 119 (28.7%) were horseshoe kidneys, 102 (24.6%) pelvic ectopic kidneys, 69 (16.7%) malrotated kidneys and 50 (12.1%) diverticular calculus. The average size (SD) of the stone was 13.9 (±6) millimeters and 193 (46.6%) patients had a pre-operative stent. In 249 cases (60.1%) a disposable scope was used. A UAS (ureteral access sheath) was used in 373 (90%) patients. A Holmium laser was used in 391 (94.4%) patients. The average (SD) operating time was 65.3 (±24.2) minutes. Hematuria, caliceal perforation and difficulty in stone localisation were mostly seen in diverticular stones and difficulty in UAS placement and lithotripsy in the cases of renal malrotation. The overall complication rate was 12%. Global stone-free rate was 79.2%. Residual fragments (RF) were significantly lesser in the pre-stented group (P <.05). Diverticular calculi was the group with more RF and needed ancillary procedures (P <.05). Retrograde intrarenal surgery in patients with anomalous kidneys is safe and effective with a high single-stage stone-free rate and low complication rate. There is a trend toward using smaller and disposable scopes and smaller UAS. Diverticular stones can still be challenging with higher rates of intraoperative hematuria, caliceal perforation and RF.


Tanita foot-to-foot bioelectrical impedance analysis system validated in older adults.
Simple, accurate, and noninvasive methods for assessing body composition are needed in many clinical, community, and research settings. The foot-to-foot bioelectrical impedance analysis (BIA) system may be one method of addressing those needs. The objective of this study was to determine the validity of a foot-to-foot BIA system for body-composition assessment of older adults. Subjects 55 years of age or older without functional limitations or cognitive impairments (N=50) were measured using both the Tanita foot-to-foot system (Tanita Corporation of America, Inc, Arlington Heights, IL) and traditional hand-to-foot BIA. The correlation for percent body fat measurements between the Tanita and traditional BIA was r=0.84 (P<.001). Percent body fat estimates from both BIA measures were significantly correlated with waist circumference, body mass index, and age (all P<.01). The Tanita BIA system provides a valid measure of percent body fat in older adults, and could be a convenient and practical approach for assessment in public health settings.


Implantation: can immunological parameters of implantation failure be of interest for pre-eclampsia?
We restate briefly why we consider that the Th1/Th2 paradigm, as useful as it has been, is now no longer adequate and is obsolete. We take as an example the role of IL-18, abortifacient at high doses but cardinal for the control of natural killer (NK) cell effects on spiral artery remodelling in mice, and likely also in humans. We then describe briefly our recent studies on cytokine defects and implantation failure in humans, a key feature being the link between uterine cytokine dysregulation and abnormal uterine vascular scores. We draw lessons for preeclampsia, and describe features of a model for its immune aetiology.


Superior turbinate eosinophilia correlates with olfactory deficit in chronic rhinosinusitis patients.
To evaluate if molecular markers of eosinophilia in olfactory-enriched mucosa are associated with olfactory dysfunction. Cross-sectional study of tissue biopsies from 99 patients, and an additional 30 patients who underwent prospective olfactory testing prior to sinonasal procedures. Tissue biopsies were processed for analysis of inflammatory markers using quantitative real time polymerase chain reaction (qRT-PCR). Ipsilateral olfactory performance was assessed using the Sniffin' Sticks (Burghart, Wedel, Germany) threshold component and the University of Pennsylvania Smell Identification Test (Sensonics, Haddon Heights, NJ). Age-adjusted data was correlated with inflammatory marker expression and clinical measures of obstruction from computed tomography and endoscopy. Gene expression of the eosinophil marker CLC (Charcot Leyden crystal protein) was elevated in superior turbinate (ST) tissue in chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) compared to ST and inferior turbinate tissue in CRS without nasal polyps (CRSsNP) and control patients (all P < 0.001, respectively). CLC in ST tissue was correlated with IL-5 and eotaxin-1 expression (all P < 0.001; P = 0.65, and 0.49, respectively). CLC expression was strongly correlated with eosinophilic cationic protein levels (P < 0.001; r = -0.76), and ST CLC expression was inversely related to olfactory threshold (P = 0.002, r = -0.57) and discrimination scores (P = 0.05, r = -0.42). In multiple linear regression of CLC gene expression, polyp status, and radiographic and endoscopic findings with olfactory threshold, CLC was the only significantly correlated variable (P < 0.05). Markers of eosinophils are elevated in the ST of patients with CRSwNP and correlate with olfactory loss. These findings support the hypothesis that olfactory dysfunction in CRS correlates local eosinophil influx into the olfactory cleft. NA. Laryngoscope, 127:2210-2218, 2017.


In vitro screening of new drugs and analogues--specificity and selectivity.
The use of human tumors for in vitro evaluation of new drugs and analogues is currently receiving widespread attention. Results from initial preclinical studies have definitely provided the impetus for continuing such investigations, refining the methodologies and establishing larger series of cell lines from biopsies so as to increase the validity of attempts to define tumour types most responsive to active new agents or specific drug combinations.


Enzyme production by industrially relevant fungi cultured on coproduct from corn dry grind ethanol plants.
Distillers dried grain with solubles (DDGS) is the major coproduct produced at a dry grind ethanol facility. Currently, it is sold primarily as a ruminant animal feed. DDGS is low cost and relatively high in protein and fiber contents. In this study, DDGS was investigated as carbon source for extracellular hydrolytic enzyme production. Two filamentous fungi, noted for their high cellulolytic and hemicellulolytic enzyme titers, were grown on DDGS: Trichoderma reesei Rut C-30 and Asper gillus niger NRRL 2001. DDGS was either used as delivered from the plant (untreated) or after being pretreated with hot water. Both microorganisms secreted a broad range of enzymes when grown on DDGS. Higher xylanase titers were obtained when cultured on hot water DDGS compared with growth on untreated DDGS. Maximum xylanase titers were produced in 4 d for A. niger and 8 d for T. reesei in shake flask cultures. Larger amounts of enzymes were produced in bioreactors (5 L) either equipped with Rushton (for T. reesei) or updraft marine impellers (A. niger). Initial production titers were lower for bioreactor than for flask cultures, especially for T. reesei cultures. Improvement of enzyme titers were obtained using fed-batch feeding schemes.


Evaluation of a modified TCLP methodology for RCRA toxicity characterization of computer CPUs.
A leaching method similar to the toxicity characteristic leaching procedure (TCLP) was designed and evaluated for testing of bulky wastes, such as discarded electronic devices. The objective was to meet the intent of the TCLP (same leaching solution, liquid-to-solid ratio and same leaching time) but to allow more representative and rapid testing. The procedure was evaluated by examining lead leaching from computer CPUs as a test case; disassembled CPUs were leached in their entirety (or close to entirety) in a large vessel using a drum rotator. The difference in rotation speed between the large-scale test and the TCLP was found to have no statistical impact on lead leaching. The lack of size reduction resulted in less reducing conditions than the standard TCLP (because of increased iron and zinc leaching), and this resulted in greater lead leaching. For electronic wastes with large amounts of steel, the large-scale procedure provides a more conservative estimate of TCLP lead leaching. The large-scale procedure greatly reduces sample processing effort but does increase the cost of analysis. Evaluation of this approach by the regulatory community is important as the CPUs tested here tended to leach lead at greater than the toxicity characteristic (TC) limit (5 mg/L) using the large-scale test, but less than the TC limit using the standard TCLP.


Upmodulation by estrogen of HLA class I expression in breast tumor cell lines.
The expression of major histocompatibility complex (MHC) class I antigens was studied in five breast carcinoma cell lines before and after treatment with 17-beta estradiol. Increased HLA class I antigen expression correlated with the presence of estrogen receptors. The modulation of expression appeared to be mediated by transcriptional mechanisms, as revealed by class I mRNA levels. To elucidate the basis of MHC class I upregulation, we examined transcriptional factor binding activity to the class I regulatory element (CRE). Our results showed that 17-beta estradiol induced increases in factor binding activity to the CRE II probe, and decreases to the CRE I probe. In addition, our results suggested that factors that bind the CRE I region may modulate the binding of CRE II. Binding to CRE II was significantly increased in extracts pretreated with a competitor that contained the CRE I sequence, and that bound NF-kB/kBF1. In addition, induction of NF-kB binding activity by the tumor necrosis factor was accompanied by a decrease in nuclear factors that bind to the CRE II region.


Sports & exercise related traumatic brain injury in the Republic of Ireland - The neurosurgical perspective.
While the concerns regarding the long-term cognitive effects of repeated sports related head injury have become a major source of debate, it is not uncommon for these patients to require neurosurgical interventions in the acute setting. The aim of this study was to provide a unique insight into the acute nature and neurosurgical management of sports and exercise related traumatic brain injury. We retrospectively analysed electronic records of all referrals made between July 2016 and December 2018 to the National Neurosurgical Centre at Beaumont Hospital to identify instances of sport and exercise related traumatic brain injuries (TBI). A sub-group analysis was carried out on patients transferred to the tertiary centre requiring neurosurgical/neuro-critical care. Over the 30-month period, 194 patients (mean age: 36) were referred withsports and exercise related TBI, of which 56 were transferred to our unit (26 adults, 30 paediatrics). The most frequently encountered sporting activities were cycling, gaelic football, horse riding and rugby. Injuries included cerebral contusions, subdural haematomas, extradural haematomas and skull fractures. Neurosurgical intervention via intracranial pressure monitoring (ICP), decompressive craniectomy and elevation of depressed skull fracture was required in 28 out of 194 patients (14.4%). 85.7% (n = 48) of patients had a discharge Glasgow Coma Scale (GCS) of 15. 4 patients had a tracheostomy in place at discharge and there were 4 mortalities. Sports and exercise activities, ranging from contact team sports to individual activities, are a common cause of traumatic brain injury and maybe associated with a significant morbidity and mortality.


Neuronavigation-guided endoscopic endonasal excision of an intraorbital intraconal cavernous hemangioma.
A 50-year-old man presented with the complaints of gradual decrease of visual acuity in his left eye since 2 years. Brain magnetic resonance imaging revealed a left intraorbital intraconal round mass lesion consistent with cavernous hemangioma. Binostril endoscopic endonasal approach was performed with the aid of neuronavigation. The lesion was well capsulated and easily dissected and resected totally without complication. Early postoperative course was uneventful. Three-month follow-up after surgery revealed that the visual acuity and visual fields of the patient were normalized, and magnetic resonance imaging demonstrated total excision of the lesion.


Photodynamic therapy in the management of potentially malignant and malignant oral disorders.
Photodynamic therapy (PDT) is a minimally-invasive surgical tool successfully targeting premalignant and malignant disorders in the head and neck, gastrointestinal tract, lungs and skin with greatly reduced morbidity and disfigurement. The technique is simple, can commonly be carried out in outpatient clinics, and is highly acceptable to patients. The role of photodynamic therapy in the management of oral potentially malignant disorders and early oral cancer is being discussed.


Strain-gauge venous occlusion plethysmography: An objective and non-invasive approach to the evaluation of venous hemodynamics in patients with acute deep-vein thrombosis undergoing post-pharmacomechanical thrombolysis.
Strain-gauge venous occlusion plethysmography (SGVOP) is a means of acquiring hemodynamic data non-invasively, unlike other methods used routinely for the diagnosis and follow-up of venous diseases. The present study compares the plethysmographic data with early- and mid-term routine data of patients with acute deep-vein thrombosis (DVT) who underwent pharmacomechanical thrombolysis. Included in this retrospective study were 118 patients with acute DVT, who underwent pharmacomechanical thrombolysis between February 2018 and July 2019. Pre- and post-procedure follow-up data including CIVIQ-20 (quality of life), VCSS (Venous Clinical Severity Score), D-Dimer, Doppler USG results, venous capacity (VC), and venous outflow (VO) obtained by SGVOP were recorded and compared. In all 118 (100%) patients who underwent the procedure, early- and mid-term patency was seen to have been provided on Doppler USG follow-up, and various degrees of venous insufficiency were identified. A statistically significant improvement was observed in VCSS, CIVIQ-20, D-Dimer, VO, and VC measurements, although when the discrepancies between CIVIQ-20 and plethysmographic measurements were examined individually during the 6-month follow-up, nine (13.1%) patients were identified with comorbidities. Pharmacomechanical thrombolysis is an effective treatment approach for patients with acute DVT. Providing non-invasive objective data supporting the diagnosis and follow-up of venous diseases, the SGVOP approach offers significant benefits and should be considered more frequently as a viable therapy.


Walk this way.
The neural mechanisms that decide when and where to walk are not well understood. In this issue of Neuron, Felsen and Mainen use an olfactory-guided orienting task to show that the superior colliculus is necessary in rodents for the normal execution of spatial locomotor choices.


Solid-phase synthesis of 3,4-dihydro-1H-pyrimidine-2-ones using sodium benzenesulfinate as a traceless linker.
The facile preparation of 3,4-dihydropyrimidine-2-one derivatives with traceless solid-phase sulfone linker strategy is described. Key steps involved in the solid-phase synthetic procedure include (i) sulfinate acidification, (ii) condensation of urea or thiourea with aldehydes and sulfinic acid, and (iii) traceless product release via a one-pot cyclization-dehydration process. A library of 18 compounds was synthesized.


Mechanical vs Bioprosthetic Aortic Valve Replacement in Patients Younger Than 70 Years of Age: A Hazard Ratio Meta-analysis.
The choice between mechanical valves (MVs) and bioprosthetic valves (BVs) in patients undergoing aortic valve surgery is complex, requiring a balance between the inferior durability of BV and the indicated long-term anticoagulation therapy with MV. This is especially challenging in the middle age group (< 70 years), which has seen an increased use of BV over recent years. A meta-analysis of randomised controlled trials (RCTs), observational studies using propensity score matching (PSM) and inverse probability weighting (IPW) was conducted to examine the clinical outcomes of patients < 70 years of age undergoing aortic valve replacement. The primary outcome was overall long-term mortality. Secondary outcomes included bleeding events, reoperation, systemic thromboembolism, and cerebrovascular accident. Fifteen studies (1 RCT, 12 PSM studies, and 2 IPW studies; aggregated sample size 16,876 patients) were included. Median follow-up was 7.8 years. Mortality was higher with BVs vs MVs (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.00-1.49), as was reoperation (HR 3.05, 95% CI 2.22-4.19). Bleeding risk was lower with BVs (HR 0.58, 95% CI 0.48-0.69), and the risk of stroke was similar in both valve types (HR 0.96, 95% CI 0.83-1.11) CONCLUSIONS: This broadest meta-analysis comparing BV and MV suggests a survival benefit for MVs in patients < 70 years of age. This should lead to reassessment of current patterns used in the choice of valves for patients < 70 among the cardiothoracic surgery community.


Diagnosis of tuberculous meningitis by detection of immunoglobulin G antibodies to purified protein derivative and lipoarabinomannan antigen in cerebrospinal fluid.
Enzyme-linked immunosorbent assay of immunoglobulin G (IgG) activity in cerebrospinal fluid (CSF) and sera was conducted prospectively in 27 patients with tuberculous meningitis (TBM) by using purified protein derivative (PPD) and lipoarabinomannan (LAM) antigens, from January 1989 to August 1990. 29 patients with aseptic meningitis and 49 patients with non-inflammatory neurological illnesses served as controls. All patients had a computed tomography (CT) scan of the head before a lumbar puncture. The IgG antibodies to the antigens were significantly elevated in TBM, and the reactivity was more frequently positive in the CSF than in the sera, suggesting a local synthesis of IgG in the central nervous system (CNS). The sensitivity and the specificity for the diagnosis of TBM were 59.2% and 93.9% for PPD antigen, and 85.2% and 95.9% for LAM antigen, respectively. Assay of IgG reactivity to LAM antigen was clinically very useful for the early diagnosis of TBM and was superior to PPD for detecting the serological evidence of TBM.


Microbial community growth and utilization of carbon constituents during thermophilic composting at different oxygen levels.
Composting is characterized by dramatic changes in microbial community structure, to a high extent driven by changes in temperature and in the composition of the organic substrate. This study focuses on the interrelationships between decomposition of major classes in the organic material and dynamics in microbial populations during thermophilic composting of source-separated organic household waste. Experiments were performed in a 200-L laboratory reactor at 16, 2.5, and 1% O(2) in the compost atmosphere. Major classes of carbon constituents were analyzed by chemical methods, and the microbial biomass and community structure determined by fatty acid analyses with phospholipid fatty acids (PLFA) and total ester-linked fatty acids (EL) methods. At all three O(2) levels, the process was characterized by a rapid increase in microbial activity and biomass in the early thermophilic phase, although this period was delayed at the lower O(2) concentrations. Starch and fat were the main substrates utilized at all three O(2) levels during this period. The depletion of the starch fraction coincided with the beginning of a microbial biomass decrease, suggesting that starch is an important carbon substrate for the growth of thermophilic microorganisms during composting. Growth yields in the microbial community based on consumption of major carbon constituent classes in the high-activity period fell between 22 and 28%. Multivariate statistical analysis of changes in fatty acid composition revealed small, but statistically significant differences in the microbial community succession. At 16% O(2), 10 Me fatty acids from Actinomycetes and cyclopropyl fatty acids (from Gram-negative bacteria) became more important with time, whereas 18:1 omega 7t was characteristic at 2.5 and 1% O(2), indicating a more stressed bacterial community at the lower O(2) concentrations. Although adequate composting was achieved at O(2) levels as low as 2.5 and 1%, it is not recommended to compost at such low levels in large-scale systems, because the heterogeneous gas transport through the material in these systems might lead to anaerobic conditions and inefficient composting.


Sleep quality among individuals with ketamine use and the mediating role of craving.
Sleep problems are common in Taiwan. Poor sleep may be associated with many illnesses, including substance use disorders. Ketamine use disorder has significantly increased in Taiwan in recent years and may lead to physical and cognitive problems. Craving for ketamine is a risk factor for ketamine use and relapse, and poor sleep quality may increase craving. This study aimed to explore the mediating effects of craving on the relationship between poor sleep quality and ketamine use. Demographic data, sleep quality, severity of dependence and craving were recorded for current ketamine users and abstinent ketamine users. Mediation analysis was used to examine the mediating effect of craving on the relationship between poor sleep and ketamine use. This study enrolled 414 current ketamine users with ketamine use disorder, 238 current ketamine users without ketamine use disorder, and 102 abstinent ketamine users with ketamine use disorder. Compared with healthy controls, all ketamine users had poor sleep quality. Poor sleep quality was associated with the initiation of and dependence on ketamine use. Craving can mediate the relationship between poor sleep quality and ketamine use. Poor sleep quality remains a problem for those abstaining from ketamine use. Poor sleep quality in ketamine users is an important issue because it is directly and indirectly through craving associated with ketamine use.


Interaction of light with the organ of Corti. I. Light guide effects in cochlear hair cells.
A cochlear postmortem preparation has been developed which allows for hydromechanical studies of the transilluminated organ of Corti. It was found that cochlear hair cells act as optical waveguides. This poperty of hair cells is important for optical cochlear investigations. It may be used in the study of the motion of single hair cells.


[Functional reconstruction of mandible by using vascularized fibular free flap and one-stage rehabilitation of the implant].
To study the characteristics of the vascularized fibular free flap and the possibility of the insertion of implant at the same time. The microvascular surgical procedure and implant technique were used in the treatment of two cases suffered from mandibular ameloblastoma. After tumor resection by partial mandiblectomy, graft of vascularized fibular free flap was performed with simultaneous insertion of 5 implant. One year later, the grafted bone was survival, the osseointegration was proceeded between the implant and grafted bone. The functional reconstruction of the mandible was excellent after prosthetic denture. This is a good approach to rehabilitate bone function by using vascularized fibular free flap and one-stage implant placement.


A highly selective colorimetric and "turn-on" fluorimetric chemosensor for detecting CN(-) based on unsymmetrical azine derivatives in aqueous media.
A novel highly selective chemosensor S1 for cyanide based on unsymmetrical azine derivative was successfully designed and synthesized, which showed both colorimetric and fluorescence turn-on responses for cyanide ions in aqueous. This structurally simple chemosensor could detect CN(-) anion over other anions in aqueous solution DMSO/H2O (v/v=3:2) undergo deprotonation reaction. Results showed that the chemosensor S1 exhibited 50 fold enhancement in fluorescence at 530nm and showed an obvious change in color from colorless to yellow that could be detected by naked eye under the UV-lamp after the addition of CN(-) in aqueous solution. Moreover, the detection limit on fluorescence response of the sensor to CN(-) is down to 6.17×10(-8)M by titration method. Test strips based on S1 were obtain, which could be used as a convenient and efficient CN(-) test kit to detect CN(-) in aqueous solution.


Differentiation of neural precursor cell-derived oligodendrocyte progenitor cells following transplantation into normal and injured spinal cords.
Demyelination contributes to the functional deficits after spinal cord injury (SCI). Therefore, remyelination may be an important strategy to facilitate repair after SCI. Oligodendrocyte precursor cells (OPCs) are immature oligodendrocytes and can differentiate into myelin-forming cells of central nervous system under certain conditions. OPC transplantation is an attractive approach for the treatment of demyelinating diseases. In this study, we transplanted OPCs expressing green fluorescent protein (GFP-OPCs) into normal and injured rat spinal cords to evaluate the differentiation of transplanted OPCs in vivo. Unfortunately, the grafted GFP-OPCs, in spinal cord whether normal or injured, were all differentiated into astrocytes, but not oligodendrocytes. Our further study indicated that inflammatory environment might not be the key factor influencing the differentiation of OPCs. Some spinal cord components, such as bone morphogenetic proteins (BMPs), were the major factors that induced OPCs to differentiate into astrocytes. The three types of BMP receptor (BMPRIA, IB and II) could all be detected in OPCs, and the astroglial differentiation of OPCs induced by spinal cord homogenate extract (SCHE) in vitro could be blocked partly by noggin, an antagonist of BMP. These results suggested that the BMPR signal transduction pathway might be one of the key factors which determine the differentiation direction of engrafted OPCs in spinal cord.


Idiopathic pulmonary fibrosis: phenotypes and comorbidities.
Idiopathic pulmonary fibrosis (IPF) is a progressive fatal disease of the lung with an unknown etiology and limited treatment options. Three distinct phenotypes of IPF have been proposed: combined pulmonary fibrosis and emphysema, disproportionate pulmonary hypertension in IPF, and rapidly progressive IPF. Although treatment options for IPF are limited, much can be done to identify and alleviate symptoms from comorbidities, potentially improving the overall quality of life and well-being of these patients. This article describes emerging evidence to support the hypothesis that there is more than one phenotype for IPF and describes the common comorbidities seen in this disease.


Detection of influenza and non-influenza respiratory viruses in lower respiratory tract specimens among hospitalized adult patients and analysis of the clinical outcome.
Lower respiratory tract infection (LRTI) is one of the most fatal diseases for adults. Influenza is a well-recognized cause of severe pneumonia; however, the outcomes of LRTI caused by non-influenza respiratory viruses (NIRVs) have not been sufficiently investigated. This study aimed to describe the characteristics and outcomes of LRTI associated with respiratory viruses (RVs) in adults. A retrospective review was performed using medical records of adult patients whose lower respiratory tract (LRT) specimens (endotracheal aspirate and bronchoalveolar lavage fluid) tested positive for RVs using multiplex PCR. Underlying comorbidities, laboratory data, and clinical outcomes were analyzed. Among the 808 LRT specimens collected from 666 adult patients, RV was identified in 115 specimens (14%) from 106 patients (16%). The underlying comorbidities and laboratory data did not differ between patients with influenza- and NIRV-related LRTI. The 14-day and 30-day mortality rates were higher in the influenza group than in the NIRV group (24% versus 7%, p = 0.03 and 33% versus 13%, p = 0.02, respectively), whereas the 90-day mortality rate did not. In a multivariate Cox model to predict 90-day mortality, shock and acute kidney injury independently predicted a higher mortality rate (hazard ratio (HR): 4.28, 95% CI: 1.46-12.58, p = 0.01 and HR: 2.80, 95% CI: 1.28-6.15, p = 0.01, respectively), whereas the detection of influenza did not. Influenza and NIRVs were associated with increased mortality due to LRTI in adults. Therefore, NIRVs are among key pathogens causing LRTI and should not be neglected by clinicians.


Transport and Polymerization of Porphyromonas gingivalis Type V Pili.
Adhesive pili (or fimbriae) in bacteria are classified into five types, among which type V pili have been most recently described. Type V pili differ from other pili types with respect to transport mechanism, structure, and pilin synthesis. Genes of type V pili are restricted to the phylum Bacteroidetes. Protein subunits that compose type V pili are transported to the cell surface as lipoprotein precursors and then polymerized into a pilus through a strand-exchange mechanism, which is demonstrated by several experiments, including palmitic acid labeling and Cys-Cys cross-linking analysis. Here, we describe the use of these methods to analyze type V pili.


Bizarre allegation of negligence in fabricated pin migration--a case report.
Kirschner's wires (popularly known as 'K-wires' or 'pins') are used commonly in various orthopaedic surgical fixations. Around the shoulder joint such pins are used for fixation of acromioclavicular joint, sternoclavicular joint, proximal humerus and clavicle. In such fixations, spontaneous loosening and extraction of pins would not cause as much anxiety and worry to the surgeon as a pin which breaks and migrates within the body. Such alarm is not just due to the potential damage that the migrating pin can cause, but also due to fear of misinterpretation of the event in legal suits as negligence and the subsequent claims for heavy damages. We present here a case where a patient attempted to raise allegation of negligence (probably planning subsequent claim for damages) by fabricating pin migration. The literature of such an unusual case is reviewed in brief.


Behavioural consequences of two chronic psychosocial stress paradigms: anxiety without depression.
Chronic stress, in particular chronic psychosocial stress, is a risk factor in the aetiology of various psychopathologies including anxiety- and depression-related disorders. Therefore, recent studies have focussed on the development of social-stress paradigms, which are believed to be more relevant to the human situation than non-social-stress paradigms. The majority of these paradigms have been reported to increase both anxiety- and depression-related behaviour in rats or mice. However, in order to dissect the mechanisms underlying anxiety or depression, animal models are needed, which specifically induce one, or the other, phenotype. Here, we study both short- (1d after stressor termination) and long-term (4d or 7d after stressor termination) behavioural and physiological consequences of two well-validated chronic psychosocial stress models: social-defeat/overcrowding (SD/OC) and chronic subordinate colony housing (CSC). We demonstrate that SD/OC and CSC result in different physiological alterations: SD/OC more strongly affecting body-weight development, whereas CSC more strongly affects adrenal and pituitary morphology. Both stressors were shown to flatten circadian locomotor activity immediately after stress termination, which normalized 7d later in SD/OC group but reversed to hyperactivity during the dark phase in the CSC group. Importantly, neither stress paradigm resulted in an increase in depression-related behaviour as assessed using the forced swim test, tail suspension test and saccharin preference test at any time-point. However, both stress paradigms lead to an anxiogenic phenotype; albeit with different temporal profiles and not towards a novel con-specific (social anxiety). CSC exposure elevates anxiety-related behaviour immediately after stressor termination, which lasts for at least 1 wk. In contrast, the anxiogenic phenotype only develops 1 wk after SD/OC termination. In conclusion, both models are unique for uncovering the molecular underpinnings of anxiety-related behaviour without conflicting depression-based alterations.


Amyloid seeding as a disease mechanism and treatment target in transthyretin cardiac amyloidosis.
Transthyretin (TTR) is a tetrameric transport protein mainly synthesized by the liver and choroid plexus. ATTR amyloidosis is characterized by the misfolding of TTR monomers and their accumulation within tissues as amyloid fibres. Current therapeutic options rely on the blockade of TTR production, TTR stabilization to maintain the native structure of TTR, amyloid degradation, or induction of amyloid removal from tissues. "Amyloid seeds" are defined as small fibril fragments that induce amyloid precursors to assume a structure rich in β-sheets, thus promoting fibrillogenesis. Amyloid seeds are important to promote the amplification and spread of amyloid deposits. Further studies are needed to better understand the molecular structure of ATTR seeds (i.e. the characteristics of the most amyloidogenic species), and the conditions that promote the formation and multiplication of seeds in vivo. The pathological cascade may begin months to years before symptom onset, suggesting that seeds in tissues might potentially be used as biomarkers for the early disease stages. Inhibition of amyloid aggregation by anti-seeding peptides may represent a disease mechanism and treatment target in ATTR amyloidosis, with an additional benefit over current therapies.


Vincristine- and cisplatin-induced apoptosis in human retinoblastoma. Potentiation by sodium butyrate.
Chemotherapy alone has largely been unsuccessful in controlling retinoblastoma growth, and has traditionally been limited in use as an alternative to irradiation for the treatment of retinoblastoma. Recently, clinical studies combining chemotherapy with local therapies, including radiotherapy, laser therapy or cryotherapy and in some cases, cyclosporine A, have been effective in treating retinoblastoma. Differentiating agents may also be combined with chemotherapy to enhance the action of cytotoxic drugs on tumor cell growth, although this approach has not been fully investigated in retinoblastoma. In this study, we evaluated the cytotoxic response of human retinoblastoma cell lines (Y79 and WERI-Rb1) to two chemotherapy agents commonly used in treating retinoblastoma, vincristine (VCR) and cisplatin (CDDP). Retinoblastoma cells have been shown to be sensitive to the differentiating agent sodium butyrate, and cell lines were also treated with a combination of VCR or CDDP with sodium butyrate, and the effects on retinoblastoma viability assessed. Both VCR and CDDP induced dose-dependent death of Y79 and WERI-Rb1 cells, accompanied by nuclear and cytoplasmic condensation and DNA laddering, features characteristic of apoptosis. Inhibitors of macromolecular synthesis, cycloheximide and actinomycin-D, significantly reduced VCR- and CDDP-induced apoptosis, although putative endonuclease inhibitors zinc sulphate and aurintricarboxylic acid had no apparent effect. Treatment with 0.5 mM or 1 mM sodium butyrate combined with VCR or CDDP significantly increased induction of apoptosis by these agents. This augmentation of chemotherapy-induced apoptosis may have implications for retinoblastoma therapy.


Exploring the barriers of utilizing theoretical knowledge in clinical settings: A qualitative study.
Although effective performance in clinical settings requires the integration between theory and practice, there is a gap between theoretical knowledge as taught in the classroom and what the students experience in clinical settings. This study aimed to elicit and explore the barriers of utilizing theoretical knowledge in clinical settings. A qualitative study was adopted with a conventional content analysis approach. Fifteen nursing and paramedic's students, faculty members and experienced nursing staff participated in the study. Data were collected by semi-structured individual interviews until data saturation and concurrently analyzed via MAXQDA 10. Five main categories emerged as barriers of utilizing theoretical knowledge in the clinical settings i.e. non-standard practices in clinical settings; lack of trust in clinical competence; lack of perceived professional support; insufficiencies in teaching and learning process; and differences between doing things in simulated and real clinical situations. Transferring theory into practice in a structured manner requires professional support in the workplace, trust and the opportunity for direct experience, using valid and up-to-date knowledge by clinical staff and bridging the simulated situations with real life scenarios.


Cells of origin of the occipito-pontine projection in the cat: functional properties and intracortical location.
Extracellular records were taken from the areas 17, 18 and 19 of anaesthetized and immobilized cats. Of the 350 cells recorded in the cortical layers IV-VI, 22 responded with an antidromic action potential to electrical stimulation of the basal pontine region. Antidromic latencies ranged between 1.5-8.8 msec (mean and SD: 3.98 +/- 1.83 msec). The recording sites of these cells were in the cortical layer V. In the areas 17 and 18 of these cells were detected only in peripheral parts of the visual field representation. Some of these cells were tested with visual stimulation. They had complex receptive fields of large sizes, they received input from either eye, and their orientation selectively was relatively low. The sample of cells had neither a preference for a certain orientation nor for any particular degree of directional specifity nor for a certain range of movement velocity.


Influence of arbuscular mycorrhiza on the growth and antioxidative activity in cyclamen under heat stress.
The influence of the arbuscular mycorrhizal (AM) fungus, Glomus fasciculatum, on the growth, heat stress responses and the antioxidative activity in cyclamen (Cyclamen persicum Mill.) plants was studied. Cyclamen plants (inoculated or not with the AM fungus) were placed in a commercial potting media at 17-20 °C for 12 weeks in a greenhouse and subsequently subjected to two temperature conditions in a growth chamber. Initially, plants were grown at 20 °C for 4 weeks as a no heat stress (HS-) condition, followed by 30 °C for another 4 weeks as a heat stress (HS+) condition. Different morphological and physiological growth parameters were compared between G. fasciculatum-inoculated and noninoculated plants. The mycorrhizal symbiosis markedly enhanced biomass production and HS + responses in plants compared to that in the controls. A severe rate of leaf browning (80-100%) was observed in control plants, whereas the mycorrhizal plants showed a minimum rate of leaf browning under HS + conditions. The mycorrhizal plants showed an increase activity of antioxidative enzymes such as superoxide dismutase and ascorbate peroxidase, as well as an increase in ascorbic acid and polyphenol contents. The 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity also showed a greater response in mycorrhizal plants than in the control plants under each temperature condition. The results indicate that in cyclamen plants, AM fungal colonisation alleviated heat stress damage through an increased antioxidative activity and that the mycorrhizal symbiosis strongly enhanced temperature stress tolerance which promoted plant growth and increased the host biomass under heat stress.


Pilea umbrosa ameliorate CCl4 induced hepatic injuries by regulating endoplasmic reticulum stress, pro-inflammatory and fibrosis genes in rat.
Pilea umbrosa (Urticaceae) is used by local communities (district Abbotabad) for liver disorders, as anticancer, in rheumatism and in skin disorders. Methanol extract of P. umbrosa (PUM) was investigated for the presence of polyphenolic constituents by HPLC-DAD analysis. PUM (150 mg/kg and 300 mg/kg) was administered on alternate days for eight weeks in rats exposed with carbon tetrachloride (CCl4). Serum analysis was performed for liver function tests while in liver tissues level of antioxidant enzymes and biochemical markers were also studied. In addition, semi quantitative estimation of antioxidant genes, endoplasmic reticulum (ER) induced stress markers, pro-inflammatory cytokines and fibrosis related genes were carried out on liver tissues by RT-PCR analysis. Liver tissues were also studied for histopathological injuries. Level of antioxidant enzymes such as catalase (CAT), superoxide dismutase (SOD), peroxidase (POD) and glutathione (GSH) decreased (p < 0.05) whereas level of thiobarbituric acid reactive substance (TBARS), H2O2 and nitrite increased in liver tissues of CCl4 treated rat. Likewise increase in the level of serum markers; alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP) and total bilirubin was observed. Moreover, CCl4 caused many fold increase in expression of ER stress markers; glucose regulated protein (GRP-78), x-box binding protein1-total (XBP-1 t), x-box binding protein1-unspliced (XBP-1 u) and x-box binding protein1-spliced (XBP-1 s). The level of inflammatory mediators such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) was aggregated whereas suppressed the level of antioxidant enzymes; γ-glutamylcysteine ligase (GCLC), protein disulfide isomerase (PDI) and nuclear erythroid 2 p45-related factor 2 (Nrf-2). Additionally, level of fibrosis markers; transforming growth factor-β (TGF-β), Smad-3 and collagen type 1 (Col1-α) increased with CCl4 induced liver toxicity. Histopathological scrutiny depicted damaged liver cells, neutrophils infiltration and dilated sinusoids in CCl4 intoxicated rats. PUM was enriched with rutin, catechin, caffeic acid and apigenin as evidenced by HPLC analysis. Simultaneous administration of PUM and CCl4 in rats retrieved the normal expression of these markers and prevented hepatic injuries. Collectively these results suggest that PUM constituted of strong antioxidant chemicals and could be a potential therapeutic agent for stress related liver disorders.


Surgical treatment of 32 cases of long-term atopic keratoconjunctivitis using the amniotic membrane.
To evaluate the use of surgical treatment with amniotic membrane for long-term atopic keratoconjunctivitis. Damaged corneas were repaired with various techniques: amniotic membrane transplantations, amniotic membrane coverings, amniotic membrane fillings (AMFs), and amniotic membrane inlay fillings, the latter of which were combined with glycerol-preserved corneal transplants. This retrospective study was conducted on 37 eyes belonging to 37 patients with atopic keratoconjunctivitis. Thirty-two patients were classified into four groups according to surgical technique. Five patients undergoing medical management served as controls. Surgical outcome was measured by recovery time and long-term visual improvement. In all surgical eyes, integrity of ocular tissues was effectively restored and symptoms were reduced at 24.4 ± 13 days post recovery. Mean best-corrected visual acuity improved from 0.6 ± 0.2 to 0.198 ± 0.16 logarithm of the minimum angle of resolution (P<0.001). There were no intraoperative or postoperative complications, with the exception of two recurring cases, both controlled by medication. Recovery time of the control groups lasted 52 ± 16 days. In controls, mean best-corrected visual acuity improved from 0.74 ± 0.15 to 0.54 ± 0.29 logarithm of the minimum angle of resolution (P ≤ 0.05). The vision improvement has significant difference for surgical treatment vs medical. (Mann-Whitney U-test, U = 119, P < 0.05, one tailed).Vision improvements remained stable during a mean follow-up period of 21.7 ± 3.8 months. Patients suffering from severe chronic atopic keratoconjunctivitis and its complications can benefit from suitable surgical treatments: transplants, covers, fillings, or corneal graft surgeries supplemented with AMFs.


The distribution of plasma proteins during early embryonic development in the sheep.
The distribution of the five plasma proteins that are quantitatively most important during development in the sheep has been studied in embryos of 15 to 21 days gestation. The three primary embryonic layers and tissues that differentiate from them were tested for the presence of alpha-fetoprotein (AFP), fetuin, albumin, transferrin and alpha 1-antitrypsin using the indirect immunoperoxidase method. Fetuin was the most prominent of these proteins particularly in the developing central nervous system. Fetuin and transferrin appeared early in the differentiating mesoderm and, with albumin and AFP, were detected in tissues originating from all three layers during the course of development. alpha 1-Antitrypsin appeared to have a limited distribution. All five plasma proteins were detected before the establishment of a circulatory system. It is suggested that their appearance in embryonic tissue is related to its stage of development and that they play an important part in early differentiation.


Caffeoyl sugar esters and an ellagitannin from Rubus sanctus.
The new natural caffeoyl esters, 3,6-di-O-caffeoyl-(alpha/beta)-glucose and 1-O-caffeoyl-beta-xylose, together with the hitherto unknown natural tannin, 2,3-O-hexahydroxydiphenoyl-4,6-O-sanguisorboyl-(alpha/beta)-glucose, have been isolated from the aqueous alcohol aerial part extract of Rubus sanctus. Establishment of all structures was based on the chemical and spectral evidence, including ESI-MS and 2D NMR.


Misfolded opsin mutants display elevated β-sheet structure.
Mutations in rhodopsin can cause misfolding and aggregation of the receptor, which leads to retinitis pigmentosa, a progressive retinal degenerative disease. The structure adopted by misfolded opsin mutants and the associated cell toxicity is poorly understood. Förster resonance energy transfer (FRET) and Fourier transform infrared (FTIR) microspectroscopy were utilized to probe within cells the structures formed by G188R and P23H opsins, which are misfolding mutants that cause autosomal dominant retinitis pigmentosa. Both mutants formed aggregates in the endoplasmic reticulum and exhibited altered secondary structure with elevated β-sheet and reduced α-helical content. The newly formed β-sheet structure may facilitate the aggregation of misfolded opsin mutants. The effects observed for the mutants were unrelated to retention of opsin molecules in the endoplasmic reticulum itself.


Solid phase microextraction for analysis of alkanes and aromatic hydrocarbons in human breath.
In this work, solid phase microextraction-gas chromatograph (SPME-GC) was applied to analyze alkanes and aromatic hydrocarbons in human breath, providing a potential non-invasive method to screen lung cancer. This method has been optimized and evaluated. It provided quantification limits ranging from 0.04 to 4.2 ng/mL, linear correlations ranging from 0.9845 to 0.9966 and R.S.D. values less than 9.8%. Total 30 breath samples, from 15 lung cancer patients and 15 healthy persons, were analyzed, and the alkanes and aromatic hydrocarbons were detected in 73.3% lung cancer patients and in 13.3% healthy persons by this method. Above all, It was demonstrated that this SPME-GC method provided a sensitive and non-invasive measure means to analyze alkanes and aromatic hydrocarbons in human breath, and brought forward a potential application for screening lung cancer.


The proprotein convertase furin colocalizes with caveolin-1 in the Golgi apparatus and endosomes of hepatocytes.
The significance of furin in the maturation and activation of a wide array of proproteins in the secretory pathway has been well demonstrated. However, despite efforts made to characterize the subcellular locations where furin activates its substrates, doubts on the proprotein-processing compartments still persist. Using in vivo gene delivery, together with high-resolution immunogold electron microscopy, we were able to assign precise subcellular locations to furin. In rat hepatocyte, the enzyme was found concentrated in the Golgi apparatus, along the basolateral (sinusoidal) plasma membrane and in underlying endosomes. An asymmetry was detected in respect to amounts of furin between the basolateral domain and the apical (canalicular) one, favoring the former. The asymmetric recycling of furin through the basolateral domain may be of high importance for the polarized secretion of processed bioactive compounds. Double immunogold labelings indicate that furin colocalizes with the caveolae/raft-marker caveolin-1 in the Golgi apparatus and in the basolateral endosomes. Furthermore, co-immunoprecipitation experiments show the possible interaction of caveolin-1 and furin. Our results suggest that, in addition to the Golgi, furin-/caveolin-1-containing endosomes could represent a compartment where furin processes its substrates at the basolateral domain of the hepatocyte.


Correction to: Thermal comfort in urban spaces: a cross-cultural study in the hot arid climate.
The article was published without issue designation resulting in regular issue compilation.


Pollution of water in Africa: a review of contaminants and fish as biomonitors and analytical methodologies-the case of Senegal.
Environmental pollution is one of the major problems facing human health, ecosystems, and biodiversity. This is particularly the case for water quality in Senegal. Fish can be used as a biomonitor of pollution by accumulating pollutants from the environment through their tissues. Fish is an indispensable element in the assessment of the quality of the environment due to the diversity of biological cycles and their position in the food chain. Fish, which is very sensitive to chemical and bacterial pollution, concentrates pollutants and is a good indicator of water quality. This review presents water pollution in Senegal and the possibility of using fish as an ideal monitoring matrix for marine environments, to detect the concentration of heavy metals and organic pollutants. The different extraction and analytical techniques used for fish biomonitoring will be also described.


Aneuploid proliferation defects in yeast are not driven by copy number changes of a few dosage-sensitive genes.
Aneuploidy-the gain or loss of one or more whole chromosome-typically has an adverse impact on organismal fitness, manifest in conditions such as Down syndrome. A central question is whether aneuploid phenotypes are the consequence of copy number changes of a few especially harmful genes that may be present on the extra chromosome or are caused by copy number alterations of many genes that confer no observable phenotype when varied individually. We used the proliferation defect exhibited by budding yeast strains carrying single additional chromosomes (disomes) to distinguish between the "few critical genes" hypothesis and the "mass action of genes" hypothesis. Our results indicate that subtle changes in gene dosage across a chromosome can have significant phenotypic consequences. We conclude that phenotypic thresholds can be crossed by mass action of copy number changes that, on their own, are benign.


Contractile response of horse deep dorsal penile vein to histamine.
The present investigation was designed to evaluate the effect of histamine on isolated rings of horse deep dorsal penile vein. Under precontracted or basal conditions, histamine evoked an endothelium-independent contraction. Preincubation of the vein rings with the selective H1 receptor antagonist, mepyramine, shifted the concentration-response curve for histamine and to the H1 receptor agonist 2-pyridylethylamine to the right in a competitive manner. Pretreatment with cimetidine, a specific H2 receptor antagonist, did not modify the pEC50 and maximal contraction of the histamine response. Cimetidine and propranolol failed to induce a change in the relaxation caused by dimaprit, the H2 receptor agonist. Histamine contraction was unaffected by thioperamide, the specific H3 receptor antagonist. (R)-alpha-methylhistamine, the H3 receptor agonist, also induced contractions which persisted in the presence of either thioperamide or tetrodotoxin. These data indicate that horse deep dorsal penile vein shows an endothelium-independent contraction response to histamine, mainly mediated by H1 receptors.


A propensity score-matched study on the short-term outcome of ruptured blood blister-like aneurysm treated by microsurgery or endovascular surgery: a single-center study of 155 cases.
Treating blood blister-like aneurysms (BBA) is a major neurosurgical challenge. Whether endovascular repair serves as a better strategy than microsurgery remains controversial. We aim to perform a propensity score-matched (PSM) retrospective study to analyze the short-term outcome in BBA patients who received microsurgery and endovascular treatment. One hundred fifty-five eligible patients with internal carotid artery BBA were retrospectively collected with demographic and angiographic baseline in a single center. Three-month outcome and adverse events were set as outcome endpoints. PSM was used to match the microsurgery and endovascular group. Matching effect was evaluated by distribution variation analysis and love plot. The outcome of neurosurgery and endovascular treatment was then compared before and after PSM. Better WFNS levels (p = .017) and modified Fisher grade (p = .027) were noted in endovascular group before matching. Other baseline including angiographic features were comparable between two groups. Before matching, the 3-month outcome of endovascular repair surgery was more favorable than microsurgery (p < .0001). The occurrence of adverse events was also higher in the microsurgery group (p = .0079). In PSM-adjusted groups, the superior outcome effect of endovascular treatment still existed but with a reduced significance (p = .004). Similar trend was also observed in the adverse event rate (p = .038). Fatality rate was comparable between two adjusted groups regardless of PSM adjustment. Endovascular surgery of BBAs exhibits overall more favorable short-term outcome regardless of PSM matching. Microsurgery does not cause a higher fatality rate, hence it could be considered a salvage plan for those high-grade BBA patients.


Photobiology of sea ice algae during initial spring growth in Kangerlussuaq, West Greenland: insights from imaging variable chlorophyll fluorescence of ice cores.
We undertook a series of measurements of photophysiological parameters of sea ice algae over 12 days of early spring growth in a West Greenland Fjord, by variable chlorophyll fluorescence imaging. Imaging of the ice-water interface showed the development of ice algae in 0.3-0.4 mm wide brine channels between laminar ice crystals in the lower 4-6 mm of the ice, with a several-fold spatial variation in inferred biomass on cm scales. The maximum quantum yield of photosynthesis, F(v) /F(m), was initially low (~0.1), though this increased rapidly to ~0.5 by day 6. Day 6 also saw the onset of biomass increase, the cessation of ice growth and the time at which brine had reached <50 psu and >-2 °C. We interpret this as indicating that the establishment of stable brine channels at close to ambient salinity was required to trigger photosynthetically active populations. Maximum relative electron transport rate (rETR(max)), saturation irradiance (E(k)) and photosynthetic efficiency (α) had also stabilised by day 6 at 5-6 relative units, ~30 μmol photons m⁻² s⁻¹ and 0.4-0.5 μmol photons m⁻²s⁻¹, respectively. E(k) was consistent with under-ice irradiance, which peaked at a similar value, confirming that daytime irradiance was adequate to facilitate photosynthetic activity throughout the study period. Photosynthetic parameters showed no substantial differences with depth within the ice, nor variation between cores or brine channels suggesting that during this early phase of ice algal growth cells were unaffected by gradients of environmental conditions within the ice. Variable chlorophyll fluorescence imaging offers a tool to determine how this situation may change over time and as brine channels and algal populations evolve.


Extrachromosomal DNA-mediated glyphosate resistance in Italian ryegrass.
An Italian ryegrass population from Arkansas, USA developed glyphosate resistance due to 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene amplification. The plants in this population with approximately 70 EPSPS copies were used in the present study for the physical mapping of amplified copies of EPSPS gene to determine the possible mechanism of EPSPS gene amplification conferring glyphosate resistance in Italian ryegrass. Fluorescence in situ hybridization (FISH) analysis of glyphosate resistant (GR) Italian ryegrass plants with approximately 70 EPSPS copies displayed EPSPS hybridization signals randomly on most of the metaphase chromosomes. Glyphosate susceptible (GS) Italian ryegrass plants with one EPSPS copy displayed single prominent EPSPS hybridization signal, which was co-localized with 5S rDNA locus along with few additional signals on the outside of chromosomes. Pulsed-field gel electrophoresis (PFGE) followed by DNA blot using EPSPS gene as a probe identified a prominent EPSPS hybridization around the 400 kb region in GR DNA samples, but not in GS DNA samples. We report the extrachromosomal DNA-mediated glyphosate resistance in Italian ryegrass. Physical mapping of amplified copies of EPSPS gene in Italian ryegrass by FISH gives us a clue that the amplified copies of EPSPS gene may be present in the extrachromosomal DNA elements. Further analysis by PFGE followed by DNA blotting revealed that the extrachromosomal DNA containing EPSPS is approximately 400 kb similar in size with that of eccDNA replicon in Amaranthus palmeri. © 2023 Society of Chemical Industry.


[Effects of antimicrobial peptides of neutrophils on tumor and normal cells in culture].
We performed a comparative study of effects of two structurally different cationic antimicrobial peptides of cathelicidin family, porcine protegrin 1 (PG1) and caprine bactenecin 5 (Bac5) on selected tumor and normal mammalian cells in vitro. Protegrins are amphiphilic beta-hairpin molecules having broad-spectrum antimicrobial activity due to their marked membranolytic properties. Bac5 belongs to the group of proline-rich peptides, which adopt a polyproline type II extended helix and kill microorganisms rather by a non-lytic mechanism. We have shown that while PG1 exerts distinct and fast cytotoxic effects on most of used tumor cells being slightly less toxic for nontransformed host cell, the proline-rich Bac5 is much less cytotoxic for all the cells tested. The toxic effects of PG1 were partially declined in the presence of 10% fetal calf serum. It was revealed that PG1 was able to interact with proteins of serpin family (as had been previously established for human defensins by Panyutich et al., 1995). Pre-incubation of PG1 with alpha1-antitrypsin caused the decrease of the cytotoxic activity of the peptide and, on the other hand, the antiprotease activity of alpha1-antitrypsin was reduced after interaction of the serpin with PG1 (not with Bac5). Confocal microscopy experiments allowed to monitor the internalization of fluorescent labeled (by BODIPY FL) peptides into target cells and their intracellular distribution. Bac5-BODIPY (at 5 microM) was rapidly taken into the cells. PG1-BODIPY at non-toxic concentrations was also able to enter the cells without significant damage to them. The comparative study of the kinetics of the peptides uptake into the target cells and the influence of low temperature, energy-depletion and endocytosis inhibitors on the process of the internalization of the peptides into the cells was carried out using flow cytometry.


Visual improvement in amblyopia after visual loss in the dominant eye.
Partial recovery from amblyopia can occur in animals if the the influence from the dominant eye is removed. This report describes a human, adult amblyope who lost central vision in the dominant eye, and regained useful vision in the amblyopic eye.


A pagetic elderly lady with back pain.
An elderly lady suffering from Paget's disease presented with severe back pain after sustaining a fall. The rise in inflammatory markers and poor response to analgesics led to the diagnosis of septic discitis [corrected] that was confirmed by MRI. A high index of suspicion for septic discitis [corrected] is necessary in elderly patients presenting with back pain and an associated rise in inflammatory markers.


Asymmetric Michael addition of α-substituted isocyanoacetates with maleimides catalyzed by chiral tertiary amine thiourea.
A highly diastereoselective and enantioselective Michael addition of α-substituted isocyanoacetates with maleimides catalyzed by bifunctional tertiary amine thioureas has been developed. Various chiral succinimide derivatives bearing adjacent quaternary and tertiary stereocenters were prepared in excellent yields (up to 98%), diastereoselectivities (up to 99:1), and enantioselectivities (up to 98% ee). The synthetic utility of chiral succinimide derivatives is also demonstrated in the preparation of h5-HT(1d) receptor agonist motifs.


Crosstalk between Raf/MEK/ERK and PI3K/AKT in suppression of Bax conformational change by Grp75 under glucose deprivation conditions.
During glucose deprivation (GD)-induced cellular stress, the molecular chaperone glucose-regulated protein 75 (Grp75)/Mortalin/PBP74/mtHSP70 (hereafter termed "Grp75") plays an important role in the suppression of apoptosis by inhibiting the Bax conformational change that delays the release of cytochrome c. The molecular pathways by which it carries out these functions are still unclear. We hypothesize that the anti-apoptotic effect by the overexpression of Grp75 was through the signal of AKT activated by classic phosphoinositide 3-kinase (PI3K) and also involved PI3K-independent pathways. Using the PC12 cell GD model, we demonstrated a novel mechanism of Grp75 activating AKT, which may be PI3K independent and associated with Raf/MEK (mitogen-activated protein kinase/ERK kinase)/ERK signaling. The PI3K inhibitor LY294002 did not influence the activation of AKT by the Grp75 overexpression under GD; however, the MEK inhibitor U0126 dramatically inhibited AKT phosphorylation in the same assay. In addition to the PI3K/AKT signal pathway, Grp75 overexpression also inhibited the Bax conformational change through the Raf/MEK/ERK signal pathway. In conclusion, Grp75 overexpression in activating AKT can be PI3K independent and associated with Raf/MEK/ERK signaling under GD. At the same time, PI3K may also crosstalk with Raf-1, in which the prosurvival signal of PI3K maintains the expression of Raf-1. The activated AKT and extracellular signal-regulated protein kinases 1 and 2 by Grp75 inhibited the Bax conformational change and subsequent apoptosis.


Enhancement of anaerobic degradation of petroleum hydrocarbons by electron intermediate: Performance and mechanism.
A quinone-respiring strain capable of degrading multitudinous petroleum hydrocarbons was isolated by selective medium and identified as Bacillus sp. (named as C8). Maximum 76.7% of total petroleum hydrocarbons (TPH) were degraded by the biosurfactant-mediated C8 with the aid of nitrate and electron intermediate (anthraquinone-2,6-disulphonate, AQDS). The quantitative real-time PCR results of several intracellular key functional genes suggested that AQDS could participate in the transformation of intermediates and accelerate the electron transfer in the degradation of TPH and nitrate, thereby eliminating the accumulation of nitrite and increasing the degradation efficiency of TPH. A strengthening mechanism, which promoted electron transport in the anaerobic denitrification degradation of petroleum hydrocarbons by quinone-respiring strain with the aid of electron intermediate, was proposed. The influencing factors were evaluated by using response surface methodology, and the TPH removal was positively related to temperature but negatively to pH.


High D-arabitol production with osmotic pressure control fed-batch fermentation by Yarrowia lipolytica and proteomic analysis under nitrogen source perturbation.
D-arabitol, a five-carbon sugar alcohol, is widely used in food and pharmacy industry as a lower calorie sweetener or intermediate. Appropriate osmotic pressure was confirmed to facilitate polyol production by an osmophilic yeast strain of Yarrowia lipolytica with glycerol. In this study, an osmotic pressure control fed-batch fermentation strategy was used for high D-arabitol producing by Y. lipolytica ARA9 with crude glycerol. Glycerol was added to the broth quantitatively not only as a substrate but also as an osmotic agent. Meanwhile, NH3·H2O was fed as a nitrogen source and pH regulator. The maximum D-arabitol production reached 118.5 g/L at 108 h with the yield of 0.49 g/g and productivity of 1.10 g/L/h, respectively. Furthermore, a comparative proteomic analysis was used to study the cellular responses under excess and deficient nitrogen sources. Thirty-one differentially expressed protein spots belonging to seven different biological processes were identified. Excess nitrogen source enhanced gluconeogenesis and pentose phosphate pathways, both of which were involved in arabitol synthesis. In addition, cell growth was facilitated by increased expression of nucleotide and structural proteins. Enhanced energy and NADPH biosynthesis were employed to create a reductive environment and quell reactive oxygen species, improving D-arabitol production. Nitrogen deficiency resulted in cell rescue and stress response mechanisms such as reactive oxygen species elimination and heat shock protein response. The identified differentially expressed proteins provide information to reveal the mechanisms of the cellular responses under nitrogen source perturbation, and also provide guidance to improve D-arabitol production in metabolic engineering or process optimization methodologies.


Factors Associated With Compliance With Self-Management Home Therapies for Spine Pain: A Survey of Participants Attending a Chiropractic Teaching Clinic in South Africa.
The purpose of this study was to determine factors that affect compliance with various prescribed home therapies based on reported feedback from participants with spine pain. This was a descriptive, quantitative, cross-sectional survey. A purposive sampling method was used to recruit 121 participants with neck and back pain attending the Durban University of Technology Chiropractic Day Clinic located in KwaZulu-Natal, South Africa. Data were collected using a self-administered questionnaire. Descriptive statistics, including frequencies and percentages, were used to summarize the data, and odds ratios (ORs) were calculated. Most participants presented with chronic pain, reporting an average severity of 6 out of 10 and little disability from the pain. Home therapy included stretches (92.2%), heat therapy (49.1%), and ice therapy (38.8%). Almost two-thirds (62.1%) of participants reported being fully compliant with the prescribed home therapy, while 32.8% reported partial compliance. The main factors that potentially affected compliance were laziness and forgetfulness. Participants who reported having depression were less compliant (OR, 0.181), while those with chronic pain were more compliant (OR, 3.74). Those who believed that home therapy would alleviate their pain were also more compliant (OR, 3.83). The study found that a majority of participants with spine pain were compliant with prescribed chiropractic home treatment. Key factors that potentially influenced compliance were identified.


Efficacy and safety of glycyrrhizic acid preparation treating comorbid liver injury in COVID-19: A systematic review.
Background: No specific drug for COVID-19 has been found, and many studies have found that different degrees of liver injury often occurred after infection with COVID-19. Glycyrrhizic acid preparation (GAP) has been frequently used clinically, often combined with conventional treatments such as antiviral therapy, to improve the prognosis of COVID-19 and patients' liver function. Aims: To critically review and analyze clinical evidence on the efficacy and safety of GAP in the treatment of COVID-19 alone and COVID-19 with comorbid liver injury. Methods: A systematic literature review was performed following a sensitive searching strategy that examines all articles published in "WHO COVID-19 Research Database," "Cochrane Library," "VIP," "CNKI," "Wanfang," and "CBM" from 2020 to July 2022. Articles were evaluated by peer reviewers and used Joanna Briggs Institute (JBI) critical appraisal tools to complete the assessment of the risk of bias. Results: Ten clinical studies were finally included, involving 598 patients with COVID-19, of whom 189 were confirmed to be with comorbid liver injury. The main GAPs used are diammonium glycyrrhizinate and magnesium isoglycyrrhizinate, which have shown efficacy in improving liver function, inhibiting inflammation, and enhancing immunity. We are still seeking more related research. Conclusion: Glycyrrhizic acid preparations (mainly diammonium glycyrrhizinate and magnesium isoglycyrrhizinate) have a considerable clinical effect on improving liver function in patients with COVID-19 alone or with comorbid liver injury. Further studies on the use of GAP in the treatment of COVID-19 with comorbid liver injury and its mechanism are still needed. Systematic Review Registration: [www.crd.york.ac.uk/prospero], identifier [CRD42021234647].


A serious case of failed extubation: difficulty removing a laser resistant tracheal tube in a 7-year-old child.
A 7-year-old girl underwent laser ablation of tonsillar remnants. Following the procedure, which was surgically uncomplicated, the laser resistant tracheal tube used could not be removed; it was firmly lodged in the larynx, immediately below the glottic opening. This case highlights the importance of careful selection of laser resistant tracheal tubes for use in paediatric patients and challenges traditional concepts of paediatric upper airway anatomy.


Diffuse epithelial keratopathy following a single instillation of topical lignocaine: the damaging drop.
Toxic corneal epitheliopathies are a known occurrence following chronic use of topical anesthetic agents in ophthalmology. We report two cases of diffuse epithelial keratopathy following a single drop of 4% lignocaine in two diabetic patients scheduled for fundus fluorescein angiography.


P53 codon 72 polymorphism in squamous cell carcinoma of the head and neck region.
The impact of codon 72 polymorphism of the human tumour suppressor gene p53 on the risk of developing squamous cell carcinomas of the head and neck (HNSCC) remains unclear because of contradictory results found by several studies. We genotyped a group of 77 patients with advanced HNSCC by using a direct sequencing method. There were no significant differences in the age of the patients at the time of the first diagnosis nor in the 5-year survival rates. There was no additive effect between different risk factors (alcohol, nicotine) and codon 72 polymorphism. Compared to the frequency of homozygosity encoding for Arg/Arg in the Eurasian population given in literature, the present study has shown a significantly higher frequency of homozygosity for Arg/Arg at codon 72 than commonly detected. These findings may indicate codon 72 polymorphism as a risk factor for HNSCC or point to a high variability of codon 72 polymorphism among ethnic groups.


Students' Learning Experiences from Didactic Teaching Sessions Including Patient Case Examples as Either Text or Video: A Qualitative Study.
The aim of this study was to explore medical students' learning experiences from the didactic teaching formats using either text-based patient cases or video-based patient cases with similar content. The authors explored how the two different patient case formats influenced students' perceptions of psychiatric patients and students' reflections on meeting and communicating with psychiatric patients. The authors conducted group interviews with 30 medical students who volunteered to participate in interviews and applied inductive thematic content analysis to the transcribed interviews. Students taught with text-based patient cases emphasized excitement and drama towards the personal clinical narratives presented by the teachers during the course, but never referred to the patient cases. Authority and boundary setting were regarded as important in managing patients. Students taught with video-based patient cases, in contrast, often referred to the patient cases when highlighting new insights, including the importance of patient perspectives when communicating with patients. The format of patient cases included in teaching may have a substantial impact on students' patient-centeredness. Video-based patient cases are probably more effective than text-based patient cases in fostering patient-centered perspectives in medical students. Teachers sharing stories from their own clinical experiences stimulates both engagement and excitement, but may also provoke unintended stigma and influence an authoritative approach in medical students towards managing patients in clinical psychiatry.


[Prevalence of thyroid autoimmunity in a group of patients with type 1 diabetes mellitus in Londrina, PR].
Thyroid autoimmunity is a frequent comorbid condition subjects with in type 1 diabetes mellitus (DM1). We evaluated the prevalence of antithyroid autoantibodies (antimicrosomal, antithyroglobulin and antithyroid peroxidase), in addition to clinical (gender, age, DM duration) and laboratory (TSH, HbA1) characteristics of 101 patients (mean age 20 +/- 9.6 years; 62 female) followed at the HC/UEL. Autoantibodies were found in 31 subjects (30.7%). In the age group <12 years, 15% had thyroid antibodies; from 12 to 18 years, 32%, and >18 years, 35.7% (p= 0.22). Among the patients with positive antibodies, 40% had some thyroid dysfunction vs only 4.4% of those without antibodies (p<0.001). The average TSH was higher in the positive than in negative group (3.75 and 2.32microU/mL, respectively; p= 0.01). The prevalence of thyroid antibodies was 30.7%, in accordance to the literature.


Structural basis for specific, high-affinity tetracycline binding by an in vitro evolved aptamer and artificial riboswitch.
The tetracycline aptamer is an in vitro selected RNA that binds to the antibiotic with the highest known affinity of an artificial RNA for a small molecule (Kd approximately 0.8 nM). It is one of few aptamers known to be capable of modulating gene expression in vivo. The 2.2 A resolution cocrystal structure of the aptamer reveals a pseudoknot-like fold formed by tertiary interactions between an 11 nucleotide loop and the minor groove of an irregular helix. Tetracycline binds within this interface as a magnesium ion chelate. The structure, together with previous biochemical and biophysical data, indicates that the aptamer undergoes localized folding concomitant with tetracycline binding. The three-helix junction, h-shaped architecture of this artificial RNA is more complex than those of most aptamers and is reminiscent of the structures of some natural riboswitches.


Interpreting infective microbiota: the importance of an ecological perspective.
Complex microbiota are being reported increasingly across a range of chronic infections, including those of the cystic fibrosis airways. Such diversity fits poorly into classical models of sterile tissue infections, which generally involve one species, and where microbe-outcome associations usually imply causality. It has been suggested that microbiota at sites of infection could represent pathogenic entities, analogous to individual species. We argue that our ability to identify causality in microbiota-disease associations is, however, inherently confounded. Although particular microbiota may be associated with clinical outcomes, niche characteristics at sites of infection will shape microbiota composition through exerting selective pressures. Here, we suggest that ecological theory can inform clinical understanding.


The stability of maternal ratings of medical student interviews.
Little information is available on the intrarater reliability of parent ratings of medical student interview skills. The aim of this study was to compare maternal ratings of a videotaped medical student interview, with ratings by the same mother of the same interview seen a month later. Thirty mothers rated 1 of 2 'medical student' interview videotapes (random allocation). An actor played the role of the student and demonstrated different student skill levels in each interview. Mothers rated the same interview again a month later (mean +/- SD 34 +/- 13 days). Maternal satisfaction was measured using the Medical Interview Satisfaction Scale (MISS, maximum score 203) and the Interpersonal Skills Rating Scale (IPS, maximum score 91) with higher scores indicating higher satisfaction. No significant differences in mean maternal ratings were observed following the first and second viewings of each interview. The average percentage difference in first and second viewing scores was MISS 4%, IPS 8% with correlation coefficients MISS 0.96, IPS 0.87 (P < 0.05). The high levels of stability in maternal evaluations of simulated medical student interviews supports the use of maternal evaluations for longitudinal monitoring of medical student performance.


Central exendin-4 infusion reduces body weight without altering plasma leptin in (fa/fa) Zucker rats.
To investigate whether chronic administration of the long-acting glucagon-like peptide-1 receptor agonist exendin-4 can elicit sustained reductions in food intake and body weight and whether its actions require an intact leptin system. Male lean and obese Zucker (fa/fa) rats were infused intracerebroventricularly with exendin-4 using osmotic minipumps for 8 days. Exendin-4 reduced body weight in both lean and obese Zucker rats, maximum suppression being reached on Day 5 in obese (8%) and Day 7 in lean (16%) rats. However, epididymal white adipose tissue weight was not reduced, and only in lean rats was there a reduction in plasma leptin concentration. Food intake was maximally suppressed (by 81%) on Day 3 in obese rats but was reduced by only 18% on Day 8. Similarly, in lean rats food intake was maximally reduced (by 93%) on Day 4 of treatment and by 45% on Day 8. Brown adipose tissue temperature was reduced from Days 2 to 4. Plasma corticosterone was elevated by 76% in lean but by only 28% in obese rats. Chronic exendin-4 treatment reduced body weight in both obese and lean Zucker rats by reducing food intake: metabolic rate was apparently suppressed. These effects did not require an intact leptin system. Neither does the absence of an intact leptin system sensitize animals to exendin-4. Partial tolerance to the anorectic effect of exendin-4 in lean rats may have been due to elevated plasma corticosterone and depressed plasma leptin levels, but other counter-regulatory mechanisms seem to play a role in obese Zucker rats.


p53 activation during ribosome biogenesis regulates normal erythroid differentiation.
The role of ribosome biogenesis in erythroid development is supported by the recognition of erythroid defects in ribosomopathies in both Diamond-Blackfan anemia and 5q- syndrome. Whether ribosome biogenesis exerts a regulatory function on normal erythroid development is still unknown. In the present study, a detailed characterization of ribosome biogenesis dynamics during human and murine erythropoiesis showed that ribosome biogenesis is abruptly interrupted by the decline in ribosomal DNA transcription and the collapse of ribosomal protein neosynthesis. Its premature arrest by the RNA Pol I inhibitor CX-5461 targeted the proliferation of immature erythroblasts. p53 was activated spontaneously or in response to CX-5461, concomitant to ribosome biogenesis arrest, and drove a transcriptional program in which genes involved in cell cycle-arrested, negative regulation of apoptosis, and DNA damage response were upregulated. RNA Pol I transcriptional stress resulted in nucleolar disruption and activation of the ATR-CHK1-p53 pathway. Our results imply that the timing of ribosome biogenesis extinction and p53 activation is crucial for erythroid development. In ribosomopathies in which ribosome availability is altered by unbalanced production of ribosomal proteins, the threshold downregulation of ribosome biogenesis could be prematurely reached and, together with pathological p53 activation, prevents a normal expansion of erythroid progenitors.