Accumulation and Depuration of Nonylphenol and Its Effect on the Expressions of Vitellogenin and Vitellogenin Receptor in Freshwater Prawn Macrobrachium rosenbergii.
Accumulation of nonylphenol (NP) in hepatopancreas, gonad, eyestalk, and muscle of freshwater prawn Macrobrachium rosenbergii following 72 h exposure to 100 µg/L NP, and depuration of NP in these tissues at 0.5-192 h post exposure were examined. We also examined the expressions of vitellogenin (Vg) and vitellogenin receptor (VgR) of prawn following 0-20 days exposure to 0, 1, 10, and 100 µg/L NP. NP accumulation in hepatopancreas and gonad with high concentration, and low concentration in muscle, but depurated faster in eyestalk and muscle. The expressions of vitellogenin (Vg) and vitellogenin receptor (VgR) increased directly with dose and time. In conclusion, NP accumulated significantly in gonad together with high Vg and VgR expressions, and depurated slow in hepatopancreas and gonad when prawns were removed back to control water. The induction of Vg and VgR under NP exposure might be a stress response in M. rosenbergii.


Collision avoidance behavior as a function of aging and tennis playing.
Daily living often requires pedestrians and drivers to adapt their behavior to the displacement of other objects in their environment in order to avoid collision. Yet little research has paid attention to the effect of age on the completion of such a challenging task. The purpose of this study was to examine the relationship between age and collision avoidance skill and whether a sporting activity affects this. Three age groups (20-30, 60-70, and 70-80 years) of tennis players and non-players launched a projectile toward a target in order to hit it before it was hit by another "object" (a stimulus represented by apparent motion of lights). If the participant judged that time-to-collision (TTC) of the moving stimulus was not long enough for him/her to launch the projectile in time to arrive before the stimulus, the participant had to inhibit the launching. Results showed that for the non-players the number of errors in the 70-80 year-old group was significantly higher than those of the 20-30 and 60-70 year-old groups, which did not differ from each other. However, this increase was not observed in the 70-80 year-old tennis players, demonstrating a beneficial effect of playing tennis on collision avoidance skill. Results also revealed that the older groups of both tennis players and non-players were subject to the typical age-related increase in response time. Additional analyses indicated that the 70-80 year-old non-players did not adjust their actions to these age-related changes in response time. The older tennis-playing participants, however, were more likely to adjust collision avoidance behavior to their diminished response times.


Gano oil: A novel antinociceptive agent extracted from Ganoderma lucidum inhibits paw oedema and relieves pain by hypnotic and analgesic actions of fatty acid amides.
Lingzhi or Reishi - Ganoderma lucidum (Fr.) P. Karst is an extensively used medicinal mushroom in folklore and traditional medicine in south East Asia to treat a number of diseases. Lingzhi is known as 'mushroom of immortality' in Chinese folklore. In Traditional Chinese Medicine it is considered as a panacea to cure all diseases. This study aims to evaluate antinociceptive effect of Gano oil, a novel fatty acid rich extract obtained from G. lucidum and identification of the active principle. Gano oil extracted from Ganoderma lucidum was evaluated for inhibition of formalin-induced paw oedema on Swiss albino mice by oral administration as well as topical application. Antinociceptive activity of Gano oil was tested by acetic acid - induced abdominal writhing test as well as hot plate test. Free radical scavenging activity was determined by DPPH assay. COX enzyme inhibiting activity was assayed using different concentrations of Gano oil exposed to LPS stimulated RAW 264.7 cell line. NF-kB inhibiting activity of Gano oil was assayed using Lentix-293T P65 Ds Red stable cell line by fluorescent imaging and flow cytometry analysis. Chemical profile of Gano oil was ascertained by HPTLC analysis and active principle was identified by HRLCMS analysis. The oral administration of Gano oil at doses of 10,25, 50 mg/kg b.wt showed 42, 58 and 73% inhibition of paw oedema while topical applications at dose of 1,5 and 10% reduced 33, 50 and 58% oedema respectively. Acetic acid writhing test showed that Gano oil inhibited 44.44% contortions (p < 0.001) and while in hot plate method Gano oil at 25 mg/kg b. wt showed response latency of 30.0 ± 2.08 s for 120 min compared to base 1.65 ± 0.32 s (p < 0.01). Gano oil at 100 μg/ml inhibited 50% COX enzyme activity (p < 0.01). High throughput flurescent imaging and flow cytometry assay revealed marked ability of Gano oil to inhibit NF-kB activity. Gano oil was found to possess dose dependent free radical scavenging activity as evident from DPPH assay. HPTLC analysis of Gano oil indicated the chemical figure print. HR LC-MS analysis showed the major chemical components were fatty acid amides namely, Oleamide, C18H35NO, M+281, Hexadecanamide, C16H33NO, M+255 and 9-oxo-10 (E) Octadecadienoic acid, C18H30O3 M+294. Fatty acid rich Gano oil extracted from G.lucidum is a novel antinociceptive agent capable to inhibit oedema by oral administration as well as topical application. The results indicate the pharmacological interest, clinical significance and therapeutic use. The finding suggests that Gano oil might be a potent natural product based analgesic. The effect might be assigned to the fatty acid amide constituents especially oleamide which has been demonstrated to have analgesic and hypnotic actions.


TRIM27-mediated ubiquitination of PPARγ promotes glutamate-induced cell apoptosis and inflammation.
Neurotoxicity induced by glutamate (Glu) is often used to study the signaling mechanism of neurological disorders. The identification of specific genetic factors that cause Glu-induced neurotoxicity provides evidence for the common pathways of neuronal apoptosis and inflammation. TRIM27 has been found to induce apoptosis and inflammation. Nevertheless, there is little evidence that TRIM27 is associated with Glu-induced neurotoxicity. We found that TRIM27 expression was increased in epilepsy patients and in HT22 cells following Glu treatment. Glu-mediated cell apoptosis, decreased PPARγ expression, and increased levels of cleaved Caspase-3 and IL-1β expression in HT22 cells were significantly inhibited by TRIM27 knockdown. TRIM27 overexpression significantly induced cell apoptosis and expression of cleaved Caspase-3 and IL-1β, but inhibited PPARγ expression in HT22 cells, which were reversed by ROZ, suggesting the involvement of PPARγ in TRIM27-mediated cell apoptosis and inflammation in HT22 cells. Mechanically, TRIM27 ubiquitinates and degrades PPARγ, following induces cleaved Caspase-3 and IL-1β expression. Clinically, increased expression of TRIM27 in epilepsy patients was associated with decreased PPARγ expression. Taken together, our study suggests that TRIM27-mediated ubiquitination of PPARγ promotes Glu-induced HT22 cell apoptosis and IL-1β release.


An fMRI study of whispering: the role of human evolution in psychological dysphonia.
Humans are the only species known to use whispering for communication, and humans are also the only species known to suffer from functional (psychological) aphonia, a condition in which only whispered and not vocalized speech can be produced. Thus, whispering is uniquely a human function and psychological aphonia is uniquely a human dysfunction; both can be considered to result from human evolution. We hypothesize that the human brain has developed one or more identifiable switching mechanisms that overlay whispering onto the mechanisms of normal speech production. Thus, for whispering the speech production system operates as for normal speech production, but the switch to whispering activates the laryngeal abductor muscle (and possibly the inferior pharyngeal constrictor) so that the larynx does not completely adduct and turbulence noise is produced at the larynx. We hypothesize that psychological aphonia results from involuntary or subconscious activation of this switching mechanism. Preliminary research leads us to hypothesize that there are two switching mechanisms. This research used functional magnetic-resonance imaging to contrast brain activity for both normal speech and whispering (versus silence) for normally phonic subjects in an imagined social situation. One pattern of results involved a decrease of overall activity for whispering, with possible activation of the corpus callosum, and possible crossover of the main locus of activation from the dominant to the nondominant side. The other involved increased overall activity for whispering versus normal voice, accompanied by an increase of activity in the frontal cortex. More participants exhibited the former pattern than the latter one. These results may be related to the fact that there are actually two types of psychological aphonia, one that occurs after bouts of severe coughing associated with lower-respiratory disorders and the other due to purely psychological factors. We hypothesize that these are associated with the two different switching mechanisms, an upper one associated with the conscious brain and a lower one associated with more basic functions such as protecting the vocal folds. Understanding brain mechanisms for voluntary whispering and relating them to the occurrence of dysphonia has obvious implications for improving clinical assessment and treatment of aphonia, and would also contribute to improved understanding of human function in general.


Simultaneous Labeling of Adipogenic and Osteogenic Differentiating Stem Cells for Live Confocal Analysis.
Adipocytes and osteoblasts derive from a common mesenchymal progenitor present in a range of connective tissues. Differentiation of the progenitors toward the two cell lineages can be induced in vitro through well-established protocols, and leads to the appearance of lipid-laden adipocytes and osteoblasts embedded in a mineralized matrix. The formation of these two lineages in cell cultures can be monitored using lipophilic dyes such as Oil Red O and substances binding to mineral deposits such as Alizarin Red S, respectively. However, these common staining techniques require cell fixation and are thus incompatible with live analyses. Recently, alternative approaches using vital stains have allowed the dual visualization and fluorescence imaging of adipogenic and osteogenic lineages in live cultures. Here we present the concomitant analysis of cultures containing adipogenic and osteogenic cell types using live staining, combining LipidTox Red and tetracycline with NucRed nuclear counterstain for confocal imaging. This approach can be applied to visualize the kinetics and 3D structure of differentiating mesenchymal cultures over time and highlights the interaction of adipose and mineralized compartments associated with bone marrow stroma.


Associations between measures of gait stability, leg strength and fear of falling.
Fear of falling (FoF) in elderly frequently leads to decreased quality of life. FoF is suggested to be associated with changes in gait quality and muscle strength with aging. The aim of this study was to determine whether gait quality and maximal voluntary torque (MVT) of knee extensor muscles are associated with FoF. We hypothesized that high between-stride variability and local divergence exponent (LDE) of trunk kinematics in gait are associated with higher FoF in non-fallers, but not in fallers. Moreover, we hypothesized that knee extensor muscle strength is associated with a high variability and LDE of trunk kinematics during gait. 134 four adults, aged 62.4 (SD 6.2) years agreed to participate. FoF was assessed on a 10-point numerical rating scale. Subjects with at least one fall in the past 12 months were considered as fallers. LDE and variability were calculated from data of a trunk-mounted inertial-sensor collected during several minutes of treadmill walking. Maximal voluntary knee extension torque (MVT) was assessed isometrically. Fall history was an effect modifier in the association between LDE and FoF only, i.e. only subjects without fall history and a high LDE had a five times higher chance of reporting FoF. Gait variability was not associated with FoF. Low MVT was associated with FoF. Multivariate analysis demonstrated that LDE was more strongly associated with FoF than MVT. Decreased stability of gait as reflected in a high LDE and low muscle strength are associated with and a potential cause of FoF in subjects without fall history.


Visual impairment increases the risk of dementia, especially in young males in a 12-year longitudinal follow-up study of a national cohort.
We investigated the effect of visual impairment (VI) on dementia development in a national cohort. In this 12-year nationwide population-based retrospective cohort study, national data were collected from National Health Insurance Cooperation of South Korea from 2002 to 2017, comprising 799,074 subjects selected from the dementia-free cohort representative of the Korean population. Crude hazard ratios (HRs) as well as age- and sex-adjusted HRs and confidence intervals (CIs) for the development of dementia were estimated using multivariable Cox regression models. VI significantly increased the risk of dementia with a HR of 2.726 (95% CI 2.251-3.300, p < 0.0001) after adjusting for age, sex, and interaction between age, sex, and VI. HR of interaction between VI and age for dementia was 0.539 (95% CI 0.436-0.667, p < 0.0001). In the sensitivity analysis after adjustment for age, sex, household income level, BMI and other comorbidities, VI showed higher risk for all the type of dementia (p < 0.0001). In subgroup analysis of VI, young males showed the highest risk for development of dementia with a HR of 2.687 (95% CI 2.219-3.254, p < 0.0001). VI significantly increased the risk of dementia in the study cohort, and young males with VI appeared to be the most susceptible to the development of dementia.


Long-term safety and clinical outcomes of intrathecal heparan-N-sulfatase in patients with Sanfilippo syndrome type A.
Currently, there is no effective therapy for mucopolysaccharidosis IIIA (MPS IIIA). Intravenously-administered enzyme replacement therapies, while effective in other forms of MPS without neurological involvement, have not been successful in patients with MPS IIIA, as they are unable to cross the blood-brain barrier to improve neurological symptoms. We evaluated the long-term safety, tolerability, and clinical outcomes of recombinant human heparan-N-sulfatase (rhHNS) administered intrathecally (IT) in children with MPS IIIA in a phase 1/2 extension study. Patients aged ≥3 years with MPS IIIA who had previously completed a phase 1/2 study and received ≥5 of the 6 planned rhHNS infusions via IT administration, were eligible for inclusion. Patients who received 10 mg in the phase 1/2 study had their dose increased to 45 mg. Patients who were treated with 45 mg or 90 mg rhHNS IT in the phase 1/2 study remained on this monthly dose in the extension study. rhHNS was administered via an intrathecal drug delivery device (IDDD). Primary endpoints included the type and severity of adverse events, presence of anti-rhHNS antibodies in the CSF and serum, and changes in laboratory values. Secondary endpoints included standardized neurocognitive assessments and brain magnetic resonance imaging. In the extension study, 12 patients with a mean (SD) age of 9.6 (7.3) years continued treatment with rhHNS IT for a median of 264.4 weeks. Ten of 12 patients completed the extension study. rhHNS IT was generally well-tolerated. All patients experienced at least one treatment-emergent adverse event (TEAE), most being mild or moderate in severity. No serious adverse events (SAEs) were considered related to the study drug, and no deaths occurred. Most SAEs were related to malfunctions of the IDDD. Declines from baseline in Bayley Scales of Infant Development, Third Edition or Kaufman Assessment Battery for Children, Second Edition, Nonverbal Index developmental quotient scores were evident at all rhHNS dosing groups: -17.97%, -18.99%, and -12.12% in the 10/45, 45, and 90 mg groups, respectively, at Month 54. Overall, rhHNS IT was well tolerated in the extension study. However, rhHNS IT was unable to slow the neurocognitive decline of patients with MPS IIIA. This study was subsequently terminated early because pre-specified efficacy criteria were not met, and the study did not yield clinical proof of concept. (Clinicaltrials.gov Identifier NCT01299727).


Rapid implementation of an evidence-based remote triaging system for assessment of suspected referrals and patients with head and neck cancer on follow-up after treatment during the COVID-19 pandemic: Model for international collaboration.
Outpatient telemedicine consultations are being adopted to triage patients for head and neck cancer. However, there is currently no established structure to frame this consultation. For suspected referrals with cancer, we adapted the Head and Neck Cancer Risk Calculator (HaNC-RC)-V.2, generated from 10 244 referrals with the following diagnostic efficacy metrics: 85% sensitivity, 98.6% negative predictive value, and area under the curve of 0.89. For follow-up patients, a symptom inventory generated from 5123 follow-up consultations was used. A customized Excel Data Tool was created, trialed across professional groups and made freely available for download at www.entintegrate.co.uk/entuk2wwtt, alongside a user guide, protocol, and registration link for the project. Stakeholder support was obtained from national bodies. No remote consultations were refused by patients. Preliminary data from 511 triaging episodes at 13 centers show that 77.1% of patients were discharged directly or have had their appointments deferred. Significant reduction in footfall can be achieved using a structured triaging system. Further refinement of HaNC-RC-V.2 is feasible and the authors welcome international collaboration.


pH-induced destabilization of lipid bilayers by a lipopeptide derived from influenza hemagglutinin.
A synthetic twenty-one amino acid peptide (AcE4K) based on the amino acid sequence of the influenza HA2 fusion peptide was coupled to a distearoylglycerol lipid anchor by amidation of an N-terminal lysine side chain. The secondary structure of Lipo-AcE4K incorporated into POPC (1-palmitoyl-2-oleoyl-sn-phosphatidylcholine) liposomes was not measurably affected by pH, but increased membrane penetration was indicated by tryptophan fluorescence. At outer monolayer concentrations up to 10 mol%, Lipo-AcE4K formed stable liposomes with POPC and EPC/Chol (egg phosphatidylcholine/cholesterol) (55:45) at pH 7.5. Acid-induced destabilization and fusion of these vesicles were demonstrated by fluorescent lipid mixing and contents leakage assays, and by freeze-fracture electron microscopy. Membrane destabilization increased with increasing lipopeptide concentrations, decreasing pH, inclusion of cholesterol, and incorporation of lipopeptide into the inner monolayer as well as the outer monolayer of the liposomes. Fusion of liposomes bearing Lipo-AcE4K with erythrocyte ghosts was demonstrated by lipid mixing and fluorescence microscopy.


Near-infrared light-triggered synergistic antitumor therapy based on hollow ZIF-67-derived Co3S4-indocyanine green nanocomplex as a superior reactive oxygen species generator.
Reactive oxygen species (ROS) with strong oxidability have been considered as effective agents for antitumor therapy through oxidative damage to lipids, proteins, DNA and RNA. In this work, a multifunctional hollow cobaltosic sulfide (Co3S4)/photosensitizer indocyanine green (ICG) nanocomplex (Co3S4-ICG) has been synthesized by efficiently loading ICG into the hollow Co3S4 to realize synergistic antitumor therapy via chemodynamic therapy (CDT), photodynamic therapy (PDT) and photothermal therapy (PTT) under near-infrared (808 nm) laser irradiation. Co3S4 nanoparticles would be degraded in tumor acidic microenvironment into Co2+, which locally triggers a Fenton-like reaction to produce cytotoxic hydroxyl radicals (OH) for CDT. Co3S4-ICG could also produce singlet oxygen (1O2) through a multi-step photochemical process for PDT under 808 nm laser irradiation. The slow release of ICG in the tumor region was achieved due to hollow-structured Co3S4 working as nanocarriers, and which has been proved an effective approach for combined CDT/PDT. In addition, Co3S4-ICG showed high photothermal conversion efficiency (40.5%) for PTT, and excellent OH generation capability via photothermal-improved Fenton reaction, leading to the synergistically improved antitumor efficacy. In vitro and in vivo experimental results confirm that the combined PTT/PDT/photothermal-enhanced CDT therapy can effectively ablate tumors with a negligible systemic toxicity. This work provides a valuable strategy for designing and constructing of a multifunctional nanoplatform for synergistic antitumor therapy of solid tumors.


Outcome of radical multiple synovectomy as a novel surgical treatment for refractory rheumatoid arthritis: implication of HLA-DRB1*0405 in post-operative results.
The authors developed a technique for radical multiple synovectomy (RaMS), a novel surgical treatment for refractory rheumatoid arthritis (RA) intended to control RA activity as much as possible. The purpose of this article is to describe the technique and its short-term results. Eighteen RA patients were followed up for at least 3 years after RaMS. Post-operative results were determined and the significance of the HLA-DRB1 alleles was studied. Six patients met the ARA criteria for clinical remission persistently and were classified as "remission" cases. Thirteen patients in whom the limited Lansbury index remained improved were rated as "improvement". The cumulative success rates for "remission" and "improvement" were 33.3% and 57.8%, respectively, at the time point of the latest observation. Remission was not achieved in any of the DRB1*0405-positive patients. Nine out of 10 DRB1*0405-negative patients showed persistent improvement. RaMs provided good results in one-third of patients with refractory RA at a minimum of 3 years. HLA-DRB1*0405 may be a good marker to follow the effects of RaMS in RA patients.


COX-2-selective inhibitor, etodolac, suppresses choroidal neovascularization in a mice model.
Cyclooxygenases (COXs) are involved in choroidal neovascularization (CNV). However, the relative contribution of COX-1 and -2 to CNV has not been determined. In this study, the expression of COX-2 was investigated in CNVs in a murine laser-induced model. Subsequently, we found that experimental CNV expressed COX-2, most remarkably around the highly vascularized lesions. To examine the effect of COX-2 inhibition on CNV, etodolac, a non-steroidal anti-inflammatory drug with a high COX-2 selectivity, was tested on murine CNV model. The results demonstrated that the intensity of fluorescein leakage from the photocoagulated lesions decreased significantly compared to the control eyes following etodolac administration. The area of CNV lesions, as examined using histological sections and choroidal flatmounts at day 7, demonstrated that the average size of the CNV lesions was significantly reduced in the etodolac-treated eyes compared to the control eyes. Together, our results demonstrated that selective COX-2 inhibition suppresses CNV.


Antibody W7C5 defines a CD109 epitope expressed on CD34+ and CD34- hematopoietic and mesenchymal stem cell subsets.
The cell surface antigen recognized by monoclonal antibody W7C5 is expressed at low levels on human CD34(+) and CD34(-) bone marrow stem cell populations but at high levels on fetal liver CD34(+) cells. To identify the recognized antigen, we performed partial amino acid sequence and MALDI analysis of purified W7C5 antigens. The analyses revealed that MoAb W7C5 detects CD109, a recently cloned glycophosphatidylinositol-linked glycoprotein. The specificity of MoAb W7C5 was further confirmed by the selective recognition of CHO cells transfected with human CD109 cDNA.


Allergic reactions to latex among health-care workers.
With the emergence of the acquired immunodeficiency syndrome (AIDS) epidemic and the practice of protecting health-care workers from all body fluids, the use of rubber gloves has increased, as has occupational allergy to latex among health-care workers. During 1991, 49 Mayo Medical Center employees sought assessment and treatment of rhinitis, conjunctivitis, contact urticaria, contact dermatitis, asthma, or eczema thought to be related to exposure to latex. Most of these persons had a history of atopy and worked in areas where rubber gloves were used and changed frequently. Of the 49 subjects, 34 had positive results of skin tests to latex products, and the sera from 19 of 35 persons tested contained increased latex-specific IgE antibodies. Employees with sensitivity to latex (and co-workers in the immediate areas) should use vinyl gloves and should notify their own health-care providers of their sensitization. Changes in job assignment may be necessary for some persons.


Ruptured uterus in a Nigerian community: a study of sociodemographic and obstetric risk factors.
Ruptured uterus is a common obstetric emergency in Nigeria, associated with high maternal and perinatal morbidity and mortality. There is a need for definitive identification of the risk factors to guide effective interventions to curb its scourge. To identify the sociodemographic and obstetric risk factors for ruptured uterus in Benin City, Nigeria, and based on this, make appropriate recommendations toward curbing the incidence and morbidity and mortality associated with it. Sociodemographic and obstetric variables in 51 women with ruptured uterus and 300 randomly selected hospital controls from the general obstetric population were compared. Fisher's exact test was used to determine statistical significance between proportions. The incidence of ruptured uterus was 1 in 426 deliveries. The risk factors found were low socioeconomic class (OR = 6.8, CI = 3.6-12.9), being unbooked for antenatal care (OR = 10.4, CI = 5.4-20.0), grand multiparity (OR = 8.7, CI = 4.0-19.1), and prolonged obstructed labor (OR = 35.3, CI = 15.3-81.6). Measures that promote education and economic empowerment of women and the utilization of modern antenatal care will reduce the prevalence of rupture of the uterus in the community.


Routine use of autotransfusion following cardiac surgery: experience in 700 patients.
An autotransfusion technique has been developed for collection and reinfusion of shed mediastinal blood. This system has been routinely applied in the postoperative management of 592 consecutive adult and 108 pediatric cardiac surgical patients. Two hundred seventy-one adult patients (46%) and thirty-six pediatric patients (33%) actually received autologous blood. Autotransfusion volume ranged from 50 to 21,350 ml per patient. In 1976 at our institution, homologous transfusion requirements averaged 8.4 +/- 0.7 units per adult patient. During 1978, with the routine use of postoperative autotransfusion, bank blood transfusions were lowered to 4.2 +/- 0.3 units per patient (p less than 0.001). In contrast to perioperative autotransfusion techniques, collection and reinfusion of shed mediastinal blood is particularly useful for intravascular volume replacement in patients with serious postoperative bleeding.


Immune privilege and FasL: two ways to inactivate effector cytotoxic T lymphocytes by FasL-expressing cells.
The theory that Fas ligand (FasL)-expressing tumours are immune-privileged and can directly counterattack Fas-expressing effector T lymphocytes has recently been questioned and several alternative mechanisms have been proposed. To address this controversial issue, we analysed the impact of FasL-expressing tumours on in vivo-primed cytotoxic T lymphocytes (CTLs) and the mechanisms involved. CTLs were obtained from the peritoneal cavity (PEL) after in vivo priming with syngeneic or allogeneic murine tumour cells. We have found that PEL populations undergo Fas-based apoptotic cell death when co-cultured with FasL-expressing tumour cells and that PEL destruction of cognate targets in a 51Cr-release assay was markedly inhibited by the pre-exposure to either cognate or non-cognate tumour cells expressing FasL. Furthermore, cytocidal function of PEL was markedly inhibited by preincubation with FasL-negative tumour cells, if and only if they were the cognate targets of the CTL; this CTL inhibition involved FasL-Fas interactions. The killing function of 'bystander' PELs, reactive to a third-party target cell, was inhibited by co-cultivation with PELs mixed with their cognate target. This activation-induced CTL fratricide was not influenced by the expression of FasL on the cognate target cells. These studies demonstrate the existence of two distinct pathways whereby FasL-expressing cells inhibit in vivo-primed FasL- and Fas-expressing CTLs: first, by FasL-based direct tumour counterattack, and second, by FasL-mediated activation-induced cell death of the CTLs, which is consistent with the concept that FasL expression in vivo could play a role in inducing immune privilege.


Vernonia cinerea regenerates tubular epithelial cells in cisplatin induced nephrotoxicity in cancer bearing mice without affecting antitumor activity.
Traditional Siddha Medicine advises using metal-based formulations to treat cancers. In the case of any toxicities during the therapy, Siddha physicians use Vernonia cinerea (VC) whole plant kashayam (crude aqueous extract-CAE) to reverse the toxic effects. To evaluate the nephroprotective activity of CAE and its fractions in cisplatin-induced nephrotoxicity and to assess whether they compromise the anticancer efficacy of cisplatin. Cisplatin-induced renal damage was induced in Ehrlich Ascites Carcinoma (EAC) bearing mice during mild phase of tumor growth. CAE and its butanol (BF) and aqueous (AF) fractions were administered orally from the 5th day for five days. Nephroprotective potential (serum urea, creatinine, renal histology) and effect of VC on cisplatin anticancer efficacy (tumor volume, viable tumor cells, percentage increase in life span (% ILS)) were calculated. CAE and its fractions significantly reversed the cisplatin-induced renal damage. CAE and BF treated animals showed regeneration of 50%-75% of proximal tubular cells. Compared to EAC control mice, the % ILS of the cisplatin-treated group was 244% and it was further extended to 379% after CAE administration. The % ILS in the CAE treated group was 1.6 times higher than the cisplatin alone treated group. GC-MS study showed the presence of astaxanthin and betulin. CAE of VC reverses cisplatin-induced kidney damage as well as regenerates proximal tubular epithelial cells, without compromising the anticancer effect of cisplatin. When CAE was further fractionated, the nephroprotective activity was retained, but the beneficial anticancer effect of cisplatin was compromised.


Can Princesses Be Powerful? A Quasi-Experimental Study Examining Children's Perceptions of Princesses and the Self.
Children's gender schematic cognitions guide their attention, affinities, and behaviors, often narrowing their opportunities. The goal of the present study is to examine how children's exposure to animated Disney princesses modeling agentic behaviors (such as being a leader) alters children's gender schematic perceptions of princesses' characteristics, and if this exposure impacts children's perceptions of their own gender-typed qualities. Interviews with 60 children from the northeast region of the United States (Mage = 4.5 years old) at the beginning and end of six weeks indicate that, as hypothesized, children's perceptions of princesses and themselves became less gender schematic after cumulative exposure to animated videos depicting princesses modeling agentic behaviors. Children's perceptions of princesses' agency and their own agency increased throughout the study, asserting that with exposure to nontraditional gender-typed characters, children begin to see themselves as less gender-typed. These findings provide new insights into the role of early children's media exposure in shaping children's gender cognitions.


Biochemical genetics and mental retardation: a study of hemoglobins, Australia antigen and the enzymes pseudocholinesterase and glucose-6-phosphate dehydrogenase.
The study reports results of investigations on hemoglobin, pseudocholinesterase, Australia antigen and glucose-6-phosphate dehydrogenase in 153 mental retardates and 161 controls. beta-thalassemia and the hemoglobin phenotype AS occurred more in patients. At the pseudocholinesterase locus, the patients had significantly higher frequencies of E1a and E1f (p less than 0.001). Mental retardation was found to be associated also with presence of Australia antigen and with G-6-PD deficiency. A model to explain these findings has been proposed.


ETV4 promotes pancreatic ductal adenocarcinoma metastasis through activation of the CXCL13/CXCR5 signaling axis.
Pancreatic ductal adenocarcinoma (PDAC) has the highest fatality rate of any solid tumor, with a five-year survival rate of only 10% in the USA. PDAC is characterized by early metastasis. More than 50% of patients present with distant metastases at the time of diagnosis, and the majority of patients will develop metastasis within 4 years after tumor resection. Despite extensive studies, the molecular mechanisms underlying PDAC metastasis remain unclear. The polyoma enhancer activator protein (PEA3) subfamily was reported to play a vital role in the initiation and progression of multiple tumors. Herein, we found that ETS variant 4 (ETV4) was highly expressed in PDAC tissues and associated with poor survival. Univariate and multivariate analyses revealed that ETV4 expression was an independent prognostic factor for patient survival. Further experiments showed that ETV4 overexpression promoted PDAC invasion and metastasis both in vitro and in vivo. For the first time, we demonstrated that, mechanistically, ETV4 increased CXCR5 expression by directly binding to the CXCR5 promoter region. Knockdown of CXCR5 significantly reversed ETV4-mediated PDAC migration and invasion, while CXCR5 overexpression exerted the opposite effects. Intriguingly, we found that CXCL13, a specific ligand of CXCR5, increased ETV4 expression and promoted PDAC invasion and metastasis by activating the ERK1/2 pathway. ETV4 knockdown significantly abrogated the enhanced migratory and invasive abilities induced by the CXCL13/CXCR5 axis. In addition, a CXCR5 neutralizing antibody disrupted the CXCL13/ETV4/CXCR5 positive feedback loop and inhibited cell migration and invasion. Overall, in this study, we demonstrated that ETV4 plays a vital role in PDAC metastasis and defined a novel CXCL13/ETV4/CXCR5 positive feedback loop. Targeting this pathway has implications for potential therapeutic strategies for PDAC treatment.


Tocilizumab reverses cerebral vasculopathy in a patient with homozygous SAMHD1 mutation.
An auto-inflammatory syndrome consequent to SAMHD1 mutations involves cerebral vasculopathy characterized by multifocal stenosis and aneurysms within large arteries, moyamoya, chronic ischemia, and early-onset strokes (SAMS). While this condition involves the innate immune system, additional clinical features mimic systemic lupus erythematosus. Mutations in this gene can also cause a subset of the rare genetic condition Aicardi-Goutières syndrome. To date, no established therapy successfully prevents disease progression. We report a corticosteroid-dependent SAMS patient, a 19-year-old male of Old Order Amish ancestry, with diffuse cerebral arteriopathy identified through contrast brain magnetic resonance arteriography (MRA) and MRI. He received subcutaneous adalimumab every 2 weeks for 9 months with minimal response. Then, he started intravenous tocilizumab (6 mg/kg/dose) every 4 weeks. He sustained steadily normalizing cerebral vasculopathy and lab abnormalities resolved, allowing prednisone reduction. We conclude that the cerebral vasculopathy of the homozygous SAMHD1 mutation-mediated auto-inflammatory disease SAMS responded favorably to tocilizumab infusion therapy.


Triclosan-induced liver and brain injury in zebrafish (Danio rerio) via abnormal expression of miR-125 regulated by PKCα/Nrf2/p53 signaling pathways.
Triclosan (TCS) is widely used in personal care products, and its chronic exposure leads to severely toxic effects in zebrafish (Danio rerio). PKCα, Nrf2 and p53 are three important signaling pathways concerned with cell development. Herein, we speculated on and verified a novel TCS regulatory pathway: (1) TCS acted on GPER (G-protein-coupled estrogen receptor) to activate MAPK/ERK pathway, further resulting in the expression changes of protein kinase C (PKC) family; (2) PKC participated in Nrf2 phosphorylation; (3) The expression of miR-125b was regulated by Nrf2; and (4) The expression changes of related genes in the PKCs-Nrf2-ARE pathway showed the specificity of zebrafish tissue and organ. TCS exposure led to down-regulation of the Nrf2 and phosphorylated Nrf2(Ser40) protein in diencephalon nucleus, stratum marginale and stratum centrale areas in adult zebrafish brain. The phosphorylated Nrf2(Ser40) was mainly expressed in PGz area, while it was not the case for Nrf2. Both Nrf2 and phosphorylated Nrf2 were activated by TCS exposure; however, the changing trend of PKCs was opposite to that of Nrf2 in the liver. Both DAPI staining and Merge images demonstrated that TCS induced oxidative phosphorylation, and phosphorylated Nrf2 is translocated into the nucleus as the transcription factor to regulate gene transcription in liver and brain. Nrf2 over-expression increased accumulation of lipid droplets in yolk, brain and liver, resulting from the upregulation of pri-miR-125b1, pri-miR-125b3, but not pri-miR-125b2. These findings reveal the upstream regulation mechanism of miR-125b for TCS-induced fat-metabolism disorder from the regulatory perspective of the pri-miR-125b promoter region.


High frequencies and co-existing of myositis-specific autoantibodies in patients with idiopathic inflammatory myopathies overlapped to rheumatoid arthritis.
A small proportion of patients with rheumatoid arthritis (RA) develop idiopathic inflammatory myopathies (IIM); however, the clinical and immunological characteristics of these patients have not been elucidated. In the present study, we evaluate the frequency of autoantibodies and the accompanying clinical features in patients with IIM overlapped to RA (IIM-RA) and in patients with IIM without RA. Twelve patients with IIM-RA were selected from 142 patients with IIM who were admitted to our hospital. Clinical and laboratory data, including autoantibody test results, were collected from patient medical records. Myositis-specific antibodies (MSAs) were analyzed by immunoprecipitation. Clinically, patients with IIM-RA were more likely to be male, to have polymyositis, and to be older at the time of IIM onset than patients with IIM without RA. Patients with IIM-RA had been treated for 2-25 years prior to the onset of IIM with more than two disease-modifying antirheumatic drugs (DMARDs). Patients with IIM-RA had a high frequency (75.0%) of positivity for MSAs, including anti-Jo-1, anti-PL-7, anti-PL-12, or anti-signal recognition particle (SRP) antibodies; anti-Jo-1 antibody was detected in 4 patients (33.3%). In addition, 2 out of 12 patients with IIM-RA were concurrently positive for two different MSAs, anti-Jo-1, and anti-PL-7 antibodies. In 3 other patients with IIM-RA, anti-Jo-1 antibody, or anti-PL-7 antibody was detected in serum samples collected 6-18 months prior to development of myositis. High frequency and coexistence of MSAs were detected in patients with IIM-RA. MSAs detected in patients with RA even without symptoms of myositis may indicate possible future development of myositis.


Advances in the knowledge of light emission by firefly luciferin and oxyluciferin.
Firefly luciferase is the most important and studied bioluminescence system. Due to very interesting characteristics, this system has gained numerous biomedical, pharmaceutical and bioanalytical applications, among others. In order to improve the use of this system, various researchers have tried to understand experimentally the colour of bioluminescence, and to create ways of tuning the colour emitted. The objective of this manuscript is to review the experimental studies of firefly luciferin and oxyluciferin, and related analogues, fluorescence and bioluminescence.


Prescription opiate medications: medical uses and consequences, laws and controls.
The proposed analysis and evaluation of the data elements in the OPP and other similar regulatory programs will support the following potential impact on the patients and physicians in Michigan and other states: Reduced rates of addictive use of prescriptions of Schedule II medications. Reduced rates of addictive patterns of prescribing of Schedule II medications. Improved the prescribing of Schedule II medication for pain disorders. Improved the prescribing of Schedule II medications in addictive disorders. Establish the need and direction for development of curriculum for Schedule II drugs for undergraduate medical education and continuing medical education. Establish the need and direction for development of curriculum for use of Schedule II medications in patients with addictive and pain disorders. Explore the need and direction for development of the monitoring system medical curriculum for Schedule III, IV, and V drugs. Demonstrate link between diversion and adverse effects on health caused by an addictive pattern of use and prescribing of Schedule II drugs


Effects of nifedipine and TMB-8 on renal vasoconstriction induced by hypertonic saline in dogs.
Intrarenal arterial infusion of hypertonic saline (+30 mEq/l NaCl in renal plasma) reduced renal blood flow and glomerular filtration rate with little change in filtration fraction in anesthetized dogs. The blood flow and the filtration rate responses were suppressed during infusion of nifedipine (0.1 microgram/kg per min). TMB-8 (50 micrograms/kg per min) also suppressed the blood flow response but not the filtration rate response. These results suggest that preglomerular vasoconstriction during hypertonic saline infusion requires Ca2+ influx via voltage-dependent Ca2+ channels and that hypertonic saline slightly contracts postglomerular vessels by activating a TMB-8-sensitive Ca2+ movement pathway.


Islet-1 expression and its colocalization with luteinising hormone, thyroid-stimulating hormone and oestrogen receptor alpha in the developing pituitary gland of the sheep foetus.
Islet-1 has been reported to be involved in pituitary development in the early stages of mouse embryogenesis. Oestrogen receptor (ER) and its expression may be involved in regulating pituitary development and its hormone-secreting function. Islet-1 expression and its correlations to ER in the developing pituitary gland are unknown. We therefore determined the pituitary cell specific expression of Islet-1 and its colocalization with ER alpha (ERalpha) in sheep foetus by immunohistochemistry. The results demonstrated that Islet-1-immunoreactive (ir) cells were distributed throughout the pituitary gland from day 60 of gestation until birth. The Islet-1-ir cell number was significant higher at day 90 and 120 of gestation compared to that at day 60 and at birth. All of the ERalpha-ir cells were colocalized with Islet-1 at day 60 of gestation, although a few ERalpha-ir cells were negative for Islet-1 in the later stage of gestation. The dominant cell type expressing Islet-1 is the gonadotroph, although small proportions of thyrotrophs and lactotrophs also express Islet-1. The proportion of luteinising hormone-ir gonadotrophs possessing Islet-1 kept rising from day 60 to day 120 of gestation and persisted until birth. The proportion of thyroid-stimulating hormone-ir cells expressing Islet-1 was at a high level from day 60-120 of the gestation and significantly declined at birth. The percentage of prolactin (PRL)-ir cells expressing Islet-1 was about 20% at day 60 of gestation. Very few PRL-ir cells contained Islet-1 in later stages of gestation. These data suggest that the development and functional establishment of pituitary gonadotrophs, thyrotrophs and lactotrophs might be regulated by the expressions of Islet-1 and ERalpha and by their interactions, although any mechanisms need to be elucidated further.


Human immunodeficiency virus (HIV)-negative plasmablastic lymphoma: a single institutional experience and literature review.
Plasmablastic lymphoma (PBL) is a rare aggressive B-cell lymphoproliferative disorder. HIV-negative PBL has not been extensively reported. Nine HIV-negative PBL patients evaluated at Moffitt Cancer Center were studied. Eight patients had extranodal diseases. All patients were treated with CHOP or hyper-CVAD. Responses were observed in 8 cases (7 complete, 1 partial responses). Four patients underwent consolidation with autologous hematopoietic stem cell transplant (HSCT) in first complete remission (CR1). At median follow-up of 23.9 months, 7 patients were alive and 5 were disease-free. Aggressive induction chemotherapy and consolidation with autologous HSCT in CR1 might be considered for patients with HIV-negative PBL.


Elevated cPLA2 levels as a mechanism by which the p70 TNF and p75 NGF receptors enhance apoptosis.
The 70-kDa TNF cell surface receptor (p70TNFR) and the related 75-kDa nerve growth factor (NGF) receptor (p75NGFR) can enhance cell death. Expression of p70TNFR or p75NGFR in HeLa cells resulted in enhanced TNF-induced apoptotic cell death with a corresponding elevation of cytosolic phospholipase A2 (cPLA2) levels. This response was apparent by 24 h, did not occur with NGF treatment or when vector or TrkA NGFR were expressed and was reversed by dexamethasone pretreatment. These findings reveal a novel mechanism by which the p70TNFR and p75NGFR achieve enhanced TNFR-mediated programmed cell death by elevating cPLA2 levels.


Sex as an important factor in nanomedicine.
Nanomedicine has demonstrated substantial potential to improve the quality and efficacy of healthcare systems. Although the promise of nanomedicine to transform conventional medicine is evident, significant numbers of therapeutic nanomedicine products have failed in clinical trials. Most studies in nanomedicine have overlooked several important factors, including the significance of sex differences at various physiological levels. This report attempts to highlight the importance of sex in nanomedicine at cellular and molecular level. A more thorough consideration of sex physiology, among other critical variations (e.g., health status of individuals), would enable researchers to design and develop safer and more-efficient sex-specific diagnostic and therapeutic nanomedicine products.


State of the CAR-T: Risk of Infections with Chimeric Antigen Receptor T-Cell Therapy and Determinants of SARS-CoV-2 Vaccine Responses.
Chimeric antigen receptor T cell (CAR-T) therapy has shown unprecedented response rates in patients with relapsed/refractory (R/R) hematologic malignancies. Although CAR-T therapy gives hope to heavily pretreated patients, the rapid commercialization and cumulative immunosuppression of this therapy predispose patients to infections for a prolonged period. CAR-T therapy poses distinctive short- and long-term toxicities and infection risks among patients who receive CAR T-cells after multiple prior treatments, often including hematopoietic cell transplantation. The acute toxicities include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. The long-term B cell depletion, hypogammaglobulinemia, and cytopenia further predispose patients to severe infections and abrogate the remission success achieved by the living drug. These on-target-off-tumor toxicities deplete B-cells across the entire lineage and further diminish immune responses to vaccines. Early observational data suggest that patients with hematologic malignancies may not mount adequate humoral and cellular responses to SARS-CoV-2 vaccines. In this review, we summarize the immune compromising factors indigenous to CAR-T recipients. We discuss the immunogenic potential of different SARS-CoV-2 vaccines for CAR-T recipients based on the differences in vaccine manufacturing platforms. Given the lack of data related to the safety and efficacy of SARS-CoV-2 vaccines in this distinctively immunosuppressed cohort, we summarize the infection risks associated with Food and Drug Administration-approved CAR-T constructs and the potential determinants of vaccine responses. The review further highlights the potential need for booster vaccine dosing and the promise for heterologous prime-boosting and other novel vaccine strategies in CAR-T recipients. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.


Lateral maxillary sinus floor elevation in the presence of a sinus osteoma: A case report.
Eventhough the lateral sinus floor elevation is a well-documented procedure, many factors can increase its difficulty. The presence an osteoma can be very challenging and must be managed with caution taking in consideration the lesions's size and extension.


Histological confinement of transglutaminase-mediated nit sheath crosslinking is essential for proper oviposition and egg coating in the human head louse, Pediculus humanus capitis.
Background Head louse females secrete liquid gel, which is mainly composed of the louse nit sheath protein 1 (LNSP1) and LNSP2, when they lay eggs. The gel is crosslinked by transglutaminase (TG) to form the nit sheath, which covers most part of egg except the top operculum area where breathing holes are located. Knowledge on the selective mechanism of nit sheath solidification to avoid uncontrolled crosslinking could lead to design a novel way of louse control, but no information is available yet. Methods To elucidate the crosslinking mechanisms of nit sheath gel inside the reproductive system of head louse females, in situ hybridization in conjunction with microscopic observation of the oviposition process was conducted. Results Histochemical analysis revealed that LNSP1 and LNSP2 are expressed over the entire area of accessory gland and uterus, whereas TG expression site is confined to a highly localized area around the opening of posterior oviduct. Detailed microscopic observations of oviposition process uncovered that a mature egg is positioned in the uterus after ovulation. Once aligned inside the uterus, the mature egg is redirected so that its operculum side tightly held by the ventral end of uterus being positioned toward the head again and its pointed bottom end being positioned toward the dorsal end of uterus, which functions as a reservoir for the nit sheath gel. Conclusions Physical separation of the TG-mediated crosslinking site from the ventral end of uterus is necessary to avoid uncontrolled crosslinking inside the uterus and to ensure selective crosslinking over only the lower part of egg without any unwanted crosslinking over the operculum during oviposition.


Characteristics of immune checkpoint regulators and potential role of soluble TIM-3 and LAG-3 in male patients with alcohol-associated liver disease.
The involvement of immune checkpoint regulators (ICs) in alcohol-associated liver diseases (ALDs) is still largely unknown. Here, we analyzed the levels of 16 soluble ICs (sICs) in male patients with ALD to determine their clinical significance. The 16 sICs were measured using a luminex-based multiplex assay in 115 patients with ALD and 47 healthy controls (HCs). The expressions of membrane-type (m) PD-1 and mCTLA-4 on CD4+ and CD8+ T lymphocytes and NK cells of 28 patients with ALD and 8 HCs were also measured. Correlation test and risk assessment were also conducted to evaluate biomarkers of ALD in clinical practice. Our results show that four sICs were upregulated (sCTLA-4, sTIM-3, sCD27, and sGITR) and two sICs were downregulated (sLAG-3 and sHVEM) in ALD. mPD-1 expression was significantly more greatly increased on CD4+T lymphocytes in the ALD group than in the HC group (p = 0.009). sTIM-3 was positively correlated, while sLAG-3 was negatively correlated with non-invasive liver fibrosis markers (AST/ALT, APRI, GPR, and FIB-4) and Maddrey discriminant function score. Risk factor analysis showed that sTIM-3 was consistently associated with ALD severity in both MDF and FIB-4 scores, and sLAG-3 was associated with FIB-4 scores. This study revealed the involvement of sCTLA-4, sTIM-3, sCD27, sGITRL, sLAG-3, and sHVEM in discriminating male patients with ALD. Expressions of sTIM-3 and sLAG-3 were correlated with liver fibrosis markers and significantly associated with ALD severity, which can be further studied as diagnostic markers and therapeutic targets in ALD.


Sequential development of diffuse large B-cell lymphoma in a patient with angioimmunoblastic T-cell lymphoma.
Lymphoma of different histologic type can occur in the same patient. Here, we describe a 64-year-old male patient with angioimmunoblastic T-cell lymphoma (AITL) who subsequently developed diffuse large B-cell lymphoma (DLBCL). At the time of initial diagnosis, histologic examination of a left inguinal lymph node of the patient and a monoclonal pattern of TCRβ gene rearrangement showed typical features of AITL, and there was no evidence of a monoclonal B-cell population. Twenty-six months later, he had generalized lymphadenopathy and organs involvement by DLBCL. A monoclonal IgH gene rearrangement proved de novo development of secondary B-cell lymphoma and excluded relapse of a primary composite lymphoma. The in situ hybridization analysis showed Epstein-Barr-encoded RNA (EBER) sporadic positivity in sample collected from AITL but extensive positivity in the immunoblasts collected from DLBCL. Our observation supports the hypothesis that Epstein-Barr virus (EBV) is etiologically related to AITL in this case. Clonal expansion of EBV-associated DLBCL is a secondary event in AITL via EBV infection or reactivation.


Peripheral facial nerve palsy in children in a Borrelia high-endemic area, a retrospective follow-up study.
To identify the incidence, aetiology and prognosis of acute peripheral facial nerve palsy (FNP) in children in the Borrelia high-endemic region of Stockholm. The present study identified children from 0 to 18 years of age who visited a paediatric emergency department for acute peripheral FNP during a 1-year period from 2014 to 2015. Data were collected retrospectively. The Sunnybrook and House-Brackmann facial grading systems were used to measure clinical outcome. A total of 77 children were identified with FNP, an estimated incidence of 30 per 100 000 children/year. Forty-five children (58%) were diagnosed with neuroborreliosis, 28 (36%) with idiopathic FNP and four (6%) with other rarer causes. Neuroborreliosis was common from June to November and mainly seen in children below 10 years of age. Six patients (8%) had remaining symptoms at least 3 months after onset; three had idiopathic facial palsy (IFP) and were all older than 10 years, one had neuroborreliosis and two had other causes. Neuroborreliosis and IFP were the major causes of FNP during the study period. Neuroborreliosis-associated facial palsy had a seasonal variation and dominated in younger ages.


Serum calprotectin: a promising biomarker in rheumatoid arthritis and axial spondyloarthritis.
Calprotectin (S100A8/S100A9 protein) is known as a damage-associated molecular pattern (DAMP) protein and reflects mainly neutrophil activation. Serum calprotectin levels might be a good alternative to acute-phase protein as a biomarker in inflammatory rheumatic diseases. The aim of this study is to investigate the association of serum calprotectin with disease activity and severity in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), and psoriatic arthritis (PsA). Serum calprotectin was measured in patients with RA, axSpA, and PsA from the prospective Swiss Clinical Quality Management (SCQM) registry. Asymptomatic first-degree relatives of RA patients were used as healthy controls (HC). Outcomes included swollen joint count (SJC), Disease Activity Score (DAS), Health Assessment questionnaire (HAQ), joint radiographs, and ultrasound power Doppler (USPD) score for RA; Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS) and coxitis for axSpA; and SJC and Disease Activity Index for PSoriatic Arthritis (DAPSA) for PsA. Comparison of outcomes by calprotectin quartile levels was performed using Kruskal-Wallis tests for continuous outcomes or trend tests for categorical outcomes. A total of 1729 subjects [RA = 969, axSpA = 451, PsA = 237, and HC = 72] were included. Median levels of serum calprotectin were higher in each disease group compared to HC (p < 0.01). In RA patients, all clinical outcomes were statistically different between quartiles of serum calprotectin, indicating an association between calprotectin levels and higher disease activity (SJC, DAS, and USPD scores) and severity (joint radiographs and HAQ). In axSpA, an association between calprotectin levels and ASDAS score (p < 0.01) and prevalence of coxitis (p = 0.02) was observed. For PsA patients, SJC and DAPSA did not differ across calprotectin quartiles. This large study supports the association of serum calprotectin levels with disease activity in both RA and axSpA, but not in PsA.


Identification of regulatory factors promoting embryogenic callus formation in barley through transcriptome analysis.
Barley is known to be recalcitrant to tissue culture, which hinders genetic transformation and its biotechnological application. To date, the ideal explant for transformation remains limited to immature embryos; the mechanism underlying embryonic callus formation is elusive. This study aimed to uncover the different transcription regulation pathways between calli formed from immature (IME) and mature (ME) embryos through transcriptome sequencing. We showed that incubation of embryos in an auxin-rich medium caused dramatic changes in gene expression profiles within 48 h. Overall, 9330 and 11,318 differentially expressed genes (DEGs) were found in the IME and ME systems, respectively. 3880 DEGs were found to be specific to IME_0h/IME_48h, and protein phosphorylation, regulation of transcription, and oxidative-reduction processes were the most common gene ontology categories of this group. Twenty-three IAA, fourteen ARF, eight SAUR, three YUC, and four PIN genes were found to be differentially expressed during callus formation. The effect of callus-inducing medium (CIM) on IAA genes was broader in the IME system than in the ME system, indicating that auxin response participates in regulating cell reprogramming during callus formation. BBM, LEC1, and PLT2 exhibited a significant increase in expression levels in the IME system but were not activated in the ME system. WUS showed a more substantial growth trend in the IME system than in the ME system, suggesting that these embryonic, shoot, and root meristem genes play crucial roles in determining the acquisition of competency. Moreover, epigenetic regulators, including SUVH3A, SUVH2A, and HDA19B/703, exhibited differential expression patterns between the two induction systems, indicating that epigenetic reprogramming might contribute to gene expression activation/suppression in this process. Furthermore, we examined the effect of ectopic expression of HvBBM and HvWUS on Agrobacterium-mediated barley transformation. The transformation efficiency in the group expressing the PLTPpro:HvBBM + Axig1pro:HvWUS construct was increased by three times that in the control (empty vector) because of enhanced plant regeneration capacity. We identified some regulatory factors that might contribute to the differential responses of the two explants to callus induction and provide a promising strategy to improve transformation efficiency in barley.


Megestrol acetate versus metronomic cyclophosphamide in patients having exhausted all effective therapies under standard care.
To evaluate the antitumour activity and safety of metronomic cyclophosphamide vs megestrol acetate in progressive and advanced cancer patients having exhausted all effective therapies under standard care. Patients were randomly assigned to receive orally metronomic cyclophosphamide (50 mg b.i.d) or megestrol acetate (160 mg only daily) until intolerance or progression (RECIST 1.0). The primary efficacy end point was a 2-month progression-free rate (PFR(2m)). According to Optimal Simon's design and the following assumptions, namely, P0=5%, P1=20%, alpha=beta=10%, the treatment is considered as effective if atleast 5 out of 44 patients achieved PFR(2m). Between September 2006 and January 2009, 88 patients were enrolled. Two patients experienced grade 3-4 toxicities in each arm (4%). One toxic death occurred in the megestrol acetate arm as a consequence of thrombosis. The metronomic cyclophosphamide arm reached the predefined level of efficacy with a PFR(2m) rate of 9 out of 44 and a PFR(4m) rate of 5 out of 44. The MA arm failed to achieve the level of efficacy with a PFR(2m) of 4 out of 44 and a PFR(4m) of 1 out of 44. The median overall survival was 195 and 144 days in the metronomic cyclophosphamide arm and megestrol acetate arm, respectively. Metronomic cyclophosphamide is well tolerated and provides stable disease in such vulnerable and poor-prognosis cancer patients. This regimen warrants further evaluations.


Real-time detection of L-glutamate released from C6 glioma cells using a modified enzyme-luminescence method.
There is an increasing interest in new strategies to detect neurotransmitters released from nerve cells in real time for brain science, drug assessment, and so on. Previously we reported real-time monitoring of dopamine release from nerve model cells by enzyme-catalyzed luminescence measurement with tyramine oxidase and peroxidase. In the present study, the system was modified with glutamate oxidase instead of tyramine oxidase to detect L-glutamate sensitively ( approximately 10 nM) and rapidly with high temporal resolution (<1 s). We applied this modified method successfully to perform real-time monitoring of L-glutamate release from brain model cell (C6 glioma cell) using a luminescence plate reader upon stimulation with high concentration of KCl (>10 mM) or 5-hydroxytryptamine (>1 microM). The measurement solution was not toxic and therefore the L-glutamate release from the cell was measured by the second stimulation after exchanging the measurement solution. We conclude that the developed monitoring system is suitable for real-time detection of dynamic L-glutamate release from nerve cells in vitro and will be suitable for application in assessment of drugs acting on the nervous system.


Tonic stretch reflex threshold as a measure of spasticity after stroke: Reliability, minimal detectable change and responsiveness.
To determine inter-rater reliability, minimal detectable change and responsiveness of Tonic Stretch Reflex Threshold (TSRT) as a quantitative measure of elbow flexor spasticity. Elbow flexor spasticity was assessed in 55 patients with sub-acute stroke by determining TSRT, the angle of spasticity onset at rest (velocity = 0°/s). Elbow flexor muscles were stretched 20 times at different velocities. Dynamic stretch-reflex thresholds, the elbow angles corresponding to the onset of elbow flexor EMG at each velocity, were used for TSRT calculation. Spasticity was also measured with the Modified Ashworth Scale (MAS). In a sub-group of 44 subjects, TSRT and MAS were measured before and after two weeks of an upper-limb intervention. The intraclass correlation coefficient was 0.65 and the 95% minimal detectable change was 32.4°. In the treated sub-group, TSRT, but not MAS significantly changed. TSRT effect size and standardized response mean were 0.40 and 0.35, respectively. Detection of clinically meaningful improvements in upper-limb motor impairment by TSRT change scores ranged from poor to excellent. Evaluation of stroke-related elbow flexor spasticity by TSRT has good inter-rater reliability. Test responsiveness is low, but better than that of the MAS. TSRT may be used to complement current scales of spasticity quantification.


Neutron capture therapy: a comparison between dose enhancement of various agents, nanoparticles and chemotherapy drugs.
The aim of this study is to compare dose enhancement of various agents, nanoparticles and chemotherapy drugs for neutron capture therapy. A (252)Cf source was simulated to obtain its dosimetric parameters, including air kerma strength, dose rate constant, radial dose function and total dose rates. These results were compared with previously published data. Using (252)Cf as a neutron source, the in-tumour dose enhancements in the presence of atomic (10)B, (157)Gd and (33)S agents; (10)B, (157)Gd, (33)S nanoparticles; and Bortezomib and Amifostine chemotherapy drugs were calculated and compared in neutron capture therapy. Monte Carlo code MCNPX was used for simulation of the (252)Cf source, a soft tissue phantom, and a tumour containing each capture agent. Dose enhancement for 100, 200 and 500 ppm of the mentioned media was calculated. Calculated dosimetric parameters of the (252)Cf source were in agreement with previously published values. In comparison to other agents, maximum dose enhancement factor was obtained for 500 ppm of atomic (10)B agent and (10)B nanoparticles, equal to 1.06 and 1.08, respectively. Additionally, Bortezomib showed a considerable dose enhancement level. From a dose enhancement point of view, media containing (10)B are the best agents in neutron capture therapy. Bortezomib is a chemotherapy drug containing boron and can be proposed as an agent in boron neutron capture therapy. However, it should be noted that other physical, chemical and medical criteria should be considered in comparing the mentioned agents before their clinical use in neutron capture therapy.


Modification of Joint Recurrence Quantification Analysis (JRQA) for assessing individual characteristics from short EEG time series.
This article proposes a modification of joint recurrence quantification analysis for identifying individual characteristics applied to human electroencephalography (EEG) using short time series. Statistical analysis of EEG characteristics facilitated the clarification of the spatial localization of identified individual characteristics. The method can be adapted for use as a stage of a rapid automatic configuration of brain-computer interface devices, which is especially relevant when working with children, due to limited opportunities for their long-term monitoring.


The clinical significance of base excess (BEB) and base excess in the extracellular fluid compartment (BEEcf) with and without correction to real oxygen saturation of haemoglobin.
Besides actual pH, base excess [ctH (+)(B) (mmol/l)] is of major importance since it is meant to reflect lactate acidosis due to foetal hypoxia; In vivo BE (B) is not independent from pCO (2). Independence is achieved by using the extended extracellular fluid (Ecf) for dilution of haemoglobin (cHb (B)) thus reducing cHb (B) to cHb (B)/3 (in the foetus to cHb (B)/4). Correction of ctH (+)(B) from the normally low foetal oxygen saturation by reoxygenation of Hb increases ctH (+)(B), resulting in 4 different variables: ctH (+)(B,act) (=BE (B)), ctH (+)(Ecf,act) (standard BE), ctH (+)(B,ox.) and ctH (+)(Ecf,ox). 3 questions arise: (i) which variable is most appropriate for perinatal acid-base studies? (ii) are there clinical advantages for using BE when compared with actual pH (UA), and (iii) what are the thresholds of the BE parameters? The Apgar 1 min and the WAS score were used thus measuring neonatal vigour and FHR characteristics during the last 30 min of 475 foetuses all delivered by the vaginal route. FHR was evaluated by computation of the WAS index . The WAS index refers to (FHM*W1)*(OZF*W2)*(OZA*W3)(-1) where fhm is mean heart frequency (bpm), ozf denotes the number of turning points (N/min) and oza refers to the oscillation amplitude/min (bpm). The weighting functions W1, W2 and W3 were computed using optimizing software. The WAS score denotes the mean of the WAS indices of the last 30 min of delivery. BE was computed according to the van Slyke/Henderson-Hasselbalch equation using pH and pCO (2) measurements; sO (2) (%) for HbF was determined according to Ruiz et al. . In vivo foetal ctH (+)(B,act) (UA) is closely correlated with pCO (2). UA: r=-0.288, P<10 (-4), N=475: whereas ctH (+)(Ecf,act) (standard BE) becomes independent from pCO (2): r=-0.0068, P=0.881. In UA blood there is no independence of the 2 blood gases pCO (2) and pO (2): both are inversely correlated: r=-0.291, P<<10 (-4). pO (2) shows no correlation with ctH (+)(B,act) (r=-0.074, P=0.105) but correlates well with ctH (+)(Ecf,act): r=-0.1722, P=0.0002. The Apgar score (1 min) is best correlated with pH (UA) (r=0.4078, P<10 (-4)(,) Spearman's rho=0.307, P<10 (-4)). Correction of ctH (+)(B,act) or ctH (+)(Ecf,act) to 100% oxygen saturation always leads to higher coefficients. Using: ctH (+)(B,ox), ctH (+)(B,act), ctH (+)(Ecf,ox) and ctH (+)(Ecf,act): rho=0.2597, 0.2394, 0.1838 and 0.1763, respectively; P all <10 (-4). The same holds true for Apgar 5 min: rho=0.2307, 0.2168, 0.1811 and 0.1771, respectively (P<10 (-4) for all). The WAS score is closely correlated with pH (UA): r=0.656, P<<10 (-4), N=475. The correlation with the 4 variables under investigation: ctH (+)(B,ox), ctH (+)(B,act), ctH (+)(Ecf,ox) and ctH (+)(Ecf,act) leads to r=-0.587, r=-0.565, r=-0.437 and r=-0.427, respectively (P<10 (-4) for all). The threshold of standard BE (ox.)(=ctH (+)(Ecf ox)) in 390 acidotic term infants with still good outcomes is -14.0 mmol/l. Actual pH (cH (+)) offers the closest correlation with 2 essential clinical parameters: FHF and Apgar scores; the advantages of ctH (+)(B) and ctH (+)(Ecf), are not self-evident; if determination of the metabolic component becomes necessary standard BE, (ctH (+)(Ecf)) should be used with correction to 100% oxygen saturation (ctH (+)(Ecf,ox.)) of haemoglobin (HbF), because this quantity (after pH (UA)) correlates best with clinical indices. However if the 'correction' is omitted the difference seems clinically irrelevant.


Accumulation of Acid Orange 7, Acid Red 18 and Reactive Black 5 by growing Schizophyllum commune.
The effect of Acid Orange 7, Acid Red 18 and Reactive Black 5 on the growth and decolorization properties of Schizophyllum commune was studied with respect to the initial pH varying from 1 to 6 and initial dye concentration (10-100 mg/L). The optimum pH value was found to be 2 for both growth and color removal of these azo dyes. Increasing the concentration of azo dyes inhibited the growth of S. commune. It was observed that S. commune was capable of removing Acid Orange 7, Acid Red 18 and Reactive Black 5 with a maximum specific uptake capacity of 44.23, 127.53 and 180.17 (mg/g) respectively for an initial concentration of 100 mg/L of the dye. Higher decolorization was observed at lower concentrations for all the dyes. Finally it was found that the percentage decolorization was more in the case of Reactive Black 5 dye compared to the other two dyes used in the present investigation.


Per anum intersphincteric rectal dissection with direct coloanal anastomosis for lower rectal cancer: the ultimate sphincter-preserving operation.
The most important goal of sphincter-preserving operations for rectal cancer is to secure a distal surgical margin of safety and the anal sphincter. However, it is not always easy to transect the rectum and to secure a distal surgical margin of safety through the abdominal approach for tumors situated extremely low in the rectum. The aim of this study was to describe and to evaluate a new technique of per anum intersphincteric rectal dissection and coloanal anastomosis. The rectum, including the entire width of the internal anal sphincter, is transected circumferentially via the anal route to secure the surgical margin of safety under direct vision and is mobilized proximally as far as possible through the intersphincteric plane. Per anum coloanal anastomosis is performed following transabdominal resection of the rectum. This technique has been used in 12 patients. There have been no instances of short-term or long-term anastomotic complications. This technique is safe when anastomosis must be performed at the dentate line. It is the best sphincter-preserving operation for lower rectal cancer and does not result in serious postoperative anal dysfunction.


Burnout amongst neurosurgical trainees in the UK and Ireland.
Burnout is becoming an increasingly recognised phenomenon within the medical profession. This study aims to investigate the presence of burnout amongst neurosurgical trainees in the UK and Ireland as well as investigating potential exacerbating and protective factors. An online survey was sent to all neurosurgical trainees in the UK and Ireland via the British Neurosurgical Trainees' Association (BNTA) mailing list. Responding participants anonymously completed the Copenhagen Burnout Inventory (CBI) and answered questions about known risk factors for burnout including workplace environment, workplace bullying, time spent on leisure activities and sleep and reported likelihood of leaving neurosurgery. We also collated data on responders' demographics. We compared CBI scores for participants with and without risk factors to determine correlation with CBI. There were 75 respondents (response rate 42%) from a range of ages and all training grades, 72% of whom were male. The median CBI score was 38.85 (IQR 17.76). Participants showed a higher degree of personal and workplace burnout (median CBIs of 47.02, IQR 25.00; and 49.14, IQR 19.64, respectively) compared with patient-related burnout (median CBI 18.67, IQR 25.00). Participants with the following self-reported risk factors were significantly more likely to have higher CBIs: workplace bullying (p = 0.01), getting on less well with colleagues (p < 0.05), working longer hours (p < 0.05) and insufficient sleep, exercise and leisure time (all p < 0.01). Those with higher CBI scores were more likely to consider leaving neurosurgical training (p = 0.01). We identified a high burnout incidence in a cohort representative of UK neurosurgical trainees, although our results may have been skewed somewhat by selection bias. We determined potential risk factors for burnout related to specific workplace stressors and time for non-work activities. In the future, changes to training curricula should address these issues, aiming to improve training, enhance patient care and reduce attrition rates.


Rapid determination of melamine and cyanuric acid in milk powder using direct analysis in real time-time-of-flight mass spectrometry.
The use of fast semi-automated method employing direct analysis in real time (DART) ion source coupled to time-of-flight mass spectrometry (TOFMS) for analysis of melamine (MEL) and cyanuric acid (CYA) in milk powder and milk based products has been demonstrated in this study. Simple sample extraction procedure employing methanol-5% aqueous formic acid mixture, which enabled disruption of melamine-cyanurate complex, was followed by direct, high-throughput (30s per run) examination of sample extracts spread on a glass rod by mass spectrometry under ambient conditions, without any prior chromatographic separation. After optimization of instrument parameter settings, limits of detection (LODs) 170 and 450microgkg(-1) were achieved for MEL and CYA, respectively. In the final phase of study, the possibility of minimizing spectral interference, thus improving method performance characteristics through the use of ultrahigh resolving power offered by Orbitrap based mass analyzer is demonstrated.


COVID-19 patient and personal safety - lessons learnt for pandemic preparedness and the way to the next normal.
The COVID-19 pandemic has profoundly challenged societies and healthcare systems in particular. To prevent the spread of SARS-CoV-2, infection prevention and control (IPC) strategies had to be developed on the local, national and international level. The aim of this study is to provide details of the COVID-19 experience at the Vienna General Hospital (VGH) in the context of the national and international COVID-19 response for learning and improvement. This is a retrospective report, outlining the evolution of IPC measures and challenges encountered at the health facility (VGH), the national (Austria) and global level between February 2020 and October 2022. The IPC strategy at the VGH has been continuously adapted to changes in the epidemiological setting, new legal directives and Austrian by-laws. The current strategy, nationally and internationally, focuses on endemicity rather than maximum transmission risk reduction. For the VGH, this has recently resulted in an increase in COVID-19 clusters. To protect our particularly vulnerable patients, many COVID-19 precautions have been maintained. Barriers to adequate IPC implementation at the VGH and other hospitals include a lack of sufficient isolation options and non-adherence with universal face mask regulations. Globally, misinformation on COVID-19 hampered an effective response. This retrospective analysis of the COVID-19 response at the VGH and international reports underline the need for pandemic preparedness, readiness and response by improving future hospital design and infrastructure, conducting regular trainings for protective attire and increasing health literacy as now recently published in a concise document by WHO.


Identification of differentially expressed genes in the developing mouse inferior colliculus.
Although injured neurons of inferior colliculus (IC) display a robust axonal outgrowth through a lesion site at postnatal day six (P6) in vitro, and are capable to re-innervate their target cells, injured neurons from P10 IC are unable to regenerate their axons across the lesion site. This axonal regenerative failure has been attributed to an increase of expression of inhibitory molecules in endogenous tissue, during development. As a first step to identify such inhibitory molecules, the present study reports the isolation of molecules differentially expressed in the IC during development. A two-directional (forward and backward) suppression subtractive hybridization (SSH) was performed on IC tissue between P6 and P10 stages. One hundred cDNAs from P6 (P6-P10) and 200 cDNAs from P10 (P10-P6)-subtracted libraries were randomly sequenced. A dot-blot screening of sequenced cDNAs revealed the differential expression for the majority of these cDNAs at their respective developmental stage. Then, the analysis of sequenced clones showed that P6 library was highly enriched in molecules expressed early in the development, such as GAP43 or vimentin proteins. By contrast, the P10 library contained mostly molecules expressed at later stages of development in the central nervous system, such as myelin-related proteins. Our results show that SSH is a suitable method for identifying differentially expressed genes in the developing IC. In addition, these results provide a foundation for further studies dealing with molecules involved in the IC development before and at the onset of hearing, some of which being probably involved in the axonal outgrowth mechanism.


Effectiveness of two sensory-based health education methods on oral hygiene of adolescent with autism spectrum disorders: An interventional study.
This study was undertaken with an aim to evaluate the effectiveness of two sensory-based interventions namely - Visual pedagogy and Mobile based application (Brush Up) on oral health education in promoting oral health status among 13-17 year old school going adolescents with Autism Spectrum Disorder (ASD) in Chennai city. An interventional parallel arm study consisting of 13- to 17-year-old school going adolescent with ASD in Chennai city. Plaque Index (Sillness and Loe, 1964) and gingival index (Loe and Sillness, 1963) were assessed at baseline, 6th week and after 12th week. A significant difference in plaque (p = < 0.001) and gingival scores (p = < 0.001) were seen among the groups after 6 and 12 weeks post-intervention. There was no statistically significant difference in dental plaque (p = 0.912, 1.023, 0.812) and gingival scores (p = 0.932, 0.264, 0.283) between the groups at all the timelines. In this present study we found that both the visual cards and mobile based application (Brush Up) had significantly reduced the dental plaque and gingival scores; hence both the modalities can be used as an effective tool in educating these children and thus improve their oral hygiene.


Anesthesiology and Critical Care Response to COVID-19 in Resource-Limited Settings: Experiences from Nepal.
It is difficult to predict the future course and length of the ongoing COVID-19 pandemic, which has devastated health care systems in low- and middle-income countries. Anesthesiology and critical care services are hard hit because many hospitals have stopped performing elective surgeries, staff and scarce hospital resources have been diverted to manage COVID-19 patients, and several makeshift COVID-19 units had to be set up. Intensive care units are overwhelmed with critically ill patients. In these difficult times, low- and middle-income countries need to improvise, perform indigenous research, adapt international guidelines to suit local needs, and target attainable clinical goals.


Analysis of unsaturated disaccharides from glycosaminoglycuronan by high-performance liquid chromatography.
A rapid and simple analytical method for unsaturated disaccharide isomers formed by enzymatic digestion from hyaluronic acid, chondroitin sulfate, dermatan sulfate, heparan sulfate, and heparin by high-performance liquid chromatography using an amine-bound silica column with a linear gradient of sodium dihydrogen phosphate was developed. The analyses were performed on isomers of two groups belonging to the chondroitin sulfate family and the heparin sulfate family. In both families, disaccharide isomers eluted in the order non-, mono-, di-, and trisulfated disaccharides by elevating salt concentrations. The method was applied to the analysis of constituent disaccharides of representative sulfated glycosaminoglycans, which proved that most constituents could be quantified separately. This method is advantageous in that enzymatic digests can be applied directly on a column without any pretreatment and good resolution of several disaccharides can be obtained by one chromatography.


Evaluation of immune response to hepatitis A vaccination and vaccine safety in juvenile idiopathic arthritis.
Autoimmune mechanisms and drugs used in treatment increase the risk of liver disease in patients with juvenile idiopathic arthritis (JIA) and hepatitis A virus (HAV) vaccination is important, especially in intermediate-endemicity areas like Turkey. In our study, we aimed to evaluate the immune response to hepatitis A vaccine and vaccine safety in children with JIA. This study was carried out in our hospital's Pediatric Rheumatology outpatient clinic and Healthy Child clinic between the years 2003 and 2008. The study group consisted of 47 children with JIA (23 male and 24 female) diagnosed according to International League of Associations for Rheumatology diagnostic criteria. The control group consisted of 67 healthy children (31 female, 36 male) who did not have a history of hepatitis A infection or vaccination. Both groups were vaccinated with two doses of hepatitis A vaccine at 6-month intervals. Anti-HAV IgG >80 MIU was accepted as positive response. There was no significant difference between the groups in terms of age and sex. None of the patients with JIA had fever, clinical worsening, or disease activation after vaccination. Anti-HAV IgG positivity rate was significantly higher in the control group (p < 0.05). Anti-HAV IgG was negative in only four cases, and they were all male patients with systemic JIA who had active disease under anti-tumor necrosis factor treatment. Hepatitis A vaccine was safe in patients with JIA, and response to vaccine did not differ between healthy children and patients with JIA except for children with active systemic JIA receiving anti-tumor necrosis factor alpha drugs.


The role of phylogenetic relatedness on alien plant success depends on the stage of invasion.
Darwin's naturalization hypothesis predicts successful alien invaders to be distantly related to native species, whereas his pre-adaptation hypothesis predicts the opposite. It has been suggested that depending on the invasion stage (that is, introduction, naturalization and invasiveness), both hypotheses, now known as Darwin's naturalization conundrum, could hold true. We tested this by analysing whether the likelihood of introduction for cultivation, as well as the subsequent stages of naturalization and spread (that is, becoming invasive) of species alien to Southern Africa are correlated with their phylogenetic distance to the native flora of this region. Although species are more likely to be introduced for cultivation if they are distantly related to the native flora, the probability of subsequent naturalization was higher for species closely related to the native flora. Furthermore, the probability of becoming invasive was higher for naturalized species distantly related to the native flora. These results were consistent across three different metrics of phylogenetic distance. Our study reveals that the relationship between phylogenetic distance to the native flora and the success of an alien species changes from one invasion stage to the other.


Motor paralysis in rats after repeated electroconvulsive shock: comparison between aural and corneal stimulation.
Daily transaural electroshock treatment of rats results in a reversible hindlimb paralysis. Assuming there is a relationship between current pathway and the route of electroshock administration we compared both the type of convulsive behavior and the incidence of paralysis produced by transcorneal shock with that of transaural stimulation. Both transaural and transcorneal stimulation induced clonic and tonic convulsions, whereas, only transaural stimulation induced a body flexion (twisting and writhing). The use of transaural electrodes induced a higher incidence of paralysis than the use of corneal electrodes. These data demonstrate that both (1) the type of convulsive behavior produced and (2) the incidence of paralysis is related to electrode placement suggesting that paralysis is a function of current pathway.


Editorial: Disparities in Access to Child Psychiatric Services: Can We Shift the Landscape?
A National Academy of Medicine report published in 1993 defined disparities in health care as "a difference in access or treatment provided to members of different racial or ethnic groups that is not justified by the underlying health conditions or treatment preferences of the groups."1 Disparities in access to and quality of mental health services have persisted for racially minoritized children and for many rural communities in the United States. The global pandemic has taken an enormous toll on the mental health and well-being of youth and their families and has exacerbated preexisting needs.2 The rapid expansion of telehealth capacity, providing services via text, telephone, or video, has provided access to a spectrum of services for individuals and expert consultation for partners in low-resource communities. Telehealth has demonstrated effectiveness for lowering the barriers to seeking treatment in rural communities for youth with suicidality, depression, and anxiety.3 However, disenfranchised, low-income populations lacking sufficient in-person care or internet broadband to support telepsychiatry services or who encounter other barriers, such as underinsurance or no insurance and limited cultural and linguistic matched services, continue to have poor access to care and are at risk for disparate outcomes.4 In the midst of a pandemic and an accelerated child and adolescent mental health emergency in the United States, disparities in access to services presents a crisis within a crisis. Is the services landscape shifting to address the need?


Differences in intravascular ultrasound findings in culprit lesions in infarct-related arteries between ST segment elevation myocardial infarction and non-ST segment elevation myocardial infarction.
Previous studies have reported diffuse destabilization of atherosclerotic plaques in acute myocardial infarction (AMI). We used intravascular ultrasound (IVUS) to assess coronary culprit lesions in ST segment elevation MI (STEMI) vs. in non-ST segment elevation MI (NSTEMI). Patient population comprised 125 STEMI and 185 NSTEMI patients. IVUS findings included ruptured plaque (a cavity that communicated with the lumen with an overlying residual fibrous cap fragment), lipid-pool like image (a pooling of hypoechoic or echolucent material covered with a hyperechoic layer), thrombus (discrete intraluminal filling defects), and plaque prolapse (tissue extrusion through the stent strut at post-stenting). Culprit lesions had larger external elastic membrane area (13.5+/-4.9mm(2) vs. 11.9+/-4.3mm(2), p=0.002), larger plaque plus media area (10.8+/-4.4mm(2) vs. 9.1+/-4.1mm(2), p=0.001), and greater plaque burden (78.7+/-10.1% vs. 74.8+/-12.0%, p=0.002), and smaller culprit lesion site calcium arc (96+/-90 degrees vs. 153+/-114 degrees , p=0.002) in patients with STEMI than in those with NSTEMI. Culprit lesion plaque ruptures, lipid-pool like images, and thrombus were observed more frequently in patients with STEMI than in those with NSTEMI (46% vs. 29%, p=0.002; 39% vs. 25%, p=0.010; and 34% vs. 21%, p=0.006, respectively). Culprit lesions were more predominantly hypoechoic in patients with STEMI than in those with NSTEMI (62% vs. 40%, p<0.001). There was a trend that post-stenting plaque prolapse was observed more frequently in patients with STEMI than in those with NSTEMI (33% vs. 24%, p=0.081). Culprit lesions in STEMI have more markers of plaque instability (more plaque rupture and thrombus, and larger plaque mass) compared with lesions in NSTEMI.


Is gold favourable than bitcoin during the COVID-19 outbreak? Comparative analysis through wavelet approach.
The novel coronavirus (COVID-19) has tremendously oscillated the global financial markets. Consequently, investors feel pressured to find safe-haven investments during the pandemic crisis. Numerous studies have evaluated bitcoin's safe-haven properties during the COVID-19; however, the present study considered gold as a potential safe-haven for investors of renowned stock markets of Asia, Europe, and the US. The present investigation computed the ratio of gold to bitcoin (Gold_Bitcoin) and compared the safe-haven properties of gold in contrast to bitcoin. The present study analysed the Morlet Wavelet approach and found that most of the time during the COVID-19, gold investments proved to be more beneficial than bitcoin. Remarkably, the findings highlighted that the Gold_Bitcoin ratio increased in higher and lower frequencies combined with CAC40. In the long run, the return on investments in gold increased in contrast to bitcoin returns pooled with DAX30. Also, the Gold_Bitcoin ratio of the US stock market increased during the one-week and one-month cycles of January and August. Likewise, the Hang Seng Index caused the Gold_Bitcoin ratio to rise at a much higher frequency (i.e., the second half of January, the first half of February and April, and the first half of June and August), whereas IBEX35 surged Gold_Bitcoin at a lower frequency (i.e., during January, February, and August). In higher frequency bands, LSE increased the Gold_Bitcoin ratio (i.e., in February and March); nevertheless, Gold_Bitcoin showed a positive connection with FTSEMIB in the one-to-two month's frequency band (i.e., throughout January, February, and August). Interestingly, the returns on the Gold_Bitcoin ratio increased in the SSEC stock market in the high-frequency band (i.e., during March, May, and July 2020).


Illumina sequencing of complete chloroplast genome of Avicennia marina, a pioneer mangrove species.
Mangrove tree Avicenna marina has great ecological significance in maintaining coastal ecosystem, but its unique potential for gene functions and genetic diversity underlying ecological adaptation remains investigation. In this study, the chloroplast genome of A. marina was first characterized by sequencing chloroplast DNA with Illumina technology. The A. marina genome was 147,909 bp in size with a typical quadripartite structure, which was deposited in GenBank under the accession number MT108381.


Endoscopic management of selected early vocal cord carcinoma.
Twenty-five previously untreated patients with selected early midcordal squamous cell carcinomas have been treated by endoscopic excisional biopsy with the carbon dioxide laser and followed for a minimum of 3 years. Twenty-four of the 25 patients are alive and free of disease, and one patient died of local and regional recurrence 2 years after attempted endoscopic excision followed by partial laryngectomy. Indications, contraindications, advantages, and complications associated with this treatment option for patients with early glottic carcinoma are discussed.


A device for investigation of natural cell mobility and deformability.
A microfluidic device made of polydimethylsiloxane was developed for continuous evaluation of natural migration mobility of many eukaryotic cells in relaxed and deformed state. The device was fabricated by standard photolithography and soft lithography techniques using the SU-8 3010 negative photoresist on a glass wafer as the master mold. The simple flow-free device exploits the chemotactic movement of cells through a set of mechanical barriers in the direction of concentration gradients of attractants. The barriers are formed by arrays of circular cross-section pillars with decreasing spacing 7, 5, and 3 μm. To pass through the obstacles, the cells are deformed and change their cytoskeletal architecture. The instantaneous migration velocities of cells are monitored in a time-lapse setup of the scanning confocal microscope. Thus, the cellular deformability and migratory activity can easily be evaluated. The functionality of the device was tested with model HeLa cells stably transfected with fluorescent Premo FUCCI Cell Cycle Sensor. The designed device has the potential to be implemented for testing the tendency of patients' tumors to metastasis.


Examining changes on testicular structure and sperm analysis of COVID-19 patients.
This study aimed to examine the testicular functions with sperm analysis of patients with COVID-19. The study was carried out with male patients aged between 18 and 50 years with positive RT-PCR test and SARS-CoV-2 virus between December 2020 and April 2021. A total of 103 participants were included in the study. The mean age was 31.24 ± 5.67 (19-45) years and the mean body mass index of the participants was 28.41 ± 4.68 kg/m2 . The patients were divided into two groups, group-1 was patients who had COVID-19, group-2 was healthy men. A semen analysis of both groups was performed, and the serum total testosterone, FSH, LH, anti-mullerian hormone and Inhibin-B tests were analysed and recorded. The testicular dimensions and testicular densities were examined by ultrasound and elastography for both groups. Comparing the patient and control groups results, this study found that the sperm count per 1 cc (p = 0.01) and total motility (p = 0.01) in group-1 was lower than in the control group, the testicular dimensions decreased (for right testis group-2 was 15.39 ± 4.78 ml versus group-1 was 12.11 ± 4.62 cm3 p < 0.01, for left testis group-2 was 16.01 ± 5.12 versus group-1 was 11.92 ± 4.78 cm3 ; p < 0.01), and the shear wave velocities were significantly higher in group-1 patients. In conclusion, sperm parameters deteriorate in men who have symptomatic disease with SARS-CoV-2 infection. The fact that the cause of this deterioration is characterized by changes at the cellular level in the testis raises doubts about the persistence of this condition.


Massive abdominal wall hibernoma: case report and literature review of a rare soft-tissue tumor.
Hibernoma is a rare benign tumor arising from remnants of fetal brown adipose tissue. This tumor was first described by Merkel in 1906. The brown fat is a specialized form of fat found in the hibernating and nonhibernating animals such as rats, cats, monkeys, rabbits, and humans. A 27-year-old man presented with a painless, enlarging, anterior abdominal wall mass, which, upon core-needle biopsy, was found to be hibernoma. This was evaluated with abdominal computed tomography, which showed a heterogeneous mass that contained fat. At operation, the entire mass measuring 30x25x6 cm lying below the external oblique muscle was excised with a cuff of normal tissue. Hibernoma is a rare, slow-growing benign soft tissue tumor composed of brown fat that is successfully treated by complete excision while preserving all related vital structures. Unlike lipoma, hibernoma is well vascularized and therefore good hemostasis must be achieved at surgery to prevent postoperative bleeding or hematoma. No case of recurrence has been previously reported.