The Ex Vivo IFN-γ Enzyme-Linked Immunospot (ELISpot) Assay.
The quantification of single cell interferon-gamma (IFN-γ) release for assessing cellular immune responses using the Enzyme-linked immunospot (ELISPOT) assay is an invaluable technique in immunology. Peripheral blood mononuclear cells (PBMC) are stimulated in vitro with recombinant proteins, peptides and recently whole malaria organisms. Stimulation may be short term (20-36 h) or long term (cultured ELISpot, up to 7 days). ELISpot is also able to quantify other cytokines secreted by antigen-specific T-cells, such as interleukin-2, interleukin-5, and other interleukins. ELISpot is playing an important role especially in vaccine research studies.


Importance of Trp139 in the product specificity of a maltooligosaccharide-forming amylase from Bacillus stearothermophilus STB04.
The maltooligosaccharide-forming amylase from Bacillus stearothermophilus STB04 (Bst-MFA) randomly cleaves the α-1,4 glycosidic linkages of starch to produce predominantly maltopentaose and maltohexaose. The three-dimensional co-crystal structure of Bst-MFA with acarbose highlighted the stacking interactions between Trp139 and the substrate in subsites - 5 and - 6. Interactions like this are thought to play a critical role in maltopentaose/maltohexaose production. A site-directed mutagenesis approach was used to test this hypothesis. Replacement of Trp139 by alanine, leucine, or tyrosine dramatically increased maltopentaose production and reduced maltohexaose production. Oligosaccharide degradation indicated that these mutants also enhance productive binding of the substrate aglycone, leading to a high maltopentaose yield. Therefore, the aromatic stacking between Trp139 and substrate is suggested to control product specificity and the oligosaccharide cleavage pattern.


Low calf circumference is an independent predictor of mortality in cancer patients: A prospective cohort study.
Loss of muscle mass is associated with worse outcomes in patients with cancer. The objective of this study was to evaluate the prognostic value of calf circumference (CC) and skeletal muscle index from computed tomography (CT) to predict mortality in patients with cancer. A single-center prospective study was conducted with patients aged ≥20 y attending a reference center of oncology and who had recent abdominal CT images. Data were collected through a semistructured form and patients' records and included sociodemographic data (sex, age and ethnicity), clinical data (primary site and staging of tumor and treatments performed), anthropometric variables (body mass index and CC), and outcome (death). Low CC for men was considered to be ≤ 34 cm and for women ≤ 33 cm. Muscle mass was assessed by CT images at the level of L3. The Cox proportional hazard model adjusted for age, sex, and staging of disease was used. A total of 250 patients were evaluated, 52.8% female, with a median age of 63 y (interquartile ratio: 55-73). Normal body mass index was identified in 44.4%; 29.2% had low skeletal muscle index, and 46.4% had low CC. Death by any cause occurred in 16%, and only low CC was a significant predictor of mortality (hazard ratio = 3.01; confidence interval 1.52-5.98; P = 0.002). Low CC can predict risk of mortality in this cohort of patients. The findings suggest the use of CC as a simple, easy, cost-effective anthropometric measurement to quickly screen patients at risk of death who could benefit from targeted care to improve their prognosis.


Gastrointestinal autonomic neuropathy in diabetes.
Gastrointestinal autonomic neuropathy represents an important and diverse, but poorly appreciated, manifestation of diabetic autonomic neuropathy that impacts negatively on quality of life. There is no test to assess gastrointestinal autonomic nerve damage directly in humans; cardiovascular autonomic reflex tests are often used as a surrogate, but are suboptimal. Gastrointestinal symptoms are common in diabetes, but usually correlate only weakly with disordered motility. Diabetic gastroparesis, or abnormally delayed gastric emptying, occurs frequently and is the best characterized manifestation of gastrointestinal autonomic neuropathy. There is a bi-directional relationship between postprandial glycaemia and the rate of gastric emptying. However, autonomic neuropathy can affect the function of any gut segment from the esophagus to the anus. Current management options for gastrointestinal autonomic neuropathy are, for the main part, empirical and sub-optimal.


Validation of the MidACE tool - Students' perceptions of the Midwifery Academic role in clinical environments.
Situating Midwifery Academics in clinical environments can have an important impact on students' clinical learning. Students' perceptions of this support role in the clinical environment using standardised measures has been under-investigated. To develop and test a tool that measures midwifery students' perceptions of the Midwifery Academic role on clinical learning and development of professional knowledge, skills and clinical capability. A staged process for tool development included draft item generation, review by expert panel for face and content validity and pilot testing with a convenience sample of undergraduate midwifery students. Dimensionality, internal consistency and test-retest reliability were evaluated. Two hundred and seventy-nine midwifery students completed an online survey (74% response rate). Responses on the ten-item tool loaded strongly on one factor, explaining 69.6% of variance. Cronbach's alpha (0.94) and test-retest reliability (intraclass coefficient=.92; 95%CI .89-.95) were good. Most students agreed that the Midwifery Academic role supported the integration of midwifery theory and practice and critical self-reflection. Areas for improvement included working in partnership with preceptors; assessing students' development; and increased presence in the clinical environment. This study established reliability and validity of the Midwifery Academic in Clinical Environments (MidACE) tool. Students perceived Midwifery Academics could contribute further to their professional knowledge, skills and clinical capability through a strong collaborative presence in the clinical environment.


Interactions in contingency tables: a brief discussion of alternative definitions.
The purpose of this note is to indicate how the disagreement between Tennant & Bebbington and Brown & Harris has arisen. The difference between the 2 pairs of authors is due, at least in part, to their use of different models for the analysis of the data in question. There can be no final answer as to which model is correct - the data are simply open to more than one interpretation. Nevertheless, it is interesting that the use of a multiplicative model, seemingly ignored by Brown & Harris, leads to a simple description of the data in which the 'vulnerability factor' and the 'provoking agent' may be considered to act independently on the response. Consequently, in stating that their data contain an interaction so obvious that it can be detected by 'visual inspection', Brown & Harris may have been somewhat rash.


Simulation and verification of P systems through communicating X-machines.
The aim of this paper is to prove the suitability of a parallel distributed computational model, communicating X-machines, to simulate in a natural way a well established model of molecular computation, P systems, and to present some further benefits of the approach allowing us to check for some formal properties. A set of rules to transform any P system with symbol-objects into a communicating X-machine model is presented and a variation of temporal logic for X-machines is briefly discussed, which facilitates model checking of desired properties of the system. Finally, the benefits resulting from the transformation are discussed.


Assessment of diversity-based approaches used by American Universities to increase recruitment and retention of biomedical sciences research faculty members: A scoping review protocol.
Diversity enriches the educational experience by improving intellectual engagement, self-motivation, citizenship, cultural engagement, and academic skills like critical thinking, problem-solving, and writing for students of all races. Faculty role models from similar backgrounds are essential for students from traditionally underrepresented groups as it sends a powerful message of support, belonging, and the confidence to pursue higher education. However, in the biomedical sciences, the percentage of historically underrepresented tenure-track faculty is far lower than that of their white colleagues. For this to change, a strong strategic plan and commitment from the university are imperative. This scoping review will assess the size and scope of available peer-reviewed research literature on diversity programs that aim to increase the recruitment and retention of biomedical sciences research faculty and are implemented and evaluated at American Universities. The information provided in this scoping review will help universities identify novel, successful diversity-based approaches for recruiting and retaining biomedical science faculty that might suit their own unique academic and geographic needs and be incorporated into their diversity initiatives and policies. The review follows the Population-Concept-Context methodology for Joanna Briggs Institution Scoping Reviews. Relevant peer-reviewed studies published in English between June 1, 2012, to June 1, 2022, will be identified from the following electronic databases; MEDLINE (PubMed), Scopus (Elsevier), EMBASE (Elsevier), CINAHL (EBSCO), and ERIC (EBSCO). The search strings using the key variables "biomedical research faculty," "recruitment/retention," "diversity/ minority/ underrepresented, and "mentoring" will be conducted using Boolean logic. Two independent reviewers will conduct all title and abstract screening, followed by a full article screening and data extraction. Due to the possible heterogeneity of the studies, we hope to use either a narrative analysis and/or descriptive figures/tables to depict the results.


Renal and femoral venous blood flows are regulated by different mechanisms dependent on α-adrenergic receptor subtypes and nitric oxide in anesthetized rats.
Venous and arterial walls are responsive to sympathetic system and circulating substances, nevertheless, very few is known about the venous blood flow regulation simultaneously to arterial vascular beds. In this study, we compared the venous and arterial blood flow regulation in visceral and muscular beds upon injection of different doses of vasoactive drugs which act in arterial vascular beds. Anesthetized adult male Wistar rats underwent to right femoral artery and vein cannulation for hemodynamic recordings and infusion of drugs. Doppler flow probes were placed around the left renal artery and vein, and left femoral artery and vein to evaluate the changes in flood flow. Phenylephrine (PHE) injection (α1-adrenergic receptor agonist) elicited vasoconstriction in all arteries and veins. Intravenous prazosin (PZS) (1mg/kg, α1-adrenergic receptor blocker) caused renal artery vasodilation, but not in the other beds. Vasoconstrictor effect of PHE was abolished by PZS in all vascular beds, except in femoral vein. Phentolamine (PTL) injection (1mg/kg, α1/α2-adrenergic receptor blocker) produced renal artery vasodilation with no change in other beds. After PTL, the vasoconstriction evoked by PHE was abolished in all vascular beds. Sodium Nitroprusside (SNP), a nitric oxide donor, elicited vasodilation in all beds, and after PTL but not post PZS injection, SNP enhanced the vasodilatory effect in femoral vein. Our findings suggest that the vasoconstriction in renal and femoral veins is mediated by different subtypes of α-adrenoceptors. The nitric oxide-dependent vasodilation in femoral vein enhances when α2-adrenoceptors are not under stimulation, but not in the other vascular beds investigated.


Epstein-Barr positive T-cell lymphoma in the ocular region.
To present two cases of rapidly growing tumors in the ocular adnexa. Both tumors were Epstein-Barr virus (EBV) positive peripheral T-cell lymphoma. Case 1 was a 60-year-old man with a non-tender ulcerating tumor involving the lateral third of both upper and lower right eyelid. Case 2 was a 55-year-old man with a swelling of the left eyelid expanding cranially and dislocating the left eye, resulting in proptosis and diplopia. Both patients underwent incisional biopsy that did not disclose the malignant nature of the tumors. Clinical evaluation resulted in suspicion of malignancy and surgical excision was performed. The tumors were found to be consistent with EBV-positive peripheral T-cell lymphoma. Peripheral T-cell lymphoma is uncommon but a diagnosis to be considered in a patient with a tumorous lesion in the eye region. Furthermore, peripheral T-cell lymphoma may be EBV-positive.


Pyruvate dehydrogenase complex deficiency and its relationship with epilepsy frequency--An overview.
The pyruvate dehydrogenase complex (PDHc) is a member of a family of multienzyme complexes that provides the link between glycolysis and the tricarboxylic acid (TCA) cycle by catalyzing the physiologically irreversible decarboxylation of various 2-oxoacid substrates to their corresponding acyl-CoA derivatives, NADH and CO2. PDHc deficiency is a metabolic disorder commonly associated with lactic acidosis, progressive neurological and neuromuscular degeneration that vary with age and gender. In this review, we aim to discuss the relationship between occurrence of epilepsy and PDHc deficiency associated with the pyruvate dehydrogenase complex (E1α subunit (PDHA1) and E1β subunit (PDHB)) and PDH phosphatase (PDP) deficiency. PDHc plays a crucial role in the aerobic carbohydrate metabolism and regulates the use of carbohydrate as the source of oxidative energy. In severe PDHc deficiency, the energy deficit impairs brain development in utero resulting in physiological and structural changes in the brain that contributes to the subsequent onset of epileptogenesis. Epileptogenesis in PDHc deficiency is linked to energy failure and abnormal neurotransmitter metabolism that progressively alters neuronal excitability. This metabolic blockage might be restricted via inclusion of ketogenic diet that is broken up by β-oxidation and directly converting it to acetyl-CoA, and thereby improving the patient's health condition. Genetic counseling is essential as PDHA1 deficiency is X-linked. The demonstration of the X-chromosome localization of PDHA1 resolved a number of questions concerning the variable phenotype displayed by patients with E1 deficiency. Most patients show a broad range of neurological abnormalities, with the severity showing some dependence on the nature of the mutation in the Elα gene, while PDHB and PDH phosphatase (PDP) deficiencies are of autosomal recessive inheritance. However, in females, the disorder is further complicated by the pattern of X-chromosome inactivation, i.e., unfavorable lyonization. Furthermore research should focus on epileptogenic animal models; this might pave a new way toward identification of the pathophysiology of this challenging disorder.


Resolving the heterogeneous tumor-centric cellular neighborhood through multiplexed, spatial paracrine interactions in the setting of immune checkpoint blockade.
Direct interactions between tumor and immune cells mediate the antitumor effect of all modern cancer immunotherapeutic agents. Simultaneously, tumor cells have evolved mechanisms of evasion including the downregulation of HLA-I potentially disrupting the mechanism of action employed by many immune checkpoint inhibitors. And yet the in situ interplay between these cells within the tumor immune microenvironment (TIME) remains elusive. Recent advances in histologic multiplex bioimaging platforms have enabled in-depth molecular characterization of single cells within spatially-preserved and clinically archived tumor tissues. Herein, we applied multiplex immunofluorescence (MxIF) to excisional lymph node biopsies from 14 patients with metastatic melanoma who experienced clear objective responses to immunotherapy (7 complete response; 7 progressive disease) to determine distinguishing features of the TIME in the pretreatment setting. Distinct regions of the TIME were evaluated using 35 proteins probing tumor, immune and vasculature components across 323 fields of view. Single cell compositional analysis confirmed established prognostic immune cell types including increased prevalence of cytotoxic T cells within the tumor core FOVs of responders. Integrating single cell quantification with the spatial arrangement of cellular neighborhoods surrounding tumor cells revealed novel, spatial immune signatures capable of stratifying TIME based on clinical response. Our analysis revealed dynamic cellular composition of the TCCN based on anatomical subregion, functional expression of HLA-I by the index tumor cell and ultimately clinical response to immunotherapy. Overall, this study provides an analytical framework to resolve the cellular complexity of the TIME, increasingly relevant to the outcomes of modern cancer immunotherapy.


Development of an Electronic Screening and Brief Intervention to Address Perinatal Substance Use in Home Visiting: Qualitative User-Centered Approach.
Perinatal substance use (SU) is prevalent during pregnancy and the postpartum period and may increase the risks to maternal and child health. Many pregnant and postpartum women do not seek treatment for SU because of fear of child removal. Home visiting (HV), a voluntary supportive program for high-risk families during the perinatal period, is a promising avenue for addressing unmet SU needs. Confidential delivery of screening and brief intervention (BI) for SU via computers has demonstrated high user satisfaction among pregnant and postpartum women as well as efficacy in reducing perinatal SU. This study describes the development of the electronic screening and BI for HV (e-SBI-HV), a digital screening and BI program that is adapted from an existing electronic screening and BI (e-SBI) for perinatal SU and tailored to the HV context. This study aimed to describe the user-centered intervention development process that informed the adaptation of the original e-SBI into the e-SBI-HV, present specific themes extracted from the user-centered design process that directly informed the e-SBI-HV prototype and describe the e-SBI-HV prototype. Adaptation of the original e-SBI into the e-SBI-HV followed a user-centered design process that included 2 phases of interviews with home visitors and clients. The first phase focused on adaptation and the second phase focused on refinement. Themes were extracted from the interviews using inductive coding methods and systematically used to inform e-SBI-HV adaptations. Participants included 17 home visitors and 7 clients across 3 Healthy Families America programs in New Jersey. The e-SBI-HV is based on an existing e-SBI for perinatal SU that includes screening participants for SU followed by a brief motivational intervention. On the basis of the themes extracted from the user-centered design process, the original e-SBI was adapted to address population-specific motivating factors, address co-occurring problems, address concerns about confidentiality, acknowledge fear of child protective services, capitalize on the home visitor-client relationship, and provide information about SU treatment while acknowledging that many clients prefer not to access the formal treatment system. The full e-SBI-HV prototype included 2 digital intervention sessions and home visitor facilitation protocols. This study describes a user-centered approach for adapting an existing e-SBI for SU for use in the HV context. Despite the described challenges, home visitors and clients generally reacted favorably to the e-SBI-HV, noting that it has the potential to fill a significant gap in HV services. If proven effective, the e-SBI-HV could provide a way for clients to receive help with SU within HV, while maintaining their privacy and avoiding the overburdening of home visitors. The next step in this study would be to test the feasibility and preliminary efficacy of the e-SBI-HV.


Transformation and Precipitation Reactions by Metal Active Gas Pulsed Welded Joints from X2CrNiMoN22-5-3 Duplex Stainless Steels.
The high alloying degree of Duplex stainless steels makes them susceptible to the formation of intermetallic phases during their exposure to high temperatures. Precipitation of these phases can lead to a decreasing of the corrosion resistance and sometimes of the toughness. Starting from the advantages of the synergic Metal Active Gas (MAG) pulsed welding process, this paper analyses the structure formation particularities of homogeneous welded joints from Duplex stainless steel. The effect of linear welding energy on the structure morphology of the welded joints was revealed by macro- and micrographic examinations, X-ray energy dispersion analyses, measurements of ferrite proportion and X-ray diffraction analysis. The results obtained showed that the transformation of ferrite into austenite is associated with the chromium, nickel, molybdenum and nitrogen distribution between these two phases and their redistribution degree is closely linked to the overall heat cycle of the welding process. The adequate control of the energy inserted in the welded components provides an optimal balance between the two microstructural constituents (Austenite and Ferrite) and avoids the formation of undesirable intermetallic phases.


Leishmania donovani promastigotes evade the activation of mitogen-activated protein kinases p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase-1/2 during infection of naive macrophages.
The protozoan parasite Leishmania fails to activate naive macrophages for proinflammatory cytokines production, and selectively impairs signal transduction pathways in infected macrophages. Because mitogen-activated protein kinases (MAPK)- and NF-kappaB-dependent signaling pathways regulate proinflammatory cytokines release, we investigated their activation in mouse bone marrow-derived macrophages (BMM) exposed to Leishmania donovani promastigotes. In naive BMM, the parasite failed to induce the phosphorylation of p38 MAPK, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK)1/2, as well as the degradation of IkappaB-alpha. The use of L. donovani mutants defective in the biosynthesis of lipophosphoglycan revealed that evasion of ERK1/2 activation requires surface expression of the repeating unit moiety of this virulence determinant. In IFN-gamma-primed BMM, L. donovani promastigotes strongly induced the phosphorylation of p38 MAPK and ERK1/2, and the use of selective inhibitors for ERK (PD98059) and p38 MAPK (SB203580) revealed that both kinases are required for L. donovani-induced TNF-alpha but not NO(2)(-) release. Collectively, these data suggest that both p38 MAPK and ERK1/2 pathways participate in some Leishmania-induced responses in IFN-gamma-primed BMM. The ability of L. donovani promastigotes to avoid MAPK and NF-kappaB activation in naive macrophages may be part of the strategy evolved by this parasite to evade innate immune responses.


Relations of magnesium intake to cognitive impairment and dementia among participants in the Women's Health Initiative Memory Study: a prospective cohort study.
To examine the associations of dietary and supplemental magnesium (Mg) as assessed by a semi-quantitative food frequency questionnaire with cognitive outcomes among ageing women. This work conducts a prospective cohort study of participants enrolled in the Women's Health Initiative Memory Study (WHIMS), which was subsequently extended and named WHIMS-Epidemiology of Cognitive Health. Forty clinical centres in the USA. Postmenopausal women aged 65-79 years without dementia on enrolment. Physician-adjudicated mild cognitive impairment (MCI) and/or probable dementia (PD). Participants were excluded (n=1006) if they had extreme values of dietary energy intake, had missing or extreme body mass index values, with prevalent MCI/PD at baseline, received only one cognitive assessment or had been followed up for <1 year. During >20 years of follow-up, 765 (11.8%) out of 6473 participants developed MCI/PD. For MCI/PD and MCI, the risks tended to be lower among participants in quintiles Q2-Q5 of Mg consumption compared with those in the lowest quintile. Participants in Q3 had a significantly lower risk of MCI/PD (HR 0.69, 95% CI 0.53 to 0.91) and MCI (HR 0.63, 95% CI 0.45 to 0.87) after multivariate adjustments. No significant association was observed between total Mg intake and PD. The association between total Mg intake, MCI/PD and MCI was non-linear as suggested by the likelihood test. Total Mg intake between the estimated average requirement and the recommended dietary allowances may associate with a lower risk of MCI/PD and MCI. NCT00685009.


RNA synthesis and number of transcribing polymerase molecules in ischemic liver nuclei.
Nuclei isolated from ischemic liver show a consistent reduction of their RNA synthesis. The reduction persists at high ionic strength and in the presence of heparin, when RNA synthesis in vitro is fully activated and occurs in the presence as well as in the absence of alpha-amanitin. Both the number of transcribing polymerase molecules and the rate of elongation of initiated polynucleotide chains seem to be equally affected.


Mesenchymal stromal cells may enhance metastasis of neuroblastoma via SDF-1/CXCR4 and SDF-1/CXCR7 signaling.
Bone marrow metastasis is frequently observed in patients with high-risk neuroblastoma. Mesenchymal stromal cells (MSCs) in bone marrow may enhance tumor metastasis through secreting stromal cell-derived factor-1 (SDF-1). Here we investigated neuroblastoma cell behaviors under the influence of MSCs and explored the function of SDF-1 signaling during metastasis. Neuroblastoma expressed both of the SDF-1 receptors CXCR4 and CXCR7. shRNA knockdown showed that these receptors were responsible for the migration of neuroblastoma towards MSCs. CXCR4 also supported neuroblastoma invasion. These effects could be effectively blocked by AMD3100, a potent SDF-1 antagonist. Our study suggests that MSCs are important for neuroblastoma metastasis via the secretion of SDF-1 and that such effect can be inhibited by AMD3100 or shRNA knockdown.


Resistance to viral infection of super p53 mice.
Induction of expression of the tumor suppressor p53 after interferon treatment has been recently demonstrated (Takaoka et al., 2003), suggesting an antiviral activity of the protein. In addition, a direct correlation between p53 levels and tumor resistance has been addressed by generating mice with an extra copy of p53 ('super p53' mice) (Garcia-Cao et al., 2002). Here, we show that vesicular stomatitis virus replication in mouse embryo fibroblasts derived from 'super p53' mice is impaired as a result of apoptosis induction via p53 activation. These findings unequivocally demonstrate an antiviral activity of p53, a process that may contribute to inhibit the spread of the virus in vivo.


Ocular ultrasonography of sea turtles.
Environmental changes contribute to the development of ophthalmic diseases in sea turtles, but information on their eye biometrics is scarce. The aim of this study was to describe ophthalmic ultrasonographic features of four different sea turtle species; Caretta caretta (Loggerhead turtle; n = 10), Chelonia mydas (Green turtle; n = 8), Eretmochelys imbricata (Hawksbill turtle; n = 8) and Lepidochelys olivacea (Olive ridley; n = 6) under human care. Corneal thickness, scleral ossicle width and thickness, anterior chamber depth, axial length of the lens, vitreous chamber depth and axial globe length were measured by B-mode sonography with a linear transducer. Carapace size and animal weight were recorded. A sonographic description of the eye structures was established. The four species presented an ovate eyeball, a relatively thin cornea, and a small-sized lens positioned rostrally in the eye bulb, near the cornea, resulting in a shallow anterior chamber. The scleral ossicles did not prevent the evaluation of intraocular structures, even with a rotated eye or closed eyelids; image formation beyond the ossicles and measurements of all proposed structures were possible. B-mode sonography was easily performed in all animals studied. The sonographic characteristics of the eye were similar among the four species. Since there was a correlation between the size of the eye structures and the size of the individual, especially its carapace size, the differences found between E. imbricata and Caretta caretta are believed to be due to their overall difference in size. Sonography is a valuable tool in ophthalmic evaluation of these species. Only minor differences were found between the species in this study, reinforcing their phylogenetic proximity and their similar functions and habitats.


[The role and significance of trust for successful institutional risk communication].
The success of institutional crisis and risk communication is based on an open and dialogue-oriented communication policy as well as on a congruence between the expectations of all parties involved and their fulfillment. Central to communication with other actors and with the population is a mutual relationship of trust. This paper describes factors that are instrumental in determining whether and to what extent institutions can establish a basis of trust and credibility. It discusses how trustworthy risk communication can succeed even in times of crisis.Successful risk communication is tied to a process that conveys credibility and competence through openness of results, convincing communication of scientific evidence, the inclusion of plural values and criteria, and the synthesis of system and orientation knowledge. Given the uncertainty of knowledge and the confusion of communication processes in society, this task is not easy to accomplish. Despite these difficulties, institutions of risk assessment and regulation can build trust and perpetuate it over time through skillful coalition-building with organizations and groups with high trust potential, transparent, open-ended forms of communication, and the involvement of stakeholders and affected individuals in risk management.


Hippocampal neuroplasticity in major depressive disorder.
One of the most replicated findings has been that hippocampus volume is decreased in patients with major depressive disorder (MDD). Recent volumetric magnetic resonance imaging (MRI) studies suggest that localized differences in hippocampal volume may be more prominent than global differences. Preclinical and post-mortem studies in MDD indicated that different subfields of the hippocampus may respond differently to stress and may also have differential levels of plasticity in response to antidepressant treatment. Advances in high-field MRI allowed researchers to visualize and measure hippocampal subfield volumes in MDD patients in vivo. The results of these studies provide the first in vivo evidence that hippocampal volume reductions in MDD are specific to the cornu ammonis and dentate gyrus hippocampal subfields, findings that appear, on the surface, consistent with preclinical evidence for localized mechanisms of hippocampal neuroplasticity. In this review we discuss how recent advances in neuroimaging allow researchers to further understand hippocampal neuroplasticity in MDD and how it is related to antidepressant treatment, memory function, and disease progression.


Experimental model of pediatric asphyxial cardiopulmonary arrest in rats.
Develop a clinically relevant model of pediatric asphyxial cardiopulmonary arrest in rats. Prospective interventional study. University research laboratory. Postnatal day 16-18 rats (n = 9/group). Anesthetized rats were endotracheally intubated and mechanically ventilated, and vascular catheters were inserted. Vecuronium was administered, and the ventilator was disconnected from the rats for 8 mins, whereupon rats were resuscitated with epinephrine, sodium bicarbonate, and chest compressions until spontaneous circulation returned. Shams underwent all procedures except asphyxia. Asphyxial arrest typically occurred by 1 min after the ventilator was disconnected. Return of spontaneous circulation typically occurred <30 secs after resuscitation. An isoelectric electroencephalograph was observed for 30 mins after asphyxia, and rats remained comatose for 12-24 hrs. Overall survival rate was 85%. Motor function measured using beam balance and inclined plane tests was impaired on days 1 and 2, but recovered by day 3, in rats after asphyxia vs. sham injury (p <.05). Spatial memory acquisition measured using the Morris-water maze on days 7-14 and 28-35 was also impaired in rats after asphyxia vs. sham injury (total latency 379 +/- 28 vs. 501 +/- 40 secs, respectively, p <.05). DNA fragmentation was detected in CA1 hippocampal neurons bilaterally 3-7 days after asphyxia. Neurodegeneration detected using Fluorojade B was seen in bilateral CA1 hippocampi and layer V cortical neurons 3-7 days after asphyxia, with persistent neurodegeneration in CA1 hippocampus detected up to 5 wks after asphyxia. CA1 hippocampal neuron survival after asphyxia was 39-43% (p <.001 vs. sham). Evidence of DNA or cellular injury was not detected in sham rats. This model of asphyxial cardiopulmonary arrest in postnatal day 17 rats produces many of the clinical manifestations of pediatric hypoxic-ischemic encephalopathy. This model may be useful for the preclinical testing of novel and currently available interventions aimed at improving neurologic outcome in infants and children after cardiopulmonary arrest.


Chemoenzymatic Synthesis of (-)-Ribisins A and B from Dibenzo[b,d]furan.
cis-Dihydrodiols, derived from monocyclic aromatic compounds, are valuable chiral pool intermediates for the synthesis of cyclic natural products. A drawback of this approach, to the synthesis of polycyclic secondary metabolites, is that additional rings must be annulated. To date, relatively few chiral natural products have been synthesized from polycyclic arene cis-dihydrodiols. Fungal metabolites, (-)-ribisins A and B, have now been obtained by functional group manipulation of a tricyclic arene metabolite, obtained from toluene dioxygenase-catalyzed regioselective and stereoselective cis-dihydroxylations of dibenzo[b,d]furan. The synthetic sequences were marginally shorter than the alternative routes, using monocyclic arene cis-dihydrodiols, and required no carbon-carbon bond-forming reactions.


Fecoprevalence and determinants of Helicobacter pylori infection among asymptomatic children in Lebanon.
Helicobacter pylori plays a major etiologic factor in the pathogenesis of chronic gastritis, peptic ulcer disease, gastric adenocarcinoma, and mucosa associated lymphoid tissue lymphoma. However, most of the infected subjects remain asymptomatic. The aim of this study is to establish fecoprevalence of Helicobacter pylori infection in a convenient non-probabilistic sample of asymptomatic Lebanese children. Four-hundred fourteen children aged between one month and 17 years of different socioeconomic standards were selected for Helicobacter pylori antigen testing in stool. Demographic characteristics, health and nutritional status were obtained through a questionnaire. Fecoprevalence of Helicobacter pylori infection was 0.21 of whom 28.7% were between 0-3 years, 34.5% between 4-9 years and 36.8% between 10-17 years. Seventy-five (86.2%) of the fecopositive children were from low socioeconomic standards and 12 (13.8%) were from middle to high socioeconomic standards (p < 0.0001). Environmental variables demonstrated higher frequency of fecopositivity in children living in overcrowded houses, lower family income and poor parental education (p < 0.05). Helicobacter pylori is prevalent in asymptomatic Lebanese children. Prevention is worthy by improving the levels of education and the standards of hygiene.


Age-related changes in cerebral lactate metabolism in sleep-disordered breathing.
Thirty-one patients, aged 22-71 years, with nocturnal apneic episodes and/or habitual snoring were studied with magnetic resonance spectroscopy (MRS) and diagnostic polysomnography separately to determine whether accumulation of lactate caused by cerebral hypoxia during sleep is associated with sleep-disordered breathing (SDB), aging and co-morbidities related to SDB. Eight proton magnetic resonance spectra for sleep and two for periods of arousal were obtained from the right centrum semiovale. All patients were evaluated for the presence or absence of co-morbidities including hypertension, cardiac disease, diabetes mellitus, and hyperlipidemia. Significant lactate signals were found in seven patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) during sleep periods, and none during periods of arousal. Aging was significantly related to the presence or absence of significant lactate signals during sleep periods as determined by logistic regression analysis (beta=0.2480; 95% confidence interval, 0.0905-0.5094; P=0.0001). Apnea index (AI), apnea-hypopnea index (AHI), and minimum value of peripheral oxyhemoglobin saturation each significantly interacted with age (P=0.0081, 0.0284, and 0.0302, respectively). Our findings suggest that SDB combined with aging is related to accumulation of lactate during sleep.


Enhancing frontal top-down inhibitory control with Go/NoGo training.
Whether and how the capacity to inhibit cognitive and motor processes can be trained and the underlying neuroplastic mechanisms remain unclear. Using electrical neuroimaging methods, we investigated how inhibitory control training regimens can be designed to enhance frontal top-down inhibition processes. We trained participants with a Go/NoGo task in which the stimulus-response mapping rules were systematically varied. This task parameter has indeed be hypothesized to determine the extent to which top-down frontal inhibition processes are involved and thus ultimately reinforced during the training. The effects of training on inhibitory control were assessed by analyzing the event-related potentials (ERPs) measured during the Go/NoGo task with a data-driven time- and electrode-wise 2 × 2 ANOVA with factors Session (beginning; end of the training) and Stimuli (Go; NoGo). To localize the sources of the ERP effects in the brain, the same statistical design was applied to distributed electrical source estimations averaged over the periods of ERP modulations. The training improved inhibitory control performance. Electrophysiologically, we found a significant Session × Stimulus interaction at 300-400 ms post-stimulus onset over centro-occipital electrodes. Statistical parametric mapping on the brain source estimations revealed an interaction within right inferior frontal cortices driven by a decrease in response strength to NoGo but not to Go trials in this region. Our collective results demonstrate that frontal top-down inhibition processes can be enhanced with specifically designed inhibitory control training regimens.


An urban air quality assessment based on a meteorological perspective.
An integrated approach to understanding all measured pollutants with multi-discipline in different time scales and understanding the mechanisms hidden under low air quality (AQ) conditions is essential for tackling potential air pollution issues. In this study, the air pollution of Sivas province was analyzed with meteorological and PM2.5 data over six years to assess the city's AQ in terms of PM2.5 pollution and analyze the effect of meteorological factors on it. It was found that the winter period (January-February-November-December) of every year except 2019-which has missing data-is the period with the highest air pollution in the province. In addition, the days exceeding the daily PM2.5 limit values in 2016, 2017, 2020, and 2021 were also seen in the spring and summer months, which inclined the study to focus on additional pollutant sources such as long-range dust transport and road vehicles. The year 2017 has the highest values and was analyzed in detail. Pollution periods with the most increased episodes in 2018 were analyzed with the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) and Dust Regional Atmospheric Model (DREAM) models. As a result of the study, the average PM2.5 values in 2017 were 31.66 ± 19.2 µg/m3 and a correlation of -0.49 between temperature and PM2.5. As a result of model outputs, it was found that the inversion is intensely observed in the province, which is associated with an increase of PM2.5 during the episodes. Dust transport from northwestern Iraq and northeastern Syria is observed, especially on days with daily average PM2.5 values above 100 µg/m3. Additionally, planetary boundary layer (PBL) data analysis with PM pollution revealed a significant negative correlation (r = -0.61). Air pollutants, particularly PM2.5, were found to be higher during lower PBL levels.


Blood product requirements in patients undergoing elective endovascular abdominal aortic aneurysm repair.
Endovascular repair (EVR) of abdominal aortic aneurysm (AAA) has many potential advantages, one of which may be reduced blood product requirements. The aim of this study was to compare the current blood product usage in our unit for three types of elective operation: EVR of AAA, open AAA repair and femorofemoral crossover grafts. Prospective data analysis with historical controls. One-hundred and thirty-two patients undergoing elective EVR of AAA, 35 patients undergoing elective open repair of AAA and 37 patients having femorofemoral crossover grafts. Data was collected on the blood product requirements of patients having EVR of AAA, with open AAA repair and femorofemoral crossover graft providing historical controls. There was no difference in the haematological parameters preoperatively between the three groups but postoperatively patients having EVR had a slightly lower haemoglobin than the open group (10.6 g/dl vs. 10.85 g/dl, p = 0.015). The number of patients who received blood transfusion in the EVR group was 82/132 (62%) and the open group 27/35 (77%), p = 0.4. Patients undergoing EVR of AAA require blood transfusion in the same numbers when compared to those undergoing open repair.


Modeling perinatal mortality in twins via generalized additive mixed models: a comparison of estimation approaches.
The analysis of twin data presents a unique challenge. Second-born twins on average weigh less than first-born twins and have an elevated risk of perinatal mortality. It is not clear whether the risk difference depends on birth order or their relative birth weight. This study evaluates the association between birth order and perinatal mortality by birth order-specific weight difference in twin pregnancies. We adopt generalized additive mixed models (GAMMs) which are a flexible version of generalized linear mixed models (GLMMs), to model the association. Estimation of such models for correlated binary data is challenging. We compare both Bayesian and likelihood-based approaches for estimating GAMMs via simulation. We apply the methods to the US matched multiple birth data to evaluate the association between twins' birth order and perinatal mortality. Perinatal mortality depends on both birth order and relative birthweight. Simulation results suggest that the Bayesian method with half-Cauchy priors for variance components performs well in estimating all components of the GAMM. The Bayesian results were sensitive to prior specifications. We adopted a flexible statistical model, GAMM, to precisely estimate the perinatal mortality risk differences between first- and second-born twins whereby birthweight and gestational age are nonparametrically modelled to explicitly adjust for their effects. The risk of perinatal mortality in twins was found to depend on both birth order and relative birthweight. We demonstrated that the Bayesian method estimated the GAMM model components more reliably than the frequentist approaches.


A one-step large-scale method for T- and B-cell depletion of mobilized PBSC for allogeneic transplantation.
The presence of T and B cells in allogeneic grafts contributes to GvHD and to EBV-associated lymphoproliferative disease (LPD). Depletion of T and B cells from the graft decreases the risk of these complications. T and B cells were depleted from mobilized peripheral stem cells from volunteer donors (n=5) using anti-CD3 and anti-CD19 Abs conjugated to magnetic microbeads, and the CliniMACS device. The function of the stem cells after depletion was evaluated using colony assays and non-obese diabetic (NOD)/SCID repopulating experiments. The mean mononuclear cell (MNC) count prior to T- and B-cell depletion was 2.19x10(10) (range 1.48-3.53). After depletion, the mean percentage of contaminating T cells was 0.02% (range 0.01-0.04%) with a mean log(10) depletion of 3.4 (range 3-3.8). The mean percentage of contaminating B cells was 0.1% (range 0.01-0.4%) with a mean log(10) depletion of 2.2 (range 1.4-3). The mean recovery of CD3- and CD19-negative MNCs after depletion was 70% (range 54-88%) and the mean recovery of CD34(+) stem cells was 69% (range 52-98%). The mean number of natural killer (NK) cells after T- and B-cell depletion was 5.2x10(8) (range 2-10x10(8)). In vitro colony assays and in vivo NOD/SCID repopulation assays showed no negative impact of this method on the function of the hematopoietic stem cells. Our results show that the CliniMACS system can be used to efficiently deplete PBSC of T and B cells simultaneously, without adverse effect on the graft.


Troponin T in elders with suspected acute coronary syndromes.
Troponin T (TnT) elevations (> or =0.1 ng/mL) indicate an increased risk of adverse outcomes in patients with acute coronary syndromes (ACS). There is little data on the prognostic significance of TnT in elders with ACS. We sought to define the ability of TnT to predict adverse outcomes in elders with suspected ACS compared with the younger cohort. This is a nested cohort study of patients aged <65 and > or =65 years with suspected ACS. Serial ECGs, CKMB and TnT assays were obtained at presentation and 4, 8, and 16 hours later. Adverse outcomes at hospital discharge included death, nonfatal myocardial infarction, coronary artery bypass grafting, and positive cardiac catheterization. A total of 695 patients were enrolled. A total of 301 (48%) were aged 65 or older. Although there was no difference in TnT sensitivity between the younger and older cohorts, there was a difference in specificity, 94% versus 83% (P <.01), respectively. In both cohorts, renal insufficiency was associated with a significantly lower TnT specificity. In both elders and younger patients with abnormal renal function, low TnT specificity warrants careful consideration of this marker as the sole criterion for aggressive medical management.


An Elderly Woman with Exertional Dyspnoea and T-Wave Inversions on Electrocardiography.
We present a case of a 75-year-old woman with cardiac dextroposition who presented for preoperative cardiac evaluation because of exertional dyspnoea. On examination, heart sounds were best appreciated on the right, and bowel sounds were heard over the left hemithorax. Electrocardiography showed widespread T-wave inversions. No coronary artery ischemia was found. A large congenital diaphragmatic hernia with displacement of the heart to the right was found on chest radiography and confirmed on computed tomography. Surgery was subsequently uneventful. In conclusion, thorough pulmonary auscultation to detect bowel sounds in the thorax increases clinical suspicion of cardiac dextroposition.


Chronic Q fever: expert opinion versus literature analysis and consensus.
Q fever has long been considered a rare disease. The extensive outbreak in the Netherlands generated a body of literature based solely on the consensus in the Netherlands. As a long-standing expert on Q fever, I offer my experience and recommendations to the E-CDC and the Dutch Q fever Consensus Group. My (biased) opinion is that experts deeply involved in the field continue to be useful in the management of outbreaks and can avoid decisions that produce an unfavorable progression in patients. Here, I propose that the definition of "chronic Q fever" be avoided and suggest a new score-based diagnosis for Q fever endocarditis and vascular infection.


Consensus guidelines on severe acute pancreatitis.
This Position Paper contains clinically oriented guidelines by the Italian Association for the Study of the Pancreas (AISP) for the diagnosis and treatment of severe acute pancreatitis. The statements were formulated by three working groups of experts who searched and analysed the most recent literature; a consensus process was then performed using a modified Delphi procedure. The statements provide recommendations on the most appropriate definition of the complications of severe acute pancreatitis, the diagnostic approach and the timing of conservative as well as interventional endoscopic, radiological and surgical treatments.


Validation of the Revised Illness Perception Questionnaire of Obstructive Sleep Apnea among Elderly Chinese in the General Population.
The prevalence of under-diagnosis among individuals with obstructive sleep apnea (OSA) is alarming, and may be associated with perceptions regarding OSA. To facilitate future studies on OSA, this study validated the revised version of the Illness Perception Questionnaire (IPQ-R) for OSA in a general population. A random anonymous population-based telephone survey interviewed 580 adults aged ≥ 50 years in Hong Kong, who self-reported not having been told by doctors as having OSA, from February 5 to March 19, 2021. The confirmatory factor analysis identified a modified 7-factor model (i.e., timeline chronic, consequence, personal control, treatment control, illness coherence, timeline cyclical, and emotional representation) that showed satisfactory model fit index and internal consistency. Nine items were removed from the original version because of low factor loadings. No floor and ceiling effects were observed. Convergent validity was supported by the positive associations between the consequence subscale with perceived negative outcomes of OSA and between the illness coherence subscale and perceived understanding of OSA symptoms. The participants tended to endorse the items of timeline chronic, treatment control, and illness coherence but not with those of emotional representations. The mean scores of the IPQ-R subscales differed by age and education level. The modified IPQ-R of OSA showed acceptable psychometric properties. It is applicable to assessing illness perceptions of OSA in the Chinese general population aged ≥ 50 years not having received OSA diagnosis. The validated tool would support future studies and health practices related to OSA.


RGD-tagged helical rosette nanotubes aggravate acute lipopolysaccharide-induced lung inflammation.
Rosette nanotubes (RNT) are a novel class of self-assembled biocompatible nanotubes that offer a built-in strategy for engineering structure and function through covalent tagging of synthetic self-assembling modules (G∧C motif). In this report, the G∧C motif was tagged with peptide Arg-Gly-Asp-Ser-Lys (RGDSK-G∧C) and amino acid Lys (K-G∧C) which, upon co-assembly, generate RNTs featuring RGDSK and K on their surface in predefined molar ratios. These hybrid RNTs, referred to as K(x)/RGDSK(y)-RNT, where x and y refer to the molar ratios of K-G∧C and RGDSK-G∧C, were designed to target neutrophil integrins. A mouse model was used to investigate the effects of intravenous K(x)/RGDSK(y)-RNT on acute lipopolysaccharide (LPS)-induced lung inflammation. Healthy male C57BL/6 mice were treated intranasally with Escherichia coli LPS 80 μg and/or intravenously with K⁹⁰/RGDSK¹⁰-RNT. Here we provide the first evidence that intravenous administration of K⁹⁰/RGDSK¹⁰-RNT aggravates the proinflammatory effect of LPS in the mouse. LPS and K⁹⁰/RGDSK¹⁰-RNT treatment groups showed significantly increased infiltration of polymorphonuclear cells in bronchoalveolar lavage fluid at all time points compared with the saline control. The combined effect of LPS and K⁹⁰/RGDSK¹⁰-RNT was more pronounced than LPS alone, as shown by a significant increase in the expression of interleukin-1β, MCP-1, MIP-1, and KC-1 in the bronchoalveolar lavage fluid and myeloperoxidase activity in the lung tissues. We conclude that K⁹⁰/RGDSK¹⁰-RNT promotes acute lung inflammation, and when used along with LPS, leads to exaggerated immune response in the lung.


Crown fire and surface fire: effects on myxomycetes inhabiting pine plantations.
Myxomycetes are heterotrophic eukaryote organisms that have three life stages, none of which are known to be resistant to fire. The response of myxobiota to different severity of fire is not well known either. We examined myxomycetes in Pinus mugo plantations following a crown fire and in Pinus sylvestris plantations following a surface fire during the first three years after the wildfire event in forested coastal sand dunes in western Lithuania. Additionally, we investigated myxomycetes in corresponding unburned stands. All studied sites (unburned and burned) bore rather different myxomycete assemblages but the disparities of the species compositions between both burn types were more pronounced showing that fire severity had stronger impact on myxomycete species composition than the pre-fire stand type. Analysis of myxomycete assemblages (including the results from field collections, bark and litter cultures) showed that surface fire sites bore the highest number of post-fire species compared to crown fire and unburned sites. Dynamic annual changes in species composition were observed in all studied sites but only crown fire plots showed a clear chronosequence of post-fire myxomycete assemblages. Fire impact promoted establishment and/or sporulation of myxomycete species that are rare in similar unburned stands, or are usually confined to other types of forests and substrata. In addition, individual myxomycete species tended to switch substratum usage during the course of vegetation succession, with a final return to their usual substrata. This possibly signaled the end of early stage of post-fire succession.


Prenatal witness stress induces intergenerational anxiety-like behaviors and altered gene expression profiles in male mice.
Prenatal cues imposed on an organism can exert long-term and even cross-generational influences on the physiology and behaviors. To date, numerous rodent models have been developed to mimic the effects of prenatal physical stress on offspring. Whether psychological stress during gestation exerts adverse influences on offspring remains investigated. Here, we report that prenatal witnessing the defeat process of the mated partner induces anxiety-like behaviors in F1 male, but not female offspring. These abnormal behaviors were not present in the F2 generation, indicating a sex-specific intergenerational effects. Genome-wide transcriptional profiling identified 71 up-regulated and 120 down-regulated genes shared in F0 maternal and F1 male hippocampus. F0 and F1 hippocampi also shared witness stress-sensitive and -resistant genes. Whole transcriptome comparison reveals that F1 dentate gyrus showed differential expression profiles from hippocampus. Few differentially expressed genes were identified in the dentate gyrus of F1 stress female mice, explaining why females were resistant to the stress. Finally, candidate drugs as the potential treatment for psychological stress were predicted according to transcriptional signatures, including the histone deacetylase inhibitor and dopamine receptor agonist. Our work provides a new model for better understanding the molecular basis of prenatal psychological stress, highlighting the complexity of stress and sex factors on emotion and behaviors.


Urinary tract infections.
Clinical presentation helps differentiate between upper and lower urinary tract infections (UTIs). UTIs are classified as either complicated or uncomplicated. A complicated UTI is associated with an underlying condition that increases the risk of failing therapy. Primary laboratory tests for UTIs consist of urinalysis and urine culture. The most common pathogen for uncomplicated cystitis and pyelonephritis is Escherichia coli. Nitrofurantoin, fosfomycin, and trimethoprim-sulfamethoxazole are first-line therapies for acute uncomplicated cystitis. Decisions regarding antibiotic agents should be individualized based on patients' allergies, tolerability, community resistance rates, cost, and availability.


Production of oxytocin receptor and cytokines in primary uterine smooth muscle cells cultivated under inflammatory conditions.
We studied the production of the oxytocin receptor and interleukins in human uterine smooth muscle cells cultured in vitro in the presence of cytokines that were shown to be elevated in gestational diseases such as intrauterine infections and chorioamnionitis. Human uterine smooth muscle cells were cultured in the absence or presence of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFalpha), or lipopolysaccharide (LPS). Additionally, cells were cultivated under hypoxic conditions (3.5% oxygen). After 6, 12, 24, and 48 hours of incubation, oxytocin receptor mRNA was measured from total RNA using quantitative, competitive reverse transcriptase-polymerase chain reaction. Secreted cytokines (IL-1beta, IL-6, or IL-8) were quantitated from supernatants after 6, 12, 24, and 48 hours of stimulation by commercially available enzyme-linked immunosorbent assay. In nonstimulated cultures basal secretion of IL-1beta, IL-6, and IL-8 was detectable. Supplementation of IL-1beta induced a statistically significant decrease in oxytocin receptor mRNA abundance, whereas IL-6, TNFalpha, LPS, or hypoxia did not significantly affect oxytocin receptor gene expression. The cytokines IL-1 and TNFalpha induced IL-6 and IL-8 release, whereas secretion of the two interleukins was not altered in the presence of LPS or hypoxia. Expression of IL-1beta was not significantly induced under inflammatory or hypoxic culture conditions. The constitutive and cytokine-inducible expression of interleukins from uterine smooth muscle cells suggests that the myometrium may contribute to the overall production of inflammatory mediators in the uterus that are thought to govern term- or infection-induced preterm labor. Down-regulation of the oxytocin receptor under IL-1beta in myometrial cells may indicate that initiation and maintenance of labor could be partially limited under severe inflammatory conditions such as chorioamnionitis.


Topology of pain networks in patients with temporomandibular disorder and pain-free controls with and without concurrent experimental pain: A pilot study.
Temporomandibular disorders (TMD) involve chronic pain in the masticatory muscles and jaw joints, but the mechanisms underlying the pain are heterogenous and vary across individuals. In some cases, structural, functional, and metabolic changes in the brain may underlie the condition. In the present study, we evaluated the functional connectivity between 86 regions of interest (ROIs), which were chosen based on previously reported neuroimaging studies of pain and differences in brain morphology identified in an initial surface-based morphometry analysis. Our main objectives were to investigate the topology of the network formed by these ROIs and how it differs between individuals with TMD and chronic pain (n = 16) and pain-free control participants (n = 12). In addition to a true resting state functional connectivity scan, we also measured functional connectivity during a 6-min application of a noxious cuff stimulus applied to the left leg. Our principal finding is individuals with TMD exhibit more suprathreshold correlations (higher nodal degree) among all ROIs but fewer "hub" nodes (i.e., decreased betweenness centrality) across conditions and across all pain pathways. These results suggest is this pain-related network of nodes may be "over-wired" in individuals with TMD and chronic pain compared to controls, both at rest and during experimental pain.


EGSnrc-based depth-dependent photon energy response and phantom scatter corrections for low-energy brachytherapy sources.
In the present study, beam quality correction, [Formula: see text], and phantom scatter correction, kphan(r), for low-energy brachytherapy sources, 131Cs, 125I, and 103Pd, are calculated using the Monte Carlo-based EGSnrc code system as a function of the distance along the transverse axis of the source. The solid-state detectors investigated are diamond, LiF, Li2B4O7, Al2O3, and radiochromic films, such as HS, EBT, EBT2, EBT3, RTQA, XRT, and XRQA. The solid phantoms investigated are polystyrene, PMMA, virtual water, solid water, plastic water (LR), A150, RW1, RW3, and WE210. For a given detector and brachytherapy source, [Formula: see text] is independent of distance in the water phantom. Meanwhile, for a given detector, kphan(r) depends on the distance from the source for the investigated solid phantoms. Moreover, the kphan(r) values do not change with the detector type for sources 131Cs, 125I, and 103Pd at all distances. The LR and A150 phantoms are water equivalent for the investigated distances of 1-5 cm. The phantoms including solid water, virtual water, and WE210 are not water-equivalent for distances beyond 1 cm. Furthermore, PMMA, polystyrene, RW1, and RW3 are not water equivalent.


Impact of Medicare coverage on basic clinical services for previously uninsured adults.
Uninsured adults receive less appropriate care and have more adverse health consequences than insured adults. Longitudinal studies would help to more clearly define the effects of health insurance on health care and health. To assess the differential effects of gaining Medicare coverage on use of basic clinical services and medications by previously insured and uninsured adults. Household survey data from the nationally representative Health and Retirement Study were used to analyze differences in receipt of basic clinical services by adults in 1996 and 2000, before and after becoming eligible for Medicare at age 65 years. A total of 2203 adults aged 60 to 64 years in 1996 who were classified as continuously uninsured (n = 167), intermittently uninsured (n = 216), or continuously insured (n = 1820) in 1994 and 1996, prior to Medicare eligibility. Individuals' reports of receiving cholesterol testing, mammography (in women), prostate examination (in men), and treatment of arthritis and hypertension in the prior 2 years. The difference in cholesterol testing between continuously insured and continuously uninsured adults was significantly reduced after Medicare eligibility (35.4% vs 17.7%; change of -17.7% [95% CI, -29.3% to -6.2%]; P =.003), and the reduction was substantially greater among those with hypertension or diabetes than among other adults (29.2% vs 7.7%; difference of 21.5% [95% CI, 0.2% to 42.9%]; P =.048). Differences in use were similarly reduced after Medicare eligibility for mammography in women (30.3% vs 15.0%; change of -15.3% [95% CI, -29.9% to -0.7%]; P =.04) and prostate examination in men (45.2% vs 20.0%; change of -25.2% [95% CI, -45.4% to -5.1%]; P =.01). Continuously uninsured adults with arthritis reported significantly greater increases in arthritis-related medical visits and limitations of activity than continuously insured adults after Medicare eligibility, but not greater increases in arthritis treatments. Among adults with hypertension, differences in use of antihypertensive medications between continuously uninsured and insured adults were essentially unchanged after Medicare coverage. Previously uninsured adults substantially increased their use of covered basic clinical services but not medications after gaining Medicare coverage. An affordable option through which near-elderly uninsured adults could purchase Medicare coverage might have similar effects.


Risk factors associated with the prevalence of neck and shoulder pain among high school students: a cross-sectional survey in China.
After the COVID-19 outbreak, many Chinese high school students have increased their dependence on electronic devices for studying and life, which may affect the incidence of neck and shoulder pain (NSP) in Chinese adolescents. To evaluate the prevalence of NSP in high school students and its associated risk factors during COVID-19, a survey was conducted among 5,046 high school students in Shanghai, Qinghai, Henan and Macao during the second semester and summer vacation of the 2019-2020 academic year. The questionnaire included questions regarding demographic characteristics, the prevalence of NSP and lifestyle factors such as sedentary behavior, poor posture and electronic device usage. Univariable and multivariable logistic regression was used to analyze the possible influencing factors for neck and shoulder pain. A total of 4793 valid questionnaires (95.0%) were collected. The results indicated that the prevalence of NSP was 23.7% among high school students. Binary logistic regression analysis revealed that female gender (P < 0.05, OR = 1.82), grade (P < 0.05, range OR 1.40-1.51) and subject selection (P < 0.05, range OR 0.49-0.68) were risk factors for NSP in high school students. Sedentary behavior (P < 0.05, range OR 1.74-2.36), poor posture (P < 0.05, range OR 1.19-2.56), backpack weight (P < 0.05, range OR 1.17-1.88), exercise style and frequency (P < 0.05, range OR 1.18-1.31; P < 0.05, range OR 0.76-0.79, respectively), and the time spent using electronic devices (P < 0.05, range OR 1.23-1.38)had a significant correlation with NSP in high school students. NSP is currently very common among high school students during the outbreak of COVID-19. Sedentary behavior, poor posture and other factors have a great impact on the occurrence of NSP in high school students. Education regarding healthy lifestyle choices should be advocated for to decrease NSP among high school students, such as more physical activity, changing poor postures and reducing the amount of time spent using electronic devices.


Pharmacokinetic parameters derived from dynamic contrast enhanced MRI of cervical cancers predict chemoradiotherapy outcome.
To assess the prognostic value of pharmacokinetic parameters derived from pre-chemoradiotherapy dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) of cervical cancer patients. Seventy-eight patients with locally advanced cervical cancer underwent DCE-MRI with Gd-DTPA before chemoradiotherapy. The pharmacokinetic Brix and Tofts models were fitted to contrast enhancement curves in all tumor voxels, providing histograms of several pharmacokinetic parameters (Brix: A(Brix), k(ep), k(el), Tofts: K(trans), ν(e)). A percentile screening approach including log-rank survival tests was undertaken to identify the clinically most relevant part of the intratumoral parameter distribution. Clinical endpoints were progression-free survival (PFS) and locoregional control (LRC). Multivariate analysis including FIGO stage and tumor volume was used to assess the prognostic significance of the imaging parameters. A(Brix), k(el), and K(trans) were significantly (P<0.05) positively associated with both clinical LRC and PFS, while ν(e) was significantly positively correlated with PFS only. k(ep) showed no association with any endpoint. A(Brix) was positively correlated with K(trans) and ν(e), and showed the strongest association with endpoint in the log-rank testing. k(el) and K(trans) were independent prognostic factors in multivariate analysis with LRC as endpoint. Parameters estimated by pharmacokinetic analysis of DCE-MR images obtained prior to chemoradiotherapy may be used for identifying patients at risk of treatment failure.


Cholecystokinin in feline vagal and sciatic nerves: concentration, molecular form and transport velocity.
The axonal transport velocity of immunoreactive cholecystokinin (CCK) was examined in the vagal and sciatic nerves of anesthetized cats after determination of the molecular form of CCK by sequence-specific radioimmunoassay and gel chromatography. Extracts of the peripheral nerve branches, corresponding spinal ganglia, brainstem and spinal cord, contained mainly CCK-8-like immunoreactivity. In addition a large molecular form eluted immediately after the void volume of Sephadex G-50 columns, and occasionally minor C-terminal fragments were discovered. A single vagal nerve and one medulla oblongata also contained gastrin-17-like material. Significant differences in the relative amounts of the molecular forms of CCK in the different regions and nerves were not apparent. The distally directed (anterograde) flux of CCK was found to be 78 fmol/h in the sciatic nerve and 50 fmol/h in the vagus. Significant retrograde transport was not detectable. Based on these figures the true velocity for the anterograde transport was estimated to be 7 mm/h for CCK in the vagus and 8 mm/h in the sciatic nerves. The results indicate that CCK-8-like peptides are rapidly transported distally without significant axonal processing of CCK precursors.


Associations with medication adherence among ethnically different pediatric patients with renal transplants.
This study examined perceived medication regimen characteristics as factors in levels of medication adherence among 26 African American and 42 European American pediatric renal transplant patients. Among both groups, perceived characteristics of their medication regimen, including pill size, pill taste and medication complexity, were found to have significantly low to moderate associations with medication adherence. These associations were stronger and more consistent across medication adherence measures among the African American patients. This supports the need to separately examine the factors contributing to medication adherence among ethnically different pediatric patients. Suggestions for promoting medication adherence among pediatric patients with renal transplants and implications for future research are discussed.


Liquid biopsy in the assessment of microRNAs in oral squamous cell carcinoma: A systematic review.
The identification of non-invasive biomarkers from biological fluids collected by liquid biopsy provides new horizons for individualized therapeutic strategies and improves clinical decision-making in OSCC patients. Circulating microRNAs have emerged as biomarkers that may reflect not only the existence of cancer, but also the dynamic, malignant potential, and drug resistance of tumors. The aim of the systematic review is to evaluate and summarize the results of the published studies regarding the use of microRNAs as biomarkers for OSCC. A literature search was conducted on PubMed, Scopus, Web of Science, and Cochrane databases till November 2020. A total of 34 studies met the inclusion criteria and were therefore subjected to quality assessment. Each study was subjected to data extraction including; patient characteristics, type of fluid sample (whole blood, plasma, serum, or saliva), molecular analysis method, specific dysregulated microRNA, and microRNA expression pattern. The analysis showed that 57 microRNAs of liquid biopsy samples of four different fluids (whole blood, serum, plasma, and saliva) were analyzed. The prognostic and therapeutic significance of these microRNAs were suggested by several studies; where 41 microRNAs were upregulated while 16 were downregulated. Scientific evidence supports the interest in the use of microRNAs in the diagnosis and prognosis in OSCC patients; however, further studies in a larger cohort of patients are mandatory to introduce liquid biopsy in the routine clinical practice for the OSCC management. Key words:Biomarkers, liquid biopsy, microRNA, oral squamous cell carcinoma, systematic review.


Expression of human cationic trypsinogen (PRSS1) in murine acinar cells promotes pancreatitis and apoptotic cell death.
Hereditary pancreatitis (HP) is an autosomal dominant disease that displays the features of both acute and chronic pancreatitis. Mutations in human cationic trypsinogen (PRSS1) are associated with HP and have provided some insight into the pathogenesis of pancreatitis, but mechanisms responsible for the initiation of pancreatitis have not been elucidated and the role of apoptosis and necrosis has been much debated. However, it has been generally accepted that trypsinogen, prematurely activated within the pancreatic acinar cell, has a major role in the initiation process. Functional studies of HP have been limited by the absence of an experimental system that authentically mimics disease development. We therefore developed a novel transgenic murine model system using wild-type (WT) human PRSS1 or two HP-associated mutants (R122H and N29I) to determine whether expression of human cationic trypsinogen in murine acinar cells promotes pancreatitis. The rat elastase promoter was used to target transgene expression to pancreatic acinar cells in three transgenic strains that were generated: Tg(Ela-PRSS1)NV, Tg(Ela-PRSS1*R122H)NV and Tg(Ela-PRSS1*N29I)NV. Mice were analysed histologically, immunohistochemically and biochemically. We found that transgene expression is restricted to pancreatic acinar cells and transgenic PRSS1 proteins are targeted to the pancreatic secretory pathway. Animals from all transgenic strains developed pancreatitis characterised by acinar cell vacuolisation, inflammatory infiltrates and fibrosis. Transgenic animals also developed more severe pancreatitis upon treatment with low-dose cerulein than controls, displaying significantly higher scores for oedema, inflammation and overall histopathology. Expression of PRSS1, WT or mutant, in acinar cells increased apoptosis in pancreatic tissues and isolated acinar cells. Moreover, studies of isolated acinar cells demonstrated that transgene expression promotes apoptosis rather than necrosis. We therefore conclude that expression of WT or mutant human PRSS1 in murine acinar cells induces apoptosis and is sufficient to promote spontaneous pancreatitis, which is enhanced in response to cellular insult.


Bright light therapy as part of a multicomponent management program improves sleep and functional outcomes in delirious older hospitalized adults.
Delirium is associated with poor outcomes following acute hospitalization. A specialized delirium management unit, the Geriatric Monitoring Unit (GMU), was established. Evening bright light therapy (2000-3000 lux; 6-10 pm daily) was added as adjunctive treatment, to consolidate circadian activity rhythms and improve sleep. This study examined whether the GMU program improved sleep, cognitive, and functional outcomes in delirious patients. A total of 228 patients (mean age = 84.2 years) were studied. The clinical characteristics, delirium duration, delirium subtype, Delirium Rating Score (DRS), cognitive status (Chinese Mini-Mental State Examination), functional status (modified Barthel Index [MBI]), and chemical restraint use during the initial and predischarge phase of the patient's GMU admission were obtained. Nurses completed hourly 24-hour patient sleep logs, and from these, the mean total sleep time, number of awakenings, and sleep bouts (SB) were computed. The mean delirium duration was 6.7 ± 4.6 days. Analysis of the delirium subtypes showed that 18.4% had hypoactive delirium, 30.2% mixed delirium, and 51.3% had hyperactive delirium. There were significant improvements in MBI scores, especially for the hyperactive and mixed delirium subtypes (P < 0.05). Significant improvements were noted on the DRS sleep-wake disturbance subscore, for all delirium-subtypes. The mean total sleep time (7.7 from 6.4 hours) (P < 0.05) and length of first SB (6.0 compared with 5.3 hours) (P < 0.05) improved, with decreased mean number of SBs and awakenings. The sleep improvements were mainly seen in the hyperactive delirium subtype. This study shows initial evidence for the clinical benefits (longer total sleep time, increased first SB length, and functional gains) of incorporating bright light therapy as part of a multicomponent delirium management program. The benefits appear to have occurred mainly in patients with hyperactive delirium, which merits further in-depth, randomized controlled studies.


Featured Reviews in Organic Chemistry.
The field of Organic Chemistry represents one of the most traditional areas of chemistry that has delivered many benefits to the community of chemists [...].


Mitral valve replacement is a viable alternative to mitral valve repair for ischemic mitral regurgitation: a case-matched study.
Comparisons of mitral valve repair with mitral valve replacement for ischemic mitral regurgitation (IMR) have been limited by differences in preoperative and operative characteristics of patients undergoing these two types of surgical treatment. We performed a propensity-based, case-matched analysis to examine whether patients who undergo mitral valve repair and those who undergo mitral valve replacement for IMR have similar long-term outcomes. We compared 65 patients who underwent mitral valve replacement for IMR between 2001 and 2010 with 65 patients who underwent mitral repair during the same period on the basis of age, concomitant coronary bypass grafting, gender, left ventricular function, preoperative pulmonary hypertension, and urgency of operation. Mitral replacement involved preservation of the subvalvular apparatus. The mean study follow-up period was 2.5 ± 2.1 years. Two patients who underwent mitral valve repair died at 30 days postoperatively and three patients died after valve replacement. Late survival was the same in the two groups (p = 0.4). Recurrent mitral regurgitation (MR) (grade 2+ or higher) at late follow-up was observed in 15 patients (23%) after repair; however, only 1 patient (2%) had MR with a grade of more than 2+. Mitral valve repair was more commonly associated with recurrent MR (grade 2+ or higher) than was mitral valve replacement (p = 0.04). Patients in both groups had similar freedom from valve-related complications and similar left ventricular function at follow-up (both p > 0.2). Mitral valve replacement remains a viable option for the treatment of IMR. Although mitral valve repair effectively protects against persistent or recurrent moderate-to-severe MR, mitral valve replacement provides better freedom from mild-to-moderate MR in this population, with a low incidence of valve-related complications. Notably, there was no significant difference in left ventricular function between the valve-repair and valve-replacement groups at follow-up.


Effects of Chamomilla recutita flavonoids on age-related liver sphingolipid turnover in rats.
The increased sphingolipid turnover in the liver is associated with elevation of free radical production and state of chronic inflammation at old age. Plant polyphenols are reported to exhibit antioxidant and anti-inflammatory effects. In the present paper, the lipids contents and ceramide production in the liver and hepatocytes as well as the correction of sphingolipid metabolism at old age using the mixture of Chamomilla recutita flavonoids (chamiloflan) or apigenin-7-glucoside or luteolin-7-glucoside alone have been investigated. To study the sphingolipids turnover, the [14C]serine-pre-labeled hepatocytes and [14C-methyl]- or [14C]palmitate-pre-labeled sphingomyelin (SM) and ceramide were used. The ceramide content was higher in the liver and hepatocytes of 24- and 27-28-month-old animals as compared to adult 3-month-old Wistar rats. An addition of flavonoids to the culture medium did not influence significantly on the lipids contents and metabolism in the isolated hepatocytes. The administration of flavonoids to old rats decreased the elevated neutral and acid SMases activities and ceramide mass and did not affect both the lipid content in the liver of adult animals and ceramide conversion to the sphingosine or SM. These results suggest that the SMases play a key role in the flavonoid-induced decrease of ceramide levels in the liver of old rats.


The β-catenin signaling pathway induces aggressive potential in breast cancer by up-regulating the chemokine CCL5.
β-Catenin signaling plays a pivotal role in the genesis of a variety of malignant tumors, but its role in breast cancer has not been fully elucidated. Here, we examined whether deregulation of β-catenin signaling is related to the aggressive characteristics of certain types of breast cancers. Analysis of cytokine levels in MDA-MB-231 cells overexpressing a constitutively active form of β-catenin (CAβ-catenin) revealed a higher level of CCL5 expression. Cells transfected with CAβ-catenin or stimulated with recombinant CCL5 exhibited increased cell invasion activity and spheroid formation in vitro. Furthermore, CAβ-catenin-transfected MDA-MB-231 cells formed larger tumor masses that contained more Ki-67-positive cells and infiltrating lymphocytes than did the control cells. An inhibitor of CCR5 and a pan-CXCR neutralizing antibody dramatically reduced CAβ-catenin-promoted activities. In addition to CCL5, 6-BIO, a chemical activator of β-catenin, induced cell invasion and spheroid formation in MDA-MB-231 cells. Furthermore, high levels of nuclear β-catenin accumulation were detected in breast cancer in patients with metastasis but not in those without metastasis. Nuclear β-catenin localization is related to increased CCL5 production in breast cancer. These findings suggest that β-catenin expression enhances tumor progression via chemokine production in breast cancers and that β-catenin signaling is a critical regulator of the aggressive traits of breast cancers.


Brain regional distributions of monoamine oxidase activities in postnatal development in normal and chronically manganese-treated rats.
To investigate the hypothesis that manganese toxicity may affect the development of the monoamine oxidases (MAOs) in brain, the regional distributions of the A (serotonin-oxidizing) and B (benzylamine-oxidizing) forms of MAO were determined in manganese-treated (1 mg or 10 mg of MnCl2.4H2O per ml of drinking water from conception onwards until the rats were used for experiments) and untreated male rats during various stages of postnatal development. The age-related variations in regional MAO-A activities (especially in pons and medulla and in cerebellum) were more marked than those in regional MAO-B activities. The MAO-A:MAO-B activity ratios decreased in all regions during development. Chronic manganese treatment (at the specified doses) did not significantly alter the age-related changes in regional MAO-A and MAO-B activities; nor were the A:B activity ratios affected. The results suggest that there is differential expression of MAO isoforms in various brain regions during postnatal development but the expression is not affected by chronic manganese toxicity.


Src/NF-κB-targeted inhibition of LPS-induced macrophage activation and dextran sodium sulphate-induced colitis by Archidendron clypearia methanol extract.
Archidendron clypearia Jack. (Fabaceae) has been traditionally used to treat various inflammatory diseases such as pain in the eyes. However, the antiinflammatory mechanism of A. clypearia has not been fully elucidated. This study examined the anti-inflammatory mechanism of a 95% methanol extract (Ac-ME) of A. clypearia in vitro and in vivo. The effect of Ac-ME on the production of inflammatory mediators in RAW264.7 cells and peritoneal macrophages and on symptoms of colitis in mouse induced by dextran sodium sulphate (DSS) was investigated. Molecular mechanisms underlying the inhibitory effects were elucidated by analyzing the activation of transcription factors and their upstream signaling as well as by evaluating the kinase activity of target enzymes in vitro and in vivo. Ac-ME dose-dependently suppressed the secretion of nitric oxide (NO) and prostaglandin (PG)E₂ from RAW264.7 cells and peritoneal macrophages stimulated by lipopolysaccharide (LPS). Ac-ME clearly reduced mRNA expression of inducible NO synthase (iNOS), cyclooxygenase (COX)-2, and tumor necrosis factor (TNF)-α by the blockade of nuclear factor (NF)-κB activation and its upstream signaling events containing protein tyrosine kinase such as Syk and Src. In agreement with this, Ac-ME directly reduced the kinase activities of Src and Syk as well as the formation of molecular signaling complex including p85. DSS-induced colitis was also remarkably inhibited by this extract through the suppression of Src and IκBα phosphorylation. Ac-ME displays strong anti-inflammatory activity in vivo by suppressing Src/Syk-mediated NF-κB activation which is linked to its ethno-pharmacological uses as an anti-gastritis remedy. Through preclinical studies, the potential therapeutic application will be tested further.


Genomic library screening for viruses from the human dental plaque revealed pathogen-specific lytic phage sequences.
Bacterial pathogenesis presents an astounding arsenal of virulence factors that allow them to conquer many different niches throughout the course of infection. Principally fascinating is the fact that some bacterial species are able to induce different diseases by expression of different combinations of virulence factors. Nevertheless, studies aiming at screening for the presence of bacteriophages in humans have been limited. Such screening procedures would eventually lead to identification of phage-encoded properties that impart increased bacterial fitness and/or virulence in a particular niche, and hence, would potentially be used to reverse the course of bacterial infections. As the human oral cavity represents a rich and dynamic ecosystem for several upper respiratory tract pathogens. However, little is known about virus diversity in human dental plaque which is an important reservoir. We applied the culture-independent approach to characterize virus diversity in human dental plaque making a library from a virus DNA fraction amplified using a multiple displacement method and sequenced 80 clones. The resulting sequence showed 44% significant identities to GenBank databases by TBLASTX analysis. TBLAST homology comparisons showed that 66% was viral; 18% eukarya; 10% bacterial; 6% mobile elements. These sequences were sorted into 6 contigs and 45 single sequences in which 4 contigs and a single sequence showed significant identity to a small region of a putative prophage in the Corynebacterium diphtheria genome. These findings interestingly highlight the uniqueness of over half of the sequences, whilst the dominance of a pathogen-specific prophage sequences imply their role in virulence.


Molecular Modeling Insights into Metal-Organic Frameworks (MOFs) as a Potential Matrix for Immobilization of Lipase: An In Silico Study.
CRL is a highly versatile enzyme that finds extensive utility in numerous industries, which is attributed to its selectivity and catalytic efficiency, which have been impeded by the impracticality of its implementation, leading to a loss of native catalytic activity and non-reusability. Enzyme immobilization is a necessary step for enabling its reuse, and it provides methods for regulating the biocatalyst's functional efficacy in a synthetic setting. MOFs represent a novel category of porous materials possessing distinct superlative features that make MOFs an optimal host matrix for developing enzyme-MOF composites. In this study, we employed molecular modeling approaches, for instance, molecular docking and MD simulation, to explore the interactions between CRL and a specific MOF, ZIF-8. The present study involved conducting secondary structural analysis and homology modeling of CRL, followed by docking ZIF-8 with CRL. The results of the molecular docking analysis indicate that ZIF-8 was situated within the active site pocket of CRL, where it formed hydrogen bonds with Val-81, Phe-87, Ser-91, Asp-231, Thr-132, Lue-297, Phe-296, Phe-344, Thr-347, and Ser-450. The MD simulation analysis revealed that the CRL and ZIF-8 docked complex exhibited stability over the entire simulation period, and all interactions presented in the initial docked complex were maintained throughout the simulation. The findings derived from this investigation could promote comprehension of the molecular mechanisms underlying the interaction between CRL and ZIF-8 as well as the development of immobilized CRL for diverse industrial purposes.


Religious and spiritual case reports on MEDLINE: a systematic analysis of records from 1980 to 1996.
To undertake a systematic analysis of case reports involving religious or spiritual issues published between 1980 and 1996. MEDLINE, the National Library of Medicine's bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, and the preclinical sciences. A search of 4,306,906 records indexed on MEDLINE from 1980 to 1996. A total of 364 abstracts were found, then subjected to coding analysis. Categories were developed for (1) types of healthcare situations involving religious/spiritual issues, (2) religious and spiritual interventions, (3) collaboration between healthcare and religious professionals, (4) psychopathology and sensitivity themes, and (5) religious faith/spiritual path. Although all of these case reports involved religious and spiritual issues, only 45 (12%) explicitly mentioned a religious professional. Of these, only 8 (2%) indicated any collaboration between healthcare and religious professionals. A paucity of published case report literature exists on religious and spiritual issues (.008% of the MEDLINE records), indicating that the increasing acceptance of these factors by patients and healthcare professionals is not yet reflected in scientific and clinical journals. A need exists for more documented examples of collaboration between healthcare and religious professionals.


Comparison of the Sensitivity to Change of the 36-Item Short Form Health Survey and the Lupus Quality of Life Measure Using Various Definitions of Minimum Clinically Important Differences in Patients With Active Systemic Lupus Erythematosus.
The Medical Outcomes Study Short Form 36 (SF-36) and Lupus Quality of Life (LupusQoL) are health-related quality of life questionnaires used in systemic lupus erythematosus (SLE). We first determined the hypothesis-testing construct validity of the SF-36 and LupusQoL against disease activity in patients with active SLE and then compared the sensitivity to change of SF-36 and LupusQoL domains according to different definitions of minimum clinically important differences (MCIDs) for improvement and worsening in the current cohort. Seventy-eight clinically active SLE patients concurrently completed both questionnaires at their baseline and followup visits. Questionnaire domain scores were correlated with the SLE Disease Activity Index 2000 (SLEDAI-2K) and evaluated for floor/ceiling effects. The sensitivity to change of domains in each questionnaire was analyzed first, according to the various MCID definitions and, second, by clinically meaningful changes in disease activity. The magnitudes of change in each domain score between the baseline and followup visit were evaluated using standardized response means. In the 78 patients, the mean ± SD SLEDAI-2K scores were 9.7 ± 4.8 at baseline and 8.8 ± 5.1 at followup. SF-36/LupusQoL domain scores did not correlate with disease activity. The SF-36 showed floor effects, and ceiling effects were evident in both questionnaires. All domains of both questionnaires showed sensitivity to change over time. Specific domains that reflected worsening or improvement differed according to differing MCID definitions. In SLE patients with active disease, both the SF-36 and LupusQoL are sensitive to change, reflecting both improvement and worsening. More importantly, the LupusQoL SLE-specific domains (planning, burden to others, body image, and intimate relationships) were largely responsive to change.


Effects of oral contraceptive pretreatment on IVF outcomes in women following a GnRH agonist protocol.
Does oral contraceptive pretreatment impact IVF-embryo transfer cycle outcomes in women following the gonadotrophin-releasing hormone agonist (GnRHa) protocol? This retrospective study was designed to compare cycle outcomes after oral contraceptive pretreatment versus the standard protocol in women within the GnRHa long protocol or the GnRHa short protocol. A total of 2052 women undergoing their first IVF treatment with the GnRHa long protocol and 3557 women with the GnRHa short protocol between 2012 and 2017 were enrolled. No significant differences in the rates of clinical pregnancy (long protocol: 49.2% versus 46.7%; short protocol: 39.4% versus 38.0%) or live birth (long protocol: 44.3% versus 41.3%; short protocol: 32.8% versus 31.4%) after fresh embryo transfer were observed between the oral contraceptive group and the control group in either the long protocol or the short protocol. Oral contraceptive pretreatment has no effect on IVF outcomes in either the GnRHa long protocol or short protocol.


Role of toll-like receptor 4 and sex in 6-hydroxydopamine-induced behavioral impairments and neurodegeneration in mice.
Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of the nigrostriatal dopaminergic neurons that are associated with motor alterations and non-motor manifestations (such as depression). Neuroinflammation is a process with a critical role in the pathogenesis of PD. In this regard, toll-like receptor 4 (TLR4) is a central mediator of immune response in PD. Moreover, there are gender-related differences in the incidence, prevalence, and clinical features of PD. Therefore, we aimed to elucidate the role of TLR4 in the sex-dependent response to dopaminergic denervation induced by 6-hydroxydopamine (6-OHDA) in mice. Female and male adult wildtype (WT) and TLR4 knockout (TLR4-/-) mice were administered with unilateral injection of 6-OHDA in the dorsal striatum, and non-motor and motor impairments were evaluated for 30 days, followed by biochemistry analysis in the substantia nigra pars compacta (SNc), dorsal striatum, and dorsoventral cortex. Early non-motor impairments (i.e., depressive-like behavior and spatial learning deficits) induced by 6-OHDA were observed in the male WT mice but not in male TLR4-/- or female mice. Motor alterations were observed after administration of 6-OHDA in both strains, and the lack of TLR4 was also related to motor commitment. Moreover, ablation of TLR4 prevented 6-OHDA-induced dopaminergic denervation and microgliosis in the SNc, selectively in female mice. These results reinforced the existence of sex-biased alterations in PD and indicated TLR4 as a promising therapeutic target for the motor and non-motor symptoms of PD, which will help counteract the neuroinflammatory and neurodegenerative processes.


Erratum.
Syed, M. I., Rutka, J. A. & Pothier, D. D.(2015) Clin. Otolaryngol. 40, 69. Application of phenol as topical anaesthesia using the Derlacki elevator for myringotomy. In the title of this article, the word 'myringotomy' was incorrectly spelt as 'miringotomy'. We apologise for this typographical error. Lachanas, V.A., Tsea, M., Tsiouvaka, S., Exarchos, S.T., Skoulakis, C.E. & Bizakis, J.G.(2015) Clin. Otolaryngol. 40, 56. The effect of active cigarette smoking on Sino-Nasal Outcome Test in 127 subjects without rhinologic disease. A prospective study. In the Results section, paragraph 2, line 3, the result "SNOT-20 +/- SD was 15.75 +/- 1.68 and 8.65 +/- 0.95" should have read "SNOT-22 +/- SD was 17.59 +/- 1.79 and 9.76 +/- 1.06". We apologise for this error.


[Closed cystostomy by puncture. Modified translumbar puncture technic for the treatment of single renal cyst].
Due to the frequent relapses in the treatment of kidney cysts by simple aspiration, the authors present a technical variation of the same, which may avoid the use of intracystic sclerosing substances. Owing to the simplicity of the method which may be performed in a clinic, its low morbility and probable effectiveness, we feel that it may be a useful procedure as a first step in the treatment of simple kidney cysts.


Draft Genome Sequence of Mycobacterium peregrinum Isolated from an HIV-Positive Patient in South Africa.
Here, we report a draft genome sequence of Mycobacterium peregrinum obtained from a sputum sample of a South African HIV-infected patient with suspected pulmonary tuberculosis. The genome described here comprises 6,931,852 bp, revealing 66.2% G+C content, 6,808 coding sequences, and 81 RNA genes.


Epitope mapping of neutralising anti-SARS-CoV-2 monoclonal antibodies: Implications for immunotherapy and vaccine design.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. This disease has currently affected more than 346 million people and resulted in more than 5.5 million deaths in many countries. Neutralising monoclonal antibodies (MAbs) against the SARS-CoV-2 virus could serve as prophylactic/therapeutic agents in COVID-19 infection by providing passive protection against the virus in individuals. Until now, no Food and Drug Administration/European Medicines Agency-approved neutralising MAb against SARS-CoV-2 virus exists in the market, though a number of MAbs have been authorised for emergency use. Therefore, there is an urgent need for development of efficient anti-SARS-CoV-2 neutralising MAbs for use in the clinic. Moreover, neutralising anti-SARS-CoV-2 MAbs could be used as beneficial tools for designing epitope-based vaccines against the virus. Given that the target epitope of a MAb is a crucial feature influencing its neutralising potency, target epitopes of neutralising anti-SARS-CoV-2 MAbs already reported in the literature and reactivity of these MAbs with SARS-CoV-2 variants are reviewed herein.