Cost-effectiveness of cardiovascular magnetic resonance imaging compared to common strategies in the diagnosis of coronary artery disease: a systematic review.
Cardiovascular magnetic resonance imaging (CMR) has established exceptional diagnostic utility and prognostic value in coronary artery disease (CAD). An assessment of the current evidence on the cost-effectiveness of CMR in patients referred for the investigation of CAD is essential for developing an economic model to evaluate the cost-effectiveness of CMR in CAD. We conducted a comprehensive search of multiple electronic databases, including PubMed, Scopus, Web of Science core collection, Embase, National Health Service Economic Evaluation Database (NHS EED), and health technology assessment, to identify relevant literature. After removing duplicates and screening the title/abstract, a total of 13 articles were deemed eligible for full-text assessment. We included studies that reported one or more of the following outcomes: incremental cost-effectiveness ratio (ICER), cost per quality-adjusted life year (QALYs), cost per life year gained, sensitivity and specificity rate as the primary outcome, and health utility measures or health-related quality of life as the secondary outcome. The quality of the included studies was assessed using the CHEERS 2022 guidelines. The findings of this study demonstrate that in patients undergoing urgent percutaneous coronary intervention, CMR over a one-year and lifetime horizon leads to higher quality-adjusted life years (QALYs) compared to current strategies in cases of multivessel disease. The systematic review indicates that the CMR-based strategy is more cost-effective when compared to standard methods such as single-photon emission computed tomography (SPECT), coronary computed tomography angiography (CCTA), and coronary angiography (CA) (CMR = $19,273, SPECT = $19,578, CCTA = $19,886, and immediate CA = $20,929). The results also suggest that the CMR strategy can serve as a cost-effective gatekeeping tool for patients at risk of obstructive CAD. A CMR-based strategy for managing patients with suspected CAD is more cost-effective compared to both invasive and non-invasive strategies, particularly in real-world patient populations with a low to intermediate prevalence of the disease.


Are neuromodulation interventions associated with changes in the gut microbiota? A systematic review.
The microbiota-gut-brain axis (MGBA) refers to the bidirectional communication between the brain and the gut microbiota and recent studies have linked the MGBA to health and disease. Research has so far investigated this axis mainly from microbiota to brain but less is known about the other direction. One approach to examine the MGBA from brain to microbiota is through understanding if and how neuromodulation might impact microbiota. Neuromodulation encompasses a wide range of stimulation techniques and is used to treat neurological, psychiatric and metabolic disorders, like Parkinson's Disease, depression and obesity. Here, we performed a systematic review to investigate whether neuromodulation is associated with subsequent changes in the gut microbiota. Searches in PsycINFO and MEDLINE were performed up to March 2022. Included studies needed to be clinical or preclinical studies comparing the effects of deep brain stimulation, electroconvulsive therapy, repetitive transcranial magnetic stimulation, transcranial direct current stimulation or vagal nerve stimulation on the gut microbiota before and after treatment or between active and control groups. Seven studies were identified. Neuromodulation was associated with changes in relative bacterial abundances, but not with (changes in) α-diversity or β-diversity. Summarizing, currently reported findings suggest that neuromodulation interventions are associated with moderate changes in the gut microbiome. However, findings remain inconclusive due to the limited number and varying quality of included studies, as well as the large heterogeneity between studies. More research is required to more conclusively establish whether, and if so, via which mechanism(s) of action neuromodulation interventions might influence the gut microbiota.


[Polysaccharide composition of mycelium and cell walls of the fungus Penicillium roqueforti].
Preliminary data on the polysaccharide composition of mycelium and cell walls of the submergedly grown fungus Penicillium roqueforti were obtained. Mild acid hydrolysis of mycelium and cell walls led to formation of glucose, mannose and galactose, whereas acid treatment under drastic conditions afforded glucosamine as the hydrolysis product of chitin, which content in the cell walls was estimated as 19%. Sequential treatment of the mycelium with hot water and 1 M NaOH at room temperature gave rise to several polysaccharide fractions, which were characterized by their monosaccharide composition. The main fraction obtained by the action of alkali, according to NMR spectroscopy, mass spectrometry and chemical methods of structural analysis data, is a linear alpha-D-glucopyranan containing blocks of (1 --> 3)-linked glucose residues interconnected by (1 --> 4)-linkages. Water-soluble polysaccharides contained linear blocks of (1 --> 5)-linked beta-galactofuranose residues, probably connected with a mannan core. The data obtained may be important for chemotaxonomy of the genus Penicillium.


Patients with palpitations experience a higher symptom burden prior to breast cancer surgery.
Anxiety, depression, sleep disturbance, fatigue, cognitive dysfunction, and pain are common symptoms reported by patients with breast cancer. Recent evidence suggests that palpitations, a feeling of the heart racing or pounding, may be equally common. Study purpose was to compare the severity and clinically meaningful occurrence rates of common symptoms and quality of life (QOL) outcomes between patients with breast cancer who did and did not report palpitations prior to surgery. Patients (n = 398) were classified as having or not having palpitations using a single item from the Menopausal Symptoms Scale. Valid and reliable measures were used to assess state and trait anxiety, depression, sleep disturbance, fatigue, energy, cognitive function, breast symptoms, and QOL. Between group differences were evaluated using parametric and non-parametric tests. Patients with palpitations (15.1%) reported significantly higher severity scores for state and trait anxiety, depression, sleep disturbance, and fatigue as well as significant decrements in energy and cognitive function (all p < .05). A higher percentage of these patients had clinically meaningful levels of state anxiety, depression, sleep disturbance and decrements in cognitive function (all p < .05). Except for spiritual well-being, QOL scores were lower in the palpitations group (all p < .001). Findings support the need for routine assessment of palpitations and management of multiple symptoms in women prior to breast cancer surgery.


Robotic versus laparoscopic gastrectomy for gastric cancer: a systematic review and meta-analysis.
To date, robotic surgery has been widely used worldwide. We conducted a systematic review and meta-analysis to evaluate short-term and long-term outcomes of robotic gastrectomy (RG) in gastric cancer patients to determine whether RG can replace laparoscopic gastrectomy (LG). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was applied to perform the study. Pubmed, Cochrane Library, WanFang, China National Knowledge Infrastructure (CNKI), and VIP databases were comprehensively searched for studies published before May 2020 that compared RG with LG. Next, two independent reviewers conducted literature screening and data extraction. The quality of the literature was assessed using the Newcastle-Ottawa Scale (NOS), and the data analyzed using the Review Manager 5.3 software. Random effects or fixed effects models were applied according to heterogeneity. A total of 19 studies including 7275 patients were included in the meta-analyses, of which 4598 patients were in the LG group and 2677 in the RG group. Compared with LG, RG was associated with longer operative time (WMD = -32.96, 95% CI -42.08 ~ -23.84, P < 0.001), less blood loss (WMD = 28.66, 95% CI 18.59 ~ 38.73, P < 0.001), and shorter time to first flatus (WMD = 0.16 95% CI 0.06 ~ 0.27, P = 0.003). There was no significant difference between RG and LG in terms of the hospital stay (WMD = 0.23, 95% CI -0.53 ~ 0.98, P = 0.560), overall postoperative complication (OR = 1.07, 95% CI 0.91 ~ 1.25, P = 0.430), mortality (OR = 0.67, 95% CI 0.24 ~ 1.90, P = 0.450), the number of harvested lymph nodes (WMD = -0.96, 95% CI -2.12 ~ 0.20, P = 0.100), proximal resection margin (WMD = -0.10, 95% CI -0.29 ~ 0.09, P = 0.300), and distal resection margin (WMD = 0.15, 95% CI -0.21 ~ 0.52, P = 0.410). No significant differences were found between the two treatments in overall survival (OS) (HR = 0.95, 95% CI 0.76 ~ 1.18, P = 0.640), recurrence-free survival (RFS) (HR = 0.91, 95% CI 0.69 ~ 1.21, P = 0.530), and recurrence rate (OR = 0.90, 95% CI 0.67 ~ 1.21, P = 0.500). The results of this study suggested that RG is as acceptable as LG in terms of short-term and long-term outcomes. RG can be performed as effectively and safely as LG. Moreover, more randomized controlled trials comparing the two techniques with rigorous study designs are still essential to evaluate the value of the robotic surgery for gastric cancer.


The late Na current as a therapeutic target: where are we?
In this article we review the late Na current which functionally can be measured using patch-clamp electrophysiology (INa,late). This current is largely enhanced under pathological myocardial conditions such as ischemia and heart failure. In addition, INa,late can cause systolic and diastolic contractile dysfunction via a Na-dependent Ca-overload of the myocyte. Moreover, INa,late plays a crucial role as ventricular and atrial proarrhythmic substrate in myocardial pathology by changing cellular electrophysiology. We summarize recent experimental and clinical studies that investigate therapeutic inhibition of this current and discuss the significance of the available data and try to answer not only the question, where we currently are but also where we may go in the near future. This article is part of a Special Issue entitled "Na(+) Regulation in Cardiac Myocytes".


Erratum to relationship of pleural fluid pH and glucose: a multi-centre study of 2,971 cases.
[This corrects the article DOI: 10.21037/jtd.2018.12.101.].


Adaptation and validation of the Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire for use in Bulgaria.
Rheumatoid arthritis (RA) is a chronic disease with an enormous impact on patients' quality of life. The Rheumatoid Arthritis Quality of Life (RAQoL) questionnaire is a disease-specific measure of QoL for individuals with rheumatoid arthritis. Our aim was to adapt and validate the RAQoL for use in Bulgaria. The development of a new language version of the RAQoL consisted of three stages: translation, field testing and psychometric evaluation. The dual-panel methodology, requiring two independent panels of Bulgarian speakers, was applied to translate the UK English version of the RAQoL into Bulgarian. Face and content validity of the translated questionnaire were assessed through cognitive debriefing interviews. Lastly, the RAQoL was administered on two occasions to a random sample of RA patients to evaluate reliability and validity. At the first occasion, the SF-36 was also administered for use as a comparator scale. The RAQoL was successfully adapted into Bulgarian and considered easy to understand, acceptable and comprehensive by RA patients. A psychometric study demonstrated that the new language version has excellent internal consistency (Cronbach's alpha coefficients = 0.93 and 0.94) and test-retest reliability (a Spearman's rank correlation coefficient = 0.97). Convergent validity was established by correlating scores on the RAQoL with a comparator measure, the SF-36. A strong correlation between RAQoL scores and the physical functioning section of the SF-36 was observed. Known group validity was established by the ability of the measure to distinguish between subgroups of patients, who differed according to their perceived general health, disease severity (p < 0.001) and whether they were experiencing a flare-up (p < 0.01). The new language version is recommended for use in future research studies, clinical trials and routine practice with Bulgarian RA patients.


Cell-type differences in the serum and cyclic AMP-dependent regulation of ornithine decarboxylase activity in two cultured fibroblast types.
Serum re-feeding stimulated ornithine decarboxylase (ODC) activity 8 to 10-fold in FS fibroblasts and 5 to 8-fold in 3T3 fibroblasts. Addition of dibutyryl cyclic AMP or 3-isobutyl-1-methylxanthine at the time of serum re-feeding further stimulated ODC activity in 3T3 fibroblasts but inhibited the serum stimulation of ODC activity in FS fibroblasts. It is suggested that serum and cyclic AMP independently regulate ODC activity in cultured fibroblasts.


Coupling pre-mRNA splicing and 3' end formation to mRNA export: alternative ways to punch the nuclear export clock.
How does a mammalian cell determine when newly synthesized mRNAs are fully processed and appropriate for nuclear export? Müller-McNicoll and colleagues (pp. 553-566) expand on mechanisms known to be mediated by nuclear export factor 1 (NXF1) by describing SR proteins as NXF1 adaptors that flag alternatively spliced and polyadenylated mRNA isoforms as cargo ready for the cytoplasm.


Effect of 5-azacytidine on rat liver alpha-fetoprotein gene expression.
Neonatal rats given 5-azacytidine intraperitoneally (30 micrograms/animal/day) on days 1-5 postpartum had 55% lower serum alpha-fetoprotein levels on day 6 compared to saline injected controls. On day 14, alpha-fetoprotein levels were 4-fold lower in 5-azacytidine treated animals. Cytosol alpha-fetoprotein was proportionately reduced. There were no significant changes in liver to body weight ratio, total serum protein, and both serum and cytosol albumin levels. The molecular basis for decreased serum alpha-fetoprotein levels was found to be a reduced concentration of alpha-fetoprotein mRNA in the livers of 5-azacytidine injected animals. These results are discussed with respect to the effects of 5-azacytidine on DNA methylation and cell differentiation.


Primary and secondary structure of 26S ribosomal RNA of Oenothera mitochondria.
The primary structure of 26S ribosomal RNA from mitochondria of the dicotyledoneous plant Oenothera berteriana is inferred from the sequence of a cloned rDNA restriction fragment. A tentative secondary structure model valid for Oenothera and for the major part of maize mitochondrial 26S rRNA has been constructed in analogy to the refined german model for E. coli L-rRNA (Maly and Brimacombe 1983). The derived structure generally matches the eubacterial model providing further support to the E. coli consensus structure. Some structural features however show eukaryotic characteristics. Possible interactions between L-rRNA, 5S rRNA and initiator-tRNA are discussed.


Expression of two zona pellucida genes is regulated by 17α-ethinylestradiol in adult rare minnow Gobiocypris rarus.
Zona pellucida (ZP) proteins are glycoproteins synthesized in liver, ovary or in both tissues in fish. In the present study, we aimed to determine the responsiveness of ZP2 and ZP3 to 17α-ethinylestradiol (EE2) in adult rare minnow Gobiocypris rarus. The full length of ZP3 cDNA was firstly characterized and its tissue distribution revealed that ZP3 mRNA was predominantly expressed in ovary of G. rarus. The gene expression profiles of ZP2, ZP3 and vitellogenin (VTG) were analyzed in gonad and liver of adult G. rarus exposed to EE2 at 1, 5, 25, and 125 ng/L for 3 and 6 days. The results show that ZP2 is more sensitive than ZP3 in gonads of both genders, and VTG in liver is extremely sensitive to EE2 in male fish. However, at lower concentrations (1 and 5 ng/L), the ZP2 in testes shows higher responsiveness to EE2 compared with VTG in rare minnow. The 5' flanking regions of ZP2 and ZP3 were isolated and the comparison of transcription factors in the regions of ZP2 and ZP3 suggested that the disparity for the responsiveness of ZP2 and ZP3 to EE2 could partly be a result of differential cis-elements such as oocyte-specific protein (Osp1) binding sites or/and sex-determining region Y (SRY) binding site.


Hydrothermal liquefaction of sewage sludge into biocrude: Effect of aqueous phase recycling on energy recovery and pollution mitigation.
Hydrothermal liquefaction (HTL) of sewage sludge is facing the challenges of low biocrude yield, a large number of intractable aqueous phase and heavy metals pollution. In this study, the aqueous phase produced by HTL was recycled as solvent with an aim to improve the biocrude yield and mitigate potential pollution. Results showed that the recycling of aqueous phase increased the biocrude yield from 17.9 to 30.5% and the energy recovery ratio from 40.3 to 61.7%. The recycling could increase the contents of Zn, Cu, Pb and Cr in solid residues by 2.7-3.0 times. It is worth emphasizing that the recycling reduced the COD of aqueous phase by 24.9%. However, the enhanced protein hydrolysis process reduced the calorific value of biocrude from 36.4 to 28.5 MJ/kg, and promoted the migration of the nitrogen to the aqueous phase, which was not environmentally favourable for the direct usage in diesel engines. Analysis showed that the ketones and the phenols in aqueous phase participated in HTL process as reactants, and the acids promoted the hydrolysis of protein in the sludge. Overall, the recycling of aqueous phase effectively improved the energy recovery and alleviated pollution of the sludge HTL.


Integrating ecosystem services value and uncertainty into regional ecological risk assessment: A case study of Hubei Province, Central China.
In the context of rapid urbanization, ecosystem services (ES) losses pose serious threats to sustainability. How to assess ecological risk based on ES value (ESV) has become an urgent problem for sustainable urbanization. However, existing regional ecological risk assessment frameworks ignore important elements, such as the assessment endpoint and uncertainty, weakening their reliability and practicability. In this study, a regional ecological risk assessment framework integrating ESV and uncertainty was proposed by introducing a classical financial indicator, the Sharpe Ratio. We take Hubei Province, Central China as a case and implemented the spatially explicit risk assessment approach based on the methods of the Markov-logistic-CA model, adjusted-based equivalent factor evaluation model, and geographic information system. The results showed that the distribution of expected ecological returns and corresponding uncertainties at county level had a remarkable spatial heterogeneity, and the assessed ecological risk index in Eastern and Western Hubei was higher than that in Central Hubei, indicating that counties in Central Hubei are the priority areas for ecological risk control. Moreover, the expansion of built-up land had the most significant effect on regional ecological risk. This regional ecological risk framework can well integrate the assessment endpoint and dynamic processes of ecological risk. Our assessment framework has potential practical value for ecological risk control and land use planning on ecosystems.


Linear relationships between mitochondrial forces and cytoplasmic flows argue for the organized energy-coupled nature of cellular metabolism.
We have studied rates of formation of glucose, urea and lactate by isolated hepatocytes incubated with a variety of inhibitors of energy transduction. Linear relationships have been found between these metabolic rates and mitochondrial forces (membrane, redox and phosphorylation potentials). The findings are suggestive of extensive enzyme organization within these metabolic pathways.


Field calibration of polyurethane foam (PUF) disk passive air samplers for PCBs and OC pesticides.
Different passive air sampler (PAS) strategies have been developed for sampling in remote areas and for cost-effective simultaneous spatial mapping of POPs (persistent organic pollutants) over differing geographical scales. The polyurethane foam (PUF) disk-based PAS is probably the most widely used. In a PUF-based PAS, the PUF disk is generally mounted inside two stainless steel bowls to buffer the air flow to the disk and to shield it from precipitation and light. The field study described in this manuscript was conducted to: compare performance of 3 different designs of sampler; to further calibrate the sampler against the conventional active sampler; to derive more information on field-based uptake rates and equilibrium times of the samplers. Samplers were also deployed at different locations across the field site, and at different heights up a meteorological tower, to investigate the possible influence of sampler location. Samplers deployed <5m above ground, and not directly sheltered from the wind gave similar uptake rates. Small differences in dimensions between the 3 designs of passive sampler chamber had no discernable effect on accumulation rates, allowing comparison with previously published data.


miR-125b regulates side population in breast cancer and confers a chemoresistant phenotype.
Resistance to chemotherapy is a major obstacle for the effective treatment of breast cancer and is partially due to the presence of drug resistant stem cell-like side population (SP). Previous studies have shown elevated miR-125b is associated with chemoresistance and metastasis; however, the relationship between miR-125b and SP cells remains unknown. In this study, we isolated and characterized SP cells in a panel of breast cancer cell lines and primary cancer cells from breast cancer patients. SP cells showed cancer stem cells (CSCs) properties, including self-renewal, resistance to chemotherapy and high expression of stem cell markers. The percentage of SP cells was higher in chemotherapy resistant patients compared to that in chemotherapy responsive patients (5.8 ± 2.4% in non-responsive patients vs. 1.2 ± 0.5% in responsive patients, P = 0.012). Importantly, SP cells had higher level of miR-125b than NSP cells and the elevated miR-125b expression in chemoresistant cancer cells were due to high percentage of SP cells. Overexpression of miR-125b correlated with an increase in tumor SP and CSC property, whereas knockdown of miR-125b correlated with decreased incidence of SP. In addition, miR-125b overexpression in breast cancer cells induced epithelial-mesenchymal transition (EMT)-like cellular marker alteration, suggesting a potential mechanism of miR-125b in the regulation of cancer stem-like SP cells. Taken together, these results suggest an important role for miR-125b in breast cancer chemoresistance by maintaining cancer stem-like SP fraction, and raise the possibility that miR-125b may be a significant prognostic response marker for cancer therapy.


Tuberous sclerosis and dysplasia of the corpus callosum. Case report of their combined occurrence in a newborn.
A neuropathological study is presented of a case showing the association of tuberous sclerosis of the brain and dysplasia of the corpus callosum as well as omphalocele and malrotated colon. No signs of tuberous sclerosis were found in the internal organs. From a review of the literature this appears to be the fourth case report of tuberous sclerosis and dysplasia of the corpus callosum. The association with omphalocele, to our knowledge, has not yet been reported.


Neuroendocrine regulation of stress in birds with an emphasis on vasotocin receptors (VTRs).
The neuroendocrine stress response of vertebrates, particularly mammals, comprises at least two types of neuropeptide containing neurons, corticotropin-releasing hormone (CRH) and vasopressin (VP) neurons, and four receptors [CRH receptor one (CRH-R1) and two (CRH-R2) and VP receptor 1a (V1aR) and 1b (V1bR)]. The avian neuropeptide CRH, a 41-amino acid peptide, has been shown to have the same amino acid sequence as humans while nonapeptide neurohormone arginine-vasotocin (AVT) is regarded as highly conserved having a single amino acid substitution compared to mammalian arginine vasopressin. Similar to mammals, birds have two receptor subtypes (CRH-R1 and CRH-R2) for CRH, however, four vasotocin receptors have been identified. Less is known about the functions of the four avian vasotocin receptors compared to homologous ones found in mammals and other vertebrate classes. Recently, chicken vasotocin receptor two (VT2R) and four (VT4R) have been characterized utilizing immunocytochemistry and an imposed stress test. The purpose of this review is to present evidence that the VT2R and VT4R are involved in the avian stress response and that the cephalic lobe of the anterior pituitary appears specialized for this function as it contains the major population of corticotropes and necessary neuroendocrine receptors to respond to stressors impacting avian species.


A Case of Varicella-Zoster Meningoencephalitis Presented by Ramsay Hunt Syndrome.
Varicella-zoster virus (VZV) reactivation can cause meningoencephalitis. Ramsay Hunt syndrome is the reactivation of VZV in facial nerve, consisting of ear pain, facial nerve paralysis, and auricular rash. We present a case of VZV meningoencephalitis presented with Ramsay Hunt syndrome. Early clinical suspicion was beneficial in starting aggressive treatment.


Analysis of foot clearance in firefighters during ascent and descent of stairs.
Slips, trips, and falls are a leading cause of injury to firefighters with many injuries occurring while traversing stairs, possibly exaggerated by acute fatigue from firefighting activities and/or asymmetric load carriage. This study examined the effects that fatigue, induced by simulated firefighting activities, and hose load carriage have on foot clearance while traversing stairs. Landing and passing foot clearances for each stair during ascent and descent of a short staircase were investigated. Clearances decreased significantly (p < 0.05) post-exercise for nine of 12 ascent parameters and increased for two of eight descent parameters. Load carriage resulted in significantly decreased (p < 0.05) clearance over three ascent parameters, and one increase during descent. Decreased clearances during ascent caused by fatigue or load carriage may result in an increased trip risk. Increased clearances during descent may suggest use of a compensation strategy to ensure stair clearance or an increased risk of over-stepping during descent.


Advanced oxidation processes and selection of industrial water source: A new sight from natural organic matter.
Natural organic matter (NOM) refers to the dissolved organic matter in natural water that can pass through 0.45 μm filter membrane. As a pivotal role in the surface water body, it has a significant effect on the efficiency of AOPs. In this study, Excitation emission matrix - parallel factor (EEM-PARAFAC) analysis is used to elucidate the changes of NOM fluorescence peaks after electrochemical oxidation process, two-dimensional correlation spectroscopy (2D-FTIR-COS) and Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) are utilized to clarify the molecular characteristics of NOM in surface water and the effects of electrochemical oxidation on NOM molecules. The results indicate that parts of NOM molecules are mineralized into simple compounds and precursors of refractory organic matters produced by some NOM molecules after AOPs. It is concluded that the precursors of these refractory organic matters may belong to terrestrial humus (C2). Therefore, for the purpose of avoiding more refractory organic pollutants produced by NOM which can reduce the performance of AOPs in the water treatment process, factories should choose water sources with less humus as industrial water supply, or degrade humus by physical or chemical methods before industrial water supply.


Rapid Access to Hydroxyfluoranthenes via a Domino Suzuki-Miyaura/Intramolecular Diels-Alder/Ring-Opening Reactions Sequence.
In this work, we developed an efficient method for the rapid construction of fluoranthene skeleton to access a variety of substituted hydroxyfluoranthenes. The 1-iodo-8-alkynylnaphthalene derivatives, which serve as substrates for the key fluoranthene-forming step, were prepared via selective monoalkynylative Sonogashira reactions of 1,8-diiodonaphthalene. The domino reaction sequence which involves a sequential Suzuki-Miyaura coupling, an intramolecular Diels-Alder reaction, and an aromatization-driven ring-opening isomerization has been shown to give substituted hydroxyfluoranthenes in up to 92% yield. This work demonstrates the utility of designing new domino reactions for rapid access to substituted polycyclic aromatic hydrocarbons (PAHs).


Correlates of elevated interleukin-6 and C-reactive protein in persons with or at high risk for HCV and HIV infections.
HIV and hepatitis C virus (HCV) infections may increase interleukin-6 (IL-6) and C-reactive protein (CRP). However, relationships between inflammatory biomarkers, chronic viral infections, clinical factors, and behavioral factors remain poorly understood. Using linear regression, we modeled cross-sectional associations between loge IL-6 or loge CRP levels and HCV, HIV, injection drug use, and comorbidity among 1191 injection drug users. Mean age was 47 years, 46.0% reported currently injecting drugs, 59.0% were HCV monoinfected, and 27% were HCV/HIV coinfected. In multivariable models, higher loge IL-6 was associated with HCV monoinfection [β = 0.191, 95% confidence interval (CI): 0.043 to 0.339] and HCV/HIV coinfection (β = 0.394, 95% CI: 0.214 to 0.574). In contrast, HCV monoinfection (β = -0.523, 95% CI: -0.275 to -0.789) and HCV/HIV coinfection (β = -0.554 95% CI: -0.260 to -0.847) were associated with lower CRP. Lower CRP with HCV infection was independent of liver fibrosis severity, synthetic function, or liver injury markers; CRP decreased with higher HCV RNA. Increased injection intensity was associated with higher IL-6 (P = 0.003) and CRP (P < 0.001); increasing comorbidity (P < 0.001) and older age (P = 0.028) were associated with higher IL-6; older age was associated with higher CRP among HCV-uninfected participants (P = 0.021). HIV and HCV infections contribute to chronic inflammation; however, reduced CRP possibly occurs through HCV-mediated mechanisms. Findings highlight potentially modifiable contributors to inflammation.


SARS-CoV-2: diagnostic and design conundrums in the context of male factor infertility.
The question of whether SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus-2 [SARS-CoV-2], leading to the COVID-19 infection) can be harboured in the testes and/or semen is currently unanswered. It is essential to understand the limitations of both antibody and real-time PCR tests in interpreting SARS-CoV-2 data in relation to analyses of semen and testicular tissue without appropriate controls. This article critically analyses the evidence so far on this, and the possible implications. The limitations of diagnostic tests in both sampling and testing methodologies, their validation and their relevance in interpreting data are also highlighted.


Understanding Sarason's concepts of school cultures and change: joining a community in school improvement efforts.
This paper describes an evolving transformative partnership between a large comprehensive university, an urban school system and a predominantly African-American, low-income neighborhood. The partnership's originating intent was to apply an array of university, civic and local resources to improve the academic performance of a neighborhood's schools and the health, welfare and economic well-being of its residents. The extent to which that partnership would precipitate transactional (Sameroff and Fiese, Handbook of early childhood intervention, Cambridge University Press, Cambridge, pp. 119-149 in 1990) synergies among the partners was unanticipated; the long-term implications for each of the partners of such unfamiliar interactional processes remain unclear but are being systematically monitored over time. Evident at this point, however, it that a process has been initiated that has impacted how the university community, the local public school system, city government and the target neighborhood relate to each other, collaborate with each other and are changing each other. The pace of that process has varied over the years and challenged each partners' expectations and assumptions about the nature and consequences of their involvement. With time and perseverance, however, it appears that all are moving toward a sense of mutual learning and trust and toward extending to each other the benefit of the doubt. This paper discusses the evolution of that process and its implications for university-school-community collaborations.


The Kushida Index as a screening tool for obstructive sleep apnoea-hypopnoea syndrome.
To test the validity of the Kushida Index for screening for sleep apnoea in a West of Scotland adult population. Specific intra-oral measurements and respiratory polysomnography were carried out on 71 patients in this prospective study. The intra-oral measurements were applied to the Kushida formula to obtain a value for the Kushida Index. This value was compared to the diagnosis obtained using polysomnography in the conventional manner. The sensitivity of the Kushida Index in this present study was 68% (95% CI 50-81) and the specificity was 71% (95% CI 52-84). The positive predictive value was 71% and the negative predictive value was 67%. The Mallampati score, Epworth sleepiness score and enlargement of the tongue, soft palate or tonsils were not statistically significantly related to a diagnosis of sleep apnoea (p >0.05). With the limited sensitivity and specificity of the Kushida Index demonstrated in this study, this test cannot be recommended as a screening tool for sleep apnoea in a West of Scotland population.


G2 sub-population in mouse liver induced into mitosis by lead acetate.
A single intracardiac dose of lead acetate (40 microgram lead/g body weight) induced a 25-fold increase in mitosis of mouse hepatocytes 5 hr after injection, as determined by autoradiography. The prompt appearance of a mitotic wave and the relatively large number of mitoses suggest that the mitotic cells were derived from a hepatocyte sub-population arrested in the G2 phase. The injection of lead also stimulated a small increase in labeled hepatocytes within 6 hr. Analysis of grain counts gave no evidence for unscheduled DNA synthesis. The incremental labeled cells may have originated from a small fraction of the G1 population that was ready to enter the S phase without the usual pre-synthetic delay.


Anti-apoptotic and anti-inflammatory effects of naringin on cisplatin-induced renal injury in the rat.
Nephrotoxicity is a common complication of cisplatin chemotherapy and thus limits the use of cisplatin in clinic. Naringin, a natural flavonoid, plays important roles in inflammation and apoptosis in some inflammatory diseases; however, its roles in cisplatin-induced nephrotoxicity remain unclear. In this study, we first assessed the involvement of ROS overproduction and inflammation in cisplatin-induced nephrotoxicity in aged rats, and then we investigated the changes of renal function, histological injury, inflammatory response, and apoptosis in renal tissues after treatment with naringin (20, 50 or 100 mg/kg body weight). Cisplatin resulted in an increase of renal markers, lipid peroxidation, protein and DNA oxidation, and ROS formation. Renal tumor necrosis factor-α (TNF-α) and nitrite levels were also elevated. Expressions of nuclear factor-kappa B (NF-κB), inductible nitric oxide synthase (iNOS), caspase-3 and p53 were up-regulated in renal tissues of Cis-treated rats compared with the normal control group. Histopathological changes were also observed in cisplatin group. Adminstration of naringin at different doses (25, 50 and 100 mg/kg) was able to protect against the deterioration in kidney function, abrogate the decline in antioxidant enzyme activities and suppressed the increase in TBARS, nitrite and TNF-α concentrations. Moreover, naringin inhibited NF-κB and iNOS pathways, caspase-3 and p53 activation and improved the histological changes induced by cisplatin. In conclusion, our studies suggest that oxidative stress and inflammation might play important roles in the development of cisplatin-induced nephrotoxicity and naringin might become an effective therapeutic strategy for this disease.


GPER mediates the effects of 17β-estradiol in cardiac mitochondrial biogenesis and function.
Considering the sexual dimorphism described in cardiac mitochondrial function and oxidative stress, we aimed to investigate the role of 17β-estradiol (E2) in these sex differences and the contribution of E2 receptors to these effects. As a model of chronic deprivation of ovarian hormones, we used ovariectomized (OVX) rats, half of which were treated with E2. Ovariectomy decreased markers of cardiac mitochondrial biogenesis and function and also increased oxidative stress, whereas E2 counteracted these effects. In H9c2 cardiomyocytes we observed that G-protein coupled estrogen receptor (GPER) agonist mimicked the effects of E2 in enhancing mitochondrial function and biogenesis, whereas GPER inhibitor neutralized them. These data suggest that E2 enhances mitochondrial function and decreases oxidative stress in cardiac muscle, thus it could be responsible for the sexual dimorphism observed in mitochondrial biogenesis and function in this tissue. These effects seem to be mediated through GPER stimulation.


Merogony and gametogony of Eimeria mccordocki (Protozoa-Eimeriidae) in the mule deer, Odocoileus h. hemionus.
Eimeria mccordocki and E. madisonensis oocysts were isolated from feces of 21 of 40 captive mule deer in Fort Collins, Colorado. The two species were separated from each other by infecting one mule deer fawn, and the life cycle of E. mccordocki was studied for the first time. Four to six-weeks-old mule deer fawns were inoculated orally with E. mccordocki and killed 9, 13 and 15 days after infection. Asexual and sexual stages of life cycle developed in the ileum of mule deer, only in the surface epithelial cells of the villi. The asexual stages consisted of two generations of meronts.


Enablers and barriers for mandatory training including Basic Life Support in an interprofessional environment: An integrative literature review.
It is vital health services have systems in place for staff mandatory training to meet safe quality health outcomes. The aim of this review is to identify enablers supporting staff attendance at mandatory training (including BLS) and barriers that pose challenges for staff participation in mandatory training that will be used to inform the development of a structured mandatory staff training program in an IPE environment. An integrative literature review was sought to answer the question: What are the enablers and barriers that influence health professional attendance and successful completion of mandatory training (including BLS) in an IPE environment? An international literature search was undertaken using advance search of the databases: Medline, CINAHL, Google Scholar and Web of Science (WoS). English language, peer reviewed articles published from 2010 to 2022 were retrieved and screened for relevance. An integrative review of papers included systematic reviews, a case study, quantitative and qualitative studies, RCT, mixed method studies and expert opinion papers. Only 34 articles were eligible for inclusion in the review based on their relevance to staff attendance at mandatory training (including BLS). Analysis of literature identified four key themes: 'mandatory training' and 'certification'; 'knowledge and skills'; 'enablers' and 'barriers' for 'mandatory training (including BLS) attendance' and 'IPE'. The literature highlighted that IPE is an appropriate means of delivering a redesign education/training process that may increase attendance at mandatory training with recommendations for increased inclusivity and interactivity as well as providing useful logistic information. The outcome of the review can inform development of an IPE Implementation Strategy in a health service aiming to improve staff attending and engaging in mandatory training. The findings are valuable to other health services seeking to improve and achieve mandatory and accreditation targets.


pH dependence of the activation parameters for chymopapain unfolding: influence of ion pairs on the kinetic stability of proteins.
We studied the irreversible thermal denaturation of chymopapain, a papain-related cysteine proteinase. It was found that this process follows simple first-order kinetics under all conditions tested. Rate constants determined by monitoring ellipticity changes at 220 or 279 nm are essentially identical, indicating that denaturation involves global unfolding of the protein. Enthalpies (DeltaH(double dagger)) and entropies (DeltaS(double dagger)) of activation for unfolding were determined at various pH values from the temperature dependence of the rate constant. In the pH range 1.1-3.0, a large variation of both DeltaH(double dagger) and DeltaS(double dagger) was observed. For the few proteins studied so far (lysozyme, trypsin, barnase) it is known that activation parameters for unfolding vary little with pH. It is proposed that this contrasting behavior of chymopapain originates from the numerous ion pairs - especially those with low solvent accessibilities - present in its molecular structure. In contrast, fewer, more exposed ion pairs are present in the other proteins mentioned above. Our results were analyzed in terms of differences in the protonation behavior of carboxylic groups between the transition (TS) and native (N) states of the protein. For this purpose, a model of independently titrating sites was assumed, which explained reasonably well the pH dependence of activation parameters, as well as the protonation properties of native chymopapain. According to these calculations, pK values of carboxyls in TS are shifted 0.6-0.9 units upwards with respect to those in N. In addition, some groups in TS appear to be protonated with unusually large enthalpy changes.


Paraventricular nucleus, stress response, and cardiovascular disease.
The paraventricular nucleus of the hypothalamus (PVN) is a complex effector structure that initiates endocrine and autonomic responses to stress. It receives inputs from visceral receptors, circulating hormones such as angiotensin II, and limbic circuits and contains neurons that release vasopressin, activate the adrenocortical axis, and activate preganglionic sympathetic or parasympathetic outflows. The neurochemical control of the different subgroups of PVN neurons is complex. The PVN has been implicated in the pathophysiology of congestive heart failure and the metabolic syndrome.


Rapport: A conceptual definition from the perspective of patients and families receiving palliative care.
To explore patient and family perceptions of rapport in interactions with health professionals and use the findings to develop a conceptual definition of rapport. We undertook a qualitative Interpretive Description study; semi-structured interviews were conducted between November 2020 and May 2021. Participants included 18 patients and 11 family members recruited using a random approach from four hospice locations in Aotearoa, New Zealand. Interviews were audio recorded, transcribed, and analysed to develop a conceptual definition of rapport using guidelines (Podsakoff et al., (2016). A COREQ checklist was completed. Four dimensions of rapport were identified which formed the basis of a conceptual definition: 1) the type of relating, 2) the essence of rapport experienced, 3) key communication characteristics, and 4) the effect on interactions. Based on patient and family experiences of rapport, this study formulated a conceptual definition of rapport. This definition will support clinical education and practice and inform future research related to rapport. A conceptual definition of rapport can provide clarity for both research and clinical practice. It may be used as a tool for health professionals to reflect upon their experiences with rapport and develop expertise in this area.


A distributed network supports spatiotemporal cerebral dynamics of visual naming.
Cerebral spatiotemporal dynamics of visual naming were investigated in epilepsy patients undergoing stereo-electroencephalography (SEEG) monitoring. Brain networks were defined by Parcel-Activation-Resection-Symptom matching (PARS) approach by matching high-gamma (50-150 Hz) modulations (HGM) in neuroanatomic parcels during visual naming, with neuropsychological outcomes after resection/ablation of those parcels. Brain parcels with >50% electrode contacts simultaneously showing significant HGM were aligned, to delineate spatiotemporal course of naming-related HGM. In 41 epilepsy patients, neuroanatomic parcels showed sequential yet temporally overlapping HGM course during visual naming. From bilateral occipital lobes, HGM became increasingly left lateralized, coursing through limbic system. Bilateral superior temporal HGM was noted around response time, and right frontal HGM thereafter. Correlations between resected/ablated parcels, and post-surgical neuropsychological outcomes showed specific regional groupings. Convergence of data from spatiotemporal course of HGM during visual naming, and functional role of specific parcels inferred from neuropsychological deficits after resection/ablation of those parcels, support a model with six cognitive subcomponents of visual naming having overlapping temporal profiles. Cerebral substrates supporting visual naming are bilaterally distributed with relative hemispheric contribution dependent on cognitive demands at a specific time. PARS approach can be extended to study other cognitive and functional brain networks.


What is the preferred hemostasis method for coronary angiography through the palmar artery access?
Trans-palmar catheterization has been considered to be safe and feasible and choosing a reliable hemostasis method is essential to confirm it. The aim of our study was to compare the efficacy and safety of three hemostasis approaches containing ulnar TR band, manual compression and wrist hyperextension in patients undergoing trans-palmar coronary angiography (CAG). In a non-randomized clinical trial, a total of 106 patients undergoing diagnostic CAG by tarns-palmar access were divided into three groups: ulnar TR band, manual compression and wrist hyperextension. Duration of primary hemostasis, patient satisfaction, puncture site pain severity, hospitalization time and local neuro-vascular complication were evaluated and compared in hospital and 30 days follow-up. The mean age of the patients was 62.9 ± 7.4 years and 72 patients (67.9%) were male. Primary hemostasis time was significantly shorter in hyperextension (11.5 ± 2.10 min) and manual compression groups (12.3 ± 2.20 min) than with TR band group (24.7 ± 10.25 min) (p value < 0.0001). Patient's satisfaction was higher in hyperextension approach (9.4 ± 0.65) than manual compression (8.8 ± 0.79) and TR band group (8.2 ± 0.90) (p value < 0.0001). The most pain was seen in the TR band and the less in hyperextension group until 4 h after the procedure (p value < 0.0001). Hematoma, numbness and ulnar artery occlusion as well as hospitalization time did not have significant statistical differences (p value > 0.05). In conclusion, between three methods of hemostasis in trans-palmar catheterization, hyperextension approach is the preferred method because of effectiveness, safety and less time consuming hemostatic method compared others.


Decline of dose coverage between intraoperative planning and post implant dosimetry for I-125 permanent prostate brachytherapy: comparison between loose and stranded seed implants.
In permanent prostate brachytherapy the dose distributions 4 weeks post implant differ from the intraoperative dose distributions. The purpose of this study is to compare intraoperative planning and post implant dosimetry for loose and stranded seed implants. This study investigates prostate dose coverage in 389 patients with stage T1 or T2 prostate cancer treated in the years 2005, 2006 and 2007. The patients received either a loose seed or a stranded seed implant. All patients had US-based intraoperative planning and CT/MRI-based post implant dosimetry after 4 weeks. Intraoperative and post implant D(90) values amounted 183+/-13 Gy (mean+/-standard deviation) and 161+/-30 Gy, respectively. Decline of D(90) values (mean and 95% confidence interval) between intraoperative planning and post implant dosimetry for RAPID strand (n=67), Intersource strand (n=136) and loose selectSeeds (n=186) implants amounted to -40 (-45 to -34) Gy, -25 (-28 to -21) Gy and -15 (-18 to -21) Gy, respectively. The patients treated in the period 2005-2007 with stranded or loose seed implants had on average adequate D(90) values of 161+/-30 Gy. Post implant D(90) values were 22+/-27 Gy lower compared to intraoperative planning. Decline of dose coverage between intraoperative planning and post implant dosimetry was significantly larger for the stranded seed implants.


Visible-Light-Promoted Xanthate-Transfer Cyclization Reactions of Unactivated Olefins under Photocatalyst- and Additive-Free Conditions.
A general visible-light-induced photocatalyst-/additive-free strategy was developed for the construction of various nitrogen-heterocycles (42 examples, up to 97% yield) such as γ-lactams, δ-lactams, pyrrolidines, indolones, quinolinones, and fused polycyclic structures at room temperature. The prominent features of this protocol are mild and environmentally friendly conditions, broad substrate scope, and good functional group tolerance. Importantly, the reaction can be performed under natural sunlight, the most sustainable energy source imaginable. Furthermore, this strategy provides straightforward access to a range of derivatives through subsequent elaboration of the xanthate group.


Development of Response Classifier for Vascular Endothelial Growth Factor Receptor (VEGFR)-Tyrosine Kinase Inhibitor (TKI) in Metastatic Renal Cell Carcinoma.
Vascular endothelial growth factor receptor (VEGFR)-targeted therapy improved the outcome of metastatic renal cell carcinoma (mRCC) patients. However, a prediction of the response to VEGFR-tyrosine kinase inhibitor (TKI) remains to be elucidated. We aimed to develop a classifier for VEGFR-TKI responsiveness in mRCC patients. Among 101 mRCC patients, ones with complete response, partial response, or ≥24 weeks stable disease in response to VEGFR-TKI treatment were defined as clinical benefit group, whereas patients with <24 weeks stable disease or progressive disease were classified as clinical non-benefit group. Clinicolaboratory-histopathological data, 41 gene mutations, 20 protein expression levels and 1733 miRNA expression levels were compared between clinical benefit and non-benefit groups. The classifier was built using support vector machine (SVM). Seventy-three patients were clinical benefit group, and 28 patients were clinical non-benefit group. Significantly different features between the groups were as follows: age, time from diagnosis to TKI initiation, thrombocytosis, tumor size, pT stage, ISUP grade, sarcomatoid change, necrosis, lymph node metastasis and expression of pAKT, PD-L1, PD-L2, FGFR2, pS6, PDGFRβ, HIF-1α, IL-8, CA9 and miR-421 (all, P < 0.05). A classifier including necrosis, sarcomatoid component and HIF-1α was built with 0.87 accuracy using SVM. When the classifier was checked against all patients, the apparent accuracy was 0.875 (95% CI, 0.782-0.938). The classifier can be presented as a simple decision tree for clinical use. We developed a VEGFR-TKI response classifier based on comprehensive inclusion of clinicolaboratory-histopathological, immunohistochemical, mutation and miRNA features that may help to guide appropriate treatment in mRCC patients.


Prognostic Implications of Elevated Pulmonary Artery Pressure After ST-Segment Elevation Myocardial Infarction.
Elevated systolic pulmonary artery pressure (SPAP) after ST-segment elevation myocardial infarction (STEMI) has been associated with adverse outcome. However, little is known about the development of increased SPAP after STEMI treated with primary percutaneous coronary intervention. The aims of this study were to investigate the incidence and determinants of elevated SPAP (SPAP ≥36 mm Hg at 12 months) after first STEMI and to analyze its prognostic implications. A total of 705 patients (60 ± 12 years; 75% men; left ventricular ejection fraction [LVEF] 47 ± 9%) with first STEMI treated with primary percutaneous coronary intervention were evaluated. Two-dimensional echocardiography was available at baseline and 12-month follow-up. Data on all-cause mortality were collected at long-term follow-up. Incident elevated SPAP was present in 5% (n = 38) of patients. Patients with incident elevated SPAP were older (66 ± 12 vs 60 ± 11 years, p = 0.001), had more systemic hypertension (58% vs 30%, p <0.001) and lower LVEF (43 ± 9% vs 48 ± 8%, p <0.001) than their counterparts. Left atrial volume was larger (23 ± 11 vs 18 ± 6 ml/m(2), p = 0.006), and moderate to severe mitral regurgitation was more prevalent in patients with incident elevated SPAP (16% vs 7%, p = 0.05). Independent correlates of incident elevated SPAP at 12-month follow-up were age (odds ratio [OR] 1.04, 95% CI 1.01 to 1.08, p = 0.01), hypertension (OR 2.52, 95% CI 1.23 to 5.14, p = 0.01), baseline LVEF (OR 0.94, 95% CI 0.90 to 0.98, p = 0.003), and baseline left atrial volume (OR 1.08, 95% CI 1.03 to 1.12, p = 0.001). Incident elevated SPAP was independently associated with all-cause mortality (hazard ratio 3.84, 95% CI 1.76 to 8.39, p = 0.001). In conclusion, although the incidence of elevated SPAP after STEMI is low, its presence is independently associated with increased risk of all-cause mortality at follow-up.


[Clinical evaluation of metronidazole in the treatment of the periodontal abscesses].
On the basis of clinical examination it has been found that Metronidazole which was applied in 24 patients suffering from periodontal abscesses produced healing effects, lessened their pain and did not cause any side reactions. The values of PI (Russell rate) were considerably lower after the treatment comparing to the initial state, which confirms the therapeutic effectiveness of the drug.


Risk Factors Associated with Severe/Critical COVID-19 in People Living with HIV-1.
Our objective was to determine the risk factors of a "severe/critical" form of COVID-19 in a cohort of people living with HIV-1 (PLWH1) followed in the Bichat University Hospital center in PARIS, FRANCE. This study was an observational retrospective monocentric cohort of PLWH1 diagnosed with COVID-19 between February 1 st and November 31 st, 2020. Risk factors associated with "severe/critical" forms were determined using stepwise forward selection. One-hundred-and-twenty-nine PLWH1 with COVID-19 were included. COVID-19 diagnosis was confirmed in 98 cases (75.9%) and deemed probable according to the association of clinical criteria and contact case in 31 cases (24.1%). Clinical presentation of COVID-19 was "asymptomatic/mild/moderate" in 95 (73.6%), "severe" in 26 (21.7%) and "critical" in eight (6%). Patients with "severe/critical" COVID-19 tended to be older (median 54 year old), have a higher BMI (median 28.8 kg/m²) and were likely to have diabetes (9 versus 5) or chronic kidney disease (5 versus 2). Transgender women had higher risk too (OR: 4.9 (IC95: 1.35-24.0)). No association was observed between severity of COVID-19 and viral suppression or CD4 rates. Risk factors for severe COVID-19 were similar in PLWH1 than in the general population and PLWH1 transgender women were at higher risk.


Lowering the Recommended Maximal Wall Thickness Threshold Improves Diagnostic Sensitivity in Asians With Hypertrophic Cardiomyopathy.
Hypertrophic cardiomyopathy (HCM) is defined as left ventricular end-diastolic maximal wall thickness (WTMax) ≥15.0 mm, without accounting for ethnicity, sex, and body size. It is well-established that Asians have smaller hearts than do Caucasians. This study aims to examine the implications of this single absolute WTMax threshold on the diagnosis of HCM in Asians. The study consisted of 360 healthy volunteers (male: n = 174; age: 50 ± 12 years) and 114 genetically characterized patients with HCM (male: n = 83; age: 52 ± 13 years; genotype-positive, n = 39). All participants underwent cardiovascular magnetic resonance. WTMax was measured semiautomatically at end-diastole according to the standard 16 myocardial segments. Healthy male volunteers had increased WTMax compared with that of female volunteers (8.4 ± 1.2 mm vs 6.6 ± 1.1 mm, respectively; P < 0.001). Conversely, WTMax was similar between male and female patients with HCM (15.2 ± 3.4 mm vs 14.7 ± 3.0 mm, respectively; P = 0.484) and between those with and without a pathogenic gene variant (P = 0.828). Using the recommended diagnostic threshold of 15.0 mm, 56 patients with HCM had WTMax <15.0 mm and no healthy volunteers had WTMax >15.0 mm (specificity of 100% and sensitivity of 51%). Lowering WTMax thresholds to 10.0 mm in female patients and 12.0 mm in male patients did not affect specificity (100%) but significantly improved sensitivity (84%). Despite lower left ventricular mass, female patients with HCM demonstrated more features of adverse cardiac remodeling than did male patients: increased myocardial fibrosis, higher asymmetric ratio, and disproportionately worse myocardial strain. The study highlights cautious application of guideline-recommended WTMax to diagnose HCM in Asians. Lowering WTMax to account for ethnicity and sex improves diagnostic sensitivity without compromising specificity.


An in-country humanitarian neurosurgical services as model for low-and-middle-income countries: The case of Cote d' Ivoire.
•Initiated in 2019, Humanitarian neurosurgery in Cote d'Ivoire is entirely supported by national non-governmental entities.•Free neurosurgical care is made possible through fundraising campaigns operated via social networking platforms.•Humanitarian neurosurgical activities in Cote d'Ivoire target children with hydrocephalus and neural tube defects.


The Effect of Continuous-Flow Left Ventricular Assist Device Duration on Postoperative Outcomes.
This study evaluated the effect of continuous-flow left ventricular assist device (CF-LVAD) duration on postoperative outcomes in heart transplant patients. United Network of Organ Sharing heart transplant follow-up data from 2005 to 2015 were obtained. Patients supported by CF-LVADs who subsequently underwent cardiac transplantation were studied. The study population was divided into three groups by CF-LVAD duration of less than 1 year, 1 to 2 years, and more than 2 years. Multivariable Cox regression analysis was used to identify predictors of overall postoperative graft survival. Kaplan-Meier survival functions were used to estimate actuarial survival at 1, 2, and 5 years after transplant. The association between CF-LVAD duration and postoperative acute rejection episodes before and after hospital discharge was assessed. Of 21,336 recipients, 4,382 had CF-LVADs before cardiac transplantation: 2,603 (59.4%) had CF-LVADs for less than 1 year, 1,178 (26.9%) for 1 to 2 years, and 601 (13.7%) for more than 2 years. Donor age, high body mass index, dialysis dependence, and poor functional status at transplant were significant predictors of poor posttransplant graft survival. CF-LVAD duration was associated with increased incidence of acute rejection before hospital discharge (odds ratio, 1.14; 95% confidence interval, 1.02 to 1.28; p = 0.019). Duration was not related to acute rejection episodes after discharge. There was no difference in survival among patients with increasing time durations (hazard ratio, 1.01; 95% CI, 0.89 to 1.15; p = 0.824). Graft survival at 1, 2, and 5 years among patient groups was not significantly different (p = 0.824 by log-rank test) CONCLUSIONS: Duration of CF-LVAD support does not affect posttransplant graft survival. Longer duration of support increases acute rejection episodes; however, this may not translate into diminished survival.


The relationship between implant stability and bone health markers in post-menopausal women with bisphosphonate exposure.
The authors assessed the relationship between implant stability and bone turnover markers in patients with and without a history of bisphosphonate (BP) exposure for treatment of osteopenia/osteoporosis. One dental implant site was evaluated in 58 post-menopausal women with a spectrum of bone health in a "best practice" prospective cohort study. Each site had a previous or simultaneous bone augmentation procedure. BP exposure at enrollment was categorized as "never" or "past/current" exposure. Implant stability was assessed by resonance frequency analysis (RFA ISQ) at surgery and 8 weeks post-implant. Bone turnover markers, C-telopeptide collagen crosslinks (sCTX) and procollagen -1 N-terminal telopeptide (P1NP), were measured pre-treatment, 1, and 8 weeks following implant surgery. Mean age was 62.4 ± 6.8 years; 66 % were osteopenic/osteoporotic. Average RFA ISQ at placement for all participants was 63.5 ± 11.3, at 8 weeks post-surgery 74.2 ± 9.4 (p < 0.01). Among "past/current" BP users, there was a significant negative correlation between RFA ISQ values at 8 weeks post-implant placement and sCTX and P1NP values at 1 week (ρ = -.65 and ρ = -.55, respectively; p < 0.01) and 8 weeks (ρ = -.64 and ρ = -.52, respectively; p < 0.05). RFA ISQ values increased between implant placement and 8 weeks post-surgery demonstrating successful osseointegration. Lower bone turnover was associated with better implant stability among patients with a history of BP exposure. Further investigation of the relationship between BP exposure and implant stability is warranted in a larger population, as results may strongly impact on clinical practice decisions.


Calculation of oxygen pressures in tissue with anisotropic capillary orientation. II. Coupling of two-dimensional planes.
The mathematical descriptions of oxygen transport in terms of two-dimensional diffusion in planes perpendicular to the capillaries can be coupled for an ensemble of planes to yield a three-dimensional description. In tissue with a distinct orientation of the oxygen supplying structures, the capillaries, this leads to a description of oxygen pressure in a whole tissue volume. Muscle tissue is an example of such tissue. The method allows calculation of oxygen pressure (pO2) at any location in the volume. Tissue volume oxygen status can be assessed by constructing a pO2 histogram, gathering pO2's at a large number of locations in the tissue.


Exploring the potential of antimalarial nanocarriers as a novel therapeutic approach.
Malaria is a life-threatening parasitic disease that affects millions of people worldwide, especially in developing countries. Despite advances in conventional therapies, drug resistance in malaria parasites has become a significant concern. Hence, there is a need for a new therapeutic approach. To combat the disease effectively means eliminating vectors and discovering potent treatments. The nanotechnology research efforts in nanomedicine show promise by exploring the potential use of nanomaterials that can surmount these limitations occurring with antimalarial drugs, which include multidrug resistance or lack of specificity when targeting parasites directly. Utilizing nanomaterials would possess unique advantages over conventional chemotherapy systems by increasing the efficacy levels while reducing side effects significantly by delivering medications precisely within the diseased area. It also provides cheap yet safe measures against Malaria infections worldwide-ultimately improving treatment efficiency holistically without reinventing new methods therapeutically. This review is an effort to provide an overview of the various stages of malaria parasites, pathogenesis, and conventional therapies, as well as the treatment gap existing with available formulations. It explores different types of nanocarriers, such as liposomes, ethosomal cataplasm, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanocarriers, and metallic nanoparticles, which are frequently employed to boost the efficiency of antimalarial drugs to overcome the challenges and develop effective and safe therapies. The study also highlights the improved pharmacokinetics, enhanced drug bioavailability, and reduced toxicity associated with nanocarriers, making them a promising therapeutic approach for treating malaria.


The pathogenesis of polycystic ovary syndrome: lessons from ovarian stimulation studies.
In polycystic ovary syndrome (PCOS) the ovary produces markedly increased amounts of both androgens and estrogens in response to gonadotropin stimulation. Distinctive responses of 17-hydroxyprogesterone and androstenedione to ovarian stimulation testing suggest that ovarian hyperandrogenism is a result of dysregulation of theca cell androgen production which is intrinsic to the ovary. The occurrence of hyperestrogenism together with hyperandrogenism in PCOS suggests that whatever the abnormality of local regulatory factors of steroidogenesis, it affects granulosa as well as theca cells. Dysregulation is often associated with an increase in the number of follicles which evade atresia and reach the 2-8 mm stage of development. Autocrine/paracrine factors, especially those which are FSH-dependent, likely play an important role in the pathogenesis of the ovarian abnormality. Both LH and insulin hypersecretion probably play a secondary role in PCOS by amplifying the preexisting ovarian dysregulation. Because FSH secretion is under tight long-loop negative-feedback control and LH is not, hyperandrogenism is the primary clinical manifestation of dysregulation of steroid production in PCOS. However, anovulation in PCOS is most likely a result of excessive estrogen and inhibin production by multiple, small follicles which inhibit FSH secretory dynamics sufficiently to prevent selection of a dominant follicle.


Theoretical models of selection and mutation on quantitative traits.
Empirical studies of quantitative genetic variation have revealed robust patterns that are observed both across traits and across species. However, these patterns have no compelling explanation, and some of the observations even appear to be mutually incompatible. We review and extend a major class of theoretical models, 'mutation-selection models', that have been proposed to explain quantitative genetic variation. We also briefly review an alternative class of 'balancing selection models'. We consider to what extent the models are compatible with the general observations, and argue that a key issue is understanding and modelling pleiotropy. We discuss some of the thorny issues that arise when formulating models that describe many traits simultaneously.


Effect of Hysterectomy due to Benign Diseases on Female Sexual Function: A Systematic Review and Meta-analysis.
Determination of the effect of hysterectomy caused by benign diseases on female sexual function. A search was performed on Scopus, PubMed, Science Direct, ProQuest, ISI Web of Knowledge, and Embase databases. The keywords included hysterectomy (as exposure) and female sexual function (as outcome). Original English observational studies, including cohort, case-control, and cross-sectional studies published as of February 2021, which reported an association between any type of hysterectomy caused by benign female disease and sexual function as an outcome, were included in the study. Studies in participants who received hormone replacement therapy and had sex other than heterosexuals were not included. There was no limit to the initial search period, and articles published by February 2021 were searched. The search process resulted in the retrieval of 5587 potentially related articles. After removing duplicated studies, the title and abstract were reviewed and 77 articles remained with the removal of unrelated items. The full text of 14 articles was published in non-English languages, and 52 articles were removed because they did not meet the inclusion criteria, and finally, 11 articles were included in the final analysis. The Newcastle-Ottawa scale was used to assess the methodological quality of included studies. The evidence was synthesized using meta-analysis via random-effect model with the Der Simonian and Laird weighted method. Publication bias was assessed using the funnel plot and Begg's and Egger's tests. The pooled standardized mean difference for sexual function in hysterectomy vs nonhysterectomy group was 0.08 (95% confidence interval, -0.38 to 0.55; I2 = 96.8%; χ2 = 307.94; p <.001; τ2 = 0.59). Publication bias and small study effects were not detected. The results of the subgroup analysis showed that the possible sources of heterogeneity are the World Bank countries classification and type of hysterectomy (in some studies, the type of hysterectomy was not specified separately for the study groups; because of this, comparisons were made between Total and supracervical/total). Pooled standardized mean difference was affected by the type of sexual function scale, World Bank countries classification, type of hysterectomy, ovary status, and reproductive status. The results of meta-regression analysis also showed that for each month of distance from hysterectomy, women's sexual function score increases by 0.18. The results of this study showed that hysterectomy caused by benign diseases does not change the sexual function significantly.


Ion-Ion Interactions in Charge Detection Mass Spectrometry.
Charge detection mass spectrometry (CDMS) is a single-particle technique where the masses of individual ions are determined by simultaneously measuring their mass-to-charge ratio (m/z) and charge. Ions are usually trapped inside an electrostatic linear ion trap (ELIT) where they oscillate back and forth through a detection cylinder, generating a periodic signal that is analyzed by fast Fourier transforms. The oscillation frequency is related to the ion's m/z, and the magnitude is related to the ion's charge. In early work, multiple ion trapping events were discarded because there was a question about whether ion-ion interactions affected the results. Here, we report trajectory calculations performed to assess the influence of ion-ion interactions when multiple highly charged ions are simultaneously trapped in an ELIT. Ion-ion interactions cause trajectory and energy fluctuations that lead to variations in the oscillation frequencies that in turn degrade the precision and accuracy of the m/z measurements. The peak shapes acquire substantial high and low m/z tails, and the average m/z shifts to a higher value as the number of trapped ions increases. The effects of the ion-ion interactions are proportional to the product of the charges and the square root of the number of trapped ions and depend on the ions' m/z distribution. For the ELIT design examined here, ion-ion interactions limit the m/z resolving power to several hundred for a typical homogeneous ion population.


[Early diagnosis of cerebral infarct. Hyperdensity of the middle cerebral artery as the first CT sign of an ischemic lesion].
An early CT sign of cerebral infarction in the sylvian area is described: the normal density value of the middle homolateral cerebral artery is increased, because of thrombotic or embolic deposits inside.


Identification of cow milk in goat milk by nonlinear chemical fingerprint technique.
The objective of this paper was to develop a nonlinear chemical fingerprint technique for identifying and detecting adulteration of goat milk with cow milk. In this study, by taking the Belousov-Zhabotinsky oscillatory chemical reaction using acetone and substrates in goat milk or cow milk as main dissipative substances, when the same dosage of goat milk and cow milk was introduced to the "H+ + Mn2+ + BrO3- + acetone" oscillating system respectively, nonlinear chemical fingerprints were obtained for goat milk and cow milk from the same origin. The results showed that inductive time value and the content of cow milk in goat milk had a linear relationship in the range of 0-100% and the corresponding regression coefficient was 0.9991. A detection limit of 0.0107 g/g was obtained, and the content of cow milk in mixed milk was calculated. The proposed method in this study was simple, economical and effective. In addition, the method did not need the pretreatment and separation of samples for identifying and evaluating cow milk adulteration in goat milk.


Fungal community analysis by large-scale sequencing of environmental samples.
Fungi are an important and diverse component of soil communities, but these communities have proven difficult to study in conventional biotic surveys. We evaluated soil fungal diversity at two sites in a temperate forest using direct isolation of small-subunit and internal transcribed spacer (ITS) rRNA genes by PCR and high-throughput sequencing of cloned fragments. We identified 412 sequence types from 863 fungal ITS sequences, as well as 112 ITS sequences from other eukaryotic microorganisms. Equal proportions of Basidiomycota and Ascomycota sequences were present in both the ITS and small-subunit libraries, while members of other fungal phyla were recovered at much lower frequencies. Many sequences closely matched sequences from mycorrhizal, plant-pathogenic, and saprophytic fungi. Compositional differences were observed among samples from different soil depths, with mycorrhizal species predominating deeper in the soil profile and saprophytic species predominating in the litter layer. Richness was consistently lowest in the deepest soil horizon samples. Comparable levels of fungal richness have been observed following traditional specimen-based collecting and culturing surveys, but only after much more extensive sampling. The high rate at which new sequence types were recovered even after sampling 863 fungal ITS sequences and the dominance of fungi in our libraries relative to other eukaryotes suggest that the abundance and diversity of fungi in forest soils may be much higher than previously hypothesized. All sequences were deposited in GenBank, with accession numbers AY 969316 to AY 970290 for the ITS sequences and AY 969135 to AY 969315 for the SSU sequences.


Photosensitization of TiO2 nanofibers by Ag2S with the synergistic effect of excess surface Ti3+ states for enhanced photocatalytic activity under simulated sunlight.
TiO2 nanofibers, with mean diameter ~200 nm, were fabricated by electrospinning and successfully photosensitized with low bandgap Ag2S nanoparticles of 11, 17, 23 and 40 nm mean sizes, with corresponding loading of 4, 10, 18 and 29 wt.% Ag2S, respectively. 17 nm Ag2S@TiO2 nanofibers exhibited optimal activity in the photodegradation of methylene blue under simulated sunlight with pseudo-first order rate constant of 0.019 min-1 compared to 0.009 min-1 for pure TiO2 nanofibers. In spite of greater visible-light absorption and reduced bandgap, larger than 17 nm Ag2S nanoparticles exhibited sluggish photodegradation kinetics probably due to less photo-induced carriers generation in TiO2 and reduced electron injection rates from the larger sized Ag2S into TiO2. Furthermore, a UV-O3 surface treatment induced excess Ti3+ surface states and oxygen vacancies which synergistically enhanced the photodegradation rate constant to 0.030 min-1 for 17 nm Ag2S@TiO2 sample which is ~70% better than the previously reported for Ag2S/TiO2 hierarchical spheres. This was attributed to the efficient charge separation and transfer driven by increased visible-light absorption, bandgap narrowing and reduced electron-hole recombination rates. The present study demonstrate the potential utilization of Ag2S@TiO2 nanofibers in filtration membranes for removal of organic pollutants from wastewater.


Time course of appearance of alpha-bungarotoxin binding sites during development of chick ciliary ganglion and iris.
The binding of [125I]alpha-bungarotoxin (ABTX) to homogenates of ciliary ganglia and irises from embryonic and posthatching chickens has been examined. Specific, high-affinity binding was found in both tissues [KD (iris) equals 2.5 nM; KD (ganglion) equals 2.7 nM]. Binding is saturated above 10 nM toxin concentration and is inhibited by low concentrations of the nicotinic antagonist d-tubocurarine. The binding may be associated with a nicotinic cholinergic receptor in both tissues. The amount of binding in the iris begins to increase soon after functional innervation is first observed, at 12 days of incubation (d.i.), and continues to increase up to four months after hatching (a.h.), the oldest age tested. In contrast, ABTX binding in the ciliary ganglion increases fourfold between 7 and 11 d.i., after which the amount of binding remains unchanged up to four months a.h. When compared to the development of choline acetyltransferase (ChAc) and acetylcholinesterase (AChE) activities in the ganglion and iris, ABTX binding follows a pattern similar to that of AChE activity. The largest increases in ChAc activity occur later than those of the postsynaptic markers. After 16 d.i. there are approximately 3 x 10(6) toxin molecules bound per neuron in the ciliary ganglion.


Blood Prostate-specific Antigen by Volume of Benign, Gleason Pattern 3 and 4 Prostate Tissue.
To evaluate how blood levels of prostate-specific antigen (PSA) relate to prostate volume of benign tissue, Gleason pattern 3 (GP3) and Gleason pattern 4 (GP4) cancer. The cohort included 2209 consecutive men undergoing radical prostatectomy at 2 academic institutions with pT2N0, Grade Group 1-4 prostate cancer and an undetectable postoperative PSA. Volume of benign, GP3, and GP4 were estimated. The primary analysis evaluated the association between PSA and volume of each type of tissue using multivariable linear regression. R2, a measure of explained variation, was calculated using a multivariable model. Estimated contribution to PSA was 0.04/0.06 ng/mL/cc for benign, 0.08/0.14 ng/mL/cc for GP3, and 0.62/0.80 ng/ml/cc for GP4 for the 2 independent cohorts, respectively. GP4 was associated with 6 to 8-fold more PSA per cc compared to GP3 and 15-fold higher compared to benign tissue. We did not observe a difference between PSA per cc for GP3 vs. benign tissue (P = 0.2). R2 decreased only slightly when removing age (0.006/0.018), volume of benign tissue (0.051/0.054) or GP3 (0.014/0.023) from the model. When GP4 was removed, R2 decreased 0.051/0.310. PSA density (PSA divided by prostate volume) was associated with volume of GP4 but not GP3, after adjustment for benign volume. Gleason pattern 4 cancer contributes considerably more to PSA and PSA density per unit volume compared to GP3 and benign tissue. Contributions from GP3 and benign are similar. Further research should examine the utility of determining clinical management recommendations by absolute volume of GP4 rather than the ratio of GP3 to GP4.


Proton-pump inhibitors are associated with increased cardiovascular risk independent of clopidogrel use: a nationwide cohort study.
Controversy remains on whether the dual use of clopidogrel and proton-pump inhibitors (PPIs) affects clinical efficacy of clopidogrel. To examine the risk for adverse cardiovascular outcomes related to concomitant use of PPIs and clopidogrel compared with that of PPIs alone in adults hospitalized for myocardial infarction. A nationwide cohort study based on linked administrative registry data. All hospitals in Denmark. All patients discharged after first-time myocardial infarction from 2000 to 2006. The primary outcome was a composite of rehospitalization for myocardial infarction or stroke or cardiovascular death. Patients were examined at several assembly time points, including 7, 14, 21, and 30 days after myocardial infarction. Follow-up was 1 year. Of 56 406 included patients, 9137 (16.2%) were re-hospitalized for myocardial infarction or stroke or experienced cardiovascular death. Of the 24 702 patients (43.8%) who received clopidogrel, 6753 (27.3%) received concomitant PPIs. The hazard ratio for cardiovascular death or rehospitalization for myocardial infarction or stroke for concomitant use of a PPI and clopidogrel among the cohort assembled at day 30 after discharge was 1.29 (95% CI, 1.17 to 1.42). The corresponding ratio for use of a PPI in patients who did not receive clopidogrel was 1.29 (CI, 1.21 to 1.37). No statistically significant interaction occurred between a PPI and clopidogrel (P = 0.72). Unmeasured and residual confounding, time-varying measurement errors of exposure, and biases from survival effects were possible. Proton-pump inhibitors seem to be associated with increased risk for adverse cardiovascular outcomes after discharge, regardless of clopidogrel use for myocardial infarction. Dual PPI and clopidogrel use was not associated with any additional risk for adverse cardiovascular events over that observed for patients prescribed a PPI alone.


Liver metabolomic characterization of Sophora flavescens alcohol extract-induced hepatotoxicity in rats through UPLC/LTQ-Orbitrap mass spectrometry.
This study aimed to observe the influence of Sophora flavescens alcohol extract (SFAE) on hepatic metabolic profiling in rats to explore the possible mechanism of hepatotoxicity induced by S. flavescens.Male Sprague-Dawley rats were randomly divided into three groups (n = 6 in each group) and administered with SFAE at different doses of 0, 1.25 and 2.5 g/kg for two weeks. Ultra-performance liquid chromatography-high resolution mass spectrometry was utilized to detect the change in the metabolites in rat liver. Principal component analysis and orthogonal partial least squares discriminant analysis were adapted to perform multivariate statistical analysis between groups and to screen the potential biomarkers. Related metabolic pathway analysis was also conducted.Results indicated that hepatic metabolites in the three groups were separated on day 14, and 25 major differential metabolites were identified. Six bile acids, four carnitines, four lysophosphatidylcholines and glutathione were closely related to hepatotoxicity. Liver metabolomic results showed that rats orally exposed to SFAE exhibited a disturbance of the metabolism of bile acids, fatty acids, glycerophospholipids and amino acids.This study provided new insights into the possible mechanism of hepatotoxicity induced by SFAE in rats.


Evaluation of rhegmatogenous retinal detachments using Optos ultrawide field fundus fluorescein angiography and comparison with ETDRS 7 field overlay.
To evaluate the ultrawide field fundus fluorescein angiography (UWFA) characteristics of rhegmatogenous retinal detachments (RRDs) and compare the findings with an early treatment diabetic retinopathy study (ETDRS) 7 field (ETDRS7F) overlay. UWFA (Optos, PLC, Dunfermline, UK) was performed in 10 eyes with macula-off RRDs in 9 patients. The findings of UWFA were compared with that of an overlay of standard ETDRS7F. Vascular dilation, tortuosity of vessels, and blockage of choroidal fluorescence were noted in all eyes in both UWFA and ETDRS7F overlay. Other findings in UWFA and ETDRS7F included peripheral perivascular staining (10 versus 4 eyes), peripheral capillary nonperfusion (CNP) (9 eyes compared to none), vascular loop formation (7 eyes versus none), optic disc hyperfluorescence (5 eyes in both), petaloid leak at macula (2 eyes in both), and neovascularization elsewhere (3 eyes versus none). Peripheral perivascular staining and leak, CNP, and vascular tortuosity are common UWFA features of RRDs. Standard ETDRS7F missed peripheral CNP, peripheral vascular loops, and peripheral retinal new vessels in all eyes compared to UWFA in the current study.


Systematic hybrid laparoscopic and endovascular treatment of median arcuate ligament syndrome: A single-center experience.
Median arcuate ligament syndrome (MALS) is caused by celiac trunk (CT) compression by the median arcuate ligament. Clinically, this pathology varies from postprandial pain (Dunbar syndrome) to a life-threatening hemorrhage because of a rupture of a gastroduodenal artery aneurysm (GAA). Due to the low prevalence of this disease, there is no standard management for MALS. This was a single-center, retrospective study of 13 patients. Two groups were identified on the basis of the initial clinical presentation: those operated for a GAA rupture (bleeding group-BG) and those operated electively for Dunbar syndrome (Dunbar syndrome group-DG). The primary endpoint was 30-day postoperative complications of a systematic laparoscopic release of the median arcuate ligament and stenting during the same procedure. Seven patients (54%) underwent elective surgery. Six patients (46%) underwent semiurgent repair under elective conditions post-embolization for GAA bleeding. The total operative time was longer in the BG (p = 0.06). Two patients in the BG suffered early major complications and needed reintervention, and those in the DG had a lower comprehensive complication index. No mortality was reported at 30 days. Overall median length of stay was 5 days (IQR: 3.5-15.3). Patients in the DG had a significantly shorter length of stay (p = 0.02). At 6 months, the primary and secondary CT stent patencies were 82% and 100%, respectively. There were no high-flow GAA recurrences. A combined approach of laparoscopic release of the median arcuate ligament and stenting during the same procedure is feasible and safe, and this approach must be systematically discussed in symptomatic patients.


Artificial reproduction of Caspian roach, Rutilus caspicus following stimulating ovulation with Ovaprim, Ovopel, and their combinations under controlled conditions.
The aim of this study was to evaluate the efficiency of different hormonal agents and their combinations for spawning induction of females Caspian roach, Rutilus caspicus. Five groups of fish were injected intraperitoneally as follows: two injections of Ovaprim (T1), two injections of Ovopel (T2), a priming dose of Ovopel with a resolving dose of Ovaprim (T3), a priming dose of Ovaprim with a resolving dose of Ovopel (T4), and two injections of sterile 0.9% NaCl solution as a control group. The results showed that no fish ovulated in the control group. In hormone-treated groups, no differences were observed in ovulation success (P > 0.05). The shortest latency time and highest working and relative fecundities were observed in fish stimulated with two injections of Ovaprim (T1 group). The mean values of fertilization success in treated fish were in the range of 87.9-93.1% and the highest values were observed in T3 and T1 groups (P < 0.05). The best results in terms of ovulation index (92.1%), hatching rate (93.7%), and survival up to the eyed egg stage (89.4%) were achieved after administering two injections of Ovaprim (T1 group). There were no significant differences in the incubation time and embryos survival rates up to absorbing the yolk sac among different groups (P > 0.05). Overall, the best results of controlled reproduction of Caspian roach were obtained after using two injections of Ovaprim. Consequently, the Ovaprim is more suitable for restocking and aquaculture purposes of endangered populations of Caspian roach.


Serotoninergic pain modulation from the rostral ventromedial medulla (RVM) in chemotherapy-induced neuropathy: The role of spinal 5-HT3 receptors.
Chemotherapy-induced neuropathy (CIN) is a common complication of cancer treatment. Although CIN is treated with antidepressants that act at serotonin (5-HT) reuptake, the mechanisms of serotoninergic modulation of nociceptive transmission during CIN remain unknown, namely as to the involvement of the rostroventromedial medulla (RVM) and the role of spinal 5-HT3 receptors (5-HT3R). Male Wistar rats were injected with the cytostatic paclitaxel or vehicle solution. One month after CIN induction, we first studied the activation of RVM neurons, and then the activation of the local serotoninergic neurons. Immunostaining of phosphorylated extracellular signal-regulated kinase (pERK) indicated increased activation in paclitaxel-injected animals. The double immunohistochemistry of pERK and tryptophan hydroxylase (TpH) showed higher expression of TpH and increased co-localization of TpH and pERK of paclitaxel-injected animals, indicating that CIN is associated with increased activation of serotoninergic RVM neurons. The 5-HT content at the spinal dorsal horn assessed by HPLC was higher in paclitaxel-injected animals. The immunohistochemical analysis of 5-HT also showed increased expression at the superficial dorsal horn (laminae I-II) of paclitaxel-injected animals. The levels of 5-HT3R detected by immunohistochemistry were higher in the superficial dorsal horn (laminae I-II) of paclitaxel-injected animals. The intrathecal administration of the 5-HT3R antagonist ondansetron reversed mechanical and cold hypersensitivity in the von Frey and cold plate tests, respectively. The results indicate that CIN is associated with increased recruitment of descending 5-HT-mediated modulation from the RVM which affects the spinal serotoninergic system and probably accounts for pain hypersensitivity due to the pronociceptive role of spinal 5-HT3R.


Internal fixation of valgus-impacted humeral head fractures using the screw-wiring technique.
Between February 1996 and July 2000 eight patients (ages 35-74 years) with nine severely impacted humeral head fractures were operated on with the aim of preserving the humeral heads. Patients were treated surgically with open reduction, autologous bone grafting, and internal fixation with a screw-wiring technique. There were no complications and all patients were satisfied with the results. After 10-63 months there was no evidence of nonunion, arthritis, avascular necrosis, or loosening of implants. The mean Constant score was 83 (66-97) points. Results of this study support the observation that four-part valgus-impacted humeral head fractures without significant lateral displacement have a low incidence of avascular necrosis.


Barriers to the initiation and maintenance of prostate specific antigen screening in Black American and Afro-Caribbean men.
Black American and Afro-Caribbean men may experience the highest incidence of prostate cancer globally. We examined the effect of race/ethnicity on the initiation and maintenance of annual prostate specific antigen screening and the role of physicians in screening continuity in these high risk groups. Stratified cluster sampling of census tract blocks in Brooklyn, New York yielded 533 male participants 45 to 70 years old. The men were classified into 4 racial/ethnic groups, including white men born in the United States, black men born in the United States, immigrant Jamaican men, and immigrant men from Trinidad and Tobago. Participants recorded the number of prostate specific antigen tests performed in the last 10 years. Subject adherence was calculated as annually screened, less than annually screened and never screened. Multinomial logistic regression was used to compare screening behavior across the ethnic groups. Overall 28.3% of participants reported annual screening, 44.5% reported screening less than annually and 27.2% reported having never been screened. Jamaicans (OR 3.1) and men from Trinidad and Tobago (OR 5.4) were more likely to screen less than annually compared to not at all. However, black American men (OR 0.3), Jamaican men (OR 0.3), and men from Trinidad and Tobago (OR 0.2) were less likely to maintain annual screening compared with white men, as were men who did not undergo an annual physical examination (OR 0.3) and those with low prostate cancer knowledge (0.5). Afro-Caribbean men are not less likely than white men to undergo initial prostate specific antigen screening but they are much less likely to maintain annual screening. Through comprehensive discussion and annual examinations physicians have an important role in ensuring prostate specific antigen screening continuity. Our results suggest the need for more culturally appropriate outreach efforts and educational interventions to improve screening compliance.


Deep Endometriosis: the Involvement of Multiple Pelvic Compartments Is Associated with More Severe Pain Symptoms and Infertility.
Endometriosis can be classified into three phenotypes: superficial, ovarian, and deep. Deep endometriosis (DE) has been associated with more severe pain symptoms, although no large-scale studies have evaluated the association between pain intensity and infertility and the different compartments of the pelvis affected by superficial and DE. This retrospective study included 1116 women who underwent laparoscopy for endometriosis treatment at two referral centers between 2009 and 2019. For the evaluation of each symptom, patients were divided according to their visual analog scale score (< 7 and ≥ 7) and fertility status. On multiple logistic regression, severe dysmenorrhea and dyschezia were correlated with DE of the posterior compartment alone (odds ratio (OR) = 1.6, confidence interval (CI) 1.09-2.34, and p = 0.02 and OR = 2.09, CI 1.36-3.23, and p < 0.01, respectively) and in combination with other compartments. DE of the posterior and lateral compartments had the most consistent statistical power (OR = 3.55 for dysmenorrhea and OR = 4.4 for dyschezia). Infertility was associated with DE of the posterior compartment alone (OR = 1.6, CI 1.06-2.54, p = 0.04) and in combination with the anterior compartment (OR = 2.62, CI 1.29-5.29, p < 0.01), with the combination of posterior and anterior compartment having the highest OR value. Severe dyschezia and infertility were also correlated with the presence of multiple localizations of DE (p = 0.04 and p < 0.01). This study confirms the association between DE and severe pain symptoms as well as the influence of the number of DE compartments on the severity of symptoms and the chance of infertility.


Ultrasound-guided aspiration of endometriomas: possible applications and limitations.
To evaluate the role of needle aspiration in the management of endometriomas. Retrospective evaluation of the activity of the section of interventional ultrasound in a single tertiary care institution. Department of Obstetrics and Gynecology, Ospedale S. Gerardo, Monza, University of Milan, Italy. Two hundred nine premenopausal patients underwent aspiration for diagnostic purpose (n = 166), for relief of symptoms (n = 25), or with therapeutic intent (n = 18). Adequate material was obtained by all punctures. Early complications (self-limiting vagal symptoms or pain) occurred in eight cases. Short-term complications consisted of acute abdominal pain in three cases and infection in one. Three women required surgical treatment of the complication. At first examination after aspiration, persistence of the cyst was observed in all but four cases, including all cases who had undergone therapeutic aspiration. Nine patients reported relief of symptoms but six other patients referred onset or worsening of pelvic discomfort after aspiration. Ultrasound-guided aspiration of endometriomas is feasible. The transvaginal route reduces early complication but implies a risk of infection of 1.3%. However, drainage alone is ineffective as a therapeutic procedure and the applications of aspiration of endometriomas appear limited to some cases with diagnostic intent.


Primary care, private physicians, and public health personnel: a conflict in expectations.
The elimination of categorical grants and their replacement by block grants provides public health departments the opportunity to integrate their services and provide general primary care to the underserved. While some may consider this an opportunity long overdue such a change may generate considerable conflict with private physicians. Questionnaire data from private physicians and health department personnel collected in North Carolina during an experimental program of primary care delivery by health department shows that there is substantial conflict. Private physicians oppose health department involvement in general primary care and in acute ambulatory care for the medically underserved. Physicians expect health departments to focus on preventive services, especially environmental monitoring and communicable disease control. Health department personnel want to expand their efforts beyond these more traditional areas into primary care and are in apparent conflict with private physicians. The community attitudes of a group of physicians within a community as well as the attitudes of a group of public health workers were found to be a major determinant of each individual's attitude toward public health, followed by the individual's age, sex, and years of working in the community.