Changes of the main components, physicochemical properties of distiller's grains after extrusion processing with focus on modification mechanism.
Distiller's grains (DGs) possessed great potential utilization value due to their rich active ingredients. However, its utilization efficiency was limited by the large amount of lignocellulose components and water-insoluble proteins. In this work, single screw extrusion was applied to modify physicochemical properties of DGs. Results indicated that extruded distiller's grains (EDGs) exhibited the lower crude fiber content (26.01%), the higher soluble fiber (9.07%) and the smaller particle size when compared with those of Control, and subsequently achieving the increased bulk density, swelling capacity and water/oil holding capacity. The crude protein in EDGs decreased slightly, while the total amount of acid hydrolyzed amino acids showed a significant increase. Additionally, the looser, coarser and fragmentary microstructure of EDGs were observed. The main macromolecules in EDGs had been modified distinctly based on thermal analysis, crystallinity and functional groups analyses, while the possible schematic diagram was conducted to better understand the modification mechanism.


Black-patch psychosis with sympathetic ophthalmitis and deafness.
A case of sympathetic ophthalmia with sensory-neural deafness, who developed a 'black patch psychosis' following loss of vision and hearing, is described. Sympathetic ophthalmitis as a cause of this variety of delirium has not been described earlier.


Oral ethanol reinforcement in the rat: effect of the partial inverse benzodiazepine agonist RO15-4513.
The partial inverse benzodiazepine agonist RO15-4513 has been found to reverse the sedating and anti-conflict effects of acute ethanol administration. In non-food or fluid-deprived rats, orally self-administering 10% ethanol in an operant situation, RO15-4513 resulted in a dose-dependent suppression on ethanol intake. Doses of 0.3, 1.0 and 3.0 mg/kg suppressed responding from approximately 25% to 60% respectively. A dose of 0.1 mg/kg had no significant effect upon responding. These findings were discussed in terms of the potential independence of brain mechanisms related to ethanol reinforcement and sedation.


Magnesium-supplemented warm blood cardioplegia in patients undergoing coronary artery revascularization.
Although there is growing evidence to suggest that the administration of magnesium (Mg2+) to patients undergoing coronary artery bypass grafting (CABG) and to patients after myocardial infarction is beneficial, the addition of Mg2+ to cardioplegic solutions remains controversial. The aim of this study was to compare the effects of intermittent warm blood cardioplegia with and without Mg2+ supplementation on the early postoperative clinical outcomes in patients undergoing both elective or urgent CABG. Four hundred patients undergoing CABG were prospectively randomized to receive either blood cardioplegia without Mg2+ (BC, n = 200) or supplemented with Mg2+ (BC-Mg2+, n = 200). Serial plasma Mg2+ concentrations were recorded at base line and postoperatively from days 1 to 4. Patient characteristics were similar and no significant differences were found in early mortality and morbidity in the two groups. Analysis of 178 patients undergoing urgent CABG for unstable symptoms (BC = 95, BC-Mg2+ = 83) demonstrated a significantly lower requirement for internal defibrillation and temporary epicardial pacing in the BC-Mg2+ group. Furthermore, there was a nearly twofold lower incidence of new postoperative atrial fibrillation in the BC-Mg2+ group compared with the BC group (19% versus 34%, p = 0.03). Postoperative plasma Mg2+ levels were consistently lower in those patients who developed new postoperative atrial fibrillation compared with those who did not (p = 0.05). The addition of Mg2+ to warm blood cardioplegia resulted in a lower incidence of intraoperative and postoperative arrhythmias in patients undergoing urgent CABG for unstable angina.


Knee kinetics and the medial femoral cartilage cross-sectional area response to loading in indviduals with anterior cruciate ligament reconstruction.
Ultrasonography is capable of detecting morphological changes in femoral articular cartilage cross-sectional area in response to an acute bout of walking; yet, the response of femoral cartilage cross-sectional area varies between individuals. It is hypothesized that differences in joint kinetics may influence the response of cartilage to a standardized walking protocol. Therefore, the study purpose was to compare internal knee abduction and extension moments between individuals with anterior cruciate ligament reconstruction who demonstrate an acute increase, decrease, or unchanged medial femoral cross-sectional area response following 3000 steps. The medial femoral cartilage in the anterior cruciate ligament reconstructed limb was assessed with ultrasonography before and immediately following 3000 steps of treadmill walking. Knee joint moments were calculated in the anterior cruciate ligament reconstructed limb and compared between groups throughout the stance phase of gait using linear regression and functional, mixed effects waveform analyses. No associations between peak knee joint moments and the cross-sectional area response were observed. The group that demonstrated an acute cross-sectional area increase exhibited 1) lower knee abduction moments in early stance in comparison to the group that exhibited a decreased cross-sectional area response; and 2) greater knee extension moments in early stance in comparison to the group with an unchanged cross-sectional area response. The propensity of femoral cartilage to acutely increase cross-sectional area in response to walking is consistent with less-dynamic knee abduction and knee extension moment profiles.


Molecular, cellular and systemic aspects of epithelial ovarian cancer and its tumor microenvironment.
Ovarian cancer encompasses a heterogeneous group of malignancies that involve the ovaries, fallopian tubes and the peritoneal cavity. Despite major advances made within the field of cancer, the majority of patients with ovarian cancer are still being diagnosed at an advanced stage of the disease due to lack of effective screening tools. The overall survival of these patients has, therefore, not substantially improved over the past decades. Most patients undergo debulking surgery and treatment with chemotherapy, but often micrometastases remain and acquire resistance to the therapy, eventually leading to disease recurrence. Here, we summarize the current knowledge in epithelial ovarian cancer development and metastatic progression. For the most common subtypes, we focus further on the properties and functions of the immunosuppressive tumor microenvironment, including the extracellular matrix. Current and future treatment modalities are discussed and finally we provide an overview of the different experimental models used to develop novel therapies.


The migraine aura as a cause of avoidance behavior.
Two patients are reported in whom the occurrence of migraine aura led to the development of avoidance behavior. In both patients the migraine aura was given a significance of doom by a previous experience. The avoidance behavior represented an attempt of the patients to deal with the visual disturbance.


Rational drug design and PPAR agonists.
Insulin resistance is a characteristic biological abnormality associated with type 2 diabetes, and is a key component of the metabolic syndrome, a condition in which an altered glucose control is associated with dyslipidemia, hypertension, and obesity. Thiazolidinediones (TZDs), a new class of oral drugs used for the treatment of type 2 diabetes, reduce insulin resistance via an action on peroxisome proliferator-activated receptors. Although the current use of TZDs is largely limited to the treatment of patients with diabetes, as recommended in the package insert, it is foreseeable that as the metabolic syndrome becomes a better understood clinical condition their use may be extended to the treatment of this cluster of disorders. The aim of the present article is to review the mechanism of action of TZDs, discuss the rationale for their use in the clinical setting, and provide an update on novel pharmacologic agents that, although not yet available for the treatment of diabetes, are likely to further enrich the repertoire of antidiabetic drugs in the very near future.


Cancer management during the COVID-19 world pandemic.
Since 2019, the world has been experiencing an outbreak of a novel beta-coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV)-2. The worldwide spread of this virus has been a severe challenge for public health, and the World Health Organization declared the outbreak a public health emergency of international concern. As of June 8, 2023, the virus' rapid spread had caused over 767 million infections and more than 6.94 million deaths worldwide. Unlike previous SARS-CoV-1 and Middle East respiratory syndrome coronavirus outbreaks, the COVID-19 outbreak has led to a high death rate in infected patients; this has been caused by multiorgan failure, which might be due to the widespread presence of angiotensin-converting enzyme 2 (ACE2) receptors-functional receptors of SARS-CoV-2-in multiple organs. Patients with cancer may be particularly susceptible to COVID-19 because cancer treatments (e.g., chemotherapy, immunotherapy) suppress the immune system. Thus, patients with cancer and COVID-19 may have a poor prognosis. Knowing how to manage the treatment of patients with cancer who may be infected with SARS-CoV-2 is essential. Treatment decisions must be made on a case-by-case basis, and patient stratification is necessary during COVID-19 outbreaks. Here, we review the management of COVID-19 in patients with cancer and focus on the measures that should be adopted for these patients on the basis of the organs or tissues affected by cancer and by the tumor stage.


Isolation and characterization of cDNA clones derived from the divergently transcribed gene in the region upstream from the human dihydrofolate reductase gene.
Transcripts initiated in the region immediately upstream from the human dihydrofolate reductase gene but transcribed from the opposite strand have been identified in human cells. These divergent upstream transcripts are polyadenylated, start at 89 base pairs upstream from the dihydrofolate reductase major initiation site, and are composed of two species of 5.0 and 3.8 kilobases in length. We have isolated complementary DNA clones derived from the divergent transcripts and identified a 3.5-kilobase open reading frame in one of these clones. Computer-assisted sequence analyses have shown that there is no significant sequence homology between the putative amino acid sequence and known protein sequences. This arrangement of two divergent transcriptional units suggests that the expression of these two genes may be regulated by a bidirectional promoter with common sequence elements.


Insertional variability of four transposable elements and population structure of the midge Chironomus riparius (Diptera).
The dipteran Chironomus riparius is found across the entire Palearctic region; its larvae are among the most abundant macroinvertebrates inhabiting inland waterbodies. Chironomid larvae have been extensively used in ecotoxicological and cytogenetic research, but relatively little is known on the population structure of this species. Transposable elements (TEs) are DNA sequences that are capable of autonomous replication; the number and genomic location of TE insertions varies across individuals; this variability is increasingly being used in population studies. Several TEs had been characterized in Chironomids; this enabled the analysis of insertional variability of four different TEs in six natural populations of C. riparius from Italy, Bulgaria and Russia using a PCR-based method, transposon insertion display (TID). The method allows to obtain dominant markers, similar to AFLP. In all populations, TE insertions showed high individual polymorphism, while median copy numbers of the same TEs did not vary between populations. Analysis of molecular variance (AMOVA) detected significant differentiation between populations for three of the TEs; although no correlation between genetic and geographic distances was found, the corresponding population structures were found to be significantly correlated and indicate a degree of isolation by distance. TEs belonging to different classes have different mechanisms of replication, resulting in different transposition rates of mobilization; the finding of mostly concordant population structuring for three of the TEs indicates that population dynamics contributed significantly in shaping the detected insertional polymorphism.


Recent trends of multi-source and non-destructive information for quality authentication of herbs and spices.
The growing concerns about the quality and safety of herbs and spices among consumers have increased the demand for technical testing. Recently, non-destructive analysis techniques have been widely studied and applied. Generally, a single technology has certain limitations, which are not enough to fully describe the characteristics of complex products (dynamic or complex structure). Combining non-destructive analysis technology (multi-source information) can overcome the above problems. The present review focused on applying multi-source and non-destructive information on herbs and spices quality authentication, including vibration spectroscopy and electronic sensor technologies. Then summarized and analyzed the authentication process for issues such as adulteration, contents prediction, geographical traceability, process and products analysis, and identification variety. Additionally, we presented trends in quality authentication, discussed the challenges and prospects, and made recommendations. This investigation provided clear evidence for the superiority of the quality authentication methods for herbs and spices based on multi-source and non-destructive information.


Further studies of the RNA synthesis phenotype selected during persistent infection with vesicular stomatitis virus.
Vesicular stomatitis virus (VSV) isolated from two independently established lines of persistently infected mouse L cells expressed an altered phenotype of RNA synthesis at 37 degrees, the temperature at which the persistently infected cultures were maintained (T.K. Frey and J.S. Youngner, 1982, J. Virol. 44, 167-174). In comparison to the viruses used to initiate the two lines, wild-type (wt) VSV and ts-0-23 (ts-, RNA+ complementation group III), the VSV expressing this RNA phenotype synthesized much less mRNA but equal or greater amounts of 40 S genomic RNA (rt- phenotype). In the line initiated with wt-VSV, at 17 days after initiation, when 85% of the clones were ts-, 36% of the ts- clones were rt-. By 63 days the VSV-PI population was uniformly ts- and rt- and this phenotype prevailed for at least 2 years of persistence. In the line initiated with ts-0-23, the rt- phenotype was stable for at least 3 years of persistence. To study the relationship of the ts- and rt- phenotypes which were coselected during persistence, ts+ revertants of a ts- rt- VSV-PI clone were isolated. All of the ts+ revertants expressed a wt-VSV phenotype of RNA synthesis at 37 degrees (rt+), indicating that the two phenotypic markers may be pleiotropic manifestations of the same mutation. rt-VSV inhibited host cell RNA and protein synthesis more slowly than did wt-VSV. However, rt-VSV synthesized equivalent or greater amounts of all the virus proteins, compared to wt-VSV, despite the reduced amount of mRNA transcription. The attenuated shutoff of host cell macromolecular synthesis by rt- VSV and the concomitant efficient 40 S genome replication and virus protein synthesis may in part explain the selective advantage of the rt- mutation during persistence. The rt- phenotype was not unique to persistent infection; ts- rt- mutants also evolved during serial undiluted passages of wt-VSV in L cells and one ts- rt- mutant was identified in a group of spontaneous mutants isolated from a wt-VSV stock.


A new class of sulfoxide surfactants derived from Tris. Synthesis and preliminary assessments of their properties.
A new class of non-ionic amphiphilic molecules suitable for biological purposes, especially extraction of membrane proteins, is reported. Such surfactants were prepared in two steps: addition of alkyl or fluoroalkyl mercaptan on Tris(hydroxymethyl)acrylamidomethane (THAM) derivatives, followed by the oxydation of sulfide group in sulfoxide moiety in order to provide water solubility to the molecule. The detergent efficiency of these new surfactants were assayed on rat liver cells.


Design, efficient synthesis, docking studies, and anticancer evaluation of new quinoxalines as potential intercalative Topo II inhibitors and apoptosis inducers.
As an extension for our earlier effort in the field of discovery of anticancer agents acting on DNA and Topo II, eighteen quinoxaline derivatives were designed and synthesized. Such members were designed to possess the main essential pharmacophoric features of DNA intercalators. The cytotoxic potential of the synthesized compounds was assessed against a group of human cancer cell lines (HCT-116, HepG2, and MCF-7). Doxorubicin as potential intercalative Topo II inhibitor, was used as a positive reference. In general, compounds 12, 15, 19, 21, and 22 showed promising anti-proliferative activities against the three cell lines with IC50 values ranging from 2.81 to 10.23 µM. The cytotoxicities of the most active compounds against normal human cells (WI-38) were evaluated, and the results revealed that these compounds have low toxicity. Further examination for the most active anti-proliferative members as Topo II inhibitors was also performed, showing a narrow range of the inhibitory activities (from 0.45 to 1.06 µM). In addition, DNA/methyl green assay was carried out to evaluate DNA-binding potential of such compounds. The results indicated that these compounds have strong to moderate DNA-binding affinities ranging from 33.48 to 51.23 µM. Further studies exhibited the capability of compound 22 to induce apoptosis in HepG2 cells and can arrest growth of such cells at G2/M phase. Also, compound 22 produced a significant increase in the level of caspase- 3 (10 folds) and caspase-9 (7 folds) compared to the control cells. Molecular docking studies were also conducted to investigate possible binding interactions between the target compounds and the DNA-Topo II complex.


Scientific rationale for a higher dose of nusinersen.
The long-term favorable safety profile of nusinersen provides an opportunity to consider a higher dose. We report on the relationships between nusinersen cerebrospinal fluid (CSF) exposure, biomarker levels, and clinical efficacy. The analyses used data from the CS3A and ENDEAR studies of nusinersen in participants with infantile-onset spinal muscular atrophy (SMA). Steady-state CSF trough (Ctrough ) levels, plasma phosphorylated neurofilament heavy chain (pNF-H) levels, body weight, and Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) scores were selected as parameters of interest. A validated population pharmacokinetic (PK) model was applied to predict the nusinersen CSF Ctrough . PK/pharmacodynamic (PK/PD) models used nusinersen CSF Ctrough measurements, which were time-matched with CHOP INTEND scores. Higher nusinersen CSF exposure was associated with a greater decrease in pNF-H levels and greater efficacy, as measured by change in the CHOP INTEND score from baseline. These findings indicate a dose-response relationship between CSF nusinersen levels and treatment response. The higher dose is predicted to lead to approximately a 2.4-fold increase in nusinersen CSF levels with fewer loading doses. PK/PD modeling indicates that a higher concentration of nusinersen may predict an additional 5-point increase in CHOP INTEND score beyond that observed with 12 mg. Our data indicate that a higher dose of nusinersen may lead to additional clinically meaningful improvement in efficacy when compared with the currently approved 12-mg dose. The efficacy, safety, and PK of a higher nusinersen dose are currently under investigation in the ongoing phase 2/3 DEVOTE study (NCT04089566).


Identification of novel RMRP mutations and specific founder haplotypes in Japanese patients with cartilage-hair hypoplasia.
Cartilage-hair hypoplasia (CHH), or metaphyseal dysplasia, McKusick type, is an autosomal recessive disease with diverse clinical manifestations. CHH is caused by mutations in RMRP (ribonuclease mitochondrial RNA processing), the gene encoding the RNA component of the ribonucleoprotein complex RNase MRP. A common founder mutation, 70A>G has been reported in the Finnish and Amish populations. We screened 11 Japanese patients with CHH for RMRP mutations and identified mutations in five probands, including three novel mutations (16-bp dup at +1, 168G>A, and 217C>T). All patients were compound heterozygotes for an insertion or duplication in the promoter or 5'-transcribed regions and a point mutation in the transcribed region. Two recurrent mutations were unique to the Japanese population: a 17-bp duplication at +3 and 218A>G. Haplotype analysis revealed that the two mutations common in Japanese individuals were contained within distinct haplotypes. Through this analysis, we have identified a unique mutation spectrum and founder mutations in the Japanese population.


Association Between Dietary Fiber Intake and Risk of Depression in Patients With or Without Type 2 Diabetes.
Depression and type 2 diabetes (T2D) are both serious public health problems, with morbidity and mortality in people increasing year by year, resulting in a heavy economic burden. A correlation between dietary fiber and both has been reported. Nevertheless, few data are available concerning dietary fiber and the risk of depression with or without T2D, which deserve further attention. We assessed the relationship between dietary fiber intake and risk of depression with or without T2D in the 2007-2014 National Health and Nutrition Examination Survey (NHANES) population. A 24-h dietary review was used to assess fiber intake. The Patient Health Questionnaire-9 was used to assess depression. Stability of the results was assessed using restricted cubic spline models and logistic regression, as well as sensitivity analyses. A total of 17,866 adults aged 20 years and older with a mean age of 49.3 ± 17.7 years were included in this study, of whom 49.5% were male. After adjusting for covariates, the association of dietary fiber intake with the risk of depression appeared to differ between non-T2D group and T2D group (OR, 0.987; 95% CI, 0.979-0.995 vs. OR, 1.003; 95% CI, 0.988-1.017). Furthermore, when dietary fiber was converted to a categorical variable, there was evidence of interaction between T2D status and fiber intake on decreasing the prevalence of depression (P-value for interaction = 0.015). Sensitivity analysis showed stable results. Our findings indicated that whether a patient has T2D may affect the relationship between dietary fiber intake and the risk of depression, which still needs to be confirmed by further randomized controlled trials.


Ambulatory management of chemotherapy-induced fever and neutropenia in adult cancer patients.
To review the literature on the management of low-risk adults with chemotherapy-induced fever and neutropenia (CIFN). Included in the review are methods to identify these patients, management options, and economic impact associated with nontraditional treatment options. A MEDLINE and bibliographic search (January 1966-December 1997) for all English-language studies evaluating the identification and treatment of adult, low-risk CIFN patients was completed. Reference lists from identified articles also served as literature sources. All human studies identified from the data sources were evaluated. Pertinent information, excluding pediatric studies, was selected and critically evaluated for discussion. Alterations in prominent bacterial isolates in CIFN, newer antibiotic choices, enhanced focus on patient comfort, and cost-containment directives have promoted recent research identifying adult cancer patients with low-risk CIFN. Using this information to select low-risk CIFN patients, several investigators have completed trials using antibiotic therapy applicable to the ambulatory setting. Additionally, some investigators have included the use of an oral outpatient antibiotic regimen. Limited data indicate that this approach is a reasonable treatment option for selected patients. A subset of adult patients with CIFN are at low risk for serious morbidity and mortality when treated with broad-spectrum antibiotics in the ambulatory setting. Managing these patients with this approach requires close patient selection, intense follow-up, data collection, and ongoing evaluation to determine efficacy and patient safety. Currently, ambulatory treatment with oral antibiotics for CIFN is not considered standard of care. Further studies of larger size designed to confirm low-risk patient characteristics and optimal antibiotic selection are required.


Microglial LOX-1/MAPKs/NF-κB positive loop promotes the vicious cycle of neuroinflammation and neural injury.
Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a member of the scavenger receptor family, recognizes multiple ligands and participates in several inflammatory responses, but its function within the central nervous system (CNS) remains unclear. In this study, we discovered an increased LOX-1 expression in activated microglia in vivo and in vitro. Employing the specific inhibitors, we found that conditioned medium of necrotic neurons (Necrotic-CM) induced microglial LOX-1 expression through the MAPKs/NF-κB pathway. Silencing LOX-1 inhibited MAPK phosphorylation, NF-κB-p65 nuclear transportation, and pro-inflammatory factor production in microglia exposed to Necrotic-CM. Furthermore, utilizing the conditioned medium of activated microglia (MG-CM), we discovered microglial LOX-1 aggravated the neuroinflammation-induced neuronal apoptosis. Collectively, a LOX-1/MPAKs/NF-κB positive loop might promote microglia activation and drive the vicious cycle of neuroinflammation and neuronal injury.


Analysis of simple reaction time to a sinusoidal grating by means of a linear filter model of the detection process.
Simple reaction time (RT) to a sinusoidal grating was analyzed in terms of a linear filter model of the detection process. First, RT contrast functions were determined over a wide range of spatial frequencies and retinal illuminances. Second, calculating the time course of the linear filter's response, theoretical visual latency contrast functions were derived for the same conditions of spatial frequency and retinal illuminance as those in the RT measurements. Comparison of the two functions showed that the contrast dependence of the RT functions was much larger than that of the visual latency functions. The discrepancy between the two functions was satisfactorily described as a power function of the slope of the filter's response at threshold level. On the basis of these results, we propose a model of the RT process. According to the model, the RT process is mediated by a cascade that consists of a level detector, which includes a linear filter followed by a threshold device, and a differentiator of the filter's response.


Removal of a ring causing penile strangulation with dental high speed turbine.
Penile strangulation is a rare emergencythat requires prompt evaluation and treatment to avoid disastrous consequences. A 33-year-old male presented to the emergency department with complaints of severe penile pain and swelling for 10 hours.Dental high speed turbine is an effective means to quickly remove plastic rings.This method can provide immediate relief with no issue of heat transfer.


A Randomized Controlled Study Comparing the Efficacy of Autologous Smashed Follicular Dermal Graft and Epidermal Cell Suspension versus Normal Saline Dressing in the Treatment of Chronic Nonhealing Trophic Ulcers in Patients with Hansen's Disease.
Trophic ulcers remain the most common reason for hospitalization in patients with Hansen's disease. With the introduction of new therapeutic regimens, leprosy can now be cured. However, complications of the disease, such as sensory loss, muscle palsy, absorption of extremities, and recurrent ulcers, still lead to substantial morbidity. The management of patients with trophic ulcers and their consequences is difficult, because it is a recurrent and recalcitrant problem. To evaluate the efficacy of autologous smashed follicular dermal graft and epidermal cell suspension (ECS) in the treatment of chronic nonhealing trophic ulcers in patients with Hansen's disease and to compare its efficacy with normal saline dressing. A total of 46 chronic nonhealing trophic ulcers were randomized into two groups (23 ulcers in each): Ulcers in Group A were treated with autologous smashed follicular dermal graft and ECS; ulcers in Group B were treated with normal saline dressings. Ulcers were assessed based on the rate of ulcer size reduction at every week till 12 weeks and then once a month till the sixth month. All 23 (100%) ulcers in Group A had healed within the study period of six months, whereas only 14 (60.9%) ulcers had healed in Group B. Nine (39.1%) ulcers in Group B had not healed even at the end of six months. All 23 (100%) ulcers in Group A had healed within eight weeks, which was statistically significant, P value <0.05. Trophic ulcers heal faster by autologous smashed follicular dermal graft and ECS, with good results of re-epithelialization of the ulcer bed than by normal saline dressing.


Detection of virus and cellular-determined antigens in situ using [125I]protein A and autoradiography.
The present paper describes the use of [125I]Protein A, isolated from Staphylococcus aureus, in detecting antigen-antibody complexes by autoradiography on single cells. the method is relatively quick, reproducible, potentially more sensitive than immunofluorescence, and should be useful in combination with conventional radioimmuno-assays. We have used it to detect the cellular expression of IgM, kappa, lambda, and beta 2-microglobulin, as well as the expression of Epstein-Barr Virus (EBV)-associated antigens expressed in human lymphoblastoid cell lines.


Differential relationships of NMDAR hypofunction and oxidative stress with cognitive decline.
NMDAR hypofunction and oxidative stress are implicated in the pathogenesis of Alzheimer's disease. D-amino acid oxidase (DAO) regulates NMDAR function. Glutathione, superoxide dismutase, and catalase are three first-line endogenous antioxidants. This study explored the associations of these potential biomarkers with mild cognitive impairment. Cognitive function and blood levels of DAO, glutathione, superoxide dismutase, and catalase were measured in 63 mild cognitive impairment patients and 24 healthy individuals every 6 months for 2 years. Among the patients, DAO and glutathione levels at baseline contributed to the cognitive decline 2 years later. Among the healthy individuals, only glutathione levels were associated with cognitive change. The four biomarkers differed in change directions (upward vs. downward) in the patients and in the healthy individuals. Among patients, glutathione levels were negatively correlated with superoxide dismutase and positively correlated with catalase, and DAO levels were negatively correlated with superoxide dismutase. To our knowledge, this is the first study to demonstrate the differential associations of NMDAR hypofunction and oxidative stress with cognitive change between the mild cognitive impairment patients and healthy people. Glutathione may be regarded as an aging marker for both mild cognitive impairment and normal aging; and DAO, a biomarker exclusively for mild cognitive impairment.


Integrated multi-omics profiling of nonfunctioning pituitary adenomas.
Genetic and epigenetic alterations are involved in pituitary adenoma pathogenesis, however the molecular basis of proliferative nonfunctioning pituitary adenomas (NFPAs) remains unclear. Here, we analyzed integrated multi-omics profiling including copy number variation (CNV), DNA methylation and gene expression of 8 NFPAs. We collected 4 highly proliferative (hpNFPA, Ki-67 ≥ 3) and 4 lowly proliferative (Ki-67 ≤ 1) NFPAs, and comprehensively assessed CNV, DNA methylation, and gene expression by Illumina HumanMethylation450 BeadChip and Affymetrix GeneChip PrimeView Human Gene Expression Array. We performed Ingenuity Pathway Analysis (IPA) for differentially expressed genes to illustrate aberrant pathways and delineated protein-protein networks of selected key genes in dysregulated pathways. Aberrant arm level CNV, dysregulated DNA methylation, and associated impacts on gene expressions were observed in 2 early occurring hpNFPAs. Chromosomal losses were associated with attenuated expression of DNA methyltransferases, further altering global methylation in these 2 samples. Correlation analysis between DNA methylation and gene expression in 8 NFPAs indicates methylation in promoter and gene body regions are both involved in gene regulation. IPA showed PPARα/RXRα, dopamine receptor signaling, cAMP-mediated signaling, and calcium signaling were all activated, while p38 MAPK and ERK5 signaling were inhibited in hpNFPAs. Moreover, selected key gene networks in hpNFPAs exhibited concurrent methylation status and expression levels of adenylate cyclase genes, G protein subunits, HLA genes, CXCL12, and CCL2. This study presents comprehensive multi-omics views of CNV, DNA methylation, and gene expression in 8 NFPAs. Pathway analysis and network maps of key genes provide clues to elucidate the molecular basis of hpNFPA.


[A preliminary evaluation on transcranial Dopplor ultrasonic scanning for differentiation of symptoms and signs in patients with ganyang shangkangzheng].
Intracranial main artery of Ganyang Shangkangzheng and its related syndrome were determined by Transcranial Doppler (TCD) Ultrasonography. The results showed that the blood flow speed in the mid-cerebral artery of 32 cases with Ganyang Shangkangzheng was obviously higher than that of the healthy group, Ganhuo Shangyan group and Gan-shenyinxu group, similar change was found in three kinds of parameters in the blood flow speed. Therefore, the results suggest that TCD in determinating the blood flow speed of middle cerebral artery can be thought as one of the diagnostic assays in differentiation of symptom and sign of Ganyang Shangkangzheng.


Early Magnetic Resonance Imaging Features of New Paramagnetic Rim Lesions in Multiple Sclerosis.
To determine early magnetic resonance imaging (MRI) features of new multiple sclerosis (MS) lesions that will develop into paramagnetic rim lesions (PRLs), which have been associated with progressive tissue injury in MS. New contrast-enhancing lesions observed on routine clinical MRI were imaged at 7 T within 4 weeks of observation, and 3 and 6 months later. The 6-month MRI was used to classify PRL status (PRL or non-PRL). The relationship between early lesion characteristics and subsequent PRL status was assessed using generalized linear mixed effects models. Random forest classification was performed to classify early predictors of subsequent PRL status. From 93 contrast-enhancing lesions in 23 MS patients, 37 lesions developed into a PRL. In lesions that developed into PRLs compared with those that did not, the average lesion T1 on the initial 7 T MRI was 1994 ms compared with 1,670 ms (p-value <0.001), and the average volume was 168.7 mL compared with 44 mL (p-value <0.001) in lesions that did not. These volume differences were also found on 3 T scans (p-value <0.001), and for intensity-normalized T1 -w (p-value = 0.011) and fluid-attenuated inversion recovery (p-value = 0.005). The area under the receiver operating characteristic curve for the random forest classification with leave-one-out cross-validation was found to be 0.86 using initial 7 T features. New MS lesions that evolve into PRLs can be identified early in lesion evolution. These findings suggest that biological mechanisms underlying PRL development begin early, which has important implications for clinical trials targeting PRLs development and subsequent therapeutics. ANN NEUROL 2023;94:736-744.


Identification of a novel allele, HLA-B*15:01:23, in a platelet donor by sequence-based typing.
HLA-B*15:01:23 has 1 synonymous nucleotide change from HLA-B*15:01:01:01 at nucleotide 393 (codon 107 glycine).


Intussusception in children with ALL receiving chemotherapy for acute lymphoblastic leukaemia.
Acute abdominal complications of chemotherapy are common but the differential diagnosis wide. We describe two cases of intussuception of the bowel in children receiving chemotherapy for acute lymphoblastic leukaemia (ALL) and discuss how a high clinical suspicion is critical for the correct diagnosis to be made rapidly.


Hepatitis B genotypes in Aboriginal and Torres Strait Islander Australians: correlation with clinical course and implications for management.
The prevalence of chronic hepatitis B (CHB) in Aboriginal and Torres Strait Islander Australians in Far North Queensland (FNQ) is greater than twice that of the general Australian population. CHB is common in Torres Strait Islanders diagnosed with hepatocellular carcinoma (HCC) - and in Aboriginals with HCC living in the Northern Territory - however, Aboriginals diagnosed with HCC in FNQ very rarely have CHB. The explanation for this apparent disparity is uncertain. To determine the HBV genotypes in the FNQ Aboriginal and Torres Strait Islander population and their correlation with clinical phenotype. We determined the HBV genotype of Aboriginal and Torres Strait Islander Australians living with CHB in FNQ and correlated this with demographic and clinical findings. 134/197 (68%) enrolled individuals had a sufficient viral load for genotyping. All 40 people with HBV/D genotype had Aboriginal heritage, whereas 85/93 (91%) with HBV/C had Torres Strait Islander heritage (P < 0.0001). Individuals with HBV/D were younger than those with HBV/C (median (interquartile range) age: 43 (39-48) vs 53 (42-66) years, P = 0.0002). However, they were less likely to be HBeAg positive (1/40 (3%) vs 23/93 (25%), P = 0.001). All three HCCs developed in Torres Strait Islanders; two-thirds were infected with HBV/C14; genotyping was not possible in the other individual. All 10 diagnoses of cirrhosis occurred in Torres Strait Islanders, 6/10 were infected with HBV/C14, genotyping was not possible in the other four individuals. HBV genotypes in Aboriginal and Torres Strait Islander Australians in FNQ differ markedly, which could explain the significant differences in the clinical phenotype in the two populations and might be used to inform cost-effective CHB care in the region.


Oxalic acid production from lipids by a mutant of Aspergillus niger at different pH.
Crude rapeseed oil and post-refining fatty acids were used as substrates for oxalic acid production by a mutant of Aspergillus niger. Both the final concentration and the yield of the product were highest at pH 4 to 5. With a medium containing 50 g lipids l(-1), production reached a maximum of 68 g oxalic acid l(-1) after 7 d. A high yield of the product (up to 1.4 g oxalic acid g(-1) lipids consumed) was achieved with oil and fatty acids combined.


Intravenous Injection of an AAV-PHP.B Vector Encoding Human Acid α-Glucosidase Rescues Both Muscle and CNS Defects in Murine Pompe Disease.
Pompe disease, a severe and often fatal neuromuscular disorder, is caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). The disease is characterized by the accumulation of excess glycogen in the heart, skeletal muscle, and CNS. Currently approved enzyme replacement therapy or experimental adeno-associated virus (AAV)-mediated gene therapy has little effect on CNS correction. Here we demonstrate that a newly developed AAV-PHP.B vector can robustly transduce both the CNS and skeletal muscles in GAA-knockout (GAAKO) mice. A single intravenous injection of an AAV-PHP.B vector expressing human GAA under the control of cytomegalovirus (CMV) enhancer-chicken β-actin (CB) promoter into 2-week-old GAAKO mice resulted in widespread GAA expression in the affected tissues. Glycogen contents were reduced to wild-type levels in the brain and heart, and they were significantly decreased in skeletal muscle by the AAV treatment. The histological assay showed no visible glycogen in any region of the brain and spinal cord of AAV-treated mice. In this study, we describe a set of behavioral tests that can detect early neurological deficits linked to extensive lysosomal glycogen accumulation in the CNS of untreated GAAKO mice. Furthermore, we demonstrate that the therapy can help prevent the development of these abnormalities.


Strontium-modified porous polyetheretherketone with the triple function of osteogenesis, angiogenesis, and anti-inflammatory for bone grafting.
Polyetheretherketone (PEEK) is a potential bone repair material because of its stable chemical and good mechanical properties. However, the biological inertness of PEEK limits its clinical application. Sr2+ has multi biological functions, including promoting bone formation and blood vessel regeneration and inhibiting inflammation. In this paper, PEEK was modified with Sr2+ with the purpose to construct PEEK bone graft material with triple functions of osteogenesis, angiogenesis, and anti-inflammatory. The results showed that Sr-modified PEEK could stably release Sr2+ for a long time in the PBS solution, and indeed could promote the proliferation and differentiation of osteoblasts, promote angiogenesis, and inhibit inflammation. Therefore, it is believed that this multifunctional PEEK with Sr2+ should show great promise for clinical applications in bone repair.


Risk of Depression in the Offspring of Parents with Depression: The Role of Emotion Regulation, Cognitive Style, Parenting and Life Events.
Children of depressed parents are at heightened risk for developing depression, yet relatively little is known about the specific mechanisms responsible. Since preventive interventions for this risk group show small effects which diminish overtime, it is crucial to uncover the key risk factors for depression. This study compared various potential mechanisms in children of depressed (high-risk; n = 74) versus non-depressed (low-risk; n = 37) parents and explored mediators of parental depression and risk in offspring. A German sample of N = 111 boys and girls aged 8 to 17 years were compared regarding children's (i) symptoms of depression and general psychopathology, (ii) emotion regulation strategies, (iii) attributional style, (iv) perceived parenting style and (v) life events. Children in the high-risk group showed significantly more symptoms of depression and general psychopathology, less adaptive emotion regulation strategies, fewer positive life events and fewer positive parenting strategies in comparison with the low-risk group. Group differences in positive and negative attributional style were small and not statistically significant in a MANOVA test. Maladaptive emotion regulation strategies and negative life events were identified as partial mediators of the association between parental depression and children's risk of depression. The study highlights the elevated risk of depression in children of depressed parents and provides empirical support for existing models of the mechanisms underlying transmission. Interestingly, the high-risk group was characterised by a lack of protective rather than increased vulnerability factors. These results are crucial for developing more effective preventive interventions for this high-risk population.


[Cell proliferation and migration in the roof of the mesencephalon (tectum) in Xenopus laevis tadpoles and adult frogs normally and in brain injury. II. Cell proliferation and differentiation of the tectum in frogs].
The proliferation and directions of cell differentiation in tectum opticum were studied in the young frogs under the conditions of normal development and upon brain trauma by means of 3H-thymidine autoradiography. The same types of cells were shown to be able of proliferation in both the cases: cells of the ventricle zone and glioblasts (gliocytes) in all other tectum layers. A study of directions of the tectum proliferating cells' differentiation in the frogs has shown that the proliferating cells differentiate mainly in the ependyme tanicytes in the ventricle layer 1 and gliocytes in the other tectum layers. The trauma did not change the direction of proliferating cells' differentiation towards the formation of neurons. The complete regeneration is observed in the tectum layer 1 only.


Sublethal stress in the intertidal zone: tidal emersion inhibits photosynthesis and retards development in embryos of the brown alga Pelvetia fastigiata.
The effect of tidal emersion on survivorship, photosynthesis and embryonic development was studied in 8 h old zygotes and 7 d old embryos of the intertidal brown alga Pelvetia fastigiata (J. Ag.) DeToni. Zygotes and embryos were outplanted for single low tides in the intertidal zone on the central coast of California (U.S.A.) during June, 1990. Both zygotes and embryos exhibited close to 100% survival when outplanted beneath the canopy of adult P. fastigiata. Embryos (7 d old) also exhibited high survival when outplanted in a red algal turf, the microhabitat where most successful recruitment occurs. However, zygotes (8 h old) experienced high mortality (65-90%) when outplanted in the turf microhabitat. Embryos and zygotes that survived emersion experienced sub-lethal stress that temporarily impaired light-saturated photosynthesis when plants were reimmersed in seawater. The effects of sub-lethal stress were more pronounced in 8 h old zygotes than 7 d embryos, and more severe in the turf microhabitat than beneath the adult Pelvetia canopy. Zygotes outplanted in the red algal turf did not re-establish net photosynthesis until at least 6 h after re-immersion. Photosynthesis was less inhibited in 8 h old zygotes outplanted beneath the adult Pelvetia canopy, and recovered to control (non-emersed) levels within 3 h of re-immersion. Embryos (7 d old) were able to achieve positive net photosynthesis immediately on re-immersion after emersion in the turf or canopy microhabitats. Emersion also retarded the rate of embryonic development in 8 h old zygotes, delaying the formation of primary rhizoids, which help to attach the plant to the substrate. For example, at 19 h post-fertilization, 75% of control (non-emersed) zygotes had developed rhizoids, compared to 3% and 30% for zygotes outplanted in the turf and canopy microhabitats. The different emersion responses of 8 h old zygotes and 7 d old embryos appeared to be related to their ability to tolerate cellular dehydration. Overall, our data suggest that the effects of sub-lethal stresses may have been underestimated in studies of intertidal ecology.


Piezoelectric-channels in MoS2-embedded polyvinylidene fluoride membrane to activate peroxymonosulfate in membrane filtration for wastewater reuse.
The conjugation of membrane filtration (MF) with advanced oxidation process (AOPs) is being considered as an alternative advanced treatment process for the potable reuse of wastewater. Beyond conventional MF/AOPs conjugation, a new downstream MF process with piezoelectric-channels induced piezo-activated peroxymonosulfate (PMS) is herein constructed to deal with antiepileptic carbamazepine (CBZ) pollutants through polyvinylidene fluoride (PVDF) membrane (PVDF-M10). Through a MF process, ca. 93.8% CBZ pollutants can be removed under an ultrasonic-assisted piezo-activation PMS, whereas only 18.3% and 60.2% CBZ can be removed by using pure PVDF membrane under the same condition and PVDF-M10 membrane without ultrasonic-assisted piezo-activation. Even after 9-cycles, CBZ removal efficiency was maintained at 56.4% under this MF process. These superior performances are attributed to the piezoelectric exfoliated-MoS2 nanosheets (E-MoS2) embedded PVDF nanofibers in PVDF-M10 membrane, which lead to rich piezoelectric-channels in the membrane. These piezoelectric-channels not only produced more charges to activate PMS to boost the yield of reactive oxide species (ROS) but also provided an ideal platform for the rapid reaction between CBZ and ROS during MF process. This investigation develops a new MF technique to conjugate piezo-activation of PMS-AOPs for the efficient removal of emerging pollutants for the potable reuse of wastewater.


Response of glutathione S-transferase Pi (GSTP1) to neoadjuvant therapy in rectal adenocarcinoma.
The response of rectal adenocarcinoma to neoadjuvant therapy is variable. Accurate prediction of response would enable selective administration of therapy. The enzyme glutathione S-transferase Pi (GSTP1) has been shown to influence response to therapy in some solid tumours. Few data are available for rectal cancer. The GSTP1 levels in rectal adenocarcinoma and adjacent normal mucosa were quantified before and after exposure to neoadjuvant therapy. Venous blood samples and biopsies of normal rectal mucosa and tumour were prospectively obtained from patients with primary rectal cancer. Patients were stratified by exposure to neoadjuvant therapy or surgery alone. GSTP1 was quantitatively measured using an enzyme-linked immunosorbent assay. Ninety-two patients (54 men; median age 68 years) were recruited. The median GSTP1 level was significantly higher in rectal adenocarcinoma than in matched normal mucosa [6.59 μg/mg vs 4.57 μg/mg; P < 0.001]. The median tumour GSTP1 level was significantly lower in the therapy group compared with unmatched samples from the no-therapy group [4.47 μg/mg vs 7.76 μg/mg; P < 0.001]. The GSTP1 level is increased in rectal adenocarcinoma compared with adjacent normal mucosa. It decreases following neoadjuvant therapy. Future studies correlating pre-therapy GSTP1 levels with pathological response would be of interest.


Effects of diazinon on the lymphocytic cholinergic system of Nile tilapia fish (Oreochromis niloticus).
Fish rearing under intensive farming conditions can be easily disturbed by pesticides, substances that have immunotoxic properties and may predispose to infections. Organophosphorus pesticides (OPs) are widely used in agricultural activities; however, the mechanism of immunotoxicity of these substances is unclear. The aim of this study was to evaluate the effect of diazinon pesticides (OPs) on the cholinergic system of immune cells as a possible target of OP immunotoxicity. We evaluated ACh levels and cholinergic (nicotinic and muscarinic) receptor concentration. Additionally, AChE activity was evaluated in mononuclear cells of Nile tilapia (Oreochromis niloticus), a freshwater fish mostly cultivated in tropical regions around the world. The obtained results indicate that acute exposure to diazinon induces an increase in ACh concentration and a decrease in nAChR and mAChR concentrations and AChE activity in fish immune cells, This suggests that the non-neuronal lymphocytic cholinergic system may be the main target in the mechanism of OP immunotoxicity. This study contributes to the understanding of the mechanisms of immunotoxicity of pollutants and may help to take actions for animal health improvement.


Biologic and physical characteristics of the non-peptidic, non-digitalis-like natriuretic hormone.
At least three independent groups of natriuretic hormones have been isolated over the past ten years. Two, atrial natriuretic factor (ANF) and brain natriuretic peptide (BNP), are proteins and the third is made up of digitalis-like substances (DLS). The present report concerns the isolation, substantial purification and biologic actions of an entirely different natriuretic hormone (NH) which appears to be steroidal in nature and an isomer of cortisone. The source of NH was uremic urine. Purification involved successive chromatographic steps including gel filtration and multiple HPLC runs through C-18 resins. A translucent crystal ultimately was obtained. The product was examined using mass spectroscopy with trimethylsilyl derivatization. Only one compound was identifiable. The characteristics of the molecule include: a molecular weight, 360.4; a molecular formula, C21H28O5; a steroidal nucleus; UV absorption at 220 and 290 nm; and intrinsic fluorescence. The onset of action occurs within minutes both in the rat and, as previously shown, in several in vitro systems including the frog skin, toad bladder, fibroblasts and renal tubular epithelial cells grown in culture and isolated perfused cortical collecting tubules. In contrast to DLS, NH has been previously shown not to cross react with digoxin antibodies. Moreover, when given to intact rats, it produces a profound natriuresis but little or no kaliuresis. In contrast to ANF and BNP the compound is active orally as well as intravenously. It is clearly different from cortisone, based both on its biologic and mass spectroscopic characteristics.


Synthetic polymer nanoparticles conjugated with FimH(A) from E. coli pili to emulate the bacterial mode of epithelial internalization.
Amphiphilic block copolymer nanoparticles are conjugated with uropathogenic Escherichia coli type 1 pilus adhesin FimH(A) through amidation chemistry to enable bladder epithelial cell binding and internalization of the nanoparticles in vitro.


Mapping Auditory Synaptic Circuits with Photostimulation of Caged Glutamate.
Photostimulation of neurons with caged glutamate is a viable tool for mapping the strength and spatial distribution of synaptic networks in living brain slices. In photostimulation experiments, synaptic connectivity is assessed by eliciting action potentials in putative presynaptic neurons via focal photolysis of caged glutamate, while measuring postsynaptic responses via intracellular recordings. Two approaches are commonly used for delivering light to small, defined areas in the slice preparation; an optical fiber-based method and a laser-scanning-based method. In this chapter, we outline the technical bases for using photostimulation of caged glutamate to map synaptic circuits, and discuss the advantages and disadvantages of using fiber-based vs. laser-based systems.


3D printed model for triple negative inflammatory breast cancer.
Access to imaging reports and review of the breast imaging directly with a patient with breast cancer helps improve the understanding of disease extent and severity. A 3D printed breast model can further enhance a patient's understanding and communication with the healthcare team resulting in improved patient comprehension and patient input with reduced treatment decision conflict. Furthermore, 3D printed models can facilitate training of residents and fellows involved in the diagnosis and treatment management of breast cancer. We present a 3D printed breast tumor model segmented from positron electron tomography/computed tomography and fabricated via desktop vat polymerization as proof of concept for treatment planning for a patient diagnosed with triple negative inflammatory breast carcinoma. We illustrate benefits and indications for 3D printing in the management of breast cancer and specifically inflammatory breast cancer in this case. Fabrication and implementation of 3D printed models enhances patient's understanding and communication with the healthcare team regarding their condition, treatment options and anticipated outcomes. It provides personalized treatment planning by examining patient-specific pathology and the anatomic spatial relationships. Furthermore, 3D printed models facilitate medical education for trainees across disciplines involved in the patient's care.


Double hairpin elements and tandem repeats in the non-coding region of Adenoides eludens chloroplast gene minicircles.
Dinoflagellate plastid genomes are unique in having a reduced number of genes, most of which are found on unigenic minicircles of 2-3 kb. Although the dinoflagellate Adenoides eludens has larger minicircles of about 5 kb, they still carry only one gene. In addition, digenic circles of about 10 kb were detected and mapped by PCR. The non-coding regions of both unigenic and digenic circles share a number of common features including a pair of conserved cores in opposite orientation, four large families of tandem repeats and a number of double hairpin elements (DHEs). They most closely resemble the non-coding regions of the Symbiodinium psbA minicircles, but are much longer, less conserved and have an even greater variety of DHEs and tandem repeats. The presence of so many recombinogenic elements suggests models for the origin of minicircles from a multigenic ancestral chloroplast genome, and raises the possibility of recombination-directed replication rather than defined replication origins in the minicircles.


Is recycling of buildings a healthy alternative for the hospital industry?
Recycling, or reuse as it's called in the construction industry, works for paper and aluminum--then, why not for entire buildings?


Photoinduced oxygen transfer and double-linkage isomerism in a cis-(NO)(NO2) transition-metal complex by photocrystallography, FT-IR spectroscopy and DFT calculations.
Photocrystallographic experiments show that laser exposure of crystals of [Ru(bpy)2(NO)(NO2)](PF6)2 at 90 K produces a double isonitrosyl-nitrito linkage isomer and provide the detailed geometry of the metastable species generated. The analysis indicates that the isomerization is accomplished through an intramolecular redox reaction involving oxygen transfer from the nitro to the nitrosyl group. At 200 K only a single (nitrito) linkage isomer is formed with a U-shaped conformation of the nitrito group rather than the Z conformation observed at 90 K. A mechanism for the isomerization is proposed based on the crystallographic results and FTIR data collected at low temperatures during the isomerization process. The study presents the first structural evidence for double linkage isomerization in transition-metal complexes.


Raloxifene and bazedoxifene as selective ALDH1A1 inhibitors to ameliorate cyclophosphamide resistance: A drug repurposing approach.
Cyclophosphamide (CP) is one of the most widely used anticancer drugs for various malignancies. However, its long-term use leads to ALDH1A1-mediated inactivation and subsequent resistance which necessitates the development of potential ALDH1A1 inhibitors. Currently, ALDH1A1 inhibitors from different chemical classes have been reported, but these failed to reach the market due to safety and efficacy problems. Developing a new treatment from the ground requires a huge amount of time, effort, and money, therefore it is worthwhile to improve CP efficacy by proposing better adjuvants as ALDH1A1 inhibitors. Herein, the database constituting the FDA-approved drugs with well-established safety and toxicity profiles was screened through already reported machine learning models by our research group. This model is validated for discriminating the ALDH1A1 inhibitors and non-inhibitors. Virtual screening protocol (VS) from this model identified four FDA-approved drugs, raloxifene, bazedoxifene, avanafil, and betrixaban as selective ALDH1A1 inhibitors. The molecular docking, dynamics, and water swap analysis also suggested these drugs to be promising ALDH1A1 inhibitors which were further validated for their CP resistance reversal potential by in-vitro analysis. The in-vitro enzymatic assay results indicated that raloxifene and bazedoxifene selectively inhibited the ALDH1A1 enzyme with IC50 values of 2.35 and 4.41 μM respectively, whereas IC50 values of both the drugs against ALDH2 and ALDH3A1 was >100 μM. Additional in-vitro studies with well-reported ALDH1A1 overexpressing A549 and MIA paCa-2 cell lines suggested that mafosfamide sensitivity was further ameliorated by the combination of both raloxifene and bazedoxifene. Collectively, in-silico and in-vitro studies indicate raloxifene and bazedoxifene act as promising adjuvants with CP that may improve the quality of treatment for cancer patients with minimal toxicities.


A comparison of hormonal profiles between breast cancer and benign breast disease: a case-control study.
Benign breast disease (BBD), particularly proliferative BBD, is an established breast cancer risk factor. However, there has been no systematic attempt to compare the hormonal profiles of the two conditions. In a case-control investigation in Athens, Greece, we compared levels of estrogens, testosterone and insulin-like growth factor-1 (IGF-1), as well as their principal binding proteins, between breast cancer patients, women with BBD by histological type (proliferative and nonproliferative) and women with no breast pathology. We studied 466 women with incident breast cancer, 704 women with BBD and 244 healthy women. We used multiple regression to compare log-transformed serum hormone levels of breast cancer patients with those of healthy women and women with BBD by histological type (proliferative and nonproliferative BBD). The hormonal profile of breast cancer in our study was in line with the generally accepted hormonal profile of this disease, as reported from large cohort studies. Compared with healthy women, breast cancer patients tended to have higher levels of steroid hormones. The evidence was strong for estrone (difference 21.5%, P < 0.001), weaker for testosterone (difference 15.8%, P = 0.07) and weaker still for estradiol (difference 12.0%, P = 0.18). Also compared with healthy women, breast cancer patients had barely higher levels of IGF-1 (difference 2.0%, P = 0.51), but had significantly lower levels of IGF binding protein 3 (IGFBP-3) (difference -6.7%, P = 0.001). Compared with women with BBD, breast cancer patients had nonstatistically significantly lower levels of steroid hormones, but they had higher levels of IGF-1 [difference 5.5%, 95% confidence interval (CI) 0.7% to 10.6%] and lower levels of IGFBP-3 (difference -3.7%, 95% CI -6.7% to -0.7%). Differences were more pronounced when breast cancer patients were contrasted to women with proliferative BBD. Our findings suggest that high levels of IGF-1 may be an important factor toward the evolution of BBD to breast cancer.


Dystrophin as a focal adhesion protein. Collocalization with talin and the Mr 48,000 sarcolemmal protein in cultured Xenopus muscle.
Monoclonal antibodies against dystrophin and the postsynaptic 58 kDa protein from Torpedo electric organ were used to localize homologs of these proteins in cultured skeletal muscle (Xenopus laevis). The Xenopus homolog is an Mr 48,000 protein and, like dystrophin, is a sarcolemmal protein. Both proteins localized precisely to talin-positive sites, hence with each other, on the substrate-apposed sarcolemma. Therefore, the first sites of appearance of dystrophin on cultured muscle cells are focal adhesions, i.e. specific sites of cytoskeleton/extracellular matrix interaction. These data also add to evidence that dystrophin and the 58 kDa act together.


Data-driven hypothesis generation among inexperienced clinical researchers: A comparison of secondary data analyses with visualization (VIADS) and other tools.
To compare how clinical researchers generate data-driven hypotheses with a visual interactive analytic tool (VIADS, a visual interactive analysis tool for filtering and summarizing large data sets coded with hierarchical terminologies) or other tools. We recruited clinical researchers and separated them into "experienced" and "inexperienced" groups. Participants were randomly assigned to a VIADS or control group within the groups. Each participant conducted a remote 2-hour study session for hypothesis generation with the same study facilitator on the same datasets by following a think-aloud protocol. Screen activities and audio were recorded, transcribed, coded, and analyzed. Hypotheses were evaluated by seven experts on their validity, significance, and feasibility. We conducted multilevel random effect modeling for statistical tests. Eighteen participants generated 227 hypotheses, of which 147 (65%) were valid. The VIADS and control groups generated a similar number of hypotheses. The VIADS group took a significantly shorter time to generate one hypothesis (e.g., among inexperienced clinical researchers, 258 seconds versus 379 seconds, p = 0.046, power = 0.437, ICC = 0.15). The VIADS group received significantly lower ratings than the control group on feasibility and the combination rating of validity, significance, and feasibility. The role of VIADS in hypothesis generation seems inconclusive. The VIADS group took a significantly shorter time to generate each hypothesis. However, the combined validity, significance, and feasibility ratings of their hypotheses were significantly lower. Further characterization of hypotheses, including specifics on how they might be improved, could guide future tool development.


Effectiveness of endoscopic sphincterotomy in complicated hepatic hydatid disease.
The aim of this study was to evaluate the results of endoscopic sphincterotomy in patients with hepatic hydatid cysts that have ruptured into the biliary tract. Over a 10-year period, 25 patients (11 men, 14 women, mean age 60 years) underwent treatment; 13 with no prior surgery were treated for biliary obstruction. Postoperative treatment was undertaken in 12 cases because of persistent drainage (8), duct obstruction (3), and postoperative pancreatitis (1). In patients who had not undergone previous surgery, cholangiographic findings were hydatid vesicles in the biliary tract (6), dilation of the biliary tract (3), biliary fistula (2), distal stenosis (1), and purulent bile content after sphincterotomy (1). In all of these cases, sphincterotomy resolved duct obstruction with no complications. All patients with persistent postoperative drainage had a fistula tract between the biliary duct and the cavity, which was resolved by endoscopic treatment in all 8. The 3 patients with postoperative biliary obstruction had hydatid vesicles in the biliary tract, one with a long stenosis resembling sclerosing cholangitis, whereas the patient with postoperative pancreatitis had a distal stenosis. Satisfactory results were obtained with endoscopic sphincterotomy, although 1 patient required a biliary prosthesis. Endoscopic sphincterotomy resolves biliary obstruction and postoperative fistulae in most patients with hepatic hydatid cysts that have ruptured into the biliary tract. In some cases, a biliary prosthesis may be required.


In vitro and in vivo studies of ultrafine-grain Ti as dental implant material processed by ECAP.
The aim of this study was to investigate the surface characterization of ultrafine-grain pure titanium (UFG-Ti) after sandblasting and acid-etching (SLA) and to evaluate its biocompatibility as dental implant material in vitro and in vivo. UFG-Ti was produced by equal channel angular pressing (ECAP) using commercially pure titanium (CP-Ti). Microstructure and yield strength were investigated. The morphology, wettability and roughness of the specimens were analyzed after they were modified by SLA. MC3T3-E1 osteoblasts were seeded onto the specimens to evaluate its biocompatibility in vitro. For the in vivo study, UFG-Ti implants after SLA were embedded into the femurs of New Zealand rabbits. Osseointegration was investigated though micro-CT analysis, histological assessment and pull-out test. The control group was CP-Ti. UFG-Ti with enhanced mechanical properties was produced by four passes of ECAP in BC route at room temperature. After SLA modification, the hierarchical porous structure on its surface exhibited excellent wettability. The adhesion, proliferation and viability of cells cultured on the UFG-Ti were superior to that of CP-Ti. In the in vivo study, favorable osseointegration occurred between the implant and bone in CP and UFG-Ti groups. The combination intensity of UF- Ti with bone was higher according to the pull-out test. This study supports the claim that UFG-Ti has grain refinement with outstanding mechanical properties and, with its excellent biocompatibility, has potential for use as dental implant material.


Risk factors for hospital-acquired urinary tract infection: a case-control study.
The objective is to assess risk factors and microbiological aspects of hospital-acquired urinary tract infection (HAUTI) on six wards of a general regional hospital in Serbia. A case-control study was nested within prospective cohort HAUTIs study conducted from January 1 to December 31, 2007. Three controls were identified for each patient with HAUTI, being chronologically the next three patients surveyed who did not develop HAUTI. The patients and controls were matched by sex and age (±5 years). Assessment of 8,467 patients during the study period revealed HAUTI in 125 (116 symptomatic and 9 asymptomatic). The overall incidence rate of HAUTI was 14.8 cases/1,000 admissions. The mean age (range) of cases and controls was 64.9 (18-85) and 65.2 (17-86), respectively. Multivariate logistic regression analysis showed that duration of catheterization >5 days (OR = 51.91; 95% CI = 23.46-114.82) and the ASA score (OR = 13.42; 95% CI = 2.14-84.30) were independently associated with increased risk of HAUTIs. The most frequently isolated Gram-negative bacteria were Enterobacter, Klebsiella sp., Proteus mirabilis and Escherichia coli. Enterococcus sp. was the most frequent Gram-positive bacteria.


Potential pitfalls and methods of improving in utero diagnosis of transposition of the great arteries, including the baby bird's beak image.
The goal of this study was to analyze our recent experience with fetuses with transposition of the great arteries (TGA) to identify potential pitfalls and possible methods to better detect conotruncal anomalies such as TGA. We analyzed all nonreferral obstetric ultrasound examinations in which we performed basic, targeted, or formal fetal echocardiography with a newborn diagnosis of TGA. Nine neonates had TGA. Five of these cases were diagnosed prenatally, and 4 of these had complex congenital heart abnormalities. In these 4 cases, there were abnormalities in the cardiac axis (n = 3), abnormal valves or ventricular size (n = 2), and ventricular septal defects (n = 3) that were detected on the 4-chamber view of the heart. In all cases that were not detected prenatally, both prospective and retrospective reviews of the 4-chamber heart appeared normal. The prospective analyses of the outflow tracts were all interpreted as normal, whereas the retrospective review showed subtle abnormalities such as the "baby bird's beak" image. In review of these cases, there was failure to show the "crisscross" relationship of the outflow tracts. In 1 case, 5 short axis views of the heart, retrospectively showed the artery originating from the left ventricle and bifurcated, representing the pulmonary artery. Transposition of the great arteries may be associated with complex cardiac disease that could be detected on the 4-chamber view of the heart. When the 4-chamber view is normal, it is important to identify the crisscross relationship of the outflow tracts. If this is not done, it is important to document that the pulmonary artery bifurcates and originates from the right ventricle. Five short axis views of the heart may be helpful to detect conotruncal abnormalities.


Preparation of the TiO2/Graphic Carbon Nitride Core-Shell Array as a Photoanode for Efficient Photoelectrochemical Water Splitting.
The photoelectrochemical (PEC) oxygen evolution reaction over a photoanode is a promising process for renewable energy. The fascinating properties of graphic carbon nitride (g-CN) in water splitting make the photoelectrode engineering of it for PEC use quite meaningful. In this work, we report the fabrication of the core-shell-structured TiO2/g-CN composite film by hydrothermal growth for TiO2 nanorod arrays and solvothermal growth for the g-CN layer. Herein, TiO2 is used as an effective electron-transfer layer, and g-CN is used as a visible light absorption layer. Different reaction conditions were investigated in order to obtain the uniform TiO2/g-CN nanorod core-shell structure. Outstanding photoelectrochemical performances of the optimized composites were obtained compared to that of pristine TiO2 or g-CN because the high-quality heterojunction between g-CN and TiO2 turned out to effectively reduce the recombination of charge carriers and improve the photoelectric conversion ability. Thus, the photocurrent density under visible light of TiO2/g-CN reached 80.9 μA cm-2, which is 21 times that of g-CN under 0.6 V (vs SCE). Finally, a systematic photoelectrocatalytic mechanism of charge carrier migration and the recombination path in the TiO2/g-CN nanorod core-shell heterojunction was proposed, which can be considered to be a probable explanation of efficient PEC performance.


Bilirubin entry into and clearance from rat brain during hypercarbia and hyperosmolality.
Brain bilirubin concentrations are increased by hyperosmolality and hypercarbia, but the mechanism is not known. The same applies to the mechanism for preferential localization of bilirubin to basal ganglia. Young Sprague-Dawley rats were used. Groups were: control (n = 15), hypercarbia (n = 16, pH approximately 6.95), and hyperosmolality (n = 13, serum osmolality approximately 390 mosm/L). Hyperbilirubinemia was induced by a 5-min infusion of 50 mg/kg bilirubin, containing approximately 20 microCi [3H]bilirubin. Rats were killed at 15-min intervals up to 60 min, and the brains were flushed in situ, dissected into seven regions, weighed, and dissolved. Brain bilirubin was determined by scintillation counting. The half-life of bilirubin in brain was calculated by exponential fitting, which also allowed an estimation of brain bilirubin at the end of the bilirubin bolus. The kinetics of bilirubin clearance from brain were first order. The half-life of bilirubin in brain was significantly prolonged in hyperosmolality (38.2 +/- 28.8 min [mean +/- SD]) compared with control (16.1 +/- 7.7 min) and hypercarbia (12.6 +/- 8.6 min) (F = 12.6, p < 0.0001 after log transformation) results. The estimated acute entry of bilirubin into brain was significantly increased in hypercarbia (13.9 +/- 7.4 nmol/g) compared with control (5.6 +/- 2.1 nmol/g) and hyperosmolality (6.5 +/- 2.1 nmol/g) (F = 19.2, p < 0.0001 after log transformation) results. There were no significant differences between brain regions in acute entry or clearance of bilirubin. The kinetics of increased brain bilirubin differ between hypercarbia (increased acute entry) and hyperosmolality (delayed clearance). Preferential localization of bilirubin to basal ganglia is not produced under, and may not be explained by, the conditions investigated.


SIMPSON - an important driver for numerical simulations in solid-state NMR spectroscopy.
We present a historical recollection on the development of the software package SIMPSON (SIMulation Package for SOlid-state Nmr). This covers a brief description of the underlying ideas and events leading to creation of SIMPSON and numerous auxiliary programs as well as comments on its impact on the development and application of solid-state NMR in research laboratories world-wide.


Partially folded conformation of the (30-51) intermediate in the disulphide folding pathway of bovine pancreatic trypsin inhibitor. 1H and 15N resonance assignments and determination of backbone dynamics from 15N relaxation measurements.
An analogue of the important folding intermediate of BPTI with only the disulphide bond between Cys30 and Cys51 has been characterized by 1H and 15N NMR techniques. In particular, the dynamics of the polypeptide backbone were characterized using (1H)-15N NOE and 15N T1 and T2 relaxation data. The intermediate is partially folded, with part of the polypeptide chain stably folded and the remainder flexible or unfolded. The folded portion consists of the major elements of native-like secondary structure interacting through the hydrophobic core of the molecule. The 15N relaxation data show that the N-terminal 15 residues are very flexible, and the (1H, 1H) NOESY data show that these residues have no NOE interactions with the remainder of the molecule. The segment of residues 37 to 41 is also flexible. These observations explain why during folding this intermediate most readily forms any of the possible disulphide bonds between Cys5, Cys14 and Cys38, including the non-native 5-14 and 5-38 bonds. The native-like folded portion of the molecule limits the possible disulphide bonds that can be formed to those in the remainder of the polypeptide chain. Also, forming the non-native disulphide bonds need not involve any disruption of that folded structure, as the Cys residues involved are in flexible regions of the molecule.


A retrospective observational study of early experiences of vedolizumab treatment for inflammatory bowel disease in the UK: The REVIVE study.
Results from clinical trials show that vedolizumab is an efficacious treatment for inflammatory bowel disease, namely Crohn's disease (CD) and ulcerative colitis (UC). However, there is limited evidence from real-world clinical practice, especially on early clinical experiences in the UK.To describe real-world early experiences of vedolizumab to treat CD and UC in the UK.A retrospective, chart review study of patients with CD or UC treated with vedolizumab across 5 UK hospitals. All eligible adults (≥18 years at initiation) with a diagnosis of CD and ≥14 weeks of data or UC and ≥10 weeks of data available following vedolizumab initiation were included.Data were analyzed for 112 patients (CD: 66; UC: 46). Patients with CD had a median of 7.4 (interquartile range 5.7-9.4) months follow-up and patients with UC had a median of 7.4 (5.6-10.2) months follow-up post-vedolizumab initiation. Most patients, 80% (53/66) with CD and 89% (41/46) with UC, remained on vedolizumab treatment at the time of data collection. No new safety signals were identified during the study.These results add to the body of evidence supporting vedolizumab as an effective and well-tolerated treatment for CD and UC in real-world clinical practice.


Plasticity in the projection from the anterior thalamic nuclei to the anterior cingulate cortex in the rat in vivo: paired-pulse facilitation, long-term potentiation and short-term depression.
Several neurophysiological and computational theories of the rodent navigational system suggest that the differing cortices of the frontal lobe and thalamus share information and therefore undergo changes in synaptic strength. We examine here for the first time three forms of synaptic plasticity in the projection from the anterior thalamic nuclei to the anterior cingulate cortex: we demonstrate that this projection is capable of expressing paired-pulse facilitation, long-term potentiation, and short-term depression. Furthermore, input/output curves show that field excitatory post-synaptic potential amplitude increased at all stimulus intensities following high-frequency stimulation. These findings add important information to our understanding of synaptic plasticity in this important pathway, which has been widely hypothesized to play important roles in memory and spatial representation in the rodent.


DNA repair in reduced genome: the Mycoplasma model.
The occurrence of bacteria with a reduced genome, such as that found in Mycoplasmas, raises the question as to which genes should be enough to guarantee the genomic stability indispensable for the maintenance of life. The aim of this work was to compare nine Mycoplasma genomes in regard to DNA repair genes. An in silico analysis was done using six Mycoplasma species, whose genomes are accessible at GenBank, and M. synoviae, and two strains of M. hyopneumoniae, whose genomes were recently sequenced by The Brazilian National Genome Project Consortium and Southern Genome Investigation Program (Brazil) respectively. Considering this reduced genome model, our comparative analysis suggests that the DNA integrity necessary for life can be primarily maintained by nucleotide excision repair (NER), which is the only complete repair pathway. Furthermore, some enzymes involved with base excision repair (BER) and recombination are also present and can complement the NER activity. The absence of RecR and RecO-like ORFs was observed only in M. genitalium and M. pneumoniae, which can be involved with the conservation of gene order observed between these two species. We also obtained phylogenetic evidence for the recent acquisition of the ogt gene in M. pulmonis and M. penetrans by a lateral transference event. In general, the presence or nonexistence of repair genes is shared by all species analyzed, suggesting that the loss of the majority of repair genes was an ancestral event, which occurred before the divergence of the Mycoplasma species.


Risk factors and clinical expression of HCV infection in hemodialysis patients.
In our Dialytic Unit, the prevalence of antibodies to HCV (anti-HCV) was 16.4% in 1990 (73 hemodialyzed) and 21% in 1991 (105 hemodialyzed). The incidence of seroconversion was 13.1%. The transaminase behavior was similar in a group of anti-HCV-positive and a group of anti-HCV-negative patients and with previous HBV infection. Blood transfusions and dialytic age did not affect anti-HCV positivity.


Lipases for biocatalysis: development of a chromatographic bioreactor.
The development of a new chromatographic reactor based on immobilized Candida rugosa lipase (CRL) is described. The chromatographic system has been used to evaluate the rate differences by which the product enantiomers of esterolytic reactions catalyzed by immobilized CRL are obtained. The method has been applied to a series of racemic 2-aryloxyalkanoic acids and isosteric analogous methyl esters and to some non-steroidal antiinflammatory drugs 2-arylpropanoic acids methyl esters in order to study the structure effects on reaction rate and enantioselectivity. Lipase from C. rugosa has been non-covalently and covalently immobilized on HPLC chromatographic silica supports to develop an immobilized enzyme reactor (IMER). The reactor was connected through a switching valve to an analytical reversed-phase column, which was used for the on-line determination of the hydrolysis rate by peak area integration. The enantiomeric excess of the hydrolytic reaction products was determined off-line on a CSP utilizing immobilized penicillin G acylase (PGA-CSP).


New potent calcimimetics: II. Discovery of benzothiazole trisubstituted ureas.
Following the identification of trisubstituted ureas as a promising new chemical series of allosteric modulators of the calcium sensing receptor (CaSR), we further explored the SAR around the urea substitution, leading to the discovery of benzothiazole urea compound 13. This compound is a potent calcimimetic with an EC50=20 nM (luciferase assay). Evaluated in an in vivo model of chronic renal failure (short term and long term in 5/6 nephrectomized rats), benzothiazole urea 13 significantly decreased PTH levels after oral administration while keeping calcemia within the normal range.


Synthesis and transdermal penetration of NSAID glycoside esters.
The glucoside and mannoside derivatives of the NSAIDs flurbiprofen, ibuprofen, ketoprofen and naproxen were synthesised and their penetration through human skin was determined. Experimental transdermal flux data showed that the parent NSAIDs penetrated human skin to a much higher extent than the glycosides.


Myosin light-chain kinase inhibitor, 1-(5-chlornaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9), inhibits catecholamine secretion from adrenal chromaffin cells by inhibiting Ca2+ uptake into the cells.
For determination of whether myosin light-chain kinase (MLCK) is involved in the secretory mechanism of adrenal chromaffin cells, the effect of a preferential inhibitor of the enzyme, 1-(5-chlornaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine (ML-9), on catecholamine secretion from cultured bovine adrenal chromaffin cells was studied. ML-9 did not affect basal catecholamine secretion, but inhibited catecholamine secretion stimulated by acetylcholine, high K+, veratridine or palytoxin. At similar concentrations to those inhibiting the secretion of catecholamine, ML-9 also inhibited increased [45Ca]2+ uptake by the cells induced by these stimulants. However, it did not inhibit catecholamine secretion induced by the Ca2+ ionophore A23187. Moreover, it did not affect catecholamine secretion from digitonin-permeabilized cells induced by a micromolar Ca2+ concentration in the presence of Mg ATP. These results indicate that ML-9 inhibits catecholamine secretion from adrenal chromaffin cells by inhibiting the transmembrane Ca2+ uptake mechanism, but not by inhibiting the intracellular Ca2+-dependent mechanism. The possible role of MLCK in stimulus-secretion coupling in adrenal chromaffin cells is discussed.


Cefdinir-associated "bloody stools" in an infant.
Cefdinir, a third-generation oral cephalosporin frequently used in pediatric populations, may cause red stools when administered with iron or products that contain iron, such as infant formula. This benign side effect is not well documented in the medical literature. We describe a 7-month-old girl who was evaluated for red stools while taking cefdinir along with an oral iron supplement.


Deciphering the complex cotton genome for improving fiber traits and abiotic stress resilience in sustainable agriculture.
Understanding the complex cotton genome is of paramount importance in devising a strategy for sustainable agriculture. Cotton is probably the most economically important cash crop known for its cellulose-rich fiber content. The cotton genome has become an ideal model for deciphering polyploidization due to its polyploidy, setting it apart from other major crops. However, the main challenge in understanding the functional and regulatory functions of many genes in cotton is still the complex cotton polyploidy genome, which is not limited to a single role. Cotton production is vulnerable to the sensitive effects of climate change, which can alter or aggravate soil, pests, and diseases. Thus, conventional plant breeding coupled with advanced technologies has led to substantial progress being made in cotton production. In the frontier areas of genomics research, cotton genomics has gained momentum accomplished by robust high-throughput sequencing platforms combined with novel computational tools to make the cotton genome more tractable. Advances in long-read sequencing have allowed for the generation of the complete set of cotton gene transcripts giving incisive scientific knowledge in cotton improvement. In contrast, the integration of the latest sequencing platforms has been used to generate multiple high-quality reference genomes in diploid and tetraploid cotton. While pan-genome and 3D genomic studies are still in the early stages in cotton, it is anticipated that rapid advances in sequencing, assembly algorithms, and analysis pipelines will have a greater impact on advanced cotton research. This review article briefly compiles substantial contributions in different areas of the cotton genome, which include genome sequencing, genes, and their molecular regulatory networks in fiber development and stress tolerance mechanism. This will greatly help us in understanding the robust genomic organization which in turn will help unearth candidate genes for functionally important agronomic traits.


Psychoneurogenic stress influences upon retention of an inhibitory avoidance response in the rat.
Hormones and peptides involved in the response of an organism to stress play a modulating role in learning and memory processes. We studied whether psychoneurogenic stressors such as sound stimulation or novelty influence retention of an inhibitory avoidance response. An impairing effect on retention was observed when these stressors were applied shortly after the acquisition trial, but not after a 3-h delay. However, sound stimulation and novelty applied shortly before the retention test may facilitate retention behavior. It is suggested that the effect of psychoneurogenic stressors on retention behavior may be linked to influences on consolidation and retrieval processes mediated through the neurohumoral response of the organism to stress.


Molecular detection of SARS-CoV-2 strains and differentiation of Delta variant strains.
The Delta variant of SARS-CoV-2 has now become the predominant strain in the global COVID-19 pandemic. Strain coverage of some detection assays developed during the early pandemic stages has declined due to periodic mutations in the viral genome. We have developed a real-time RT-PCR (RT-qPCR) for SARS-CoV-2 detection that provides nearly 100% strain coverage, and differentiation of highly transmissible Delta variant strains. All full or nearly full (≥28 kb) SARS-CoV-2 genomes (n = 403,812), including 6422 Delta and 280 Omicron variant strains, were collected from public databases at the time of analysis and used for assay design. The two amino acid deletions in the spike gene (S-gene, Δ156-157) that is characteristic of the Delta variant were targeted during the assay design. Although strain coverage for the Delta variant was very high (99.7%), detection coverage for non-Delta wild-type strains was 93.9%, mainly due to the confined region of design. To increase strain coverage of the assay, the design for CDC N1 target was added to the assay. In silico analysis of 403,812 genomes indicated a 95.4% strain coverage for the CDC N1 target, however, in combination with our new non-Delta S-gene target, total coverage for non-Delta wild-type strains increased to 99.8%. A human 18S rRNA gene was also analyzed and used as an internal control. The final four-plex RT-qPCR assay generated PCR amplification efficiencies between 95.4% and 102.0% with correlation coefficients (R2 ) of >0.99 for cloned positive controls; Delta and non-Delta human clinical samples generated PCR efficiencies of 93.4%-97.0% and R2 > 0.99. The assay also detects 98.6% of 280 Omicron sequences. Assay primers and probes have no match to other closely related human coronaviruses, and did not produce a signal from samples positive to selected animal coronaviruses. Genotypes of selected clinical samples identified by the RT-qPCR were confirmed by Sanger sequencing.


Mapping evidence on the risk factors associated with pediatric cancers in sub-Saharan Africa: a scoping review.
The rarity and heterogeneity of pediatric cancers make it difficult to assess risk factors associated with the development of cancer in this group. This also determines the quantity and quality of evidence for etiological factors linked to pediatric cancers. Evidence on the risk factors associated with pediatric cancers is scarce; however, it has been accumulating slowly over the years. As the disease burden shifts from communicable to non-communicable diseases, most of these low- to middle-income countries (LMICs) find themselves overburdened with changing health care priorities and needs. In sub-Saharan Africa, it is of major importance to pay particular attention to risk factors associated with pediatric cancer. To map evidence on risk factors associated with pediatric cancers in sub-Saharan Africa (SSA). This review was guided by Arksey and O'Malley's framework for conducting scoping reviews. Four electronic databases were searched in December 2018, and another manual search was conducted in February 2022 to include newly published eligible articles. The databases searched included PubMed and Health Source: Nursing/Academic Edition. We also searched articles from an academic search engine, Google scholar. This review included articles reporting the relevant outcomes of this study and articles reporting cancers in children in the 0-15 years age range. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) extension for scoping reviews (PRISMA-ScR): checklist and explanation. We retrieved 7391 articles from the initial database. The final number of studies that were included for data extraction was 15. Evidence from the retrieved studies suggests that most childhood cancers in the SSA region are infection-induced. The type of cancer mostly reported is Burkitt Lymphoma and is diagnosed mostly in the tropical region of SSA. The type of risk factors was divided into three types: infection-induced, genetic, and demographic risk factors. Overall, based on the articles retrieved, there was limited evidence on the risk factors associated with pediatric cancers in SSA. The limited evidence on the risk factors coupled with the lack of evidence on the true burden of these malignancies in the SSA hampers efforts to set priorities for childhood cancer control. Formulation of effective preventative (where possible) measures and treatment regimens will need proper assessment of risk factors.


The impact of video games on training: can it change the game of endotracheal intubation?
In recent years, several studies have demonstrated that the experience derived from video games improves interventions that require technical skills. Airway management is crucial to anesthesiologists, requiring technical and non-technical skills. We evaluated the benefits of video games for video stylet-guided tracheal intubation, which allows the use of video technology in airway management of residents with anesthesiology training. In the present study, the residents working in the Department of Anesthesiology and Reanimation at the Health Sciences University of Kartal Dr. Lütfi Kırdar City Hospital in Istanbul were assigned to two groups. Active users who played video games on a regular basis formed study group (n = 14), while those who did not have video gaming habits were assigned to the control group (n = 15). Female patients with the American Society of Anesthesiologists (ASA) I and II classification undergoing elective open or laparoscopic gynecological surgery through tracheal intubation under general anesthesia were included in the study. Female patients elective open and laparoscopic gynecological surgery under GA were included in the study. Time to intubate the trachea by using video stylet in (Group 1) was found to be 29 s on average, and it was 59.9 s for Group 2 ( p < 0.01) The average number of tracheal intubation attempts was 1.1 in Group 1, and 1.4 in Group 2 (p = 0.19). Video gaming experience improves the visual attention.Those accustomed to playing with video games, video stylet- guided tracheal intubation, performed intubation in less time.


The expression changes of transcription factors including ANKZF1, LEF1, CASZ1, and ATOH1 as a predictor of survival rate in colorectal cancer: a large-scale analysis.
Transcription factors (TFs) are essential for many biological processes and regulate the expression of several genes. This study's objective was to analyze the abnormalities in TF expression, their impact on patient prognosis, and related pathways in colorectal cancer (CRC). The expression alterations of all TFs were investigated using the cancer genome atlas and GSE39582 data. Clinical data were also used to study the association between TFs expression and patient prognosis through the Cox regression test, and a predictive model of CRC patient survival was constructed based on TFs expression. Co-expression network was used to discover TF-related pathways. To validate the findings, the RT-qPCR method was applied to CRC samples and adjacent normal tissue. The findings revealed that ANKZF1, SALL4, SNAI1, TIGD1, LEF1, FOXS1, SIX4, and ETV5 expression levels increased in both cohorts and were linked to the poor prognosis. NR3C2, KLF4, CASZ1, FOXD2, ATOH1, SALL1, and RORC expression, on the other hand, exhibited a significant decrease, and their increase was related to the good prognosis of patients. The patient mortality risk model based on expression of mentioned TFs revealed that, independent of clinical characteristics, the expression of ANKZF1, LEF1, CASZ1, and ATOH1 could accurately predict patient survival rates. According to the co-expression network, increased transcription factors were linked to metastatic pathways, while decreasing TFs were involved to apoptotic pathways. RT-qPCR findings showed that FOXS1 expression was markedly overexpressed in CRC samples. However, in CRC samples, the expression of CASZ1 decreased. In CRC, TFs expression of ANKZF1, LEF1, CASZ1 and ATOH1 are deregulated, which are associated with prognosis in patients. According to our findings, changes in the expression of the mentioned TFs have the potential to be considered diagnostic and prognostic biomarkers for CRC patients.


Vaccine Hesitancy in Women's Health.
The development of vaccines is considered one of the greatest breakthroughs of modern medicine, saving millions of lives around the world each year. Despite vaccines' proven success, vaccine hesitancy remains a major issue affecting vaccine uptake. Common themes exist in patients' apprehension to receive vaccines. Women's health providers possess an important role in addressing these concerns and dispelling common misconceptions that may increase vaccine hesitancy thereby reduce vaccine uptake. This review aims to explore many of these topics as they are related to women's health and provide strategies for providers to implement which may reduce vaccine hesitancy among our patients.


Persistent oral candidosis by non-albicans Candida strains including Candida glabrata in a human immunodeficiency virus-infected patient observed over a period of 6 years.
A 38-year-old woman infected with human immunodeficiency virus (HIV) presented with persistent oral candidosis in which non-albicans Candida strains were the predominant yeasts in most of the examinations performed over a period of 6 years. Oral treatment with fluconazole had no effect on clinical signs of oral candidosis. In 8 of a total of 11 specimens, Candida glabrata, Candida parapsilosis and Candida tropicalis were at least suspected as the causative pathogens of oral candidosis. The non-response to fluconazole in our patient could be explained by in vitro resistance to fluconazole of detected Candida glabrata and Candida tropicalis isolates.