Expression pattern and diagnostic value of ferroptosis-related genes in acute myocardial infarction.
Ferroptosis is a form of regulatory cell death (RCD) caused by iron-dependent lipid peroxidation. The role of ferroptosis in the process of acute myocardial infarction (AMI) is still unclear and requires further study. Therefore, it is helpful to identify ferroptosis related genes (FRGs) involved in AMI and explore their expression patterns and molecular mechanisms. The AMI-related microarray datasets GSE66360 and GSE61144 were obtained using the Gene Expression Omnibus (GEO) online database. GO annotation, KEGG pathway enrichment analysis and Protein-protein interaction (PPI) analysis were performed for the common significant differential expression genes (CoDEGs) in these two datasets. The FRGs were obtained from the FerrDb V2 and the differentially expressed FRGs were used to identify potential biomarkers by receiver operating characteristic (ROC) analysis. The expression of these FRGs was verified using external dataset GSE60993 and GSE775. Finally, the expression of these FRGs was further verified in myocardial hypoxia model. A total of 131 CoDEGs were identified and these genes were mainly enriched in the pathways of "inflammatory response," "immune response," "plasma membrane," "receptor activity," "protein homodimerization activity," "calcium ion binding," "Phagosome," "Cytokine-cytokine receptor interaction," and "Toll-like receptor signaling pathway." The top 7 hub genes ITGAM, S100A12, S100A9, TLR2, TLR4, TLR8, and TREM1 were identified from the PPI network. 45 and 14 FRGs were identified in GSE66360 and GSE61144, respectively. FRGs ACSL1, ATG7, CAMKK2, GABARAPL1, KDM6B, LAMP2, PANX2, PGD, PTEN, SAT1, STAT3, TLR4, and ZFP36 were significantly differentially expressed in external dataset GSE60993 with AUC ≥ 0.7. Finally, ALOX5, CAMKK2, KDM6B, LAMP2, PTEN, PTGS2, and ULK1 were identified as biomarkers of AMI based on the time-gradient transcriptome dataset of AMI mice and the cellular hypoxia model. In this study, based on the existing datasets, we identified differentially expressed FRGs in blood samples from patients with AMI and further validated these FRGs in the mouse time-gradient transcriptome dataset of AMI and the cellular hypoxia model. This study explored the expression pattern and molecular mechanism of FRGs in AMI, providing a basis for the accurate diagnosis of AMI and the selection of new therapeutic targets.


Oxidative stress responses as a marker of toxicity in mice exposed to polluted groundwater from an automobile junk market in South-Western Nigeria.
The global trade in used vehicles and their components generates huge financial benefits but leads to detrimental environmental consequences including groundwater pollution and potential adverse health effects mediated by free-radical processes such as lipid peroxidation. We investigated oxidative stress responses in thirty-six, female mice orally exposed (via drinking) to graded concentrations (0%, 50%, and 100%) of groundwater from a well located within a major automobile junk market in SW-Nigeria containing extremely high levels of arsenic (0.332 ± 0.089 mg/l) and seventeen PAHs, which serves as domestic water supply. Blood samples from the mice were assayed for selected biochemical parameters at intervals of 7, 14, and 28 days. A significant dose- and duration-dependent increase in malondialdehyde (MDA) and Myeloperoxidase (MPO) confirmed oxidative stress onset due to exposure to the polluted well-water, while a significant decline in nitric oxide (NO-) levels may suggest impaired endothelial smooth-muscle relaxation which may lead to the development of metabolic diseases over time. Superoxide dismutase (SOD) and reduced glutathione (GSH) showed a contrasting trend with Glutathione peroxidase (GPx), while Glutathione-S-Transferase (GST) declined significantly by the 28th day. Two clusters were identified by principal component analysis-one involving MDA, SOD, and GSH suggesting that antioxidant responses driven mainly by SOD and GSH proved insufficient in scavenging the free radicals generated by lipid peroxidation. NO- and total protein clustered together possibly due to the significant declines in both over the study period. Histological examination of liver tissue of exposed mice corroborated the above findings and highlights the need for urgent remedial action.


Cost of ambulatory care for the pediatric intestinal failure patient: One-year follow-up after primary discharge.
Survival of children with intestinal failure has improved over the last decade, resulting in increased health care expenditures. Our objective was to determine outpatient costs for the first year after primary discharge. A retrospective analysis was performed in pediatric intestinal failure (PIF) patients between 2010 and 2012. Patients were stratified into 3 groups (1=enteral support with no devices [7 patients], 2=enteral support with devices (gastrostomy and/or ostomy) [19 patients], 3=home parenteral nutrition (HPN) [22 patients]). Data abstraction included clinical characteristics and costs related to medication, enteral/parenteral nutrition, and supplies were calculated. Data were analyzed using one way ANOVA. Forty-eight patients (mean age 7.6months; 31 males [65%]) were studied. See attached table for results. HPN patients had significantly more ambulatory visits (p<0.0001), number of admitted days (p=0.01), and productive days lost (p<0.0001). Total cost of care was significantly higher for HPN patients (mean=$320,368.50, p<0.0001) when compared to other groups. Costs covered by the health care system were significantly higher for patients on HPN (mean=$316,101.56, p<0.0001). The outpatient expenditures to care for PIF patients in the first year post primary discharge are significant. Our single payer health care system supports the majority of costs, but families are also incurring expenses related to travel and lost productivity. Children on HPN have more visits to hospital, but have access to more funding options. Children solely on gastrostomy or stoma therapy, however, have a significantly greater personal financial burden.


Magnetoencephalographic study of the cortical activity elicited by human voice.
In an attempt to identify voice-specific neural activities in auditory cortex in humans, we recorded cortical magnetic responses. Volunteers were instructed to listen to vocal and instrumental sounds matched in fundamental-frequency, duration, temporal envelope and average root mean square power. The stimuli were sounds produced by four singers and four musical instruments at each of two fundamental frequencies: 220 Hz (musical note A3) and 261.9 Hz (C3). Two components of the evoked responses were analyzed, one at approximately 100 ms (N1m) and the other 400 ms after the stimulus onset (sustained field, SF). The source locations of equivalent current dipoles for both components were estimated around the Heschl's gyrus in both hemispheres. Compared with the instrumental sound, the source strength of the SF component for the voice was significantly larger.


Anxiety and depression in patients with inflammatory bowel disease: comparisons with chronic liver disease patients and the general population.
Studies on anxiety and depression in inflammatory bowel disease (IBD) yielded inconsistent results. We compared anxiety and depression of patients with Crohn's disease (CD) and ulcerative colitis (UC) controlled for sociodemographic and medical variables with age- and sex-matched controls. In all, 422 IBD patients (50% females, 314 CD, 108 UC) of different settings were compared with 140 age- and sex-matched patients with chronic liver diseases (CLD) of a tertiary care center and with 422 age- and sex-matched persons of a representative sample of the general German population (GP). Anxiety and depression and probable mental disorder were assessed by the German version of the Hospital Anxiety and Depression Scale. Comparisons between CD and UC were adjusted for medical (disease activity, number of IBD-associated diseases) and sociodemographic factors (age, gender, marital status). CD and UC patients did not differ in the levels of anxiety and depression or in the frequency of a probable mental disorder. The levels of anxiety and depression of IBD patients with active disease were higher than that of the GP, but not of the IBD patients in remission. The depression score of the CLD sample was higher than that of the IBD sample (P<0.001), but not the anxiety score. Mental disorders were more frequent in IBD patients with slight (27.7%) and moderate/severe disease activity (49.3%) compared to GP (10.4%) (P<0.001), but not in IBD patients in remission (11.3%). Patients with active IBD should be screened for anxiety and depression.


Alteration of monocyte subsets and their functions in thalassemia patients.
Infection is one of the leading causes of mortality in thalassemia patients. This study aimed to examine qualitative and quantitative changes in monocytes in thalassemia patients. Monocytes were isolated from peripheral blood mononuclear cells and separated into subpopulations by flow cytometry. Cytokine levels were measured using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and sandwich enzyme-linked immunosorbent assay (ELISA). The primary endpoint was monocyte-derived TNF-α expression. A total of 78 patients and 26 controls were included. The mean log (TNF-α fold-change) by qRT-PCR was significantly lower in all thalassemia groups, at 1.27 in controls, versus 0.97 (p = 0.0014) in non-transfusion-dependent thalassemia (NTDT), 0.96 (p = 0.0004) in non-splenectomized transfusion-dependent thalassemia (TDT-NS), and 0.87 (p < 0.0001) in splenectomized transfusion-dependent thalassemia (TDT-S). Similarly, the mean 2-h TNF-α level measured by sandwich ELISA assay was significantly lower in all thalassemia groups, at 98.16 pg/mL in controls, versus 56.45 pg/mL (p = 0.0093) in NTDT, 39.05 pg/mL (p = 0.0001) in TDT-NS and 32.37 pg/mL (p < 0.0001) in TDT-S. Likewise, TDT patients had a significantly decreased percentage of non-classical monocytes, by approximately half compared to controls. Our results show that thalassemia major patients have clearly impaired monocyte counts and function.


Network pharmacology and in vitro study of Fengreqing oral liquid in the intervention of wind-heat pattern.
To investigate the underlying mechanism of the effect of Fengreqing oral liquid (, FOL) on wind-heat pattern (WHP). In this study, we predicted the potential targets of FOL via the approach of network pharmacology and verified it by in vitro inflammation model. In the network pharmacology part, two strategies, namely the direct target search and the indirect one, were used to collect the target sets of FOL in WHP treatment. The enrichment analysis was carried out by David database and ClueGo plug-in in Cytoscape. Furthermore, the potential targets were mapped in the candidate pathways. In the verification experiment section, in vitro model of lipopolysaccharide (LPS) induced RAW 264.7 was used to confirm the predictive results in the network pharmacology part. Through the two screening strategies, a total of 141 non-repetitive intervention targets of FOL on WHP were obtained. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the intervention effect was mainly focused on the anti-inflammatory effect, and the Toll-like receptor signaling pathway was one of the most critical regulatory pathways. Further mapping analysis showed that phosphatidylinositol 3-kinase (PI3K)-protein kinase B (AKT) signaling transfer might be the key part of regulating the concentration of inflammation mediators of FOL in the Toll-like receptor signaling pathway. In vitro experiment showed that FOL significantly reduced the levels of NO, IL-1, IL-6, and TNF-α produced by RAW264.7 induced by LPS. Further immunofluorescence found that this effect is related to the regulation of PI3K-AKT pathway activity by FOL. FOL can intervene in WHP by regulating the content of inflammatory mediators via the PI3K-AKT pathway.


Adverse effects of extradural and intrathecal opiates: report of a nationwide survey in Sweden.
The Swedish Society of Anaesthetists conducted a nationwide retrospective survey of clinical experience with extradural and intrathecal opiates. Special interest was focused on the frequency and type of ventilatory depression. The questionnaire was answered by 84 of 93 departments (90%). Up to May 1981 extradural morphine had been given to approximately 6000-9150 patients, extradural pethidine to 220-450 and intrathecal morphine to 90-150 patients. Ventilatory depression requiring treatment with naloxone was reported in 23 patients treated with extradural morphine (0.25-0.40%) and in six given intrathecal morphine (4-7%). In 22 patients the administration of extradural morphine was considered as a major contributory factor for the occurrence of ventilatory depression. Only two of these 22 patients experienced ventilatory depression later than 6 h after the last dose of opiates (S.C., i.m., i.v. or extradural). Patients aged 70 yr or more, those receiving thoracic extradural puncture and those with reduced ventilatory capacity seemed to be overrepresented.


Long-Range Coulomb Effect in Intense Laser-Driven Photoelectron Dynamics.
In strong field atomic physics community, long-range Coulomb interaction has for a long time been overlooked and its significant role in intense laser-driven photoelectron dynamics eluded experimental observations. Here we report an experimental investigation of the effect of long-range Coulomb potential on the dynamics of near-zero-momentum photoelectrons produced in photo-ionization process of noble gas atoms in intense midinfrared laser pulses. By exploring the dependence of photoelectron distributions near zero momentum on laser intensity and wavelength, we unambiguously demonstrate that the long-range tail of the Coulomb potential (i.e., up to several hundreds atomic units) plays an important role in determining the photoelectron dynamics after the pulse ends.


Deep-learning approach to detect childhood glaucoma based on periocular photograph.
Childhood glaucoma is one of the major causes of blindness in children, however, its diagnosis is of great challenge. The study aimed to demonstrate and evaluate the performance of a deep-learning (DL) model for detecting childhood glaucoma based on periocular photographs. Primary gaze photographs of children diagnosed with glaucoma with appearance features (corneal opacity, corneal enlargement, and/or globe enlargement) were retrospectively collected from the database of a single referral center. DL framework with the RepVGG architecture was used to automatically recognize childhood glaucoma from photographs. The average receiver operating characteristic curve (AUC) of fivefold cross-validation was 0.91. When the fivefold result was assembled, the DL model achieved an AUC of 0.95 with a sensitivity of 0.85 and specificity of 0.94. The DL model showed comparable accuracy to the pediatric ophthalmologists and glaucoma specialists in diagnosing childhood glaucoma (0.90 vs 0.81, p = 0.22, chi-square test), outperforming the average of human examiners in the detection rate of childhood glaucoma in cases without corneal opacity (72% vs. 34%, p = 0.038, chi-square test), with a bilateral corneal enlargement (100% vs. 67%, p = 0.03), and without skin lesions (87% vs. 64%, p = 0.02). Hence, this DL model is a promising tool for diagnosing missed childhood glaucoma cases.


Creating a Practical Transformational Change Management Model for Novel Artificial Intelligence-Enabled Technology Implementation in the Operating Room.
To identify change management (CM) strategies for implementing novel artificial intelligence and similar novel technologies in operating rooms and create a new CM model for future trials and applications inspired by the abovementioned strategies and established models. Key phases of technology implementation were defined, and strategies for transformational CM were created and applied in a recent CM experience at our institution between October 15, 2020 and October 15, 2021. We appraised existing CM models and propose the newly created model. The key phases of the technology implementation were as follows: (1) team assembly; (2) committee approvals; (3) CM; and (4) system installation and go-live. Key strategies were (1) assemble team with necessary expertise; (2) anticipate potential institutional cultural and regulatory hurdles; (3) add agility to project planning and execution; (4) accommodate institutional culture and regulations; (5) early clinical partner buy-in and stakeholder engagement; and (6) consistent communication, all of which contributed to the new CM model creation. Key CM strategies and a new CM model addressing the unique needs and characteristics of operating room novel technology implementation were identified and created. The new model may be customized and tested for individual institution and project's needs and characteristics.


Operative managements of extracranial carotid artery aneurysms: a report of three cases and literature review.
The purpose of this study is to report the treatment approaches and postoperative outcomes of extracranial carotid artery aneurysms (ECAAs) and discuss the symptoms, related risk factors, etiology, diagnostic methods, treatments, and follow-up period complications. We describe three patients with symptomatic extracranial carotid artery aneurysms; one of them was treated with end-to-end anastomosis of the extracranial internal carotid artery (EICA) after the resection of the aneurysm, while the other two patients were deployed with Willis covered stents in the extracranial internal carotid artery. All of the patients were in good condition when discharged home. After a mean follow-up period of 8 months, all the patients were alive and only one of them had the neurologic deficit. Additionally, we reviewed the relative literatures. Both of the surgical and endovascular treatments have relatively satisfactory outcomes in ECAA patients. However, it is necessary to provide individualized treatments to different patients according to the characteristics of the aneurysms.


Sustainable synthetic methods: domino construction of dihydropyridin-4-ones and beta-amino esters in aqueous ethanol.
Domino reactions were designed to allow the byproduct of an upstream reaction to be internally recycled to catalyze a downstream reaction in a one-pot tandem sequence. Nitroarene reduction by In(0) generates an amine and In (III) byproducts. Addition of aldehyde followed by Danishefsky's diene or silyl ketene acetal provides access to dihydropyridin-4-ones or beta-amino esters, respectively, in yields that are comparable or superior to the reported stepwise reactions.


Addressing the unmet need in lung cancer: The potential of immuno-oncology.
Chemotherapy is currently the standard of care for non-oncogene-driven advanced non-small cell lung cancer (NSCLC). Due to improvements in chemotherapeutic choices and supportive care, patients currently typically undergo multiple lines of chemotherapy as their disease progresses. Although treatments have improved over recent years, limited benefits are seen, especially in patients receiving later-line chemotherapy, as response rates can be low, response duration short and survival poor. Furthermore, only a small percentage of patients derive benefit from later-line therapy, with most experiencing deteriorating quality of life and significant toxicities. More recently, molecular targeted therapies have provided improvements in outcomes. However, these treatments only offer a clear benefit in subsets of tumours harbouring the appropriate genomic alteration (mutation, amplification, translocation). Most of the genomic abnormalities susceptible to therapeutic intervention are detected in adenocarcinoma, mainly in never smokers, while alterations in the genome of other histological subtypes are known but specific agents targeting these alterations have yet to be developed. Thus, the therapeutic management of these subtypes represents an ongoing challenge. Recent advances in immunotherapy have highlighted the potential of immuno-oncology based treatments for NSCLC, offering the potential to provide durable responses and outcomes regardless of histology or mutation status. This review discusses the current unmet medical needs in NSCLC, the limits of current first-line and later-line chemotherapy and targeted agents, and the emergence of new therapeutic strategies.


Consensus molecular subtype differences linking colon adenocarcinoma and obesity revealed by a cohort transcriptomic analysis.
Colorectal cancer (CRC) is the third-leading cause of cancer-related deaths in the United States and worldwide. Obesity-a worldwide public health concern-is a known risk factor for cancer including CRC. However, the mechanisms underlying the link between CRC and obesity have yet to be fully elucidated in part because of the molecular heterogeneity of CRC. We hypothesized that obesity modulates CRC in a consensus molecular subtype (CMS)-dependent manner. RNA-seq data and associated tumor and patient characteristics including body weight and height data for 232 patients were obtained from The Cancer Genomic Atlas-Colon Adenocarcinoma (TCGA-COAD) database. Tumor samples were classified into the four CMSs with the CMScaller R package; body mass index (BMI) was calculated and categorized as normal, overweight, and obese. We observed a significant difference in CMS categorization between BMI categories. Differentially expressed genes (DEGs) between obese and overweight samples and normal samples differed across the CMSs, and associated prognostic analyses indicated that the DEGs had differing associations on survival. Using Gene Set Enrichment Analysis, we found differences in Hallmark gene set enrichment between obese and overweight samples and normal samples across the CMSs. We constructed Protein-Protein Interaction networks and observed differences in obesity-regulated hub genes for each CMS. Finally, we analyzed and found differences in predicted drug sensitivity between obese and overweight samples and normal samples across the CMSs. Our findings support that obesity impacts the CRC tumor transcriptome in a CMS-specific manner. The possible associations reported here are preliminary and will require validation using in vitro and animal models to examine the CMS-dependence of the genes and pathways. Once validated the obesity-linked genes and pathways may represent new therapeutic targets to treat colon cancer in a CMS-dependent manner.


123I-iomazenil: a quantitative study of the central benzodiazepine receptor distribution.
Fourteen patients with temporal lobe epilepsy, 9 patients after amygdalohippocampectomy and 3 healthy volunteers were examined with the new benzodiazepine receptor marker 123I-Iomazenil and SPECT. For comparison perfusion SPECT studies with 99mTc-HMPAO were done and a quantitative ROI analysis of the data performed. This quantitative analysis consisted of calculation of right-to-left ratios for 123I-Iomazenil SPECTs, whereby values of 1 were obtained with narrow standard deviations. ROI measurements of the medial occipital, frontal and parietal cortex, the cerebellum and white matter showed a pattern of benzodiazepine receptor concentration in concordance with that previously found in PET and autoradiographic studies, if 123I-Iomazenil ROIs were normalized to the corresponding 99mTc-HMPAO ROIs. The abnormal distribution in the temporal lobes will not be discussed in this paper.


Dynamic orthognathic surgical procedure (DOSP) in asymmetric maxillomandibular dysmorphism secondary to unilateral micrognathia: Outcomes of 12 consecutive cases.
This study aimed to evaluate the outcomes following a dynamic orthognathic surgical procedure performed at the end of growth to treat asymmetric maxillomandibular deformities linked to unilateral micrognathia when conventional orthognathic surgery was not feasible. The dynamic orthognathic surgical procedure (DOSP) combined concomitant mandibular distraction osteogenesis with contralateral poorly stabilized sagittal split osteotomy and Le Fort I osteotomy. Cephalometric studies were retrospectively conducted on pre- and postoperative lateral and frontal cephalographs, and maxillomandibular movements were calculated. Outcome scores were computed by both experts and laypersons based on photographic analyses. There was a significant postoperative increase in height of the micrognathic ramus in all patients (n = 12; p = 0.002). The angle between the occlusal cant and horizontal reference plane decreased significantly in all of the patients, as did the angle between the midline sagittal plane and mandibular tilt (p < 0.001). Postoperative outcome scores showed significant improvements in all cases, according to both expert and layperson groups. This procedure allows correction of maxillomandibular asymmetries linked to micrognathia. However, it cannot resolve all the factors participating in facial asymmetry, such as those originating in the oculo-auriculo-ventricular spectrum or complex tumor sequelae, and second-step procedures may be required.


Rare SLC1A1 variants in hot water epilepsy.
Hot water epilepsy is sensory epilepsy, wherein seizures are triggered by an unusual stimulus: contact with hot water. Although genetic factors contribute to the etiology of hot water epilepsy, molecular underpinnings of the disorder remain largely unknown. We aimed to identify the molecular genetic basis of the disorder by studying families with two or more of their members affected with hot water epilepsy. Using a combination of genome-wide linkage mapping and whole exome sequencing, a missense variant was identified in SLC1A1 in a three-generation family. Further, we examined SLC1A1in probands of 98 apparently unrelated HWE families with positive histories of seizures provoked by contact with hot water. In doing so, we found three rare variants, p.Asp174Asn, p.Val251Ile and p.Ile304Met in the gene. SLC1A1 is a neuronal glutamate transporter which limits excitotoxicity and its loss-of-function leads to age-dependent neurodegeneration. We examined functional attributes of the variants in cultured mammalian cells. All three non-synonymous variants affected glutamate uptake, exhibited altered glutamate kinetics and anion conductance properties of SLC1A1. These observations provide insights into the molecular basis of hot water epilepsy and show the role of SLC1A1 variants in this intriguing neurobehavioral disorder.


Multiple Sclerosis Lesion Segmentation with Tiramisu and 2.5D Stacked Slices.
In this paper, we present a fully convolutional densely connected network (Tiramisu) for multiple sclerosis (MS) lesion segmentation. Different from existing methods, we use stacked slices from all three anatomical planes to achieve a 2.5D method. Individual slices from a given orientation provide global context along the plane and the stack of adjacent slices adds local context. By taking stacked data from three orientations, the network has access to more samples for training and can make more accurate segmentation by combining information of different forms. The conducted experiments demonstrated the competitive performance of our method. For an ablation study, we simulated lesions on healthy controls to generate images with ground truth lesion masks. This experiment confirmed that the use of 2.5D patches, stacked data and the Tiramisu model improve the MS lesion segmentation performance. In addition, we evaluated our approach on the Longitudinal MS Lesion Segmentation Challenge. The overall score of 93.1 places the L 2-loss variant of our method in the first position on the leaderboard, while the focal-loss variant has obtained the best Dice coefficient and lesion-wise true positive rate with 69.3% and 60.2%, respectively.


Herpes-like virus detection in infected Crassostrea gigas spat using DIG-labelled probes.
An in situ hybridization protocol for detecting the herpes-like virus which infects French Pacific oysters, Crassostrea gigas, was developed. Two DNA probes were synthesized by incorporation of digoxigenin 11-dUTP during PCR. Two oyster herpes-like virus specific primer pairs, A5/A6 and C1/C6, were used. Both DIG-labelled probes were able to detect 50 pg of herpes-like virus PCR amplified DNA in Southern blot hybridizations. The probes hybridized with viral DNA in paraffin sections of infected C. gigas spat. No non-specific binding was observed. The ability of the defined in situ hybridization technique to diagnose herpes-like virus infections in oysters was compared with light and transmission electron microscopy techniques in infected and non-infected spat. In situ hybridization assays were also conducted on paraffin sections to determine virus distribution within the host and to study the pathogenesis infection. In situ hybridization confirmed that the expression pattern of the herpes-like virus was restricted to connective tissues as described previously by light and transmission electron microscopy. However, this technique also allowed the detection of viral DNA in the oyster nervous system. Some labelled cells were observed in the visceral ganglion of infected oyster spat.


Respiratory mechanics in the adult respiratory distress syndrome.
Recent methods developed for noninvasive determination of the mechanical properties of the respiratory system have been discussed. These methods have already provided valuable information in patients mechanically ventilated in the ICU setting, and could readily be applied to ARDS. More extensive use of such methods should help to provide a better understanding of the physiologic processes and adaptive mechanisms present in both health and disease.


Choice of abdominal incision and risk of trauma to the urinary bladder and bowel in multiple cesarean sections.
To determine if the midline subumbilical incision reduces the risk of trauma to bladder and bowel in women undergoing multiple cesarean sections. Retrospective analysis of hospital histories of 3164 women who had repeat cesarean sections at a referral maternity hospital. The clinical records of women who had between one and eight cesarean sections over a 4-year period to October 2002 were examined for entries on injury to bladder and bowel. The frequency of these injuries in relation to abdominal incision used was determined. Multiple logistic regression analysis was performed to assess the influence of cesarean number, abdominal incision, intraperitoneal adhesions, operator experience, and anterior placenta previa on risk of bladder injury. Frequency of trauma to bladder and bowel associated with either Pfannenstiel or midline incision. There were 3164 women who met the inclusion criteria to the study. The midline incision was associated with significantly higher risk than Pfannenstiel for injury to the bladder (P<0.0001, OR 6.7, 95% CI 2.6-16.5). For both incisions, injury to the bladder increased with rising cesarean number. In addition, for a given cesarean other than primary, bladder trauma was more likely with the midline incision. The risk of injury to bowel was higher with the midline incision (RR 5.5), but there were too few events to permit Chi square analysis. In repeat cesarean section, the midline incision is associated with a higher risk of bladder and bowel injury than Pfannenstiel.


Inhibition of Heat Shock Factor 1 Signaling Decreases Hepatoblastoma Growth via Induction of Apoptosis.
Although rare compared with adult liver cancers, hepatoblastoma (HB) is the most common pediatric liver malignancy, and its incidence is increasing. Currently, the treatment includes surgical resection with or without chemotherapy, and in severe cases, liver transplantation in children. The effort to develop more targeted, HB-specific therapies has been stymied by the lack of fundamental knowledge about HB biology. Heat shock factor 1 (HSF1), a transcription factor, is a canonical inducer of heat shock proteins, which act as chaperone proteins to prevent or undo protein misfolding. Recent work has shown a role for HSF1 in cancer beyond the canonical heat shock response. The current study found increased HSF1 signaling in HB versus normal liver. It showed that less differentiated, more embryonic tumors had higher levels of HSF1 than more differentiated, more fetal-appearing tumors. Most strikingly, HSF1 expression levels correlated with mortality. This study used a mouse model of HB to test the effect of inhibiting HSF1 early in tumor development on cancer growth. HSF1 inhibition resulted in fewer and smaller tumors, suggesting HSF1 is needed for aggressive tumor growth. Moreover, HSF1 inhibition also increased apoptosis in tumor foci. These data suggest that HSF1 may be a viable pharmacologic target for HB treatment.


The role of carotid duplex scanning in surgical decision making.
Eighty-one patients suspected of having cerebrovascular disease had 157 carotid arterial systems studied by both duplex ultrasonography and contrast arteriography to better define the role of carotid duplex scanning in the surgical decision-making process. These studies were reviewed in a blinded fashion in conjunction with history and physical examination data by two surgeons, one operating on only symptomatic lesions, the other operating on both symptomatic and asymptomatic lesions. Results were analyzed to ascertain if there was agreement regarding decisions for carotid endarterectomy based on scan findings compared with decisions based on arteriographic findings. Scans were also compared with arteriograms and data were analyzed by decision matrix analysis. The accuracy of duplex scanning in relation to arteriography was 81% for detection of disease, 90% for the detection of ulceration, 83% for the detection of a critical stenosis, and 99% for the detection of total arterial occlusion. There was agreement between the two studies regarding the need for carotid surgery in 91% and 89% of carotid arteries, according to surgeons A and B, respectively. Regardless of the surgeons' indications for carotid endarterectomy, duplex ultrasonography provides sufficient information for proper surgical decision making in a high percentage of patients. The accuracy of duplex scanning and the risks of contrast arteriography suggest a possible future role for the routine use of duplex ultrasonography with selective utilization of arteriography in the surgical decision-making process in patients being evaluated for cerebrovascular occlusive disease.


GABAergic dysfunction in mood disorders.
The authors review the available literature on the preclinical and clinical studies involving GABAergic neurotransmission in mood disorders. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter present almost exclusively in the central nervous system (CNS), distributed across almost all brain regions, and expressed in interneurons modulating local circuits. The role of GABAergic dysfunction in mood disorders was first proposed 20 years ago. Preclinical studies have suggested that GABA levels may be decreased in animal models of depression, and clinical studies reported low plasma and CSF GABA levels in mood disorder patients. Also, antidepressants, mood stabilizers, electroconvulsive therapy, and GABA agonists have been shown to reverse the depression-like behavior in animal models and to be effective in unipolar and bipolar patients by increasing brain GABAergic activity. The hypothesis of reduced GABAergic activity in mood disorders may complement the monoaminergic and serotonergic theories, proposing that the balance between multiple neurotransmitter systems may be altered in these disorders. However, low GABAergic cortical function may probably be a feature of a subset of mood disorder patients, representing a genetic susceptibility. In this paper, we discuss the status of GABAergic hypothesis of mood disorders and suggest possible directions for future preclinical and clinical research in this area.


The one-step synthesis of polymer-based magnetic γ-Fe2O3/carboxymethyl cellulose nanocomposites.
A novel one-step procedure is described for synthesizing water soluble biocompatible nanocomposites from maghemite nanoparticles and carboxymethyl cellulose (CMC). The procedure allows the magneto-sensitive nanocomposites with a controlled content of the inorganic phase. The maghemite formation has been proved by X-ray diffraction analysis and Mossbauer spectroscopy. An average diameter of the maghemite nanoparticles is equal to 11nm according to transmission electron microscopy. As shown by FTIR spectroscopy, the nanoparticles bind to the polymer matrix via electrostatic and coordination interactions. The diameter of the nanocomposites in dilute aqueous solutions vary from 50nm at the iron content of 2-4.3wt.% to 140nm at the iron content of 5.2-8.6wt.%. The study of specific magnetization of the nanocomposites vs. applied magnetic field indicates their ferromagnetic properties. The saturation magnetization and coercive force of the sample with the maximum maghemite content (8.6wt.%) are 11.5emu/g and 30.08Oe, respectively. The nanocomposite motion has been shown to be controlled by an external magnetic field. The biocompartible maghemite-CMC nanocomposites seem to be promising for encapsulation and delivery of biologically active compounds.


[Fatal iatrogenically-induced hyperglycemia following accidental glibenclamide ingestion].
A 2 9/12 years old girl had swallowed 8 to 9 tablets Euglucon N. By concatenation of unfortunatable facts the infant died of hyperglycaemia. The findings from this case should contribute to differentiate also in medical textbooks therapeutic recommendations.


Coronary artery calcium and physical function in older adults: the Cardiovascular Health Study.
In older adults without clinical cardiovascular disease, coronary artery calcium (CAC) is associated with other subclinical vascular diseases, which, in turn, predict physical dysfunction. However, the association between CAC and physical function is unstudied. In 387 older community-dwellers from the Cardiovascular Health Study without clinical cardiovascular diseases (mean age +/- standard deviation = 78.7 +/- 3.7, 35% men, 22% African Americans), CAC was measured using electron beam tomography, and physical performance was assessed by usual pace gait speed, chair stand, and tandem stand. Differences in physical performance across CAC quartiles were investigated in the whole cohort and by gender. Associations with gait speed (m/s) were assessed in multivariable models using both the continuous form of CAC score (log(CAC)) and quartiles of CAC, adjusting for demographics and comorbidities. No differences in physical performance were observed across CAC quartiles in the whole group. In gender-stratified analyses, a significant association was shown among women, who had progressively lower gait speed across CAC quartiles: Those with CAC > 220 walked more than 0.1 m/s slower than those with CAC < 35 (age-adjusted ptrend =.017). After multivariable adjustment, the association remained statistically significant for women in both linear (log(CAC) and gait speed, p =.025) and logistic models: Each of the top three CAC quartiles (35-220, 221-659, and > or = 660) had a more than twofold odds of walking slower than 1 m/s, compared to the lowest CAC quartile (< 35; p =.021). In this sample of older community-dwellers without overt cardiovascular disease, CAC was inversely related to gait speed in women, but not in men.


Mechanisms for the emergence of catecholamine-sensitive adenylate cyclase and beta-adrenergic receptors in cultured hepatocytes. Dependence on protein and RNA synthesis and suppression by isoproterenol.
Adult male rat hepatocytes, which normally respond poorly to beta-adrenergic agents, acquire such responsiveness during primary monolayer culture. We here show that the rise in catecholamine-sensitive adenylate cyclase activity in hepatocytes in vitro is closely paralleled by an increase in the ability to bind the beta-adrenoceptor ligand [125I]cyanopindolol. The emergence of beta-adrenergic responsiveness did not require cell attachment or serum. Addition of dexamethasone, insulin, thyroxine or dihydrotestosterone to the cultures, singly or in combination, did not prevent the augmented beta-adrenergic responsiveness. The increase in catecholamine-sensitive adenylate cyclase activity and [125I]cyanopindolol binding could be blocked by cycloheximide or actinomycin D. Exposure of the cultures to isoproterenol at 3-hourly intervals led to a dose-dependent suppression of the rise in isoproterenol-responsive adenylate cyclase and prevented the increase in beta-adrenoceptor binding.


In vitro autoradiography of [3H]acetylcholine binding in rat hind limb muscles.
The morphological distribution of acetylcholine receptors in normal and denervated rat tibialis anterior and soleus muscles was studied by in vitro quantitative autoradiography with [3H]acetylcholine (ACh). In normal muscles [3H]ACh binding was restricted to the neuromuscular junction, while denervated muscles showed binding also in extrajunctional areas. After denervation there was also an increase in the junctional binding.


A paleogenome from a Holocene individual supports genetic continuity in Southeast Alaska.
Many specifics of the population histories of the Indigenous peoples of North America remain contentious owing to a dearth of physical evidence. Only few ancient human genomes have been recovered from the Pacific Northwest Coast, a region increasingly supported as a coastal migration route for the initial peopling of the Americas. Here, we report paleogenomic data from the remains of a ∼3,000-year-old female individual from Southeast Alaska, named Tatóok yík yées sháawat (TYYS). Our results demonstrate at least 3,000 years of matrilineal genetic continuity in Southeast Alaska, and that TYYS is most closely related to ancient and present-day northern Pacific Northwest Coast Indigenous Americans. We find no evidence of Paleo-Inuit (represented by Saqqaq) ancestry in present-day or ancient Pacific Northwest peoples. Instead, our analyses suggest the Saqqaq genome harbors Northern Native American ancestry. This study sheds further light on the human population history of the northern Pacific Northwest Coast.


Adrenaline in various organs of the rat: its origin, location and diurnal fluctuation.
In order to examine the origin and location of adrenaline in peripheral organs of mammals, adrenaline and noradrenaline were measured in several organs of the rat after adrenalectomy, guanethidine treatment and imipramine injection. One week after bilateral adrenalectomy, adrenaline disappeared almost completely from the heart, spleen and submaxillary gland. Chronic administration of guanethidine caused decreases in both noradrenaline and adrenaline in the peripheral organs. Injection of imipramine induced a reduction of adrenaline concentration in the spleen and submaxillary gland. It is considered that adrenaline in the peripheral organs of mammals is mostly derived from the adrenal gland and that circulating adrenaline is taken up by sympathetic nerve endings in the organs. The adrenaline content of the peripheral organs increased after electric foot-shock and changed according to the time of day. The peak of the circadian rhythm appeared about 6 hours after the peak of the urinary adrenaline rhythm. These findings suggest that adrenaline in body organs plays some role in the responses of the sympathetic nervous system to stressful conditions or even to daily activities.


Genetic demonstration of mitotic recombination in cultured Chinese hamster cell hybrids.
Chinese hamster ovary cell hybrids were constructed that are heterozygous for two markers, leuS and emtB, linked to the long arm of chromosome 2. In addition, the chromosome 2 carrying the wild-type leuS and emtB alleles contains, on its short arm, a homogeneously staining region (hsr) in which the gene encoding dihydrofolate reductase (dhfr) is amplified approximately 50-fold. This provides a convenient cytogenetic and biochemical means to distinguish the chromosome 2s from the different parents. Analysis of emetine-resistant segregants isolated from such hybrids identified three distinct classes of segregants. One rare class of segregants loses the wild-type leuS and emtB gene functions on the long arm of the hsr chromosome 2 (H-2) but retains the amplified dhfr genes on the opposite arm. Detailed genetic analysis of two such segregants that did not arise by chromosome loss or deletion revealed that new gene linkage relationships had been established on the H-2 chromosome in each, demonstrating that the segregation events in these cell lines involved mitotic recombination.


Influential articles on shoulder arthroplasty: bibliometric analysis and visualized study.
Shoulder arthroplasty has had increasing global demand, technical development, and research interest in the past few decades, with the publication of numerous articles. However, little is known about the characteristics and evaluation of these articles. Our objective was to study and analyze the top 100 cited articles in shoulder arthroplasty research. Publications on shoulder arthroplasty from inception to 2022 were retrieved from the Web of Science. The top 100 publications were defined by the number of citations, and their characteristics were recorded and analyzed. A visualized study of the articles was performed using VOSviewer software. The top 100 cited articles were published between 1981 and 2018, with the 2000s the most productive decade. Citations per article ranged from 103 to 822. The countries with the most articles were the United States followed by France and Switzerland. Most of the articles were level III evidence. The keywords for the articles were primarily in 5 clusters: infection, fracture, osteoarthritis, perioperative complications, and prosthetic design. The characteristics of influential articles on shoulder arthroplasty were thoroughly analyzed. Most studies focused on surgical techniques and perioperative complications with a relatively low level of evidence.


Decreased expression of BRCA1-associated protein 1 predicts unfavorable survival in gastric adenocarcinoma.
BRCA1-associated protein 1 (BAP1) has been reported as a novel tumor suppressor, while in gastric adenocarcinoma, the function of this protein was still await to be uncovered. Based on a large group of patients with gastric adenocarcinoma, our study aimed to have a further understanding about the correlation of BAP1 expression and patients' clinical outcomes. We performed quantitative PCR and Western blot to examine BAP1 expression in 38 cases of gastric adenocarcinoma samples and adjacent non-cancerous tissues. Immunochemistry was used to evaluate BAP1 expression in a large cohort of 474 paraffin-embedded specimens. The clinical and prognostic significance of BAP1 expression was statistically analyzed. Postoperative survival between groups was using Kaplan-Meier analysis. BAP1 was overexpressed in paracancerous normal mucosa compared with gastric cancer. Decreased BAP1 expression was associated with higher histologic grade (P = 0.044), tumor infiltration (P < 0.001), metastasis status (P = 0.023), and TNM stage (P < 0.001). Patients with low expression of BAP1 had shorter overall survival compared with those with high expression (P < 0.001). Patients' survival in stage N0 could be stratified by the expression of BAP1. Multivariate analysis showed that in gastric adenocarcinoma, BAP1 expressing level was an independent prognostic factor (RR = 0.575, P < 0.001). Decreased expression of BAP1 suggests pessimistic prognosis for gastric adenocarcinoma patients. Further studies are warranted.


Debate: Whether level I evidence comparing thoracic endovascular repair and medical management is necessary for uncomplicated type B aortic dissections.
Type B aortic dissections continue to be one of the most challenging clinical scenarios confronting vascular surgeons. In the era of open surgery, the therapeutic options were limited to medical management of hypertension and large open thoracoabdominal operations. In the current endovascular era, the operative strategies have become less invasive but the questions regarding therapeutic approaches have become more numerous and complex. In patients with acute uncomplicated type B aortic dissections, we are still unsure as to which patients are best treated with medical therapy alone or with the addition of early endovascular repair. Data from single centers and registries have provided some guidance; however, questions remain. Perhaps level 1 evidence from well-designed randomized controlled trials will answer all of our questions. This is the topic of the current debate.


How should we define appropriate patients for percutaneous transluminal renal angioplasty treatment?
Renovascular hypertension (RVH) is one of the most common causes of secondary hypertension and can result in resistant hypertension. RVH is associated with an increased risk for progressive decline in renal function, cardiac destabilization syndromes including "flash" pulmonary edema, recurrent congestive heart failure, and cerebrocardiovascular disease. The most common cause of renal artery stenosis (RAS) is atherosclerotic lesions, followed by fibromuscular dysplasia. The endovascular technique of percutaneous transluminal renal angioplasty (PTRA) with or without stenting is one of the standard treatments for RAS. Randomized controlled trials comparing medical therapy with PTRA to medical therapy alone have failed to show a benefit of PTRA; however, the subjects of these randomized clinical trials were limited to atherosclerotic RAS patients, and patients with the most severe RAS, who would be more likely to benefit from PTRA, might not have been enrolled in these trials. This review compares international guidelines related to PTRA, reevaluates the effects of PTRA treatment on blood pressure and renal and cardiac function, discusses strategies for the management of RVH patients, and identifies factors that may predict which patients are most likely to benefit from PTRA.


[Mechanism of disorders of inhibition of electrogenesis in spinal alpha-motor neurons in experimental local botulin poisoning].
Disorders of postsynaptic inhibition and of the spinal cord alpha-motoneurons were studied in cats with experimental local botulinum intoxication. A significant decrease of the reciprocal, and, to a lesser extent, of polysynaptic inhibitory postsynaptic potential (IPSP) was noted. With the appearance of total paralysis of the muscles in the poisoned extremity there proved to be an even greater depression of the reciprocal and polysynaptic IPSP; however, they never disappeared or turned into depolarization potentials. Synaptic permeability of motor neurons as a rule decreased during the IPSP development, this indirectly indicating a reduction of ion transport.


The effect of early treatment at the initial stage 3 moderate phase of retinopathy of prematurity on severe retinal changes.
To compare the outcome of early treatment at the initial stage 3 moderate phase of retinopathy of prematurity (ROP) with that at prethreshold ROP. The outcome of treatment of 117 very-low-birth-weight infants was reviewed. Sixty-eight infants underwent their first treatment at prethreshold ROP (group A). The other 49 infants underwent their first treatment at the initial stage 3 moderate phase of ROP (pre-prethreshold ROP) (group B). The first treatment was performed by laser photocoagulation or cryotherapy. Eleven clinical variables were included in the evaluation of the two groups. The outcome of treatment of the two groups was compared as favorable or unfavorable. Logistic regression analysis was performed to assess the relation between each independent variable and an unfavorable outcome. The extent of contiguous stage 3 moderate ROP and that of cumulative stage 3 moderate ROP were significantly smaller in group B. There were nine unfavorable outcomes in group A, but none in group B. Logistic regression analysis showed that the extent of cumulative stage 3 moderate ROP and the presence of zone 1 retinopathy were major predictive factors for unfavorable outcome in the treatment of very-low-birth-weight infants. Early treatment at the initial stage 3 moderate phase of ROP decreases the occurrence of severe retinal changes.


Maternal knowledge, outcome expectancies and normative beliefs as determinants of cessation of exclusive breastfeeding: a cross-sectional study in rural Kenya.
Despite the importance of multiple psychosocial factors on nutrition-related behavior, very few studies have explored beyond the role of mothers' knowledge and perception of child-focused outcomes on the duration of exclusive breastfeeding in Africa. Our objective was to determine the relationships among mothers' knowledge, outcome expectancies, normative beliefs, and cessation of exclusive breastfeeding in rural Kenya. A cross-sectional survey was conducted among 400 mothers of children, 0-24 months old, in rural Kenya. Early child-feeding practices, knowledge of breastfeeding recommendations, beliefs associated with impact of exclusive breastfeeding on child- and mother-focused outcomes and perception of acceptability of exclusive breastfeeding by important others were examined. Cox regression analysis was used to assess the relationship between independent variables of interest and cessation of exclusive breastfeeding. Being knowledgeable of breastfeeding-related recommendations, positive beliefs on the impact of exclusive breastfeeding on child- focused outcomes, having a more positive perception of the impact of exclusive breastfeeding on mother-focused outcomes and a more positive perception of acceptability of exclusive breastfeeding by important others were associated with significantly lower risks of premature cessation of exclusive breastfeeding. In addition to knowledge levels, mothers' beliefs play an important role in mothers' decisions to practice exclusive breastfeeding. Mother's beliefs on the impact of exclusive breastfeeding on the mother's health, physical appearance and ability to engage in other activities were shown to have the strongest relationship with premature cessation of exclusive breastfeeding. Addressing these beliefs has the potential to contribute to more effective exclusive breastfeeding promotion efforts in rural Kenya.


Association between β+252 tumour necrosis factor polymorphism and asthma in western Saudi children.
There is strong evidence that supports the role of tumour necrosis factors (TNF-alpha/beta) as common genetic factors, located on 6p21.1-6p21.3 loci, in the pathogenesis of asthma disease. In this study, we extended our research work on TNFA to include the genotyping of Saudi asthmatic children as regards to TNFB gene (namely as lymphotoxin-α, LTA). We examined 60 asthmatic Saudi children compared to 56 healthy non-asthmatics using the PCR-RFLP analyses to identify the polymorphism +252A>G in intron 1 in lymphotoxin-α gene. We identified 55% of the allele A of the LTA∗NcoI polymorphism in subjects with asthma disease, and 45% of the allele G. In this study, the frequency of the LTA∗NcoI-A/A genotype was 40% preferably to the LTA∗NcoI-G/A and LTA∗NcoI-G/G genotypes. In addition, the severe persistent asthmatic cases were associated with the LTA∗NcoI-AA genotype at a frequency of 80%, while the genotype LTA∗NcoI-GG are associated with the mildest form of the disease. Consequently, one could predict the severity of asthma and hence the polymorphism of the LTA∗NcoI. Herein, we stated that more than 93% of Saudi children under investigation lived in the randomized areas of western regions of Saudi Arabia. In conclusion, genotype frequencies for the LTA+252 polymorphisms were significantly different from the controls. These findings may have implications for future early intervention studies by helping to identify infants at increased risk for wheezing and childhood asthma.


Endobronchial metastasis of ovarian cancer rescued by tumor ablation and a self-expanding hybrid stent: A case report and review of the literature.
Tracheal stenosis caused by malignancy is a life-threatening complication. Herein, we performed tumor ablation and airway stenting using a hybrid stent on a patient with upper tracheal stenosis caused by endobronchial metastasis of ovarian cancer. To date, only 9 cases of endobronchial metastasis of ovarian cancer have been reported. This is the first reported case of endobronchial metastasis in the upper part of the trachea, which had a favorable outcome after tumor ablation as a sequential treatment and use of a hybrid stent. In addition, 10 cases of endobronchial metastasis of ovarian cancer, including ours and other case reports, were reviewed.


Pulmonary lesions: correlative study of dynamic triple-phase enhanced CT perfusion imaging with tumor angiogenesis and vascular endothelial growth factor expression.
To investigate value of the quantitative perfusion parameters of dynamic triple-phase enhanced CT in differential diagnosis of pulmonary lesions, and explore the correlation between perfusion parameters of lung cancer with microvessel density (MVD) and vascular endothelial growth factor (VEGF). 73 consecutive patients with lung lesions who successfully underwent pre-operative CT perfusion examination with dynamic triple-phase enhanced CT and received a final diagnosis by postoperative pathology or a clinical follow-up. The cases were divided into malignant and benign groups according to the pathological results. CT perfusion parameters, such as Median, Mean, Standard deviation (Std), Q10, Q25, Q50, Q75, Q90 of pulmonary artery perfusion (PAP), bronchial artery perfusion (BAP), perfusion index (PI) and arterial enhancement fraction (AEF) were obtained by performing computed tomography perfusion imaging (CTPI). Computed tomography perfusion (CTP) parameters were compared between malignant and benign lesions. The receiver operating characteristic (ROC) curve was used to assess the diagnostic efficiency of CTP parameters in diagnosing malignant lesions. The correlations between CTP parameters with MVD and VEGF were analysed in 36 lung cancer patients who had extra sections be used for immunohistochemistry staining of CD34 and VEGF. BAP (Mean, Std, Q90) and PI Std of benign lesions were higher than malignant lesions (p < 0.05), and PAP (Q10, Q25), PI (Median, Mean, Q10, Q25, Q50) of malignant lesions were higher than the benign (p < 0.05). The area under the ROC curve of PI Mean, PI Q10 and PI Std was 0.722 (95% CI = [0.595-0.845]), 0.728 (95% CI = [0.612-0.844]) and 0.717 (95% CI = [0.598-0.835]) respectively. Partial perfusion parameters of BAP and AEF Q10 were positively correlated with MVD (p value range is < 0.001-0.037, ρ value range is 0.483-0.683), and partial perfusion parameters of PI were negatively correlated with MVD (p value range is 0.001-0.041,ρvalue range is - 0.523-- 0.343). Partial perfusion parameters of BAP and AEF Q10 were positively correlated with VEGF (p value range is 0.001-0.016, ρvalue range is 0.398-0.570), meanwhile some perfusion parameters of PAP and PI were negatively correlated with VEGF (p value range is 0.001-0.040, ρ value range is - 0.657-0.343). Quantitative parameters of dynamic triple-phase enhanced CT can provide diagnostic basis for the differentiation of lung lesions, and there were connection with tumor angiogenesis and vascular endothelial growth factor expression.


Organ culture of adult amphibian heart: a fine structural analysis.
Pieces of hearts from adult newts were cultured up to 2 months. Within 7 days of culture, approximately 37% of the cardiac explants were attached to the substrate and more than 33% of the attached explants and approximately 15% of the unattached explants established pulsation rates ranging from 3 to 67 beats/min. The control and cultured explants were processed at weekly intervals for electron microscopy. The diameter of the control cardiac muscle cells ranged approximately 3-5 micron. The cell surface was provided with microvilli. The intercellular spaces ranged approximately 150-500 A. The intercalated discs lacked the step-like courses observed in the mammalian cardiac muscle. Sarcoplasmic reticulum was scanty. Desmosomal-dense materials were frequently continuous with the Z-bands of both control and cultured cardiac muscle cells. The transverse tubular system and gap junction were absent in newt ventricles. The functional implications of these characterisitics are discussed. At the end of 1 week of culture, the surfaces of the explants were covered by one or more layers of non-muscle cells, and the core of the explants consisted mostly of cardiac muscle cells. In a few cardiac muscle cells the myofibrillar organization was disrupted, resulting in the distribution of scattered patches of myofibrils and free myofilaments in the sarcoplasm. A small number of intact muscle cells contained a considerable number of dense granules in the sarcoplasm. At 15 days in culture, a large number of muscle cells showed structural features reminiscent of embryonic cardiac muscle cells. These cells possessed patches of myofibrils, scattered myofilaments and scanty sarcoplasmic reticulum along with other cellular organelles and inclusions. Several of these altered cardiac muscle cells contained mitotic figures. The cardiac explants maintained the initial beating rate until the end of 2 months of culture, except for the 11% of the explants which stopped beating. By 3-4 weeks in culture, most of the cardiac muscle cells possessed the altered cell morphology mentioned above. The explants after 60 days in culture became more flattened than the earlier explants. The intact cardiac muscle cells were rare, and the cores of the explants were mostly occupied by the altered cardiac muscle cells. It is evident from our studies that the cardiac muscle cells have undergone dedifferentiation in long-term culture, and that this dedifferentiation process has yet had no effect in the maintenance of contractility of the explants. Furthermore, these dedifferentiated cardiac muscle cells are capable of DNA synthesis and mitosis.


Valproic acid improves the tolerance for the stress in learned helplessness rats.
In this study, we investigated whether previously stressed rats with learned helplessness (LH) paradigm could recover from depressive-like behavior four weeks after the exposure, and also whether chronic treatment with valproic acid (VPA) could prevent behavioral despair due to the second stress on days 54 in these animals. Four weeks after induction of LH, we confirmed behavioral remission in the previously stressed rats. Two-way analysis of variance (ANOVA) performed with two factors, pretreatment (LH or Control) and drug (VPA or Saline), revealed a significant main effect of the drug on immobility time in forced swimming test. Post hoc test showed a shorter immobility time in the LH+VPA group than in the LH+Saline group. Immunohistochemical study of synapsin I showed a significant effect of drug by pretreatment interaction on immunoreactivity of synapsin I in the hippocampus: its expression levels in the regions were higher in the LH+VPA group than in the LH+Saline group. These results suggest that VPA could prevent the reappearance of stress-induced depressive-like behaviors in the rats recovering from prior stress, and that the drug-induced presynaptic changes in the expression of synapsin I in the hippocampus of LH animals might be related to improved tolerance toward the stress.


Performance characteristics of unsedated ultrathin video endoscopy in the assessment of the upper GI tract: systematic review and meta-analysis.
Reports on the performance of unsedated ultrathin endoscopy via the transnasal (uTNE) and transoral (uTOE) routes are conflicting. We aimed to estimate the technical success rate, patient preference, and acceptability of uTNE and uTOE alone and in comparison with conventional EGD (cEGD; with or without sedation). A systematic review and meta-analysis was performed on all primary studies reporting the outcomes of interest. Electronic databases (Cochrane library, MEDLINE, EMBASE) were searched on February 1, 2014. Thirty-four studies met the inclusion criteria with 6659 patients in total. The pooled technical success rate was 94.0% for uTNE (95% confidence interval [CI], 91.6-95.8; 30 studies) and 97.8% for uTOE (95% CI, 95.6-98.9; 16 studies). The difference in proportion of success for uTNE compared with cEGD was -2.0% (95% CI, -4.0 to -1.0; 18 studies), but that difference was not significant when uTNE < 5.9 mm in diameter was used (-1.0%; 95% CI, -3.0 to .0; 9 studies). There was no significant difference in success rate between uTOE and cEGD (.0%; 95% CI, -1.0 to 2.0; 10 studies). The pooled difference in proportion of patients who preferred uTNE over cEGD was 63.0% (95% CI, 49.0-76.0; 10 studies), whereas preference for uTOE versus cEGD was not significantly different (38.0%; 95% CI, -4.0 to 80.0; 2 studies). Acceptability was high for both uTNE (85.2%; 95% CI, 79.1-89.9; 16 studies) and uTOE (88.7%; 95% CI, 82.4-92.9; 10 studies). Technical success rate for uTNE < 5.9 mm is equivalent to cEGD. uTNE has high patient acceptability, with better patient preference, and therefore could be a useful alternative to cEGD for screening purposes. uTOE had a similar technical success rate but an equivocal preference to cEGD.


Advancement of cancer immunotherapy using nanoparticles-based nanomedicine.
Cancer has complex pathophysiology and is one of the primary causes of death and morbidity across the world. Chemotherapy, targeted therapy, radiation therapy, and immunotherapy are examples of traditional cancer treatments. However, these conventional treatment regimens have many drawbacks, such as lack of selectivity, non-targeted cytotoxicity, insufficient drug delivery at tumor sites, and multi-drug resistance, leading to less potent/ineffective cancer treatment. Due to its immanent biophysical property and ability to change in numerous ways, nano-technology has completely transformed how cancer is identified and treated in recent years. Furthermore, nanotechnology providing solutions to these restrictions and boosting cancer therapy. Nanoparticles are widely used nanomedicine platform in cancer immunotherapy due to their excellent physicochemical properties that include size, shape, and surface features, resulting into desirable biological interactions and have been categorized into several types. Nanoparticles can also be potentially be up taken by antigen-presenting cells that promote the cytosolic delivery of encapsulated antigens and adjuvants. Furthermore, nanoparticles can be fine-tuned and functionalized with specific moieties to promote their efficacy in targeting and delivering cargo materials to specific locations. In this review, we summarized and discussed nanoparticles and potential features to be used as carriers in cancer immunotherapy, the current status of different types of nanoparticles, and the importance of their functionalization. Furthermore, we have also discussed nanoparticles-based nanomedicine in targeted delivery of encapsulated cancer immunotherapeutic and their involvement in the modulation of the tumor microenvironment, promoting cancer immunotherapy.


Synthesis of diverse β-quaternary ketones via palladium-catalyzed asymmetric conjugate addition of arylboronic acids to cyclic enones.
The development and optimization of a palladium-catalyzed asymmetric conjugate addition of arylboronic acids to cyclic enone conjugate acceptors is described. These reactions employ air-stable and readily-available reagents in an operationally simple and robust transformation that yields β-quaternary ketones in high yields and enantioselectivities. Notably, the reaction itself is highly tolerant of atmospheric oxygen and moisture and therefore does not require the use of dry or deoxygenated solvents, specially purified reagents, or an inert atmosphere. The ring size and β-substituent of the enone are highly variable, and a wide variety of β-quaternary ketones can be synthesized. More recently, the use of NH4PF6 has further expanded the substrate scope to include heteroatom-containing arylboronic acids and β-acyl enone substrates.


Neuroembryology and brain malformations: an overview.
Modern neuroembryology integrates descriptive morphogenesis with more recent insight into molecular genetic programing and data enabled by cell-specific tissue markers that further define histogenesis. Maturation of individual neurons involves the development of energy pumps to maintain membrane excitability, ion channels, and membrane receptors. Most malformations of the nervous system are best understood in the context of aberrations of normal developmental processes that result in abnormal structure and function. Early malformations usually are disorders of genetic expression along gradients of the three axes of the neural tube, defective segmentation, or mixed lineages of individual cells. Later disorders mainly involve cellular migrations, axonal pathfinding, synaptogenesis, and myelination. Advances in neuroimaging now enable the diagnosis of many malformations in utero, at birth, or in early infancy in the living patient by abnormal macroscopic form of the brain. These images are complimented by modern neuropathological methods that disclose microscopic, immunocytochemical, and subcellular details beyond the resolution of MRI. Correlations may be made of both normal and abnormal ontogenesis with clinical neurological and EEG maturation in the preterm or term neonate for a better understanding of perinatal neurological disease. Precision in terminology is a key to scientific communication.


Thiazolo[4,5-d]pyrimidines. Part II. Synthesis and anti-human cytomegalovirus activity in vitro of certain acyclonucleosides and acyclonucleotides derived from the guanine analogue 5-aminothiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione.
The synthesis and in vitro antiviral activity of certain hydroxyalkoxymethyl, hydroxyalkyl, hydroxyalkenyl and phosphonoalkenyl derivatives of the guanine congener 5-aminothiazolo[4,5-d]pyrimidine-2,7(3H,6H)-dione are reported. The compounds of this study were selected for their structural similarity to acyclonucleosides with known anti-herpesvirus activity. 5-Amino-3-[(Z)-4-hydroxy-2-buten-1-yl]thiazolo[4,5-d]pyrimidine-2, 7(3H,6H)- dione was the only member of the series to display significant in vitro activity against human cytomegalovirus (HCMV); however, this compound did not inhibit other herpesviruses, human immunodeficiency virus type 1 or murine cytomegalovirus. It was found to have a cytotoxicity profile similar to that of ganciclovir (DHPG). The antiviral effect was found to be sensitive to the initial viral input and the time of addition during the virus replication cycle. Significantly, the compound was found to have equal anti-HCMV activity, against standard virus strains, to DHPG, but also showed potent activity against DHPG-resistant virus strains, except for a strain mutated in the UL97 (phosphotransferase) gene.


Effects of ketamine on liver blood flow and hepatic oxygen consumption. Studies in the anaesthetised greyhound.
The effects of three increasing doses of ketamine on the blood flow to, and oxygen consumption of, the liver, were studied in seven anaesthetised greyhounds. Hepatic arterial and portal venous blood flows were measured continuously using electromagnetic flow probes, and mean arterial pressure and cardiac output monitored as appropriate. Ketamine, even at the highest dose, had little effect on the blood flow to the liver: hepatic arterial blood flow and portal venous blood flow did not differ significantly from their baseline values. However, the oxygen delivery to the liver decreased due, probably, to an increase in oxygen consumption by the pre-portal organs.


Prognostic and predictive values of baseline and mid-treatment FDG-PET in oropharyngeal carcinoma treated with primary definitive (chemo)radiation and impact of HPV status: Review of current literature and emerging roles.
This study provides a review of the literature assessing whether semiquantitative PET parameters acquired at baseline and/or during definitive (chemo)radiotherapy ("prePET" and "iPET") can predict survival outcomes in patients with oropharyngeal squamous cell carcinoma (OPC), and the impact of human papilloma virus (HPV) status. A literature search was carried out using PubMed and Embase between 2001 to 2021 in accordance with PRISMA. The analysis included 22 FDG-PET/CT studies [1-22], 19 pre-PET and 3 both pre-PET and iPET, The analysis involved 2646 patients, of which 1483 are HPV-positive (17 studies: 10 mixed and 7 HPV-positive only), 589 are HPV-negative, and 574 have unknown HPV status. Eighteen studies found significant correlations of survival outcomes with pre-PET parameters, most commonly primary or "Total" (combined primary and nodal) metabolic tumour volume and/or total lesional glycolysis. Two studies could not establish significant correlations and both employed SUVmax only. Two studies also could not establish significant correlations when taking into account of the HPV-positive population only. Because of the heterogeneity and lack of standardized methodology, no conclusions on optimal cut-off values can be drawn. Ten studies specifically evaluated HPV-positive patients: five showed positive correlation of pre-PET parameters and survival outcomes, but four of these studies did not include advanced T or N staging in multivariate analysis, and two studies only showed positive correlations after excluding high risk patients with smoking history or adverse CT features. Two studies found that prePET parameters predicted treatment outcomes only in HPV-negative but not HPV-positive patients. Two studies found that iPET parameters could predict outcomes in HPV-positive patients but not prePET parameters. The current literature supports high pre-treatment metabolic burden prior to definitive (chemo)radiotherapy can predict poor treatment outcomes for HPV-negative OPC patients. Evidence is conflicting and currently does not support correlation in HPV-positive patients.


Impulsivity, aggression, and neuroendocrine responses to serotonergic stimulation in substance abusers.
Alterations in the activity of central serotonergic systems have been implicated in impulsive and aggressive behavior. We examined the neuroendocrine and psychological responses of 24 substance users with differing levels of aggressiveness and impulsivity to the oral administration of an indirect serotonin agonist fenfluramine (60 mg) or placebo given in a double-blind crossover design. All subjects were volunteers on a closed research ward and were abstinent from drugs for a minimum of 5 days. Baseline plasma prolactin (PRL) levels were greater in the groups with higher levels of self-reported aggressiveness and impulsivity. When adjusted for the baseline, PRL and cortisol responses 180 min after fenfluramine administration were significantly elevated in subjects with higher levels of aggressiveness and impulsivity. Peak cortisol levels were correlated with impulsivity. PRL and cortisol responses to fenfluramine were more strongly correlated with impulsivity than aggressiveness. Also, the more impulsive subjects reported a decrease in subjective states of depression, hostility and anxiety after drug treatment. These data further support the hypothesis of altered serotonergic activity in aggressive and impulsive behaviors.


Silk Fibroin/Collagen Blended Membrane Fabricated via a Green Papermaking Method for Potential Guided Bone Regeneration Application: In Vitro and In Vivo Evaluation.
Guided bone regeneration (GBR) technology is a commonly used surgical procedure for the repair of damaged periodontal tissues. Poor mechanical property and rapid degradation rate are the major reasons for GBR membrane failure in clinical applications. Herein, we applied a green papermaking method to fabricate silk fibroin (SF) membranes blended with collagen and tested their performance. The results showed that the blended SF75 (SF and collagen in a weight ratio of 75:25) membranes are biocompatible with good mechanical properties in the wet condition and appropriate biodegradation rate. MC3T3-E1 osteoblast cell adhesion and proliferation on the membranes were improved by the hybrid biological functions of SF and collagen. Subcutaneous implantation in rats for 9 weeks demonstrated that the membranes induced a less severe inflammatory response. The biodegradation time of the SF75 membranes was appropriate for tissue regeneration. This research, for the first time, reports a blended membrane prepared from silk fibroin and collagen with an ecofriendly method, which shows promise for application in guided bone regeneration.


An overview of the pharmacological activities of scopoletin against different chronic diseases.
Chronic diseases are considered a major public health concern worldwide, and most of these diseases like cancer, cardiovascular, metabolic, and neurological disorders occur due to atypical regulation of multiple signaling pathways. It has also been observed that most of the currently approved therapies for these diseases fail to show prolonged efficacy due to their mono-targeted nature and are associated with the development of chemoresistance, thus restricting their utility. The plant-derived compounds, on the other hand, show multi-targeted nature, and thus these phytochemicals have gained wide attention as they offer negligible side effects. The present review aims to recapitulate the potential effects of one such phytochemical, Scopoletin, which was found to have a diverse range of pharmacological activities such as anti-cancer, anti-diabetic, anti-inflammatory, cardioprotective, hepatoprotective, etc. Scopoletin modulated multiple molecular signatures in cancer, including AMPK, EGFR, MAPK/ ERK, NF-κB, PI3K/Akt/ mTOR, and STAT3; regulated the levels of critical markers of metabolic diseases such as ALT, AST, TG, and TC; inflammatory diseases such as ILs and TNFs; neurological diseases such as AChE, etc. thus relieving the symptoms and severity associated with these diseases. Further, this compound has a non-toxic nature and possesses an excellent pharmacokinetic property, which warrants further investigation in clinical settings for developing it as a potential drug.


Weight changes of cross-desert migrants at an oasis -do energetic considerations alone determine the length of stopover?
Trans-Saharan insectivorous passerine night migrants stopping-over at a small oasis in Sinai were weighed as frequently as possible, throughout the entire length of fall and spring migration passages. Due to the small size of the oasis and the intensive trapping effort, most stopping-over birds were captured and weighed throughout a sizeable portion of their stopover period. Weights at first capture were either similar in both seasons, or greater in fall than in spring. In some species fall migrants that stayed one day were heavier than those staying longer. In other species, and for all species in spring, weights of birds that stayed one day did not differ from those staying longer. In most species the weight of birds that stayed for more than one day did not vary significantly between arrival and departure, and cases of weight gains were commoner in fall than in spring. Trends of weight changes of an individual during stopover were usually inconsistent, but the longer it stayed, more it gained (in fall), or less it lost (in spring). It is proposed that stopping-over birds do not always resume their migration only after their fat reserves have been replenished, but that their decision to take off, or the reappearance of the migration impulse, are also controlled by a time program incorporated into their endogenous migration scheme, which constantly updates the time left for sampling and refuelling. It seems that in spring less time is allotted for the whole migration program, hence the time constraint overrides then all other tactical considerations, such as the state of fat reserves, and the weather.


Challenges experienced by parents living with a child with attention deficit hyperactivity disorder.
The aim of this South African study was to explore parents' experiences of living with a child with attention deficit hyperactivity disorder (ADHD). A qualitative research design was followed. Purposive sampling was used to select ten parents living with children diagnosed with ADHD receiving outpatient treatment at a psychiatric facility. Data, collected through unstructured individual interviews, were analysed using open coding. Measures to ensure trustworthiness and ethical research practices were applied. Five themes emerged: burden of care; emotional effects; social effects; impact of the educational challenges, and attempts to cope with the burden of care. Parents living with a child with ADHD experience stress as they struggle to cope with the child's symptoms amidst the stigmatising attitudes from family and community members. Parents experience burdensome emotions and impaired social and occupational functioning. Health care practitioners need to take note of the challenges inherent to parenting a child with ADHD in order to provide multi-disciplinary interventions aimed at empowering and supporting parents.


Integration of enzyme-encapsulated mesoporous silica between nanohole array electrode and hydrogel film for flow-type electrochemical biosensor.
We herein propose a simple and sensitive electrochemical flow biosensor platform without an external flow device. The sensing unit comprises a platinum nanohole array electrode deposited on a nanoporous track-etched membrane (PtNH/NPM), a packed-layer of glucose oxidase-encapsulated mesoporous silica particles (GOD/MPS), and bovine serum albumin hydrogel film (BSA gel film). This sensing unit was fixed at the open window at the side of the plastic container with internal solution containing NaCl as osmotic reagent. When the sample glucose solution (0.10 mL) was pipetted at the sensing unit, a portion of the sample solution (5 μL) was spontaneously transferred into the BSA gel film. The concentration gradient of NaCl between the internal solution and the BSA gel film induced osmotic flow of water toward the internal solution. This osmotic flow assisted delivery of glucose to the GOD/MPS and enzymatically generated H2O2 to the PtNH/NPM. The proposed sensor could be used repeatedly and produced a linear current response for glucose, with a limit of detection of 16 μM. These sensor performances confirmed availability of the sensor design utilizing the osmotic flow.


Degradation mechanism of Bisphenol S via hydrogen peroxide/persulfate activated by sulfidated nanoscale zero valent iron.
Fenton-like oxidation processes are widely used to degrade recalcitrant organic pollutants, but are limited by narrow application pH and low reaction efficiency. This study investigated the synchronous activation of H2O2 and persulfate (PDS) by sulfidated zero valent iron (S-nZVI) in ambient conditions for Fenton-like oxidation of bisphenol S (BPS), an estrogenic endocrine-disrupting chemical. The activation of S-nZVI induced H2O2 or PDS could be greatly enhanced with the assistance of PDS and H2O2, respectively, even across a wide range of pH value (3-11). The first-order rate constant of S-nZVI/H2O2/PDS, S-nZVI/PDS and S-nZVI/H2O2 systems was found to be 0.2766 min-1, 0.0436 min-1, and 0.0113 min-1, respectively. A significant synergy between H2O2 and PDS was achieved when the PDS-H2O2 molar ratio was above 1:1, and where sulfidation promoted iron corrosion and decreased solution pH were observed in the S-nZVI/H2O2/PDS system. Radical scavenging experiments and electron paramagnetic resonance (EPR) investigations suggest that both SO4•- and •OH were generated and that •OH played a crucial role in BPS removal. Furthermore, four BPS degradation intermediates were detected and three degradation pathways were proposed in line with the HPLC-Q-TOF-MS analysis. This study demonstrated that compared to the traditional Fenton-like system, the S-nZVI/H2O2/PDS system could be a more efficient, advanced oxidation technology capable of being used across a broad pH range for emerging pollutants' degradation.


Chemical ionization pyrolytical spectra of DNA.
The chemical ionization-pyrolytical (CI-Py) spectra of DNA and deuterated DNA (Herring Sperm) are recorded. The 200-800 a.m.u. region is examined for CH4, NH3, ND3, electron-capture and OH- CI spectra. The origin of major ion species is discussed.


Disease-modifying effect of etanercept versus sulphasalazine on spinal mobility in patients with ankylosing spondylitis.
To model the estimated disease-modifying effect of etanercept over sulphasalazine in patients with ankylosing spondylitis. A post hoc analysis of data from the Ankylosing Spondylitis Study Comparing ENbrel and Sulfasalazine Dosed Weekly (ASCEND) study was performed using the Natural History Staggered Start (NHSS) method. A mixed model with a linear effect over time was fitted to the ASCEND data and resampling was performed to generate confidence intervals. At week 16, the total additional improvement in Bath Ankylosing Spondylitis Metrology Index of the etanercept arm over the sulphasalazine arm was 0.62 points, of which 31% (0.19 points) was estimated to be due to disease-modifying effect. The analysis of ASCEND data suggests that etanercept may have a larger disease-modifying effect than sulphasalazine. Further research is needed with more objective measures such as magnetic resonance imaging or X-radiography to confirm these results.


Observations on the structure and levels of expression of murine spermatozoan abnormalities with special reference to tail deformations.
Spermatozoan abnormalities have been studied by light and electron microscopy in the cauda epididymidis of 3 month old Balb/c and C57Bl mice. A qualitative account of the different abnormality-types at both levels of microscopy is given, with special emphasis on tail-defects which have so far received little attention. Quantitative data by light microscopy are also provided in an attempt to correlate structural abnormalities with the difference in fertility between these strains.


Bone remodelling in implanted proximal femur using topology optimization and parameterized cellular model.
The clinical relevance of bone remodelling predictions calls for accurate finite element (FE) modelling of implant-bone structure and musculoskeletal loading conditions. However, simplifications in muscle loading, material properties, has often been used in FE simulations. Bone adaptation induces changes in bone apparent density and its microstructure. Multiscale simulations, involving optimization methods and biomimetic microstructural models, have proven to be promising for predicting changes in bone morphology. The objective of the study is to develop a novel computational framework to predict bone remodelling around an uncemented femoral implant, using multiscale topology optimization and a parameterized cellular model. The efficacy of the scheme was evaluated by comparing the remodelling predictions with those of isotropic strain energy density (SED) and orthotropy based formulations. The characteristic functional groups and low-density regions of Ward's triangle, predicted by the optimization scheme, were comparable to micro-CT images of the proximal femur. Although the optimization scheme predicted well comparable material distribution in the 2D femur models, the obscured material orientations in some planes of the 3D model indicate the need for a more robust modelling of the boundary conditions. Regression analysis revealed a higher correlation (0.6472) between the topology optimization and SED models than the orthotropic predictions (0.4219). Despite higher bone apposition of 10-20% around the distal tip of the implant, the bone density distributions were well comparable to clinical observations towards the proximal femur. The proposed computational scheme appears to be a viable method for including bone anisotropy in the remodelling formulation.


Pharmacokinetics of antimicrobial drugs in cystic fibrosis. Beta-lactam antibiotics.
The pharmacodynamics and pharmacokinetics of beta-lactam antibiotics in patients with cystic fibrosis are discussed. A hypothetical dosing regimen based on these principles is considered. The usual dosing regimens may be suboptimal. New dosage regimens should be studied using prospective, controlled, randomized and blinded clinical trials.


Lectin-binding patterns on the plasma membranes of dissociated rat liver cells.
Carbohydrate moieties on the surface of dissociated rat liver cells were examined electron microscopically using ferritin- or horseradish peroxidase (HRP)-conjugated lectins as probes. Rat liver was fixed by perfusion with 0.7% glutaraldehyde via the portal vein and dissociated into single cells with gentle homogenization. Concanavalin A (Con A), Ricinus communis agglutinin (RCA), and wheat germ agglutinin (WGA) bound almost evenly to the entire cell surface of hepatocytes as well as of endothelial cells. Ulex europaeus agglutinin I (UEA-I) and peanut agglutinin (PNA) revealed no binding to any region. Dolichos biflorus agglutinin (DBA) was found to bind exclusively to the sinusoidal surface of hepatocytes and to endothelial cell surfaces. Soybean agglutinin (SBA)-binding was restricted to the endothelial cell surfaces and part of the sinusoidal microvilli of hepatocytes. Regional differences in lectin-binding pattern were visualized between the sinusoidal and the lateral or bile-canalicular surfaces of the hepatocytes. A polarity may exist on the hepatocyte cell surfaces in terms of the distribution pattern of the carbohydrate moieties, especially those of N-acetylgalactosamine.


Global Patterns of Subgenome Evolution in Organelle-Targeted Genes of Six Allotetraploid Angiosperms.
Whole-genome duplications (WGDs) are a prominent process of diversification in eukaryotes. The genetic and evolutionary forces that WGD imposes on cytoplasmic genomes are not well understood, despite the central role that cytonuclear interactions play in eukaryotic function and fitness. Cellular respiration and photosynthesis depend on successful interaction between the 3,000+ nuclear-encoded proteins destined for the mitochondria or plastids and the gene products of cytoplasmic genomes in multi-subunit complexes such as OXPHOS, organellar ribosomes, Photosystems I and II, and Rubisco. Allopolyploids are thus faced with the critical task of coordinating interactions between the nuclear and cytoplasmic genes that were inherited from different species. Because the cytoplasmic genomes share a more recent history of common descent with the maternal nuclear subgenome than the paternal subgenome, evolutionary "mismatches" between the paternal subgenome and the cytoplasmic genomes in allopolyploids might lead to the accelerated rates of evolution in the paternal homoeologs of allopolyploids, either through relaxed purifying selection or strong directional selection to rectify these mismatches. We report evidence from six independently formed allotetraploids that the subgenomes exhibit unequal rates of protein-sequence evolution, but we found no evidence that cytonuclear incompatibilities result in altered evolutionary trajectories of the paternal homoeologs of organelle-targeted genes. The analyses of gene content revealed mixed evidence for whether the organelle-targeted genes are lost more rapidly than the non-organelle-targeted genes. Together, these global analyses provide insights into the complex evolutionary dynamics of allopolyploids, showing that the allopolyploid subgenomes have separate evolutionary trajectories despite sharing the same nucleus, generation time, and ecological context.


A gene,imz, affecting the pH sensitivity of zygote formation inPhysarum polycephalum.
Mating inPhysarum polycephalum involves the fusion of two haploid amoebae and the differentiation of the resulting diploid zygote into a multinucleate plasmodium. Mating proceeds optimally with amoebae growing on an agar medium at pH 5.0. At pH 6.2, the amoebae still grow normally, but mating is completely blocked. The barrier at pH 6.2 is not in the differentiation step, since preformed diploids readily convert to plasmodia at this pH. The barrier can be overcome by raising the ionic strength of the agar medium; the effect, moreover, is not ion-specific. We have discovered a genetic locus,imz (ionicmodulation of zygote formation), that affects the upper pH limit for mating; the respective limits associated with the two known alleles,imz-1 andimz-2, are pH 5.6 and pH 6.0 at low ionic strength. Animz-1×imz-2 mating displays the pH 6.0 limit;imz-2 is therefore "dominant". We suggest that this new gene affects a cell component that is exposed to the exterior of the amoeba and is involved in the fusion step of mating.


Gradual decorrelation of CA3 ensembles associated with contextual discrimination learning is impaired by Kv1.2 insufficiency.
The associative network of hippocampal CA3 is thought to contribute to rapid formation of contextual memory from one-trial learning, but the network mechanisms underlying decorrelation of neuronal ensembles in CA3 is largely unknown. Kv1.2 expressions in rodent CA3 pyramidal cells (CA3-PCs) are polarized to distal apical dendrites, and its downregulation specifically enhances dendritic responses to perforant pathway (PP) synaptic inputs. We found that haploinsufficiency of Kv1.2 (Kcna2+/-) in CA3-PCs, but not Kv1.1 (Kcna1+/-), lowers the threshold for long-term potentiation (LTP) at PP-CA3 synapses, and that the Kcna2+/- mice are normal in discrimination of distinct contexts but impaired in discrimination of similar but slightly distinct contexts. We further examined the neuronal ensembles in CA3 and dentate gyrus (DG), which represent the two similar contexts using in situ hybridization of immediate early genes, Homer1a and Arc. The size and overlap of CA3 ensembles activated by the first visit to the similar contexts were not different between wild type and Kcna2+/- mice, but these ensemble parameters diverged over training days between genotypes, suggesting that abnormal plastic changes at PP-CA3 synapses of Kcna2+/- mice is responsible for the impaired pattern separation. Unlike CA3, DG ensembles were not different between two genotype mice. The DG ensembles were already separated on the first day, and their overlap did not further evolve. Eventually, the Kcna2+/- mice exhibited larger CA3 ensemble size and overlap upon retrieval of two contexts, compared to wild type or Kcna1+/- mice. These results suggest that sparse LTP at PP-CA3 synapse probably supervised by mossy fiber inputs is essential for gradual decorrelation of CA3 ensembles.


Draft Genome Sequence of a Polyhydroxyalkanoate-Producing Bacillus cereus Strain Isolated from Nuevo Leon State, Mexico.
Polyhydroxyalkanoates (PHA) are microbially produced biopolymers which are biodegradable and biocompatible. These compounds produced by microorganisms have been described as a potent alternative to synthetic plastics, which are often recalcitrant. Here, we report the draft genome sequence of a PHA-producing Bacillus cereus isolated in our laboratory.


Interactions involved in ovomucin gel-forming properties: a rheological-biochemical approach.
Different kinds of interactions involved in the properties of ovomucin gel formation from hen egg white were studied by combining physical and biochemical methods. A decrease in viscosity of the ovomucin gel was observed when it was subjected to chymotrypsin or sonication treatment. The viscosity decrease correlated with a change from non-Newtonian to Newtonian properties of the ovomucin gel. By treatment of the gel with either 5 M guanidinium HCl, 6 M urea, or 5% sodium dodecyl sulfate a change from non-Newtonian to Newtonian properties was also obtained. Although high ionic strength or sialic acid liberation from the ovomucin gel by neuraminidase treatment provoked a decrease in viscosity, it was not followed by a change in non-Newtonian properties. The results obtained suggest that different noncovalent interactions might be involved in gel formation. Electrostatic interactions (partially destroyed by sialic acid removal or 2 M NaCl) and hydrophobic interactions might be responsible for protein-mucin and mucin-mucin interactions. Other bonds susceptible to chymotrypsin treatment and sonication would be involved in the interaction between mucin subunits.


Life in a dark biosphere: a review of circadian physiology in "arrhythmic" environments.
Most of the life with which humans interact is exposed to highly rhythmic and extremely predictable changes in illumination that occur with the daily events of sunrise and sunset. However, while the influence of the sun feels omnipotent to surface dwellers such as ourselves, life on earth is dominated, in terms of biomass, by organisms isolated from the direct effects of the sun. A limited understanding of what life is like away from the sun can be inferred from our knowledge of physiology and ecology in the light biosphere, but a full understanding can only be gained by studying animals from the dark biosphere, both in the laboratory and in their natural habitats. One of the least understood aspects of life in the dark biosphere is the rhythmicity of physiology and what it means to live in an environment of low or no rhythmicity. Here we describe methods that may be used to understand rhythmic physiology in the dark and summarise some of the studies of rhythmic physiology in "arrhythmic" environments, such as the poles, deep sea and caves. We review what can be understood about the adaptive value of rhythmic physiology on the Earth's surface from studies of animals from arrhythmic environments and what role a circadian clock may play in the dark.