Proteins related to ictogenesis and seizure clustering in chronic epilepsy.
Seizure clustering is a common phenomenon in epilepsy. Protein expression profiles during a seizure cluster might reflect the pathomechanism underlying ictogenesis. We performed proteomic analyses to identify proteins with a specific temporal expression pattern in cluster phases and to demonstrate their potential pathomechanistic role. Pilocarpine epilepsy model mice with confirmed cluster pattern of spontaneous recurrent seizures by long-term video-electroencpehalography were sacrificed at the onset, peak, or end of a seizure cluster or in the seizure-free period. Proteomic analysis was performed in the hippocampus and the cortex. Differentially expressed proteins (DEPs) were identified and classified according to their temporal expression pattern. Among the five hippocampal (HC)-DEP classes, HC-class 1 (66 DEPs) represented disrupted cell homeostasis due to clustered seizures, HC-class 2 (63 DEPs) cluster-onset downregulated processes, HC-class 3 (42 DEPs) cluster-onset upregulated processes, and HC-class 4 (103 DEPs) consequences of clustered seizures. Especially, DEPs in HC-class 3 were hippocampus-specific and involved in axonogenesis, synaptic vesicle assembly, and neuronal projection, indicating their pathomechanistic roles in ictogenesis. Key proteins in HC-class 3 were highly interconnected and abundantly involved in those biological processes. This study described the seizure cluster-associated spatiotemporal regulation of protein expression. HC-class 3 provides insights regarding ictogenesis-related processes.


The effect of new oral anticoagulants and extended thromboprophylaxis policy on hip and knee arthroplasty outcomes: observational study.
The efficacy and safety of the new oral anticoagulants (NOAC) and the benefits of extended duration thromboprophylaxis following hip and knee replacements remain uncertain. This observational study describes the relations between thromboprophylaxis policies following hip and knee replacements across England's NHS and patient outcomes between January 2008 and December 2011. From the national administrative database, we analyzed mortality, thromboembolic complications, emergency readmission, and bleeding rates for 201,418 hip and 230,282 knee replacements. There were no differences in outcomes for either LMWH or NOAC. We found no advantage in favor of any single anticoagulation policy or in changing policy. This study supports the American Academy of Orthopaedic Surgeons' recommendation that the choice and duration of thromboprophylaxis prophylaxis be decided by the treating surgeon.


[Characteristics and influencing factors of newly HIV infection among newly confirmed HIV/AIDS cases in Ningbo city, 2017-2020].
Objective: To identify the characteristics and influencing factors of local HIV infection among newly confirmed cases in Ningbo from 2017 to 2020 to provide evidence for traceability investigations on critical cases and facilitate the detection procedures and reduce new HIV infection. Methods: From January 1, 2017, to December 31, 2020, the newly confirmed HIV/AIDS in Ningbo were recruited. An epidemiological questionnaire was used to collect relevant information, including demography, sexual behaviors, results of HIV antibody tests, and the route of HIV transmission. According to the HIV testing, history of risk behaviors, and the level of CD4+ lymphocytes after confirmation, the HIV infection was acquired in the previous year, or the place was in Ningbo. The EpiData 3.1 and SPSS 23.0 software were used for input, sorting database and statistical analysis. Results: A total of 2 044 HIV/AIDS on-site investigations were completed. The average age of the subjects was (40.6±15.3) years old, including 1 684 males (82.4%), 758 unmarrieds (37.1%), 1 072 (52.5%) registered as permanent residents in Ningbo, 1 253 (61.3%) with junior high school education or below, 979 (47.9%) lived in Ningbo for more than five years. The proportion of local, new HIV infections was 34.34% (702/2 044). Multivariate logistic analysis showed that the proportion of local newly HIV infection was higher among those who were confirmed in 2020 (compared with the 2017 confirmed cases, OR=1.422, 95%CI:1.092-1.851), whose occupations were students/teachers/cadres/retirees (compared to commercial service/catering/public place service personnel, OR=1.682, 95%CI: 1.307-2.165), meeting sex partners via male social software locally in the last year (compared with without using related dating software, OR=1.353, 95%CI: 1.073-1.706). Conclusions: The proportion of local HIV infection of newly confirmed HIV/AIDS was relatively high in Ningbo city from 2017 to 2020. Meeting gay sex partners through local male social software appeared a risk factor for local newly HIV infection. Traceability investigations and internet intervention should be carried out for MSM. While male social software should be focused on identifying and controlling the risk of local newly HIV infection.


Rotator cuff tear--relationship between clinical and anatomopathological findings.
Rotator cuff tears (RCT) are frequent and increase with age. Why do only a relatively small percentage cause a permanent severe handicap justifying surgery? Is there a relationship between size and site of the tear and the clinical symptoms? How do they influence the postoperative result? These questions were answered in a prospective study of 76 operated patients. We adopted D. Patte's classification of the RCT into four groups according to the site and size of the lesion. Our figures were compared with those obtained by Patte in an analogous study of 256 cases. Of the tears in our series, 56.5% belonged to groups I and II, which means that only the supraspinatous and occasionally also the subscapular muscles were involved. In 100% of the cases in group I we found only pain, whereas a pure symptomatology with pain alone was presented in only 51% of group II, in 48% of group III, and in 0% of group IV. Groups III (35.5%) and IV (8%) represent more extensive tears, involving not only the anterior part of the rotator cuff, e.g., the supraspinatous tendon, but also to a more or less severe extent, the infraspinatous and sometimes even the teres minor. In group IV the extensive tear is combined with osteoarthritic changes. In both groups a mixed symptomatology (pain and pseudoparalysis) is the rule. The result of operative treatment is satisfactory in all groups as far as pain relief is concerned. The improvement of active ROM is not as evident and seems, as expected, to be related to the severity of the lesion.(ABSTRACT TRUNCATED AT 250 WORDS)


Enabling early detection of knee osteoarthritis using diffusion-relaxation correlation spectrum imaging.
To present a technique that enables detection of early stage OA of the knee using diffusion-relaxation correlation spectrum imaging (DR-CSI). Fifty-five early osteoarthritis patients (OA, Kellgren-Lawrence [KL] score 1 to 2; mean age, 56.4 years) and 49 healthy volunteers (mean age, 56.7 years) were underwent magnetic resonance imaging (MRI) with T2-mapping and DR-CSI techniques. Maps of mean apparent diffusion coefficient (ADC), T2 relaxation time and volume fraction Vi for DR-CSI compartment i (A, B, C, D) sensitivity, specificity, and positive and negative likelihood ratio (PLR, NLR) were assessed to determine the diagnostic accuracy for detection of early-stage degeneration of knee articular cartilage. The structural abnormalities of articular cartilage were evaluated using modified Whole-Organ MR Imaging Scores (WORMS). All intra- and interobserver agreements for DR-CSI compartment volume fractions and modified WORMS of cartilage were excellent. Early OA versus the controls had higher VC, lower VA and VB (p<0.001), but comparable VD (p>0.05). VA, VB and VC had a moderate association with WORMS. No significant correlation was identified between VD and WORMS. VC had better ability than VA,VB, VD, T2 and ADC to discriminate early OA patients from healthy controls (area under the curve, 0.898). Sensitivity, specificity, PLR, and NLR of VC with a cut-off value of 29.9% were 81.8% (95% confidence interval [CI], 69.1-90.9%), 95.9% (86-99.5%), 20.05% (5.13-78.34%), and 0.19% (0.11-0.33%). DR-CSI compartment volume fractions may be sensitive indicators for detecting early-stage degeneration in knee articular cartilage.


A sticky situation for targeted cancer therapy.
In this issue of Cell Chemical Biology, Andlovic et al.1 unravel how certain fusicoccin toxins synergize with interferon-α to kill cancer cells. The results suggest that fusicoccins potentiate apoptosis by "sticking together" 14-3-3 protein-protein interactions.


Invasive carp alter trophic niches of consumers and basal resources in African reservoirs.
Environmental pollution and biological invasions are key drivers of biodiversity change. However, the effects of invasion and pollution on food webs remain largely unexplored. Here, we used stable isotopes to examine the effects of common carp Cyprinus carpio and pollution on trophic dynamics in six small reservoirs. Our results revealed that the trophic niche widths of invertebrates, vertebrates, and invasive carp did not significantly differ among reservoirs with different pollution statuses. However, we found low niche conservatism among reservoirs, suggesting that while niche width may remain consistent, there is a shift in the position of the niches in isotopic space under both pollution and invasion scenarios. Niche conservatism among reservoirs was generally higher in invertebrates, but this was also regardless of reservoir condition (i.e. presence or absence of pollution and invasion). These results suggest that invasion by species coupled with organic pollution may cause subtle yet differing effects on components of a food web (basal end-members, invertebrates and vertebrates). Our findings provide a baseline measure of the potential in the development of detection and response strategies for carp invasions and organic pollution.


Neurofibromatosis Type 1-Associated Plexiform Neurofibromas of the Face and Adjacent Head Regions: Topography of Lesions and Surgical Treatment Data of 179 Patients.
Facial plexiform neurofibromas (FPNF) are rare tumors frequently diagnosed in patients with neurofibromatosis type 1 (NF1), a tumor predisposition syndrome. FPNF often grows invasively and destructively, which may complicate surgical treatment. Data on the frequency, location, and surgical procedures of patients with NF1-associated FPNF are scarce. This study provides treatment data from a nationally networked reference center for the treatment of NF1 patients. The localization and treatment data of 179 NF1 patients with FPNF were analyzed. Photographically documented tumors of the study area, further determined by imaging, were manually transferred to a facial scheme and digitized. The digitized registrations of the facial extensions of the tumors of each patient were overlaid in a single image (Photoshop™), so that the file of the facial scheme contained the sum of the tumor localization. Finally, the frequency of tumor localization was indicated with a color code. The frequency of tumor extension-related coded colors was applied to outline the lesions' topography on schematic face drawings (heat map). The distribution of the tumors showed no side preference. The need for the treatment of patients with orbital/periorbital manifestations became evident in the graphic representations. Tumors do not respect anatomical units. However, the classification of the face according to dermatomes, especially the trigeminal nerve, offers indications of tumor spread and guides treatment planning. The mean number of surgical measures per patient was 2.21 (median: 1). Extensive swelling, hematoma, and delayed wound healing were all common postoperative complications. The color-coded, schematic overview of the frequency distribution of cutaneous tumor spread in NF1 patients with FPNF illustrates the importance of orbital/periorbital and cheek tumor manifestations in patients' treatment needs. The imaging procedure is suitable for controlling natural tumor growth in the same way as the documentation of the post-surgical course. Repeated interventions in the region are included in surgical planning of the progressing tumor disease.


[Passive smoking. Acute effects on the lung function of sensitive persons].
From the relationship between the degree of air pollution due to tobacco and its acute effects on healthy persons it is possible to estimate the still tolerable level of air pollution for healthy adults. The results and conclusions of the studies published by now on acute effects of passive smoking on patients with bronchial asthma are partially contradictory and do not allow a reliable estimation of the upper limit of tobacco smoke exposure for this particularly sensitive group. Because of methodological problems in studies with symptomatic asthmatics, further studies should be conducted which investigate patients with hayfever and asthma out of the pollen season, clinically healthy subjects with nonspecific bronchial hyperreactivity upon pharmacological challenge, and subjects who claim sensitivity to tobacco smoke.


Expression of podoplanin in the mouse salivary glands.
Podoplanin is one of the most highly expressed lymphatic-specific genes. Here, we report the distribution of cells expressing podoplanin in mouse salivary glands. We immunohistochemically investigated the distribution of cells expressing podoplanin in mouse major salivary glands by laser-scanning microscopy. The expression of endothelial cell marker PECAM-1 was tested to discriminate lymphatic endothelium from salivary gland cells, and myoepithelial cells were identified by an antibody for P-cadherin. The podoplanin expression was rarely found in acini of the parotid gland but clearly found at the basal portion of acini in the submandibular and sublingual glands. The number of portion reacted with anti-podoplanin is greater in the sublingual gland than in the submandibular gland. The expression was also found at the basal portion of ducts in all major salivary glands. The P-cadherin expression was rarely found in acini of the parotid gland but found in acini of the sublingual gland and on ducts in parotid and sublingual glands, corresponding to the area of podoplanin expression. It was suggested that the acinar and myoepithelial cells in the salivary glands have the ability to express podoplanin, and that the expression may be concerned with the mucous saliva excretion.


Targeted correction of a chromosomal point mutation by modified single-stranded oligonucleotides in a GFP recovery system.
Synthetic oligonucleotides had been employed in DNA repair and promised great potentials in gene therapy. To test the ability of single-stranded oligonucleotide (SSO)-mediated gene repair within a chromosomal site in human cells, a HeLa cell line stably integrated with mutant enhanced green fluorescence protein gene (mEGFP) in the genome was established. Transfection with specific SSOs successfully repaired the mEGFP gene and resulted in the expression of functional fluorescence proteins, which could be detected by fluorescence microscopy and FACS assay. Western blot showed that EGFP was only present in the cells transfected with correction SSOs rather than the control SSOs. Furthermore, DNA sequencing confirmed that phenotype change resulted from the designated nucleotide correction at the target site. Using this reporter system, we determined the optimal structure of SSO by investigating the effect of length, modifications, and polarities of SSOs as well as the positions of the mismatch-forming nucleotide on the efficiency of SSO-mediated gene repair. Interestingly, we found that SSOs with mismatch-forming nucleotide positioned at different positions have varying potencies that homology at the 5'-end of SSOs was more crucial for the SSO's activity. These results provided guidance for designing effective SSOs as tools for treating monogenic inherited diseases.


Imaging Features of Chronic Bronchitis with Preserved Ratio and Impaired Spirometry (PRISm).
The purpose of the study was to investigate the quantitative chest tomographic features of chronic bronchitis with preserved ratio and impaired spirometry (PRISm), including airway wall area, emphysema index, and lung capacity. An observational, cross-sectional study of 343 patients at the Ninth Hospital of Xi'an Affiliated Hospital of Xi'an Jiaotong University between October 2014 and September 2017. The patients were divided into three groups: 77 cases of chronic bronchitis with normal lung function (forced expiratory volume in one second/forced vital capacity) (FEV1/FVC > 70%, FEV1%pred > 80%), 80 cases of chronic bronchitis with PRISm (FEV1/FVC > 70%, FEV1%pred < 80%), and 186 cases of the early chronic obstructive pulmonary disease (COPD) (FEV1/FVC < 70%, FEV1%pred > 50%, that is, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grade 1 + 2). We compared and analyzed the differences in imaging between the chronic bronchitis with PRISm and the other two groups. Compared with the early COPD group, the PRISm group revealed significant differences in airway wall area, emphysema index, and lung capacity (P < 0.05). Compared with the chronic bronchitis with normal lung function group, the PRISm group showed increased WA%LUL5, decreased lung capacity, and higher mean lung density. In terms of airway wall area and emphysema index, patients with chronic bronchitis with PRISm were essentially no different than those with chronic bronchitis without abnormal spirometry, whereas for symptoms, they are more like GOLD 1 and 2 patients. Our findings show that it is not yet clear whether it constitutes an intermediate stage of chronic bronchitis with normal lung function that progression to early COPD.


Structural types of marginal (lamina I) neurons projecting to the dorsal reticular nucleus of the medulla oblongata.
The morphological features of lamina I neurons labelled from the medullary dorsal reticular nucleus with free or wheat germ agglutinin conjugated horseradish peroxidase and cholera toxin subunit B, were studied in the three standard anatomical planes in the rat. Orientation and way of branching of the dendritic arbors were further analysed by the method of Sholl in cells labelled with cholera toxin subunit B. Most marginal cells belong to the multipolar type (70%) of our Golgi-based classification, and a minority to the pyramidal (15%) and flattened (15%) types. Following unilateral lesions severing the greatest part of the cuneate fasciculus, a considerable decrease of the numbers of labeled cells of the three types was observed caudal and ipsilaterally to the lesion. Contralateral labelling of multipolar and pyramidal cells was less decreased, and that of flattened cells was apparently unchanged. While multipolar cells, which make up the bulk of marginal spinobulbar neurons, appear to have no other supraspinal target, pyramidal and flattened cells have been labelled from the mesencephalon and the thalamus, respectively. It is suggested that the three structural cell types subserve different aspects of the spinofugal nociceptive output.


Data of microstructure and mechanical properties of carbon foams derived from sucrose/polyacrylamide hydrogel.
An easy method that combined gel casting and physical foaming was used to fabricate modified carbon foams. The design of carbon foams from sucrose/polyacrylamide hydrogel is a new concept for controlling the microstructure and improving the compressive properties of carbon foams. This article provides the micrographs obtained from optical and scanning electron microscope for foaming solution and carbon foams. Weight loss data used to construct the thermo-gravimetric curves are included. Load-displacement data constructing the stress-strain curves and the derived compressive properties are also included.


Contribution to the study of Aspergillus fumigatus Fresenius.
50 Strains of Aspergillus fumigatus were studied for enzymatic and physiologic profile. Proteolytic and lipolytic activity were lacking. Various ribonucleases and sacchrolytic enzymes were found.


Bioinspired fractal electrodes for solar energy storages.
Solar energy storage is an emerging technology which can promote the solar energy as the primary source of electricity. Recent development of laser scribed graphene electrodes exhibiting a high electrical conductivity have enabled a green technology platform for supercapacitor-based energy storage, resulting in cost-effective, environment-friendly features, and consequent readiness for on-chip integration. Due to the limitation of the ion-accessible active porous surface area, the energy densities of these supercapacitors are restricted below ~3 × 10-3 Whcm-3. In this paper, we demonstrate a new design of biomimetic laser scribed graphene electrodes for solar energy storage, which embraces the structure of Fern leaves characterized by the geometric family of space filling curves of fractals. This new conceptual design removes the limit of the conventional planar supercapacitors by significantly increasing the ratio of active surface area to volume of the new electrodes and reducing the electrolyte ionic path. The attained energy density is thus significantly increased to ~10-1 Whcm-3- more than 30 times higher than that achievable by the planar electrodes with ~95% coulombic efficiency of the solar energy storage. The energy storages with these novel electrodes open the prospects of efficient self-powered and solar-powered wearable, flexible and portable applications.


A 24-week randomised controlled trial comparing usual care and metabolic-based diet plans in obese adults.
Usual care (UC) practice for weight management often includes providing standardised, ad libitum, low-calorie nutrition plans. However, weight loss using such plans appears comparable with metabolic-based diet (MD) plans that are closer to resting energy expenditure (REE) level. In addition, MD plans are approximately 250-750 kcal/day higher in caloric values compared with UC plans. Therefore, the purpose of this study was to compare weight loss and eating behaviour differences between UC and MD plans. Seventy-four obese (30.0-51.7 kg/m(2) ) adults (21-67 years) voluntarily participated in a 24-week randomised study. UC men and women received a fixed, ad libitum, 1600 and 1200 kcal/day nutrient plan, respectively. MD participants received an individualised treatment plan based from measured REE. Bodyweight and eating behaviours (i.e. intake, restraint and uncontrolled eating) were assessed over time. Intent-to-treat analysis indicated no significant difference in weight loss (UC: -5.7 ± 6.3% vs. MD: -5.3 ± 7.1% p = 0.67) between groups over time. There was no difference in daily energy intake (UC: 2490 ± 576 kcal/day vs. MD: 2525 ± 475 kcal/day) at 24 weeks between groups. Both groups experienced a significant improvement (p < 0.05) in eating dietary restraint and uncontrolled eating yet there was no difference between groups. From this study, UC calorie plans do not generate more weight loss or improve eating behaviours in comparison with MD calorie plans. As treatment effects are comparable, clinicians can select UC or MD plan options based on clinician and patient preference.


Aromatic analogues of DNA minor groove binders--synthesis and biological evaluation.
Nine carbocyclic analogues of mono- and bis-lexitropsins and two analogues of pentamidine with unsubstituted N-terminal amine group were synthesized. We have investigated the cytotoxic activity of new aromatic analogues of DNA binding ligands in MCF-7 breast cancer cells and assessed their ability to act as inhibitors of topoisomerase I and II. These studies indicate that aromatic analogues of bis-netropsin contain two identical units tethered by alkyloxyl chains are a potent catalytic inhibitor of both topoisomerases and exhibit moderate cytotoxicity in MCF-7 breast cancer cells.


Confounding variables affecting in vitro fertilization success: a decade of experience.
To evaluate etiology of infertility, female age, ovarian response and stimulation protocol in affecting in vitro fertilization (IVF) success. Retrospective analysis was used. Computer records of all 5209 cycles initiated in 2391 couples from February 1, 1984 to December 31, 1993 were analyzed. There were 644 intrauterine, 24 solely ectopic and 7 heterotopic pregnancies. Pregnancy rates increased with number of embryos transferred with a significant increase still found between transfer of three or four embryos. Multiple gestations also increased in association with an increasing number of embryos transferred. Pregnancy rates per cycle did not decline with repeated cycles. Reduced pregnancy rates were associated with a primary diagnosis of male infertility. Covariates associated with a better pregnancy rate were younger age of the female partner or higher peak preovulatory serum estradiol. Routine administration of GnRH-agonist was associated with a reduced cycle cancellation rate, an increase in oocytes retrieved and an improved pregnancy rate. Couples with male infertility and increased female age should be counselled regarding the reduced prognosis for success.


Preventing osteolytic lesions and osteomyelitis in multiple myeloma.
Multiple myeloma is a hematological malignancy affecting the plasma cells. It is the second most common hematologic cancer in adults. Over 90% of patients develop local osteolytic lesions and skeletal-related events at some point during the progression of the disease. Bone lesions can induce severe pain and immobility and can also increase the risk of fractures and osteomyelitis. Skeletal complications are associated with poor clinical outcomes, affecting quality of life and mortality. Current standards of care for myeloma, e.g., autologous stem-cell transplantation (ASCT) and chemotherapy, do not lessen the risk of adverse events in bone. Once bone lesions are present, bone-targeted interventions are limited, with bone antiresorptive drugs being a mainstay of treatment. This review highlights the growing literature surrounding osteolytic lesions and bone infections associated with multiple myeloma and assesses current and emerging treatments. Emerging evidence from clinical trials suggests that denosumab can reduce skeletal-related events, and the potential application of bortezomib/1D11 can reduce bone destruction and pathological fractures in MM patients. Once established, bone lesions are prone to develop osteomyelitis - especially in immunocompromised individuals. Antibiotics and surgical interventions have been used to manage bone infections in most reported cases. As the bone infection risk associated with MM bone lesions become more evident, there is scope to improve patient management by mitigating this risk with prophylactic antimicrobial therapy.


Updated diagnosis and graft involvement for visceral leishmaniasis in kidney transplant recipients: a case report and literature review.
Visceral leishmaniasis (VL) has become a rising concern to transplantation teams, being associated with graft dysfunction and reduced survival of renal transplant recipients. Here, we describe a case of VL occurring in a kidney transplant (KT) recipient in Italy, a country in which Leishmania infantum is endemic and we reviewed the literature on the clinical course and diagnosis of VL in KT recipients residing or travelling to southern Europe. The VL case was diagnosed 18 months after transplant and 28 days after the onset of symptoms by quantitative PCR (qPCR) on peripheral blood. A graft biopsy showed renal involvement, and PCR performed on graft tissue displayed the presence of Leishmania DNA. The retrospective confirmation of Leishmania-positive serology in a serum sample collected before transplantation, as well as the absence of anti-Leishmania IgG in the graft donor strongly suggest that reactivation of a latent parasitic infection caused VL in the current case. VL is often underdiagnosed in transplant recipients, despite the presence of latent Leishmania infection being reported in endemic countries. This case report, as well as the literature review on leishmaniasis in KT recipients, underline the importance of rapid VL diagnosis to promptly undergo treatment. Serology is scarcely sensitive in immunocompromised patients, thus molecular tests in peripheral blood should be implemented and standardized for both VL identification and follow-up.


Endoscopic third ventriculostomy for patients with Blake's pouch cyst with adult-onset hydrocephalus: Importance of improved cerebrospinal fluid flow in the prepontine cistern - A case report.
Blake's pouch cyst (BPC) is a posterior fossa cystic malformation that commonly occurs in children with rare adult onset. Herein, we report a case of adult onsets BPC. A 61-year-old man presented with gait and cognitive disturbance. Preoperative magnetic resonance imaging (MRI) revealed scarring in the prepontine cistern, and cine phase-contrast MRI revealed no pulsation. Endoscopic third ventriculostomy (ETV) was performed with opening the scarring in the prepontine cistern. Postoperative cine phase-contrast MRI revealed that cerebrospinal fluid (CSF) flow in the prepontine cistern improved, resolving the patient's symptoms. We report a case of adult-onset BPC. The mechanism by which is becomes symptomatic is still unclear. We opened the scar in prepontine cistern in addition to ETV with good results. In this report, we discussed the importance of the improvement in CSF dynamics in the prepontine cistern.


[Lengthening of the 1. metacarpal according to Matev after loss of the thumb].
In cases where loss of the thumb has occurred, the gripping function of the hand can be pariallly restored by the process of extending the first metacarpel. In our opinion the method according to Matev, involving distraction and the interpositioning of a bony wedge is a relatively simple operation and compared with similar methods has the advantage of achieving positive results in regard to the length. The only prerequisite for this method is good skin and soft tissue condition in the area of the stump.


American College of Medical Genetics and Genomics technical standards and guidelines: microarray analysis for chromosome abnormalities in neoplastic disorders.
Microarray methodologies, to include array comparative genomic hybridization and single-nucleotide polymorphism-based arrays, are innovative methods that provide genomic data. These data should be correlated with the results from the standard methods, chromosome and/or fluorescence in situ hybridization, to ascertain and characterize the genomic aberrations of neoplastic disorders, both liquid and solid tumors. Over the past several decades, standard methods have led to an accumulation of genetic information specific to many neoplasms. This specificity is now used for the diagnosis and classification of neoplasms. Cooperative studies have revealed numerous correlations between particular genetic aberrations and therapeutic outcomes. Molecular investigation of chromosomal abnormalities identified by standard methods has led to discovery of genes, and gene function and dysfunction. This knowledge has led to improved therapeutics and, in some disorders, targeted therapies. Data gained from the higher-resolution microarray methodologies will enhance our knowledge of the genomics of specific disorders, leading to more effective therapeutic strategies. To assist clinical laboratories in validation of the methods, their consistent use, and interpretation and reporting of results from these microarray methodologies, the American College of Medical Genetics and Genomics has developed the following professional standard and guidelines.


Clinical correlates of elevated serum concentrations of cytokines and autoantibodies in patients with spinal cord injury.
To determine the serum cytokine profiles of patients with spinal cord injury (SCI) and varying clinical presentations relative to healthy, able-bodied, age-matched control subjects. Cross-sectional study. Clinical research unit. People with SCI (N=56) and different clinical presentations, and healthy, able-bodied, age-matched control subjects (N=35). Not applicable. Serum levels of the proinflammatory cytokines interleukin (IL) 1beta, IL-6, tumor necrosis factor alpha (TNF-alpha), the anti-inflammatory cytokines IL-4 and IL-10, the regulatory cytokine IL-2, the IL-1 receptor antagonist (IL-1RA), and autoantibodies against myelin-associated glycoprotein and GM(1) ganglioside (anti-GM(1)) immunoglobulin (IgG and IgM), as determined by enzyme-linked immunosorbent assay. The relationship between elevated serum cytokine levels and clinical variables was also studied. SCI subjects exhibited serum concentrations of IL-6, TNF-alpha, IL-1RA, and anti-GM(1) (IgG) that were greater (P<.05) than control group values. Elevated cytokine concentrations were not associated with high white blood cell counts, level of injury, or American Spinal Injury Association classification; they were evident in SCI subjects who were asymptomatic for medical complications, but were further elevated in subjects with pain, urinary tract infection (UTI), and pressure ulcers. Elevated levels of circulating proinflammatory cytokines and autoantibodies are present in the serum of SCI subjects without medical complications, and are further elevated in SCI subjects with neuropathic pain, UTI, or pressure ulcers, relative to healthy, able-bodied control subjects. These findings may be indicative of a protective autoimmunity, simply a consequence of occult or evident infection, or evidence of cytokine dysregulation that may contribute to an immune-mediated impairment of axonal conduction.


Response of the bacterial community in oil-contaminated marine water to the addition of chemical and biological dispersants.
The use of dispersants in different stages of the oil production chain and for the remediation of water and soil is a well established practice. However, the choice for a chemical or biological dispersant is still a controversial subject. Chemical surfactants that persist long in the environment may pose problems of toxicity themselves; therefore, biosurfactants are considered to constitute an environmentally friendly and effective alternative. Nevertheless, the putative effects of such agents on the microbiomes of oil-contaminated and uncontaminated marine environments have not been sufficiently evaluated. Here, we studied the effects of the surfactant Ultrasperse II® and the surfactin (biosurfactant) produced by Bacillus sp. H2O-1 on the bacterial communities of marine water. Specifically, we used quantitative PCR and genetic fingerprint analyses to study the abundance and structure of the bacterial communities in marine water collected from two regions with contrasting climatic conditions. The addition of either chemical surfactant or biosurfactant influenced the structure and abundance of total and oil-degrading bacterial communities of oil-contaminated and uncontaminated marine waters. Remarkably, the bacterial communities responded similarly to the addition of oil and/or either the surfactant or the biosurfactant in both set of microcosms. After 30 days of incubation, the addition of surfactin enhanced the oil-degrading bacteria more than the chemical surfactant. However, no increase of hydrocarbon biodegradation values was observed, irrespective of the dispersant used. These data contribute to an increased understanding of the impact of novel dispersants on marine bacteriomes before commercial release into the environment.


Fatty, fatty, two-by-four: weight-teasing history and disturbed eating in young adult women.
We investigated the long-term effect of weight teasing during childhood. Young adult women (n = 1533; aged 18-26 years) from 3 large universities participated in a survey (Fall 2009 to Spring 2010) that assessed disturbed eating behaviors; weight status at ages 6, 12, and 16 years; and weight-teasing history. Nearly half of the participants were weight-teased as a child. Participants who experienced childhood weight teasing were significantly more likely to have disturbed eating behaviors now than non-weight-teased peers. As the variety of weight teasing insults recalled increased, so did disturbed eating behaviors and current body mass index. Those who recalled their weight at ages 6, 12, or 16 years as being heavier than average endured weight teasing significantly more frequently and felt greater distress than their lighter counterparts. Weight teasing may contribute to the development of disturbed eating and eating disorders in young women. Health care professionals, parents, teachers, and other childcare givers must help shift social norms to make weight teasing as unacceptable as other types of bullying. To protect the health of children, efforts to make weight teasing unacceptable are warranted.


Analysis of grain growth, structural and magnetic properties of Li-Ni-Zn ferrite under the influence of sintering temperature.
The effect of sintering temperature (TS) on the structural and magnetic properties of Li 0.15 Ni 0.3 Zn 0.4 Fe 2.15 O 4 is investigated and discussed. The sample is synthesized by the sol-gel auto combustion method and sintered at 1373-1573 K for 5 h. Phase identification of the powder sample was performed by using the X-ray diffraction (XRD). The XRD patterns confirmed the formation of single phase cubic spinel structure. The bulk density is correlated with TS. From the energy-dispersive X-ray spectroscopy study, it is observed that the percentage of the elements in the component phases is well consistent with the nominal composition of the composites. Field Emission Scanning Electron Microscopy showed that the average grain size (D) is increased with increasing TS. The frequency (100 Hz-120 MHz) dependent complex initial permeability spectra and relative quality factor increased with sintering temperature up to 1523 K then decreased for further increase in temperature. The complex initial permeability has been explained with the help of microstructure, and the redistribution of cations in their sites.


Environmental toxicology of testicular cancer.
Testicular cancer incidence appears to be increasing. In many regions, industrialization results in the production of potentially carcinogenic environmental toxins. We review the available data linking environmental toxins to testicular germ cell tumors (TGCT). A PubMed review of the English literature was performed to identify studies evaluating the relationship between environmental toxins and TGCT. Many environmental toxins have been implicated in the development of TGCT, including organochlorines, polychlorinated biphenyls, polyvinyl chlorides, phthalates, marijuana, and tobacco. Variable levels of evidence exist and significant study design limitations preclude a definitive etiologic role for individual environmental toxins. Environmental toxins may play an important but undetermined role in the development of TGCT. Further work is needed to evaluate specific toxins and TGCT carcinogenesis.


Congenital myopathy with myasthenic features and congenital cataract in two siblings.
Two siblings with congenital myopathy showing myasthenic manifestations together with congenital cataract are reported. Their muscle weakness fluctuated and was alleviated by edrophonium chloride. Their serum creatine kinase activity was elevated, and the waning phenomenon was observed on repetitive nerve stimulation. Biopsied muscle showed degenerative changes with type 1 fibre predominance and abnormal morphology of neuromuscular junctions.


Videofluoroscopic swallow study training for radiologists-in-training: a survey of practice and training needs.
There is a lack of formal, published videofluoroscopic swallow study (VFSS) training targeting radiologists, yet radiology senior medical officers and resident medical officers (i.e., radiologists-in-training, known in Australia as "registrars") are expected to be involved in VFSS interpretation of anatomical anomalies and reporting. This study investigated whether VFSS training is delivered to registrars during their specialist radiology training, whether it is a perceived need and, if so, to determine the desired content for inclusion in a targeted training package. A cross-sectional, mixed methods study design was used. An internet-based survey was circulated via convenience and snowball sampling to radiologists (both senior medical officers and registrars) and speech-language pathologists across Australia in October-November 2017. Surveys also were distributed to practitioners based in New Zealand and the United Kingdom, as they practised within similar health systems, and it was anticipated they may have similar VFSS training practices. The radiology survey contained 36 questions and the speech-language pathology survey contained 44 questions. Participants were asked the following: (1) Report their current VFSS radiology registrar training environment; (2) Advise whether radiology registrars need VFSS training; (3) Recommend the content, format, training intensity, and evaluation methods for an effective radiology registrar training package. Demographic data were analysed descriptively, and open-ended responses were analysed using qualitative content analysis. 21 radiology senior medical officers and registrars and 150 speech-language pathologists predominantly based at Australian tertiary hospital settings completed the survey. Most respondents (90.6%) identified that VFSS training is needed for radiology registrars. Only one speech-language pathologist respondent reported that they deliver VFSS training for radiology registrars. Specific content and teaching modalities for a VFSS training package, including diagnosing anatomical anomalies associated with dysphagia were recommended. While most of the radiologists and speech-language pathologists surveyed did not deliver VFSS training to radiology registrars, they identified that targeted training is needed to improve radiology registrars' effectiveness and engagement in VFSS clinics. The training package content, format and evaluation methods recommended by participants will inform the development of a VFSS training package targeting radiology registrars to be piloted at an Australian tertiary hospital.


Characterization of the pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate hydrolase activity in rat liver. Identity with alkaline phosphatase.
The tissue content of pyridoxal 5'-phosphate is controlled principally by the protein binding of this coenzyme and its hydrolysis by a cellular phosphatase. The present study identifies this enzyme and its intracellular location in rat liver. Pyridoxal-P is not hydrolyzed by the acid phosphatase of intact lysosomes. At pH 7.4 and 9.0, the subcellular distribution of pyridoxal-P phosphatase activity is similar to the for p-nitrophenyl-P, and the major portion of both activities is found in the plasma membrane fraction. The ratio of specific activities for pyridoxal-P and p-nitrophenyl-P hydrolysis remains relatively constant during the isolation of plasma membranes. These activities also behave concordantly with respect to pH rate profile, pH-Km profile, and response to chelating agents, Zn2+, Mg2+, and inhibitors. Kinetic studies indicate that pyridoxal-P binds to same enzyme sites as beta-glycerophosphate and phosphorylcholine. The data strongly favor alkaline phosphatase as the enzyme which functions in the control of pyridoxal-P and pyridoxamine-P metabolism in rat liver. Alkaline phosphatase was solubilized from isolated plasma membranes. The kinetic properties of the enzyme are not markedly altered by its dissociation from the membrane matrix. However, there are significant differences in its behavior toward Mg2+ which suggest a structural role for Mg2+ in liver alkaline phosphatase.


Effects of restricted feeding schedules on circadian organization in squirrel monkeys.
Free running circadian rhythms of motor activity, food-motivated lever-pressing, and either drinking (N = 7) or body temperature (N = 3) were recorded from 10 squirrel monkeys maintained in constant illumination with unlimited access to food. Food availability was then restricted to a single unsignaled 3-hour interval each day. The feeding schedule failed to entrain the activity rhythms of 8 monkeys, which continued to free-run. Drinking was almost completely synchronized by the schedule, while body temperature showed a feeding-induced rise superimposed on a free-running rhythm. Nonreinforced lever-pressing showed both a free-running component and a 24-hour component that anticipated the time of feeding. At the termination of the schedule, all recorded variables showed free-running rhythms, but in 3 animals the initial phase of the postschedule rhythms was advanced by several hours, suggesting relative coordination. Of the remaining 2 animals, one exhibited stable entrainment of all 3 recorded rhythms, while the other appeared to entrain temporarily to the feeding schedule. These results indicate that restricted feeding schedules are only a weak zeitgeber for the circadian pacemaker generating free-running rhythms in the squirrel monkey. Such schedules, however, may entrain a separate circadian system responsible for the timing of food-anticipatory changes in behavior and physiology.


Astigmatism outcomes of scleral tunnel and clear corneal incisions for congenital cataract surgery.
To evaluate astigmatism outcomes after congenital cataract surgery with intraocular lens implantation using clear corneal or scleral tunnel incisions. We retrospectively reviewed the medical records of 46 children (67 eyes), aged 2 months to 12 years, who had undergone nontraumatic cataract extraction and intraocular lens implantation between 1996 and 2001, using a scleral tunnel incision (group 1), or a clear corneal incision (group 2). Refractive astigmatism was measured at 1 week, 3 months, and 5 months after surgery. Paired t-test was used to compare those variables, and Spearman's correlation was used to determine their relation to patient's age. Mean+/-SD astigmatism at 1 week postoperatively was 3.1+/-2.8 Diopter (D) and 2.1+/-1.7 D in groups 1 and 2, respectively. It significantly reduced to 1.1+/-1.2 D and 0.9+/-1.0 D, respectively, in the two groups at 5 months postoperatively (P<0.007). In both groups patients' age was significantly correlated with 1-week postoperative astigmatism (group 1: r=0.64; P=0.001; group 2: r=-0.58; P=0.003), and with the change in cylinder magnitude between 1 week and 3 months postoperatively (group 1: r=-0.67; P=0.001; group 2: r=0.50; P=0.013). Children who underwent congenital cataract surgery using clear corneal or scleral tunnel incisions showed high postoperative astigmatism at 1 week postoperatively, which spontaneously reduced during 5 months follow-up. Therefore, suture removal is not necessary in those cases.


Characterization of a modified rotating disk reactor for the cultivation of Staphylococcus epidermidis biofilm.
The purpose of this study was to develop a system that would allow biofilms to be cultivated under strictly defined conditions in terms of dissolved oxygen, fluid shear and to assess whether the method was suitable for the detection of respiratory activity stratification in biofilm samples. The system is a modified version a commercially available laboratory biofilm reactor and incorporates a number of features such as the provision of defined levels of dissolved oxygen, constant average shear, enhanced gas-liquid mass transfer, aseptic operation and the ability to remove biofilm for ex situ analysis during or after continuous cultivation. The system was shown to be effective for the characterization of the effects of dissolved oxygen on a pure culture of Staphylococcus epidermidis. The versatility of the system offers the potential for cultivating pure culture biofilm in defined, controlled conditions and facilitates a range of analyses that can be performed ex situ. The ability to provide strict regulation of environmental conditions and enhanced transfer of oxygen to the biofilm during cultivation are important, first because oxygen is known to regulate biofilm development in several micro-organisms and second because many conventional biofilm cultivation systems may not provide adequate oxygen supply to the biofilm.


Collagen in the extracellular matrix of cultured scleroderma skin fibroblasts: changes related to ascorbic acid-treatment.
The synthesis of collagen and its deposition into the extracellular matrix were studied in scleroderma and normal skin fibroblast cultures using immunocytochemistry, electron microscopy and electrophoretic analysis. Indirect immunofluorescence localized type I collagen to intracellular granules of normal skin fibroblasts but not to the extracellular matrix. A 48-h ascorbic acid-treatment of scleroderma and normal skin fibroblasts induced the appearance of fibrillar, collagen-containing deposits in the extracellular space as indicated by indirect immunofluorescence and electron microscopy. Interestingly, similar type I collagen-containing fibrils were observed in cultures of scleroderma skin fibroblasts even without preceding ascorbic acid treatment. Electrophoretic analysis revealed that ascorbic acid increases the conversion of procollagen to collagen to same extent both in scleroderma and control cell layers. The accumulation of collagen to the cell layer of scleroderma fibroblasts was increased when compared to normal skin fibroblasts; whereas the relative conversion of procollagen to collagen was identical in scleroderma and normal fibroblasts. The results show that the conversion of procollagen to collagen in the cell layers of both scleroderma and normal skin fibroblasts is dependent on ascorbic acid, due to improved secretion of procollagen molecules in the presence of ascorbic acid.


Influences of exercise and endurance training on the oxygen dissociation curve of blood under in vivo and in vitro conditions.
In experiments with graded exercise of 15 men (6 untrained, 3 semitrained, 6 endurance-trained) the trained subjects showed a massive shift to the right of the in vivo O2 dissociation curve (ODC) of femoral venous blood. At a saturation of 20 to 25% (18 mkp/sec) Po2 was about 9 mm Hg higher for the trained than for the untrained group. The following factors play a role: 1. The 2,3-diphosphoglycerate [2,3-DPG] concentration was increased by 15 to 20% in the trained group which explains about 2 mm Hg of the diffenence in Po2-2. Exercise acidosis in the femoral venous blood depends to a large extent on CO2 in the trained, but on lactic acid in the untrained group. At low saturations the CO2-Bohr effect increases sharply thus having a greater importance in the trained subjects. This factor can explain about 2 mm Hg of the difference. However, influence of chloride and 2,3-DPG on the Bohr effect must be taken into consideration. 3. Since the large ODC-shift to the right of the trained group was not reproducible under in vitro conditions, it is suggested that a rapidly decaying unknown substance accounts for the remaining difference in Po2.


The role of adipokines in systemic sclerosis: a missing link?
Systemic sclerosis is a multiorgan autoimmune disease characterized by vasculopathy and tissue fibrosis of unknown etiology. Recently, adipokines (cell signaling proteins secreted by adipose tissue) have attracted much attention as a cytokine family contributing to the various pathological processes of systemic sclerosis. Adipokines, such as leptin, adiponectin, resistin, adipsin, visfatin or chemerin are a heterogenic group of molecules. Adiponectin exhibits anti-fibrotic features and affects inflammatory reactions. Leptin promotes fibrosis and inflammation. Resistin was linked to vascular involvement in systemic sclerosis. Visfatin was associated with regression of skin lesions in late-stage systemic sclerosis. Chemerin appears as a marker of increased risk of impaired renal function and development of skin sclerosis in the early stage of systemic sclerosis. Vaspin was indicated to have a protective role in digital ulcers development. Novel adipokines-adipsin, apelin, omentin and CTRP-3-are emerging as molecules potentially involved in SSc pathogenesis. Serum adipokine levels may be used as predictive and diagnostic factors in systemic sclerosis. However, further investigations are required to establish firm correlations between distinct adipokines and systemic sclerosis.


Two-dimensional gel analysis of protein expression profile in squamous cervical cancer patients.
Screening in cervical cancer is progressing to find out candidate genes and proteins, which may work as biological markers and play a role in tumor progression. We examined the protein expression patterns of squamous cell carcinoma (SCC) tissues from Korean women using two-dimensional polyacrylamide gel electrophoresis (2-DE) and matrix-assisted laser desorption/ionization-time of fight (MALDI-TOF) mass spectrometer. Normal cervix and SCC tissues were solubilized and 2-DE was performed using the pH 3-10 linear IPG strips of 17 cm length and silver stained. Protein expression was evaluated using PDQuest 2-D software. The differentially expressed protein spots were identified with MALDI-TOF mass spectrometer and the peptide mass spectra identification was performed using Mascot program searching the Swiss-prot or NCBInr databases. A total of 35 proteins were detected in SCC. 17 proteins were up-regulated and 18 proteins were down-regulated. Among the proteins identified, 12 proteins (pigment epithelium derived factor, annexin A2 and A5, keratin 19 and 20, heat shock protein 27, smooth muscle protein 22 alpha, alpha-enolase, squamous cell carcinoma antigen 1 and 2, glutathione S-transferase, apolipoprotein a1) were previously known proteins involved in tumor and 21 proteins were newly identified in this study. 2-DE offers total protein expression profiles of SCC tissues and further characterization of proteins that are differentially expressed will give a chance to identify tumor-specific diagnostic markers for SCC.


Oxidation of vitamin E and vitamin C and inhibition of brain mitochondrial oxidative phosphorylation by peroxynitrite.
The effects of peroxynitrite (PN; product of the reaction between nitric oxide and superoxide) on mitochondrial respiration as well as oxidation of alpha-tocopherol and ascorbic acid were studied. Mitochondria were isolated from brain hemispheres of 4-month-old male Fisher rats by standard centrifugation procedures utilizing Ficoll gradients. Treatment of brain mitochondria with PN caused a concentration-dependent impairment of oxidative phosphorylation and depletion of the endogenous antioxidants alpha-tocopherol and ascorbic acid. PN-induced mitochondrial dysfunction was characterized by 1) decreases in state 3 respiration and oxidative phosphorylation, 2) loss of respiratory control [ratio of ADP-stimulated (state 3) to basal (state 4) respiration], and 3) uncoupling of oxidative phosphorylation. PN did not function as a pure uncoupler, insofar as the increase in state 4 respiration was accompanied by a larger decrease in state 3 respiration. This contrasts with the uncoupling action of the protonophore carbonyl cyanide m-chlorophenylhydrozone, which increases both state 3 and state 4 respiration. PN-induced reduction in respiratory control and oxidative phosphorylation closely paralleled the oxidation of membrane tocopherol and were preceded by loss of ascorbate. alpha-Tocopherol (the most potent biological lipid antioxidant) may have a unique role in protecting mitochondrial membranes from oxidative stress. The two antioxidant nutrients alpha-tocopherol and ascorbate (which interact with each other and glutathione) may be intimately involved in protecting mitochondria in situations in which excessive release of superoxide and nitric oxide occurs under normal and/or pathological conditions.


Cerebrospinal fluid monoamine metabolite concentrations in depressive disorder: A meta-analysis of historic evidence.
Altered monoaminergic functions have been implicated in the pathophysiology of depressive disorder. However, previously reported cerebrospinal fluid (CSF) monoamine metabolite concentrations in major depression have been inconsistent. We performed a meta-analysis of historic evidence to determine whether CSF monoamine metabolite levels were different between patients with depression and normal controls, and could be used as depression biomarkers. Relevant studies that investigated CSF 5-hydroxyindoleacetic acid (5-HIAA), homovanillic acid (HVA), and 3-methoxy-4-hydroxyphenylglycol (MHPG) levels in patients with depression and normal controls were identified in PubMed, Web of Science, PsycINFO, and Embase databases through September 5, 2017, using a synonymous search for depression, CSF, normal, control, and each monoamine metabolite name, and in the reference lists of the acquired articles. Obtained records were individually scrutinized for eligibility. Our search strategy identified 26 studies, including our own. We employed random effects modeling and adopted "Hedges's g" as an index of effect size. In the meta-analyses, no significant difference was observed in CSF 5-HIAA or MHPG levels between patients with depressive disorder and controls. In contrast, CSF HVA was significantly decreased in patients with depression (Hedges's g = -0.30, P = 0.0000025), and these results remained significant after patients with bipolar disorder were excluded (Hedges's g = -0.37, P = 0.000061). In the meta-regression, sex was significantly associated with the Hedges's g of CSF HVA (Q = 4.41, P = 0.036). This meta-analysis revealed that only CSF HVA, and not 5-HIAA or MHPG, levels were decreased in depressive disorder. The reduction in the CSF HVA concentration in patients with depression may guide future studies on depression and serve as a useful biomarker of depressive disorder.


Purification and biochemical characterization of a nattokinase by conversion of shrimp shell with Bacillus subtilis TKU007.
BSN1, a nattokinase, was purified from the culture supernatant of Bacillus subtilis TKU007 with shrimp shell wastes as the sole carbon/nitrogen source. The BSN1 was purified to homogeneity by three-step procedure with a 515-fold increase in specific activity and 12% recovery. The molecular masses of BSN1 determined by SDS-PAGE and gel filtrations were approximately 30 kDa and 28 kDa, respectively. The results of peptide mass mapping showed that four tryptic peptides of BSN1 were identical to the nattokinase from B. subtilis (GenBank accession number gi14422313) with 37% sequence coverage. The N-terminal amino acid sequence of the first 12 amino acids of BSN1 was AQSVPYGISQIK. The optimum pH, optimum temperature, pH stability, and thermal stability of BSN1 were 8, 40 °C, pH 4-11, and less than 50°C, respectively. BSN1 was inhibited completely by PMSF, indicating that the BSN1 was a serine protease. Using this method, B. subtilis TKU007 produces a nattokinase/fibrinolytic enzyme and this enzyme may be considered as a new source for thrombolytic agents.


Manic depressive illness in a founder population.
Manic depressive illness (MDI) segregates within a founder population originating from S, a mountain village in Southern Italy. Identity by descent of affected persons cannot be established by direct genealogical methods. A 56 000 persons family reconstruction data base encompasses the whole population of S in the 17th and 18th centuries, and part of the population of S and neighbouring villages in the 19th and 20th centuries. We selected 10 MDI probands who were members of the S population and not evident close relatives of each other. A total of 10 other MDI probands not evidently related to the S population formed a first control group. A second control group was formed with 10 not closely related persons originating within the S population. We determined the founders common ancestors to all the probands of one group but not ancestors to the probands of other groups, and computed the genetic contribution of each founder to each proband. The distance between probands in the S MDI group was calculated with respect to all the founders. In all, 17 founders present in the ascendancy of all individuals of the S MDI group are not present in the ascendancy of the control groups: MDI patients are derived from a subpopulation within S. Two S MDI probands are far from one another in respect of the 'nonspecific' founders, but are very close in respect of the specific founders: a putative MDI trait originated from specific founders of the MDI subpopulation, and hence is identical by descent in the S population.


Transrectal ultrasound of rectal tumors.
Since preoperative staging of rectal tumors is important in planning treatment, we evaluated transrectal ultrasound (TRUS) staging of rectal neoplasms. In 35 consecutive rectal tumors, we compared TRUS staging results with final pathologic staging. TRUS predicted the degree of tumor invasion in 19 of 24 patients (79%) and the presence or absence of lymph node metastasis in 11 of 15 patients (73%). TRUS overestimated the degree of tumor invasion in four patients (17%) and underestimated invasion in one patient (4%). The depth of tumor invasion was correctly predicted in all 14 tumors located within 6 cm from the anal verge, but, beyond 6 cm, only 5 of 10 tumors (50%) were staged correctly (p = 0.005). In the group of 11 patients who underwent preoperative radiotherapy, pretreatment TRUS predicted the depth of tumor invasion in only six patients (55%) and overestimated tumor invasion in five patients (45%), suggesting that nearly half of these tumors were downstaged by radiotherapy. TRUS accurately predicts the degree of tumor invasion, especially in tumors closer to the anal verge, allowing for better treatment planning in patients with low to middle rectal neoplasms.


Different models of frailty in predementia and dementia syndromes.
Dementia is an increasingly common disease in the aging population, and the numbers are expected to rise exponentially in coming years. Therefore, there is a critical need to potentially individualize new strategies able to prevent and to slow down the progression of predementia and dementia syndromes. Despite a substantial increase in the epidemiological and clinical evidence on frailty, there is no consensus on its definition or on what criteria should be used to identify older individuals with frailty. Frailty appears to be a nonspecific state of vulnerability, which reflects multisystem physiological change. In fact, current thinking is that not only physical but also psychological, cognitive and social factors contribute to this multidimensional syndrome and need to be taken into account in its definition and treatment. Cognition has already been considered as a component of frailty, and it has been demonstrated that it is associated with adverse health outcomes. In a recent population-based study, physical frail demented patients were at higher risk of all-cause mortality over 3- and 7-year follow-up periods. Several studies have also reported that physical frailty is associated with low cognitive performance, incidence of Alzheimer's disease (AD), and mild cognitive impairment, and AD pathology in older persons with and without dementia. Most frailty instruments use a dichotomous scoring system classifying a person as either frail or not frail, while a continuous or an ordinal scoring system on multiple levels would be preferable to be used as an outcome measure. Recently, a Multidimensional Prognostic Index (MPI), derived from a standardized comprehensive geriatric assessment, was effective in predicting short- and long-term mortality risk in hospitalized patients with dementia. Overall taken together these findings supported the concept that outcome measures linked to multidimensional impairment may be extremely important in making clinical decisions, especially for monitoring drug treatment in randomized clinical trials also for predementia and dementia syndromes.


Ultrastructure and secretion of glandular trichomes in species of subtribe Cajaninae Benth (Leguminosae, Phaseoleae).
The subtribe Cajaninae of papilionoid legumes has a pantropical distribution and comprises approximately 490 species. These species have diversified throughout dry environments where there are high temperatures and strong light. The subtribe stands out because all its representatives have vesicular glands. In addition, bulbous-based and capitate trichomes are important secretory structures present in all genera of the Cajaninae. We analyzed the ultrastructure and histochemistry of these glandular trichome types in leaflets of the three species of the subtribe. Using transmission electron microscopy and histochemical analyses, we link the glandular secretions to subcellular structures. We here report for the first time the type of exudate and ultrastructure of the glands of subtribe Cajaninae. Terpenoids and phenolics were confirmed by histochemistry tests, and we observed that the organelles responsible for biosynthesis of oils are the most representative in these glands. Each glandular trichome showed particular ultrastructural features compatible with the compounds produced. We suggest that these glandular trichomes, with their respective exudates, act in defense against herbivory and against possible damage by ultraviolet radiation.


Sensitivity analysis of misclassification: a graphical and a Bayesian approach.
Misclassification can produce bias in measures of association. Sensitivity analyses have been suggested to explore the impact of such bias, but do not supply formally justified interval estimates. To account for exposure misclassification, recently developed Bayesian approaches were extended to incorporate prior uncertainty and correlation of sensitivity and specificity. Under nondifferential misclassification, a contour plot is used to depict relations among the corrected odds ratio, sensitivity, and specificity. Methods are illustrated by application to a case-control study of cigarette smoking and invasive pneumococcal disease while varying the distributional assumptions about sensitivity and specificity. Results are compared with those of conventional methods, which do not account for misclassification, and a sensitivity analysis, which assumes fixed sensitivity and specificity. By using Bayesian methods, investigators can incorporate uncertainty about misclassification into probabilistic inferences.


Genomic analysis of a new type VI secretion system in Vibrio parahaemolyticus and its implications for environmental adaptation in shrimp ponds.
The type VI secretion system (T6SS) in Vibrio spp. is often used to kill heteroclonal neighbors by direct injection of toxic effectors, but its strategies in aquacultural environments receive limited attention. In this study, we conducted genomic analysis for a T6SS-harboring plasmid in V. parahaemolyticus strain VP157. Coculture assays were further conducted to verify its antibacterial function. The results showed that strain VP157 harbored a 132-kb plasmid, pVP157-1, which consists of two fragments: an 87.8-kb fragment identical to plasmid pTJ114-1 and a 44.2-kb T6SS gene cluster with only 4% DNA identity to T6SS1 in the V. parahaemolyticus reference genome. Gene-by-gene analysis of six genes representing core T6SS components suggested that each gene has distinct evolutionary origins. In vitro experimental evolution revealed that pVP157-1 can excise from the VP157 genome with an excision rate of 4%. A coculture assay suggested that strain VP157 had significantly higher antibacterial activity against Bacillus pumilus and V. cholerae than the strain without pVP157-1(VP157∆T6SS). In contrast, a rapid decline was observed for the proportion of VP157∆ T6SS in a mock microbial community, which decreased from 10.7% to 2.1% in 5 days. The results highlighted that the acquisition of T6SS fostered the fitness of V . parahaemolyticus in a complex environment.


Combined retropleural thoracotomy and posterior spinal approach for thoracic dumbbell Schwannoma: Case series and review of the literature.
Dumbbell schwannomas of the thoracic spine are challenging to cure surgically. Surgeons are familiar with posterolateral approaches to the spine, however, these may provide inadequate exposure for large tumors extending to ventral extraspinal compartments. Ventrolateral transpleural approaches offer direct access to the ventral thoracic spine and intrathoracic cavity, though are associated with increased morbidity and pulmonary complications, and may necessitate a staged procedure in order to address concomitant dorsal pathology. Herein we describe our experience with single-stage, posterior approach to dumbbell schwannomas with large ventral extraspinal components, and review the literature regarding surgical approaches for these tumors. Retrospective review of patients who underwent a single-stage, posterior spinal surgery for thoracic dumbbell schwannomas from 2008 to 2018. Inclusion criteria were age > 18 years and ventral thoracic tumor component. Three patients underwent a simultaneous retropleural thoracotomy and posterior spinal approach, through a single incision, for the resection of dumbbell (intradural and extradural) schwannomas. Mean age was 49.7 years and 2 patients were female. All patients were neurologically intact at baseline. Lesions were 4-8.2 cm in the largest dimension (mean 6.1 cm). GTR was achieved in all patients. One pleural rent occurred intraoperatively; there were no other intraoperative or perioperative complications. At a mean follow-up of 14.1 months all patients remained motor and sensory intact and there was no evidence of recurrence. The combined retropleural thoracotomy-posterior spinal approach provides safe and sufficient access for resection of large dumbbell schwannomas of the thoracic spine.


Hydrogels based on seafood chitin: From extraction to the development.
Chitin is extensively applied in vast applications due to its excellent biological properties, such as biodegradable and non-toxic. About 50 % of waste generated during seafood processing is chitin. Conventionally, chitin is extracted via chemical method. However, it has many shortcomings. Many novel extraction methods have emerged, including enzymatic hydrolysis, microbial fermentation, ultrasonic or microwave-assisted, ionic liquids, and deep eutectic solvents. Chitin and its derivatives-based hydrogels have attracted much attention due to their excellent properties. Nevertheless, they all have many limitations. Therefore, the preparation and application of chitin and its derivatives-based hydrogels are still facing great challenges. This review focuses on the challenges and prospects for sustainable chitin extraction from seafood waste and the preparation and application of chitin and its derivatives-based hydrogels. First section summarizes the mechanism and application of several methods of extracting chitin. The different extraction methods were evaluated from the aspects of yield, degree of acetylation, and protein and mineral residuals. The shortcomings of the extraction methods are also discussed. Next section summarizes the preparation and application of chitin and its derivatives-based hydrogels. Overall, we hope this mini-review can provide a practical reference for selecting chitin extraction methods from seafood and applying chitin and its derivatives-based hydrogels.


Insights gained from single-cell RNA analysis of murine endothelial cells in aging hearts.
Aging is the strongest risk factor for cardiovascular disease, with progressive decline in the function of vascular endothelial cells (ECs) with age. Systematic analyses of the effects of aging on different cardiac EC types remain limited. Here, we constructed a scRNA atlas of EC transcriptomes in young and old mouse hearts. We identified 10 EC subclusters. The multidimensionally differential genes (DEGs) analysis across different EC clusters shows molecular changes with aging, showing the increase in the overall inflammatory microenvironment and the decrease in angiogenesis and cytoskeletal support capacity of aged ECs. And we performed an in-depth analysis of 3 special ECs, Immunology, Proliferating and Angiogenic. The Immunology EC seems highly associated with some immune regulatory functions, which decline with aging at different degrees. Analysis of two types of neovascular ECs, Proliferating, Angiogenic, implied that Angiogenic ECs can differentiate into multiple EC directions after initially originating from proliferating ECs. And aging leads to a decrease in the ability of vascular angiogenesis and differentiation. Finally, we summarized the effects of aging on cell signaling communication between different EC clusters. This cardiac EC atlas offers comprehensive insights into the molecular regulations of cardiovascular aging, and provides new directions for the prevention and treatment of age-related cardiovascular disease.


Pain as a complication of use of opiate antagonists for symptom control in cholestasis.
Controlled trials have suggested that opiate antagonist therapy may be effective for the treatment of the symptoms of cholestasis. The oral opiate antagonist naltrexone in particular has started to enter into routine clinical use for amelioration of cholestatic itch. Attention regarding the side effects of opiate antagonist therapy has, to date, largely focused on an opiate withdrawal-type reaction (which can be controlled effectively by titrated therapy introduction regimens). Here we describe 3 cases of a further clinically important side effect, loss of control of pain resulting from other pathologies, which in each case necessitated the withdrawal of hitherto clinically effective opiate antagonist therapy. Of the 14 patients treated by our unit with opiate antagonist agents for the control of cholestatic symptoms, 13 (93%) showed resolution of, or significant improvement in, symptoms. Of the 13 patients showing a clinical response, 7 (54%) subsequently had to discontinue therapy because of side effects (including the 3 patients with uncontrolled pain). It is our experience that in the routine clinical setting, opiate antagonists are highly effective for the treatment of cholestatic symptoms. In practice, however, their usefulness is limited by their side-effect profile.


Systemic collateral and pulmonary artery stenosis in patients with congenital pulmonary valve atresia and ventricular septal defect.
Angiograms of 30 patients with congenital pulmonary valve atresia, ventricular septal defect, and large systemic-pulmonary collateral arteries (SPCAs) were evaluated. All had aortography, 28 had SPCA arteriography, and 26 had right ventriculography. Seventeen (65%) of 26 patients had a right ventricular infundibulum, 23 (77%) had a pulmonary artery confluence, and five of the nine patients without a right ventricular infundibulum had a confluence. Sixty-six SPCAs of aortic origin were seen; 28 (42%) had narrowing and 21 patients (70%) had one or more narrowed SPCAs. Five patients had collaterals from internal mammary, subclavian or innominate arteries. Fourteen (47%) had hilar pulmonary artery stenosis. Of these 14 patients mild peripheral stenosis was demonstrated in five. Right aortic arch was present in 15 patients (50%). Complete angiographic delineation of pulmonary vasculature is an essential procedure for preoperative detection of pulmonary and SPCA stenoses in these patients.


Relationship between self-discrepancy and worries about penis size in men with body dysmorphic disorder.
We explored self-discrepancy in men with body dysmorphic disorder (BDD) concerned about penis size, men without BDD but anxious about penis size, and controls. Men with BDD (n=26) were compared to those with small penis anxiety (SPA; n=31) and controls (n=33), objectively (by measuring) and investigating self-discrepancy: actual size, ideal size, and size they felt they should be according to self and other. Most men under-estimated their penis size, with the BDD group showing the greatest discrepancy between perceived and ideal size. The SPA group showed a larger discrepancy than controls. This was replicated for the perceptions of others, suggesting the BDD group internalised the belief that they should have a larger penis size. There was a significant correlation between symptoms of BDD and this discrepancy. This self-actual and self-ideal/self-should discrepancy and the role of comparing could be targeted in therapy.


Development rates, fecundity and survival of developmental stages of the ticks Rhipicephalus appendiculatus, Boophilus decoloratus and B. microplus under field conditions in Zimbabwe.
To determine development rates, fecundity and survival of Rhipicephalus appendiculatus, Boophilus decoloratus and B. microplus, a study was carried out in long and short grass in the highveld of Zimbabwe. Engorged adult females of the three species and engorged larvae and nymphs of R. appendiculatus were buried beneath the soil in small cages in the rainy, cool and hot seasons in 1980 and 1981. Half the number of cages were examined regularly to determine development rates and half were left undisturbed to determine survival rates and the fecundity of engorged females. Development was most rapid during warm conditions and slowest during cool conditions, but high temperatures appeared to prolong the preoviposition periods of all species. The relationship between fluctuating temperatures and rate of development in the field was defined using a least-squares procedure. Survival of engorged females was usually high, but was reduced by predation when they were not protected. Fecundity was reduced in long grass during the cool season and in short grass during the hot season. A higher percentage of eggs hatched in the rainy season than in the cool or dry seasons. The survival of engorged larvae and nymphs was usually high in all seasons. Engorged nymphs were the hardiest stage and eggs the most suceptible stage to adverse microclimatic conditions.


Contributions and achievements on schistosomiasis control and elimination in China by NIPD-CTDR.
Being a zoonotic parasitic disease, schistosomiasis was widely spread in 12 provinces of Southern China in the 1950s, severly harming human health and hindering economic development. The National Institute of Parasitic Diseases at the Chinese Center for Diseases Control and Prevention, and Chinese Center for Tropical Diseases Research (NIPD-CTDR), as the only professional institution focussing on parasitic diseases at the national level, has played an important role in schistosomiasis control in the country. In this article, we look back at the changes of schistosomiasis endemicity and the contribution of NIPD-CTDR to the national schistosomiasis control programme. We review NIPD-CTDR's activities, including field investigations, design of control strategies and measures, development of diagnostics and drugs, surveillance-response of endemic situation, and monitoring & evaluation of the programme. The NIPD-CTDR has mastered the transmission status of schistosomiasis, mapped the snail distribution, and explored strategies and measures suitable for different types of endemic areas in China. With a good understanding of the life cycle of Schistosoma japonicum and transmission patterns of the disease, advanced research carried out in the NIPD-CTDR based on genomics and modern technology has made it possible to explore highly efficient and soft therapeutic drugs and molluscicides, making it possible to develop new diagnostic tools and produce vaccine candidates. In the field, epidemiological studies, updated strategies and targeted intervention measures developed by scientists from the NIPD-CTDR have contributed significantly to the national schistosomiasis control programme. This all adds up to a strong foundation for eliminating schistosomiasis in China in the near future, and recommendations have been put forward how to reach this goal.


Biparametric versus Multiparametric Magnetic Resonance Imaging for Assessing Muscle Invasion in Bladder Urothelial Carcinoma with Variant Histology Using the Vesical Imaging-Reporting and Data System.
The diagnostic performance of contrast medium-free biparametric magnetic resonance imaging (bpMRI; combining T2-weighted imaging [T2WI] and diffusion-weighted imaging [DWI]) for evaluating variant-histology urothelial carcinoma (VUC) remains unknown. To compare the diagnostic performance of bpMRI and multiparametric MRI (mpMRI; combining T2WI, DWI, and dynamic contrast-enhanced MRI]) for assessing muscle invasion of VUC. This multi-institution retrospective analysis included 118 patients with pathologically verified VUC who underwent bladder mpMRI before transurethral bladder tumor resection between 2010 and 2019. Three board-certified radiologists separately evaluated two sets of images, set 1 (bpMRI) and set 2 (mpMRI), in accordance with the Vesical Imaging Reporting and Data System (VI-RADS). The histopathology results were utilized as a reference standard. Receiver operating characteristic curve analysis, Z test, and Wald test were used to assess diagnostic abilities. Sixty-six (55.9%) and 52 (44.1%) of the 118 patients with VUC included in the analysis (mean age, 71 ± 10 yr; 88 men) had muscle-invasive bladder cancer (MIBC) and non-MIBC, respectively. For the diagnosis of MIBC, the areas under the curve for bpMRI were significantly smaller than those for mpMRI (0.870-0.884 vs 0.902-0.923, p < 0.05). The sensitivity of bpMRI was significantly lower than that of mpMRI for all readers with a VI-RADS cutoff score of 4 (65.2-66.7% vs 77.3-80.3%, p < 0.05). The specificity of bpMRI and mpMRI did not differ significantly for all readers (88.5-90.4 vs 88.5-92.3, p > 0.05). A limitation of the study is the limited sample size because of the rarity of VUC. In patients with VUC, on applying VI-RADS, the diagnostic results of bpMRI were inferior to those of mpMRI for evaluating muscle invasion. Therefore, mpMRI-based methods are recommended for evaluating muscle invasiveness of VUC. Contrast medium-free biparametric magnetic resonance imaging (bpMRI)-based Vesical Imaging Reporting and Data System (VI-RADS) can accurately diagnose pure urothelial carcinomas, similar to conventional multiparametric magnetic resonance imaging-based VI-RADS. However, bpMRI-based VI-RADS may misdiagnose muscle invasiveness of urothelial carcinoma with variant histology, particularly when its cutoff score is 4.


Nifedipine effects in severe myocardial ischaemia in the dog due to left anterior descending coronary occlusion with left circumflex coronary artery constriction.
The effects of nifedipine were studied in a model of local myocardial ischaemia, comprising anaesthetized thoracotomized dogs in which a critical constriction of the left circumflex coronary artery (LCX) was combined with sudden occlusion of the left anterior descending coronary artery (LAD). Since more than one coronary artery is involved in ischaemic heart disease, the model seems to reflect the clinical situation very closely. In this model, infusion of 1 microgram kg-1 min-1 nifedipine increased myocardial blood flow within the stenosed area served by the LCX as well as in the myocardial region supplied by the LAD, mainly in the subepicardium. Accordingly, the drug reduced ischaemic ST-segment elevation only in the epicardium. It is suggested that nifedipine directed flow to the sub-epicardium of the ischaemic area by improving the collateral circulation. This redistribution of flow resulted in a decrease in the endo/epicardial flow ratio. Nifedipine did not change the inhomogeneity of electrical activation indicating that it has no effect on the ischaemia-induced conduction delay. At the same time nifedipine was not able to reduce either the number of extrasystoles appearing in the early postocclusion and reperfusion phase or the incidence of ventricular fibrillation occurring mainly during reperfusion.


Coupled Gluteus Maximus and Gluteus Medius Recruitment Patterns Modulate Hip Adduction Variability During Single-Limb Step-Downs: A Cross-Sectional Study.
Examining the coordinated coupling of muscle recruitment patterns may provide insight into movement variability in sport-related tasks. The purpose of this study was to examine the relationship between coupled gluteus maximus and medius recruitment patterns and hip-adduction variability during single-limb step-downs. Cross-sectional. Biomechanics laboratory. Forty healthy adults, including 26 women and 14 men, mean age 23.8 (1.6) years, mean body mass index 24.2 (3.1) kg/m2, participated. Lower-extremity kinematics were acquired during 20 single-limb step-downs from a 19-cm step height. Electromyography (EMG) signals were captured with surface electrodes. Isometric hip-extension strength was obtained. Hip-adduction variability, measured as the SD of peak hip adduction across 20 repetitions of the step-down task, was measured. The mean amplitudes of gluteus maximus and gluteus medius EMG recruitment were examined. Determinism and entropy of the coupled EMG signals were computed with cross-recurrence quantification analyses. Hip-adduction variability correlated inversely with determinism (r = -.453, P = .018) and positively with entropy (r = .409, P = .034) in coupled gluteus maximus/medius recruitment patterns but not with hip-extensor strength nor with magnitudes of mean gluteus maximus or medius recruitment (r = -.003, .081, and .035; P = .990, .688, and .864, respectively). Hip-adduction variability during single-limb step-downs correlated more strongly with measures of coupled gluteus maximus and medius recruitment patterns than with hip-extensor strength or magnitudes of muscle recruitment. Examining coupled recruitment patterns may provide an alternative understanding of the extent to which hip neuromuscular control modulates lower-extremity kinematics beyond examining muscle strength or EMG recruitment magnitudes.


Medin co-aggregates with vascular amyloid-β in Alzheimer's disease.
Aggregates of medin amyloid (a fragment of the protein MFG-E8, also known as lactadherin) are found in the vasculature of almost all humans over 50 years of age1,2, making it the most common amyloid currently known. We recently reported that medin also aggregates in blood vessels of ageing wild-type mice, causing cerebrovascular dysfunction3. Here we demonstrate in amyloid-β precursor protein (APP) transgenic mice and in patients with Alzheimer's disease that medin co-localizes with vascular amyloid-β deposits, and that in mice, medin deficiency reduces vascular amyloid-β deposition by half. Moreover, in both the mouse and human brain, MFG-E8 is highly enriched in the vasculature and both MFG-E8 and medin levels increase with the severity of vascular amyloid-β burden. Additionally, analysing data from 566 individuals in the ROSMAP cohort, we find that patients with Alzheimer's disease have higher MFGE8 expression levels, which are attributable to vascular cells and are associated with increased measures of cognitive decline, independent of plaque and tau pathology. Mechanistically, we demonstrate that medin interacts directly with amyloid-β to promote its aggregation, as medin forms heterologous fibrils with amyloid-β, affects amyloid-β fibril structure, and cross-seeds amyloid-β aggregation both in vitro and in vivo. Thus, medin could be a therapeutic target for prevention of vascular damage and cognitive decline resulting from amyloid-β deposition in the blood vessels of the brain.


Follow-up after patch aortoplasty for coarctation of aorta.
Patch aortoplasty (PA) for coarctation of aorta (COA) can lead to aneurysm formation at the repair site. X-ray, echocardiogram and computed tomography are unreliable for diagnosis of this complication. To evaluate prospectively patients with PA for COA by magnetic resonance imaging (MRI) to detect presence of aneurysm at the repair site. All patients who underwent PA at the authors' institution were identified. MRI was performed in transverse and long axis oblique views on all patients except those who had, or were going to have, aortic angiography for other reasons. Details of the surgical procedure were obtained from the hospital records. Of the 18 patients studied, 15 had MRI and three had aortic angiography. Age at PA ranged from one week to 13.3 years (mean 6.3 years). The interval from PA to MRI or angiography was 9.5 years (range four to 12.5). No aneurysm was detected in any patient. Recoarctation was diagnosed in two patients not previously suspected but discovered on MRI. At PA the intimal shelf causing coarctation was either not excised or only minimally trimmed in 14 of 15 instances. The incidence of late aneurysm formation following PA for COA is low in the authors' patients, possibly due to minimal intimal damage at repair, although these patients should be followed longer. MRI was useful for assessment of aneurysm and restenosis.


High-energy tibial shaft fractures.
High-energy tibial fractures are common injuries that are managed by most practicing orthopaedic surgeons. Many methods of treatment are available. This article reviews the options for skeletal stabilization, the risks and benefits of each, and the necessary concepts that effect outcome.


Radiochemical studies relevant to 86Y production via 86Sr(p,n)86Y for PET imaging.
A novel production technique of yttrium-86 based on bombardment of deposited strontium carbonate was investigated. (86)Y was produced via proton-induced reactions on SrCO(3) target that was prepared by the sedimentation method. Production yield of 0.37mCi/microAh at 30 microA was measured by means of gamma-ray spectrometry for natural target. The separation of (86/87/88)Y from Cu and Sr was carried out by two ion-exchange columns.


C4 plants of high biomass in arid regions of asia-occurrence of C4 photosynthesis in Chenopodiaceae and Polygonaceae from the Middle East and USSR.
Measurements of δ13C values were used as a diagnostic test for the possible occurrence of C4 photosynthesis in 175 species of the Chenopodiaceae and 18 species of the genus Calligonum (Polygonaceae) from deserts of the Middle East and USSR. Eighty percent of the Chenopodiaceae (predominantly members of the genera Aellenia, Anabasis, Haloxylon, Salsola and Suaeda) and all species of the genus Calligonum showed C4-like δ13C values. Several features of these plants disclose some new facets of C4 photosynthesis. Some of the Haloxylon and Calligonum species are trees or tall shrubs and in Middle Asia are dominant members of plant communities characterized by high biomass. Many C4 species of the Chenopodiaceae and Polygonaceae in their natural, Middle and Central Asian desert habitats, experience temperatures far below the freezing point for a long period of the year. Several of these C4 species are of considerable economic value.


Effects of picrotoxin and strychnine on fish retinal S-potentials: evidence for inhibitory control of depolarizing responses.
Simultaneous recording of the light evoked electrical signals from different classes of slow(S)-potential unit in the isolated fish retina established that picrotoxin, an antagonist of GABA, selectively suppresses the depolarizing component of C-type S-potentials. In contrast, equivalent concentrations of strychnine have no effect on S-potentials, but suppress a component of transient amacrine cell responses. On the basis of these and other experimental data [3,4] we propose a network diagram for the C-type S-potential units in the cyprinid fish retina. This network includes a GABA-ergic feed-back loop and is essentially similar to that proposed by Fuortes and Simon [5].


Isosilybin regulates lipogenesis and fatty acid oxidation via the AMPK/SREBP-1c/PPARα pathway.
It is well known that the excessive accumulation of lipid in hepatocytes is one of the important causes of non-alcoholic fatty liver disease (NAFLD). The purpose of this study was to explore the effects of isosilybin on lipid metabolism in free fatty acids (FFAs) or TO901317-induced HepG2 cells. Cells were treated with FFAs (oleic acid: palmitic acid, 2:1) or TO901317 to induce steatosis in vitro. Intracellular triglyceride (TG) content was quantified using commercial assay kits. The mRNA and protein expression of genes involved in fatty acid uptake, synthesis and oxidation were analyzed by RT-qPCR and western blotting. Selected biological pathways regulated by isosilybin treatment were determined by GO and KEGG analysis. The results showed that isosilybin significantly reduced TG levels in FFAs- and TO901317-induced HepG2 cells. Further studies showed that isosilybin treatment decreased the mRNA and protein expression of lipid synthesis genes Srebp-1c, Pnpla3, Acc and Fas, as well as the mRNA expression of fatty acid uptake gene CD36, whereas increased the mRNA levels of lipid oxidation genes Pparα, Acox1 and Cpt1α, as well as the mRNA expression of lipid export gene Mttp, in FFAs-induced HepG2 cells. Moreover, TO901317 was employed to induce endogenous lipid synthesis and steatosis, and the expression of Srebp-1c and its target genes in TO901317-induced hepatocytes was basically similar to that in FFAs-induced hepatocytes following isosilybin treatment. We also observed the increased level of phosphorylated AMP kinase (AMPK) after isosilybin treatment, while this effect was reversed after further treatment with AMPK inhibitor, compound C. The results of GO and KEGG analysis indicated that the pathways of fatty acid and TG metabolism were regulated by isosilybin. Interestingly, we found that treatment with the diastereoisomer A of isosilybin increased TG level, while exposure to the diastereoisomer B of isosilybin decreased TG level in FFAs-induced HepG2 cells. The above results suggest that isosilybin can inhibit lipid synthesis and activate lipid oxidation through AMPK signaling pathway, thereby improving steatosis of hepatocytes, and isosilybin B is the basis of its active substance.


Antigen specificities and functional properties of MR1-restricted T cells.
MR1 is an MHC class I-like molecule with unique structural and biological features that make it an important member among the molecules involved in antigen presentation to T cells. Distinctive features include ubiquitous expression of the MR1 gene and its monomorphism. Another relevant property is that the MR1 protein appears at very low levels on the plasma membrane and its surface expression is regulated by antigen binding. Finally, the nature of presented antigens differs from those that bind other presenting molecules and includes small metabolites of microbial and self-origin, small drugs and tumor-associated antigens. This opinion paper describes in detail some of those features and discusses recent literature in the field.


Postnatal lead exposure alters spontaneous cerebellar Purkinje neuron discharge.
The effects of early postnatal lead administration on the spontaneous activity of cerebellar Purkinje neurons were studied electrophysiologically in adult male Sprague-Dawley rats. Newborn rat litters were divided into three groups and injected daily from Day 1 to Day 20 after birth with 8 mg NaAc/kg, 1 mg PbAc/kg, or 8 mg PbAc/kg intraperitoneally. Purkinje neurons in all three groups showed regular and sustained discharge. However, the mean spontaneous firing rate was significantly lower in the 8-mg PbAc/kg group (26.13 +/- 1.28 Hz) compared to the NaAc controls (32.39 +/- 1.93, P greater than 0.01). Furthermore, the distribution of the firing rates of the Purkinje cells were different in the two groups, with an obvious loss of faster firing cells in the 8-mg PbAc/kg group. No differences were seen between the 1-mg PbAc/kg group and the NaAc controls. As the 8-mg PbAc/kg group weighed significantly less than the NaAc group, malnourished animals were produced by using oversized litters, to control for any changes caused by the lower body weight. However, when compared to concomitantly raised controls, no changes could be seen in Purkinje cell discharge in the malnourished animals. It is concluded that neonatal exposure to lead can cause permanent changes in spontaneous Purkinje cell discharge.


Recombinant outer membrane secretin PilQ(406-770) as a vaccine candidate for serogroup B Neisseria meningitidis.
Secretin PilQ is an antigenically conserved outer membrane protein which is present on most meningococci. This protein naturally expressed at high levels and is essential for meningococcal pilus expression at the cell surface. A 1095 bp fragment of C-terminal of secretin pilQ from serogroup B Neisseria meningitidis was cloned into prokaryotic expression vector pET-28a. Recombinant protein was overexpressed with IPTG and affinity-purified by Ni-NTA agarose. BALB/c mice were immunized subcutaneously with purified rPilQ(406-770) mixed with Freund's adjuvant. Serum antibody responses to serogroups A and B N. meningitidis whole cells or purified rPilQ(406-770) and functional activity of antibodies were determined by ELISA and SBA, respectively. The output of rPilQ(406-770) was approximately 50% of the total bacterial proteins. Serum IgG responses were significantly increased in immunized group with PilQ(406-770) mixed with Freund's adjuvant in comparison with control groups. Antisera produced against rPilQ(406-770) demonstrated strong surface reactivity to serogroups A and B N. meningitidis tested by whole-cell ELISA. Surface reactivity to serogroup B N. meningitidis was higher than serogroup A. The sera from PilQ(406-770) immunized animals were strongly bactericidal against serogroups A and B. These results suggest that rPilQ(406-770) is a potential vaccine candidate for serogroup B N. meningitidis.


Tissue plasminogen activator for the treatment of intraabdominal abscesses in a neonate.
Fibrinolytic agents have been used successfully in the management of loculated empyema; however, their use in the treatment of intraabdominal abscesses is limited. The authors describe the case of a 4-week-old girl with intraabdominal abscesses secondary to intestinal perforation that were not amenable to percutaneous drainage, but were managed successfully with intracavitary administration of tissue-plasminogen activator. This case represents the first report in a human, in which tissue-plasminogen activator was used to facilitate percutaneous drainage of an intraabdominal abscess. It is also the first time a fibrinolytic agent has been used for this purpose in a child.